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.

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.

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.

【Objective】 To compare the difference in the detection rate of microorganisms in cord blood between BACTEC FX and BacT/ALERT 3D automated blood culture systems, and to compare the influence of incubation time and different types of culture sample on the detection rate of microorganisms in cord blood. 【Methods】 Cord blood samples prepared from April to August 2020 in Sichuan Cord Blood Bank(n=4 358) were selected, and 20 mL of plasma was used as culture samples for microbial detection. In addition, cord blood samples prepared in the same months of 2021(n=4 057) were selected, and 19 mL of plasma plus 1 mL of final product was used as culture samples for microbial detection. The total sample size was 8 415, of which 4 849 samples(2 458 in plasma group and 2 391 in plasma plus final product group) were assigned to the BACTEC FX system, and 3 566 samples(1 900 in the plasma group and 1 666 in the plasma plus final product group) to the BacT/ALERT 3D system. All samples were cultured for 7 days, and culture data were recorded on day 5 and day 7. Positive results were confirmed by Gram staining. 【Results】 The positive rate detected by the BACTEC FX system was higher than that of the BacT/ALERT 3D system(4.08% vs 2.69%), with statistically significant difference(P<0.05). The positive rates of BACTEC FX and BacT / ALERT 3D on day 7 increased by 8% and 4.26% respectively compared with on day 5. When the culture sample types were concerned, the BACTEC FX showed statistically significant difference in positive rate between plasma group and plasma plus final product group(P<0.05), while no significant difference was found in positive rate(P>0.05) detected by the BacT/ALERT 3D system. With quality control strains, there were significant differences in TTP between these two systems for Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Clostridium sporogenes, and Bacillus subtilis(P<0.05), but no significant difference for Aspergillus brasiliensis and Candida albicans(P>0.05). 【Conclusion】 This study suggests that the selection of BACTEC FX blood culture system with incubation time of not less than 7 days and plasma plus final product as culture samples may improve the detection rate of microorganisms in cord blood.

OBJECTIVE Alzheimer's disease(AD)is the most common neurodegenerative disease worldwide.Neuroinflammation is a potential target for the patients with AD.It is attributed to activated microglia and the release of various inflammatory mediators from infec-tion,ischemia and toxin accumulation.Accumulating evi-dence has indicated that the cGAS-STING pathway driven neuroinflammation in neurological disease.TSG is a main natural active ingredient that derived from polyg-onum multiflorum.Previous research from our group found that TSG has beneficial effects of anti-aging,anti-inflammatory action and improving memory function in APP/PS1 transgenic AD mice.Here,we investigated the effects of TSG on cognitive impairment and neuroinflam-mation in APP/PS1-AD mice and explore the underly-ing mechanism by which TSG ameliorates memory func-tion in the cGAS-STING-mediated inflammatory response.METHODS The Morris water mace test and the novel object recognition test were performed to test the effects of TSG on spatial learning and cognitive and memory abil-ity in APP/PS1 double transgenic AD mice model.In addi-tion,real-time quantitative PCR,Western blotting,ELISA analysis,and flow cytometry to examine gene and pro-tein expression of cGAS-STING related pro-inflammatory cytokines and chemokines.Statistical analyses were ana-lyzed using the SPSS 25.0 package by analysis of vari-ance(ANOVA).Neuman-Keuls or Tukey's multiple-com-parisons test were conducted as ANOVA justified post hoc comparisons between group means.RESULTS We demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation.The expressions of serum inflammatory cytokines and the activation of microglia in cerebral cor-tex and hippocampus were suppressed after TSG treat-ment,which was probably attributable to the decrease of cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)triggered immune response.Additionally,the data showed that TSG treatment reduced the expression level of inflammatory cytokines(IL-1β,TNF-α,IFN-β,IFN-α)in microglial cells BV2 primed with LPS and IFN-γ.CONCLUSION TSG implicated the health benefits in preventing cognitive disorders by inhib-iting neuroinflammation via cGAS-STING signalling path-way in AD.

Objective:To investigate the application value of Da Vinci robotic transanal minimally invasive surgery (R-TAMIS) for local resection of rectal neoplasms.Methods:The retros-pective and descriptive study was conducted. The clinicopathological data of 7 rectal neoplasms patients undergoing R-TAMIS in Daping Hospital of Army Medical University from June 2017 to March 2021 were collected. There were 3 males and 4 females, aged (60±7)years. Observation indicators: (1) intraoperative situations; (2) postoperative recovery; (3) postoperative histopatholo-gical examinations; (4) follow-up. Follow-up was conducted using telephone interview or outpatient examination to detect readmission of patients within postoperative 30 days, tumor recurrence and metastasis and survival of patients. Follow-up was performed at postoperative 1, 3, 6 months and once every 6 months thereafter up to April 2021. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Intraoperative situations. All the 7 patients underwent R-TAMIS successfully without conversion to laparotomy or laparoscopic surgery. Of the 7 patients, 2 cases underwent full-thickness rectal resection and 5 cases underwent submucosal dissection of tumor. The rectal wounds were not sutured in 2 cases because of large lesions, and the rectal wounds were sutured with synthetic sutures in 5 cases after resection of lesions. Transanal drainage tube was placed in 2 cases and not in 5 cases. The volume of intra-operative blood loss of the 7 patients was 15(range, 2?50)mL. The total operation time of the 7 patients was (91.4±18.4)minutes, including (19.1±2.3)minutes for transanal platform placement and Da Vinci robotic surgical system installation, and (72.3±16.6)minutes for operation. There was no intraoperative complication such as urethral injury. (2) Postoperative recovery. All the 7 patients started water drinking and out-of-bed activities at postoperative day 1 and liquid food intake at postoperative day 2. The time to postoperative first flatus of the 7 patients was 1(range, 1?3)days. The two cases with transanal drainage underwent removing of transanal drainage at postoperative day 2. There was no postoperative complication and the duration of postoperative hospital stay of the 7 patients was 3(range, 3?9)days. (3) Postoperative histopathological examinations. Of the 7 patients, 3 cases had villous adenoma, 2 cases had villous adenoma combined with high grade intraepithelial neoplasia, local canceration and tumor invasion into submucosa (stage SM1), 1 case had villous adenoma combined with high grade intraepithelial neoplasia, local canceration and tumor localized in the inner mucosa (stage Tis) and 1 case had moderately differentiated adeno-carcinoma with tumor invasion into superficial muscle layer (stage T2). All the 7 patients had negative surgical margins with none of tumor cell remained in the base. (4) Follow-up. All the 7 patients were followed up for 18(range, 1?42)months. One of the 7 patients showed rectal adenocarcinoma with tumor invasion into superficial muscle layer by the postoperative histopathological examina-tion and was recommended for remedial radical surgery. The patient refused further surgery and underwent 3 courses of oral capecitabine chemotherapy. The other 6 patients did not receive postoperative chemotherapy. None of 7 patients underwent readmission within postoperative 30 days, and no patient had tumor local recurrence, distant metastasis or death during the follow-up.Conclusion:R-TAMIS for local resection of rectal neoplasms is safe and feasible for patients with rectal adenoma and early rectal cancer, with reliable short-term efficacy and short-term oncological efficacy.