Cancer immunotherapy has emerged as a promising strategy. However, low response rates and immune-related side effects have plagued immunotherapy. Metallic nanoparticles, utilizing metals as their framework, are gaining prominence in cancer immunotherapy. Metal ions have shown the ability to modulate immune status by activating the cGAS-STING pathway and inducing immunogenic cell death (ICD), thereby enabling multidimensional activation of immunotherapy. Metallic nanoparticles offer significant advantages in cancer immunotherapy, leading to their increasing use in enhancing therapeutic outcomes. In view of the ever-increasing research on metallic nanoparticles, this review presents the construction, characterization, and enhanced cancer immunotherapeutic effects of different types of metal nanosystems from the perspective of the immunoregulatory mechanisms of metal ions. We delve into the current limitations and future directions of metallic nanoparticles in this rapidly evolving field. To the best of our knowledge, this review offers the most up-to-date and systematic analysis of metallic nanoparticles in immunotherapeutic applications. It is anticipated that this review of metallic nanoparticles will inspire a more refined and intelligent design of metallic nanoparticles for future research, paving the way for advancing their clinical applications.

Image 1.

Psoriasis, a chronic, immune-mediated inflammatory disease characterized by hyperproliferation of keratinocytes, is difficult to cure and prone to relapse, often leading to systemic damage. Triptolide (TPL) can modulate cutaneous immune responses and inflammation, yet its therapeutic window is narrow with significant toxicity. To enhance skin targeting and retention of TPL while reducing systemic absorption and toxicity, a TPL/hyaluronic acid/phospholipid polymeric micelle (TPL/HA-DOPE) was constructed via HA's targeting of the CD44 receptor on skin cells. The prepared TPL/HA-DOPE exhibited a uniform spherical morphology with particle size of (130.4±1.23) nm, drug loading capacity of (19.74±0.084) %, and encapsulation efficiency of (85.53±1.34) %. Transdermal permeation studies in vitro and in vivo demonstrated that TPL/HA-DOPE not only enhanced uptake in HaCaT cells but also exhibited excellent skin retention. In a murine model of psoriasis, the TPL/HA-DOPE gel at the dose of 50 μg/(kg•d) showed the most significant improvement in erythema, scaling, and epidermal thickening. Histological analysis confirmed that TPL/HA-DOPE markedly reduced stratum corneum thickness, epidermal hyperplasia, and inflammatory cell infiltration. Ki67 immunostaining proved that its anti-inflammatory mechanism might be achieved by reducing the number of Ki67-positive cells and lowering the levels of inflammatory factors IL-6 and TNF-α. The above results demonstrate that HA-DOPE as a drug delivery carrier for the treatment of psoriasis-like skin diseases has high value of scientific research and good prospects for clinical application.

ObjectiveTo observe the effect of Xiaoke drink on insulin resistance in ob/ob mice and explore the mechanism. MethodEighteen ob/ob mice were randomly assigned into model， Xiaoke drink （17.68 g·kg^-1）， and atorvastatin （0.01 g·kg^-1） groups （n=6）， and six C57BL/6 mice were selected as the normal group. Mice in the normal and model groups were administrated with the same amount of distilled water. Fasting body weight， weekly food intake， and weekly water intake were measured at a fixed time. Fasting plasma glucose （FPG） and 2-hour post-load plasma glucose （2 hPG） were measured before and after 8-week intervention. After intervention， total cholesterol （TC）， triglyceride （TG）， fasting insulin （FINS）， Homeostasis Model Assessment-Insulin Resistance （HOMA-IR）， blood routine， and alkaline phosphatase （ALP） were measured. Western blot was employed to determine the expression levels of ubiquitin-specific protease 20 （USP20） and 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMGCR） in the liver. The pancreas was stained with hematoxylin-eosin for observation. ResultCompared with the model group， the Xiaoke drink group showed decreased body weight of ob/ob mice （P<0.05， P<0.01）， declined growth trend of body weight （P<0.05， P<0.01）， reduced weekly average water intake， lowered levels of FPG， 2 hPG， TC， and HOMA-IR （P<0.05， P<0.01）， and down-regulated expression level of USP20 in the liver （P<0.05）. HMGCR content was positively correlated with USP20 expression. In addition， Xiaoke drink promoted the recovery of islet tissue morphology and function in ob/ob mice. ConclusionXiaoke drink can ameliorate insulin resistance in ob/ob mice by inhibiting USP20/HMGCR expression， reversing cholesterol biosynthesis process， and reducing cholesterol level.

Objective: To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie diet-induced pneumonia through proteomics analysis. Methods: Based on the Gene Expression Omnibus (GEO) database, lung tissue samples from normal and high-fat diet (HFD) fed mice in the GSE16377 dataset were selected as test cohorts to identify differentially expressed genes and conduct bioinformatics analyses. In the animal experiments, mice were randomly divided into the control (N), high-calorie diet pneumonia (M), and Yinlai decoction treatment (Y) groups. Mice in the M group received high-calorie feed and a 0.5 mg/mL lipopolysaccharide solution spray for 30 min for 3 d. The mice in the Y group were intragastrically administered 2 mL/10 g Yinlai decoction twice daily for 3 d. Pathological evaluation of the lung tissue was performed. Differentially expressed proteins (DEPs) in the lung tissue were identified using quantitative proteomics and bioinformatics analyses. The drug-target relationships between Yinlai decoction and core DEPs in the lung tissue were verified using AutoDock Vina and Molecular Graphics Laboratory (MGL) Tools. DEPs were verified by western blot. Results: GEO data mining showed that an HFD altered oxidative phosphorylation in mouse lung tissue. The Yinlai decoction alleviated pathological damage to lung tissue and pneumonia in mice that were fed a high-calorie diet. A total of 47 DEPs were identified between the Y and M groups. Enrichment analysis revealed their association with energy metabolism pathways such as the tricarboxylic acid cycle (TCA) and oxidative phosphorylation. The protein-protein interaction network revealed that Atp5a1, Pdha1, and Sdha were the target proteins mediating the therapeutic effects of Yinlai decoction. Molecular docking results suggested that the mechanism of the therapeutic effect of Yinlai decoction involves the binding of brassinolide, praeruptorin B, chrysoeriol, and other components in Yinlai decoction to Atp5a1. Conclusion The Yinlai decoction alleviated lung tissue damage and pneumonia in mice that were fed a high-calorie diet by regulating the TCA and oxidative phosphorylation. Our study highlights the importance of a healthy diet for patients with pneumonia and provides a scientific basis for the prevention and treatment of pneumonia through dietary adjustments.

Objective:To observe the efficacy and safety of subretinal injection of Aflibercept for the treatment of refractory or recurrent polypoidal choroidal vasculopathy (PCV).Methods:A prospective clinical research. From January to June 2022, 18 patients of 18 eyes with PCV diagnosed in The Affiliated Eye Hospital of Nanchang University were included in the study. All patients underwent best corrected visual acuity (BCVA), indocyanine green angiography and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The large choroidal vessel thickness (LVCT), central retinal thickness (CRT), sub-foveal choroidal thickness (SFCT) and retinal pigment epithelium detachment (PED) height were measured by enhanced depth imaging technique of OCT. The choroidal vascular index (CVI) was calculated. There were 18 patients of 18 eyes, 11 males of 11 eyes and 7 females of 7 eyes. The age was (64.22±3.86) years old. The disease duration was (5.22±1.80) years. The patient had received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs for (7.72±1.36) times. The logMAR BCVA of the affected eyes was 1.28±0.25. The SFCT, CRT, LVCT, PED height were (436.56±9.80), (432.44±44.29), (283.78±27.10), (342.44±50.18) μm, respectively, and CVI was 0.65±0.01. All eyes were treated with a single subretinal injection of 40 mg/ml Aflibercept 0.05 ml (including Aflibercept 2.0 mg). According to the results of OCT and BCVA after treatment, the lesions were divided into active type and static type. The active lesions were treated with intravitreal injection of Aflibercept at the same dose as before. Quiescent lesions were followed up. Examinations were performed 1-3, 6, 9 and 12 months after treatment using the same equipment and methods before treatment. The BCVA, LVCT, CRT, SFCT, PED height, CVI, interretinal or subretinal fluid, lesion regression rate, injection times, and complications during and after treatment were observed. The BCVA, SFCT, CRT, LVCT, PED height and CVI before and after treatment were compared by repeated measures analysis of variance.Results:Eighteen eyes received subretinal and/or intravitreal injection of Aflibercept (1.61±0.85) times (1-4 times). At the last follow-up, the polypoid lesions regressed in 4 eyes and PED disappeared in 1 eye. Compared with before treatment, BCVA ( F=50.298) gradually increased, CRT ( F=25.220), PED height ( F=144.16), SFCT ( F=69.77), LVCT ( F=136.69), CVI ( F=72.70) gradually decreased after treatment. The differences were statistically significant ( P<0.001). Macular hole occurred in 1 eye after treatment, and the hole closed spontaneously 3 months after treatment. No serious complications such as retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage occurred during and after treatment. Conclusion:Subretinal injection of Aflibercept is safe and effective in the treatment of refractory PCV.

Objective:To observe the efficacy and safety of vitrectomy combined with subretinal injection of alteplase (tPA) and intravitreal injection of Conbercept in the treatment of large area submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV).Methods:A retrospective clinical study. From January to September 2021, 32 eyes of 32 patients with massive SMH secondary to PCV diagnosed in the Affiliated Eye Hospital of Nanchang University were included in the study. Large SMH was defined as hemorrhage diameter ≥4 optic disc diameter (DD). There were 32 patients (32 eyes), 20 males and 12 females. The mean age was (72.36±8.62) years. All patients had unilateral disease.The duration from onset of symptoms to treatment was (7.21±3.36) days. All patients underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examination. BCVA examination was performed using the international standard visual acuity chart, which was converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The central macular thickness (CMT) was measured by spectral domain-OCT. The average size of SMH was (6.82±1.53) DD. The logMAR BCVA 1.73±0.44; CMT was (727.96±236.40) μm. All patients were treated with 23G pars plana vitrectomy combined with subretinal injection of tPA and intravitreal injection of Conbercept. At 1, 3, 6 and 12 months after treatment, the same equipment and methods were used for relevant examinations before treatment. The changes of BCVA and CMT, the clearance rate of macular hemorrhage, and the complications during and after surgery were observed. BCVA and CMT before and after treatment were compared by repeated measures analysis of variance.Results:Compared with before treatment, BCVA gradually increased at 1, 3, 6 and 12 months after treatment, and the differences were statistically significant ( F=77.402, P<0.001). There was no significant difference in BCVA between any two groups at different time points after treatment ( P>0.05). Correlation analysis showed that BCVA at 12 months after treatment was negatively correlated with the course of disease ( r=-0.053, P=0.774). One week after treatment, macular hemorrhage was completely cleared in 30 eyes (93.75%, 30/32). The CMT was (458.56±246.21), (356.18±261.46), (345.82±212.38) and (334.64±165.54) μm at 1, 3, 6 and 12 months after treatment, respectively. Compared with before treatment, CMT decreased gradually after treatment, and the difference was statistically significant ( F=112.480, P<0.001). There were statistically significant differences in different follow-up time before and after treatment ( P<0.001). The number of treatments combined with Conbercept during and after surgery was (4.2±1.8) times. At the last follow-up, there was no recurrence of SMH, retinal interlamellar effusion and other complications. Conclusion:Subretinal injection of tPA combined with intravitreal injection of Conbercept is safe and effective in the treatment of large SMH secondary to PCV, and it can significantly improve the visual acuity of patients.

ObjectiveTo investigate the safety and efficacy of endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips in the treatment of cirrhotic patients with gastric varices and gastric-renal shunt （GRS）. MethodsThe patients who attended Beijing Ditan Hospital， Capital Medical University， due to liver cirrhosis and gastric varices from February to June 2023 were enrolled， and all patients were confirmed to have GRS and received endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips. The primary evaluation index was alleviation or disappearance of varicose veins after surgery， and the secondary evaluation indices were surgical completion and complications. ResultsA total of 11 patients were enrolled in this study， among whom there were 7 male patients and 4 female patients， with a median age of 55 years. Of all patients， 1 had Child class A liver function， 7 had Child class B liver function， and 3 had Child class C liver function. The maximum （median） diameter of the shunt was 8 mm， and the minimum （median） diameter of the shunt was 4 mm. The median blood flow velocity of the target vessel was 11 cm/s before treatment and 5 cm/s after occlusion with metal clips. The median amount of tissue adhesive injected was 2 mL， and the amount of lauromacrogol used was 1 mL. Disappearance of blood flow signals was observed in all patients after surgery （100%）， and the success rate of surgery was 100%. No patient experienced rebleeding after follow-up for 6 weeks. Gastroscopy at 1 month after surgery showed that gastric varices were eradicated or almost disappeared in 9 patients and were alleviated in 2 patients. ConclusionEndoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips is a feasible， safe， and effective treatment method for cirrhotic patients with gastric varices and GRS.

Objective To compare the categorical agreement between drug susceptibility testing(DST)and whole genome sequencing(WGS)for the detection of drug resistance in Mycobacterium tuberculosis(MTB),and to explore the characteristics of WGS for MTB drug resistance detection.Methods A total of 71 MTB clinical isolates retained in West China Hospital of Sichuan University from 2018 to 2020 were included in this study.The MTB strains were tested for resistance to 14 anti-tuberculosis drugs,including Isoniazid(INH),Rifampicin(RIF),Rifabutin(RFB),Ethambutol(EMB),Streptomycin(SM),Moxifloxacin(MFX),Ofloxacin(OFX),Levofloxacin(LFX),Amikacin(AMK),Kanamycin(KAN),Capreomycin(CPM),Para-aminosalicylic acid(PAS),Ethionamide(ETH)and Clofazimine(CLO),using both DST(colorimetric redox indicator meth-od)and WGS methods.Kappa test was performed to analyze the results of drug resistance detection for both methods.Results Based on DST and WGS methods to detect anti-tuberculosis drug resistance in seventy-one MTB clinical isolates,the results showed that the agreement rate of RIF,RFB,SM,MFX,OFX and LFX ex-ceeded 90.00％,and the kappa values were all greater than 0.80,with near perfect agreement;The agreement rates of INH and EMB were 84.51％and 81.69％,and Kappa values were 0.68 and 0.54,respectively,with fair agreement.No more than two drug resistant MTB strains of AMK and KAN were detected by both meth-ods,and the resistance rate was less than 3.00％.The agreement rates of CPM,ETH,PAS,and CLO ranged from 61.97％to 91.55％,and the Kappa values were less than 0.40,with slight or fair agreement.Conclusion There are differences in the ability of WGS to detect resistance to various anti-tuberculosis drugs,and it is more effective in detecting resistance to six anti-tuberculosis drugs,including RIF,RFB,SM,MFX,OFX and LFX,while there are still certain differences in detecting resistance to other anti-tuberculosis drugs compared with DST.It is necessary to further clarify the detailed resistance mechanisms of relevant anti-tu-berculosis drugs and to explore the standardization of WGS for drug resistance detection.

Objective To explore the impact of non-pharmaceutical interventions(NPIs)on the prevalence of respiratory pathogens in adults,and to understand the scientific value and long-term effect of NPIs.Methods A retrospective study was conducted to collect the clinical data and laboratory examination data of adult patients with respiratory tract infection in West China Hospital,Sichuan University from 2017 to 2023,and the patho-gen,population,season and other aspects were analyzed in different periods.The analysis period included 2017 to 2019(before the implementation of NPIs),2020 to 2022(during the implementation of NPIs),and January to December 2023(after the implementation of NPIs).Results A total of 33 068 adult patients with respira-tory tract infection were included.The overall prevalence of 8 adult respiratory pathogens from 2017 to 2019(26.95％)was higher than that from 2020 to 2022(8.70％),and the difference was statistically significant(P＜0.05).There were significant differences in the prevalence of pathogens among different genders,ages and seasons in the first,middle and last three periods of NPIs implementation(P＜0.05).Before the imple-mentation of NPIs,the seasonal peak of respiratory prevalence appeared from January to March each year.With the implementation of NPIs,the seasonal peak of respiratory prevalence appeared from January to March 2020(10.09％),October to December 2021(9.32％),July to September 2022(15.23％),respectively.After the implementation of NPIs,the seasonal peak of respiratory prevalence appeared from October to December 2023(21.20％).Among the 8 pathogens,the change of prevalence of influenza A virus H1N1(2009)was the most obvious,and the prevalence was 17.42％,0.00％and 6.99％before,during and after the implementation of NPIs,respectively.Conclusion Due to the influence of NPIs and other factors,the epidemic characteristics of respiratory pathogens have changed from 2017 to 2023.Attention to the emerging characteristics of patho-gen prevalence is important for the prevention,diagnosis and control of respiratory infectious diseases during public health emergencies.