1.Study on the apoptosis-inducing effect of esculetin on acute myeloid leukemia HL-60 cells via regulating the AKT/SKP2/MTH1 pathway
Weihua SONG ; Fuying CHU ; Wei XIE ; Jinliang CHEN ; Ping ZHAO ; Hong QIU ; Jian TAO ; Xiang CHEN
China Pharmacy 2026;37(1):36-41
OBJECTIVE To investigate the apoptosis-inducing effect of esculetin (Esc) on acute myeloid leukemia (AML) HL-60 cells by regulating the protein kinase B (AKT)/S-phase kinase-associated protein 2 (SKP2)/MutT homolog 1 (MTH1) pathway. METHODS AML HL-60 cells were randomly divided into control group (routine culture), Esc low-concentration group (L-Esc group, 25 μmol/L Esc), Esc medium-concentration group (M-Esc group, 50 μmol/L Esc), Esc high-concentration group (H-Esc group, 100 μmol/L Esc), and high-concentration of Esc+ SC79 (AKT agonist) group (100 μmol/L Esc+5 μmol/L SC79). Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species (ROS) in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3], AKT/SKP2/MTH1 pathway-related proteins (p-AKT, AKT, SKP2, MTH1), along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase (PI3K), cyclin-dependent kinase inhibitor 1 (P21) and cyclin-dependent kinase inhibitor 1B (P27). RESULTS Compared with control group, the cell viability, colony number, and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2, MTH1 and Bcl-2 were significantly decreased (P<0.05), while ROS level, apoptosis rate, and the expression levels of Bax, cleaved caspase-3, P21 and P27 proteins were significantly increased (P<0.05). Moreover, the effects of Esc exhibited concentration-dependence (P<0.05). Compared with H-Esc group, above indexes of high-concentration of Esc+ SC79 group were reversed significantly (P<0.05). CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway, thus inhibiting the proliferation of HL-60 cells.
2.Efficacy analysis of robotic versus laparoscopic-assisted right hemicolectomy
Bang LIU ; Peiyao WANG ; Zhaoxiong ZHANG ; Daohan WANG ; Wenxin ZHANG ; Pengyu CHEN ; Hengbin ZHAO ; Yongjia YAN ; Weihua FU
Chinese Journal of Digestive Surgery 2025;24(4):521-527
Objective:To investigate the short-term efficacy of robotic versus laparoscopic-assisted right hemicolectomy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 99 patients of right colon cancer who were admitted to Tianjin Medical University General Hospital from January 2020 to December 2023 were collected. There were 50 males and 49 females, aged 69(range, 26?89)years. Of the 99 patients, 41 patients undergoing robotic-assisted right hemicolectomy were divided into the robotic group, and 58 patients undergoing laparoscopic-assisted right hemicolectomy were divided into the lapa-roscopic group. Patients received robotic-assisted or laparoscopic-assisted right hemicolectomy operated by the same major surgeon. Observation indicators:(1) propensity score matching status and com-parison of clinical data of patients between the two groups after matching; (2) intraoperative and postoperative conditions.Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶1 nearest neighbor matching method. The caliper value was set as 0.1. Results:(1) Propensity score matching status and comparison of clinical data of patients between the two groups after matching. Of the 99 patients, 82 patients were successfully matched, with 41 cases in each of the robotic group and the laparoscopic group. After propensity score matching, the elimination of history of abdominal operation confounding bias ensured comparability. (2) Intraoperative and postoperative conditions. After propensity score matching, the operation time of the robotic group was 215(range, 130?340)minutes, the volume of intraoperative blood loss was 50(range, 10?400)mL, the number of lymph node dissected was 21(range, 5?55), the number of intensive care unit stay was 15, time to postoperative first flatus was 3(range, 1?12)days, time to postoperative first food intake was 4(range, 2?14)days, duration of postoperative hospital stay was 8(range, 5?25)days. The above indicators of the laparoscopic group were 210(range, 140?370)minutes, 50(range, 5?150)mL, 19(range, 5?34),20, 3(range, 0?9)days, 5(range, 2?10)days, 8(range, 6?17)days, respectively. There was no significant difference in the above indicators between patients of the two groups ( Z=?0.94, ?1.87, ?1.32, χ2=1.25, Z=0.13, ?0.83, ?0.65, P>0.05). There was no patient converted to open operation in the robotic group, versus 1 patient converted to open operation in the laparoscopic group, showing no significant difference between patients of the two groups ( P>0.05). There were 6 cases in the robotic group and 4 cases in the laparoscopic group with complications, showing no significant difference between the two groups ( χ2=0.46, P>0.05). Both groups of patients achieved R 0 resection and had no readmission 30 days after surgery. The hospital expense was (11.0±1.8)×10 4 yuan of the robotic group, versus (9.0±1.7)×10 4 yuan of the laparoscopic group, showing a significant difference between the two groups ( t=?5.27, P<0.05). Conclusion:Robot-assisted right hemicolectomy is non inferior to laparoscopic-assisted right hemicolectomy in safety and efficacy, but with higher hospitalization costs.
3.Mechanism of telomerase inhibitor BIBR1532 combined with autophagy inhibitor CQ in suppressing survival of melanoma cells
Weihua GONG ; Lan CHEN ; Kun ZHAO ; Zhui KE ; Qing XU ; Xianling GUO
China Oncology 2025;35(5):431-439
Background and purpose:Melanoma is a highly invasive malignant tumor originating from melanocytes,which poses a great threat to human life and health around the world,and its morbidity and mortality have been rising continuously in recent years.Telomerase and autophagy play crucial roles in cell proliferation,survival and stress response.Telomerase maintains the replication ability of cells by prolonging telomeres at the ends of chromosomes,and autophagy,as a self-degradation mechanism of cells,can not only help cells remove damaged components to promote survival,but also induce cell death under certain conditions.In the tumor environment,they are often abnormally activated or out of balance,and participate in the occurrence and development of many cancers,including melanoma.This study investigated the roles of telomerase and autophagy in melanoma progression and evaluated the potential synergistic therapeutic effects of combined application of telomerase inhibitor BIBR1532 and autophagy inhibitor chloroquine(CQ)in melanoma treatment.Methods:Malignant melanoma cells A375 were treated with telomerase inhibitor BIBR1532.The cell viability was assessed using the cell counting kit-8(CCK-8)assay,and the cell apoptosis was detected using the Annexin Ⅴ/propidium iodide(PI)double staining method.Additionally,the expressions of autophagy-related proteins LC3-Ⅱand p62 were detected by Western blot,and the changes in autophagy flux were observed using dual-tagged adenovirus transfection technology.Based on these studies,BIBR1532 and the autophagy inhibitor CQ were further applied in combination to analyze cell proliferation,apoptotic rate,changes in mitochondrial membrane potential,and cell cycle distribution,and the cloning formation experiment was used to verify the cell's proliferative capacity,thereby comprehensively evaluating the efficacy of this combined treatment strategy.Results:Telomerase inhibitor BIBR1532 at a concentration of 50 μmol/L significantly inhibited the growth of malignant melanoma cells A375 and induced apoptosis.At the same concentration,BIBR1532 upregulated the expression of the autophagy-related protein LC3-Ⅱ in A375 cells,while downregulating the expression of p62 protein.By transducing A375 cells with a dual-tagged adenovirus,it was observed that autophagy flux was significantly enhanced after treatment with BIBR1532.Furthermore,the combined application of BIBR1532(50 μmol/L)and the autophagy inhibitor CQ(20 μmol/L)significantly promoted the death of A375 cells,induced apoptosis and destruction of mitochondrial membrane potential,caused cell cycle arrest at the G2/M phase,and significantly inhibited the cell's clonogenic ability.Conclusion:Telomerase inhibitor BIBR1532 not only inhibits the proliferation of malignant melanoma cells but also activates the autophagy process in these cells,and inhibition of the autophagy response by autophagy inhibitor CQ can enhance the sensitivity of malignant melanoma cells to telomerase inhibitor BIBR1532.
4.Establishment and practice of scientific research project-based experimental system—exploration of"5+3"integration Medical Immunology experimental teaching
Haiying FU ; Yanling WANG ; Hongyan YUAN ; Dongmei YAN ; Weihua NI ; Yan QI ; Dong LI ; Xia CHEN ; Wei YANG
Chinese Journal of Immunology 2025;41(1):195-197,201
Theory and technology of Medical Immunology are widely used in scientific research.Our teaching and research group uses experimental teaching of Medical Immunology as a platform to carry out practice of scientific research project-based experi-mental system among"5+3"integration students.By completing a mini-project research including experimental design-experimental operation-research article writing,students cultivated scientific research thinking and exercised scientific research practice ability,and generally reported that the course is very difficult,but after completing it,it is very rewarding.
5.Clinical characteristics and treatment strategies for thyroid carcinoma combined with cervical vagus nerve schwannoma
Weihua JIAN ; Zhen CHEN ; Jianhua FENG ; Wensong CAI ; Bo XU
Chinese Journal of Endocrine Surgery 2025;19(4):547-551
Objective:To investigate the diagnostic and surgical strategies in managing patients with coexisting thyroid carcinoma and cervical vagal schwannoma.Methods:We retrospectively analyzed three cases treated at Guangzhou First People’s Hospital between Jun. 2019 and Dec. 2024.Results:All patients presented with neck masses or thyroid nodules. Ultrasonography identified suspicious malignant thyroid nodules and lateral neck lesions—interpreted as metastatic lymphadenopathy in two cases and as a possible nerve sheath tumor in one. Fine-needle aspiration cytology (FNAC) of thyroid nodules yielded Bethesda VI results in all cases. FNAC of the lateral neck lesions revealed no evidence of malignancy in all cases; in one case, a core needle biopsy confirmed a vagal schwannoma. Two patients underwent MRI, which supported the diagnosis of vagal schwannoma. Surgical management included single-stage resection in two patients and staged surgery in one. Postoperative histopathology confirmed papillary thyroid carcinoma and schwannoma in all cases. Transient postoperative hoarseness occurred in two patients, with recovery within 3-6 months.Conclusions:When thyroid carcinoma is complicated by cervical vagal schwannoma, the schwannoma may be misdiagnosed as metastatic cervical lymph nodes, potentially leading to iatrogenic vagus nerve injury during neck dissection. Although cervical vagal schwannoma can be diagnosed preoperatively, simultaneous surgical treatment of both conditions may increase the risk of vocal cord paralysis, and in severe cases, result in airway compromise. Therefore, comprehensive preoperative evaluation is important. It is recommended to classify cases based on the anatomical locations of the thyroid carcinoma and vagal schwannoma to guide surgical planning, and to use intraoperative nerve monitoring to enhance surgical safety and avoid serious complications.
6.Efficacy analysis of robotic versus laparoscopic-assisted right hemicolectomy
Bang LIU ; Peiyao WANG ; Zhaoxiong ZHANG ; Daohan WANG ; Wenxin ZHANG ; Pengyu CHEN ; Hengbin ZHAO ; Yongjia YAN ; Weihua FU
Chinese Journal of Digestive Surgery 2025;24(4):521-527
Objective:To investigate the short-term efficacy of robotic versus laparoscopic-assisted right hemicolectomy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 99 patients of right colon cancer who were admitted to Tianjin Medical University General Hospital from January 2020 to December 2023 were collected. There were 50 males and 49 females, aged 69(range, 26?89)years. Of the 99 patients, 41 patients undergoing robotic-assisted right hemicolectomy were divided into the robotic group, and 58 patients undergoing laparoscopic-assisted right hemicolectomy were divided into the lapa-roscopic group. Patients received robotic-assisted or laparoscopic-assisted right hemicolectomy operated by the same major surgeon. Observation indicators:(1) propensity score matching status and com-parison of clinical data of patients between the two groups after matching; (2) intraoperative and postoperative conditions.Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶1 nearest neighbor matching method. The caliper value was set as 0.1. Results:(1) Propensity score matching status and comparison of clinical data of patients between the two groups after matching. Of the 99 patients, 82 patients were successfully matched, with 41 cases in each of the robotic group and the laparoscopic group. After propensity score matching, the elimination of history of abdominal operation confounding bias ensured comparability. (2) Intraoperative and postoperative conditions. After propensity score matching, the operation time of the robotic group was 215(range, 130?340)minutes, the volume of intraoperative blood loss was 50(range, 10?400)mL, the number of lymph node dissected was 21(range, 5?55), the number of intensive care unit stay was 15, time to postoperative first flatus was 3(range, 1?12)days, time to postoperative first food intake was 4(range, 2?14)days, duration of postoperative hospital stay was 8(range, 5?25)days. The above indicators of the laparoscopic group were 210(range, 140?370)minutes, 50(range, 5?150)mL, 19(range, 5?34),20, 3(range, 0?9)days, 5(range, 2?10)days, 8(range, 6?17)days, respectively. There was no significant difference in the above indicators between patients of the two groups ( Z=?0.94, ?1.87, ?1.32, χ2=1.25, Z=0.13, ?0.83, ?0.65, P>0.05). There was no patient converted to open operation in the robotic group, versus 1 patient converted to open operation in the laparoscopic group, showing no significant difference between patients of the two groups ( P>0.05). There were 6 cases in the robotic group and 4 cases in the laparoscopic group with complications, showing no significant difference between the two groups ( χ2=0.46, P>0.05). Both groups of patients achieved R 0 resection and had no readmission 30 days after surgery. The hospital expense was (11.0±1.8)×10 4 yuan of the robotic group, versus (9.0±1.7)×10 4 yuan of the laparoscopic group, showing a significant difference between the two groups ( t=?5.27, P<0.05). Conclusion:Robot-assisted right hemicolectomy is non inferior to laparoscopic-assisted right hemicolectomy in safety and efficacy, but with higher hospitalization costs.
7.Clinical characteristics and treatment strategies for thyroid carcinoma combined with cervical vagus nerve schwannoma
Weihua JIAN ; Zhen CHEN ; Jianhua FENG ; Wensong CAI ; Bo XU
Chinese Journal of Endocrine Surgery 2025;19(4):547-551
Objective:To investigate the diagnostic and surgical strategies in managing patients with coexisting thyroid carcinoma and cervical vagal schwannoma.Methods:We retrospectively analyzed three cases treated at Guangzhou First People’s Hospital between Jun. 2019 and Dec. 2024.Results:All patients presented with neck masses or thyroid nodules. Ultrasonography identified suspicious malignant thyroid nodules and lateral neck lesions—interpreted as metastatic lymphadenopathy in two cases and as a possible nerve sheath tumor in one. Fine-needle aspiration cytology (FNAC) of thyroid nodules yielded Bethesda VI results in all cases. FNAC of the lateral neck lesions revealed no evidence of malignancy in all cases; in one case, a core needle biopsy confirmed a vagal schwannoma. Two patients underwent MRI, which supported the diagnosis of vagal schwannoma. Surgical management included single-stage resection in two patients and staged surgery in one. Postoperative histopathology confirmed papillary thyroid carcinoma and schwannoma in all cases. Transient postoperative hoarseness occurred in two patients, with recovery within 3-6 months.Conclusions:When thyroid carcinoma is complicated by cervical vagal schwannoma, the schwannoma may be misdiagnosed as metastatic cervical lymph nodes, potentially leading to iatrogenic vagus nerve injury during neck dissection. Although cervical vagal schwannoma can be diagnosed preoperatively, simultaneous surgical treatment of both conditions may increase the risk of vocal cord paralysis, and in severe cases, result in airway compromise. Therefore, comprehensive preoperative evaluation is important. It is recommended to classify cases based on the anatomical locations of the thyroid carcinoma and vagal schwannoma to guide surgical planning, and to use intraoperative nerve monitoring to enhance surgical safety and avoid serious complications.
8.Clinical outcomes of ultrasonic bone scalpel-assisted laminotomy in the management of thoracic spinal stenosis
Guangshen LI ; Chunmao CHEN ; Weihua ZHU ; Aibing HUANG ; Jian BIAN ; Haijun LI
Chinese Journal of Orthopaedics 2025;45(11):719-727
Objective:This study introduces a novel segmented and layered thoracic laminoplasty technique for the treatment of thoracic spinal stenosis (TSS) caused by ossification of the posterior longitudinal ligament (OPLL) and ligamentum flavum (OLF). The goal is to simplify the surgical procedure, improve safety, reduce iatrogenic injuries, and validate its clinical outcomes through follow-up.Methods:A retrospective analysis was conducted on 23 patients (10 males, 13 females; mean age 58.83±12.01 years) treated at Taizhou People's Hospital Affiliated to Nanjing Medical University from January 2018 to December 2023. Transverse grooves were created at the superior and inferior vertebral pedicle levels, utilizing the intervertebral ligamentum flavum as a segmental demarcation reference. Partial removal of the distal lamina and medial of the inferior articular process was performed through a cortical window. Under direct visualization, complete removal of ossified ligamentum flavum, proximal portion of lamina, superior articular process. The treatment effect was evaluated by clinical symptoms, signs, Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS), imaging results (CT and MRI) and complications before or after surgery.Results:All 23 procedures were successfully completed with a mean operative duration of 180(150, 220) min, the surgical time for 71 segments were 67.5(53.8, 120.0) minutes and intraoperative blood loss of 200(100, 300) ml, demonstrating a low intraoperative dural tear rate of 8.70% (2/23). Postoperative imaging (CT/MRI) confirmed adequate decompression in all cases, with significant symptom improvement at final follow-up 21(9, 39) months: 47% (7/15) of patients achieved marked relief of lower limb numbness, 82% (14/17) showed substantial motor recovery, and 54% (7/13) exhibited improved gait stability. Functional outcomes revealed significant enhancements, with JOA scores increasing from 8(6, 8) preoperatively to 9(8, 10) postoperatively ( P<0.05; 43.80% improvement rate) and VAS scores decreasing from 6(5, 7) to 2(1, 4) ( P<0.05). The complications were two dural tears and one suture reaction. Conclusions:Ultrasonic osteotome-assisted segmented layered laminectomy is a safe, effective, and straightforward technique for treating thoracic spinal stenosis caused by OPLL and OLF. It offers shorter operative times, minimal complications, and significant clinical improvement, making it a promising technique for broader clinical adoption.
9.Advances in the application of machine learning-related combined models in infectious disease prediction
Weihua HU ; Huimin SUN ; Yikun CHANG ; Jinwei CHEN ; Zhicheng DU ; Yongyue WEI ; Yuantao HAO
Chinese Journal of Epidemiology 2025;46(6):1085-1094
When the epidemiology of infectious diseases is more complex, it is often difficult for disease prediction studies based on a single model to capture the multidimensional nature of disease transmission. In recent years, combining different models to improve infectious disease prediction has gradually become a research trend and hotspot. Existing studies have shown that combined models usually have higher prediction performance and better generalization ability. The current combined models mainly combine machine learning and other models, including time-series models, dynamic models, etcetera. In addition, integrated learning that combines diverse machine learning techniques also holds significant importance across various research domains. This paper reviews the progress of applying combined models around machine learning in infectious disease prediction to promote the innovation and practice of combined models for infectious diseases and help to build smarter and more efficient infectious disease early warning and prediction methods and systems.
10.Progress in application of compartment model-related combined models in infectious disease prediction
Weihua HU ; Huimin SUN ; Yikun CHANG ; Jinwei CHEN ; Zhicheng DU ; Yongyue WEI ; Yuantao HAO
Chinese Journal of Epidemiology 2025;46(7):1289-1296
Methods such as compartmental models, agent-based models, time series models, and machine learning can be used for the prediction of infectious disease incidence. When disease epidemics are complex, it is often difficult to use a single model to comprehensively and accurately capture the multi dimensional nature of the disease. Exploring the combined application of different models has gradually become a research trend and hotspot in recent years, and the prediction performance of combined models is often better than that of single ones. Current research related to combined models mainly focus on machine learning or compartmental models. In this review, we focus on the combination of compartmental models and other models, and summarize their combination principles, application progress, and advantages or disadvantages for the purpose of promoting the innovation and application of combined models for infectious disease incidence prediction, and establishing a more intelligent and efficient early warning and prediction method or systems for the prevention and control of infectious disease.

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