OBJECTIVES: To investigate the effects of dihydroartemisinin (DHA) combined with doxorubicin (DOX) on proliferation and apoptosis of triple-negative breast cancer cells and explore the underlying molecular mechanism. METHODS: MDA-MB-231 cells were treated with 50, 100 or 150 μmol/L DHA, 0.5 μmol/L DOX, or with 50 μmol/L DHA combined with 0.5 μmol/L DOX. The changes in proliferation and survival of the treated cells were examined with MTT assay and colony-forming assay, and cell apoptosis was analyzed with flow cytometry. Western blotting was performed to detect the changes in protein expression levels of PCNA, cleaved PARP, Bcl-2, Bax, STAT3, p-STAT3, HIF-1α and survivin. RESULTS: The IC₅₀ of DHA was 131.37±29.87 μmol/L in MDA-MB-231 cells. The cells with the combined treatment with DHA and DOX showed significant suppression of cell proliferation. Treatment with DHA alone induced apoptosis of MDA-MB-231 cells in a dose-dependent manner, but the combined treatment produced a much stronger apoptosis-inducing effect than both DHA and DOX alone. DHA at 150 μmol/L significantly inhibited clone formation of MDA-MB-231 cells, markedly reduced cellular expression levels of PCNA, p-STAT3, HIF-1α and survivin proteins, and obviously increased the expression level of cleaved PARP protein and the Bax/Bcl-2 ratio, and the combined treatment further reduced the expression level of p-STAT3 protein and increased the Bax/Bcl-2 ratio. CONCLUSIONS DHA combined with DOX produces significantly enhanced effects for inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 cells possibly as result of DHA-mediated negative regulation of the STAT3/HIF-1α pathway.
Humans ; STAT3 Transcription Factor/metabolism* ; Apoptosis/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Doxorubicin/pharmacology* ; Triple Negative Breast Neoplasms/metabolism* ; Cell Line, Tumor ; Artemisinins/pharmacology* ; Female ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Survivin

BACKGROUND: The combination of immune checkpoint inhibitors and chemotherapy (ICI + Chemo) shows promise in treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), but some patients received limited benefit and the prognostic factors of the treatments remain unclear. Furthermore, ICIs efficacy in subsequent treatments needs further evaluation. METHODS: A systematic search on PubMed, Embase, the Cochrane Library, and major conference proceedings was conducted to identify relevant studies for meta-analysis. The study was designed to compare ICI + Chemo with chemotherapy in first-line treatment and identify efficacy predictors, and to evaluate ICIs alone in subsequent-line treatment for RM-NPC, with a focus on progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (AEs). RESULTS: Fifteen trials involving 1928 patients were included. Three trials compared ICI + Chemo with chemotherapy as a first-line treatment, while 12 trials evaluated ICIs alone in subsequent-line treatment of RM-NPC patients. First-line ICI + Chemo showed superior PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.43-0.63; P <0.001) and ORR (risk ratio [RR] = 1.14, 95% CI, 1.05-1.24; P <0.001) compared to chemotherapy, without increased AEs (RR = 1.01, 95% CI, 0.99-1.03; P = 0.481). Neither programmed death-ligand 1 (PD-L1) nor other factors predicted the efficacy of ICI + Chemo vs . chemotherapy. Subsequent-line ICIs alone had a median PFS of 4.12 months (95% CI, 2.93-5.31 months), an ORR of 24% (95% CI, 20-28%), with grade 1-5/grade 3-5 AEs at 79%/14%. However, ICIs alone were associated with significantly shorter PFS (HR = 1.31, 95% CI, 1.01-1.68; P = 0.040) than chemotherapy alone. CONCLUSIONS ICI + Chemo confers superior survival benefits compared to chemotherapy in first-line RM-NPC treatment, independent of PD-L1 expression or other factors. However, ICIs alone demonstrate a manageable safety profile but do not surpass chemotherapy in efficacy for subsequent-line treatment.
Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Nasopharyngeal Carcinoma/drug therapy* ; Nasopharyngeal Neoplasms/drug therapy* ; Neoplasm Recurrence, Local/drug therapy*

Objective:To explore the technical points and precautions of using bilateral free posteromedial thigh flap to reconstruct bilateral breasts.Methods:A retrospective analysis was conducted on the clinical data of patients who underwent bilateral mastectomy and bilateral free posteromedial thigh flap transplantation for bilateral breast reconstruction at Hunan Cancer Hospital from June 2020 to January 2023. The operation was carried out simultaneously by two groups of doctors. Breast surgeons performed modified radical mastectomy for breast cancer or subcutaneous mastectomy. The flap group prepared bilateral free posteromedial thigh flaps. The posteromedial thigh flaps were designed in three patterns: transverse, vertical and oblique. The intrathoracal vessels were used as recipient vessels in all cases. There were two types of vascular anastomosis method: ① For flaps with single vascular pedicle, the artery was anastomosed with the proximal end of the internal thoracic artery, and the only accompanying vein was anastomosed with the proximal end of the internal thoracic vein, or the two accompanying veins were anastomosed with the proximal and distal ends of the internal thoracic vein; ② For flaps with dual vascular pedicles, arteries were anastomosed with the proximal and distal ends of the internal thoracic artery, and the accompanying veins on both sides communicated with the proximal and distal ends of the internal thoracic vein, respectively. Normal distribution measurement data were expressed as Mean±SD.Results:A total of 9 female patients were enrolled, aged 29 to 43 years, with an average age of 38.3 years. Among them, bilateral breast cancer was considered in 4 cases, unilateral breast cancer with multiple nodules in the opposite breast was in 3 cases, and bilateral multiple nodules along with high-risk of developing breast cancer suggested by gene testing were found in 2 cases. Modified radical mastectomy for breast cancer and nipple-sparing subcutaneous mastectomy were performed in 7 and 11 breasts, respectively. There were three design method for the posteromedial thigh flap: horizontal design (6 thighs); vertical design (6 thighs); diagonal design (6 thighs). A total of 18 posteromedial thigh flaps were raised. Four different types of posteromedial thigh flaps were used: gracilis muscle flap (6 thighs); great adductor muscle perforator flap (5 thighs); great adductor muscle flap (5 thighs); femoral gracilis flap+ adductor magnus flap (2 thighs). The skin flaps harvested were (18.9±0.6) cm in length, (7.2±0.4) cm in width and (4.2±0.3) cm in thickness. The average weight of the skin flaps were 235 grams (185-355 grams). The aforementioned vascular anastomosis method ① and ② were carried out in 15 and 3 breasts, respectively. The patients were followed up for 6 to 32 months, with an average of 17.3 months. All skin flaps survived, and the reconstructed breasts presented with good appearance, good elasticity, and no skin flap contraction or deformation occurred; scarring on the donor area was linear and mild; there was no significant impact on lower limb movement. The breast shape was satisfactory, and there was no recurrence of breast cancer.Conclusion:The application of bilateral free posteromedial thigh flap transplantation for reconstruction of bilateral breasts has flexible flap preparation and vascular anastomosis forms, which can achieve satisfactory result of bilateral symmetry.

Objective To observe the value of transabdominal bowel ultrasound for monitoring therapeutic efficacy of vedolizumab in patients with moderate-to-severe ulcerative colitis.Methods Totally 47 ulcerative colitis patients with Mayo endoscopic score(MES)≥2 and treated with vedolizumab were retrospectively included.Transabdominal bowel ultrasound examinations were performed at baseline,at the end of induction therapy,also 3 and 6 months after maintenance therapy,while colonoscopy was performed at baseline and 6 months after maintenance therapy.According to colonoscopy results 6 months after maintenance therapy,the patients were divided into improved group(MES≤1 or MES reduction≥1,n=25)and non-improved group(n=22),and ultrasonic findings of sigmoid colon were compared between and within groups.Results At baseline,no significant difference of ultrasonic findings of sigmoid colon was observed between groups(all P＞0.05),whereas differences of bowel wall thickness at the end of induction therapy,of Limberg grade and abnormal perienteric lymph nodes 3 months after maintenance therapy,as well as bowel wall stratification 6 months after maintenance therapy were noticed between groups(all P＜0.05).Within improved group,compared with those in baseline,bowel wall thickness improved at all time points after the beginning of treatment,Limberg grade improved 3 and 6 months after maintenance therapy,while bowel wall stratification,abnormal perienteric lymph node and perienteric fat edema improved 6 months after maintenance therapy(all P＜0.05).Meanwhile,no significant change of ultrasonic findings of sigmoid colon was observed in non-improved group during the above periods(all P＞0.05).Conclusion Transabdominal bowel ultrasound could be used to accurately monitor the therapeutic efficacy of vedolizumab in patients with moderate-to-severe ulcerative colitis.

In drug clinical trials,the protection of subjects'privacy should take precedence over scientific exploration and societal benefits.This paper compared the differences in legal systems for the protection of subjects'privacy in China and abroad by employing methods such as literature review,case analysis,and comparison of domestic and foreign situations.It also elucidated the current ethical challenges faced by the protection of subjects'privacy,which primarily included imperfect laws and regulations,insufficient protection awareness among relevant personnel,risks of privacy breaches in critical links,and increased difficulty in data confidentiality under emerging technologies.From the perspective of responsible innovation,specific paths were proposed to protect subjects'privacy by using the four-dimensional structure of"prediction-reflection-negotiation-feedback,"maintaining a balance between ethical principles and technological innovation,ensuring the ethical and compliant nature of drug clinical trials,and thus better contributing to the cause of human health.

Objective: To explore the cross sectional and longitudinal associations between 24 hour movement behaviors and physical fitness in preschool children, and to adopt the method of equal time substitution analysis to evaluate the impact of time redistribution of different activity behaviors on physical fitness scores,so as to provide a scientific basis for promoting the health of preschool children. Methods: A total of 193 preschool children aged 3-6 years were selected from three Shanghai districts (Jing an, Baoshan, Jiading) from October to December 2023 by the stratified cluster random sampling method. The 24 hour movement behaviors were monitored via 7 day accelerometry, and physical fitness was measured according to the National Physical Fitness Measurement Standards (Revised 2023, preschool section). From October to December 2024, the follow up of physical fitness among preschool children used the same testing method. The comparison between groups was conducted by t-test. Compositional regression analyses evaluated the relationship of 24 hour movement behaviors and physical fitness among preschool children. Results: At baseline, moderate to vigorous physical activity (MVPA) time was significantly higher in boys [(84.10±25.78)min/d] than in girls [( 70.44± 25.98)min/d]; the composite physical fitness score was significantly higher in boys (71.65±8.69) than in girls (68.84±9.89), and the differences were statistically significant ( t =3.65, 2.10, both P <0.01). After adjusting for gender, age and body mass index, the results of component multiple linear regression analysis showed that MVPA time proportion was positively correlated with the composite physical fitness score at baseline among preschool children ( β =6.61), but was negatively correlated with two legged continuous hopping time at 1 year ( β =-1.12) (both P <0.05). Light physical activity (LPA) time proportion was negatively correlated with walking on the balance beam time at 1 year ( β =-4.44), and sedentary behavior (SB) time proportion was negatively correlated with the composite score of physical fitness at baseline ( β =-6.55) (both P <0.05). Isotemporal substitution analysis revealed that replacing 10 minutes of sleep (SP), SB, and LPA with MVPA increased the baseline physical fitness composite score by 0.750, 0.689 and 0.575 units, respectively; at 1 year follow up, the composite score increased by 1.440, 1.419 and 1.430 units, respectively (all P <0.05). Conversely, replacing MVPA with 10 minutes of SP, SB, and LPA,resulted in decreases in baseline physical fitness composite scores of 0.836, 0.777 and 0.669 units, and reductions of 1.613, 1.592 and 1.598 units at 1 year follow up (all P < 0.05 ). Conclusions Preschool children s 24 hour movement behaviors, especially MVPA, are closely related to physical health. Implementing appropriate strategies to increase physical activity and reduce sedentary time may improve the physical fitness of preschoolers.

Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

Objective To explore the influencing factors of liver fibrosis in patients with metabolic dysfunction-associated fatty liver disease(MAFLD)complicated with chronic hepatitis B(CHB),and to find clinically convenient predictive parameters for assessing liver fibrosis risk.Methods A retrospective analysis was conducted on 221 cases of MAFLD with CHB diagnosed and treated at the Second Hospital of Lanzhou University between January 2015 and August 2022.Patients were divided into low-risk(FIB-4<1.30,n=84),medium-risk(1.30≤FIB-4≤2.67,n=94)and high-risk(FIB-4>2.67,n=43)liver fibrosis groups based on the Fibrosis-4(FIB-4)index.General clinical data,laboratory indicators and composite indicators were compared among the three groups.Variables were screened using forward stepwise regression,and binary logistic regression analysis was performed to determine independent predictors of liver fibrosis.A prediction model was constructed and evaluated using receiver operating characteristic(ROC)curve analysis.Results Age,AST and Triglyceride-glucose index(TyG)were independent risk factors for liver fibrosis in patients with MAFLD combined with CHB,while platelet-to-lymphocyte ratio(PLR)was an independent protective factor(all P<0.05).ROC curve analysis showed that the area under the curve(AUC)for age,AST,TyG,PLR,age-AST and AST-TyG in predicting liver fibrosis were 0.668,0.764,0.680,0.738,0.856 and 0.805,respectively.At the optimal cut-off values,the sensitivities were 86.0%,67.4%,93.0%,62.8%,86.0%and 79.1%,and the specificities were 43.3%,82.0%,51.7%,86.0%,71.3%and 70.2%.Conclusion Age,AST,TyG and PLR are influencing factors of liver fibrosis in MAFLD combined with CHB patients.The parameters established based on these factors may predict the risk of liver fibrosis,and combined prediction can improve predictive efficacy.

Objective To assess the clinical value of a novel surgical technique—Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in the resection of anterior mediastinal masses. Methods Patients who underwent tubeless subxiphoid uniportal video-assisted thoracoscopic surgery via balance-shaped sternal elevation device in anterior mediastinal masses process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to April 2025 were included, and their clinical data were analyzed. Results A total of 4 patients were included, with 2 males and 2 females, aged 58-75 years. The diameter of the tumor was 2.5-3.0 cm. The operation time was 60.0-150.0 min, intraoperative blood loss was 5-10 mL, pain score on the 3rd day after surgery was 0 points, and postoperative hospital stay was 2-3 days. All patients achieved complete resection of the masses and thymus without perioperative complications. Conclusion The tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device technique optimizes surgical visualization and instrument maneuverability while avoiding complications related to conventional anesthesia and tubing, thereby markedly enhancing the minimally invasive profile of anterior mediastinal masses resections. In addition to maintaining procedural safety, this approach effectively reduces postoperative pain and accelerates patient recovery, highlighting its potential for widespread clinical adoption.

Objective To investigate the effects of adiponectin(APN)on the proliferation,migration,and invasion of ovarian cancer cells and its potential association with the phosphatidylinositol 3-kinase(PI3K)/pro-tein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.Methods A2780 and SK-OV3 cell lines were selected.AdipoR1 mRNA expression was detected by real-time polymerase chain reaction(RT-PCR).The CCK-8 assay was employed to evaluate APN-induced proliferation,while scratch wound heal-ing and Transwell assays were conducted to assess migration and invasion capabilities.Western blot analysis was performed to measure the expression levels of PI3K,Akt,mTOR,and their phosphorylated forms(p-Akt,p-mTOR)at different time points(0-60 min)after APN treatment and across intervention groups(APN,LY294002,APN+LY294002).Results Both A2780 and SKOV3 cells expressed AdipoR1 mRNA.Compared with the control group,APN significantly enhanced the proliferation,migration,and invasion of o-varian cancer cells(P＜0.05).Under the stimulation of APN,the expression levels of p-Akt and p-mTOR in A2780 and SKOV3 cells showed a significant upward trend.The peak expression of p-Akt and p-mTOR in A2780 cells was observed at 30 minutes,while in SKOV3 cells,it occurred at 60 minutes.The expression lev-els of p-Akt and p-mTOR were significantly reduced in the LY294002 group and APN+LY294002 group(P＜0.001).Conclusion APN enhances the proliferation,migration,and invasion behavior of ovarian cancer cells by activating the PI3K/Akt/mTOR signaling pathway,and its effect can be reversed by PI3K inhibitors,providing a theoretical basis for targeted intervention in ovarian cancer progression.