BACKGROUND:Mesenchymal stem cells show extremely therapeutic potential for radiation-induced lung injury through delivering exosomes.Age is a primary factor affecting the function and biological efficacy of mesenchymal stem cells.OBJECTIVE:To investigate the protective effects of exosomes derived from bone marrow mesenchymal stem cells of different mouse ages on radiation-induced lung injury in mice.METHODS:Bone marrow mesenchymal stem cells of young mice and old mice were obtained by whole bone marrow adherent culture.The exosomes were isolated from the supernatant of passage 3 bone marrow mesenchymal stem cells.Ten 2-month-old C57BL/6J mice were randomly selected as the control group after anesthesia and not irradiated.The remaining 30 2-month-old C57BL/6J mice were used to establish a mouse radiation-induced lung injury model and were randomly divided into three groups.Exosomes derived from bone marrow mesenchymal stem cells of young mice,exosomes derived from bone marrow mesenchymal stem cells of old mice,and PBS were injected through the tail vein,respectively.The survival rate of mice was monitored.The lung function,lung inflammation and fibrosis were assessed at 1 and 12 weeks after irradiation.RESULTS AND CONCLUSION:(1)The concentrations of particles and proteins in exosomes derived from bone marrow mesenchymal stem cells of young mice were higher than those in exosomes derived from bone marrow mesenchymal stem cells of old mice.(2)Compared with the control group,the survival rate of mice in the PBS group was low,and lung inflammation was obvious at week 1 after irradiation,and the levels and mRNA expressions of interleukin-1β,interleukin-6,and tumor necrosis factor-α were increased.Collagen deposition in lung tissues was observed at week 12 after irradiation,and the mRNA level of E-cadherin was decreased,while the mRNA levels of α-smooth muscle actin,transforming growth factor-β1,and β-catenin were increased.(3)Compared with the PBS group,the survival rate of mice in the exosome group was significantly improved,and the level of proinflammatory factors and their mRNA expression were reduced at week 1 after irradiation,the mRNA level of E-cadherin was increased,and the mRNA levels of α-smooth muscle actin,transforming growth factor β1 and β-catenin were reduced at week 12 after irradiation.(4)Among all the above indicators,the therapeutic effect of exosomes derived from bone marrow mesenchymal stem cells of young mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.(5)The results showed that exosomes derived from bone marrow mesenchymal stem cells of young mice contained more particles and proteins,and the effect of alleviating early inflammation and late fibrosis of radiation-induced lung injury in mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.

BACKGROUND:Mesenchymal stem cells show extremely therapeutic potential for radiation-induced lung injury through delivering exosomes.Age is a primary factor affecting the function and biological efficacy of mesenchymal stem cells.OBJECTIVE:To investigate the protective effects of exosomes derived from bone marrow mesenchymal stem cells of different mouse ages on radiation-induced lung injury in mice.METHODS:Bone marrow mesenchymal stem cells of young mice and old mice were obtained by whole bone marrow adherent culture.The exosomes were isolated from the supernatant of passage 3 bone marrow mesenchymal stem cells.Ten 2-month-old C57BL/6J mice were randomly selected as the control group after anesthesia and not irradiated.The remaining 30 2-month-old C57BL/6J mice were used to establish a mouse radiation-induced lung injury model and were randomly divided into three groups.Exosomes derived from bone marrow mesenchymal stem cells of young mice,exosomes derived from bone marrow mesenchymal stem cells of old mice,and PBS were injected through the tail vein,respectively.The survival rate of mice was monitored.The lung function,lung inflammation and fibrosis were assessed at 1 and 12 weeks after irradiation.RESULTS AND CONCLUSION:(1)The concentrations of particles and proteins in exosomes derived from bone marrow mesenchymal stem cells of young mice were higher than those in exosomes derived from bone marrow mesenchymal stem cells of old mice.(2)Compared with the control group,the survival rate of mice in the PBS group was low,and lung inflammation was obvious at week 1 after irradiation,and the levels and mRNA expressions of interleukin-1β,interleukin-6,and tumor necrosis factor-α were increased.Collagen deposition in lung tissues was observed at week 12 after irradiation,and the mRNA level of E-cadherin was decreased,while the mRNA levels of α-smooth muscle actin,transforming growth factor-β1,and β-catenin were increased.(3)Compared with the PBS group,the survival rate of mice in the exosome group was significantly improved,and the level of proinflammatory factors and their mRNA expression were reduced at week 1 after irradiation,the mRNA level of E-cadherin was increased,and the mRNA levels of α-smooth muscle actin,transforming growth factor β1 and β-catenin were reduced at week 12 after irradiation.(4)Among all the above indicators,the therapeutic effect of exosomes derived from bone marrow mesenchymal stem cells of young mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.(5)The results showed that exosomes derived from bone marrow mesenchymal stem cells of young mice contained more particles and proteins,and the effect of alleviating early inflammation and late fibrosis of radiation-induced lung injury in mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.

ObjectiveTo observe the clinical efficacy of acupuncture combined with bloodletting and cupping in the treatment of chronic spontaneous urticaria（CSU） and to explore its potential mechanisms of action. MethodsSeventy CSU patients were randomly divided into loratadine group and acupuncture + bloodletting group， with 35 patients in each group. The loratadine group received oral loratadine tablets， 10 mg once daily in the evening. The acupuncture + bloodletting group received acupuncture at Zhongwan （CV 12）， Guanyuan （CV 4）， Tianshu （ST 25）， Zusanli （ST 36）， Sanyinjiao （SP 6）， Xuehai （SP 10）， Quchi （LI 11）， Hegu （LI 4）， Taichong （LR 3）， Baihui （GV 20）， and Shenting （GV 24）， once daily，along with bloodletting and cupping at Dazhui （GV 14） and Geshu （BL 17）， every other day. Both groups were treated for 4 weeks. The 7-day urticaria activity score（UAS7） was assessed before and after the treatment， and levels of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， eosinophil cationic protein （ECP）， plasma tissue factor （TF）， activated factor Ⅶ （FⅦa）， prothrombin fragment 1+2 （F1+2）， D-dimer （D-D） and complement component 5a （C5a） were detected. ResultsA total of 65 patients were included in the final analysis， 32 in the loratadine group and 33 in the acupuncture + bloodletting group. Before treatment， there was no significant difference in UAS7 score， serum IgE， IL-4， IL-5， ECP levels， or plasma TF， FⅦa， F1+2， D-D， C5a levels between groups （P＞ 0.05）. After treatment， both groups showed significant reductions in UAS7 score， serum IgE， IL-4， IL-5， and plasma TF， FⅦa， F1+2， D-D， and C5a levels compared to those before treatment （P＜0.01）. However， after treatment， there was no significant difference in UAS7 score and serum ECP， IgE， IL-4， IL-5 levels between groups （P＞0.05）. The acupuncture + bloodletting group showed lower plasma TF， FⅦa， F1+2， D-D and C5a levels compared to the loratadine group （P＜0.05 or P＜0.01）. ConclusionAcupuncture combined with bloodletting and cupping can effectively improve the skin symptoms of CSU patients and reduce the levels of inflammatory factors. The potential mechanism of action may involve the regulation of the coagulation-complement-mast cell activation axis， thereby inhibiting mast cell degranulation.

Objective To analyze the adverse reaction reports （ADRs） of drug-induced liver injury in recent ten years, explore the characteristics and related rules of drug-induced liver injury, and provide reference for clinical safe drug use. Methods ADRs in our hospital from 2011 to 2021 which belonged to drug-induced liver injuries were collected, and Pareto analysis was carried on. Results In 259 ADR reports, the most common type of drug-induced liver injury was hepatocellular injury （37.84%）. The age of drug-induced liver injury was mainly over 46 years, totaling 195 （75.28%）. Drugs were mainly distributed in cardiovascular system medicine （44.02%）, anti-infective medicine （23.94%）and anti-tumor medicine （11.58%）. Among the cardiovascular drugs, atorvastatin calcium 40mg and over 40mg were the highest proportion, with 53 cases （46.49%）. The main anti-infectious drugs were cephalosporins （29.03%）, carbapenem （19.35%）， antifungal （17.74%）and quinolones （11.29%）. Adverse reactions occurred within 6 days （69.88%）, the duration of adverse reactions was 1-2 weeks （31.66%）, and most patients were improved （47.88%） or cured （37.07%）. Conclusion For middle-aged and elderly patients, when the application of cardiovascular system drugs, anti-infective drugs or anti-tumor drugs, it is necessary to monitor the liver function changes of patients for at least 6 days. If there are abnormalities, the drugs should be stopped or given treatment in time, to avoid the progress of drug-induced liver injury.

Objective: To explore the therapeutic effects of different surgical methods for temporomandibular joint disc reduction and anchoring surgery, providing reference for optimizing this surgical procedure. Method: The study was approved by the hospital ethics committee. 173 patients (195 joints) who underwent temporomandibular joint disc repositioning and anchoring surgery were selected for retrospective analysis. Patients were categorized into groups A (traditional preauricular incision-scalpel/tissue scissors anterior attachment release), 35 patients (40 joints), B (traditional preauricular incision-plasma bipolar radiofrequency electrode anterior attachment release), 42 patients (46 joints), C (revised tragus incision - scalpel/tissue scissors anterior attachment release), 50 patients (58 joints), and D (revised tragus incision-plasma bipolar radiofrequency electrode anterior attachment release), 46 patients (51 joints). After a 6-month postoperative follow-up, the differences in maximum mouth opening (MMO), visual analogue scale (VAS), effective rate of joint disc reduction, incidence of preauricular numbness, obvious scars among patients in each group at 1, 3, and 6 months were compared postoperatively. Results: After surgery, the MMO of all four groups of patients initially shrunk and then gradually increased compared to before surgery. At the 1-month follow-up after surgery, the plasma bipolar radiofrequency release (B+D) group had a smaller impact on the patient’s MMO compared to the surgical knife/tissue scissors release (A+C) group (P < 0.05). Postoperative VAS scores for all four groups showed a gradual decrease from pre-operative levels, with the (B+D) group scoring significantly lower in the first month post-surgery compared to the (A+C) group (P < 0.05). Six months post-surgery, the rate of joint disc reduction of the four groups were higher than 95%, with no significant differences observed between the groups (P > 0.05). Patients in the revised tragus incision (C+D) group experienced a lower rate of preauricular numbness compared to those in the traditional preauricular incision (A+B) group (4.59% vs. 12.79%, P < 0.05), The incidence of obvious scars in the (C+D) group was significantly lower than that in the (A+B) group (3.67% vs. 23.26%, P < 0.05). Conclusion The revised tragus incision is superior to traditional preauricular incision in terms of protecting the auriculotemporal nerve and the scars were more inconspicuous. Further, the plasma bipolar radiofrequency electrode is superior to the scalpel/tissue scissors in terms of mouth opening recovery and pain control. For temporomandibular joint disc reduction and anchoring surgery, a modified tragus incision combined with plasma bipolar radiofrequency electrode to release the anterior attachment of the joint disc can be recommended as a surgical option.

Objective To establish an expert consensus on the management of low anterior resection syndrome(LARS)in patients with rectal cancer post-surgery(hereinafter referred to as"consensus"),aiming to standardize the related work of medical institutions in the context of post-operative LARS.Methods A comprehensive search of domestic and international databases was conducted to collect guidelines,expert consensuses,systematic reviews,evidence summaries,and original research related to post-operative LARS in rectal cancer published from the establishment of the databases until August 2024.Based on clinical practice experience,a preliminary draft of the"consensus"was formed.From September to November 2024,22 experts were invited to participate in 2 rounds of expert consultations,during which the draft content was revised and improved,and the final version of the"consensus"was determined through expert validation.Results A total of 22 experts responded,achieving a response rate of 100％.The effective recovery rate of the consultation questionnaires in both rounds was 100％,with an expert authority coefficient of 0.89,a judgment coefficient of 0.97,and a familiarity degree of 0.84.The Kendall harmony coefficients for the 2 rounds of expert consultations were 0.122 and 0.136,respectively(P＜0.001).This consensus covers 5 main aspects:definition,assessment,prevention,treatment,and follow-up management of LARS.Conclusion This consensus demonstrates a high level of scientific rigor and can provide a strong reference for clinical nursing personnel in the specialized care of rectal cancer patients with post-operative LARS.

Objective:To investigate the uptake patterns of 18F-fluorodeoxy glucose ( 18F-FDG) in the endometrium using positron emission tomography (PET) imaging and to differentiate these from stage IA endometrial cancer. Methods:From September 2022 to April 2024, a prospective inclusion of 354 women without gynecological diseases and no hormone usage who underwent 18F-FDG PET-CT examinations at the affiliated hospital of Qingdao University were set as the physiological group, while a group containing 42 cases of Stage IA endometrial carcinoma was also set. The physiological group was divided into five groups based on the menstrual cycle: menstrual period, proliferative phase, ovulatory phase, secretory phase, and menopausal phase. The images were analyzed using visual and quantitative measurements; quantitative analysis indicators were standardized uptake value maximum (SUVmax) and the region of interest/liver ratio (R/L value). Receiver operating characteristic (ROCs) curve was used to determine the optimal cutoff values for SUVmax and R/L value. A clinical model was established using binary logistic regression, and ROC curves were drawn to evaluate the predictive performance of the model. Results:The uptake of 18F-FDG in the endometrium exhibited cyclical variations throughout different physiological phases, with higher uptakes observed during the menstrual and ovulation phases (SUVmax values of 6.66±3.26 and 3.89±1.21, respectively), which are significantly higher than those in the proliferative phase [median SUVmax of 2.54 (2.02, 3.47)], secretory phase (SUVmax of 2.55±0.86), and menopausal phase [SUVmax median of 2.04 (1.69, 2.29)]. During the menstrual and ovulation phases, the radiotracer accumulation patterns were triangular in 105 cases, oval in 32 cases, and round-like in 2 cases. All 42 cases of endometrial cancer showed 18F-FDG uptake, with radiotracer accumulation patterns being round-like in 17 cases, oval in 10 cases, triangular in 9 cases, and irregular in 6 cases. There were statistically significant differences in the shapes of radiotracer concentration between the menstrual, ovulatory periods, and endometrial carcinoma (both P＜0.001). The SUVmax and R/L values in menstrual period and ovulatory period were significantly lower than that in endometrial carcinoma group ( P＜0.001). During the menstrual phase, the optimal cutoff values for SUVmax and R/L in distinguishing between endometrial and endometrial cancer were 12.59 and 3.81, respectively, with corresponding AUCs of 0.885 and 0.842. After incorporating endometrial uptake morphology into the model, the AUCs was improved to 0.969 and 0.948, respectively. During the ovulatory phase, the optimal cutoff values for SUVmax and R/L were 5.96 and 2.85, respectively, with AUCs of 0.984 and 0.968. After integrating endometrial uptake morphology into the model, the AUCs were increased to 0.999 and 0.998, respectively. Conclusions:The 18F-FDG PET imaging of the endometrium shows higher uptake during the menstrual and ovulatory periods, primarily triangular in shape; endometrial carcinoma uptake is significantly higher than the physiological uptake during the menstrual and ovulatory periods, mainly in circular, oval, and irregular shapes. When SUVmax≥5.96, R/L≥2.85, combined with the physiological cycle of the subjects and the morphological characteristics of the radiotracer concentration, it is possible to effectively differentiate between physiological uptake and Stage IA endometrial carcinoma.

Objective To evaluate the efficacy and safety of Qixian Tongluo Formula in the treatment of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome,and to preliminarily explore the molecular mechanism of Qixian Tongluo Formula in improving impaired motor function from the perspective of cross-kingdom regulation of Chinese medicine microRNA(miRNA).Methods A pragmatic randomized controlled trial was conducted with 102 patients in the recovery period of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome in our hospital.Patients were randomly divided into trial group and control group,with 51 cases in each group.The control group received standard Western medicine standard treatment,while the trial group received Qixian Tongluo Formula in addition to the standard treatment,with one dose per day,boiled in water,and taken warm after breakfast and dinner for a course of 2 months.The disability rate was used as the main efficacy indicator,and the incidence of adverse reactions was used as a safety indicator.miRNA from patient serum and Qixian Tongluo decoction were extracted respectively,and high-throughput sequencing was performed.The two sequences were compared to screen out the cross-kingdom gene transfer of Chinese medicine miRNA.Finally,its target genes of miRNA were predicted,and GO function and KEGG pathway enrichment analysis were carried out.Results A total of 67 patients completed the clinical trial,including 36 cases in the trial group and 31 cases in the control group;The disability rate in the trial group(13.9%)was lower than that in the control group(35.5%)(P<0.05);The incidence of adverse reactions was similar between the trial group(7.69%)and the control group(6.06%)(P>0.05);A total of 9530 Qixian Tongluo decoction miRNA sequences were screened,with 150 potentially involved in cross-kingdom gene transfer,including families such as miR-15 and miR-17;According to the target gene prediction of the top 10 miRNAs in cross-kingdom gene transfer of Chinese medicine,345 overlapping target genes were obtained;GO functional enrichment analysis revealed 16 biological processes,7 cellular components,and 2 molecular functions among the top 25 enriched functions,while KEGG pathway analysis mainly focused on the transforming growth factor-βsignaling pathway,neurotrophin signaling pathway,which are closely related to neural repair and functional recovery processes such as glial scar formation and synaptic plasticity after cerebral ischemia.Conclusion Qixian Tongluo Formula can significantly improve the functional independence level of patients with kidney deficiency and blood stasis syndrome in the recovery period of paralysis after cerebral infarction,offering a safe and effective treatment option for these patients;There were a large number of miRNAs in Qixian Tongluo decoction,some of which could cross-kingdom transferred into the human blood circulation,and promote the recovery of motor function in patients with cerebral infarction through multi-target,multi link and multi pathway gene network regulation.This study provides a new idea for subsequent clinical and basic research.

Background and Aims:According to the Chinese Guidelines for the Diagnosis and Treatment of Colorectal Cancer(2023 Edition),patients with early-stage colorectal cancer who present with high-risk factors require additional radical surgery following endoscopic resection.However,due to the relatively low rate of lymph node metastasis in early colorectal cancer,some patients may not benefit from such supplemental surgery.Therefore,accurately identifying patients who are truly likely to benefit and refining the indications for supplemental surgery are pressing clinical challenges.This study was conducted to investigate the risk factors and distribution patterns of lymph node metastasis following additional radical surgery through retrospectively analyzing a large single-center cohort,thereby providing evidence-based support for clinical decision-making.Methods:Clinicopathologic data were retrospectively reviewed for patients with early-stage colorectal cancer who underwent additional radical surgery at Fudan University Shanghai Cancer Center between 2008 and 2023.Binary Logistic regression and multivariate analyses were performed to identify risk factors associated with lymph node metastasis,and the distribution characteristics of metastatic lymph nodes were further examined.Results:A total of 417 patients were included in the study,with lymph node metastasis confirmed in 36 cases(8.63％)postoperatively.Over time,the number of patients undergoing supplemental surgery increased,while the proportion of cases with residual cancer decreased.Among 243 patients included in the risk factor analysis,univariate analysis indicated that submucosal invasion depth of SM2 or greater,poor tumor differentiation,positive vascular invasion,and tumor location were high-risk factors for lymph node metastasis.Multivariate analysis identified invasion depth(P=0.039)and tumor location(P=0.014)as independent risk factors.Among the metastatic cases,58.3％involved a single lymph node;63.9％of metastases were limited to the first station,and 36.1％extended to the second station,with no metastasis found at the third station.Only four patients had preoperative imaging suggestive of lymph node enlargement.Conclusion:Although the number of supplemental surgeries following endoscopic resection of early-stage colorectal cancer has increased significantly,the actual rate of lymph node metastasis remains low,suggesting a potential risk of overtreatment.Submucosal invasion depth ≥SM2 and tumor location are independent risk factors for metastasis.D2 lymph node dissection is deemed necessary,while the diagnostic value of imaging remains limited.Clinical decisions should prioritize precision and individualized treatment planning.

Objective To provide experimental evidence for selecting acupuncture timing in clinical practice,the optimal time for enhancing the brain effects of electroacupuncture at the Hegu acupoint(LI4)by observing brain imaging data,hemodynamic changes and differences in brain functional connectivity across the twelve traditional Chinese time periods were determined.Methods Thirty-six C57BL/6 mice were randomly divided into 12 groups corresponding to each of the twelve time periods(Zi,Chou,Yin,Mao,Chen,Si,Wu,Wei,Shen,You,Xu,Hai),with 3 mice per group.Each mouse received electroacupuncture stimulation using the same protocol.Brain imaging data and dynamic hemodynamic changes were collected using functional ultrasound imaging(FUS)ultrasound imaging technology every 0.4 s over a total duration of 420 s,covering pre-acupuncture(resting state),during acupuncture(task state),and post-acupuncture(post-task state)phases.The hippocampal region(HIP)was used as the observation point to analyze changes in functional connectivity between HIP and other brain regions before and after acupuncture.Results Compared to other time periods,the Mao group exhibited the largest whole-brain activation area and the highest average activation signal intensity.The hemodynamic signal increase in the hippocampal region was more pronounced,and the post-acupuncture blood flow signal intensity remained significantly higher than the pre-acupuncture resting state.Functional connectivity data revealed that,using 0.2 as the standard value,the Mao group showed the greatest number of altered brain regions before and after acupuncture.Notably,only in the Mao group was there a significant enhancement in connectivity between the bilateral hippocampal regions.Conclusion The immediate effects of electroacupuncture at the Hegu acupoint(LI4)and brain functional connectivity vary significantly across different time periods,aligning with the traditional Chinese medicine theory of meridian qi and blood flow.Mao time is identified as the optimal period.