Fucoidan(FUC)is a natural seaweed-derived drug.Previously,our experiments have shown that FUC can significantly inhibit the cell viability of human osteosarcoma 143B cells and induce cell death,but the mechanism remains unclear.Ferroptosis,a novel form of cell death,has emerged as an important target for tumor therapy.This study aims to investigate whether FUC induces ferroptosis of 143B cells and elucidate its underlying molecular mechanisms.CCK-8 and LDH assays result showed that FUC(10,100,400 μg/mL)significantly reduced cell viability of 143B cells and induced cell death.Calce-in-AM staining,FeRhoNox-1 staining,and C11 BODIPY 581/591 staining indicated that FUC obviously increased the levels of labile iron pool(LIP),Fe2+,and lipid reactive oxygen species(Lip ROS)in 143B cells.Chemical colorimetric analysis revealed that FUC markedly decreased intracellular Glutathi-one(GSH)contents.Real-time quantitative PCR showed that FUC dramatically reduced the mRNA lev-els of ferroptosis-related factors solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),while increasing the mRNA levels of prostaglandin endoperoxide synthase 2(PTGS2)and acyl-CoA synthetase long-chain family member 4(ACSL4).Western blotting analysis demonstrated that FUC significantly reduced the protein levels of SLC7A11 and GPX4,and the ratios of p-PI3K/PI3K,p-AktSer473/Akt,and p-AktThr308/Akt,but increased the protein level of ACSL4.Immunofluorescence staining showed that FUC obviously inhibited the nuclear translocation of p-AktSer473.The ferroptosis in-hibitor ferrostatin-1(Fer-1)and iron chelator deferoxamine(DFO)remarkably suppressed cell death in-duced by FUC in 143B cells.Additionally,the PI3K/Akt pathway activator 740Y-P significantly inhibi-ted FUC-induced iron overload and lipid peroxidation in 143B cells,and restored the protein levels of SLC7A11 and GPX4.In conclusion,FUC can induce ferroptosis of 143B cells by inhibiting the PI3K/Akt signaling pathway,which may be a potential target for the prevention and treatment of osteosarcoma.

Objective:To observe the intervention effect of personalized nutrition program combined with rehabilitation training in stroke rehabilitation patients.Methods:86 stroke rehabilitation patients who were admitted to our hospital from January 2023 to June 2024 were prospectively selected,they were divided into control group and study group according to the random number table method,with 43 cases in each group,the control group received rehabilitation training,while the study group received personalized nutrition program combine with rehabilitation training.Simple Fugl Meyer motor function(FMA)score,immune function indicators[immunoglobulin(Ig)A,IgG,complement C3,IgM,complement C4],National Institutes of Health Stroke Scale(NIHSS),nutritional status indicators[albumin(ALB),prealbumin(PA),total protein(TP),hemoglobin(HB)],Stroke Specific Quality of Life Scale(SS-QOL),Barthel Index(BI)score were compared between the two groups.Results:NIHSS score in the study group at 8 weeks after intervention was lower than that in the control group,and SS-QOL score,BI score,FMA score,IgM,IgA,IgG,complement C3,complement C4,ALB,HB,TP and PA were higher than those in the control group(P＜0.05).Conclusion:Personalized nutrition program combined with rehabilitation training in stroke rehabilitation patients,can reduce neurological damage,improve limb motor function,enhance nutritional status,immunity,and quality of life.

Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

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

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

A 52-year-old male patient with recurrent Hodgkin′s lymphoma was treated with a combination therapy of gemcitabine, oxaliplatin, and sintilimab for 6 cycles, and sintilimab monotherapy for 15 cycles. Because of disease progression, the therapy was switched to decitabine (10 mg intravenous infusion on day 1-5) and penpulimab (200 mg intravenous infusion on day 8), with 21 days as one cycle. On the 5th day after the last administration of the 10th cycle, the patient experienced discomfort such as headache and poor appetite; on the 7th day, he suddenly developed unconscious and faint. The patient had a body temperature of 38.1 ℃ and mild yellowish skin and mucous membranes throughout the body. Laboratory tests showed platelet count 9×10 9/L, red blood cell count 4.1×10 12/L, hemoglobin 113 g/L, prothrombin time 15.6 s, blood creatinine 101.6 μmol/L, total bilirubin 61.1 μmol/L, and creatine kinase isoenzyme 43 U/L. Based on laboratory and imaging examinations, immune checkpoint inhibitors causing acquired thrombotic thrombocytopenic purpura was considered. The patient underwent 3 times of plasma exchanges, and received intravenous infusion of methylprednisolone 80 mg once daily and other symptomatic treatments for 5 days. The patient′s yellowish skin and mucous membranes throughout the body disappeared. The glucocorticoid was decreased gradually. Two months later, the patient′s laboratory test indicators such as platelet count and total bilirubin returned to normal.

A 20-year-old male patient with T-lymphoblastic lymphoma/leukemia received 9/10 human leukocyte antigen-compatible unrelated peripheral blood stem cell transplantation. He was transplanted with 5.91×10 8 mononuclear cells/kg and 2.88×10 6 CD34 + cells/kg, and neutrophil engraftment was obtained at +11 days and platelet engraftment at +9 days. After transplantation, he presented with repeatedly increased serum creatinine levels, BK virus (BKV) -associated hemorrhagic cystitis, and BKV viremia. BK virus nephropathy was diagnosed based on renal biopsy and metagenomic next-generation sequencing. After adjusting the immunosuppressant, intravenous immunoglobulin, and donor lymphocyte infusion treatment, the patient’s renal function deteriorated progressively, and he eventually died of multiple organ failure at +289 days.

Objective:To discusses the feasibility and clinical efficacy of the chimeric musculocutaneous flap pedicled with a superior gluteal artery perforator (SGAP) in treatment of Grade Ⅳ pressure sore around ischial tuberosity.Methods:A retrospective case study was conducted on 8 patients with Grade Ⅳ pressure sores around ischial tuberosity and treated in the Department of Plastic Surgery and Burns, the Affiliated Hospital of Zunyi Medical University from May 2019 to June 2023. The patients included 5 males and 3 females, aged 66.8 (40-78) years. All patients had paraplegia for 2 months to 10 years (mean, 59.2 months) and were complicated with hypoproteinemia. Two of the patients were also with sepsis. History of the Grade Ⅳ pressure sore was up to 1 month to 3.5 years (mean, 19.3 months). The sores were located on the right hip in 5 patients and left hip in 3 patients. The tissue defects of the pressure sore measured at 5 cm×5 cm to 6 cm×9 cm in size and all extended to the ischial tuberosity. Chimeric musculocutaneous flaps pedicled with a SGAP were used in the treatment of defect. The flap size ranged from 4 cm×8 cm to 7 cm×15 cm, and the muscular flap were at 8 cm×4 cm×2 cm to 14 cm×7 cm×5 cm in size. The muscular flaps were used to fill the cavities formed by the ulcer, while the flaps were used to cover the wounds. Donor and recipient site were sutured directly. The postoperative follow-ups were conducted at outpatient clinic and via telephone and WeChat interviews, and focused on evaluations of flap survival, complications, flap appearance and the recurrence of ulcer.Results:All the 8 flaps survived. All patients were included in the 3 to 16 months of postoperative follow-up, with 11.8 months in average. One flap had a partial edge split due to excessive pressure during negative pressure drainage, and healed after debridement and re-suture. Otherwise, the rest of 7 patients had primary healing at both the donor and recipient sites. All flaps had good appearance without ulceration, infection or recurrence of pressure sore.Conclusion:The chimeric musculocutaneous flap pedicled with SGAP offers a reliable blood supply, flexible rotation and sufficient tissue volume. It can be used to effectively reconstruct Grade Ⅳ pressure sore around ischial tuberosity with a reliable clinical effect.

Objective:To investigate the surgical technique and clinical outcomes of the tri-lobed chain medial plantar perforator flaps for reconstruction of soft tissue defects in palmar hand.Methods:A retrospective analysis was conducted on 6 patients (4 males and 2 females; aged 21-63 years with mean age of 39.2 years) who had soft tissue defects in palmar hands and were reconstructed with tri-lobed chain medial plantar perforator flaps in the Department of Plastic Surgery and Burns, the Affiliated Hospital of Zunyi Medical University between July 2024 and April 2025. All defects were located on palmar aspect of the injured hands. Following admission, debridement, fracture reduction and fixation and tendon repairs were carried out in primary surgery for 5 patients who had traumatic injuries with digital or metacarpal fractures and tendon ruptures, and stage-II surgery for soft tissue reconstruction was conducted at 7-9 days later. The patient with scar contracture received preoperative evaluation then followed by a scar excision and release surgery, prior to a reconstructive surgery for soft tissue defects. Four patients presented with multi-site defects, of whom, 1 patient had proximal phalangeal defects of index and middle fingers and a defect of metacarpophalangeal joint of ring finger, 1 patient had a defect of metacarpophalangeal joint of index finger and defects of proximal phalanges of middle and ring fingers, 1 patient had defects of proximal phalanges of index, middle and little fingers, and 1 patient had defects of proximal phalanges of middle, ring and little fingers. Of the patients with finger defects, the sizes of defect ranged from 2.0 cm ×1.8 cm to 6.0 cm×2.8 cm and the defects were reconstructed with individually harvested tri-lobed chain medial plantar perforator flaps. Two patients had soft tissue defects in palmar hands and they were measured at 6.0 cm×5.5 cm and 6.0 cm×7.0 cm in size. The palmar defects were reconstructed using combined tri-lobed chain flaps with the sizes of individual lobulated flap ranging from 2.1 cm×1.9 cm to 6.0 cm×2.9 cm. All foot donor sites were primarily closed with interrupted sutures. Postoperative management included routine anti-inflammatory, anticoagulant and antispasmodic treatment. Patients were discharged at 8-10 days after surgery and the postoperative follow-ups were conducted at outpatient clinic to monitor flap survival, contour, hand function, donor site healing, scar formation and foot function.Results:All flaps survived with primary healing of donor sites. Over the 1 to 9 (mean 6.1) months of postoperative follow-up, all flaps survived well with colour and thickness matching with the surrounding hand skin. At 6 months after surgery, two-point discrimination (TPD) of flaps achieved to 8-11 (mean 8.6) mm. According to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, 4 patients achieved function recovery of fingers in excellent and 2 in good. Donor sites exhibited linear scars without painful scarring or paraesthesia, with normal ankle function and gaits.Conclusion:Tri-lobed medial plantar perforator flaps can be used to reconstruct soft tissue defects in palmar hand with primary and direct closure of the flap donor sites. They can simultaneously reconstruct multiple or a large defects, and provide satisfactory aesthetic and functional outcomes. It is a feasible surgical option.

In this report, the protective effect and molecular mechanism of Chaihu Shugan San-containing serum on corticosterone(CORT)-induced mitochondrial damage in pheochromocytoma(PC12) cells was studied based on CORT-induced rat PC12 cell model. The cultured cells were divided into five groups: blank control group, CORT group(400 μmol·L~(-1) CORT), Chaihu Shugan San-containing serum group(400 μmol·L~(-1) CORT + 10% Chaihu Shugan San-containing serum), control serum group(400 μmol·L~(-1) CORT + 10% control serum), and fluoxetine group(400 μmol·L~(-1) CORT + 10% fluoxetine-containing serum). The study was carried out by cell activity detection, mitochondrial morphology observation, membrane potential measurement, energy metabolism analysis, and mitochondrial dynamics-related protein detection. The results showed that CORT treatment significantly reduced the survival rate of PC12 cells, altered mitochondrial morphology, and decreased mitochondrial membrane potential and adenosine triphosphate(ATP) synthetic rate. Both Chaihu Shugan San-and fluoxetine-containing serum significantly increased the survival rate of CORT-treated PC12 cells and the ATP synthetic rate in the mitochondria. Unlike fluoxetine, Chaihu Shugan San-containing serum significantly inhibited the decrease in mitochondrial membrane potential caused by CORT and increased the oxygen consumption rate(OCR) values of both mitochondrial maximum respiration and reserve respiration capacity. Western blot analysis showed that CORT induced upregulated protein expressions of dynamin-related protein 1(Drp1) and peroxisome proliferator-activated receptor gamma co-activator 1α(PGC-1α) in PC12 cells and specific protein expression of optic atrophy protein 1(OPA1), yet it repressed the protein expressions of silent information regulator 1(SIRT1) and mitochondrial fusion protein 1(Mfn1) in PC12 cells. Both Chaihu Shugan San-and fluoxetine-containing serum significantly inhibited the protein expression of Drp1. However, only Chaihu Shugan San-containing serum could significantly inhibit the CORT-induced upregulation protein of PGC-1α. RESULTS:: herein suggest that Chaihu Shugan San-containing serum can alleviate CORT-induced damage in PC12 cells, which may be related to the mitochondrial fragmentation/lipid peroxidation protection by Drp1 inhibition, as well as mitochondrial dynamics and energy metabolism mediated by PGC-1α/SIRT1 signaling pathway.
Animals ; PC12 Cells ; Rats ; Mitochondrial Dynamics/drug effects* ; Mitochondria/metabolism* ; Corticosterone/adverse effects* ; Membrane Potential, Mitochondrial/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Protective Agents/pharmacology* ; Cell Survival/drug effects*