Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.

The objective of this study was to investigate whether Stenotrophomonas maltophilia(S.maltophilia)induces ferroptosis,a form of iron-dependent cell death,leading to an inflamma-tory response in RAW 264.7 macrophages by elevating oxidative stress levels.RAW 264.7 cells were stimulated with varying concentrations of S.maltophilia.The concentrations of TNF-αand IL-1β were quantified using ELISA kits to assess the impact of S.maltophilia on the inflammatory response in RAW 264.7 cells.The activities of glutathione(GSH)and malondialdehyde(MDA)levels were measured using GSH and MDA assay kits to evaluate changes in oxidative stress.West-ern blot analysis was employed to detect the expression levels of COX-2,xCT,GPX4,and other proteins involved in ferroptosis signaling pathways,thereby investigating the effect of S.malto-philia on ferroptosis in RAW 264.7 cells.The results demonstrated that S.maltophilia induced concentration-dependent increases in inflammation and oxidative stress in RAW 264.7 cells,up-regulated the expression of COX-2 protein and down-regulated the expression of xCT and GPX4.Pretreatment with the ROS inhibitor N-acetylcysteine(NAC)significantly mitigated the S.malto-philia-induced oxidative stress and ferroptosis signaling activation,thereby alleviating the inflam-matory response.Furthermore,treatment with the ferroptosis inhibitor Fer-1 directly suppressed the activation of the ferroptosis signaling pathway and reversed the inflammation induced by S.maltophilia.These findings suggest that S.maltophilia triggers inflammation in RAW 264.7 cells by activating the ferroptosis signaling pathway via an increase in oxidative stress levels.

The acquired immune deficiency syndrome(AIDS)-induced fever is mainly characterized by long-term,recurrent and irregular symptom,which poses a major threat to the quality of life of the AIDS patients.Tradition-al Chinese Medicine(TCM)has offered an approach of treatment determination based on syndrome differentiation and formula corresponding to syndrome on basis of the idea of'same disease,different therapies'.The earliest or-igin of the idea of'same disease,different therapies' can be traced back to'Huang Di Nei Jing',it plays a signifi-cant role in the theory of TCM after continuous enrichment and development by ancient medical families.The indi-vidualized therapeutic regimen is formulated based on the etiology,pathogenesis and physical condition(such as qi-insufficiency constitution,phlegm-dampness constitution),emphasizing the vital role of'treatment determina-tion based on syndrome differentiation'in the treatment process,highlighting the importance of personnel experi-ence of doctors,and showing the precise effect of TCM on treatment of AIDS-induced fever.

The objective of this study was to investigate whether Stenotrophomonas maltophilia(S.maltophilia)induces ferroptosis,a form of iron-dependent cell death,leading to an inflamma-tory response in RAW 264.7 macrophages by elevating oxidative stress levels.RAW 264.7 cells were stimulated with varying concentrations of S.maltophilia.The concentrations of TNF-αand IL-1β were quantified using ELISA kits to assess the impact of S.maltophilia on the inflammatory response in RAW 264.7 cells.The activities of glutathione(GSH)and malondialdehyde(MDA)levels were measured using GSH and MDA assay kits to evaluate changes in oxidative stress.West-ern blot analysis was employed to detect the expression levels of COX-2,xCT,GPX4,and other proteins involved in ferroptosis signaling pathways,thereby investigating the effect of S.malto-philia on ferroptosis in RAW 264.7 cells.The results demonstrated that S.maltophilia induced concentration-dependent increases in inflammation and oxidative stress in RAW 264.7 cells,up-regulated the expression of COX-2 protein and down-regulated the expression of xCT and GPX4.Pretreatment with the ROS inhibitor N-acetylcysteine(NAC)significantly mitigated the S.malto-philia-induced oxidative stress and ferroptosis signaling activation,thereby alleviating the inflam-matory response.Furthermore,treatment with the ferroptosis inhibitor Fer-1 directly suppressed the activation of the ferroptosis signaling pathway and reversed the inflammation induced by S.maltophilia.These findings suggest that S.maltophilia triggers inflammation in RAW 264.7 cells by activating the ferroptosis signaling pathway via an increase in oxidative stress levels.

The acquired immune deficiency syndrome(AIDS)-induced fever is mainly characterized by long-term,recurrent and irregular symptom,which poses a major threat to the quality of life of the AIDS patients.Tradition-al Chinese Medicine(TCM)has offered an approach of treatment determination based on syndrome differentiation and formula corresponding to syndrome on basis of the idea of'same disease,different therapies'.The earliest or-igin of the idea of'same disease,different therapies' can be traced back to'Huang Di Nei Jing',it plays a signifi-cant role in the theory of TCM after continuous enrichment and development by ancient medical families.The indi-vidualized therapeutic regimen is formulated based on the etiology,pathogenesis and physical condition(such as qi-insufficiency constitution,phlegm-dampness constitution),emphasizing the vital role of'treatment determina-tion based on syndrome differentiation'in the treatment process,highlighting the importance of personnel experi-ence of doctors,and showing the precise effect of TCM on treatment of AIDS-induced fever.

ObjectiveTo evaluate the validity of four screening questionnaires on chronic obstructive pulmonary disease (COPD) among community residents in Shanghai, and to provide a scientific basis for selecting suitable screening questionnaires and plans for the community use. MethodsA multi-stage random sampling method was used to select community residents aged ≥40 for COPD questionnaire screening and spirometry. The screening questionnaires included the COPD Population Screener Questionnaire (COPD-PS), the COPD Screening Questionnaire (COPD-SQ), the COPD Diagnosis Questionnaire (CDQ), and the Lung Function Questionnaire (LFQ). The diagnostic gold standard for COPD was defined as a ratio of post-bronchodilator forced expiratory volume in one second to forced vital capacity (FEV1/FVC) less than 0.7. The receiver operating characteristic (ROC) curve was used to assess the validity of each questionnaire, and DeLong’s test was used to compare the area under the curve (AUC) of different questionnaires. ResultsAmong the 1 122 residents screened, 99 (8.8%) were diagnosed with COPD based on the gold standard criteria. The AUC values for the four questionnaires ranged from 0.643 to 0.682, with no statistically significant differences in screening accuracy among them (P>0.05). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for each questionnaire at recommended cut-off points were as follows: COPD-PS (sensitivity: 33.3%, specificity: 84.9%, PPV: 17.6%, NPV: 92.9%), COPD-SQ (34.3%, 85.8%, 19.0%, 93.1%), CDQ (73.7%, 42.4%, 11.0%, 94.4%), and LFQ (48.5%, 74.8%, 15.7%, 93.8%). Optimal cut-off values for this population differed from the recommended values. When selecting the optimal cut-off value, the sensitivity of COPD-PS (58.6%), COPD-SQ (55.6%), and LFQ (64.7%) increased, while the specificity of CDQ (75.9%) increased. The AUC of sequential lung function testing for all four screening questionnaires increased to 0.7 or above. The optimal cut-off values for the four questionnaires in this population differed from the recommended values. When applying the optimal cut-off values, the sensitivity of three questionnaires increased: COPD-PS (58.6%), COPD-SQ (55.6%), and LFQ (64.7%), while the specificity of CDQ rose to 75.9%. The AUC of each questionnaire increased to above 0.7 when followed by sequential lung function testing. ConclusionThe COPD-PS, COPD-SQ, CDQ, and LFQ have limited value for COPD screening among Shanghai community residents, indicating that further refinement of these tools is needed.

Objective: To evaluate the clinical effect of clear aligners in the anterior region in non-extraction cases by establishing a three-dimensional model of crown-root fusion to guide clinical application. Methods: Eleven patients visiting the orthodontic department of Xuzhou Stomatological Hospital from December 2020 to December 2021 were collected, and the orthodontic plan was designed using Maestro 3D Dental Studio scheduling software to obtain the expected three-dimensional model of the patient's orthodontic treatment result. CBCT, intraoral scan, and 3D reconstruction software were used to create a postoperative model of the patient. The crown and root data were aligned in Geomagic Studio 2014, and differences in torque and axial inclination between the actual model after treatment and the predicted model of the anterior teeth before treatment were compared in 3-matic. Results: The actual torque angles of the anterior teeth were all smaller than the predicted angles before treatment, with the highest realization rate of 77.55% for lateral incisors and the lowest of 60.70% for central incisors; the actual axial inclination angles of the anterior teeth were also smaller than the predicted angles before treatment, with the highest realization rate of 81.49% for central incisors and the lowest of 74.95% for cuspids. Conclusion A digital model of crown-root integration based on a combination of 3D reconstruction and intraoral scanning techniques is advantageous in assessing the efficacy of clear aligners. In non-extraction cases with clear aligner, the efficiency of movement is higher for small areas of the anterior region.

Objective:To learn about the incidence of hypertension in residents of arsenic exposure areas of Togtoh County, Inner Mongolia Autonomous Region, and to analyze the influencing factors of hypertension.Methods:In Inner Mongolia Autonomous Region, Ciweigou of Togtoh County, a drinking water-type endemic arsenic poisoning area, and Lanjiayao of Horinger County, a non-arsenic poisoning area with similar living habits and economic conditions, permanent residents who had lived for ≥10 years were selected as the survey subjects. Totally 116 residents of Ciweigou (exposure group) and 68 residents of Lanjiayao (control group) were included in the survey. Blood pressure was measured and the contents of arsenic, selenium, lead and chromium in urine were detected, multivariate logistic regression was used to analyze the influencing factors of hypertension.Results:The detection rates of hypertension in exposure group and control group were 53.45% (62/116) and 70.59% (48/68), respectively, and the difference between the two groups was statistically significant (χ 2 = 5.33, P = 0.022). The contents of arsenic, selenium and chromium in urine of exposure group were higher than those of control group, and the content of lead in urine was lower than that of control group, and the differences were statistically significant ( Z = 13.04, 6.34, 11.28, - 9.91, P < 0.001). The results of multivariate logistic regression analysis showed that female, age ≥60 years old and high urinary arsenic content were the influencing factors of hypertension [odds ratio ( OR) = 2.074, 2.004, 0.424, 95% confidence interval ( CI): 1.113 - 3.866, 1.035 - 3.879, 0.219 - 0.820] in arsenic exposure areas. Conclusion:Female, age ≥60 years old and high urinary arsenic content are the influencing factors of hypertension in arsenic exposure areas of Togtoh County, Inner Mongolia Autonomous Region.

Objective: To investigate whether plague phages were present in the indicator animals of plague foci in Yunnan Province, and to explore their epidemiological significance. Methods: Anus swabs were collected from indicator animals (dogs or cats) of the 41 plague affected villages in 26 towns of 10 cities (counties, districts) of Yunnan plague foci from November of 2015 to March of 2018. The Yersinia pestis phages were isolated by plague vaccine strain EV76. The isolation of plague phages from different plague foci, the isolation of plague phages from different canine species (cats), the polymorphism of plaque and the host spectrum of phages were analyzed. Results: A total of 1 014 indicator animals (1 003 dogs and 11 cats) were studied, and 102 of plague phages were isolated. In the 10 cities (counties, districts), plague phages were only not isolated from Lancang County, and the plague phages were isolated from the other 9 cities (counties, districts). The separation rates from high to low were as follows: Yiliang County (21.00%, 21/100), Menghai County (19.23%, 25/130), Yuanjiang County (11.63%, 10/86), Midu County (11.50%, 13/113), Wenshan County (10.10%, 10/99), Mile Country (7.07%, 7/99), Lianghe County (6.67%, 7/105), Baoshan Longyang District (4.90%, 5/102) and Gengma County (3.81%, 4/105). Of the 102 plague phages, 75 were isolated from the native dogs (Chinese pastoral dogs, 9.32%, 75/805), 20 from the pug dogs (13.70%, 20/146), 5 from the wolf dogs (17.24%, 5/29), 1 from Samoye (1/4) and 1 from Alaska dog (1/2). The plaque of the phage was divided by five appearance of complete lysis (the plate was clear), large (2.5-4.0 mm), big (1.5-< 2.5 mm), middle (0.5-< 1.5 mm) and small (< 0.5 mm). The representative phages were all of the Myoviridae family. Most of the phages could lysis the strains of Yersinia pestis, and some phages could lysis Shigella and type 5 Yersinia pseudotuberculosis (PST5). Conclusion The plague phages are present in the plague foci of Yunnan, and the phages are polymorphic.

Objective: To observe the effect of infiltration resin combined with cold light whitening in the treatment of dental fluorosis. Methods: According to the distance between teeth and the long axis of each tooth, 18 anterior teeth were divided equally and randomly between group A and B. Samples in group A underwent cold light whitening, while samples in group B were treated with infiltration resin combined with cold light whitening. The color was measured before and after the treatment. Then, 6 teeth (the first subgroup) were randomly selected from the 18 anterior teeth after measurement for scanning electron microscopy (SEM) to observe the surface microstructure of the teeth. Then, another 6 teeth (the second subgroup) were selected from the remaining 12 teeth for the measurement of the color level and ΔE after being dyed with tea. Results: After treatment, the color level changed significantly in group A and B (P < 0.05), ΔE in group A and B was 13.75, 14.98. There was no significant difference in the color level change between group B and group A, there was a significant difference in the ΔE between the two groups (t = -3.58, P < 0.05). SEM showed that the enamel surface was intact and that the enamel space was filled in group B. In group A, the enamel surface was reduced and uneven, and the characteristic badminton racquet shape of the enamel was not obvious. The color level was lower in both groups after staining, and these differences were significant (P < 0.05), ΔE in group A and B was 19.69, 18.95. There was no significant difference in the color level (t = 1.00, P > 0.05) and ΔE (t = 0.02, P > 0.05) between two groups. Conclusion Cold light whitening combined with infiltration resin is better for treating dental fluorosis than cold light whitening alone.