Cancer represents a major worldwide disease burden marked by escalating incidence and mortality. While therapeutic advances persist, developing safer and precisely targeted modalities remains imperative. Nanomedicines emerges as a transformative paradigm leveraging distinctive physicochemical properties to achieve tumor-specific drug delivery, controlled release, and tumor microenvironment modulation. By synergizing passive enhanced permeation and retention effect-driven accumulation and active ligand-mediated targeting, nanoplatforms enhance pharmacokinetics, promote tumor microenvironment enrichment, and improve cellular internalization while mitigating systemic toxicity. Despite revolutionizing cancer therapy through enhanced treatment efficacy and reduced adverse effects, translational challenges persist in manufacturing scalability, longterm biosafety, and cost-efficiency. This review systematically analyzes cutting-edge nanoplatforms, including polymeric, lipidic, biomimetic, albumin-based, peptide engineered, DNA origami, and inorganic nanocarriers, while evaluating their strategic advantages and technical limitations across three therapeutic domains: immunotherapy, chemotherapy, and radiotherapy. By assessing structure-function correlations and clinical translation barriers, this work establishes mechanistic and translational references to advance oncological nanomedicine development.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Nanoparticles/chemistry* ; Animals ; Nanomedicine/methods* ; Drug Delivery Systems/methods* ; Drug Carriers/chemistry* ; Radiotherapy/methods*

Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as ¹³¹I,¹⁷⁷Lu, or ¹⁸F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, ¹⁸F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).

Objective To investigate the role of lipopolysaccharide(LPS)in regulating the inflammatory response of neutrophil through the leucine-rich α-2 glycoprotein 1(LRG1)/Rho-associated protein kinase(ROCK1)signaling.Methods HL-60 cells were treated with 1 μmol/L all-trans retinoic acid(ATRA)and 12.5 μL/mL dimethyl sulfoxide(DMSO)for 72 h and 96 h,and the morphological changes were observed by Wright-Giemsa staining.The expression of CD11b was detected by flow cytometry.LPS induced the activation of dHL-60 and human peripheral blood neutrophils.The transcription and secretion levels of LRG1,ROCK1 and inflammatory cytokines were detected by qPCR and ELISA,respectively.The expression levels of LRG1 and ROCK1 after the activation of dHL-60 were detected by Western blotting.Furthermore,dHL-60 was treated with the recombinant protein LRG1 and ROCK1 inhibitor Y-27632;the transcription levels of inflammatory cytokines were detected by qPCR.Results Neutrophils were activated by LPS.The expression levels of LRG1 and ROCK1 were significantly increased,and the transcription levels of inflammatory cytokines were significantly increased.The recombinant protein LRG1 activated dHL-60 in vitro,and the transcription levels of ROCK1 and inflammatory cytokines were significantly increased.Using the ROCK1 inhibitor Y-27632,the production levels of inflammatory cytokines were significantly reduced.Conclusion LPS can regulate the production levels of neutrophil inflammatory cytokines through activating the LRG1/ROCK1 signaling,thus exacerbating the inflammatory response.

ObjectiveTo investigate the effect of modified Weijingtang on the pyroptosis of RAW264.7 macrophages via the cysteinyl aspartate-specific protease-1 （Caspase-1）/gasdermin D （GSDMD） pathway. MethodLipopolysaccharide （LPS） was used to induce pyroptosis of RAW264.7 cells. The blank group was treated with the blank serum， and the intervention groups were treated with the sera containing different doses of modified Weijingtang. After 24 h， the viability of cells in different groups was examined by the cell counting kit-8 （CCK-8）. The pyroptosis and morphology of cells in each group were observed by a scanning electron microscope and a phase-contrast microscope， respectively. The mRNA and protein levels of nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）， Caspase-1， and GSDMD in each group were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The levels of interleukin （IL）-18 and IL-1β in each group were measured by enzyme-linked immunosorbent assay. ResultUnder the electron microscope， RAW264.7 cells presented the best morphology and structure in the blank group and obvious pyroptosis and leakage of cell contents in the model （LPS） group. Compared with the model group， the intervention groups showed reduced pyroptosis to varying degrees， and the high-dose group had the closest cell morphology and structure to the blank group. Under the optical microscope， RAW264.7 cells were spherical in the blank group and irregular with protrusions in the model group. Compared with the model group， the intervention groups showed improved cell morphology， and the cell morphology in the group with the dose of 20% was the closest to that in the blank group. The mRNA and protein levels of NLRP3， Caspase-1， and GSDMD in the model group were higher than those in the blank group （P<0.05）. Compared with the model group， each intervention group showed down-regulated expression of the above indicators （P<0.05）. Compared with the blank group， the model group presented elevated levels of IL-18 and IL-1β （P<0.05）， which were lowered in the intervention （10%， 20%） groups （P<0.01）. ConclusionModified Weijingtang inhibits the pyroptosis of macrophages by down-regulating the Caspase-1/GSDMD pathway and reducing the release of proinflammatory cytokines.

Objective:To investigate the effects of long non-coding RNA (lncRNA) Gm13568 on the activation of A1 astrocytes and the progress of experimental autoimmune encephalomyelitis (EAE) in mice.Methods:A recombinant lentiviral vector (LV-Inhibit-Gm13568) carrying astrocyte-specific promoter of glial fibrillary acidic protein (GFAP) was established to inhibit the function of endogenous Gm13568. A control vector (LV-ctrl) was established as well. The recombinant vectors were packaged. C57BL/6 mice were injected with 1×10 7 transforming units of viral suspension via the tail vein and 7 d after the injection, myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55) was used to establish the mouse model of EAE. Four groups, PBS group, EAE group, LV-ctrl+ EAE group and LV-Inhibit-Gm13568+ EAE group, were included in this study. Clinical signs of the mice were monitored daily in a double-blinded manner. The mice were sacrificed 23 d after the EAE model was established and the spinal cord tissues were collected. The expression of Serping 1, C3, Srgn and H2-T23 at mRNA level was detected by real-time PCR. Changes in the expression of IL-6, TNF-α, macrophage chemotactic protein-1 (MCP-1) and interferon-inducible protein-10 (IP-10) were measured. Western blot was used to investigate the expression of GFAP and Notch1 in spinal cord tissues and the phosphorylation of signal transduction and transcription activator 3 (STAT3). The expression of Notch1 intracellular domain (NICD) and GFAP in spinal cord tissues was detected by immunofluorescence. Furthermore, the infiltration of inflammatory cells and the demyelination of spinal cord were observed using HE and Luxol fast blue (LFB) staining methods. Results:Compared with PBS group, A1 astrocytes were activated and Notch1 expression was significantly up-regulated in EAE group and LV-ctrl+ EAE group. The clinical score of mice in LV-Inhibit-Gm13568+ EAE group was decreased from an average score of 3.5 to less than 1 on 23 d after antigen induction and the clinical symptoms were alleviated as compared with the mice in LV-ctrl+ EAE group. Meanwhile, the activation of A1 astrocytes was down-regulated, and the production of inflammatory cytokines and chemokines was also reduced. The expression of Notch1, GFAP and NICD at protein level and the phosphorylation of STAT3 were significantly reduced. Moreover, the infiltration of inflammatory cells and demyelination of spinal cord tissues were alleviated significantly.Conclusions:LncRNA Gm13568 might regulate the activation of A1 astrocytes via the Notch1/STAT3 pathway, thus affecting the production of inflammatory cytokines and chemokines and participating in the process of EAE.

【Objective】 To explore the status of HBV infection and low viral load of HBV DNA in blood donor samples implicated in TMA triplex reactive but discriminatory test non-reactive samples. 【Methods】 A total of 51 996 samples were detected by Procleix Panther nucleic acid detection(NAT) system from January 2020 to March 2021, and 86 of them were TMA triplex reactive but discriminatory test non-reactive. HBV serological markers (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc) were detected by electrochemiluminescence. Single-donation(ID) NAT was conducted in some TMA triplex + /discriminatory test-samples using Roche NAT. 【Results】 Out of 86 TMA triplex + /discriminatory test-samples, anti-HBc were positive in 89.53% (77/86), anti-HBe positive in 27.90% (24/86) and anti-HBs positive in 65.12% (56/86). 15 donors carried anti-HBs, anti-HBe and anti-HBc, 34 both anti-HBs and anti-HBc, 1 both anti-HBs/anti-HBe, 8 both anti-HBe/anti-HBc, 6 solo anti-HBs, and 20 solo anti-HBc. The positive rate of HBV serological markers was 97.67% (84/86). HBV DNA in 5 out of the 10 samples was qualitatively detected by Roche ID NAT, and one of them presented HBV DNA < 20 IU/mL. 【Conclusion】 Most TMA triplex + /discriminatory test-samples were occult hepatitis B infection.

Tooth decay is prevalent, and secondary caries causes restoration failures, both of which are related to demineralization. There is an urgent need to develop new therapeutic materials with remineralization functions. This article represents the first review on the cutting edge research of poly(amido amine) (PAMAM) in combination with nanoparticles of amorphous calcium phosphate (NACP). PAMAM was excellent nucleation template, and could absorb calcium (Ca) and phosphate (P) ions via its functional groups to activate remineralization. NACP composite and adhesive showed acid-neutralization and Ca and P ion release capabilities. PAMAM+NACP together showed synergistic effects and produced triple benefits: excellent nucleation templates, superior acid-neutralization, and ions release. Therefore, the PAMAM+NACP strategy possessed much greater remineralization capacity than using PAMAM or NACP alone. PAMAM+NACP achieved dentin remineralization even in an acidic solution without any initial Ca and P ions. Besides, the long-term remineralization capability of PAMAM+NACP was established. After prolonged fluid challenge, the immersed PAMAM with the recharged NACP still induced effective dentin mineral regeneration. Furthermore, the hardness of pre-demineralized dentin was increased back to that of healthy dentin, indicating a complete remineralization. Therefore, the novel PAMAM+NACP approach is promising to provide long-term therapeutic effects including tooth remineralization, hardness increase, and caries-inhibition capabilities.
Amines ; pharmacology ; Calcium ; Calcium Phosphates ; chemistry ; pharmacology ; Dentin ; chemistry ; Humans ; Nanocomposites ; chemistry ; Nanoparticles ; Tooth Remineralization ; methods

Objective To investigate the clinical effect of reconstruction of soft tissue defect in non-weight-bearing area of the foot with trimmed free anterolateral thigh muscle flap combined with skin grafting. Methods From January, 2009 to January, 2017, 25 patients with soft tissue defect in foot and ankle were treated with transplan-tation of the trimmed free anterolateral thigh muscle flap combined with skin grafting. Of the 25 cases, there were 5 cases located in medial foot, 10 cases in dorsum of foot, 7 cases in external of foot and 3 cases in the toe. The areas of wounds were 8.0 cm ×6.0 cm to 18.0 cm ×10.0 cm. The anterolateral thigh muscle flap was from 4.0 cm ×3.0 cm ×0.3 cm to 10.0 cm×8.0 cm×1.5 cm. All the cases were operated in fracture fixation and wound without obvious infection. Early rehabilitative exercise under the protection of orthosis were done after 4 weeks of the operation and to assess. The injuried limb function were assessed in 1 year postoperatively according to Marylands scale. Results All cases were followed-up for 12 to 24 months (average, 16.2 months). All the muscle flaps and skin survived. The healing time were 12 to 24 days, averaged of 17.1 days. Patients could wear shoes normally and resume normal life and work. The appearance and walking function were satisfying and no further debulking procedures were needed . The surgery function were assessed according to Marylands scale, and the results was 22 cases for excellent, and 3 cases for good. Conclusion Ttrimmed free anterolateral thigh muscle flap combined with skin grafting is a good option for the repair of foot and ankle defect at non-weight-bearing area, and it has the advantages such as the doner site is small inva-sive, the muscle flap is easy to be harvested, and can avoid debulking surgery to wear shoes normally.

Objective To estimate the incidence of drop out of treatment in patients with access to methadone maintenance treatment and explore the correlation and interaction between insufficient methadone dosage and morphine positive urine on the drop out in Guangxi Zhuang Autonomous Region.Methods Face to face interview was conducted in 1 031 patients at 3 methadone maintenance treatment clinics in Guangxi.Results The study included 1 031 participants,40.6％ of them (419/1 031) had stopped treatment.The drop out rates in urine morphine positive group and methadone dosage ＜ 100 mg/d group were 57.6％ (99/172) and 37.4％ (347/929) respectively,higher than those in urine morphine negative group and methadone dosage ≥ 100 mg/d group (42.3％,363/ 859,and 26.5％,27/102).Orderly logistic regression analysis results showed that after adjusted factors,such as gender,age,marital status,ethnic group,patients who received a dosage less than 1 00 mg/day (OR=3.05,95％CI:1.84-5.06) and had morphine positive urine (OR=2.25,95％CI:1.59-3.19) were more likely to drop out of the treatment.Interaction analysis showed that dosage less than 100 mg/d and morphine positive urine during treatment had additive interaction (RERI=256.46,AP=0.87,S=8.05) and multiplication interaction (OR=2.45,95％CI:1.71-3.49).Conclusion Insufficient dosage and morphine positive urine were significantly correlated with drop out of treatment in patients with access to methadone maintenance treatment.

Objective To reveal the prevalence and the related factors of hepatitis B (HepB) virus infection among HIV/AIDS patients.Methods We conducted a cross-sectional study in two HIV clinics,affiliated to local Centers of Disease Control and Prevention in Guangxi Zhuang Autonomous Regional.A face-to-face interview,with questionnaire was conducted to collect information on socio-demographic characteristics,drug use,and sexual behavior.Blood samples were used to test HBsAg.x2 test or Fisher's exact test and unconditional logistic regression models were used to identify the influencing factors.Results The prevalence of HBV and HIV co-infection was 13.85％ (113/816).Results from multivariate logistic regression analyses showed that age (25-45),family history of HBV and history of HepB vaccination were independent influencing factors for HBV and HIV coinfection,with OR (95％ CI) as 1.738 (1.031-2.931),2.898 (1.678-5.005) and 1.744 (1.052-2.892),respectively.Conclusion The prevalence of HBV among HIV/AIDS patients was significantly higher than that in general population.HIV/AIDS patients aged between 25 and 45 and with family history of HBV were more likely to be infected with HBV,while HepB vaccination was associated with the reduction of HIV/HBV coinfection.Specific comprehensive prevention and treatment programs on HIV/AIDS patients need to be set up.