Plant-derived exosome-like nanovesicles (PELNs), characterized by a natural lipid bilayer membrane, have rapidly emerged as a prominent research frontier in medicine owing to their unique biological properties and robust therapeutic potential. This review comprehensively examines the biological profiles, mechanistic functions, and recent engineering advancements of PELNs. In terms of composition, PELNs are uniquely enriched in plant-specific glycolipids, phosphatidylserine, secondary metabolites, and highly stable 2'-O-methylated miRNAs. This distinct molecular makeup endows them with exceptional biocompatibility, negligible immunogenicity, and the capacity for cross-species molecular communication. Mechanistically, PELNs demonstrate profound anti-inflammatory efficacy by suppressing the NF-κB and NLRP3 inflammasome pathways. They also serve as potent immune modulators, driving macrophage M1/M2 polarization and regulating T cell activity. Additionally, PELNs exhibit promising antitumor capabilities, targeting malignancies via reactive oxygen species (ROS) induction, TRAIL pathway activation, and tumor microenvironment remodeling. Crucially, the plant miRNAs encapsulated within PELNs remain highly stable in the gastrointestinal tract, allowing them to selectively alter gene expression in specific gut microbiota communities. This interaction deeply influences host immunity and metabolism, highlighting the vital role in cross-species regulation. Advancements in bioengineering have further expanded the clinical utility of PELNs. Targeted delivery efficiency can be significantly amplified via surface functionalization (e.g., folate and RGD sequences) and state-of-the-art drug loading technologies such as sonication and electroporation. Consequently, engineered PELNs surpass traditional synthetic nanocarriers in penetrating natural physiological barriers, particularly for oral and transdermal drug administration. Despite these advantages, clinical translation is currently hindered by the lack of standardized isolation protocols, challenges in scalable manufacturing, and the need for robust quality control frameworks. Looking forward, the integration of multi-omics approaches and AI-driven “molecular fingerprinting”—coupled with the design of synthetic biomimetic vesicles—will be instrumental in overcoming these bottlenecks, ultimately establishing PELNs as a next-generation platform for precision medicine and targeted nanotherapeutic delivery.

ObjectiveTreadmill exercise intervention was evaluated for its effects on addictive behavior, learning and memory, and hippocampal neuroinflammation in methamphetamine (MA)-addicted mice, and transcriptomic screening was performed to identify candidate molecules involved in exercise-mediated attenuation of MA-related neuronal injury. MethodsTwo-month-old male C57BL/6 mice were randomly assigned to four groups: control (C), exercise control (CE), methamphetamine (M), and methamphetamine plus exercise (ME). Mice in the M and ME groups received intraperitoneal injections of MA (1 mg/kg) once daily for 7 consecutive days to establish the addiction model, whereas mice in the C and CE groups received equal volumes of saline. Subsequently, mice in the CE and ME groups underwent treadmill exercise at 12 m/min for 60 min/d for 2 weeks. Conditioned place preference (CPP), the Y-maze, and the Morris water maze (MWM) were used to assess addictive behavior, spatial recognition memory, and spatial learning and memory, respectively. Hippocampal neuronal ultrastructure was examined by transmission electron microscopy (TEM), and microglia-related responses were evaluated by immunofluorescence staining for ionized calcium-binding adapter molecule 1 (Iba-1) in the hippocampal CA1 region. Previously generated and publicly available RNA-seq data from brain tissue of the C, M, and ME groups were reanalyzed, with three biological samples per group. Differentially expressed genes (DEGs) were re-screened using the criteria of P<0.05 and fold change>1.5 or <0.67, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. NLR family CARD domain containing 5 (Nlrc5) was further validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot was used to determine the protein expression of NLRC5, nuclear factor kappa B (NF‑κB), interleukin-1β (IL-1β), postsynaptic density-95 (PSD-95), and synaptophysin. ResultsTreadmill exercise significantly attenuated MA-induced conditioned place preference and improved learning and memory performance in both the Y-maze and MWM tests. Exercise increased exploration time and distance in the novel arm of the Y-maze, shortened escape latency, and increased the number of platform crossings in the MWM. Average swimming speed during the probe trial did not differ significantly among groups, suggesting that the MWM differences were not attributable to obvious differences in swimming performance. TEM revealed that MA exposure induced mitochondrial swelling, disrupted cristae, reduced organelle abundance, and nuclear envelope abnormalities in hippocampal neurons, whereas these ultrastructural changes were alleviated after exercise. Immunofluorescence staining showed that MA increased Iba-1 fluorescence intensity in the hippocampal CA1 region, while treadmill exercise significantly reduced this change. Transcriptomic analysis identified 160 DEGs associated with MA exposure and 58 DEGs associated with exercise intervention, with 9 overlapping DEGs. KEGG enrichment analysis showed that MA-related DEGs were enriched in the NOD-like receptor signaling pathway. Among the overlapping DEGs, Nlrc5, which was downregulated after MA exposure and restored following exercise intervention, was selected as a candidate gene for further validation. RT-qPCR confirmed that treadmill exercise reversed the MA-induced decrease in Nlrc5 mRNA expression. Western blot analysis further showed that treadmill exercise increased NLRC5, PSD-95, and synaptophysin protein expression while reducing NF-κB and IL-1β expression. ConclusionTwo weeks of treadmill exercise attenuated MA-induced conditioned place preference and ameliorated learning and memory impairment, alleviated hippocampal neuroinflammation and neuronal ultrastructural damage, and restored the expression of synapse-related proteins. Transcriptomic screening combined with molecular validation demonstrated that exercise intervention was accompanied by restoration of NLRC5 expression, reduced NF‑κB and IL-1β expression, and increased PSD-95 and synaptophysin expression. These findings suggest that NLRC5 may represent a candidate molecule involved in exercise-mediated amelioration of MA-related neuronal injury. However, the present results mainly demonstrate coordinated changes in NLRC5 expression, inflammatory indicators, and cognitive outcomes rather than a direct causal relationship, and the specific role of NLRC5 requires further functional validation.

Radiogenomics, an extension of radiomics, explores the relationship between imaging features and underlying gene expression patterns. This field is instrumental in providing reliable imaging surrogates, thus potentially representing an alternative to genetic testing. The rapidly growing area of radiogenomics that utilizes ultrasound (US) imaging seeks to elucidate the connections between US image characteristics and genomic data. In this review, the authors outline the radiogenomics workflow and summarize the applications of US-based radiogenomics. These include the prediction of gene variations, molecular subtypes, and other biological characteristics, as well as the exploration of the relationships between US phenotypes and cancer gene profiles. Although the field faces various challenges, US-based radiogenomics offers promising prospects and avenues for future research.

Objective To analyse the clinical efficiency of endolymphatic sac surgery (ESS) in the management of Meniere’s disease (MD). Methods A retrospective analysis was conducted on 274 patients with MD who were hospitalized for treatment in Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University from January 2009 to August 2023. All patients received lifestyle management and drug treatment such as diuretics. For those whose conditions were not well controlled 3 to 6 months after the initial treatment, intratympanic glucocorticoid (ITG) or ESS treatment was carried out. Six months after the treatment, the classes of vertigo relief and hearing changes in the patients were evaluated. After adjusting the confounding factors through propensity score matching (PSM), the impact of ESS on the prognosis of MD patients was evaluated. Results Among 274 patients, 194 and 80 patients underwent ITG and ESS, respectively. Eighty patients were enrolled into each group after PSM. Before and after PSM, the rate of patients reaching vertigo relief class A in ESS group was higher than that in the ITG group (P＝0.004); there was no significant difference in hearing preservation between the two groups. Kaplan-Meier curve analysis showed that vertigo relief in the ESS group was better than that in the ITG group (P=0.029); there was no statistically significant difference in hearing preservation between the two groups. Conclusion When the initial treatment for patients with MD is ineffective, choosing ESS is more beneficial than ITG for controlling vertigo.

Objective:To investigate the effects and mechanisms of cyclic adenosine monophosphate (cAMP) on cisplatin-induced acute kidney injury (AKI).Methods:GSE227970 dataset derived from human renal tubular epithelial cells (HK-2 cells) in the GEO database was downloaded, and Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis were performed in normal and cisplatin-damaged cells. Eighteen 8-week-old male C57BL/6J mice with body weight of (22±2) g were randomly divided into normal group, cisplatin group and cAMP group according to random number table method, with 6 mice in each group. cAMP group was intraperitoneally injected with 30 mg/kg glumine cyclic adenosine monophosphate, while normal group and cisplatin group were intraperitoneally injected with the same volume of 0.9% sodium chloride solution for 10 consecutive days. The cisplatin and cAMP groups were intraperitoneally injected with 20 mg/kg cisplatin once on the 8th day. The body weight and kidney weight of mice were weighed, and kidney weight to body weight ratio was calculated. The blood urea nitrogen (BUN) and serum creatinine (Scr) in mice were detected. HE staining was used to evaluate the degree of renal injury. Western blotting was used to detect the protein expression of AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling pathway in renal tissues. In vitro experiments, HK-2 cells were set up in normal group, cisplatin group, cAMP group and cAMP+AMPK inhibitor group. Immunofluorescence was used to detect the protein expression of phosphorylated (p)-AMPK in HK-2 cells. Adenosine triphosphate content and ratio of NAD + to NADH in cells were detected. Flow cytometry was used to detect cell apoptosis. Results:Biological signal analysis showed that axon guidance, Ras-related protein 1 signaling pathway and cAMP signaling pathway were significantly changed in cisplatin group. The body weight, kidney weight and kidney weight/body weight ratio in cisplatin group were significantly lower than those in normal group (all P<0.05). However, after cAMP treatment, kidney weight was significantly higher compared with cisplatin group ( P<0.05), and body weight and kidney weight/body weight ratio also increased, but the differences were not statistically significant (both P>0.05). BUN, Scr and renal tubular injury score in cisplatin group were significantly higher than those in normal group (all P<0.05). After cAMP treatment, BUN, Scr and renal tubular injury score were significantly lower than those in cisplatin group (all P<0.05). Western blotting results showed that cAMP treatment could significantly increase the decreased AMPK/ACC signaling pathway protein in the renal tissues of cisplatin-induced mice (all P<0.05). In vitro experiments, immunofluorescence detection showed that the expression of p-AMPK protein in cisplatin-induced HK-2 cells decreased, and the addition of cAMP increased the expression of p-AMPK protein in cisplatin-induced HK-2 cells (all P<0.05). cAMP treatment could alleviate cisplatin-induced injury in HK-2 cells, restore the reduction of adenosine triphosphate content and NAD +/NADH ratio, and reduce the apoptosis induced by cisplatin (all P<0.05), while AMPK inhibitor could eliminate the protective effect of cAMP on cisplatin-induced injury in HK-2 cells. Conclusion:cAMP can play a protective role in renal injury caused by cisplatin, and its mechanism may be related to activation of AMPK/ACC signaling pathway.

Objective:To summarize and analyze the clinical features of patients with inflammatory bowel disease (IBD) accompanied by axial spondyloarthritis (ax-SpA) .Methods:A descriptive case series study was conducted. Consecutive IBD patients with ax-SpA admitted to Peking Union Medical College Hospital from January 2012 to December 2023 were enrolled, and the clinical data were collected and analyzed descriptively.Results:A total of 21 IBD patients with ax-SpA were enrolled, including 14 males (66.7%) and 7 females (33.3%). The median age at IBD diagnosis was 29 (24, 42) years. Among them, 10 had ulcerative colitis (UC) and 11 had Crohn's disease (CD). In 11 patients (52.4%), ax-SpA was diagnosed before IBD, while in 7 patients (33.3%), IBD was diagnosed before ax-SpA; the remaining 3 patients (14.3%) were diagnosed simultaneously. Thirteen patients (61.9%) had other extraintestinal manifestations, with 12 involving mucocutaneous manifestations. Nineteen patients including 9 UC and 10 CD were followed up for a median duration of 34 (12, 57) months. Among UC patients, 5 (55.6%) were escalated from conventional therapy to biologics or small-molecule drugs, and 6 (66.7%) developed opportunistic infections. Among CD patients, 3 (30.0%) were escalated to biologic therapy, and 2 (20.0%) developed opportunistic infections. Three patients (15.8%) underwent intestinal resection surgery.Conclusions:IBD patients with ax-SpA are predominantly male, with a similar proportion of UC and CD. There is no clear sequential pattern in the diagnosis timing of IBD and ax-SpA. These patients often present with other extraintestinal manifestations of IBD, primarily mucocutaneous manifestations.

Objective:To investigate the clinical effect of lingual mucosal augmentation urethroplasty with non-transecting urethral cavernous anastomosis in the treatment of traumatic urethral stricture.Methods:The clinical data of 39 patients with traumatic urethral stricture admitted to our clinical center from March 2023 to December 2023 were retrospectively analyzed. Their mean age was (49.7±2.0)years. The cause of urethral injury was pelvic fracture in 32 cases, riding injury in 5 cases, and iatrogenic injury in 2 cases. Suprapubic vesicostomy tube was indwelled before operation in 39 cases. There was 1 case with hypospadias and 1 case with urethral false passage. 9 patients had urethral dilatation before surgery, 5 had internal urethrotomy operation, 5 had urethroplasty, and 22 had no history of urethral surgery. The International Erectile Function Index (IIEF-5)score of 39 cases last 1 month before surgery was collected and classified.In which, the IIEF-5 score of 19 cases with no or mild erectile dysfunction was median 20 (18, 23)points, the MSHQ-Ejd score was median 16 (11, 19)points, and the number of effective erections was median 4(3, 5)times on the NPT. And in which, the IIEF-5 score of 20 cases with moderate to severe erectile dysfunction was median 10 (3, 14)points, the MSHQ-Ejd score was median 3(1, 7)points, and the number of effective erections was median 1(0, 2)times on the NPT. All 39 cases underwent non-transecting anastomotic lingual mucosal augmentation urethroplasty. The central tendon of the perineum and the ventral side of the bulbar urethra were preserved through perineal approach. The dorsal side of the urethra was mobilized and through the dorsal side of the urethra, the scar of the urethra was enucleated along the mucosa of the urethra. Then the ventral mucosa of the urethra was anastomosed end to end and the dorsal urethra was repaired by lingual mucosa transplantation. The Clavien-Dindo complication grading system was performed. The catheter was removed 4 weeks after operation, and urine flow rate was recorded 1 month after extubation. IIEF-5 score, MSHQ-Ejd score and NPT were recorded 6 months after operation.Results:The mean operation time of 39 cases was (118.0±18.3)min. 39 cases were followed up for median 8.0(6.0, 10.0)months. The Q max ≥15 ml/s in 24 cases. The Q max <15ml/s in 13 cases, of which, the Q max ≥15 ml/s after 1 internal urethrotomy operation in 10 cases and Q max≥15 ml/s after 2 internal urethrotomy operations in 3 cases. 2 cases were still failed to urinate and Q max≥15 ml/s after end-to-end urethral anastomosis. All 39 cases’ Clavien-Dindo complications were graded Ⅰ.Of the 19 cases with no or mild erectile dysfunction, the IIEF-5 score was median 20(17, 23)points, the MSHQ-Ejd score was median 16(11, 19)points, and the number of effective erections was median 4(3, 4)times on the NPT postoperatively, all were not significantly different from those before operation ( P> 0.05). Of the 20 cases with moderate and severe erectile dysfunction, the IIEF-5 score was median 9(4, 13)points, the MSHQ-Ejd score was median 4(2, 7)points, and the number of effective erections was median 1(0, 2)times on the NPT postoperatively, and all were not significantly different from those before operation ( P>0.05). Conclusions:Non-transecting anastomotic lingual mucosal augmentation urethroplasty is a reliable surgical method with few complications for traumatic urethral stricture. Moreover, the operation has little effect on the sexual function of patients.

Objective:To investigate the treatment strategies for vesicovaginal fistula（VVF）in women following cervical cancer radiotherapy.Methods:A retrospective analysis was performed on the clinical data of 33 female patients with post-radiotherapy VVF after cervical cancer treatment at Shanghai Sixth People’s Hospital between January 2020 and June 2024. The patients were categorized into three groups based on surgical approaches：Group A（11 patients）：Underwent prone-position VVF repair. Mean age：（50.0±9.6）years；mean radiotherapy sessions：（22.6±2.2）. All had simple VVF without concurrent intestinal or surrounding soft-tissue fistulas. Among them，1 patient previously received laparoscopic VVF repair，1 transvaginal VVF repair，and 2 gracilis muscle flap packing for VVF repair. One month prior to surgery，the average daily usage of urine pads was 16.7（12.8，25.7）pieces，and the quality of life（QOL）score stood at 4.0（4.0，5.0）points. Preoperative cystoscopy revealed that 8 cases had fistulas located in the trigonal region of the bladder，while 3 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings，measured under a microscope，was 1.2（0.8，1.6）cm. Based on the Goh classification criteria for vesicovaginal fistulas，this group included 3 cases of type 1，4 cases of type 2，2 cases of type 3，and 2 cases of type 4；7 cases of type A and 4 cases of type B；as well as 3 cases of typeⅠ，7 cases of type Ⅱ，and 1 case of type Ⅲ.Group B（20 patients）：Underwent gracilis muscle flap packing for VVF repair. Mean age：（58.6±8.8）years；mean radiotherapy sessions：（29.8±3.9）. Three patients had concurrent rectovaginal fistulas and received colostomy for fecal diversion. History of previous interventions：3 had laparoscopic VVF repair，4 transvaginal VVF repair，and 1 both transvaginal and laparoscopic VVF repair. One month prior to surgery，the average daily usage of urine pads was 19.7（15.8，27.7）pieces，and the QOL score stood at 5.0（5.0，6.0）points. Preoperative cystoscopy revealed that 13 cases had fistulas located in the trigonal region of the bladder，while 7 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings，measured under a microscope，was 1.8（1.0，3.2）cm. Based on the Goh classification criteria for vesicovaginal fistulas，this group included 4 cases of type 1，9 cases of type 2，3 cases of type 3，and 4 cases of type 4；6 cases of type A，11 cases of type B and 3 cases of type C；as well as 1 cases of type Ⅱ，and 19 case of type Ⅲ. Group C（2 patients）：Underwent ureterocutaneous diversion. Ages：67 and 73 years；radiotherapy sessions：51 and 60，respectively. Both had concurrent rectovaginal fistulas and bladder soft-tissue fistulas. The patient presented with recurrent thigh abscesses accompanied by fever. One month prior to surgery，the daily usage of urine pads was 29 and 23 pieces，respectively，and the QOL score was 6 points. Cystoscopic examination revealed that the vesicovaginal fistulas were located in the trigone of the bladder，with diameters of 3 cm and 4 cm，respectively. Additionally，partial defects were noted in the ventral wall of the urethra，while no bladder soft tissue fistulas were detected. According to the Goh classification for vesicovaginal fistulas，both cases were categorized as type 4，type C，and type Ⅲ. For Groups A and B，urinary catheters were indwelled for 3 weeks postoperatively，then removed to assess spontaneous urination and incontinence. QOL was evaluated，with a minimum 6-month follow-up. For confirmed postoperative VVF recurrence，re-repair was performed 3?6 months later based on patient preference. For Group C，double-J stents were placed in the ureters，and stoma bags were applied 3 days postoperatively. Stents were replaced every 1?2 months，with QOL assessment. Successful fistula repair in Groups A and B was defined as the absence of vaginal leakage confirmed by cystoscopy after six months of the procedure with no vaginal leakage. For Group C，surgical success was determined by the resolution of perineal urinary leakage and improvement in QOL.Results:All 33 patients completed surgery successfully. Group A：Follow-up duration：16.3（9.6，24.6）months. Surgical repair succeeded in 7 patients，with unobstructed spontaneous urination and no vaginal incontinence. Four patients had VVF recurrence：2 refused further treatment，and 2 underwent repeat gracilis muscle flap packing. One was successfully repaired，while one recurrence case refused further treatment. Group B：Follow-up duration：17.0（9.5，24.8）months（8?32 months）. Thirteen patients restored spontaneous urination without recurrence. Seven had recurrence：5 refused further surgery，and 2 underwent re-repair. One repair succeeded without incontinence，while one recurrence case refused treatment. Group C：Follow-up durations were 6 and 22 months. Perineum remained dry without incontinence（no urine pads needed），and no recurrence of thigh soft-tissue redness/infection occurred. QOL scores were 2 and 3，respectively.Conclusions:Post-radiotherapy VVF in women after cervical cancer presents complex and variable conditions. The primary goal of treatment should be to improve patients’ quality of life. Treatment approaches should be selected based on the complexity of urinary fistulas and local tissue conditions. In general，patients who are younger，have received lower doses of radiation therapy，present with smaller fistula diameters，have well-vascularized and elastic perifistular tissues，and have no concurrent tissue fistulas are candidates for prone-position VVF repair. Patients who do not meet the criteria for transvaginal repair，have a history of at least two previous repair attempts，or have concurrent vaginorectal fistulas require gracilis muscle flap packing for VVF repair. Patients with three or more types of concurrent tissue fistulas，extensive pale and inelastic perifistular tissues，and who are not amenable to repair surgery undergo ureterocutaneous diversion.

Objective To explore the quality markers of Puerariae Lobatue Radix;To predict its"efficacy component group"with alcohol detoxification and liver protection effects.Methods Fingerprints of 26 batches of Puerariae Lobatue Radix samples from different origins in China was established.Multivariate statistical analysis was employed to identify quality markers,while network pharmacology and molecular docking were used to predict the potential"efficacy component group".Results UPLC fingerprint analysis calibrated 11 common peaks.Clustering analysis classified 26 batches of samples into 3 categories,and 7 quality markers were ultimately screened through multivariate statistical analysis,including mirificin,puerarin,puerarin-6''-O-xyloside,3'-methoxypuerarin,ononin,genistin and daidzin.Network pharmacology revealed that all 7 markers interacted with targets related to alcohol-associated liver disease,identifying 19 core targets such as TNF,CASP3,BCL2,MMP9,IL2,and 93 signaling pathways involving IL-17 and PI3K-Akt signaling pathways.Molecular docking demonstrated strong binding affinity between the 7 markers and target proteins,with binding energies<-5 kcal/mol.Conclusion The"efficacy component group",main targets and signaling pathways predicted in this study can provide support for the research on the mechanism,material basis and quality control of the alcohol detoxification and liver protection effects of Puerariae Lobatue Radix.

Objective:To evaluate the efficacy and safety of peri-diaphragmatic hydrodissection in assisting microwave ablation（MWA）of right subphrenic colorectal liver metastasis（CRLM）.Methods:A retrospective analysis was conducted on 101 patients with right subphrenic CRLMs（206 lesions）who underwent percutaneous ultrasound-guided MWA at the Sixth Affiliated Hospital，Sun Yat-sen University from June 2020 to June 2023. Patients were divided into contrast-enhanced ultrasound（CEUS）with hydrodissection group（ n=63）and artificial ascites/pleural effusion group（ n=38，there were 17 patients with artificial pleural effusion，21 patients with artificial ascites）. In the CEUS with hydrodissection group，the peri-diaphragmatic water dissection was established during the post-vascular phase of CEUS. Lesion detection rates，visualization scores，local tumor progression（LTP），and complications were compared between the two groups. Results:In both the CEUS with hydrodissection group and the artificial ascites/pleural effusion group，the lesion detection rates（96.9% and 98.7%）and visualization scores［（3.7 ± 1.3）points and（4.6 ± 0.7）points］improved with water dissection assistance compared to conventional ultrasound［detection rates of 57.5% and 55.7%，visualization scores of（1.9 ± 1.0）points and（2.6 ± 1.5）points］and CEUS alone［detection rates of 78.0% and 78.5%，visualization scores of（3.1 ± 1.5）points and（3.7 ± 1.6）points］（all P<0.001）. The CEUS with hydrodissection group achieved comparable success rates（96.8% vs. 97.4%， P>0.99）but required less saline［60（30，90）ml vs. 500（500，1 000）ml， P<0.001］than artificial ascites/pleural effusion group. No significant differences were observed in LTP rates，complications，or pain scores（all P>0.05）. Conclusions:CEUS combined with peri-diaphragmatic hydrodissection improves detection rates and visualization of right subphrenic CRLM while reducing fluid volume compared to artificial hydrothorax/ascites，serving as a safe and effective adjunct for percutaneous MWA.