Objective To develop an erythrocyte-based delivery system for butyrylcholinesterase(BChE)that is capable of prophylaxis against organophosphorus nerve agents.Methods Recombinant BChE was produced and analyzed for oligomerization via polyacrylamide gel electrophoresis(PAGE)and Western blotting.A modified hypotonic preswelling method was employed to prepare BChE-loaded erythrocytes.The drug loading capacity and encapsulation efficiency were quantified using enzyme-linked immunosorbent assay(ELISA).Catalytic activity was assessed in vitro with an activity detection kit.The system was characterized via scanning electron microscopy(SEM),flow cytometry and a hematology analyzer.Results Recombinant BChE predominantly existed as dimers(85％dimer,15％monomer).The optimized volume ratio of erythrocytes to hypotonic solution was determined as 1:7.Compared with native and empty erythrocytes,BChE-loaded erythrocytes exhibited significantly higher catalytic activity(P＜0.001).The mean corpuscular volume of BChE-loaded erythrocytes increased(P＜0.001),while the mean content of corpuscular hemoglobin and hemoglobin in erythrocytes per 100 mL decreased(P＜0.001).SEM revealed no morphological differences(biconcave disc shape).Hypotonic preswelling moderately increased erythrocyte apoptosis(P＜0.001),but no statistical difference was observed between BChE-loaded and hypotonic-treated erythrocytes(P＞0.05).CD47 expression remained unchanged compared to native erythrocytes(P＞0.05).Conclusion The modified hypotonic preswelling method can generate BChE-loaded erythrocytes that retain the characteristics of native erythrocytes while conferring catalytic activity,offering a novel strategy for clinical intervention against organophosphorus poisoning.

Genitourinary system tumors, as a major clinical challenge posing a serious threat to human health, urgently require breakthroughs in the construction of a precision diagnosis and treatment system. The innovative application of molecular imaging technologies, particularly the development of novel molecular probes, is revolutionizing the diagnostic and therapeutic paradigms for urinary tumors. The application of novel molecular probes in the early diagnosis and staging of genitourinary tumors, the role of multimodal molecular imaging probes in guiding precision surgery/radiotherapy, and the clinical translation challenges and strategies for theranostic-integrated probes are systematically reviewed in this article to provide valuable insights and references for related research and clinical practice.

This paper introduces Professor SUN Shentian's clinical experience in the treatment of refractory facial paralysis with acupuncture and moxibustion. Professor SUN believes that the etiology of refractory facial paralysis is complex. Acupuncture and moxibustion treatment should be based on cortical localization, Baihui (GV20), lower 1/5 of motor area and brainstem area are selected, and repetitive transcranial acupuncture is applied. Under the ultrasonic positioning, acupuncture is performed on the starting and ending points of the mimetic muscles in different lesion sites. Combined with the TCM pathogenesis of refractory facial paralysis with deficiency of healthy qi and retention of pathogenic factors, acupuncture and moxibustion treatment takes strengthening the healthy qi and eliminating pathogenic factors as the core, and reuses the acupoints of yangming meridians (Yingxiang [LI20], Sibai [ST2], Dicang [ST4], Hegu [LI4], Zusanli [ST36], etc.) as the main acupoints to dredge the meridians. The main facial mimetic muscles and related collateral points are selected for cluster needling to dredge the collaterals. Acupuncture at Yangbai (GB14)-toward-Tongziliao (GB1), Sibai (ST2)-toward-Dicang (ST4), Dicang (ST4)-toward-Jiache (ST6) is applied and combined with the needle-sticking and lifting technique to nourishing tendons. Qihai (CV6) and Guanyuan (CV4) are selected for acupuncture before moxibustion. In addition, Professor SUN emphasizes that the three methods of kneading, acupuncture and moxibustion should be used in Yifeng (TE17), Qianzheng (Extra) and Xiaguan (ST7). Professor SUN combines TCM syndrome differentiation with modern technology, which has the advantages of accurate positioning and diverse techniques, and provides a new idea for the treatment of refractory facial paralysis.
Humans ; Moxibustion ; Acupuncture Therapy ; Facial Paralysis/therapy* ; Female ; Male ; Acupuncture Points ; Middle Aged ; Adult

Objective:To identify individuals with accelerated aging under the frailty index (FI) as a proxy indicator of biological age, and to investigate the associations of age at menarche, age at menopause, and reproductive lifespan with frailty status and multi-timepoint FI trajectories among Chinese adult women.Methods:The current study included 302 471 women from the China Kadoorie Biobank 2004-2008 baseline survey data. Their age at menarche and menopause were self-reported, and the duration of reproductive lifespan was calculated by subtracting the two ages. The baseline FI was constructed using 28 baseline variables, including diseases, symptoms, and anthropometric measurements. Frailty status was categorized into three groups: non-frail (FI≤0.10), pre-frail (0.10

In recent years, with continuous advancements in molecular biology and gene testing technologies, the diagnosis and treatment of colorectal cancer have been rapidly transitioning toward precision medicine. The application of molecular classification, target detection, and liquid biopsy technologies has driven ongoing updates to clinical guidelines. Multidisciplinary team colla-boration, innovations in precision surgical techniques, and the widespread adoption of neoadjuvant combination therapies have collectively promoted more individualized and scientific management of colorectal cancer. Looking ahead,the authors believe that as multi-omics biomarkers, organoid models, and artificial intelligence are increasingly integrated into clinical practice, precision diagnosis and treatment of colorectal cancer will deepen further, offering patients more efficient and personalized therapeutic options.

Objective:To analyze the clinical characteristics of locally advanced rectal cancer patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy combined with immunotherapy.Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 46 patients with locally advanced rectal cancer who were admitted to 6 medical centers, including Beijing Friendship Hospital of Capital Medical University et al, from June 2021 to November 2022 were collected. There were 29 males and 17 females, aged (61±4)years. Patients received neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitor therapy, and under-went radical total mesorectal excision during 6-12 weeks after radiotherapy. Observation indicators: (1) comparison of clinical characteristics between pCR and non-pCR patients;(2) postoperative complications and adverse reactions of pCR and non-pCR patients. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. Results:(1) Comparison of clinical characteristics between pCR and non-pCR patients. Before neoadjuvant therapy, there were 14 cases aged ≥50 years and 6 cases aged <50 years in pCR patients, versus 25 cases and 1 case in non-pCR patients, showing a significant difference between the two groups ( P<0.05). After neoadjuvant therapy, cases in clinical stage T0, T1, T2, T3, T4 were 11, 1, 5, 3, 0 for pCR patients versus 7, 4, 2, 11, 2 for non-pCR patients, cases of tumor regression grade 1, 2, 3, 4 were 11, 8, 1, 0 for pCR patients versus 7, 14, 4, 1 for non-pCR patients, cases in low-risk, medium-risk, high-risk of neoadjuvant rectal scoring and grading were 20, 0, 0 for pCR patients versus 4, 18, 4 for non-pCR patients, respectively, showing significant differences in above indicators between the two groups ( Z=-2.256, -2.104, -5.458, P<0.05). (2) Postoperative complications and adverse reactions of pCR and non-pCR patients. Postoperative complications occurred in 2 cases of pCR patients and 5 cases of non-pCR patients, postoperative adverse reactions occurred in 11 cases of pCR patients and 10 cases of non-pCR patients, showing no significant difference between the two groups ( P>0.05). Conclusion:Compared with locally advanced rectal cancer patients aged ≥50 years, those aged <50 years have significant benefits from neoadjuvant chemoradiotherapy combined with immunotherapy. Clinical T staging and magnetic resonance imaging-detected tumor regression grade after neoadjuvant therapy have predictive value for patients with pCR .

Objective:To identify individuals with accelerated aging under the frailty index (FI) as a proxy indicator of biological age, and to investigate the associations of age at menarche, age at menopause, and reproductive lifespan with frailty status and multi-timepoint FI trajectories among Chinese adult women.Methods:The current study included 302 471 women from the China Kadoorie Biobank 2004-2008 baseline survey data. Their age at menarche and menopause were self-reported, and the duration of reproductive lifespan was calculated by subtracting the two ages. The baseline FI was constructed using 28 baseline variables, including diseases, symptoms, and anthropometric measurements. Frailty status was categorized into three groups: non-frail (FI≤0.10), pre-frail (0.10

In recent years, with continuous advancements in molecular biology and gene testing technologies, the diagnosis and treatment of colorectal cancer have been rapidly transitioning toward precision medicine. The application of molecular classification, target detection, and liquid biopsy technologies has driven ongoing updates to clinical guidelines. Multidisciplinary team colla-boration, innovations in precision surgical techniques, and the widespread adoption of neoadjuvant combination therapies have collectively promoted more individualized and scientific management of colorectal cancer. Looking ahead,the authors believe that as multi-omics biomarkers, organoid models, and artificial intelligence are increasingly integrated into clinical practice, precision diagnosis and treatment of colorectal cancer will deepen further, offering patients more efficient and personalized therapeutic options.

Objective:To analyze the clinical characteristics of locally advanced rectal cancer patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy combined with immunotherapy.Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 46 patients with locally advanced rectal cancer who were admitted to 6 medical centers, including Beijing Friendship Hospital of Capital Medical University et al, from June 2021 to November 2022 were collected. There were 29 males and 17 females, aged (61±4)years. Patients received neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitor therapy, and under-went radical total mesorectal excision during 6-12 weeks after radiotherapy. Observation indicators: (1) comparison of clinical characteristics between pCR and non-pCR patients;(2) postoperative complications and adverse reactions of pCR and non-pCR patients. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. Results:(1) Comparison of clinical characteristics between pCR and non-pCR patients. Before neoadjuvant therapy, there were 14 cases aged ≥50 years and 6 cases aged <50 years in pCR patients, versus 25 cases and 1 case in non-pCR patients, showing a significant difference between the two groups ( P<0.05). After neoadjuvant therapy, cases in clinical stage T0, T1, T2, T3, T4 were 11, 1, 5, 3, 0 for pCR patients versus 7, 4, 2, 11, 2 for non-pCR patients, cases of tumor regression grade 1, 2, 3, 4 were 11, 8, 1, 0 for pCR patients versus 7, 14, 4, 1 for non-pCR patients, cases in low-risk, medium-risk, high-risk of neoadjuvant rectal scoring and grading were 20, 0, 0 for pCR patients versus 4, 18, 4 for non-pCR patients, respectively, showing significant differences in above indicators between the two groups ( Z=-2.256, -2.104, -5.458, P<0.05). (2) Postoperative complications and adverse reactions of pCR and non-pCR patients. Postoperative complications occurred in 2 cases of pCR patients and 5 cases of non-pCR patients, postoperative adverse reactions occurred in 11 cases of pCR patients and 10 cases of non-pCR patients, showing no significant difference between the two groups ( P>0.05). Conclusion:Compared with locally advanced rectal cancer patients aged ≥50 years, those aged <50 years have significant benefits from neoadjuvant chemoradiotherapy combined with immunotherapy. Clinical T staging and magnetic resonance imaging-detected tumor regression grade after neoadjuvant therapy have predictive value for patients with pCR .

Objective:To explore the effects of miR-21-5p exosomes derived from human umbilical cord mesenchymal stem cells on apoptosis of human granular cells.Methods:A granular cell apoptosis model was constructed by treating KGN cells with different concentrations (0 μmol/L, 30 μmol/L, 60 μmol/L, and 100 μmol/L) of phosphoramide nitrogen mustard for 48 h. The mRNA and protein levels of bax and bcl2 were detected using qPCR and Western blotting, respectively. The apoptosis rate was measured using flow cytometry to screen for the optimal concentration of phosphoramide nitrogen mustard for constructing an apoptosis model. Hsa-miR-21-5p overexpression plasmid was used for instantaneously transfecting human umbilical cord mesenchymal stem cells, and the expression level of hsa-miR-21-5p was detected by qPCR. The miR-21-5p exosomes were separated and identified by flow cytometry and electron microscope. Different concentrations (5 μg/mL, 10 μg/mL and 15 μg/mL) of miR-21 exosomes were added into successful KGN cell apoptosis model to overexpress miR-21. The mRNA and protein levels of bax and bcl2 were detected using qPCR and Western blotting, respectively. PKH-26 was used to trace the position of human granular cells. Results:The levels of bax mRNA and protein in KGN cells treated with 60 μmol/L phosphoramide nitrogen mustard were significantly higher than those in the 0 μmol/L phosphoramide nitrogen mustard group (all P<0.001), while the levels of bcl2 mRNA and protein were significantly higher than those in the 0 μmol/L phosphoramide nitrogen mustard group ( P=0.005, P<0.001). The apoptosis rate of KGN cells after 60 μmol/L phosphoramide nitrogen mustard intervention was (38.10±2.90)%, while the apoptosis rate of KGN cells after 30 μmol/L phosphoramide nitrogen mustard intervention was (16.75±2.55)%, they were all significantly higher than that of the 0 μmol/L phosphoramide nitrogen mustard intervention group ( P=0.020, P=0.006). Hsa-miR-21-5p was transiently transfected into human umbilical cord blood mesenchymal stem cells, and the expression of has-miR-21-5p was higher than that in control group detected by qPCR ( P<0.001). The positive rate of surface protein CD9, CD63 and CD81 was 14.9%, 16.4% and 31.4%. The exosome was observed as "tea tray" or "concave hemisphere" by electron microscope. The exosome labeled by PKH-26 entered the granular cells and exerted biological effects. There was no statistically significant difference in bax mRNA expression levels between the 5 μg/mL, 10 μg/mL, and 15 μg/mL empty plasmid exosomes groups and the 60 μmol/L phosphoramide nitrogen mustard group (all P>0.05). However, the expression levels of bax mRNA in the 5 μg/mL, 10 μg/mL, and 15 μg/mL miR-21-5-p exosomes groups were lower than those in the 60 μmol/L phosphoramide nitrogen mustard group ( P=0.008, P=0.003, P<0.001). However, there was no statistically significant difference in the expression of bcl2 mRNA among the groups (all P>0.05). From the perspective of protein levels, there was no statistically significant difference in BAX protein expression between the 5 μg/mL, 10 μg/mL, and 15 μg/mL empty exosomes groups and 60 μmol/L phosphoramide nitrogen mustard group (all P>0.05), while the 5 μg/mL, 10 μg/mL, and 15 μg/mL miR-21-5-p exosomes groups showed a decrease in BAX protein expression compared with the 60 μmol/L phosphoramide nitrogen mustard group, and the differences were statistically significant (all P<0.001). However, there was no statistically significant difference in the expression of BCL2 protein among the intervention groups (all P>0.05). Conclusion:Hsa-miR-21-5p exosomes derived from human umbilical cord blood mesenchymal stem cells can effectively exert the anti-apoptotic effect.