Aging has emerged as a cutting edge and hotspot in global life science field， with anti-aging and geriatric disease prevention and treatment becoming critical issues urgently demanding solutions in international medical communities. In the face of the challenge of accelerating global population aging， in-depth exploration of aging mechanisms and the development of effective intervention strategies hold significant scientific and clinical value. This study supported by the national key research and development program of China， employed the essence-Qi-spirit theory of Qiluo doctrine as its guiding framework， focusing on the key scientific issue of the core traditional Chinese pathogenesis of aging， namely "depletion of kidney essence， deficiency of primordial Qi， and impairment of body and spirit". The treatment principle of "tonifying the kidney to replenish essence， harmonizing Yin and Yang， warming and invigorating primordial Qi， and nourishing the body and spirit" was established. Centered on holistic aging， systemic aging， and aging-related diseases， the research integrated multidisciplinary research approaches to construct multi-modal aging models and a multi-dimensional evaluation system， and it utilized multi-omics technologies to deeply analyze aging mechanisms. By systematically reviewing historical kidney-tonifying and anti-aging formulas and combining big data with artificial intelligence technologies， an information database of anti-aging traditional Chinese medicine substance was developed to reveal the differences and synergistic effects of various treatment methods and formulas on anti-aging. Based on this treatment method， the research integrated two millennia of kidney-tonifying medicinal experience to develop the innovative anti-aging traditional Chinese medicine， namely Bazhi Bushen capsules. It was validated that this capsule can delay holistic and systemic aging through multiple targets and mechanisms， thereby elucidating the scientific connotation of the essence-Qi-spirit theory of Qiluo doctrine in guiding anti-aging research from multiple dimensions and providing robust support for leveraging the advantages of traditional Chinese medicine to occupy the commanding heights of international anti-aging research.

[Objective] To establish a new scoring system to predict the perioperative outcomes (operation time, intraoperative blood loss, and trifecta achievement) in patients undergoing robot-assisted partial nephrectomy (RAPN) by integrating the RENAL and Mayo adhesive probability (MAP) scores. [Methods] Clinical data of 178 patients with renal cell carcinoma who underwent RAPN performed by the same surgeon in our hospital during Jan.2015 and Jan.2022 were retrospectively analyzed.The RENAL and MAP scores of all patients were calculated.Linear regression and logistic regression were used to evaluate the associations between the components of the RENAL and MAP scores (a total of 6 variables) and perioperative outcomes.The factors with significant associations were then included into logistic regression analysis to identify independent predictors for constructing an assessment system for perioperative outcomes, and the receiver operating characteristic (ROC) curve was plotted to calculate the area under the curve (AUC) to predict its efficacy. [Results] Multivariate linear regression analysis showed that tumor size (β=6.14, 95%CI: 1.93—10.34, P=0.004), exophytic rate (β=10.60, 95%CI: 3.44—17.76, P=0.004), and perinephric fat thickness (β=16.48, 95%CI: 8.52—24.45, P<0.001) were significantly associated with operation time.Tumor size (β=10.55 95%CI: 5.60—15.49, P<0.001) was associated with both intraoperative blood loss and trifecta achievement (OR=1.73, 95%CI: 1.26—2.36, P=0.001). Multivariate logistic regression analysis of these 3 factors identified tumor size (OR=9.07, 95% CI: 1.18—69.45, P=0.03) and perinephric fat thickness (OR=2.28, 95%CI: 1.86—6.04, P=0.01) as independent predictors of perioperative outcomes.Based on these findings, the tumor size and perinephric fat thickness (RP) scoring was constructed, which demonstrated better predictive ability than RENAL score or MAP score alone (RP vs.RENAL vs.MAP: 0.766 vs.0.548 vs.0.684). [Conclusion] The RP score includes fewer variables than the RENAL and MAP scores but outperforms them.

Objective:To find out whether the performance of a China-made high performance human centrifuge can satisfy the need of high G training by conducting physiological experiments.Methods:The dynamic physical performance of the anti-G equipment with the human centrifuge was tested before 5 subjects underwent the gradual-onset rate (GOR) run and rapid onset rate (ROR) run experiments. The G onset rate of GOR was 0.1 G/s. The relaxed G-tolerance under GOR (GOR tolerance 1) and the anti-G straining maneuver aided G-tolerance under GOR (GOR tolerance 2) were tested respectively. The G onset rate of ROR was 3 G/s, and the closed-loop mode and pre-programed mode were employed respectively. The closed-loop mode involved 5 G 10 s and 8 G 10 s, where the subjects were required to manipulate the joystick to ensure that the real-time curve of the load matched the target curve. In the pre-programmed mode, the subjects were exposed to 8 G 10 s passively, without any operation requirements. A subjective evaluation form was filled out by subjects after the experiments, in which the 14 indexes for evaluation were about the gondola facilities and environment, running processes, medical monitoring and overall assessment.Results:Both the oxygen mask and anti-G suit achieved full pressurization within 2.0 s. The GOR tolerance 1 was [4.0(3.8, 4.6)] G while the GOR tolerance 2 was (6.2±0.5) G, suggesting a statistically significant difference ( Z=-2.63, P=0.008). The HP anti-G straining maneuver effect was (2.0±0.6) G. All the 5 subjects finished the 5 G 10 s experiment in a closed-loop mode. Three of them attempted 8 G 10 s in the closed-loop mode (1 subject achieved only 7.6 G peak acceleration, and the other 2 achieved full 8 G 10 s exposure), while the remaining 2 completed the 8 G 10 s in the pre-programmed mode. In the closed-loop mode, it was found that the stick force was too strong, the guiding G and real time G curve were not easy to distinguish for some of the subjects because the curve colors were similar, and that the subjects could not see the G curves clearly in case of a grayout. Both seat comfort and the voice quality of communication got the highest subjective assessment score [5.0(4.0, 5.0)] while the sensation of tumble got the lowest score (2.8±0.8). The median or mean scores of other subjective evaluation indexes ranged from 3.0 to 4.6 points. The overall score of subjective assessment was [4.0(3.5, 4.0)] points. Conclusions:The China-made high performance human centrifuge can meet the requirements of 8.0 G high G training, which can be made more effective and comfortable if the strong stick force and feeling of tumble during stop running are overcome.

Objective:To investigate the value of targeted three-dimensional contrast-enhanced ultrasound（3D-tCEUS）in efficacy evaluation of non-surgical treatments for renal cell carcinoma（RCC）.Methods:Forty nude mice with subcutaneous xenograft tumor model of human RCC（786-O cells）were divided into four groups based on different treatment methods：control，thermal ablation（TA），sunitinib（Suni），and TA+Suni. 3D-tCEUS were performed on days 1，3，7，and 14 post-treatment using self-developed vascular endothelial growth factor receptor 2（VEGFR2）targeted microbubbles. Tumor overall volume（V T）and non-enhanced volume（V N）were measured，from which the volume of the active（enhanced）region was calculated as V A = V T - V N. The tumor total and active area volume was standardized as V T st and V A st（standardized tumor volume = tumor volume after treatment / tumor volume at the beginning of treatment）. Tumor growth curves were plotted and tumor inhibition rates calculated for V T and V A respectively. Quantitative parameters，including the area under the curve（AUC）and the difference in peak intensity before and after burst（dTE），were obtained from the viable tumor enhanced region，and the standardized targeted quantitative parameters were derived by calculating the ratios of parameters at various time points post-treatment to those pre-treatment. The differences in V T st，V A st，AUC and dTE between different treatment groups at different time points were compared. At the end of the experiment，tumor tissues were obtained for immunohistochemical staining to observe the expression of VEGFR2 and CD31 antigens. Results:During the treatment period，no statistically significant differences in weight changes were observed among groups（all P > 0.05）. When V T was taken as the research object，V T st increased across all groups during the treatment period，with the TA group showing the most significant growth，while the TA + Suni group exhibited the smoothest increase in growth curve. When analyzing the tumor enhanced region，tumor growth trend of V A st was different with V T st for all groups；the Suni group showed a slow upward trend，whereas the TA + Suni group showed a continuous decline. Significant differences in tumor inhibition rate originated from V T and V A were noted within the same experimental group（ P < 0.05 for all experimental groups）. One day post-treatment，the AUC and dTE of the TA group were higher than that of the Control group，while the dTE of the TA + Suni group was lower than that of the Control group（all P < 0.05）. By day 3，statistically significant differences in AUC and dTE were observed between each experimental group and Control groups（all P < 0.05）. At day 14，the TA group showed increased AUC and dTE compared with those before treatment，while all other groups，particularly Suni group and TA + Suni group，demonstrated significant reductions（all P < 0.05）. Immunohistochemical results revealed the highest VEGFR2 and CD31 positivity in the TA group，followed by the Control group，while the Suni and TA + Suni groups exhibited lower rates. Conclusions:The combination of TA and targeted therapy effectively induces RCC cells death，demonstrating superior efficacy compared to monotherapy. 3D-tCEUS serves as a accurate and reliable tool for early evaluating the efficacy of non-surgical RCC treatments.

AIM:To explore the protective effect of total flavonoids from rhododendron(TFR)on oxi-dative stress injury in the brain of rats subjected to cerebral ischemia/reperfusion(I/R).METHODS:For-ty male SD rats were randomly divided into 5 groups:sham operation group(Sham group),cere-bral ischemia-reperfusion group(MCAO group),and Cerebral Ischemia/Reperfusion with TFR treat-ment groups(TFR 50,100,200 mg/kg groups).The MCAO group and TFR-treated groups underwent ischemia/reperfusion surgery,and the TFR-treated groups received TFR intragastrically for 14 consecu-tive days following the ischemia/reperfusion injury.After 14 days,comparisons were made in terms of neurological function scores,serum inflammatory factors,oxidative stress indicators,and brain injury markers.Additionally,histological examination of brain tissue morphology using Hematoxylin and Eo-sin(HE)staining,observation of cerebral blood flow through cerebral blood flow imaging,and measurement of lactate dehydrogenase(LDH),neu-ron-specific enolase(NSE)activity in serum,inter-leukin-1(IL-1),interleukin-6(IL-6)levels,superox-ide dismutase(SOD)activity,malondialdehyde(MDA)content,nitric oxide(NO)content,and nitric oxide synthase(NOS)activity were performed.RE-SULTS:Compared to the Sham group,MCAO rats exhibited abnormal neurological function scores,severe damage to the microstructure of brain tis-sue,noticeable changes in brain morphology,ele-vated activities of LDH and NSE,increased levels of IL-1 and IL-6,elevated MDA content,and de-creased SOD,NOS activity,and NO content.In com-parison to the MCAO group,rats treated with TFR at doses of 50,100,and 200 mg/kg showed recov-ery of abnormal neurological function scores,re-duced damage to the microstructure of brain tis-sue,decreased activities of LDH and NSE,lowered levels of IL-1 and IL-6,reduced MDA content,and increased SOD,NOS activity,and NO content.CON-CLUSION:Total flavonoids from Rhododendron can protect against cerebral ischemia/reperfusion inju-ry,reducing oxidative stress levels.

Objective:To establish a novel rapid HIV-1 nucleic acid detection method based on reverse transcription-recombinase aided amplification（RT-RAA）and clustered regularly interspaced short palindromic repeats（CRISPR）technology.Methods:A total of 610 full-length HIV-1 genome sequences reported in China were analyzed，and primers targeting the relatively conserved region of the HIV-1 pol gene and three crRNAs were designed. The crRNAs were validated and screened，and the CRISPR detection system was optimized to establish a “one-pot” HIV-1 RT-RAA/CRISPR assay. Ten recombinant plasmids representing HIV-1 subtypes reported in China were constructed and serially diluted to evaluate the subtype coverage and sensitivity of the assay. The specificity of the assay was evaluated using plasma samples from hepatitis B virus（HBV），hepatitis C virus（HCV）and treponema pallidum（TP）-infected individuals. The clinical performance of the assay was preliminarily evaluated using 45 clinical samples（25 plasma samples from HIV-1 infected individuals and 20 plasma samples from healthy individuals）.Results:The crRNA combination demonstrated higher sequence coverage and higher terminal fluorescence compared to single crRNA. The HIV-1 RT-RAA/CRISPR assay established with the crRNA combination could complete the detection in 30 minutes. This method could detect all 10 reported HIV-1 subtypes in China，with a sensitivity as low as 1-10 copies/μl. No cross-reactivity was observed with HBV，HCV and TP. The results of clinical sample testing were 100% concordant with those of real time fluorescence quantitative RT-PCR assay.Conclusion:This study established a novel HIV-1 RT-RAA/CRISPR nucleic acid detection method with broad subtype coverage，simplicity，rapidity，high sensitivity，and strong specificity. The method shows potential for application in point-of-care testing of HIV-1.

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Clinical chemotherapy for prostate cancer is still compromised by high treatment thresholds and severe off-target toxicity of drugs. Given the limited progress in improving therapeutic outcomes and reducing toxicity with the existing toolbox, efforts to broaden the chemotherapeutic window are highly desired. Here, we discover that gossypol (GSP, a natural compound) dramatically enhances the chemosensitivity of cabazitaxel (CTX), even at previously ineffective concentrations. Based on this interesting finding, we exploit a carrier-free chemotherapeutic nano-booster for prostate cancer treatment, which is molecularly co-assembled by GSP and cabazitaxel (CTX). GSP not only readily forms nanoassembly with CTX, but also functions as a chemotherapeutic enhancer that unlocks an ultra-low-dose chemotherapeutic window. Not only that, precise dual-drug nanoassembly confers CTX a significantly larger maximum tolerable dose. As expected, the nano-booster exerts striking therapeutic benefits in mouse prostate tumor xenograft models. This study advances chemotherapeutic window expansion and self-sensitized chemotherapy toward clinical applicability.

Cannabidiol (CBD), a non-psychoactive cannabinoid, shows great promise in treating methamphetamine (METH) addiction. Nonetheless, the molecular target and the mechanism through which CBD treats METH addiction remain unexplored. Herein, CBD was shown to counteract METH-induced locomotor sensitization and conditioned place preference. Additionally, CBD mitigated the adverse effects of METH, such as cristae loss, a decline in ATP content, and a reduction in membrane potential. Employing an activity-based protein profiling approach, a target fishing strategy was used to uncover CBD's direct target. ATP5A1, a subunit of ATP synthase, was identified and validated as a CBD target. Moreover, CBD demonstrated the ability to ameliorate METH-induced ubiquitination of ATP5A1 via the D376 residue, thereby reversing the METH-induced reduction of ATP5A1 and promoting the assembly of ATP synthase. Pharmacological inhibition of the ATP efflux channel pannexin 1, blockade of ATP hydrolysis by a CD39 inhibitor, and blocking the adenosine A1 receptor (A1R) all attenuated the therapeutic benefits of CBD in mitigating METH-induced behavioral sensitization and CPP. Moreover, the RNA interference of ATP5A1 in the ventral tegmental area resulted in the reversal of CBD's therapeutic efficacy against METH addiction. Collectively, these data show that ATP5A1 is a target for CBD to inhibit METH-induced addiction behaviors through the ADO-A1R signaling pathway.

Objective To explore the risk factors of venous thromboembolism(VTE)following laparoscopic urological surgery and to construct a predictive model.Methods A retrospective analysis was conducted on the clinical data from 846 laparoscopic surgery patients admitted to the Urology Department of Hainan Cancer Hospital from January 2020 to January 2023.Patients were divided into VTE group(n=64)and non-VTE group(n=782)based on postoperative VTE confirmed by imaging examination.Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for VTE after laparoscopic urological surgery.A predictive model was developed using regression coefficients from the multivariate analysis,and its predictive accuracy was assessed using a nomogram.Additionally,its sensitivity and specificity were evaluated through the construction of a receiver operating characteristic(ROC)curve and a calibration curve.The clinical application of predictive model was evaluated using a decision curve analysis.Results The incidence of VTE after laparoscopic urological surgery was 7.6%(64/864).Significant differences were observed between two groups in age,body mass index(BMI),hypertension,diabetes,malignant tumor,history of abdominal surgery,previous VTE,operation time≥4 h,preoperative fibrinogen levels,preoperative prothrombin time,postoperative D-dimer(D-D)levels,Caprini score and postoperative immobilization time(P<0.05).Increasing age,higher BMI,history of malignancy,abdominal surgery,and previous VTE,longer operation and postoperative immobilization time,and higher postoperative D-D levels and Caprini score were identified as independent risk factors for the development of VTE after urological laparoscopy(P<0.05).Based on the regression coefficients between independent risk factors,a predictive model was constructed as P=ex/(1+ex),where X=0.054×age+0.105×BMI+0.902×history of abdominal surgery+1.172×previous VTE+0.787×operation time+1.546×malignant tumor+0.867×postoperative D-D+1.303×Caprini score+0.544×postoperative immobilization time-13.888.The model demonstrated a discriminant evaluation C-index of 0.827,and the area under the ROC curve for the combined independent risk factors is 0.827(95%CI 0.776-0.878),with a sensitivity of 64.1%,and specificity of 87.7%.Calibration and decision curves indicated that high predictive accuracy and clinical application of the model.Conclusions Increasing age,higher BMI,history of malignancy,abdominal surgery,and previous VTE,longer operation and postoperative immobilization time,and higher postoperative D-D and Caprini score are independent risk factors for the development of VTE after urological laparoscopy.