Pancreatic cancer is characterized by nerve invasion and a high mortality rate， and its pathological process depends on the complex interaction network between tumor and the nervous system. Based on the concept of “pancreatic cancer neuroecology”， this article analyzes the mechanism of action of peripheral motor nerve， sensory nerve， and central nerve in tumorigenesis， pain regulation， and cachexia formation and emphasizes the synergistic regulatory role of immune cells， Schwann cells， and extracellular matrix in the microenvironment of perineural invasion. At the same time， this article further elaborates on the metabolic interaction and chemotaxis between neuraxis and tumor， the effect on promoting chemotherapy resistance， and the dynamic relationship between neuroplasticity and tumor adaptability. In clinical practice， this article summarizes the key value of perineural invasion in prognostic evaluation， preoperative evaluation， and the selection of surgical strategy. In addition， this article reviews the basic research advances in the biomarkers and potential targets associated with perineural invasion in pancreatic cancer and points out the limitations of current model and transformation research. In the future， systematically analyzing the nerve-tumor-immune network and targeting its key nodes may provide multi-dimensional strategies and new breakthroughs for the precise intervention of pancreatic cancer， the reversal of drug resistance， and the relief of symptoms.

Objective To analyze the correlation of inflammatory indicators of neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),monocyte-to-lymphocyte ratio(MLR),and systemic immune-inflammation index(SII)with traditional Chinese medicine(TCM)syndrome types and Chinese version of Thyroid Imaging Reporting and Data System(C-TIRADS)classification and properties of nodules in the patients with thyroid nodules(TN),thus to provide evidence for guiding TCM syndrome differentiation and treatment,and for assessing C-TIRADS classification and properties of the nodules in patients with TN.Methods A retrospective analysis was carried out in 140 inpatients who were diagnosed as TN and had underwent thyroidectomy during the period of January 2021 to January 2024 in the Department of General Surgery of Guangzhou Integrated Chinese and Western Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine(Guangzhou Hospital of Integrated Traditional and West Medicine).The patients were allocated to various group with reference to TCM syndrome types,C-TIRADS classification,and the properties of TN.The correlation of each clinical indicator with TCM syndrome types and C-TIRADS classification and properties of TN was analyzed.The Spearman correlation coefficient was employed for evaluating the correlation of clinical indicators with the C-TIRADS classification and properties of TN,receiver operating characteristic curve(ROC)was used to analyze the predictive value of NLR,MLR,PLR,and SII for the properties of nodules in patients with TN,and the Youden's Index was used to determine the cutoff value for optimal prediction.Results(1)According to the criteria of TCM syndrome differentiation,72 cases were differentiated as qi stagnation and phlegm obstruction syndrome,65 cases as phlegm accumulation and blood stasis syndrome,and 3 cases as heart-liver yin deficiency syndrome.For the number of cases of heart-liver yin deficiency syndrome was too small,only the first two syndromes were included for the analysis.(2)The levels of free T3(FT3)and free T4(FT4)in the patients of qi stagnation and phlegm obstruction syndrome were higher,and the levels of anti-thyroid peroxidase antibody(A-TPO),anti-thyroglobulin antibody(A-TG),neutrophil(NEU),NLR,and SII were lower than those in the patients of phlegm accumulation and blood stasis syndrome,the differences being all statistically significant(P<0.05 or P<0.01).(3)The levels of NLR,PLR,and SII in the patients with C-TIRADS3 classification were lower than those in the patients with C-TIRADS4 classification,the differences being all statistically significant(P<0.05 or P<0.01);no statistically significant difference of MLR was presented between the patients with C-TIRADS3 classification and those with C-TIRADS4 classification(P>0.05).(4)The levels of NLR,PLR,MLR,and SII in patients with benign nodules were lower than those in patients with malignant nodules,the differences being statistically significant(P<0.05 or P<0.01).(5)The Spearman correlation analysis showed that NLR,PLR,and SII were positively correlated with the C-TIRADS classification of the nodules,and NLR,PLR,MLR,and SII were positively correlated with the properties of the nodules,the differences being all statistically significant(P<0.05 or P<0.01).(6)The levels of NLR,MLR,PLR,and SII in patients with high-risk TN exerted a certain predictive value for the properties of the nodules,and their area under the curve(AUC)was 0.645,0.641,0.604,and 0.716,respectively,the differences being statistically significant(P<0.05 or P<0.01).For the prediction of nodule properties by NLR,MLR,PLR,and SII levels in patients with high-risk TN,their cutoff values and the corresponding sensitivities and specificities were 2.261(0.551,0.791),138.108(0.735,0.527),5.132(0.714,0.495),493.114(0.776,0.615),respectively;and their Youden's Index was 0.342,0.262,0.209,0.391,respectively.Conclusion The results indicated that in patients with TN,the FT3 and FT4 levels are positively correlated with the qi stagnation and phlegm obstruction syndrome;the values of A-TPO,A-TG,NEU,NLR,and SII are positively correlated with the phlegm accumulation and blood stasis syndrome;NLR,PLR and SII values are positively correlated with C-TIRADS classification;NLR,PLR,PLR,SII values are positively correlated with malignant TN.NLR,MLR,PLR,SII values exert high efficiency for the prediction of the properties of nodules in patients with TN.

Objective To investigate the role of low-density lipoprotein receptor-related protein 1(LRP1),the key gene of epithelial-mesenchymal transition,in silicosis fibrosis progression,and to preliminarily explore its regulatory mechanisms.Methods Gene set variation analysis(GSVA)was employed on GSE70866 and GSE49072 from Gene Expression Omnibus(GEO)database to assess the activity of the epithelial-mesenchymal transition gene set.LRP1 was screened via Venn diagram intersection.A multivariable Cox proportional hazards regression model(adjusted for age and sex)was constructed to validate the independent prognostic value of LRP1.Patients were grouped based on LRP1 expression,and its function mechanisms in pulmonary were explored through differential analysis,enrichment analysis,correlation analysis,and immune infiltration analysis.The silicosis model was established by a single intratracheal injection of 10 mg SiO2 suspension in C57BL/6J mice,with 100 μL of 0.9%saline administered as the control group.Pathological changes were assessed by hematoxylin-eosin staining in lung tissues.EMT model was induced in A549 cells by TGF-β1 at varying time points.LRP1 mRNA levels were measured by qPCR in lung tissues and A549 cells of TGF-β1-induced EMT model.Protein expression of LRP1,E-Cadherin,α-SMA,collagen I,p-PI3K,PI3K,p-mTOR and mTOR were detected by Western blot in lung tissues and A549 cells.Results The epithelial-mesenchymal transition gene set score was significantly higher in patients than in healthy control,with high-score patients showing reduced survival time(P<0.01).Bioinformatics analysis revealed that LRP1 primarily acts through the mTOR signaling pathway.Immune infiltration analysis demonstrated enhanced activities of activated dendritic cells,effector memory CD4+T cells,and Th17/Th2 cells in LRP1 high-expression patients,suggesting its potential regulatory role in adaptive immune responses.Histopathological observation confirmed obvious silica nodule formation in lung tissues of mouse silicosis model.RT-qPCR and Western blot analyses showed that the expression levels of LRP1 mRNA and protein were significantly downregulated in both silicosis mouse lungs and A549 cells(P<0.05).E-cadherin protein expression was downregulated,while α-SMA and collagen I expression were upregulated(P<0.05).Furthermore,the phosphorylation ratios of PI3K(p-PI3K/PI3K)and mTOR(p-mTOR/mTOR)were significantly increased(P<0.05).Conclusion LRP1 downregulation may activate the PI3K/mTOR signaling pathway,promoting the EMT process and fibrosis in silicosis.Targeting LRP1 regulation might become a new therapeutic strategy for silicosis.

Objective To observe the effect of wrist-hand orthosis combined with modified constraint-induced movement therapy(mCIMT)on upper limb and hand function in patients with stroke. Methods From February,2022 to December,2023,32 patients after stroke in Huashan Hospital,Fudan University were randomly assigned to control group(n=16)and experimental group(n=16).Both groups underwent routine re-habilitation,and wore constraint glove almost four hours a day.The experimenal group wore dynamic wrist-hand orthosis four hours everyday,additionally;five days every week,for three weeks.They were evaluated with Wolf Motor Function Test(WMFT),Action Reach Arm Test(ARAT),the strength of gripping,Amount of Use(AOU)and Quality of Movement(QOM)of Motor Activity Log(MAL),Hamilton Anxiety Scale(HAMA)and Hamil-ton Depression Scale(HAMD)before and after treatment,while root mean square ratio of affected/healthy exten-sor muscle of wrist was measured with surface electromyography Results After treatment,the scores of WMFT,ARAT,MAL-QOM,HAMA and the root mean square ratio of affected/healthy extensor muscle of wrist improved in both groups(|t|＞2.179,P＜0.05),and the improvement of WMFT score and the strength of gripping was greater in the experimental group than in the control group(|t|＞2.343,P＜0.05);the strength of gripping,the scores of MAL-AOU and HAMD improved in the experimental group(|t|＞2.819,P＜0.05). Conclusion mCIMT assisted with dynamic wrist-hand orthosis could improve upper limb and hand function in stroke pa-tients.

Objective To investigate the effects of sugammadex on postoperative pulmonary com-plications(PPCs)and postoperative recovery after thoracoscopic lung resection surgery.Methods A total of 263 patients scheduled for thoracoscopic lung resection surgery between November 2021 and July 2023,112 males and 151 females,aged 18-64 years,BMI 18.5-28.0 kg/m2,ASA physical status Ⅰ-Ⅲ,were randomly divided into three groups:the sugammadex group(group S,n=88),the neostigmine group(group N,n=87),and the control group(group C,n=88).The patient was sent to postanesthesia care unit(PACU)after operation,when the train of four(TOF)count reached 2,group S was given sugamma-dex 2 mg/kg,group N was given neostigmine 0.04 mg/kg+atropine 0.02 mg/kg,and group C was given equal volume of normal saline.The incidence of PPCs from the end of the surgery to the time of discharge was recorded.The time from the end of surgery to extubation,the time from drug administration to recovery of the train of four ratio(TOFr)to 0.9,the TOFr immediately after extubation,the length of stay in PACU,hypoxemia after extubation(SpO2＜90％)were recorded,and the incidence rate of postoperative residual neuromuscular block(PRNB)was calculated.The time of first getting out of the bed for activity,the number of total and effective compressions by the analgesia pump within 48 hours after surgery,the inci-dence of rescue analgesia,the clinical pulmonary infection score(CPIS),the numbers of postoperative nau-sea and vomiting(PONV),total drainage of the chest tube,duration of the chest tube insertion,and the length of postoperative hospital stay were recorded.Results Compared with group C,the incidence of PPCs,PRNB and hypoxemia after extubation were significantly decreased,time from the end of surgery to extubation,time from drug administration to recovery of TOFr to 0.9,the length of stay in PACU,and the first postoperatively out of bed activity time were significantly shortened,the TOFr immediately after extuba-tion was significantly increased,and CPIS was significantly decreased in group S(P＜0.05);the time from the end of surgery to extubation,time from drug administration to recovery of TOFr to 0.9,the length of stay in PACU were significantly shortened,the TOFr immediately after extubation was significantly in-creased,PRNB after extubation were significantly decreased in group N(P＜0.05).Compared with group N,the incidence of PRNB after extubation were significantly decreased,the time from the end of surgery to extubation,the time from drug administration to recovery of TOFr to 0.9,the length of stay in PACU,and the first postoperatively out of bed activity time were significantly shortened,the TOFr immediately after ex-tubation was significantly increased in group S(P＜0.05).There was no significant difference in other in-dexes between the three groups.Conclusion Sugammadex can rapidly antagonize the residual muscle re-laxation,decrease the rate of PPCs and PRNB,and promote rapid recovery of patients after thoracoscopic lung resection surgery.

ObjectiveTo investigate the effect of speech imagery therapy combined with traditional dysarthria training on dysarthria in children with cerebral palsy. MethodsFrom August to December, 2022, 21 children with cerebral palsy combined with dysarthria in Wuhu Fifth People's Hospital were randomly divided into three groups A, B and C. Group A was given traditional dysarthria training for 30 minutes everytime, group B was given implantable speech imagery combined with traditional dysarthria training for 40 minutes everytime, and group C was given additional speech imagery combined with traditional dysarthria training for 40 minutes everytime, five days a week, for three weeks. Articulation and Phonology Assessment Scale, Mouth Sensory-Motor Assessment Scale, and mandibular distance, tongue distance and vowel space area (VSA) were evaluated before and after treatment. ResultsThere was no significant difference in all the indexes among three groups before treatment (F < 1.247, P > 0.05). After treatment, the scores of phonological function and sensory-motor assessment scale increased (|t| > 2.575, P < 0.05), and the mandibular distance and VSA increased in groups A and B (|t| > 2.632, P < 0.05). The d-value of phonological function before and after treatment was more in groups B and C than in group A (P < 0.05), and no difference was found in the d-value of other indexes before and after treatment among three groups (P > 0.05). ConclusionBoth speech imagery therapies are effective in improving diction clarity, oral range of motion, and motion control ability in children with cerebral palsy, and are more effective in improving articulatory clarity than traditional speech-language training.

Objective:To explore the regulatory effect of exosomes derived from healthy human adipose stem cells (ADSC) on the fibrosis of localized scleroderma fibroblasts (LSFs) in vitro. Methods:From January 2021 to January 2022, fat from 10 healthy donors in Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences was collected by liposuction. Adipose stem cells were isolated and cultured in vitro, and exosomes (ADSC-Exo) were collected. Fibroblasts were isolated from skin tissue of 15 patients with localized scleroderma during the same period and cultured in vitro. Induced differentiation and staining, nanoparticle tracking analysis, transmission electron microscopy, PKH26 staining and Western blotting were used to identify ADSC and their exosomes. The effect of ADSC on the expression of fibrosis markers [collagen Ⅰ, collagen Ⅲ, α-smooth muscle actin (α-SMA)] in LSFs through its exosomes was examined by extracellular vesicle secretion inhibition assay. The proliferation and migration abilities of LSFs treated with ADSC-Exo were tested by CCK-8 method and scratch test. Real-time quantitative PCR, immunofluorescence staining and Western blotting were used to detect the expression levels of collagen Ⅰ, collagen Ⅲ, α-SMA, transforming growth factor β (TGF-β) and p-Smad2/3 in LSFs. Independent sample t-test was used to compare between the two groups. One-way ANOVA was used for multi-group comparison, and SNK- q test was used for pairwise comparison. Results:ADSC and LSFs were successfully isolated and cultured in vitro, and ADSC-Exo was extracted. Extracellular vesicle secretion inhibition assay demonstrated that ADSC decreased fibrotic markers of LSFs by secreting extracellular vesicles. Results of CCK-8 and scratch test showed that the proliferation and migration ability of LSFs was decreased by ADSC-Exo treatment. The results of real-time quantitative PCR, immunofluorescence staining and Western blotting showed that compared with the control group, the expressions of collagen Ⅰ, α-SMA, TGF-β and p-Smad 2/3 in the ADSC-Exo treatment group were significantly decreased. Conclusion:In vitro, ADSC-Exo can affect the biological behavior and reduce the expression of fibrosis markers in LSFs by inhibiting the TGF-β/Smad pathway.

Objective:To explore the regulatory effect of exosomes derived from healthy human adipose stem cells (ADSC) on the fibrosis of localized scleroderma fibroblasts (LSFs) in vitro. Methods:From January 2021 to January 2022, fat from 10 healthy donors in Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences was collected by liposuction. Adipose stem cells were isolated and cultured in vitro, and exosomes (ADSC-Exo) were collected. Fibroblasts were isolated from skin tissue of 15 patients with localized scleroderma during the same period and cultured in vitro. Induced differentiation and staining, nanoparticle tracking analysis, transmission electron microscopy, PKH26 staining and Western blotting were used to identify ADSC and their exosomes. The effect of ADSC on the expression of fibrosis markers [collagen Ⅰ, collagen Ⅲ, α-smooth muscle actin (α-SMA)] in LSFs through its exosomes was examined by extracellular vesicle secretion inhibition assay. The proliferation and migration abilities of LSFs treated with ADSC-Exo were tested by CCK-8 method and scratch test. Real-time quantitative PCR, immunofluorescence staining and Western blotting were used to detect the expression levels of collagen Ⅰ, collagen Ⅲ, α-SMA, transforming growth factor β (TGF-β) and p-Smad2/3 in LSFs. Independent sample t-test was used to compare between the two groups. One-way ANOVA was used for multi-group comparison, and SNK- q test was used for pairwise comparison. Results:ADSC and LSFs were successfully isolated and cultured in vitro, and ADSC-Exo was extracted. Extracellular vesicle secretion inhibition assay demonstrated that ADSC decreased fibrotic markers of LSFs by secreting extracellular vesicles. Results of CCK-8 and scratch test showed that the proliferation and migration ability of LSFs was decreased by ADSC-Exo treatment. The results of real-time quantitative PCR, immunofluorescence staining and Western blotting showed that compared with the control group, the expressions of collagen Ⅰ, α-SMA, TGF-β and p-Smad 2/3 in the ADSC-Exo treatment group were significantly decreased. Conclusion:In vitro, ADSC-Exo can affect the biological behavior and reduce the expression of fibrosis markers in LSFs by inhibiting the TGF-β/Smad pathway.

Chronic hepatitis B virus (HBV) infection is the main cause of viral hepatitis, liver cirrhosis, and primary liver cancer. At present, nucleos(t)ide analogues (NUC) and pegylated interferon α used in clinical practice cannot directly target covalently closed circular DNA, and it is difficult to achieve clinical cure of chronic hepatitis B patients; therefore, it is urgently needed to develop direct-acting antiviral agents targeting all stages of the HBV replication cycle. Capsid assembly modulator (CpAM) targets the assembly of viral capsids through various mechanisms, thereby exerting a direct-acting antiviral effect. Its combination with NUC should have a good synergistic antiviral effect, but the results of existing clinical trials have shown that chronic hepatitis B patients who received a limited course of antiviral therapy with CpAM and NUC all experienced off-therapy viral rebound. Based on the mechanism of action of these two types of drugs, this article provides a reasonable explanation for the above clinical trial results and points out that a longer course of antiviral therapy with CpAM and NUC may be needed in the future clinical trials with safe drug withdrawal as the end point of observation, so as to deplete or silence the pool of covalently closed circular DNA and increase the possibility of safe drug withdrawal in CHB patients. In addition, further studies are needed to explore antiviral therapeutic strategies with a combination of multiple targets.