1.Prodrug-based combinational nanomedicine remodels lipid metabolism for reinforced ferroptosis and immune activation.
Ling LIN ; Zaixiang FANG ; Guohao LIU ; Yiwei LIU ; Zhiqian LI ; Dayi PAN ; Yunkun LI ; Hemi KANG ; Xiaoding SHEN ; Jingyao ZHANG ; Qiyong GONG ; Kui LUO ; Jing JING
Acta Pharmaceutica Sinica B 2025;15(5):2746-2763
Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8+ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.
2.Application effect of double eyelid plasty with the levator palpebrae superioris aponeurosis fiber flap method
Guohao LI ; Huaiwei LIAO ; Yan SHI ; Yuhan QI ; Huicai WEN
Chinese Journal of Plastic Surgery 2025;41(1):1-7
Objective:To explore the clinical application effect of double eyelid plasty using the levator palpebrae superioris aponeurosis fiber flap.Methods:In March 2021, 3-mm-wide tissue strips were vertically harvested from the mid-upper eyelids from 5 adult Han cadavers with single eyelids, provided by the Anatomy Lab of Nanchang Vocational Health College, and then Masson staining was performed to track the levator aponeurosis fiber. A descriptive case series study was performed. From February 2021 to February 2022, eligible patients who were prospectively collected from the Outpatient Department of the First Affiliated Hospital of Nanchang University underwent double eyelid plasty. The levator palpebrae superioris aponeurosis fiber flap was dissected and repositioned between the orbicularis oculi muscles at the upper and lower edge of incision. The surgical site was closed by a three-layer multi-faceted suture fixation: the muscle of orbicularis oculi at lower edge of incision was sutured to the flap root and tarsal upper edge; the upper and the muscle of orbicularis oculi at the upper and lower edge were sutured to the flap end; the skin was sutured to the muscle of orbicularis oculi and flap end. Postoperatively, incision healing and complications were monitored. Twelve months after surgery, two independent attending plastic surgeons evaluated double eyelid height, curvature, symmetry, and incision scar. The patients were asked to evaluate the effect as satisfied, relatively satisfied, or dissatisfied.Results:Masson staining of 5 lateral upper eyelid specimens revealed that in single-eyelid cases, the levator palpebrae superioris aponeurosis diverged into fibers at the white line, penetrated the orbicularis oculi loosely, and extended to the eyelid margin. Fourty female patients with single or hidden double eyelids were included, aged 18-38 years. After 12 months’ follow-up, all patients had good incision healing without major complications. Twelve months after the operation, the result of doctor evaluation was as followed: 40 cases had proper line height and natural curvature; 38 cases had good line retention, 2 cases had shallower lines; 39 cases had good symmetry, 1 case had asymmetry; 40 cases had no sunken scar. The result of patient satisfaction was as satisfied (35 cases), relatively satisfied (2 cases), dissatisfied (3 cases), with a 92.5% (37/40) satisfaction rate.Conclusion:The levator palpebrae superioris aponeurosis fiber flap method can reconstruct upper eyelid tissue, with natural dynamic double eyelids with few complications and high patient satisfaction.
3.Total 3D laparoscopic ileal ureters replacement for bilateral ureters combined with bladder augmentation in the management of post-radiotherapy bilateral ureteral strictures and contracted bladder
Wanwei HUANG ; Xianshen SHA ; Yibao ZHANG ; Guohao WU ; Feng LUO ; Zhihui CHEN ; Dongming YE ; Xue-song LI ; Caiyong LAI
Journal of Peking University(Health Sciences) 2025;57(4):789-795
Objective:To retrospectively evaluate the clinical efficacy and safety of total 3D laparo-scopic ileal ureters replacement for bilateral ureters combined with bladder augmentation in patients with post-radiotherapy long-segment bilateral ureteral strictures and contracted bladder.Methods:Clinical data of two patients(aged 72 and 54 years)with radiation-induced long-segment bilateral ureteral stric-tures and reduced bladder capacity,treated at the Sixth Affiliated Hospital of Jinan University from Octo-ber 2023 to June 2024,were analyzed.Both presented with bilateral flank pain,recurrent chills/fever,urinary frequency,and urgency.Preoperative ureteral stricture lengths were measured as follows:left 10.4 cm and right 8.7 cm in the first case;left 10.6 cm and right 11.7 cm in the second case.Bladder capacity assessed by nephrostomy-assisted antegrade urography was 90 mL and 130 mL respectively.Both underwent single-position,one-stage totally 3D laparoscopic bilateral ileal ureteral replacement and blad-der augmentation based on membrane anatomy principles,with regular postoperative follow-up.Results:Procedures were completed by the same experienced urologist.Operative times were 420 min and 355 min,with intraoperative blood loss of 50 mL(no transfusion required).Postoperative bowel function re-sumed at the end of 4.5 and 3 days.No major perioperative complications occurred.Ureteral stents were removed at 2 months postoperatively,with imaging showing improved hydronephrosis,unobstructed ure-teral drainage,symmetrical bladder morphology,and smooth walls.Postoperative bladder capacities were 230 mL and 250 mL.Follow-up durations were 10 and 8 months.Both patients experienced significant relief of flank pain and lower urinary tract symptoms.No complications(enteric fistula,urinary fistula,or metabolic acidosis)were observed.At the final follow-up,one patient had mildly elevated serum cre-atinine,while the other showed reduced levels compared with preoperative values;both remained stable.Conclusion:Membrane anatomy-based dissection facilitates safe mobilization of fibrotic ureters with mini-mal bleeding and collateral damage.Total intracorporeal 3D laparoscopic ileal ureters replacement for bi-lateral ureters combined with bladder augmentation effectively addresses long-segment ureteral obstruction and improves bladder capacity.This approach is technically safe and feasible,though further validation with larger clinical cohorts is warranted.
4.Total 3D laparoscopic ileal ureters replacement for bilateral ureters combined with bladder augmentation in the management of post-radiotherapy bilateral ureteral strictures and contracted bladder
Wanwei HUANG ; Xianshen SHA ; Yibao ZHANG ; Guohao WU ; Feng LUO ; Zhihui CHEN ; Dongming YE ; Xue-song LI ; Caiyong LAI
Journal of Peking University(Health Sciences) 2025;57(4):789-795
Objective:To retrospectively evaluate the clinical efficacy and safety of total 3D laparo-scopic ileal ureters replacement for bilateral ureters combined with bladder augmentation in patients with post-radiotherapy long-segment bilateral ureteral strictures and contracted bladder.Methods:Clinical data of two patients(aged 72 and 54 years)with radiation-induced long-segment bilateral ureteral stric-tures and reduced bladder capacity,treated at the Sixth Affiliated Hospital of Jinan University from Octo-ber 2023 to June 2024,were analyzed.Both presented with bilateral flank pain,recurrent chills/fever,urinary frequency,and urgency.Preoperative ureteral stricture lengths were measured as follows:left 10.4 cm and right 8.7 cm in the first case;left 10.6 cm and right 11.7 cm in the second case.Bladder capacity assessed by nephrostomy-assisted antegrade urography was 90 mL and 130 mL respectively.Both underwent single-position,one-stage totally 3D laparoscopic bilateral ileal ureteral replacement and blad-der augmentation based on membrane anatomy principles,with regular postoperative follow-up.Results:Procedures were completed by the same experienced urologist.Operative times were 420 min and 355 min,with intraoperative blood loss of 50 mL(no transfusion required).Postoperative bowel function re-sumed at the end of 4.5 and 3 days.No major perioperative complications occurred.Ureteral stents were removed at 2 months postoperatively,with imaging showing improved hydronephrosis,unobstructed ure-teral drainage,symmetrical bladder morphology,and smooth walls.Postoperative bladder capacities were 230 mL and 250 mL.Follow-up durations were 10 and 8 months.Both patients experienced significant relief of flank pain and lower urinary tract symptoms.No complications(enteric fistula,urinary fistula,or metabolic acidosis)were observed.At the final follow-up,one patient had mildly elevated serum cre-atinine,while the other showed reduced levels compared with preoperative values;both remained stable.Conclusion:Membrane anatomy-based dissection facilitates safe mobilization of fibrotic ureters with mini-mal bleeding and collateral damage.Total intracorporeal 3D laparoscopic ileal ureters replacement for bi-lateral ureters combined with bladder augmentation effectively addresses long-segment ureteral obstruction and improves bladder capacity.This approach is technically safe and feasible,though further validation with larger clinical cohorts is warranted.
5.Application effect of double eyelid plasty with the levator palpebrae superioris aponeurosis fiber flap method
Guohao LI ; Huaiwei LIAO ; Yan SHI ; Yuhan QI ; Huicai WEN
Chinese Journal of Plastic Surgery 2025;41(1):1-7
Objective:To explore the clinical application effect of double eyelid plasty using the levator palpebrae superioris aponeurosis fiber flap.Methods:In March 2021, 3-mm-wide tissue strips were vertically harvested from the mid-upper eyelids from 5 adult Han cadavers with single eyelids, provided by the Anatomy Lab of Nanchang Vocational Health College, and then Masson staining was performed to track the levator aponeurosis fiber. A descriptive case series study was performed. From February 2021 to February 2022, eligible patients who were prospectively collected from the Outpatient Department of the First Affiliated Hospital of Nanchang University underwent double eyelid plasty. The levator palpebrae superioris aponeurosis fiber flap was dissected and repositioned between the orbicularis oculi muscles at the upper and lower edge of incision. The surgical site was closed by a three-layer multi-faceted suture fixation: the muscle of orbicularis oculi at lower edge of incision was sutured to the flap root and tarsal upper edge; the upper and the muscle of orbicularis oculi at the upper and lower edge were sutured to the flap end; the skin was sutured to the muscle of orbicularis oculi and flap end. Postoperatively, incision healing and complications were monitored. Twelve months after surgery, two independent attending plastic surgeons evaluated double eyelid height, curvature, symmetry, and incision scar. The patients were asked to evaluate the effect as satisfied, relatively satisfied, or dissatisfied.Results:Masson staining of 5 lateral upper eyelid specimens revealed that in single-eyelid cases, the levator palpebrae superioris aponeurosis diverged into fibers at the white line, penetrated the orbicularis oculi loosely, and extended to the eyelid margin. Fourty female patients with single or hidden double eyelids were included, aged 18-38 years. After 12 months’ follow-up, all patients had good incision healing without major complications. Twelve months after the operation, the result of doctor evaluation was as followed: 40 cases had proper line height and natural curvature; 38 cases had good line retention, 2 cases had shallower lines; 39 cases had good symmetry, 1 case had asymmetry; 40 cases had no sunken scar. The result of patient satisfaction was as satisfied (35 cases), relatively satisfied (2 cases), dissatisfied (3 cases), with a 92.5% (37/40) satisfaction rate.Conclusion:The levator palpebrae superioris aponeurosis fiber flap method can reconstruct upper eyelid tissue, with natural dynamic double eyelids with few complications and high patient satisfaction.
6.Correlation between serum ischemia modified albumin and calmodulin expression levels and neurological impairment in patients with cerebral small vessel disease
Lianghe DU ; Guohao ZHAO ; Qiaoyan LI
Chinese Journal of Primary Medicine and Pharmacy 2024;31(1):23-28
Objective:To investigate the correlation between serum ischemia modified albumin (IMA) and calmodulin (CaM) expression levels and neurological impairment in patients with cerebral small vessel disease.Methods:The clinical data of 140 patients with cerebral small vessel disease (CSVD) who received treatment at The Third People Hospital in Liaocheng between April 2020 and December 2021 were retrospectively analyzed. On admission, serum levels of CaM and IMA were measured using an enzyme-linked immunosorbent assay and an albumin-cobalt binding test. Patients' neurological function was evaluated using the National Institutes of Health Stroke Scale (NIHSS). Patients' transient cerebral ischemia, urinary incontinence, and gait disturbance were evaluated using the National Institute of Neurological Disorders and Stroke Scale. Patients' cognitive function was evaluated using the Montreal Cognitive Assessment scale. The influential factors of serum IMA and CaM expression levels in patients with CSVD were analyzed. The factors that affect the severity of neuological imairment in patients with CSVD and their correlation with serum IMA and CaM expression levels were analyzed.Results:The gender, age, presence or absence of gait disorders, and presence or absence of urinary incontinence of patients were not correlated with serum IMA and CaM levels (all P > 0.05). The serum levels of IMA [(38.5 ± 5.3) × 103U/L, (38.5 ± 4.7) × 103U/L, (39.0 ± 4.4) × 103U/L] and CaM [(190.4 ± 34.5) μg/L, (191.2 ± 26.7) μg/L, (199.7 ± 24.8) μg/L] in patients with cognitive impairment, dizziness and vertigo, and transient cerebral ischemia were significantly higher than those in patients with normal cognitive function, patients without dizziness and vertigo, or patients without transient cerebral ischemia [(27.3 ± 4.4) × 103U/L, (21.0 ± 3.8) × 103U/L, (20.5 ± 5.1) × 103U/L, (180.6 ± 29.6) μg/L, (179.5 ± 28.6) μg/L, (168.6 ± 32.4) μg/L, t = 14.10, 24.36, 22.50, all P < 0.05]. There were significant differences in cognitive impairment (38/16/9), dizziness and vertigo (39/16/8), transient cerebral hemorrhage (35/16/9), NIHSS score [(3.6 ± 0.8) points, (7.5 ± 0.9) points, (16.2 ± 3.2) points], CaM levels [(125.3 ± 20.5) μg/L, (185.5 ± 23.6) μg/L, (237.9 ± 54.3) μg/L], and IMA levels [(21.2 ± 3.5)] × 103 U/L, [(38.5 ± 4.3) × 103 U/L, (74.9 ± 5.4) × 103 U/L] among patients with mild, moderate, and severe neurological impairment ( t = 32.87, 11.28, 12.42, 34.59, 151.73, 147.84, all P < 0.05). The results of multivariate analysis indicated that cognitive impairment ( OR = 1.578, 95% CI: 1.043-2.386), transient cerebral ischemia ( OR = 2.396, 95% CI: 1.156-4.969), dizziness and vertigo ( OR = 1.906, 95% CI: 1.086-3.345), NIHSS score ( OR = 2.171, 95% CI: 1.162-4.056), CaM level ( OR = 2.022, 95% CI: 1.268-3.224), and increased IMA levels ( OR = 2.090, 95% CI: 1.313-3.325) were independent influential factors for worsened neurological impairment (all P < 0.05). The serum levels of IMA and CaM in patients with CSVD were significantly positively correlated with the severity of neurological impairment ( r = 5.45, 8.33, both P < 0.05). Conclusion:The elevated serum levels of IMA and CaM in patients with CSVD serve as independent risk factors for neurological impairment, and these levels are positively correlated with the severity of neurological impairment.
7.LncRNA MAGI2-AS3 enhances cisplatin sensitivity of non-small cell lung cancer cells by regulating the miR-1269a/PTEN/AKT pathway
Xirui FAN ; Zhilin QI ; Yuanjie DENG ; Zihan YANG ; Li SUN ; Guohao LI ; Juanjuan LIANG ; Fei WU ; Liwen YUAN
Journal of Southern Medical University 2024;44(10):2033-2043
Objective To investigate the mechanism mediating the regulatory effect of lncRNA MAGI2-AS3 on cisplatin(DDP)resistance in non-small cell lung cancer(NSCLC).Methods MAGI2-AS3 and miR-1269a expression levels were detected by qRT-PCR in DDP-sensitive lung cancer cell lines(A549 and H1299)and their resistant counterparts(A549/DDP and H1299/DDP).In A549 and H1299 cells with MAGI2-AS3 silencing and A549/DDP and H1299/DDP cells overexpressing MAGI2-AS3,the effects of 20 μmol/L DDP on cell viability and apoptosis were examined with CCK-8 assay,colony formation assay,flow cytometry and Western blotting,and the changes in epithelial-mesenchymal transition(EMT)were assessed with wound healing and Transwell assays.The interaction between MAGI2-AS3,miR-1269a and PTEN was predicted using GEPIA,StarBase and miRDB and verified with luciferase reporter gene assay and radioimmunoprecipitation(RIP)assay.A miR-1269a mimic and pcDNA3.1-PTEN plasmid were used to perform the rescue assay.Results MAGI2-AS3 expression was significantly downregulated in lung cancer tissues(P<0.05)in association with a poor prognosis(P<0.05).In the two DDP-resistant lung cancer cell lines,MAGI2-AS3 expression was significantly lowered as compared with the sensitive cells.Silencing MAGI2-AS3 significantly enhanced cell viability and promoted EMT of A549 and H1299 cells irrespective of DDP treatment,and also decreased DDP-induced apoptosis of the cells.In A549/DDP and H1299/DDP cells,MAGI2-AS3 overexpression strongly repressed cell viability and EMT irrespective of DDP treatment and promoted DDP-induced cell apoptosis.Luciferase reporter gene and RIP assays confirmed the binding of MAGI2-AS3 with miR-1269a and the binding of miR-1269a with 3'-UTR domain of PTEN.The rescue assay demonstrated that MAGI2-AS3 acted as a sponge for miR-1269a to promote PTEN expression and downregulate AKT phosphorylation,thus inhibiting EMT and promoting DDP-induced apoptosis of A549/DDP cells.Conclusion MAGI2-AS3 enhances DDP sensitivity of NSCLC by targeted regulation of the miR-1269a/PTEN/AKT signaling axis.
8.Combining robot-assisted gait training with task-oriented training can improve the walking ability of children with dyskinetic cerebral palsy
Huachun XIONG ; Suya YUAN ; Ning XIAO ; Yang LI ; Guohao TANG ; Huiling ZHAO ; Huanhuan FENG ; Wenbin MENG ; Jing LU
Chinese Journal of Physical Medicine and Rehabilitation 2024;46(9):806-811
Objective:To observe the effect of combining robot-assisted gait training (RAGT) with task-oriented training (TOT) on the walking ability of children with dyskinetic cerebral palsy (DCP).Methods:Sixty DCP children were randomly divided into a conventional intervention group, an RAGT group, and a combined intervention group, each of 20. All of the children received conventional rehabilitation therapy, while the RAGT and combined intervention groups were additionally provided with RAGT, and RAGT combined with TOT, respectively. Before the experiment and after 12 and 24 weeks of treatment, the subjects′ walking ability was evaluated using the 10-metre walk test (10MWT), and the D energy zone (standing position) and the E energy zone (walking, running and jumping) of the Gross Motor Function Measurement-88 (GMFM-88) instrument.Results:After 12 and 24 weeks of treatment, the average 10MWT speed and D and E energy zone scores of all three groups had improved significantly. After 24 weeks the combined group′s averages on all three measures were significantly better than those of the other two groups.Conclusion:RAGT combined with TOT and conventional rehabilitation training significantly improves the walking ability of DCP children.
9.Prognostic factors for glioblastoma:a retrospective single-center analysis of 176 adults
Guohao HUANG ; Yongyong CAO ; Lin YANG ; Zuoxin ZHANG ; Yan XIANG ; Yuchun PEI ; Yao LI ; Wei CHEN ; Shengqing LYU
Journal of Army Medical University 2024;46(17):2002-2008
Objective To explore the clinical features,treatment and prognosis of glioblastomas(GBM)in adults.Methods A retrospective cohort study was performed on 176 adult GBM patients admitted to our department from January 2015 to December 2021.Chi-square test was used to investigate the clinical differences between isocitrate dehydrogenase(IDH)mutant and wild-type GBM.Kaplan-Meier and Log-Rank tests were employed to plot survival curve and compute the survival analysis.Multivariate Cox regression model was applied to identify the independent prognostic factors.Results IDH wild-type GBM account for 89.2%and had significantly differences from the IDH-mutant GBM in terms of age of onset,Karnofsky(KPS)score at admission,symptoms of neurological deficit,and methylation status of O6-methylguanine-DNA-methyltransferase(MGMT)promoter(P<0.05).For the IDH wild-type GBM patients receiving conventional therapy,univariate Cox hazard analysis showed gross total resection,methylation of MGMT promoter,initiation of radiation within the 5th to 6th week after surgery,and adjuvant temozolomide(TMZ)chemotherapy ≥6 cycles were favorable prognostic factors for overall survival(OS);GBMs in the left hemisphere,involvement of single lobe,methylation of MGMT promoter,and initiation of radiation within the 5th to 6th week after surgery were favorable prognostic factors for progression free survival(PFS)(all P<0.05).Moreover,multivariate Cox hazard regression analysis indicated that methylation of MGMT promoter,and initiation of radiation within the 5th to 6th week after surgery,and adjuvant TMZ chemotherapy ≥6 cycles were independent protective factors for OS,and GBMs in the left hemisphere,involvement of single lobe and methylation of MGMT promoter were independent protective factors for PFS in the GBM patients(all P<0.05).Conclusion The clinical and prognostic features are totally different between IDH mutant and wild-type GBM,and molecular detections are needed for the further pathological classification.Methylation of MGMT promoter is a primary marker of favorite prognosis for IDH wild-type GBM,and slightly delay in radiotherapy(the 5th to 6th week after surgery)can effectively improve the survival prognosis of IDH wild-type GBM.
10.Two-sample Mendelian randomization analysis of the causal relationship between blood eosinophils and allergic rhinitis
Xinlong LI ; Guohao DENG ; Na LIN ; Guolin TAN ; Honghui LIU
Journal of Central South University(Medical Sciences) 2024;49(5):705-711
Objective:Previous studies have revealed a correlation between eosinophils and allergic rhinitis,but the causal relationship has not been fully confirmed.This study aims to evaluate the causal link between blood eosinophils and allergic rhinitis using the Mendelian randomization(MR)method. Methods:Summary data from the Genome-Wide Association Study Catalog(GWAS)for eosinophil count(exposure variable)and allergic rhinitis(outcome variable)were collected.GWAS data for the exposure variable were obtained from the IEU Open GWAS Project developed by the Integrative Epidemiology Unit at the University of Bristol,while data for the outcome variable were sourced from the FinnGen Biobank(Finland)database.The causal relationship between eosinophils and allergic rhinitis was analyzed using the two-sample MR method with inverse variance weighted(IVW)analysis.Sensitivity analyses were conducted using the weighted median method,MR-Egger regression,leave-one-out analysis,and funnel plots. Results:An increase in blood eosinophil count showed a potential causal relationship with an increased risk of allergic rhinitis(OR=1.187,95%CI 1.051 to 1.341,P=0.006).This finding was consistent across the weighted median method and MR-Egger regression.Leave-one-out analysis indicated that no single nucleotide polymorphism significantly influenced the causal inference. Conclusion:There is a causal association between increased eosinophil count and a higher risk or worsening of allergic rhinitis.

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