Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Objective:To investigate the establishment, structural, and bonding interface characteristics of an artificial caries-affected dentin model with demineralization and discoloration as a basis of research on caries-affected dentin bonding repair.Methods:One hundred intact molars without caries were collected (acquired from Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University from March to May 2023) and prepared as 5 mm thick dentin specimens. Then, they were screened and divided into 3 parts. One part of dentin specimens was subjected to bacterial biofilms to prepare artificial carious dentin (ACD). They were further ground by 600-grit SiC paper for 0, 12, 24, 36, and 48 s, respectively to obtain 5 groups with different layers of ACD: ACD-0, 12, 24, 36, and 48 s. Sound dentin was used as the control group. To determine the preparation parameter for artificial caries-affected dentin (ACAD), the first part of specimens was used for bacterial visualization observation ( n=3) and demineralization analysis experiments (micro-CT, Raman spectroscopy, and surface micro-hardness analyses, n=3). Another part of dentin specimens was allocated to 3 groups: control group (sound dentin), artificial caries-infected dentin group (ACD-0 s) and ACAD group (prepared according to the parameter determined by the experiments above). They were used for color tests ( n=10), Raman spectroscopy analysis ( n=6) and scanning electron microscope (SEM) observation ( n=1), thus comparing color, chemical composition and structure, and micro-morphology of 3 groups. The rest of dentin specimens were divided into 2 groups: sound dentin and ACAD ( n=6), which were bonded to composite resin with Single Bond Universal in a self-etch mode. Then, the bonding interface was measured using an electron probe micro-analyzer (EPMA). Results:The depth of bacterial invasion for ACD-0 s was (142.4±25.8) μm. And obvious bacteria were observed in the dentin tubules for the ACD-12 s group. For micro-CT, the demineralization depth was (283.9±25.6) μm for ACD-0 s and (139.2±27.9) μm for ACD-36 s. The grey values in some regions of the dentin surface for ACD-48 s resembled those of sound dentin. For Raman spectroscopy, the peak ratio of phosphate to amide Ⅰ was significantly lower for ACD-24 s [4.2 (3.2,6.7)] than ACD-36 s [6.7 (6.0,7.7)] ( P<0.05). Additionally, there was no significant difference in surface micro-hardness between ACD-24 s [8.3 (7.0,10.2) HV] and ACD-36 s [10.2 (9.1,11.4) HV] ( P>0.05). The preparation parameter of ACAD was determined to be grinding for 36 s based on the experimental results above. The brightness (L * value) and the yellow-blue chromaticity (b * value) of ACAD (76.69±2.54, 33.15±1.89) were significantly lower than those of the control group (85.23±1.68, 35.87±1.55) ( P<0.05). The red-green chromaticity (a * value) of ACAD (5.38±1.20) was significantly higher than that of the control group (0.71±0.86) ( P<0.05). Moreover, the collagen structure parameter in Raman spectroscopy (the peak ratio of amide Ⅲ to CH 2) of ACAD (1.089 7±0.038 5) was significantly higher than that of the control group (0.985 2±0.020 1) ( P<0.05). As shown in EPMA, the hybrid layer of ACAD [(4.72±1.03) μm] was significantly thicker than that of sound dentin [(3.02±0.66) μm] ( F=21.09, P<0.001) in a self-etch mode. Conclusions:ACAD is established through bacterial biofilm challenges followed by grinding for 36 s. It is partly demineralized and discolored with collagen structure changes, making it suitable for research on caries-affected dentin bonding.

Objective:To investigate the establishment, structural, and bonding interface characteristics of an artificial caries-affected dentin model with demineralization and discoloration as a basis of research on caries-affected dentin bonding repair.Methods:One hundred intact molars without caries were collected (acquired from Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University from March to May 2023) and prepared as 5 mm thick dentin specimens. Then, they were screened and divided into 3 parts. One part of dentin specimens was subjected to bacterial biofilms to prepare artificial carious dentin (ACD). They were further ground by 600-grit SiC paper for 0, 12, 24, 36, and 48 s, respectively to obtain 5 groups with different layers of ACD: ACD-0, 12, 24, 36, and 48 s. Sound dentin was used as the control group. To determine the preparation parameter for artificial caries-affected dentin (ACAD), the first part of specimens was used for bacterial visualization observation ( n=3) and demineralization analysis experiments (micro-CT, Raman spectroscopy, and surface micro-hardness analyses, n=3). Another part of dentin specimens was allocated to 3 groups: control group (sound dentin), artificial caries-infected dentin group (ACD-0 s) and ACAD group (prepared according to the parameter determined by the experiments above). They were used for color tests ( n=10), Raman spectroscopy analysis ( n=6) and scanning electron microscope (SEM) observation ( n=1), thus comparing color, chemical composition and structure, and micro-morphology of 3 groups. The rest of dentin specimens were divided into 2 groups: sound dentin and ACAD ( n=6), which were bonded to composite resin with Single Bond Universal in a self-etch mode. Then, the bonding interface was measured using an electron probe micro-analyzer (EPMA). Results:The depth of bacterial invasion for ACD-0 s was (142.4±25.8) μm. And obvious bacteria were observed in the dentin tubules for the ACD-12 s group. For micro-CT, the demineralization depth was (283.9±25.6) μm for ACD-0 s and (139.2±27.9) μm for ACD-36 s. The grey values in some regions of the dentin surface for ACD-48 s resembled those of sound dentin. For Raman spectroscopy, the peak ratio of phosphate to amide Ⅰ was significantly lower for ACD-24 s [4.2 (3.2,6.7)] than ACD-36 s [6.7 (6.0,7.7)] ( P<0.05). Additionally, there was no significant difference in surface micro-hardness between ACD-24 s [8.3 (7.0,10.2) HV] and ACD-36 s [10.2 (9.1,11.4) HV] ( P>0.05). The preparation parameter of ACAD was determined to be grinding for 36 s based on the experimental results above. The brightness (L * value) and the yellow-blue chromaticity (b * value) of ACAD (76.69±2.54, 33.15±1.89) were significantly lower than those of the control group (85.23±1.68, 35.87±1.55) ( P<0.05). The red-green chromaticity (a * value) of ACAD (5.38±1.20) was significantly higher than that of the control group (0.71±0.86) ( P<0.05). Moreover, the collagen structure parameter in Raman spectroscopy (the peak ratio of amide Ⅲ to CH 2) of ACAD (1.089 7±0.038 5) was significantly higher than that of the control group (0.985 2±0.020 1) ( P<0.05). As shown in EPMA, the hybrid layer of ACAD [(4.72±1.03) μm] was significantly thicker than that of sound dentin [(3.02±0.66) μm] ( F=21.09, P<0.001) in a self-etch mode. Conclusions:ACAD is established through bacterial biofilm challenges followed by grinding for 36 s. It is partly demineralized and discolored with collagen structure changes, making it suitable for research on caries-affected dentin bonding.

Objective:To analyze the short-term efficacy and safety of robot-assisted laparoscopic partial nephrectomy（RAPN）for non-metastatic pathological stage T 3a renal cell carcinoma. Methods:The clinical and pathological data of 45 patients with pathologically confirmed non-metastatic T 3a renal cell carcinoma who underwent RAPN at Sun Yat-sen University Cancer Center between January 2016 and December 2023 were retrospectively reviewed. There were 30 males and 15 females. The average age of the cohort was（54.3±10.7）years，and the average clinical tumor diameter was（4.9±1.8）cm. Of all the patients，35（77.8%）were asymptomatic，7（15.6%）presented with hematuria，and 3（6.7%）presented with lumbar pain. Preoperative imaging assessed 34 patients（75.6%）as having clinical stage T 3a，all suspected of involving the collecting system or perirenal fat invasion；the remaining 11 patients（24.4%）were assessed as having stage T 1-2 disease. The median R.E.N.A.L. nephrectomy score was 8.0（7.0，10.0）. A history of hypertension，diabetes，or chronic kidney disease was present in 18 patients（40.0%）. The primary endpoint was progression-free survival，and the secondary endpoints included postoperative complications and short-term renal function outcomes. Survival curve was estimated using the Kaplan-Meier method，and renal function comparisons were made using the paired t-test. Results:The RAPN was performed through a transabdominal approach in 32 patients（71.1%），with a median estimated blood loss of 150.0（50.0，300.0）ml. Seven（15.6%）patients required intraoperative blood transfusion. The median length of postoperative hospital stay was 4.0（4.0，6.0）days. Postoperative complications occurred in 6 patients（13.3%），including 5（11.1%）with mild complications and 1（2.2%）with a severe complication. Renal function returned to baseline in 24 of 39 evaluable patients（61.5%），while 3 patients（7.7%）developed surgery-related chronic kidney disease 3 to 12 months postoperatively，but none required dialysis. The median follow-up time was 31.8（22.7，50.9）months，12（26.7%）patients received programmed cell death protein 1 inhibitor adjuvant therapy postoperatively. During follow-up，3 patients experienced tumor recurrence，the 3-year progression-free survival rate of the entire cohort was 95.4%.Conclusions:For some carefully selected patients with T 3a renal cell carcinoma，RAPN performed by experienced surgeons is a feasible and safe option，providing excellent short-term oncological outcomes，complication control，and renal function recovery. The long-term efficacy remains to be seen.

Objective:To analyze the short-term efficacy and safety of robot-assisted laparoscopic partial nephrectomy（RAPN）for non-metastatic pathological stage T 3a renal cell carcinoma. Methods:The clinical and pathological data of 45 patients with pathologically confirmed non-metastatic T 3a renal cell carcinoma who underwent RAPN at Sun Yat-sen University Cancer Center between January 2016 and December 2023 were retrospectively reviewed. There were 30 males and 15 females. The average age of the cohort was（54.3±10.7）years，and the average clinical tumor diameter was（4.9±1.8）cm. Of all the patients，35（77.8%）were asymptomatic，7（15.6%）presented with hematuria，and 3（6.7%）presented with lumbar pain. Preoperative imaging assessed 34 patients（75.6%）as having clinical stage T 3a，all suspected of involving the collecting system or perirenal fat invasion；the remaining 11 patients（24.4%）were assessed as having stage T 1-2 disease. The median R.E.N.A.L. nephrectomy score was 8.0（7.0，10.0）. A history of hypertension，diabetes，or chronic kidney disease was present in 18 patients（40.0%）. The primary endpoint was progression-free survival，and the secondary endpoints included postoperative complications and short-term renal function outcomes. Survival curve was estimated using the Kaplan-Meier method，and renal function comparisons were made using the paired t-test. Results:The RAPN was performed through a transabdominal approach in 32 patients（71.1%），with a median estimated blood loss of 150.0（50.0，300.0）ml. Seven（15.6%）patients required intraoperative blood transfusion. The median length of postoperative hospital stay was 4.0（4.0，6.0）days. Postoperative complications occurred in 6 patients（13.3%），including 5（11.1%）with mild complications and 1（2.2%）with a severe complication. Renal function returned to baseline in 24 of 39 evaluable patients（61.5%），while 3 patients（7.7%）developed surgery-related chronic kidney disease 3 to 12 months postoperatively，but none required dialysis. The median follow-up time was 31.8（22.7，50.9）months，12（26.7%）patients received programmed cell death protein 1 inhibitor adjuvant therapy postoperatively. During follow-up，3 patients experienced tumor recurrence，the 3-year progression-free survival rate of the entire cohort was 95.4%.Conclusions:For some carefully selected patients with T 3a renal cell carcinoma，RAPN performed by experienced surgeons is a feasible and safe option，providing excellent short-term oncological outcomes，complication control，and renal function recovery. The long-term efficacy remains to be seen.

Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost, sustainability, and tissue targeting. Thus, they hold promise for disease treatment and drug delivery. In this study, we proposed a time-efficient method, PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles (GDNVs). Subsequently, curcumin (CUR) was loaded onto GDNV by ultrasonic incubation. The optimum conditions for ginger-derived nanovesicles loaded with curcumin (CG) were ultrasound time of 3 min, a carrier-to-drug ratio (GDNV:CUR) of 1:1. The study achieved a high loading capacity (94.027% ± 0.094%) and encapsulation efficiency (89.300% ± 0.344%). Finally, the drugs' in vivo distribution and anti-colitis activity were investigated in mice. CG was primarily distributed in the colon after oral administration. Compared to CUR and GDNV, CG was superior in improving disease activity, colon length, liver and spleen coefficients, myeloperoxidase activity, and biochemical factor levels in ulcerative colitis (UC) mice. In addition, CG plays a protective role against UC by modulating serum metabolite levels and gut flora. In summary, our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.

Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost,sustainability,and tissue targeting.Thus,they hold promise for disease treatment and drug delivery.In this study,we proposed a time-efficient method,PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles(GDNVs).Subse-quently,curcumin(CUR)was loaded onto GDNV by ultrasonic incubation.The optimum conditions for ginger-derived nanovesicles loaded with curcumin(CG)were ultrasound time of 3 min,a carrier-to-drug ratio(GDNV:CUR)of 1∶1.The study achieved a high loading capacity(94.027％±0.094％)and encapsu-lation efficiency(89.300％±0.344％).Finally,the drugs'in vivo distribution and anti-colitis activity were investigated in mice.CG was primarily distributed in the colon after oral administration.Compared to CUR and GDNV,CG was superior in improving disease activity,colon length,liver and spleen coefficients,myeloperoxidase activity,and biochemical factor levels in ulcerative colitis(UC)mice.In addition,CG plays a protective role against UC by modulating serum metabolite levels and gut flora.In summary,our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.

In the field of ethics,issues related to brain-computer interface(BCI)technology mainly focus on physical and mental ethics,as well as social ethics,including personal privacy rights,whether a person is a person in the complete sense,the attribution of social responsibility.The population involved includes patients,doctors,and the whole social group in which patients live.In addition to analyzing physical and mental ethical risks,this paper also analyzed the potential ethical issues that may exist in the future large-scale application of BCI based on the current research status,mainly including the right of informed consent,privacy,and decision-making of physical and mental ethical risks,the responsibility attribution and fairness of social ethical risks,the responsibility ascription and equity of social ethical risk,and the question that whether the brain is the carrier of machine or the machine is the continuation of the brain in future ethical risks.Solutions have been proposed in the three levels of individual,system,and institution to provide governance recommendations for the future development of BCI.In addition,local data was obtained by collecting and summarizing relevant opinions through social research.Based on these,the future risks of BCI were introduced for the first time,and from the perspective of ethics,solutions to future problems were explored.

Postoperative pain seriously affects the recovery process of patients, resulting in prolonged hospital stay and increased care costs. Appropriate application of patient-controlled analgesia devices can effectively relieve perioperative acute pain. In 1994 patient-controlled analgesia began to be used in Peking Union Medical College Hospital, and the Acute Pain Service Working Group was established in 2004. With the cooperation of anesthesiologists and specialist nurses, the group jointly has implemented the whole process and standardized management based on patient-controlled analgesia, and constantly improved and innovated working methods, laying a solid foundation for the development of postoperative pain management. This paper systematically reviews and summarizes the work from the aspects of clinical focus, nursing management experience, promotion and dissemination of pain treatment concepts, and development of acute pain service model under the new situation, with the hope of providing valuable reference for comprehensively strengthening pain management in the process of diagnosis and treatment, and enhancing patients' satisfaction with perioperative analgesia services.

Objective To compare and analyze the efficacy and risks of percutaneous CT/ultrasound-guided bipolar radiofrequency ablation(RFA)under local anesthesia with robotic-assisted laparoscopic partial nephrectomy(RAPN)for the treatment of sporadic small renal mass.Methods A retrospective study was conducted on 93 consecutive patients with T1a stage small renal mass during Mar.2019 and Oct.2021.Among them,51 underwent RAPN,and 42 underwent RFA.General information,tumor characteristics,perioperative and follow-up data were collected and statistically analyzed.Results There were no significant differences in general information and tumor characteristics between the two groups(P＞0.05).The operation time[(96.0±20.0)min vs.(113.5±24.1)min,P＜0.001],hospital stay[(3.5±0.8)day vs.(6.9±1.8)day,P＜0.001],and hospital costs[(2.4±0.7)ten thousand yuan vs.(6.6±0.4)ten thousand yuan,P＜0.001]were significantly decreased in the RFA group than in the RAPN group.There were no significant differences in the incidence of perioperative complications and long-term disease-free survival rate between the two groups(P＞0.05).However,the difference between one-year postoperative estimated glomerular filtration rate(eGFR)and preoperative eGFR was significantly lower in the RFA group than in the RAPN group[-2.3(-4.7-1.3)mL/(min·1.73 m2)vs.-5.0(-9.1 2.8)mL/(min·1.73 m2),P=0.003],and the reduction of one-year postoperative creatinine and preoperative creatinine was slightly lower in the RFA group than in the RAPN group[4.0(-0.2-5.5)μmol/L vs.4.5(1.8-9.2)μmol/L,P=0.122].Conclusion RFA can achieve comparable disease-free survival rate as RAPN in the treatment of T1a renal tumor,and can effectively preserve renal function,reduce medical costs,save medical resources,and lower the incidence of perioperative complications.