Objective To explore the effect of ionizing radiation on the fertility of male mice and its offspring and the intergenerational and transgenerational genetic effect mechanism of ionizing radiation through sperm DNA methylation sequencing.Methods Eight-week-old(8 w)C57BL/6 male mice were irradiated with 60Co radiation source at a dose of 3 Gy(3 Gy-F0 group,n=60)and non-irradiated mice of the same age were used as controls(0 Gy-F0 group,n=60).Afetr 5-,6-,7-,8-,9-,10-,11-,and 12-week radiation,the mice began to breed with healthy females,and the first generation(F1 generation)male mice then breed with healthy female mice to obtain the offspring(F2 generation)male mice.The structure of testis was detected by hematoxylin-eosin staining;serum follicle-stimulating hormone(FSH),testosterone(T)and luteinizing hormone(LH)levels were determined by enzyme-linked immunosorbent assay.Automatic sperm analysis system was used to detect sperm concentration and activity.The DNA of F0 generation sperm was extracted and analyzed by genome-wide DNA methylation sequencing.MassARRAY methylation sites were detected in sperm DNA of F1 generation mice and verified by quantitative polymerase chain reaction(qPCR).Results Compared with the 0 Gy-F0 group,male mice in the 3 Gy-F0 group gradually regained their reproductive ability 7 weeks after ionizing radiation.There was no significant difference in the number of surviving offspring between the 3 Gy-F0 group and 0 Gy-F0 group 10-11 weeks after radiation(P＞0.05).There were no significant differences in body weight,testicular morphology,or sperm concentration of F1 generation mice between the 3 Gy-F1 group and the 0 Gy-F1 group(all P＞0.05).However,compared with the 0 Gy-F1 group,the contents of LH,FSH and T in the 3 Gy-F1 group were all decreased(all P＜0.05),the testicle volume,total sperm motility rate,forward motility rate and the fertility were considerably decreased(all P＜0.05).DNA methylation sequencing showed that more differentially methylated genes were enriched in the pathway regulating microtubule formation.MassARRAY methylation sites analysis showed that the methylation level of Mid1 was significantly increased(P＜0.05 or P＜0.01).Mid1 was verified down-regulated in Fl and F0 sperm by qPCR(P＜0.05 or P＜0.01).However,there were no significant differences in volume of testes,testicular index,sperm concentration,sperm motility,hormone levels or Mid1 expression level between 0 Gy-F2 and 3 Gy-F2 mice in F2 generation male mice(all P＞0.05).Conclusion Sperm damage in mice caused by ionizing radiation at a dose of 3 Gy can recover by itself.However,it may decrease sperm activity by regulating Mid1 methylation level of sperm in F1 mice,thus affect the fertility of F1 mice,but has no effect on the fertility of male F2 mice.

Objective To explore the causal relationship between gut microbiota and colorectal cancer,and to investigate whether metabolites have a mediating effect through Mendelian randomization(MR)analysis.Methods Genome-wide association studies data of 473 gut microbiota,233 metabolites,and colorectal cancer were obtained from public databases.Bidirectional MR analyses were performed between gut microbiota,metabolites,and colorectal cancer,respectively.Subsequently,a two-step MR was used to explore whether specific gut microbiota affect the occurrence and development of colorectal cancer through metabolites.Results The study found that the abundances of 7 gut microbiota were positively correlated with the risk of colorectal cancer:Alloprevotella,Atopobiaceae,Clostridium S felsineum,Hungatella,Microvirga,Peptococcia and Ruminococcus A;The abundances of 4 gut microbiota were negatively correlated with the risk of colorectal cancer:Paenibacillales,Prevotella buccae,Psychroserpens and Succinivibrionaceae.Through the two-step mediation analysis,it was confirmed that the ratio of Triglycerides to total lipids ratio in medium very low-density lipoprotein could reduce the impact of Clostridium S felsineum as a risk factor for the occurrence of colorectal cancer.Conclusion The results of this study confirm the causal relationship between some gut microbiota,metabolites,and colorectal cancer,and discover potential interaction chains,providing ideas for the pathogenesis and prevention of colorectal cancer.

Objective:To observe the effect of electroacupuncture at the Shuigou point on systolic phenotype-related factors and on the JAK1/STAT3 signaling pathway of the middle cerebral artery smooth muscle cells in rats modeling cerebral infarction; and to explore the molecular mechanism of treating cerebral infarction with electroacupuncture.Methods:A total of 108 healthy male Wistar rats were randomly divided into a blank group ( n=6), a sham operation group ( n=6), a model group ( n=48) and an electroacupuncture group ( n=48). The model and electroacupuncture groups were randomly divided into eight phase subgroups at 1h, 3h, 6h, 12h, 24h, 72h, 7d and 14d after the modeling of middle cerebral artery occlusion (MCAO), with six rats in each group. The electroacupuncture groups received electric acupuncture at the Shuigou acupoint for 20min after successful modeling. Neurological Severity scoring (NSS) was used to evaluate the neurological impairment. PLN protein expression in the middle cerebral artery and the expression of JAK1 and STAT3 proteins in the rats′ brain tissue were detected using western blotting. PDGF-AA content in the middle cerebral artery was measured using enzyme-linked immunosorbent assays. Results:Compared with the blank and sham operation groups, the average NSS score and PDGF-AA protein expression had increased significantly in the model and electroacupuncture groups. PLN protein expression had decreased significantly at 12h-14d in the model group, but decreased significantly at 12h-7d in the electroacupuncture group. Compared with those two groups, there was a significant increase in JAK1 protein expression at 1h-72h, 3h-6h, 24h-72h, and14d in the model group. In the electroacupuncture group the corresponding significant increases were over 1h-14d, 1h-6h, 24h, 72h, and 14d. STAT3 protein expression had increased significantly in the model group over 6h-14d and 3h-14d. In the electroacupuncture group those increases were over 6h-14d. Compared to the model group, a significant increase was observed in the expression of PLN protein at 14d, with a significant decrease in NSS at 72h, 7d and 14d. PDGF-AA protein had increased significantly at 6h-7d. For JAK1 protein that was at 12h and 14d, and for STAT3 protein it was over 12h-72h and at 14d.Conclusion:Electroacupuncture at the Shuigou point may regulate the expression of PDGF-AA and the JAK/STAT signaling pathway so as to regulate the normal expression of PLN, and thus smooth muscle contraction to maintain the normal functioning of the middle cerebral artery. This may be one of the molecular mechanisms by which electroacupuncture at the Shuohui point improves nerve functioning in treating cerebral infarction.

To address the challenges of complex digital model management and difficulties in model interoperability during the development of sophisticated products,this paper proposes an intelligent cloud architecture-based method for MBSE(model-based systems engineering)model microservice aggregation and adaptive integration.By introducing ontology semantic annotation and hash encoding mechanisms,we achieve unified encapsulation and service-oriented management of heterogeneous modeling tool resources.Combined with model virtual execution modes and dynamic resource orchestration technology,we design a task-oriented of Model-Based Microservice Deployment Framework,significantly improving model service scheduling efficiency and resource utilization.Leveraging a service-cluster-based model aggregation approach,we employ Hamming distance to calculate model capability compatibility,optimizing model discovery and orchestration processes.The prototype implementation and multi-phase experimental validation conducted in a domestic private cloud environment demonstrate that the proposed method effectively supports digital development across the entire lifecycle of aerospace products,enhancing model resource sharing and system integration efficiency.

Alcohol abuse is a global public health problem.Excessive drinking not only damages digestive tract,cardiovascu-lar and endocrine systems,but also damages central nervous system(CNS).Recent studies have shown that alcohol interacts with neu-roimmune system to alter neuroimmune signaling and molecular expression,thereby leading to neuroinflammation and regulating a wide range of brain functions.Microglia is main cell of CNS involved in neuroimmune responses.Microglia is activated by alcohol and acts on neurons,leading to neuropsychiatric diseases,such as neuronal loss,abnormal synaptic connections,cognitive decline and motor dysfunction.Alcohol chronically stimulates digestive tract and also affects microglia along gut-brain axis.Neural properties of microglia and related immune factors and their important roles in neuroinflammation provide a new insight into neuroimmune mecha-nisms underlying alcohol-induced changes in brain function and behavior.This review discusses progress of role of microglia and their immune signaling in alcohol-induced neuroinflammation,and provides theoretical basis for further research on neurobiological mecha-nism and treatment of alcohol abuse.

Objective To explore the causal relationship between gut microbiota and colorectal cancer,and to investigate whether metabolites have a mediating effect through Mendelian randomization(MR)analysis.Methods Genome-wide association studies data of 473 gut microbiota,233 metabolites,and colorectal cancer were obtained from public databases.Bidirectional MR analyses were performed between gut microbiota,metabolites,and colorectal cancer,respectively.Subsequently,a two-step MR was used to explore whether specific gut microbiota affect the occurrence and development of colorectal cancer through metabolites.Results The study found that the abundances of 7 gut microbiota were positively correlated with the risk of colorectal cancer:Alloprevotella,Atopobiaceae,Clostridium S felsineum,Hungatella,Microvirga,Peptococcia and Ruminococcus A;The abundances of 4 gut microbiota were negatively correlated with the risk of colorectal cancer:Paenibacillales,Prevotella buccae,Psychroserpens and Succinivibrionaceae.Through the two-step mediation analysis,it was confirmed that the ratio of Triglycerides to total lipids ratio in medium very low-density lipoprotein could reduce the impact of Clostridium S felsineum as a risk factor for the occurrence of colorectal cancer.Conclusion The results of this study confirm the causal relationship between some gut microbiota,metabolites,and colorectal cancer,and discover potential interaction chains,providing ideas for the pathogenesis and prevention of colorectal cancer.

Alcohol abuse is a global public health problem.Excessive drinking not only damages digestive tract,cardiovascu-lar and endocrine systems,but also damages central nervous system(CNS).Recent studies have shown that alcohol interacts with neu-roimmune system to alter neuroimmune signaling and molecular expression,thereby leading to neuroinflammation and regulating a wide range of brain functions.Microglia is main cell of CNS involved in neuroimmune responses.Microglia is activated by alcohol and acts on neurons,leading to neuropsychiatric diseases,such as neuronal loss,abnormal synaptic connections,cognitive decline and motor dysfunction.Alcohol chronically stimulates digestive tract and also affects microglia along gut-brain axis.Neural properties of microglia and related immune factors and their important roles in neuroinflammation provide a new insight into neuroimmune mecha-nisms underlying alcohol-induced changes in brain function and behavior.This review discusses progress of role of microglia and their immune signaling in alcohol-induced neuroinflammation,and provides theoretical basis for further research on neurobiological mecha-nism and treatment of alcohol abuse.

Objective:To observe the effect of electroacupuncture at the Shuigou point on systolic phenotype-related factors and on the JAK1/STAT3 signaling pathway of the middle cerebral artery smooth muscle cells in rats modeling cerebral infarction; and to explore the molecular mechanism of treating cerebral infarction with electroacupuncture.Methods:A total of 108 healthy male Wistar rats were randomly divided into a blank group ( n=6), a sham operation group ( n=6), a model group ( n=48) and an electroacupuncture group ( n=48). The model and electroacupuncture groups were randomly divided into eight phase subgroups at 1h, 3h, 6h, 12h, 24h, 72h, 7d and 14d after the modeling of middle cerebral artery occlusion (MCAO), with six rats in each group. The electroacupuncture groups received electric acupuncture at the Shuigou acupoint for 20min after successful modeling. Neurological Severity scoring (NSS) was used to evaluate the neurological impairment. PLN protein expression in the middle cerebral artery and the expression of JAK1 and STAT3 proteins in the rats′ brain tissue were detected using western blotting. PDGF-AA content in the middle cerebral artery was measured using enzyme-linked immunosorbent assays. Results:Compared with the blank and sham operation groups, the average NSS score and PDGF-AA protein expression had increased significantly in the model and electroacupuncture groups. PLN protein expression had decreased significantly at 12h-14d in the model group, but decreased significantly at 12h-7d in the electroacupuncture group. Compared with those two groups, there was a significant increase in JAK1 protein expression at 1h-72h, 3h-6h, 24h-72h, and14d in the model group. In the electroacupuncture group the corresponding significant increases were over 1h-14d, 1h-6h, 24h, 72h, and 14d. STAT3 protein expression had increased significantly in the model group over 6h-14d and 3h-14d. In the electroacupuncture group those increases were over 6h-14d. Compared to the model group, a significant increase was observed in the expression of PLN protein at 14d, with a significant decrease in NSS at 72h, 7d and 14d. PDGF-AA protein had increased significantly at 6h-7d. For JAK1 protein that was at 12h and 14d, and for STAT3 protein it was over 12h-72h and at 14d.Conclusion:Electroacupuncture at the Shuigou point may regulate the expression of PDGF-AA and the JAK/STAT signaling pathway so as to regulate the normal expression of PLN, and thus smooth muscle contraction to maintain the normal functioning of the middle cerebral artery. This may be one of the molecular mechanisms by which electroacupuncture at the Shuohui point improves nerve functioning in treating cerebral infarction.

Objective:To explore the effect and safety of mesenchymal stem cell exosome microneedle introduction in the treatment of melasma.Methods:Thirty cases of female patients with stable melasma in the Department of Dermatology, Changsha Meilai Medical Beauty Hospital, aged (36±5) years and with a disease duration of (42.4±20.7) months, from July 2021 to July 2022, were retrospectively included. According to Fitzpatrick skin typing, 23 cases of type Ⅲ and 7 cases of type Ⅳ were included. All patients were locally anesthetized with lidocaine cream for 30 min, and rolled with a 0.5 mm needle in a zigzag pattern with even force, in the order of the right cheek, the left cheek, the forehead, the nose, the mandible, and the upper lip. During the rolling process, 3 ml of MSC exosome medical liquid wound dressing was applied to the facial skin, and after it was fully absorbed, exosome was locally readministered in the area of melasma. Treatment ended with a slight redness at the site of application. 1 MSC exosome wound dressing was appllied as a cold compress for 15 min after treatment. Treatment was given once every 2 weeks for 6 consecutive sessions. All the patients were followed up at 4 and 12 weeks after the last session, and the area and severity index of melasma (MASI) were scored before and after the treatment, the clinical efficiency and patient satisfaction rate and the incidence of adverse reactions were also counted.Results:At 4 and 12 weeks after the end of treatment, the skin color of all 30 patients was brighter than that before treatment, and no recurrence of melasma symptoms seen. At 12 weeks after the end of treatment, the decrease rate of MASI score was 66.1%, among which the decrease rate of MASI score in patients with type Ⅲ melasma was 63.9%, and the decrease rate of MASI score in patients with type Ⅳ melasma was 63.9%. Among the 30 patients, 1 case was cured, 25 cases showed obvious improved, 4 cases were improved, and no cases were ineffective, with an effective rate of 86.7% (26/30). Five patients were very satisfied, 18 patients were satisfied, 6 patients were generally satisfied, and 1 patient was dissatisfied; the patient satisfaction rate was 76.7% (23/30). No serious adverse reactions occurred in all patients.Conclusions:MSC exosome microneedle introduction is safe and effective in the treatment of melasma without serious adverse reactions.

Objective:To compare the consistency of preoperative frailty assessment in elderly colorectal cancer patients using Frailty Phenotype (FP), FRAIL Scale (FS), Clinical Frailty Scale (CFS), and Edmonton Frailty Scale (EFS), and their predictive performance in predicting the postoperative complication, so as to provide reference for nurses to choose appropriate frailty assessment tools.Methods:From December 2020 to October 2021, 207 elderly patients who underwent radical surgery for colorectal cancer at the General Surgery of the First Affiliated Hospital of Soochow University were selected as the study subject by convenience sampling. FP, FS, CFS, and EFS were used to assess patients' frailty. Taking postoperative complications as the outcome indicator, the predictive performance of four frailty assessment tools was compared using the receiver operating characteristic (ROC) curve and Bayes discriminant analysis.Results:The frailty detection rates of FP, FS, CFS, and EFS in 207 elderly colorectal cancer patients were 19.8% (41/207), 11.6% (24/207), 22.2% (46/207), and 10.1% (21/207), respectively. The areas under the ROC curves of FP, FS, CFS, and EFS were 0.714, 0.643, 0.737, and 0.665, respectively, with statistically significant differences (all P<0.01). Pairwise comparison found that there were statistically significant differences in the area under the ROC curve between FP and FS, FS and CFS, CFS and EFS ( P<0.05). The cross validation accuracy of FP, FS, CFS and EFS in predicting the postoperative complication in elderly colorectal cancer patients was 78.7%, 68.6%, 76.3%, and 75.8%, respectively. Conclusions:FP and CFS have moderate predictive performance for postoperative complications in elderly colorectal cancer patients, and there is no difference in predictive performance between the two. Both CFS and FP can be used for the assessment of preoperative frailty in elderly colorectal cancer patients, but considering clinical applicability, CFS is recommended.