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.

OBJECTIVES: To analyze bone mass distribution and the factors affecting bone mass in a general Chinese Han cohort undergoing physical examinations at our center. METHODS: We retrospectively collected the data of bone mineral density (BMD) measurements from 30 599 healthy Han Chinese adults (age≥20 years) who underwent dual-energy X-ray absorptiometry scans at our hospital from July, 2013 to July, 2023. Basic parameters including height, body weight, and gender were recorded, and descriptive statistics and correlation analyses were performed using R software. RESULTS: In this cohort, the male individuals had a mean peak BMD of 1.00±0.12 g/cm² in the lumbar vertebrae, 0.94±0.14 g/cm² in the femoral neck, and 0.99±0.13 g/cm² in the total hip, significantly higher than the values in the female individuals [0.99±0.12 g/cm² in the lumbar vertebrae (P=0.022), 0.79±0.11 g/cm² in the femoral neck (P<0.001), and 0.88±0.11 g/cm² in the total hip (P<0.001)]. In the overall cohort, the BMD values of the lumbar spine and femur decreased with age after reaching their peak levels. There was a positive correlation between BMD value and body mass index (BMI) in both male and female individuals. The 2013-2014 period recorded the lowest BMD values in the lumbar, hip, and femoral neck, which tended to increase steadily in the following years (2015-2023). CONCLUSIONS Our data suggest that the BMD values vary among different populations, and future multi-center studies using more accurate BMD detection technology are warranted to capture the variation patterns of BMD with demographic characteristics of specific populations.
Humans ; Bone Density ; Absorptiometry, Photon ; Male ; Female ; Retrospective Studies ; Osteoporosis/diagnostic imaging* ; Adult ; Middle Aged ; Lumbar Vertebrae/diagnostic imaging* ; China/epidemiology* ; Femur Neck/diagnostic imaging* ; Aged ; Beijing/epidemiology* ; Young Adult

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.

AIM: To investigate the pharmacokinetic properties of the main active components of Dalitong extract in SD rats after oral administration using UPLC-MS / MS. METHODS: An UPLC-MS / MS method was established to simultaneously detect tetrahydropalmatine, nobiletin and costunolide in the plasma and tissues of SD rats. The method was applied to investigate the pharmacokinetic characteristics and tissue distribution. RESULTS: After a single oral administration, the three active components were rapidly absorbed into the body, with a peak concentration (Cmax) of (13.73 ± 7.50), (27.01 ± 17.69) and (6.73 ± 29.94) ng / mL for tetrahydropalmatine, nobiletin, and costunolide, respectively. The time to reach the peak concentration (Tmax) was (1.40 ± 0.93), (0.63 ± 0.28) and (2.38 ± 8.81) h, respectively. The area under the curve (AUC) was (80.43±40.03), (41.30±28.69) and (303.90 ± 136.69) ng · h · mL

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 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 compare the efficacy of double filtration plasmapheresis(DFPP),centrifugal therapeutic plasma exchange(cTPE)and centrifugation-filtration plasmapheresis(CFPP)in improving renal insufficiency after kidney transplantation,as well as the differences in inducing plasma exchange-related adverse reactions.Methods Clinical data from 46 patients who underwent plasma exchange after renal transplantation in our hospital were retrospectively collected,and patiens were divided into DFPP group(n=33),cTPE group(n=7)and CFPP group(n=6).Changes in peripheral blood creatinine,albumin,hemoglobin,platelets,fibrinogen levels and urine volume before and after TPE were compared and analyzed among the three groups.Results Among the DFPP group,cTPE group and CFPP group,the creatinine after TPE decreased by(31.40±25.38)%,(58.91±19.75)%and(39.44±28.64)%,respectively,with cTPE group significant-ly higher than the DFPP group(P＜0.05),but no significant differences between the DFPP group and cTPE group(P＞0.05);the urine volume after TPE increased by(49.33±30.03)%,(54.62±39.32)%and(68.89±23.00)%,showing no significant differences(P＞0.05);the hemoglobin after TPE decreased by(11.97±5.94)%,(20.17±5.75)%and(9.65±8.75)%,respectively,with the cTPE group significantly higher than the DFPP group and CFPP group(P＜0.05),but no significant difference between the DFPP group and CFPP group(P＞0.05).The platelet count after TPE decreased by(37.88±18.39)%,(24.56±12.36)%and(21.40±12.51)%,respectively,with no significant differences between the three groups(P＞0.05);the fibrinogen after TPE decreased by(0.57±0.20)%,(0.14±0.06)%and(0.26±0.22)%,re-spectively,with the DFPP group significantly higher than the cTPE group(P＜0.05),but the CFPP group had no significant difference with cTPE group or DFPP group(P＞0.05);the albumin after TPE decreased by(11.41±5.97)%,(14.67±6.52)%and(25.18±5.10)%,respectively,with cTPE group and DFPP group significantly lower than the CFPP group(P＜0.05,P＜0.001),but with no significant difference between the DFPP group and cTPE group(P＞0.05).Conclusion The effect of three plasma exchange methods varies on renal function,anemia and coagulation function of patients after kid-ney transplantation.It is necessary to consider the the patient's disease characteristics and treatment needs,as well as the laboratory′s technical conditions and plasma supply when selecting TPE methods.

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.

Objectives:To explore the influencing factors of daily living abilities in patients with traumatic spinal cord injury.Methods:A cross-sectional study was conducted on 148 patients with traumatic spinal cord injury admitted to our hospital from January 2019 to January 2023.Factors that may affect the daily living abilities of patients were collected,including gender,age,marital status,course of injury,cause of in-jury,level of injury,American Spinal Injury Association(ASIA)impairment scale(AIS),surgical situation and urination pattern.The spinal cord independence measure Ⅲ(SCIM-Ⅲ)was used to evaluate the daily living abilities in patients with traumatic spinal cord injury.The relationship between the influencing factors and daily living abilities was analyzed by single factor analysis,and multiple linear regression was applied to ana-lyze the impact of the influencing factors on daily living abilities.Results:Univariate analysis showed that the level of injury,AIS and,the urination pattern had significant effects on daily living abilities(P＜0.05),while gender,age,marital status,course of injury,cause of injury,surgical situation had no significant effects on daily living abilities.With regard to the level of injury,patients with sacral spinal cord injury had the best daily living abilities,and patients with cervical spinal cord injury were the worst in daily living abilities.Regarding AIS,patients of level A were the worst in daily living abilities,and patients of level E were the best.In terms of urination pattern,patients who could spontaneous voiding were the best in daily living abil-ities,while those with indwelling catheter/bag had the worst daily living abilities.There were statistically significant differences in self-care,respiratory and sphincter management,movement and total scores between patients with different injury levels,urination patterns and AIS(P＜0.01).Multiple linear regression showed that injury level,urination pattern and AIS were the main factors affecting the daily living abilities.Conclusions:The level of injury,AIS,and the urination pattern are the main factors affecting the daily living abilities of patients with traumatic spinal cord injury,and patients with injury of cervical cord,AIS level A,and indwelling catheter/bag have poor daily living abilities.

Objective:To quantitatively evaluate left ventricular myocardial work in patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) by pressure strain loop (PSL) technique.Methods:A total of 103 T2DM patients diagnosed at the Heping Hospital Affiliated to Changzhi Medical College from April 2022 to May 2023 were selected. They were divided into three groups based on their fatty liver ultrasound findings: group A (34 cases without NAFLD), group B (37 cases with mild NAFLD), and group C (32 cases with moderate to severe NAFLD). All patients underwent routine echocardiography, which measured the end diastolic left ventricular diameter (LVIDd), end systolic left ventricular diameter (LVIDs), end diastolic interventricular septum (IVSTd), left ventricular posterior wall thickness (LVPWTd), and end systolic left atrial diameter (LAD). The biplane Simpson method was used to measure left ventricular ejection fraction (LVEF), end diastolic left ventricular volume (LVEDV), and end systolic left ventricular volume (LVESV). PSL technology was applied to analyze the overall longitudinal strain (GLS), global work index (GWI), global effective work (GCW), global ineffective work (GWW), and overall work efficiency (GWE) of the left ventricular myocardium. We compared the conventional echocardiography parameters and myocardial work parameters among three groups, and analyzed the correlation between myocardial work parameters and GLS and glycosylated hemoglobin (HbA 1c). Results:The differences in body mass index (BMI), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) between group B and group A were statistically significant (all P<0.05); There was a statistically significant difference in BMI, HbA 1c, and low density lipoprotein cholesterol (LDL-C) between group C and group B (all P<0.001); The differences in BMI, HbA 1c, ALT, AST, triglyceride (TC), high density lipoprotein cholesterol (HDL-C), and LDL-C between group C and group A were statistically significant (all P<0.05). The GWI and GCW in group B were lower than those in group A (all P<0.05), while the absolute GLS, GCW, GWI, and GWE in group C were lower than those in group A, and GWW was higher than those in group A (all P<0.05); The absolute values of GLS, GCW, GWI, and GWE in group C were lower than those in group B ( P<0.05). The correlation analysis results showed that GLS and HbA 1c were negatively correlated with GCW and GWI ( r=-0.571, -0.533, -0.273, -0.223, P<0.05). Conclusions:PSL technology can quantitatively evaluate left ventricular myocardial work in patients with T2DM combined with NAFLD, and can detect early impairment of left ventricular systolic function in patients. It has clinical reference value in evaluating overall and local cardiac function.