ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， the combination of serum pharmacochemistry， response profile of absorbed components in serum， network pharmacology and drug-likeness prediction was used to screen the potential active ingredients of Yanghetang against breast cancer. MethodsUPLC-Q-TOF-MS/MS was used to identify the main components in different solvent extracts of Yanghetang， and serum pharmacochemistry was applied to analyze the absorbed components from the serum of female SD rats after 0.5， 1， 2 h of administration. Combined with the response characteristic values of serum drug components obtained from UNIFI 1.8.2， the absorbed prototype components and metabolites were screened to get the absorbed components of Yanghetang with a significant patterns of elimination and growth. Network pharmacology was applied to construct a drug-component-pathway-target-disease network， and molecular docking was performed between absorbed components and key targets of breast cancer， and the drug similarity was analyzed by SwissADME. ResultsForty-two compounds were identified in Yanghetang samples extracted with different solvents， of which 16 compounds were common to the three different extraction solvents（methanol， 50% methanol and water）. The results of drug-containing serum analysis showed that there were 16 absorbed components in serum， including 5 prototypes and 11 metabolites. Network pharmacology results showed that Yanghetang against breast cancer involved 15 key targets such as proto-oncogene tyrosine-protein kinase Src（SRC）， epidermal growth factor receptor（EGFR） and phosphoinositide 3 kinase catalytic alpha polypeptide（PIK3CA）. Molecular docking results showed that 16 potential active ingredients were well combined with the predicted targets. Combined with drug likenesses， 12 compounds in the absorbed components of Yanghetang were considered to have potential for anti-breast cancer activity， mainly including α-pinene and γ-eudesmol and their metabolites， of which one was from Ephedrae Herba， one was from Rehmanniae Radix， and eight were from Cinnamomi Cortex. ConclusionThe chemical components of Yanghetang mainly include polysaccharides， monoterpene glycosides and coumarins， and its prototype components mainly undergo oxidation， hydrolysis and acetylation after entering the blood. Its anti-breast cancer mechanism may be related to the regulation of signaling pathways such as the mitogen-activated protein kinase（MAPK） and phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）. The results of this study can lay a foundation for further exploration of Yanghetang in the treatment of breast cancer.

BACKGROUND:Fixed-point rotation manipulation of cervical spine is a mechanical operation with high technical requirements,but the biomechanics of fixed-point manipulation of cervical spine still lacks relevant quantitative data.Moreover,the research on the influencing factors of cervical fixed-point rotation manipulation includes many parameters and there are differences,so it is necessary to further analyze its influencing factors to improve its related data. OBJECTIVE:To quantify the biomechanical parameters of cervical spine fixed-point rotation manipulation,explore the correlation between different biomechanical parameters,and the influence of individual characteristics of the subjects on the biomechanical parameters of cervical spine fixed-point rotation manipulation. METHODS:Totally 35 cases of cervical spondylosis were Outpatients from Orthopedic Department of Renai Branch of the First Affiliated Hospital of Guangxi University of Chinese Medicine and selected as the subjects investigated.Wearable mechanical measuring gloves were used to collect biomechanical parameters of cervical spine fixed-point rotation manipulation,including:thumb preload,thumb maximum thrust,palm preload,palm wrench force,and palm wrench maximum force.Personal characteristic parameters were collected,including age,height,weight,and neck circumference.The key biomechanical parameters in the process of cervical spine fixed-point rotation manipulation were analyzed and different individual characteristics were quantified.The results of biomechanical parameters were analyzed using Spearman correlation analysis.The possible effects of different individual characteristic parameters on biomechanics were analyzed. RESULTS AND CONCLUSION:(1)Compared with bilateral mechanical parameters,there was no significant difference between left manipulation and right manipulation(P>0.05).(2)The average of thumb preload force was(7.21±1.19)N;the average of thumb maximum thrust was(28.40±4.48)N;the average of palm preload was(5.67±2.49)N;the average of palm wrench force was(10.90±5.11)N,and the average of palm wrench maximum force was(16.00±7.27)N.(3)There was a significant positive correlation between palm preload and palm wrench force(Rs=0.812,P<0.01).There was a significant positive correlation between palm preload and palm wrench maximum force(Rs=0.773,P<0.01).There was a significant positive correlation between palm wrench force and palm wrench maximum force(Rs=0.939,P<0.01).(4)The weight was positively correlated with thumb preload,palm preload,palm wrench force and palm wrench maximum force(P<0.05).(5)These findings confirm that there is a certain biomechanical standard value in the operation of cervical spine fixed-point rotation manipulation to treat cervical spondylosis.There is no significant difference between the left and right manipulations,which indicates that the manipulation has good consistency and repeatability.There is consistency and coordination among palm preload force,palm wrench force,and palm wrench maximum force.Their contributions to the therapeutic effect are similar.Body weight is an important factor affecting cervical spine fixed-point rotation manipulation.

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

To investigate the effect of isthmin-1 (ISM1) on the invasion and metastasis of pancreatic cancer and its underlying mechanism, this study analyzed the expression of ISM1 in pancreatic cancer patients and normal pancreatic tissues using The Cancer Genome Atlas (TCGA) database. Western blot was employed to detect differences in ISM1 protein expression between pancreatic cancer cell lines (Aspc1, Bxpc3, PANC1, SW1990) and the pancreatic epithelial cell line (hPNE). Cell models with stable ISM1 overexpression and knockdown were constructed, and changes in cell migration and invasion capabilities were assessed via Transwell invasion assays and wound healing assays. Meanwhile, Western blot was used to detect the expression levels of key markers of epithelial-mesenchymal transition (EMT). Furthermore, TCGA and the Gene Expression Omnibus (GEO) database were utilized to analyze pathways regulated downstream of ISM1 and the mechanisms promoting pancreatic cancer invasion and metastasis. Immunoprecipitation combined with mass spectrometry (IP-MS) was used to screen for vimentin as an ISM1-binding protein, and the interaction between ISM1 and vimentin was verified by immunofluorescence and co-immunoprecipitation (Co-IP). Bxpc3 cells overexpressing ISM1 were treated with the protein synthesis inhibitor cycloheximide (CHX) to detect vimentin protein stability. The results indicate that ISM1 promotes the EMT process by inhibiting vimentin degradation, thereby enhancing the invasion and metastasis of pancreatic cancer. This study provides new experimental evidence for elucidating the mechanism of pancreatic cancer metastasis.

Minimal access breast surgery with the assistance of an endoscopy or robot has been an important advancement in surgical treatment in recent years. Compared to conventional open surgery, minimal access breast surgery only requires small incisions in concealed areas such as axillary fossa, avoiding visible scars on the surface of the breast, significantly improving the postoperative aesthetic appearance and patient satisfaction. With the rapid development of minimal access breast surgery, several institutions have established their own distinctive techniques. The concept of membrane anatomy in the breast, for example, has led to more natural-looking breast reconstruction following endoscopic procedures. The adoption of the reverse space dissection technique has greatly optimized the workflow of endoscopic breast cancer resection. Intraoperative navigation system for endoscopic breast-conserving surgery could allow precise localization of excision margins. Furthermore, the widespread use of the cold dissection technique for flap separation has reduced surgical duration and minimized flap damage. The emergence of unique techniques in the field of minimal access breast surgery promises to further advance and promote the adoption of minimal access breast surgery in China.

Objective:To examine the postoperative prosthesis-related complications, short-term surgical outcomes and patient satisfaction with breast reconstruction between patients who underwent endoscopic assisted versus conventional nipple sparing mastectomy and immediate prothesis breast reconstruction.Methods:This study was a retrospective cohort study. A retrospective analysis was performed on clinical data of 104 women with breast cancer who received nipple sparing mastectomy and immediate prothesis breast reconstruction from August 2021 to August 2022 at the Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. They were divided into two groups according to the surgical approach. A total of 53 patients, aged (43.3±9.9) years (range: 25 to 66 years), underwent endoscopic nipple sparing mastectomy (E-NSM group) and immediate prothesis breast reconstruction. The other 51 patients aged (39.9±7.8) years (range: 25 to 54 years) underwent conventional open surgery (C-NSM group). Short-term surgical outcomes including operation time, postoperative hospital stay, postoperative blood loss, and postoperative drainage volume in 2 days were recorded. Patient satisfaction with breast reconstruction was compared using the Wilcoxon rank sum test. Postoperative prothesis-related complications were investigated to determine the experience to deal with them.Results:No postoperative prosthesis-related infection, prosthesis loss, or necrosis of the nipple-areola complex occurred in the E-NSM group, while 1 patient suffered from hematoma, whose wound was skinned with resuture after disinfection. Five patients in the C-NSM group had prosthesis-related infection, 2 of them received prosthesis removal surgery combined with sufficient antimicrobial agent, another one underwent surgery for subcutaneous placement of the drain, as well as antimicrobial agent therapy, and the rest of them healed up only with antimicrobial agent therapy. All recovered well after treatment. One patient recovered from necrosis of the nipple-areola complex through periodic iodophor disinfection and dressing which ended in improvement of necrotic areas, another patient who had hematoma accepted the same treatment mentioned above and also healed. All the patients mentioned above are now in stable conditions. Patients in the E-NSM group had higher satisfaction with the cosmetic results of the breast prosthesis implant than those in the C-NSM group ( Z=-4.511, P<0.01). Conclusions:Both surgical approaches were proven to be safe and effective with a low rate of postoperative prosthesis-related complications. Patients in the E-NSM group were more satisfied with the cosmetic results of breast reconstruction than those in the C-NSM group.

Minimal access breast surgery with the assistance of an endoscopy or robot has been an important advancement in surgical treatment in recent years. Compared to conventional open surgery, minimal access breast surgery only requires small incisions in concealed areas such as axillary fossa, avoiding visible scars on the surface of the breast, significantly improving the postoperative aesthetic appearance and patient satisfaction. With the rapid development of minimal access breast surgery, several institutions have established their own distinctive techniques. The concept of membrane anatomy in the breast, for example, has led to more natural-looking breast reconstruction following endoscopic procedures. The adoption of the reverse space dissection technique has greatly optimized the workflow of endoscopic breast cancer resection. Intraoperative navigation system for endoscopic breast-conserving surgery could allow precise localization of excision margins. Furthermore, the widespread use of the cold dissection technique for flap separation has reduced surgical duration and minimized flap damage. The emergence of unique techniques in the field of minimal access breast surgery promises to further advance and promote the adoption of minimal access breast surgery in China.

Objective:To examine the postoperative prosthesis-related complications, short-term surgical outcomes and patient satisfaction with breast reconstruction between patients who underwent endoscopic assisted versus conventional nipple sparing mastectomy and immediate prothesis breast reconstruction.Methods:This study was a retrospective cohort study. A retrospective analysis was performed on clinical data of 104 women with breast cancer who received nipple sparing mastectomy and immediate prothesis breast reconstruction from August 2021 to August 2022 at the Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. They were divided into two groups according to the surgical approach. A total of 53 patients, aged (43.3±9.9) years (range: 25 to 66 years), underwent endoscopic nipple sparing mastectomy (E-NSM group) and immediate prothesis breast reconstruction. The other 51 patients aged (39.9±7.8) years (range: 25 to 54 years) underwent conventional open surgery (C-NSM group). Short-term surgical outcomes including operation time, postoperative hospital stay, postoperative blood loss, and postoperative drainage volume in 2 days were recorded. Patient satisfaction with breast reconstruction was compared using the Wilcoxon rank sum test. Postoperative prothesis-related complications were investigated to determine the experience to deal with them.Results:No postoperative prosthesis-related infection, prosthesis loss, or necrosis of the nipple-areola complex occurred in the E-NSM group, while 1 patient suffered from hematoma, whose wound was skinned with resuture after disinfection. Five patients in the C-NSM group had prosthesis-related infection, 2 of them received prosthesis removal surgery combined with sufficient antimicrobial agent, another one underwent surgery for subcutaneous placement of the drain, as well as antimicrobial agent therapy, and the rest of them healed up only with antimicrobial agent therapy. All recovered well after treatment. One patient recovered from necrosis of the nipple-areola complex through periodic iodophor disinfection and dressing which ended in improvement of necrotic areas, another patient who had hematoma accepted the same treatment mentioned above and also healed. All the patients mentioned above are now in stable conditions. Patients in the E-NSM group had higher satisfaction with the cosmetic results of the breast prosthesis implant than those in the C-NSM group ( Z=-4.511, P<0.01). Conclusions:Both surgical approaches were proven to be safe and effective with a low rate of postoperative prosthesis-related complications. Patients in the E-NSM group were more satisfied with the cosmetic results of breast reconstruction than those in the C-NSM group.

Objective: To compare the long-term clinical and radiographic outcomes of transforaminal endoscopic lumbar discectomy (TELD) versus microdiscectomy (MD). Methods: The data of 154 patients with lumbar disc herniation (LDH) who underwent TELD (n = 89) or MD (n = 65) were retrospectively analyzed. The patients’ clinical outcomes were evaluated using visual analogue scales for leg and low back pain, the Japanese Orthopaedic Association (JOA) score, and the Oswestry Disability Index (ODI). The evolution of radiographic manifestations was observed during follow-up. Potential risk factors for a poor clinical outcome were investigated. Results: During a mean follow-up of 5.5 years (range, 5–7 years), the recurrence rate was 4.49% in the TELD group and 1.54% in the MD group. All scores significantly improved from preoperatively to postoperatively in both groups (p < 0.01). The improvement in the ODI and JOA scores was significantly greater in the TELD than MD group (p < 0.05). Forty-seven patients (52.8%) in the TELD group and 32 (49.2%) in the MD group had Modic changes before surgery, most of which showed no changes at the last follow-up. The degeneration grades of 292 discs (71.0%) were unchanged at the last follow-up, while 86 (20.9%) showed improvement, mostly at the upper adjacent segment. No significant difference was observed in the intervertebral height index or paraspinal muscle-disc ratio. Conclusion Both TELD and MD provide generally satisfactory long-term clinical outcomes for patients with LDH. TELD can be used as a reliable alternative to MD with less surgical trauma. Modic type II changes, decreased preoperative intervertebral height, and a high body mass index are predictors of a poor prognosis.