Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca²⁺ overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM. Our results revealed the remarkably upregulation of Trdn-as in the hearts of the DCM mice and cardiomyocytes treated with high glucose (HG). Knocking down Trdn-as in cardiac tissues significantly improved cardiac dysfunction and remodeling in the DCM mice. Conversely, Trdn-as overexpression resulted in cardiac damage resembling that observed in the DCM mice. At the cellular level, Trdn-as induced Ca²⁺ overload in the SR and mitochondria, leading to mitochondrial dysfunction. RNA-seq and bioinformatics analyses identified calsequestrin 2 (Casq2), a primary calcium-binding protein in the junctional SR, as a potential target of Trdn-as. Further investigations revealed that Trdn-as facilitated the recruitment of METTL14 to the Casq2 mRNA, thereby enhancing the m⁶A modification of Casq2. This modification increased the stability of Casq2 mRNA and subsequently led to increased protein expression. When Casq2 was knocked down, the promoting effects of Trdn-as on Ca²⁺ overload and mitochondrial damage were mitigated. These findings provide valuable insights into the pathogenesis of DCM and suggest Trdn-as as a potential therapeutic target for this condition.
Animals ; Diabetic Cardiomyopathies/pathology* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac/metabolism* ; Mice ; Calsequestrin/genetics* ; Calcium/metabolism* ; Male ; Sarcoplasmic Reticulum/metabolism* ; Methyltransferases/metabolism* ; Mice, Inbred C57BL ; Mitochondria, Heart/metabolism* ; Disease Models, Animal ; Mitochondria/metabolism*

AIM:To explore the therapeutic effect of teprenone(geranylgeranylacetone,GGA)on lipopolysac-charide(LPS)-induced cardiac dysfunction and its mechanism.METHODS:(1)Eight-week-old male C57BL/6 wild-type mice and carboxyl terminus of heat shock protein 70(HSP70)-interacting protein(CHIP)gene knockout mice were randomly divided into control group,LPS group,LPS+GGA group and GGA group,with 8 mice in each group.The model was established by intraperitoneal injection of LPS(25 mg/kg),and 1 h after LPS stimulation,mice were given intraperito-neal injection of GGA(100 mg/kg).The technique of high-resolution ultrasonography system was used to evaluate the car-diac function of mice.The serum of mice from each group were collected to detect the levels of creatine kinase-MB(CK-MB)and lactate dehydrogenase(LDH).HE staining was performed to observe histological changes of cardiac tissues.ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in cardiac tissues.West-ern blot was used to detect the protein levels of HSP70,CHIP,karyopherin-α 2(KPNA2),myeloperoxidase(MPO),vas-cular cell adhesion molecule(VCAM),intercellular cell adhesion molecule(ICAM),and nuclear factor-κB(NF-κB)in cardiac tissues.(2)In vitro cell inflammation model was established using mouse myocardial cells HL-1 stimulated with LPS.ELISA was used to detect the levels of TNF-α and IL-6 in cell supernatants.Western blot was used to detect the pro-tein expression levels of HSP70,CHIP,and KPNA2 in myocardial cells.Immunofluorescence staining was performed to observe the content of nuclear NF-κB.RESULTS:(1)GGA effectively improved cardiac function of LPS-stimulated mice,significantly increased ejection fraction and left ventricular fractional shortening(P<0.01),reduced serum levels of CK-MB and LDH(P<0.01),and alleviated myocardial injury.(2)GGA significantly reduced the release of TNF-α and IL-6 caused by LPS(P<0.01),as well as nuclear translocation of NF-κB,decreased the levels of KPNA2,MPO,VCAM and ICAM in cardiac tissues,and increased the levels of HSP70 in cardiac tissues and cells(P<0.01).(3)In CHIP knockout myocardial cells and mice,GGA failed to inhibit LPS-induced inflammatory response and lost its effect on im-proving cardiac function.CONCLUSION:The protective effect of GGA against LPS-caused cardiac dysfunction of mice is related to increasing expression of HSP70 and promoting CHIP activation,which inhibits the translocation of NF-κB into nucleus and suppresses inflammatory factor release.CHIP knockout abolishes the effects of GGA on reducing LPS-induced inflammatory response and myocardial injury.

Objective : To understand the epidemiological characteristics of notifiable respiratory infectious diseases in Huzhou City, Zhejiang Province from 2017 to 2022, so as to provide insights into formulation of respiratory infectious disease prevention and control strategies. Methods: The data pertaining to notifiable respiratory infectious disease in Huzhou City from 2017 to 2022 were collected through the Infectious Disease Report Information System of Chinese Disease Prevention and Control Information System. Epidemiological characteristics of notifiable respiratory infectious disease was analyzed using a descriptive epidemiological method. : Results Conclusions: A total of 31 314 cases of notifiable respiratory infectious diseases were reported in Huzhou City from 2017 to 2022, with an average annual reported incidence of 169.12/105. The reported incidence of notifiable respiratory infectious diseases appeared a tendency towards a rise in Huzhou City from 2017 to 2022 (P<0.05). The top six reported diseases in terms of case numbers were influenza (20 048 cases), tuberculosis (6 920 cases), COVID-19 (1 893 cases), mumps (1 413 cases), pertussis (475 cases) and scarlet fever (442 cases), accounting for 99.61% of the total cases. The incidence of influenza, COVID-19 and pertussis showed a tendency towards a rise, the incidence of mumps and tuberculosis showed a tendency towards a decline (all P<0.05), and scarlet fever remained at a low-level incidence (P>0.05). Respiratory infectious diseases were mainly reported in winter (January, February and December), with 14 644 cases accounting for 46.77%. There were 15 068 cases reported in schools and kindergartens, accounting for 48.12%. The incidence showed a U-shaped variation with age, with the highest incidence in residents at ages of 10 years and below (987.68/105), and showing a tendency towards a rise in residents at ages of 60 years and above. The incidence of respiratory infectious diseases in Huzhou City from 2017 to 2022 increased significantly. Influenza, tuberculosis, COVID-19, mumps and pertussis are key notifiable respiratory infectious diseases. Residents at ages of 10 years and below and 60 years and above should be given a high priority for respiratory infectious disease control.

Objective:To explore the value of difference value and relative value of pulmonary vascular quantitative parameters of biphasic CT in diagnosis of chronic obstructive pulmonary disease (COPD) and high-risk groups.Methods:The study was a cross-sectional study. A retrospective study of 624 patients who underwent biphasic chest CT scanning in the Second Affiliated Hospital of PLA Naval Medical University from August 2018 to December 2020. Subjects were divided into three groups according to pulmonary function test: normal group ( n=321), preserved ratio impaired spirometry (PRISm) ( n=204) and COPD group ( n=99). The pulmonary vascular quantitative parameters were obtained by the workstation, including the number of pulmonary vessels (N total), cross-sectional area less than that of 5 mm 2 (N CSA5), vessel area (VA total) of 9, 12, 15, 18, 21 mm from the pleura, total blood vessels volume (TBV) and total blood vessels volume under 5 mm 2 (BV5) at expiratory and inspiratory phase. The difference value, relative value of biphasic CT were calculated. ANOVA test or Kruskal-Wallis H test was used to compare the differences of pulmonary vascular quantitative parameters among the three groups, and LSD or Bonferroni tests were used for multiple comparisons. Results:The N total, N CSA5, VA total of the whole lung in the inspiratory phase at the level of 9, 12, 15, 18 and 21 mm from the pleura and TBV, BV5 in the normal group, PRISm group and COPD group, showed an overall trend of decreasing and then increasing, and the PRISm group was lower than those of the normal group ( P<0.05). The differences in N total, N CSA5, VA total between the COPD group and the normal group at the level of 9 and 21 mm from the pleura were not statistically significant ( P>0.05), while the N total, N CSA5, V Atotal of biphasic difference value and relative value in COPD group demonstrated a significant difference from those in normal group ( P<0.05). Conclusion:The difference value and relative value of pulmonary vascular quantitative parameters in biphasic CT are more useful than single inspiratory-phase vascular parameters to differentiate the changes in pulmonary vascular remodeling between COPD patients and the normal population, and also to complement the pulmonary vascular characteristics of the PRISm population, which can provide a basis for early warning of COPD and high-risk populations.

Objective: To investigate the trends in incidence and epidemiological characteristics of notifiable infectious diseases in Huzhou City, Zhejiang Province from 2005 to 2023, so as to provide insights into optimizing infectious disease surveillance and control. Methods: Data of notifiable infectious disease cases in Huzhou City from 2005 to 2023 were collected from the Infectious Disease Report Information System of Chinese Disease Prevention and Control Information System. Trends in incidence were analyzed using annual percent change (APC) and average annual percent change (AAPC). The population distribution and seasonal characteristics were descriptively analyzed. Results: From 2005 to 2023, a total of 504 283 cases of notifiable infectious diseases were reported in Huzhou City, with an annual crude incidence rate of 892.65/105 and a standardized incidence rate of 989.21/105. The incidence rate of notifiable infectious diseases in Huzhou City showed an upward trend (AAPC=8.886%, P<0.05), of which there was an obvious upward trend from 2021 to 2023 (APC=95.996%, P<0.05). After the removal of COVID-19 incidence, the incidence trend was basically unchanged (AAPC=7.970%, P<0.05). From 2005 to 2023, the incidence rate of class A and B notifiable infectious diseases showed no obvious trend (P>0.05), and the incidence rate of class A and B respiratory infectious diseases showed an upward trend (AAPC=6.958%, P<0.05). After the removal of COVID-19 incidence, the two showed a downward trend (AAPC=-7.680% and -8.660%, both P<0.05). The incidence rate of class A and class B intestinal infectious diseases, blood-borne and sexually transmitted infectious diseases showed a downward trend (AAPC=-14.849% and -5.977%, both P<0.05), while the incidence rates of natural and insect-borne infectious diseases did not show a significant trend (P>0.05). The overall incidence rate of class C infectious diseases showed an upward trend (AAPC=13.058%, P<0.05). The incidence rate ratio (IRR) of notifiable infectious diseases between males and females was 1.26 (95%CI: 1.25-1.27). A total of 204 043 cases under 10 years were reported, accounting for 40.46%. The peak incidence of class A and B respiratory infectious diseases was in January, May and June, while that of class A and B intestinal infectious diseases was from June to October. The peak incidence of class C respiratory infectious diseases was in January, March, April and December, while that of class C intestinal infectious diseases was from May to August and from November to December. Conclusions The incidence rate of notifiable infectious diseases in Huzhou City showed an upward trend from 2005 to 2023, which was more obvious from 2021 to 2023. Men and children under 10 years were the high-risk population. The incidence of respiratory and intestinal infectious diseases had obvious seasonal characteristics.

Objective: To investigate the epidemilogical characteristics of pulmonary tuberculosis in Huzhou City, Zhejiang Province from 2014 to 2023, so as to provide the basis for formulating prevention and control measures for the construction of "TB-free city". Methods: The data of pulmonary tuberculosis cases in Huzhou City from 2014 to 2023 was collected through the Infectious Disease Reporting Management System of Chinese Disease Prevention and Control Information System. The onset time, region, and population distribution characteristics of the cases were described. Results: A total of 11 598 cases of pulmonary tuberculosis were reported in Huzhou City from 2014 to 2023, with an average annual incidence of 37.42/105. The reported incidence decreased from 47.50/105 in 2014 to 28.36/105 in 2023 (P<0.05), with an annual decline rate of 5.57%. There were 6 304 etiological positive cases, accounting for 54.35%. The peak season for pulmonary tuberculosis cases was from March to September, with the highest seasonal ratio of 112.48% in May. The average annual reported incidence rates in Anji County and Changxing County were relatively high (46.14/105 and 41.15/105). The reported incidence rate of pulmonary tuberculosis in Huzhou City increased with age (P<0.05), peaking at 97.36/105 in the group aged 75 to <80 years. There were 7 991 male pulmonary tuberculosis cases and 3 607 female cases, with a male-to-female ratio of 2.22∶1. The average annual incidence rates of pulmonary tuberculosis was higher in males than in females (50.39/105 vs. 23.87/105). Farmers were the primary occupation affected, with 6 350 cases accounting for 54.75%. Conclusions The reported incidence rate of pulmonary tuberculosis in Huzhou City decreased from 2014 to 2023, with a high incidence in spring and summer. The incidence rates in Anji County and Changxing County were higher than Huzhou City's average. Male, elderly residents and farmers were the key populations for pulmonary tuberculosis prevention and control.

Objective:To assess the effectiveness of a model created using clinical features and preoperative chest CT imaging features in predicting the chronic obstructive pulmonary disease (COPD) among patients diagnosed with lung cancer.Methods:A retrospective analysis was conducted on clinical (age, gender, smoking history, smoking index, etc.) and imaging (lesion size, location, density, lobulation sign, etc.) data from 444 lung cancer patients confirmed by pathology at the Second Affiliated Hospital of Naval Medical University between June 2014 and March 2021. These patients were randomly divided into a training set (310 patients) and an internal test set (134 patients) using a 7∶3 ratio through the random function in Python. Based on the results of pulmonary function tests, the patients were further categorized into two groups: lung cancer combined with COPD and lung cancer non-COPD. Initially, univariate analysis was performed to identify statistically significant differences in clinical characteristics between the two groups. The variables showing significance were then included in the logistic regression analysis to determine the independent factors predicting lung cancer combined with COPD, thereby constructing the clinical model. The image features underwent a filtering process using the minimum absolute value convergence and selection operator. The reliability of these features was assessed through leave-P groups-out cross-validation repeated five times. Subsequently, a radiological model was developed. Finally, a combined model was established by combining the radiological signature with the clinical features. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) curves were plotted to evaluate the predictive capability and clinical applicability of the model. The area under the curve (AUC) for each model in predicting lung cancer combined with COPD was compared using the DeLong test.Results:In the training set, there were 182 cases in the lung cancer combined with COPD group and 128 cases in the lung cancer non-COPD group. The combined model demonstrated an AUC of 0.89 for predicting lung cancer combined with COPD, while the clinical model achieved an AUC of 0.82 and the radiological model had an AUC of 0.85. In the test set, there were 78 cases in the lung cancer combined with COPD group and 56 cases in the lung cancer non-COPD group. The combined model yielded an AUC of 0.85 for predicting lung cancer combined with COPD, compared to 0.77 for the clinical model and 0.83 for the radiological model. The difference in AUC between the radiological model and the clinical model was not statistically significant ( Z=1.40, P=0.163). However, there were statistically significant differences in the AUC values between the combined model and the clinical model ( Z=-4.01, P=0.010), as well as between the combined model and the radiological model ( Z=-2.57, P<0.001). DCA showed the maximum net benifit of the combined model. Conclusion:The developed synthetic diagnostic combined model, incorporating both radiological signature and clinical features, demonstrates the ability to predict COPD in patients with lung cancer.

ObjectiveTo analyze the polarized light microscopic characteristics， the composition of physical phases and their relative contents of Maifanitum from different origins， and to establish the Fourier characteristic fingerprint of Maifanitum powder crystals by X-ray diffraction（XRD）. MethodA total of 26 batches of Maifanitum samples were selected， and the microscopic characteristics of the sample powders and grinding flakes were observed by polarized light microscopy under single polarized light and orthogonal polarized light， and the main phase compositions and their relative contents were analyzed by powder crystal XRD technique， and the XRD Fourier characteristic fingerprint of Maifanitum was established. The incident light source of XRD was Cu target Kβ radiation， the light tube voltage and light tube current were 40 kV and 40 mA， respectively， the divergence slit was 1°， the scattering slit was 1°， the receiving slit was 0.2 mm， the scanning speed was 5°·min^-1 with continuous scanning and scanning range of 5-90°（2θ）， and the step length was 0.02°. ResultThe polarized light micrographs of powders and grinding flakes of Maifanitum were obtained， and the main phases were plagioclase， potassium feldspar and quartz， and a few samples also contained illite， pyrite， iron dolomite， calcite， iron amphibole and chlorite， etc. The relative total content of feldspar phases was 61.9%-82.4%， and the relative content of quartz was 12.6%-33.6%. The XRD Fourier fingerprint analysis method of Maifanitum with 13 common peaks as the characteristic fingerprint information was established， and the similarity calculated by the mean correlation coefficient method was 0.920 9-0.997 7， the similarity calculated by the mean angle cosine method was 0.940 5-0.998 4， the similarity calculated by the median correlation coefficient method was 0.921 1-0.997 5， and the similarity calculated by the median angle cosine method was 0.947 5-0.998 2. ConclusionThe polarized light microscopic identification characteristics of Maifanitum are mainly plagioclase， quartz and potassium feldspar， and the technique of powder crystal XRD Fourier fingerprint analysis can be used for the identification of Maifanitum.

Objective:To compare the clinical value of visual analogue scale （VAS）, Lebel scale and total nasal symptom scores （TNSS） in evaluating nasal allergen provocation test （NAPT）. Methods:A total of 151 patients suspected of allergic rhinitis admitted to the Department of Otolaryngology-Head and Neck Surgery of our hospital from April 2020 to September 2020 were included, of which 76 were positive for house dust mites and 75 were negative for allergens. Nasal airway resistance（NAR） was measured by active anterior nasal manometry. Nasal symptoms were evaluated by VAS, Lebel and TNSS. House dust mite allergen was used for NAPT by spray method. An increase≥40% in NAR was used as the gold standard for objective evaluation of NAPT. ROC curves of VAS, Lebel and TNSS were drawn to compare the evaluation effectiveness of different subjective evaluation methods, and the optimal critical point of each ROC curve was obtained. Results:With NAR increased by ≥40% as the gold standard, the area under ROC curve of VAS was 0.884, and the sensitivity and specificity were 97.75% and 80.65%, respectively. The area under ROC curve of Lebel was 0.773, and the sensitivity and specificity were 68.54% and 75.81%, respectively. The area under ROC curve of TNSS was 0.792, and the sensitivity and specificity were 68.54% and 79.03%, respectively. There was no significant difference between Lebel and TNSS（P>0.05）. The VAS differed significantly from Lebel and TNSS（P<0.05）. The Kappa values of VAS, Lebel, TNSS and NAR were 0.803, 0.432 and 0.459, respectively. Conclusion:The VAS, Lebel, TNSS subjective scale and NAR are consistent in evaluating the efficacy of NAPT, with the VAS assessment showing highest consistency with NAR. As objective assessment instruments are not widely used in China, subjective assessment method could be adopted to evaluate the efficacy of NAPT in clinical practice, and VAS scale is recommended as a priority.
Animals ; Humans ; Allergens ; Nasal Provocation Tests/methods* ; Rhinitis, Allergic/diagnosis* ; Nose ; Pyroglyphidae