Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.

Cholesterol(CH)plays a crucial role in enhancing the membrane stability of drug delivery systems(DDS).However,its association with conditions such as hyperlipidemia often leads to criticism,overshadowing its influence on the biological effects of formulations.In this study,we reevaluated the delivery effect of CH using widely applied lipid microspheres(LM)as a model DDS.We conducted comprehensive in-vestigations into the impact of CH on the distribution,cell uptake,and protein corona(PC)of LM at sites of cardiovascular inflammatory injury.The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage.Then,the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy.Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma(PPAR-γ)expression in vascular endothelial cells and estrogen receptor alpha(ERα)protein levels in myocardial cells,thereby enhancing LM uptake at cardiovascular inflam-mation sites.Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V(Apoa5);this may be a major contributing factor to their prolonged circu-lation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites.It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations.The findings enhance the conceptualization of CH and LM delivery,providing novel strategies for investigating prescription factors' bioactivity.

OBJECTIVE: To investigate the therapeutic potential of octaarginine (R8)-modified essential oil from Fructus Alpiniae zerumbet (EOFAZ) lipid microspheres (EOFAZ@^R8LM) for cardiovascular therapy. METHODS: EOFAZ@^R8LM was developed by leveraging the volatilization of EOFAZ and integrating it with the oil phase of LM, followed by surface modification with cell-penetrating peptide R8 to target the site of vascular endothelial injury. The therapeutic effects of this formulation in alleviating lipopolysaccharide-induced vascular endothelial inflammation were evaluated by assessing mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels, as well as inflammatory factors interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels. RESULTS: EOFAZ@^R8LM effectively delivered EOFAZ to the site of injury and specifically targeted the mitochondria in vascular endothelial cells, thereby ameliorating mitochondrial dysfunction through regulation of MMP and reduction of intracellular ROS levels. Moreover, it attenuated the expression levels of IL-6 and IL-1β, exerting protective effects on the vascular endothelium. CONCLUSION Our findings highlight the significant therapeutic potential of EOFAZ@^R8LM in cardiovascular therapy, providing valuable insights for developing novel dosage forms utilizing EOFAZ for effective treatment against cardiovascular diseases.

Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.

Objective To investigate the effect of angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and AngII receptor (ATR) gene polymorphisms combined with climatic factors on the incidence of essential hypertension (EH) in Tibetan population in Gannan area. Methods A follow-up study was conducted to select 671 Tibetan people in Gannan area who were physically examined in April 2019 at the Health Management Center of the Second Hospital of Lanzhou University and agreed to be enrolled as a fixed cohort, and the blood pressure values of the enrolled subjects were measured after 3.5 years of follow-up, and a total of 501 cases were obtained. At the same time, the peripheral blood of all subjects was collected and the polymorphisms of AGT, ACE and ATR genes were detected by gene chip technology, and the possible interactions were analyzed by logistic regression model, fork generation method and multifactor-dimensionality reduction (MDR). Results Sunshine time was a protective factor for the incidence of hypertension in the Tibetan population of Gannan (OR=0.781), while relative humidity (OR=1.182), air pressure (OR=1.338) and temperature (OR=1.449) were the risk factors for the incidence of hypertension. According to the results of partial correlation analysis, temperature had no effect on the incidence of hypertension after controlling air pressure. There was an additive interaction between high air pressure and the polymorphisms of rs699 (OR=1.650, 95%CI: 1.293-2.399, P<0.001) and rs5049 (OR=1.711, 95%CI: 1.337-4.920, P<0.001) genes of AGT gene; there was a multiplicative interaction between relative humidity and rs699 (OR=0.472, 95%CI: 0.120-0.783, P<0.05);there was a multiplicative interactions between the altitude ≥ 3000m and rs699 (OR=1.503, 95%CI: 1.220-3.174, P<0.01), rs5049 (OR=1.673, 95%CI: 1.380-3.961, P<0.001) or rs2148582 (OR=0.519, 95%CI: 0.284-0.716, P<0.05).However, there was no interaction between climatic factors and ACE or ATR gene polymorphisms on the incidence of hypertension. Conclusion Climatic factors and altitude ≥3 000 m are closely related to the incidence of hypertension in the Tibetan population of Gannan area, and the interaction between AGT gene polymorphisms and climatic factors affects the incidence of hypertension in the population of this area.

Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.

BACKGROUND:Current studies have shown that electronic moxibustion can improve memory function in amnestic mild cognitive impairment;however,its mechanism of action needs to be further investigated.The atrophy of hippocampal volume and impairment of functional connectivity are important imaging markers of amnestic mild cognitive impairment.Whether electronic moxibustion can regulate the volume of hippocampal subregion of partients with amnestic mild cognitive impairment is worth studying. OBJECTIVE:To observe the effect of electronic moxibustion on the volume of hippocampal subregions in patients with amnestic mild cognitive impairment. METHODS:Forty patients with amnestic mild cognitive impairment were recruited from April 1,2018 to January 31,2019 at the community service centers around the Second Affiliated Hospital of Shenzhen University(Baoan Hospital of Southern Medical University),Shenzhen,China.They were randomly divided into treatment group(n=20)and control group(n=20).The treatment group was treated with electronic moxibustion of regulating the mind and benefiting the intelligence,while the control group was treated with placebo moxibustion.Moxibustion was given at 45 oC,20 minutes each time,once a day,5 times a week,for 8 weeks in total.Memory evaluation using Rivermead behavioral memory test and magnetic resonance imaging scanning for detecting the hippocampal subregion volume were performed for each patient before and after treatment,and cognitive function of each patient was assessed using Montreal cognitive assessment and mini-mental state examination.Correlation of hippocampal subregion volumes with scores on each scale was analyzed. RESULTS AND CONCLUSION:After treatment,the volumes of the left parasubiculum and the left hippocampal-amygdala migrating area increased in the treatment group but decreased in the control group,and there was a significant difference between the two groups(P＜0.05).Compared with the pre-treatment data,the Rivermead behavioral memory test,Montreal cognitive assessment,and mini-mental state examination scores were significantly higher in the treatment group after treatment(P＜0.05),while there was no significant change in the three scale scores in the control group after treatment(P＞0.05).The three scale scores were higher in the treatment group than in the control group after treatment(P＜0.05).Pearson correlation analysis showed that the changes in the volume of the left parasubiculum was significantly and positively correlated with the Rivermead behavioral memory test scale score in the treatment group(r=0.418,P=0.014).To conclude,electronic moxibustion can improve memory in patients with amnestic mild cognitive impairment,and the mechanism may be the regulation of structural plasticity in hippocampal subregions.

Objective To explore the inhibitory effect of 17-DMAG on the growth and angiogenesis of PD-1 humanized mouse liver cancer transplantation tumors.Methods 30 PD-1 humanized mice were selected,and a human HepG2 cell suspension was injected into the subcutaneous tissue of the right inguinal region to construct a human liver cancer transplant tumor model.Tumor-bearing humanized mice were randomly divided into three groups(10 mice per group):① model group(injected with 10 mg/kg of physiological saline),②17-DMAG group(intraperitoneal injection of 17-DMAG at 25 mg/kg,3 times/week),and③cisplatin group(intraperitoneal injection of 20 mg/kg,2 times per week).The experiment lasted for 4 weeks.After injection,the length and shortest diameter of humanized mouse transplanted tumors were measured to calculate the volume,and tumor mass was measured to calculate the tumor inhibition rate.At the same time,immunohistochemical method were used to detect the expression of CD31(tumor microvessel density,MVD)and vascular endothelial growth factor(VEGF)in tumor tissue.Results The tumor volume and mass of the 17-DMAG group and cisplatin group were significantly reduced compared to those of the model group(P＜0.05),and the tumor inhibition rate of the 17-DMAG group was slightly higher than that of the cisplatin group.However,there were no significant differences in tumor mass,volume,and tumor inhibition rate between the 17-DMAG group and cisplatin group.The number of MVD-labeled microvessels and level of VEGF expression in the 17-DMAG group and cisplatin group were lower than those in the model group(P＜0.05),and those of the 17-DMAG group were also lower than those in the cisplatin group(P＜0.05).Conclusions 17-DMAG can inhibit the growth of humanized mouse liver cancer xenografts by reducing the expression of VEGF in liver cancer xenograft tissue,thereby inhibiting the generation of tumor neovascularization.

Objective:To investigate the Kub stage classification of clinical renal tuberculosis and provide a reference for disease evaluation and management.Methods:A retrospective analysis was conducted on clinical data from 180 patients diagnosed with renal tuberculosis who were admitted to the First Affiliated Hospital of Dali University between January 2011 and December 2022. The 180 cases included 82 males and 98 females. The average age was (44.56±9.62) years. The tuberculosis lesions of 101 cases were on left kidney, while that of 79 cases were on right kidney. Localized/multiple lesions were observed in 118 cases, whereas extensive destruction was found in 62 cases. Moreover, the ureters were involved in 165 cases, and bladder invasion occurred in 139 cases. For patients undergoing renal preservation treatment, a comprehensive approach was employed, including ureteral stricture stenting and regular replacement of double-J stent, percutaneous nephrostomy, excision of tuberculosis lesions or partial nephrectomy, ureter reconstruction, and sigmoidocystoplasty. In cases requiring nephrectomy, either laparoscopic or open surgical approaches are utilized. Based on the results of patient imaging and endoscopy, staging and classification were performed based on the extent of tuberculosis lesions involving the kidneys (K), ureters (u), and bladder (b). The state for each above organ was divided into four stages: K stage (K 1-4), u stage (u 0-u 3), and b stage (b 0-b 3), which were then combined with the actual disease condition for further categorization. The classifications included local intrarenal type(K 1-2u 0b 0), local renal-ureteral involvement type(K 1-2u 1-2b 0-2), multiple renal-ureteral invasion type(K 3u 1-3b 0-2) and extensive destruction type(K 4u 1-3b 1-3). Further analysis was conducted on kidney preservation and subsequent disease progression among patients with different subtypes. Results:Among the 180 patients, 15 cases of local intrarenal type underwent kidney-preserving treatment. Out of these cases, 6 patients (4 patients in stage K 1u 0b 0 and 2 patients in stage K 2bu 0b 0) achieved clinical cure after receiving a pure durative anti-tuberculosis for two years. Additionally, 4 patients in stage K 2au 0b 0 attained clinical cure following anti-tuberculosis drugs combined with partial nephrectomy after two years of follow-up. Furthermore, 5 patients in stage K 2bu 0b 0 underwent ureteroscopy and D-J stent placement for regular stent replacement. The stents were subsequently removed after two years, and the patients remained clinically stable. Among the 47 cases with localized renal-ureteral involvement type, all initially underwent kidney-preserving treatment. Of these, 5 patients in stage K 1u 1b 0-2 achieved clinical remission, while disease progression necessitated nephrectomy for 3 patients in stage K 2au 1-2b 0-2 and 7 patients in stage K 2bu 1-2b 0-2. The remaining patients maintained stable conditions. Among the 56 cases of multiple renal-ureteral invasion type, stable conditions were observed in 9 out of 24 patients with stage K 3u 1-2b 0-2, while disease progression necessitated nephrectomy in 15 cases. Nephrectomy was performed for all 32 patients with stage K 3u 3b 0-2. In instances of extensive destruction type, nephrectomy was conducted for all 62 cases. The progression rates of the local renal-ureteral involvement type and the multiple renal-ureteral invasion type were 21.28% (10/47) and 48.39% (15/31), and the difference was statistically significant ( P<0.05). The kidney preservation rates of the local renal-ureteral involvement type and multiple renal-ureteral invasion type were 78.72% (37/47) and 16.07% (9/56), and the difference was statistically significant ( P<0.001). Conclusions:The Kub stage classification can provide reference to management and monitoring for renal tuberculosis. The patients in the local intrarenal type and local renal-ureteral involvement type are often treated with anti-tuberculosis plus ureteral stent implantation or partial nephrectomy or ureteral reconstruction. The patients in the multiple renal-ureteral invasion type and extensive destruction type are mostly managed by nephrectomy.