Triple-negative breast cancer (TNBC) is aggressive, with high recurrence rates and poor prognosis. Paclitaxel (PTX) remains a key chemotherapeutic agent for TNBC, but its efficacy diminishes due to the emergence of drug resistance, largely driven by cancer stem-like cells (CSCs), vasculogenic mimicry (VM) formation and tumor immunosuppressive microenvironment (TIME). Pyruvate kinase M2 (PKM2) is highly expressed in TNBC, and is a potential target for TNBC treatment. In this study, we developed a biomimetic codelivery system using albumin nanoparticles (termed S/P NP) to co-encapsulate PTX and shikonin (SHK), a natural inhibitor of PKM2. By inhibiting PKM2, SHK suppressed β-Catenin signaling, thereby reversing CSC stemness and preventing VM formation. The S/P NP system exhibited tumor-targeting delivery effect and significantly inhibited TNBC growth and lung metastasis. Mechanistically, the treatment reversed epithelial-mesenchymal transition (EMT) and stem-like properties of TNBC cells, suppressed VM formation, and remodeled the TIME. It reduced immunosuppressive cells (M2 macrophages, MDSCs) while promoting anti-tumor immunity (M1 macrophages, dendritic cells, cytotoxic T cells, and memory T cells). This dual-action strategy holds promise for improving TNBC therapy by targeting CSCs, VM, and the immune microenvironment, and for overcoming PTX resistance and reducing metastasis.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.

OBJECTIVE: To investigate the clinical characteristics and genetic etiology of a Chinese pedigree affected with Hereditary dentin dysplasia type II (DD-II) due to variant of dentin sialophosphoprotein (DSPP) gene. METHODS: A child diagnosed with DD- II at the Third Clinical Division of Peking University Hospital of Stomatology in December 2021 and her family members were selected as study subjects. Clinical data were retrospectively analyzed. Saliva samples were collected from the proband, her parents and sister for genomic DNA extraction. Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing and TOPO-TA cloning sequencing. The candidate variant was also subjected to bioinformatics analysis using Mutation Taster v2021. Secondary and tertiary structures of the wild-type and variant DSPP proteins were predicted with psipred v4.0 and PyMOL v2.3 software, respectively. The pathogenicity of the variant was classified based on the guidelines from American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Peking University Hospital of Stomatology (Ethics No.: PKUSSIRB-202162021). RESULTS: The proband and her mother and sister had all exhibited typical clinical manifestations of hereditary DD-II. The primary dentition of the proband displayed yellowish brown discoloration, wear, and obliteration in the chamber and root canal, while the permanent teeth of the proband's sister and mother appeared nearly normal in both color and appearance, though with obliteration in the chamber and root canal. Her father showed normal dentition. WES identified a heterozygous c.1915_1918delAAGT, p.(Lys639Glnfs*674) frameshift variant in the DSPP gene. Sanger sequencing and TOPO-TA cloning sequencing confirmed the presence of this variant in the proband, the proband's sister, and the mother, while the proband's father was negative for the variant, indicating an autosomal dominant inheritance pattern. The variant was predicted to be pathogenic by Mutation Taster v2021. Prediction of the secondary structure of the DSPP protein showed that the variant has changed it from coil to helix. The tertiary structure prediction of the DSPP protein showed change of the spatial structure of the variant DSPP, with the loops in the variant region replaced by helices at multiple sites. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+PM2_Supporting+PP1+PP4). CONCLUSION Phenotypic analysis and genetic testing of this family has clarified the clinical diagnosis of hereditary DD- II. The c.1915_1918delAAGT variant probably underlay the pathogenesis of DD-II in this family. Above results have expanded the phenotypic spectrum of the disease and may contribute to further clinical and genetic research on this disease.
Humans ; Pedigree ; Female ; Extracellular Matrix Proteins/chemistry* ; Male ; Sialoglycoproteins/chemistry* ; Dentin Dysplasia/genetics* ; Asian People/genetics* ; Phosphoproteins/chemistry* ; Child ; Mutation ; China ; Exome Sequencing ; Adult ; East Asian People

Objective:To compare the clinical efficacy of laparoscopic-assisted, totally laparoscopic, and robotic radical gastrectomy (for total or distal gastrectomy) in real-world practice, clarify the advantages and disadvantages of each approach, and provide evidence for clinical surgical selection.Methods:A retrospective analysis was conducted on 225 patients who underwent radical gastrectomy for gastric cancer at the Zhejiang Provincial People′s Hospital from January 2022 to September 2023, including 100 cases of total gastrectomy and 125 cases of distal gastrectomy. Patients were divided into three groups based on the surgical approach: laparoscopic-assisted group, totally laparoscopic group, and robotic group. Perioperative indicators (operation time, intraoperative blood loss, number of lymph nodes dissected, etc.), inflammatory and nutritional indicators (C-reactive protein, white blood cell count, albumin, etc.), and postoperative recovery indicators (time to oral feeding, time to first flatus, length of hospital stay, etc.) were compared among the three groups.Results:In total gastrectomy, there were statistically significant differences among the three groups in C-reactive protein ( P<0.001), operation time ( P=0.002), time to oral feeding ( P<0.001), and intraoperative blood loss ( P<0.001). In distal gastrectomy, significant differences were observed in C-reactive protein ( P<0.001), operation time ( P<0.001), time to oral feeding ( P=0.002), and length of hospital stay ( P<0.001). No statistically significant differences were found in the incidence of postoperative complications or the number of lymph nodes dissected among the three groups (all P>0.05). Conclusions:Each of the three surgical approaches has its own advantages and disadvantages. The laparoscopic-assisted approach has low hardware requirements and shorter hospital stay after distal gastrectomy, making it suitable for widespread application. The robotic approach causes less trauma and milder inflammatory response but has high equipment and maintenance costs, requiring selection based on actual clinical conditions.

Objective:To explore the diagnostic value of multiparametric magnetic resonance imaging (mp-MRI) combined with computed tomography (CT) for brucellar spondylitis (BS).Methods:From March 2019 to March 2024, patients with suspected BS admitted to Yili Kazakh Autonomous Prefecture Friendship Hospital were selected as study subjects. Their clinical characteristics, laboratory tests, and imaging findings (mp-MRI and CT) were analyzed.Results:A total of 60 suspected BS patients were enrolled, including 43 males and 17 females. Among them, 39 cases (65.00%) were diagnosed with BS, while 21 cases (35.00%) were non-BS. CT examination was performed in 48 patients, mp-MRI in 40 patients, and both examinations in 28 patients. Among CT-examined patients, there were 28 BS cases, 1 case had cervical spine involvement, 3 case had thoracic spine involvement, 3 case had thoracolumbar spine involvement, and 21 case had lumbosacral spine involvement. There were 16 cases involved 2 vertebrae, 3 cases involved 3 vertebrae, and 9 cases involved > 3 vertebrae.There were 15 cases had vertebral osteophyte formation, 28 cases had vertebral bone destruction, 22 cases had intervertebral space stenosis, 25 cases had uneven intervertebral disc density, 28 cases had thickening of soft tissues around the vertebrae, 19 cases had paravertebral abscesses, and 6 cases had spinal canal stenosis. In the mp-MRI examination of patients, there were 30 BS patients, among whom 1 case had cervical spine involvement, 2 case had thoracic spine involvement, 4 case had thoracolumbar spine involvement, and 23 case had lumbosacral spine involvement. There were 16 cases involved 2 vertebrae, 3 cases involved 3 vertebrae, and 11 cases involved > 3 vertebrae, 24 cases had intervertebral space stenosis, 27 cases had intervertebral disc destruction. There were 27 cases had swelling and thickening of soft tissues around the vertebrae, and 21 cases had paravertebral, psoas major muscle, and/or spinal canal abscesses. The BS group showed lower fractional anisotropy value and higher apparent diffusion coefficient value compared to the non-BS group, with statistically significant differences ( t = 5.26, 5.63, P < 0.001). The mp-MRI combined with CT showed higher sensitivity (86.36%, 19/22) and specificity (5/6) for BS diagnosis compared to mp-MRI alone (78.57%, 11/14; 80.77%, 21/26) and CT alone (56.25%, 9/16; 71.88%, 23/32). Conclusions:BS patients present diverse imaging manifestations. The combination of mp-MRI and CT demonstrates better diagnostic efficacy for BS than single examinations alone, showing good diagnostic value.

Objective:To explore the diagnostic value of multiparametric magnetic resonance imaging (mp-MRI) combined with computed tomography (CT) for brucellar spondylitis (BS).Methods:From March 2019 to March 2024, patients with suspected BS admitted to Yili Kazakh Autonomous Prefecture Friendship Hospital were selected as study subjects. Their clinical characteristics, laboratory tests, and imaging findings (mp-MRI and CT) were analyzed.Results:A total of 60 suspected BS patients were enrolled, including 43 males and 17 females. Among them, 39 cases (65.00%) were diagnosed with BS, while 21 cases (35.00%) were non-BS. CT examination was performed in 48 patients, mp-MRI in 40 patients, and both examinations in 28 patients. Among CT-examined patients, there were 28 BS cases, 1 case had cervical spine involvement, 3 case had thoracic spine involvement, 3 case had thoracolumbar spine involvement, and 21 case had lumbosacral spine involvement. There were 16 cases involved 2 vertebrae, 3 cases involved 3 vertebrae, and 9 cases involved > 3 vertebrae.There were 15 cases had vertebral osteophyte formation, 28 cases had vertebral bone destruction, 22 cases had intervertebral space stenosis, 25 cases had uneven intervertebral disc density, 28 cases had thickening of soft tissues around the vertebrae, 19 cases had paravertebral abscesses, and 6 cases had spinal canal stenosis. In the mp-MRI examination of patients, there were 30 BS patients, among whom 1 case had cervical spine involvement, 2 case had thoracic spine involvement, 4 case had thoracolumbar spine involvement, and 23 case had lumbosacral spine involvement. There were 16 cases involved 2 vertebrae, 3 cases involved 3 vertebrae, and 11 cases involved > 3 vertebrae, 24 cases had intervertebral space stenosis, 27 cases had intervertebral disc destruction. There were 27 cases had swelling and thickening of soft tissues around the vertebrae, and 21 cases had paravertebral, psoas major muscle, and/or spinal canal abscesses. The BS group showed lower fractional anisotropy value and higher apparent diffusion coefficient value compared to the non-BS group, with statistically significant differences ( t = 5.26, 5.63, P < 0.001). The mp-MRI combined with CT showed higher sensitivity (86.36%, 19/22) and specificity (5/6) for BS diagnosis compared to mp-MRI alone (78.57%, 11/14; 80.77%, 21/26) and CT alone (56.25%, 9/16; 71.88%, 23/32). Conclusions:BS patients present diverse imaging manifestations. The combination of mp-MRI and CT demonstrates better diagnostic efficacy for BS than single examinations alone, showing good diagnostic value.

Objective:To compare the clinical efficacy of laparoscopic-assisted, totally laparoscopic, and robotic radical gastrectomy (for total or distal gastrectomy) in real-world practice, clarify the advantages and disadvantages of each approach, and provide evidence for clinical surgical selection.Methods:A retrospective analysis was conducted on 225 patients who underwent radical gastrectomy for gastric cancer at the Zhejiang Provincial People′s Hospital from January 2022 to September 2023, including 100 cases of total gastrectomy and 125 cases of distal gastrectomy. Patients were divided into three groups based on the surgical approach: laparoscopic-assisted group, totally laparoscopic group, and robotic group. Perioperative indicators (operation time, intraoperative blood loss, number of lymph nodes dissected, etc.), inflammatory and nutritional indicators (C-reactive protein, white blood cell count, albumin, etc.), and postoperative recovery indicators (time to oral feeding, time to first flatus, length of hospital stay, etc.) were compared among the three groups.Results:In total gastrectomy, there were statistically significant differences among the three groups in C-reactive protein ( P<0.001), operation time ( P=0.002), time to oral feeding ( P<0.001), and intraoperative blood loss ( P<0.001). In distal gastrectomy, significant differences were observed in C-reactive protein ( P<0.001), operation time ( P<0.001), time to oral feeding ( P=0.002), and length of hospital stay ( P<0.001). No statistically significant differences were found in the incidence of postoperative complications or the number of lymph nodes dissected among the three groups (all P>0.05). Conclusions:Each of the three surgical approaches has its own advantages and disadvantages. The laparoscopic-assisted approach has low hardware requirements and shorter hospital stay after distal gastrectomy, making it suitable for widespread application. The robotic approach causes less trauma and milder inflammatory response but has high equipment and maintenance costs, requiring selection based on actual clinical conditions.

Objective:To study lncRNA MEG3 expression and its relationship with Th17/CD4+T cells in patients with non-small cell lung cancer(NSCLC)with different pleural effusion severity and prognosis.Methods:A total of 104 NSCLC malignant pleural effusion patients admitted to Quanzhou First Hospital Affiliated to Fujian Medical University from January 2020 to December 2022 were selected as research subjects,and divided into three groups based on amount of pleural effusion,including small amount of pleural effusion group(35 cases),moderate amount of pleural effusion group(42 cases)and large amount of pleural effusion group(27 cases).According to actual development and prognosis of patient's disease,they were divided into good prognosis group(29 cases without recurrence and metastasis)and poor prognosis group(75 cases with recurrence and metastasis).Another 60 patients with benign pleural effusion due to pneumonia who were treated in Quanzhou First Hospital Affiliated to Fujian Medical University at same time were selected as control group.MEG3 expression in pleural effusion of two groups was detected by real-time fluorescent quantita-tive PCR,and peripheral venous blood of subjects was collected.Th17 cell and CD4+T cell ratios of peripheral blood were detected by flow cytometry,and Th17/CD4+T was calculated.lncRNA MEG3 and peripheral blood Th17 and CD4+T levels in each group of patients compared.Logistic regression analysis was used to analyze pleural effusion and prognostic factors in NSCLC.Results:lncRNA MEG3 expression and CD4+T percentage in pleural effusion in NSCLC group were lower than control group,while Th17 percentage and Th17/CD4+T were higher than control group(P<0.05).lncRNA MEG3 expression and CD4+T percentage in large pleural effusion group were lower than small and moderate pleural effusion groups.lncRNA MEG3 expression and CD4+T percentage in modarate pleural effusion group were lower than small pleural effusion group,while Th17 percentage and Th17/CD4+T in large pleural effusion group were higher than small and moderate pleural effusion groups.Th17/CD4+T was higher in small amount pleural effusion group(P<0.05).lncRNA MEG3 expression and CD4+T percentage in poor prognosis group were lower than those in good prognosis group,while Th17 percentage and Th17/CD4+T were higher than good prognosis group(P<0.05).Logistic regression analysis showed that lncRNA MEG3 was a protective factor for NSCLC pleural effusion,and Th17/CD4+T was a risk factor(P<0.05),lncRNA MEG3 was a protective factor of NSCLC prognosis,and Th17/CD4+T was a risk factor(P<0.05).Conclusion:lncRNA MEG3 expression and Th17/CD4+T in NSCLC patients with different pleural effusion severity and prognosis is not same.lncRNA MEG3 is a risk factor for NSCLC pleural effusion and prognosis,while Th17/CD4+T is a risk factor,which can be used as an effective biomarker for pleural effusion severity and progno-sis diagnosis.

Objective:To explore the application value of intraoperative ultrasound localization in laparoscopic surgery for non extraluminal gastrointestinal stromal tumors.Methods:A retrospective analysis was conducted on the clinical data of 13 patients with non extraluminal gastrointestinal stromal tumors treated with laparoscopic surgery at Zhejiang Provincial People′s Hospital from January 2023 to March 2024. Ultrasound localization was used during the surgery. An analysis was conducted on indicators such as the patient′s surgical approach, surgical duration, intraoperative blood loss, time of first postoperative meal intake, length of hospital stay, and incidence of postoperative complications.Results:Among the 13 patients, there were 7 males and 6 females, and all patients successfully completed the surgery. The operation time was (71.54±19.51)minutes, the intraoperative blood loss was (20.0±16.8)ml, the first postoperative feeding time was (3.08±1.38)days, and the postoperative hospitalization time was (6.92±2.69)days. All 13 patients did not undergo conversion to open surgery during the operation, and the operation was smooth. There was no major bleeding or iatrogenic injury during the operation. There was no bleeding, abdominal infection, anastomotic fistula, anastomotic stenosis, etc. after the operation. There were no unplanned cases of reoperation, and all recovered well and were discharged smoothly. There were no discomfort symptoms during the 3-month follow-up after the operation.Conclusions:Intraoperative ultrasound can accurately locate tumors in laparoscopic non cavity growth gastrointestinal stromal tumor surgery, which is beneficial for the smooth progress of the surgery and the formulation of surgical strategies, and has obvious safety and reliability.