Background The active metabolite of benzo[a]pyrene (BaP), 7,8-dihydroxy-9,10-epoxybenzo[a]pyrene (BPDE), can form adducts with DNA, but the spectrum of BPDE-DNA adducts is unclear. Objective To identify the distribution of BPDE adduct sites and associated genes at the whole-genome level by chromatin immunoprecipitation followed by sequencing (ChIP-Seq), and serve as a basis for further exploring the toxicological mechanisms of BaP. Methods Human bronchial epithelial-like cells (16HBE) were cultured to the fourth generation inthe logarithmic growth phase. Cells were harvested and added to chromatin immunoprecipitation lysis buffer. The lysate was divided into experimental and control groups. The experimental group received a final concentration of 20 μmol·L⁻¹ BPDE solution, while the control group received an equivalent volume of dimethyl sulfoxide solution. The cells were then incubated at 37 °C for 24 h. Chromatin fragments of 100-500 bp were obtained through sonication. BPDE-specific antibody (anti-BPDE 8E11) was used to enrich DNA fragments with BPDE adducts. High-throughput sequencing was conducted to detect BPDE adduct sites. The top 1000 peak sequences were subjected to motif analysis using MEME and DREME software. BPDE adduct target genes at the whole-genome level were annotated, and Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of BPDE adduct target genes were conducted using bioinformatics techniques. Results The high-throughput sequencing detected a total of 842 BPDE binding sites, distributed across various chromosomes. BPDE covalently bound to both coding and non-coding regions of genes, with 73.9% binding sites located in intergenic regions, 19.6% in intronic regions, and smaller proportions in upstream 2 kilobase, exonic, downstream 2 kilobase, and 5' untranslated regions. Regarding the top 1000 peak sequences, four reliable motifs were identified, revealing that sites rich in adenine (A) and guanine (G) were prone to binding. Through the enrichment analysis of binding sites, a total of 199 BPDE-adduct target genes were identified, with the majority located on chromosomes 1, 5, 7, 12, 17, and X. The GO analysis indicated that these target genes were mainly enriched in nucleic acid and protein binding, participating in the regulation of catalytic activity, transport activity, translation elongation factor activity, and playing important roles in cell division, differentiation, motility, substance transport, and information transfer. The KEGG analysis revealed that these target genes were primarily enriched in pathways related to cardiovascular diseases, cancer, and immune-inflammatory responses. Conclusion Using ChIP-Seq, 199 BPDE adduct target genes at genome-wide level are identified, impacting biological functions such as cell division, differentiation, motility, substance transport, and information transfer. These genes are closely associated with cardiovascular diseases, tumors, and immune-inflammatory responses.

Objective To investigate the current status,evolving hotspots,and emerging trends in the field of human re-source allocation research in public hospitals,both domestically and internationally,to provide a reference for future research di-rections in China.Methods CiteSpace was used to conduct a visual analysis of the research literature on human resource alloca-tion in public hospitals based on China National Knowledge Infrastructure(CNKI)and the Web of Science(WOS).The analysis encompassed co-authorship,institutional collaboration,keyword co-occurrence and clustering,and burst detection.Results A total of 1 417 Chinese articles and 981 international articles were included.Domestic research in this field focused more on healthcare reform and management,resource allocation,hierarchical diagnosis,and treatment,and informatization and efficiency improvement.On the contrary,international research primarily centered on the employee satisfaction,healthcare system quality,work environment and medical staff.Future trends in domestic research included cost reduction,efficiency enhancement,and a greater emphasis on public welfare in public hospitals,while international research was beginning to explore the influence of polit-ical concepts in this field.Conclusion Compared to international research,domestic research needs to further improve its theo-retical and localized understanding,broaden its research scope,explore the interdisciplinary collaboration opportunities,and delve into research directions such as the application of artificial intelligence and automation technology in healthcare services,management of a diverse workforce,and innovative management techniques and applications.

Objective:To analyze the differences in clinical and endoscopic ultrasonography (EUS) findings between diffuse and focal IgG4-related autoimmune pancreatitis (IgG4-AIP).Methods:Data of patients diagnosed as having IgG4-AIP who underwent EUS at Chinese PLA General Hospital from September 2011 to April 2022 were retrospectively collected. General clinical data, EUS features, and postoperative pathology were analyzed for characteristic differences.Results:A total of 40 patients were included in the study, 60.03±10.87 years old, a higher proportion of males (85.0%, 34/40). All patients underwent EUS, and 28 underwent EUS-guided fine-needle aspiration. Among the 40 patients, 29 (72.5%) had diffuse type and 11 (27.5%) had focal type. Abdominal pain [65.5% (19/29) VS 18.2% (2/11), χ2=5.393, P=0.020] and thickening of the bile duct wall [51.7% (15/29) VS 9.1% (1/11), χ2=4.394, P=0.036] were more common in the diffuse type, while main pancreatic duct dilation [45.5% (5/11) VS 10.3% (3/29), χ2=4.146, P=0.042] was more common in the focal type, with the lesion most commonly located in the pancreatic head (90.9%, 10/11). There was no significant difference in the presence of chronic pancreatitis parenchymal changes between the two groups [34.5% (10/29) VS 27.3% (3/11), χ2=0.003, P=0.955]. Conclusion:There are certain differences in abdominal pain and biliary and pancreatic duct lesions between diffuse and focal AIP. The high expression of chronic pancreatitis characteristics is not observed in either group, which provides clues for the classification of AIP in clinical practice.

To summarize the nursing experience of a patient with intestinal fistula after laparoscopic extended radical resection of rectal cancer plus ileostomy.Nursing points include:multi-disciplinary joint formulation of systemic treatment and nursing plan;using fistula isolation technology to isolate and drain digestive fluid;implementing incision segmentation management to promote infection control and tissue growth.After careful treatment and nursing care,the intestinal fistula was closed after 38 days of surgery,and the wound healed after 52 days of surgery.

Objective By observing the effects of"three methods and three points"tuina technique on the expression of interleukin-17F(IL-17F),interleukin-17 receptor C(IL-17RC),activator 1 of nuclear transcription factor-κB(Act1),tumour necrosis factor receptor-associated factor 6(TRAF6)and M1 microglial cell expression in the spinal dorsal horn of rats with mild chronic compressive injury(minor CCI)model,we explored the immediate analgesic mechanism of tuina on peripheral neuropathic pain(pNP).Methods Thirty-six SD rats were divided into the sham group,the model group and the tuina group according to the random number method,twelve rats in each group,and the minor CCI model was replicated by ligating the right sciatic nerve.The rats in the tuina group were subjected to pointing,plucking and kneading at the BL37,BL57 and GB34 points on the affected side using a tuina simulator,while the sham group and the model group were only grasped and restrained,and were intervened for one time.The mechanical pain test and cold plate test were used to evaluate the response of rats to mechanical stimulation and cold stimulation after immediate intervention.The protein expression of IL-17F and TRAF6 in the spinal dorsal horn of rats in each group was detected by Western blotting.The mRNA expression of IL-17F,IL-17RC,Act1 and TRAF6 in the spinal dorsal horn of rats in each group was detected by real-time PCR.The average fluorescence intensity of M1 microglia in the spinal dorsal horn of rats in each group was detected by immunofluorescence.Results Behavioral results showed that before intervention,compared with the sham group,paw mechanical withdraw threshold(PMWT)decreased and cold sensitivity threshold(CST)increased in the model group and the tuina group;after tuina intervention,PMWT in the tuina group was increased,and CST was decreased compared with the model group;after intervention,PMWT in the tuina group was increased,while CST was decreased(P＜0.05).RT-PCR results showed that compared with the sham group,mRNA expression levels of IL-17F,IL-17RC,TRAF6 and Act1 in the spinal dorsal horn of the model group were increased;compared with model group,the mRNA expression levels of above indexes in the tuina group were decreased(P＜0.05).Western boltting results showed that compared with the sham group,the expression levels of IL-17F and TRAF6 protein in the spinal dorsal horn of the model group were increased;compared with the model group,the expression levels of IL-17F and TRAF6 protein in the tuina group decreased(P＜O.05).Immunofluorescence results showed that the mean fluorescence intensity of CD40 in the spinal dorsal horn of model group was enhanced compared with the sham group;compared with the model group,the mean fluorescence intensity of CD40 in the tuina group was decreased(P＜0.05).Conclusion The"three methods and three points"tuina technique can produce immediate analgesia by inhibiting the expression of IL-17F,IL-17RC,Act1,TRAF6 and the activation of M1 microglia in the dorsal horn of the spinal cord after one intervention.

Objective To explore the analgesic initiation mechanism of"three-manipulations and three-acupoints"of tuina on minor chronic constriction injury(minor CCI)model rats.Methods According to the random number table method,35 SD rats were randomly divided into five groups:normal group,sham group,model group,tuina group,and tuina+MK-801 group.The model group,tuina group,and tuina+MK-801 group were subjected to ligation of the right sciatic nerve trunk to establish a minor CCI rat model.The sham group was only exposed to the right sciatic nerve without ligation,and the normal group was not subjected to any operation.The normal group was not subjected to any intervention measures.On the seventh day after modeling,the model group and the sham group underwent 9 minutes of grasping restraint,while the tuina group underwent one intervention of three-manipulations(point method,dialing method,and kneading method)and three-acupoints(right"Yinmen"(BL37),"Chengshan"(BL57),and"Yanglingquan"(GB34)acupoints)with each manipulation and acupoint intervention for 1 minute for a total of 9 minutes.The tuina+MK-801 group received intrathecal injection of MK-801 from the fifth to seventh days after modeling,with a dose of 6 μg(10 μL)per day,tuina intervention was performed 30 minutes after the last intrathecal injection,and the specific operation of tuina was the same as that of the tuina group.Before modeling,after modeling,and after intervention,each group of rats was subjected to cold sensitivity threshold(CST)and mechanical withdrawal threshold(MWT)testing.After intervention,immunohistochemistry was used to detect the positive expression of cyclic guanosine monophosphate(cGMP)in the spinal dorsal horn(SDH)at L4-6 segments;protein expressions of N-methyl-D-aspartate receptor 1(NMDAR1),neurogenic nitric oxide synthase(nNOS),soluble guanylyl cyclase β(sGCβ),and protein kinase G1(PKG1)in SDH at L4-6 segments were detected by Western blotting;mRNA expressions of NMDAR1,nNOS,sGCβ,cGMP,and PKG1 in SDH at L4-6 segments were detected by real-time PCR.Results Compared with the normal and sham groups,after modeling,CST increased and MWT decreased in the model group,tuina group and tuina+MK-801 group(P＜0.05);after intervention,the positive protein expression of cGMP was increased,the protein expressions of NMDAR1,nNOS,sGCβ,and PKG1 were increased,and mRNA expressions of NMDAR1,nNOS,sGCβ,cGMP,and PKG1 were increased in SDH at L4-6 segments in the model group(P＜0.05).Compared with the model group,after intervention,CST decreased and MWT increased in the tuina group and tuina+MK-801 group(P＜0.05);the positive protein expression of cGMP was decreased,the protein expressions of NMDAR1,nNOS,sGCβ,and PKG1 were decreased,and mRNA expressions of NMDAR1,nNOS,sGCβ,cGMP,and PKG1 were decreased in SDH at L4-6 segments in the tuina group and tuina+MK-801 group(P＜0.05).Conclusion One-time tuina intervention can effectively improve the symptoms of thermal and mechanical hyperalgesia induced by peripheral nerve injury,which may initiate analgesia through the NMDAR1/cGMP/protein kinase G signaling pathway,thereby exerting immediate analgesic effect.

Objective We aimed to observe the clinical efficacy and safety of Compound Congrong Yizhi Capsule in subjects with mild to moderate Alzheimer's disease (AD). Methods A total of 65 subjects with mild to moderate AD who visited the Affiliated Hospital of Qingdao University and Xuanwu Hospital of Capital Medical University from February 2023 to February 2024 were selected and divided into the Compound Congrong Yizhi Capsule group (40 cases) and the Donepezil Hydrochloride group (25 cases) for a 6-month treatment. The primary outcome measures included the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score and Auditory Verbal Learning Test (AVLT) score. Secondary outcome measures included the Mini-Mental State Examination (MMSE),Activities of Daily Living (ADL),Rey-Osterrieth Complex Figure Test (ROCFT),Trail Making Test (TMT),Verbal Fluency Test (VFT),Symbol Digit Modalities Test (SDMT),Digital Span Test (DST),Clock Drawing Test (CDT),and Boston Naming Test (BNT) scores,as well as clinical biochemical indicators including blood lipids,blood glucose,liver and kidney function. Results Compared with the Donepezil Hydrochloride group after treatment,subjects in the Compound Congrong Yizhi Capsule group showed an increase in ADAS-Cog and AVLT-total scores,and a decrease in MMSE,Rey-Osterrieth Complex Figure Copy Test,and CDT scores (P<0.05). Additionally,there was an increase in alanine aminotransferase (ALT),blood urea nitrogen(BUN),and total bilirubin (TBIL) levels,and a decrease in indirect bilirubin (IBIL) levels (P<0.05).Conclusion Compound Congrong Yizhi Capsule exerts a regulatory effect on cognitive function in subjects with AD,especially in the cognitive domains of episodic memory and visual-spatial processing ability. It also improves certain clinical indicators such as ALT,BUN,TBIL,and IBIL. This suggests that the early intervention with Compound Congrong Yizhi Capsule in AD can effectively improve symptoms,delay disease progression,and fully embody the concept of traditional Chinese medicine's preventive approach to illness.

Objective:The aim of this study is to examine the impact of inosine pretreatment in pregnant rats on as-trocyte(Ast)responses in the maternal inflammation-induced periventricular leukomalacia(PVL)model in offspring.Methods:The pregnant rats were divided into Control,PVL,and IN-PVL groups.In the PVL group,pregnant rats at gestational day 17(E17)received intraperitoneal injections of lipopolysaccharide(LPS)at a dose of 350 μg/kg for 2 days.In the IN-PVL group,pregnant rats at E1 were administered an inosine solution(1 mg/ml,25 ml/day)for 16 days followed by intraperitoneal injections of LPS for 2 days.Newborn 7-day-old rat brains from each group of pregnant rats were collected,and the protein expression of myelin basic protein(MBP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1 β(IL-1β),interleukin-4(IL-4),interleukin-10(IL-10),glial fibrillary acidic protein(GFAP),complement 3(C3),S100 calcium binding protein A10(S100A10),platelet-derived growth factor(PDGF),chemokine ligand 1(CXCL1),and connexin 43(Cx43)were detected by immunofluorescence staining or Western Blot.Results:The PVL group exhibited a decrease in myelin MBP color area and an increase in hypertrophic Ast in contrast to the Control group.Additionally,protein expression levels of proinflammatory factors(TNF-α,IL-6,IL-1β),GFAP,A1 Ast marker C3,and Ast linker Cx43 were significantly elevated in the PVL group compared to the Control group(P＜0.05).Conversely,protein expression levels of anti-inflammatory factors(IL-4,IL-10),MBP,A2 Ast marker S100A10,and Ast secreted products(PDGF,CXCL 1)were significantly decreased in the PVL group com-pared to the Control group(P＜0.05).Inosine pretreatment effectively reversed the expression levels of these proteins(P＜0.05).Conclusion:Inosine pretreatment of pregnant rats improved cerebral hypomyelination in offspring PVL neonatal rats by regulation of Ast responsiveness and the secretion of pro-myelinating substances.

Objective To explore the analgesic initiation mechanism of three-manipulation and three-acupoint tuina in model rats with minor chronic constriction injury(CCI).Methods Fifty-six SD rats were divided randomly into eight groups:normal group,sham group,model 1 group,model 2 group,tuina 1 group,tuina 2 group,tuina 1+transient receptor potential vanilloid-1(TRPV1)antagonist group,and tuina 2+transient receptor potential ankyrin 1(TRPA1)antagonist group.The model,tuina,and tuina+antagonist groups were established with minor CCI models.The tuina and tuina+antagonist groups received the three-method three-point intervention(point method,dial method,kneading method,Yinmen point,Chengshan point,Yanglingquan point)7 days after modeling.The model and sham groups were subjected to grasping restraint,and the normal group received no intervention.After the respective interventions,each group was tested for changes in mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)to detect different types of pain.The nitric oxide(NO)content of the dorsal root ganglion(DRG)was determined by the nitrate reductase method,and changes in protein and gene expression levels of components of the TRPV1/TRPA1-NO-cGMP-protein kinase G(PKG)signaling pathway in the DRG of each group were determined by enzyme-linked immunosorbent assay,Western blot,and qPCR.Results Compared with the model group,MWT and TWL were prolonged in the tuina 1 and tuina 2 groups.Expression levels of TRPV1,TRPA1,NO,soluble guanylate cyclase-β,cGMP,and PKG1 in the DRG were significantly decreased in the tuina 1,tuina 2,tuina 1+TRPV1 antagonist,and tuina 2+TRPA1 antagonist groups.Conclusions Tuina can effectively improve the symptoms of thermal and mechanical hyperalgesia caused by peripheral nerve injury after one-time intervention.Tuina can exert immediate and continuous analgesic effects via the TRPV1/TRPA1-NO-cGMP-PKG signaling pathway.

Alzheimer’s disease (AD) is a neurodegenerative disease that has become increasingly serious with the aging of human society. It has become an important factor that hinders the development of society, making early diagnosis and intervention of great significance. In recent years, with the continuous development of computer technology, deep learning has shown superior performance in processing AD big data, identifying effective detection indices, and improving detection accuracy. In this paper, the research progress of deep learning in early diagnosis of AD in areas such as neuroimaging data, electroencephalogram, blood and genetic data, and multimodal fusion data was mainly introduced. Common deep learning models were summarized, and future research directions in this field were discussed.