Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

Objective To investigate the metabolic characteristics of patients with early-onset type 2 diabetes mellitus(T2DM)and to develop a risk prediction model for microvascular complications.Methods A retrospective study was conducted on 980 T2DM patients admitted for treatment between April 2020 and April 2024.Based on age at diagnosis,the patients were divided into two groups,an early-onset T2DM group(age at diagnosis<40 years,n=265)and a late-onset T2DM group(age at diagnosis≥40 years,n=715).Differences in metabolic indicators between the two groups were compared.Patients in the early-onset group were further divided into a complication subgroup(n=142)and a non-complication subgroup(n=123)based on the presence or absence of microvascular complications.Data on baseline characteristics,metabolic parameters,and laboratory indicators were collected and compared between the two groups.Multivariate logistic regression analysis was used to identify independent risk factors for microvascular complications,and a nomogram prediction model was constructed.The model's discriminative performance was assessed using receiver operating characteristic(ROC)curves,and its calibration was evaluated using calibration curves and the Hosmer-Lemeshow test.Decision curve analysis(DCA)was also performed to assess the model's clinical utility.Results Compared with the late-onset group,patients in the early-onset group exhibited more pronounced metabolic abnormalities,including higher body mass index(BMI),proportion of family history of diabetes mellitus,glycated hemoglobin(HbA1c)levels,total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),triglyceride-glucose index(TyG),and lactate dehydrogenase(LDH)levels(all P<0.05),along with a shorter disease duration and lower levels of high-density lipoprotein cholesterol(HDL-C)(P<0.05).According to a multivariate analysis,systolic blood pressure(SBP),total bilirubin(TBIL),HDL-C,LDL-C,TyG,and LDH were identified as independent risk factors for microvascular complications in patients with early-onset T2DM.A predictive model based on these factors was established as the follows,Log(P)=-19.915+0.017×SBP-0.136×TBIL-1.241×HDL-C+0.684×LDL-C+0.769×TyG+0.050×LDH.The area under the ROC curve(AUC)was 0.864(95%CI,0.820-0.907),and the Hosmer-Lemeshow test indicated good model fit(χ2=10.286,P=0.246).The slope of the DCA curve was also close to 1.Conclusion The nomogram prediction model based on SBP,TBIL,HDL-C,LDL-C,TyG,and LDH demonstrates good predictive performance for microvascular complications and can provide a reference for clinical risk stratification and individualized intervention.

Orodispersible films (oral dispersible films), a novel form of oral solid dosage forms, are widely used for patients with dysphagia and those with uncontrollable autonomic behavior. In this study, suvorexant orodispersible film was prepared by hot melt extrusion technology, and the disintegration time, mechanical properties, in vitro dissolution and pharmacokinetics were evaluated, compared with other orodispersible films and commercially available tablets Belsomra. All experiments were approved by the Committee on the Management and Use of Laboratory Animals of Academy of Military Medical Sciences (IACUC-DWZX-2024-504). The results showed that the dissolution rate of suvorexant orodispersible film was faster and the mechanical strength was better than that of other commercially available orodispersible film, which could meet the needs of storage and transportation. Differential scanning calorimetry and X-ray diffraction results showed that suvorexant was dispersed within the orodispersible film in an amorphous state. The in vitro dissolution of the film was observed to be four times faster than that of the commercial tablets, achieving complete dissolution within five minutes. Pharmacokinetic evaluations in Beagle dogs revealed that the self-formulated orodispersible film exhibited no significant differences in the area under the blood concentration-time curve when compared with Belsomra. However, the film showed a faster onset of action, with a peak time that was twice as rapid, and a maximum blood concentration that was twice as high as that of Belsomra. Leveraging hot melt extrusion technology, the suvorexant orodispersible film offers a straightforward, continuous production process with consistent quality. It serves as an excellent platform for the development of solvent-free film preparations tailored for patients with special needs.

The rheological properties of drug and carrier materials have a wide range of guiding significance for the formulation and process development of solid dispersions. In this study, the rheological properties of materials with different drug carrier ratios were systematically studied with suvorexant as the model drug and copovidone as the carrier material, which provided a sufficient basis for determining the formulation and process of solid dispersions. The optimal suvorexant-copovidone ratio obtained by oscillating temperature scanning was 1∶4. If the ratio is greater than 1∶ 4, the glass transformation temperature of the material will increase significantly, and the solubilization effect of the solid dispersion will show a downward trend. The results of oscillation temperature scanning and oscillation temperature sweep can show that when the extrusion temperature is greater than 150 ℃, the viscosity of the material is less than 10 000 Pa·s, and the melt can be extruded smoothly, and the best extrusion temperature of 160-180 ℃ can be obtained by combining the dissolution results. Finally, the dissolution of suvorexant tablets guided by rheological property studies in multiple media is similar to that of the commercially available tablets Belsomra. Therefore, rheological studies can screen and optimize the formulation and process of suvorexant solid dispersions at the mechanism level, which is of great significance to improve the success rate of R&D and shorten the R&D cycle of solid dispersions prepared by hot melt extrusion.

A 11-year old female patient with severe thalassemia, receipt a lentivirus-based cell and gene therapy (CGT) therapy in Shenzhen Children′s Hosptial on July 27th, 2021. At the two follow-up visits after discharge, patient were continuously tested positive for HIV screening through HIV Ag/Ab Combo assay (chemiluminescence Immunoassay), and the viral load results of HIV-1 nucleic acid testing (NAT) were both>5 000 copies/ml. The patient can be diagnosed with HIV infection according to the National Guideline for Detection of HIV/AIDS(2020 Revised Edition). The thorough investigation findings and supplementary experiment results indicated that the false-positive HIV-1 NAT results was caused by cross-reactivity between the target sites detected by conventional HIV-1 NAT reagents and the lentiviral vectors fragments integrated into the genome of patient′s hematopoietic stem/progenitor cells. In conclusion, it is important for laboratories to select appropriate HIV-1 NAT testing platforms which won′t cause cross-reactivity for the testing of samples from patients who have been treated with HIV-derived vectors. It is also recommended to design and develop NAT testing platforms with multiple target regions labeled by different fluorescents for HIV NAT supplementation experiment to reduce the risk of false-positive diagnoses of HIV infection.

ObjectiveTo evaluate the effect of antihypertensive and lipid-regulating Chinese patent medicine combined with conventional Western medicine in the treatment of hypertension with dyslipidemia. To carry out the evidence synthesis of clinical research and provide evidence-based evidence support for clinical decision-making. MethodThe databases including China National Knowledge Infrastructure （CNKI），Wanfang Data Knowledge Service Platform （WF），VIP，SinoMed，Embase，PubMed，Web of Science （WOS），and the Cochrane Library were searched for randomized controlled trials （RCT） of all listed Chinese patent medicines in the treatment of hypertension with dyslipidemia from the establishment of the databases to April 15，2023. The literature was screened and extracted，and the risk of bias tool 2.0 （RoB2） was used to assess the quality and risk of bias of the methodology. Revman 5.4.1 software was used to analyze the outcome indicators. Grading of Recommendations Assessment，Development and Evaluation （GRADE） was applied to assess the quality of evidence formed by clinical research data. The inclusion and recommendation of Chinese patent medicines in the National Drug Catalogue for Basic Medical Insurance，Work-related Injury Insurance and Maternity Insurance （2022） and domestic guidelines and consensus were searched to form a bubble chart. ResultA total of 15 studies were included. The evaluation of the methodological quality of each study showed that the risk of bias stemmed from the lack of blinding and allocation concealment，and low sample size. The comprehensive analysis of clinical studies showed that Dengzhan Shengmai capsules combined with rosuvastatin and amlodipine besylate，Yindan Xinnaotong capsules combined with simvastatin and levamlodipine tablets，Xiaoshuan Tongluo capsules combined with nifedipine controlled release tablets and pravastatin sodium tablets，Xinshubao capsules combined with atorvastatin calcium tablets and irbesartan，Wenyading capsules combined with enalapril，and Jiangzhining tablets combined with conventional Western medicines were all superior to conventional Western medicines used in the control group in improving systolic blood pressure （SBP），diastolic blood pressure （DBP），cholesterol （TC），triglyceride （TG），low density lipoprotein cholesterol （LDL-C），and high density lipoprotein cholesterol （HDL-C）. There was no significant difference in the incidence of adverse reactions between the two groups. The GRADE evaluation of the main outcome indicators showed that the evidence quality of SBP and incidence of adverse reactions was graded as B，that of DBP as C，and that of total TC，TG，LDL-C，and HDL-C as D. The evaluation of Chinese patent medicines covered by medical insurance and recommended by guidelines and consensus showed that Yindan Xinnaotong soft capsules，Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules belonged to class B drugs of medical insurance，and were recommended for 7，6 and 3 times in the guidelines and consensus，respectively. ConclusionCompared with simple medicine treatment，Chinese patent medicine combined with conventional Western medicine has more advantages in improving blood pressure and blood lipid，and shows higher safety. Among them，Yindan Xinnaotong soft capsules，Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules have stronger clinical applicability and economy. All the trials included in this article adhered to the principle of randomization and reported the outcome measures. However，the quality of evidence in related clinical studies was low. In terms of trial design，large-sample，multi-center，blinded randomized controlled trials based on the consolidated standards of reporting trials （CONSORT） statement are still needed for comprehensive trial designs and reporting，to further improve the GRADE quality evaluation and guideline formulation under the guidance of evidence-based medicine，so as to provide higher quality evidence-based research evidence for clinical decision-making.

Objective To investigate the effect of sanguinarine(SAN)on proliferation and ferroptosis of colorectal cancer cells.Methods SW620 and HCT-116 cells treated with different concentrations of SAN were examined for cell viability changes using CCK8 assay to determine the IC50 of SAN in the two cells.The inhibitory effects of SAN on proliferation,invasion and migration of the cells were evaluated using colony-forming assay and Transwell assays.ROS production in the treated cells was analyzed with flow cytometry,and lipid peroxide production was assessed by detecting malondialdehyde(MDA)level.Glutathione(GSH)levels in the cells were detected,and Western blotting was used to detect the expressions of ferroptosis-related proteins STUB1 and GPX4.Results SAN significantly inhibited the proliferation,invasion and migration of SW620 and HCT-116 cells.SAN treatment significantly promoted ROS production,increased intracellular MDA level,and lowered GSH level in the two cells(P<0.05).Western blotting showed that SAN significantly upregulated the expression of STUB1 and down-regulated the expression of its downstream protein GPX4(P<0.05).Conclusion SAN induces ferroptosis in colorectal cancer cells by regulating STUB1/GPX4,which may serve as a new therapeutic target for colorectal cancer.

Objective:To analyze the clinical characteristics, muscle imaging and pathological features of patients with anti-signal recognition particle positive immune-mediated necrotizing myopathy (SRP-IMNM).Methods:Nine patients with SRP-IMNM were collected in the Neuromuscular Disease Center of Jiaozuo People′s Hospital from May 2018 to May 2023, who were confirmed by skeletal muscle pathology and myositis-specific autoantibodies detection, and their clinical manifestations, muscle imaging and muscle pathology characteristics were systematically summarized.Results:Among the 9 patients with SRP-IMNM, there were 7 females and 2 males. The age of onset ranged from 18 to 59 years. All the patients presented proximal muscle weakness. Seven patients experienced neck weakness, and dysphagia was present in 5 patients. Laboratory examinations showed elevated serum creatine kinase levels in all 9 patients (1 866-6 725 U/L). Eight patients were combined with other antibodies positivity, except for anti-SRP antibody. Among them, 7 patients were combined with anti-Ro-52 antibody positivity, 4 patients combined with anti-Ro-52 antibody positivity alone, and 3 patients combined with 3 or more positive antibodies simultaneously. Those patients who presented with interstitial lung disease and cardiac involvement were all combined with other antibodies positivity. Seven patients completed thigh muscle magnetic resonance imaging (MRI), which showed diffuse skeletal muscle oedema, partial muscle atrophy and fatty replacement, primarily affecting the posterior thigh muscle group. Two patients underwent shank muscle MRI. The soleus involvement was evident, while the tibialis anterior muscle and gastrocnemius muscles were involved in 1 patient. All 9 patients showed varying degrees of scattered muscle fiber necrosis and regeneration on muscle biopsies. In 1 patient, a small amount of inflammatory cell infiltration was observed. Pipestem capillaries were observed in 4 patients. Immunohistochemical staining revealed a small number of CD68-positive lymphocytes in 8 patients. Additionally, 5 patients showed upregulation of major histocompatibility complex Ⅰ expression on the muscle fiber membrane, while 6 patients showed deposition of membrane attack complex (C5b-9) on non-necrotic muscle fibers and capillaries. P62 staining showed homogeneous fine-granular in sarcoplasm in 6 patients.Conclusions:In addition to proximal muscle weakness, patients with SRP-IMNM often experience neck weakness and dysphagia. Those with multiple antibodies are more likely to develop interstitial lung disease and cardiac involvement. SRP-IMNM patients have diffuse oedema in the affected muscles, and the posterior thigh muscles are more prone to atrophy and fatty tissue formation. C5b-9 deposition and pipestem capillaries are significant pathological features of SRP-IMNM, which provide additional evidence for clinical diagnosis.

Objective To investigate the effect of sanguinarine(SAN)on proliferation and ferroptosis of colorectal cancer cells.Methods SW620 and HCT-116 cells treated with different concentrations of SAN were examined for cell viability changes using CCK8 assay to determine the IC50 of SAN in the two cells.The inhibitory effects of SAN on proliferation,invasion and migration of the cells were evaluated using colony-forming assay and Transwell assays.ROS production in the treated cells was analyzed with flow cytometry,and lipid peroxide production was assessed by detecting malondialdehyde(MDA)level.Glutathione(GSH)levels in the cells were detected,and Western blotting was used to detect the expressions of ferroptosis-related proteins STUB1 and GPX4.Results SAN significantly inhibited the proliferation,invasion and migration of SW620 and HCT-116 cells.SAN treatment significantly promoted ROS production,increased intracellular MDA level,and lowered GSH level in the two cells(P<0.05).Western blotting showed that SAN significantly upregulated the expression of STUB1 and down-regulated the expression of its downstream protein GPX4(P<0.05).Conclusion SAN induces ferroptosis in colorectal cancer cells by regulating STUB1/GPX4,which may serve as a new therapeutic target for colorectal cancer.