Objective To explore the protective effect of polydatin and its mechanism on secondary liver injury in silicosis rats based on network pharmacology and animal experiments. Methods i) Network pharmacology study. Based on multiple databases, the targets of polydatin effect related to silicosis and liver injury were collected, and the common targets of polydatin-silicosis-liver injury were screened to construct a protein-protein interaction network. Enrichment analyses were performed to identify core targets involved in the effects of polydatin on silicosis-associated secondary liver injury. The mechanism of action of polydatin in relieving silicosis and silicosis-associated secondary liver injury was investigated, in which polydatin served as molecular docking ligand. ii) Animal experimental validation. Specific pathogen free male SD rats were randomly divided into three groups, with 10 rats per group. Rats in the model and intervention groups received 1 mL of a silica suspension at a mass concentration of 50 g/L for modeling using a one-time non-tracheal exposure method. Then rats in the intervention group were injected intraperitoneally with polydatin solution at 30 mg/kg body weight, once daily starting from the first day after silica exposure, whereas rats in the control group received no treatment. Lung and liver histopathology of rats, which were randomly sacrificed on days 28 and 56 post-exposure in both groups, were examined. Biomarkers of liver injury and hepatic oxidative stress were measured, and hepatic expression of nuclear factor erythroid 2-related factor 2 (NRF2) related proteins was detected by Western blotting. Results i) Network pharmacology study results. A total of 137 polydatin-related targets, 14 812 silicosis-related targets, and 3 038 liver injury-related targets were identified, among which 69 were common targets and 28 were key targets. Gene Ontology analysis indicated that the key targets were involved in 1 883 pathways. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified 137 pathways related to the targets. Molecular docking showed good binding affinities between polydatin and B-cell lymphoma 2 (BCL2), interleukin 6 (IL-6), tumor necrosis factor (TNF), and NRF2. ii) Animal experimental validation results. Compared with the control group, rats in the model group showed increased collagen deposition in both lung and liver tissues, with hepatic degeneration, necrosis, and inflammatory cell infiltration on days 28 and 56 after silica exposure. The collagen in lung and liver tissues of rats on days 28 and 56 after silica exposure increased in the model group compared with the control group (all P<0.05). Meanwhile, serum alanine aminotransferase and aspartate aminotransferase activities, hepatic lactate dehydrogenase 5 activities and NADPH: quinone oxidoreductase 1 (NQO1) expression in liver tissue increased (all P<0.05), whereas hepatic superoxide dismutase activity and NRF2 expression were decreased (all P<0.05). The level of malondialdehyde and the relative expression of heme oxygenase-1 (HO-1) protein in liver tissue in rat of model group were higher than those in the control group (all P<0.05). These alterations were ameliorated in rats of the intervention group compared with the model group (all P<0.05). Conclusion Polydatin exerts protective effects against secondary liver injury in rats with silicosis. These effects may be mediated by regulation of core targets such as BCL2, IL6, TNF, and NRF2, modulation of inflammatory pathways including TNF and IL17 signaling, and activation of the NRF2/HO-1 pathway, thereby exerting synergistic anti-inflammatory, antioxidant, and antifibrotic effects via the "lung-liver axis".

Objective To investigate the feasibility of simultaneous multi-slice(SMS)acquisition combined with single-shot echo-planar imaging(SSEPI)multi-model diffusion weighted imaging(DWI)for breast lesions.Methods Totally 108 cases of breast lesions were retrospectively enrolled and divided into malignant group(n=66)and benign group(n=42)based on pathology.3.0T MR scanner was used to acquire SSEPI and SMS-SSEPI multi-b values DWI,7 derived parameters were obtained through post-processing with mono-exponential,fractional-order calculus(FROC)and continuous-time random walk(CTRW)models.Then the imaging quality and derived parameters of SMS-SSEPI and SSEPI DWI were compared between groups.Spearman correlation analysis was performed to explore the relationships of corresponding parameters between SMS-SSEPI DWI and SSEPI DWI.Diagnostic performance of each parameter for distinguishing malignant and benign lesions was evaluated according to the area under the receiver operating characteristic curve(AUC).Results Background noise score of SMS-SSEPI DWI was lower than that of SSEPI DWI(P＜0.05),whereas no significant difference of overall imaging quality,normal anatomical structure depiction,lesion conspicuity,geometric distortion,signal-to-noise ratio(SNR)nor contrast-to-noise ratio(CNR)was found between SMS-SSEPI DWI and SSEPI DWI(all P＞0.05).Parameters derived from SMS-SSEPI DWI were all moderately to highly positively correlated with those from SSEPI DWI(rs=0.66-0.98).Malignant lesions exhibited significantly lower apparent diffusion coefficient(ADC),diffusion coefficient based on FROC(DFROC),fractional order derivative in space(βFROC),diffusion coefficient based on CTRW(DCTRW),temporal diffusion heterogeneity index(αCTRW)and spatial diffusion heterogeneity index(βCTRW)values,but higher spatial parameter(μFROC)value than benign lesions(all P＜0.05).AUC of SMS-SSEPI DWI derived parameters for differentiating malignant from benign lesions were 0.699-0.900,of those from SSEPI DWI were 0.654-0.887,while in both SMS-SSEPI DWI and SSEPI DWI,DFROC had the highest diagnostic efficacy(AUC=0.900,0.887).Conclusion SMS-SSEPI DWI could be used to effectively differentiate malignant and benign breast lesions.

BACKGROUND:Acupotomy is an effective method for the treatment of cervical spondylosis with definite clinical efficacy,but its key molecular mechanism is still unclear.OBJECTIVE:To observe the effect of acupotomy intervention on the expression of fibroblast growth factor family and kinase insert domain protein receptor in the splenius capitis muscles of rats with cervical spondylosis,and to study the therapeutic mechanism of acupotomy in cervical spondylosis.METHODS:The Genomics Expression Omnibus Database was searched to obtain the microarray dataset GSE153761,which was compatible with the study,and a bioinformatics approach was used for the initial screening of targets,followed by animal experiments.Twenty-four 6-month-old SPF grade Sprague-Dawley rats were randomly divided into four groups.The model of cervical spondylosis was established by unbalanced dynamic and static forces in the model and acupotomy groups.The muscles and ligaments were not cut in the sham operation group.After successful modeling,acupotomy intervention was performed in the acupotomy group,once a week,3 times in total.Normal rats were selected as controls.The posteroanterior and lateral X-rays of the cervical spine were taken for modeling verification;the open-field tests were performed in all rats to observe behavioral changes;the pathological structure of the splenius capitis muscles was observed by hematoxylin-eosin staining;the mRNA and protein expression of fibroblast growth factor family and kinase insert domain protein receptor in the splenius capitis muscles was detected by fluorescent quantitative PCR and immunohistochemical method,respectively.RESULTS AND CONCLUSION:Bioinformatics results indicated that fibroblast growth factor family/kinase insert domain protein receptor is an important signal axis for activating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.After modeling,the intervertebral space of the rats was narrowed,and the anterior and posterior borders of the vertebral body and the articular process were hyperosteogenous.In the open-field tests,the total distance and average speed in the model group were decreased after modeling(P<0.05),while the total rest time in the model group was increased(P<0.05).After treatment,the total distance and average speed in the acupotomy group were greater than those in the model group(P<0.05),while the total rest time in the acupotomy group was shorter than that in the model group(P<0.05).The pathological changes of the splenius capitis muscles indicated damage to the cervical muscle,and acupotomy improved cervical muscle strain.Compared with the normal group,The mRNA and protein expressions of fibroblast growth factor 7,fibroblast growth factor 9,fibroblast growth factor 10,fibroblast growth factor 18,and kinase insert domain protein receptor in the splenius capitis muscles were increased in the model group compared with the normal group(P<0.05).In contrast,acupotomy treatment could downregulate the above indicators(P<0.05).Thus,acupotomy may repair cervical muscle strain by regulating the expression of fibroblast growth factor 7,fibroblast growth factor 9,fibroblast growth factor 10,fibroblast growth factor 18,and kinase insert domain protein receptor,thereby improving intervertebral disc degeneration,which may be the key target for acupotomy treatment of cervical spondylosis.

BACKGROUND:Acupotomy is an effective method for the treatment of cervical spondylosis with definite clinical efficacy,but its key molecular mechanism is still unclear.OBJECTIVE:To observe the effect of acupotomy intervention on the expression of fibroblast growth factor family and kinase insert domain protein receptor in the splenius capitis muscles of rats with cervical spondylosis,and to study the therapeutic mechanism of acupotomy in cervical spondylosis.METHODS:The Genomics Expression Omnibus Database was searched to obtain the microarray dataset GSE153761,which was compatible with the study,and a bioinformatics approach was used for the initial screening of targets,followed by animal experiments.Twenty-four 6-month-old SPF grade Sprague-Dawley rats were randomly divided into four groups.The model of cervical spondylosis was established by unbalanced dynamic and static forces in the model and acupotomy groups.The muscles and ligaments were not cut in the sham operation group.After successful modeling,acupotomy intervention was performed in the acupotomy group,once a week,3 times in total.Normal rats were selected as controls.The posteroanterior and lateral X-rays of the cervical spine were taken for modeling verification;the open-field tests were performed in all rats to observe behavioral changes;the pathological structure of the splenius capitis muscles was observed by hematoxylin-eosin staining;the mRNA and protein expression of fibroblast growth factor family and kinase insert domain protein receptor in the splenius capitis muscles was detected by fluorescent quantitative PCR and immunohistochemical method,respectively.RESULTS AND CONCLUSION:Bioinformatics results indicated that fibroblast growth factor family/kinase insert domain protein receptor is an important signal axis for activating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.After modeling,the intervertebral space of the rats was narrowed,and the anterior and posterior borders of the vertebral body and the articular process were hyperosteogenous.In the open-field tests,the total distance and average speed in the model group were decreased after modeling(P<0.05),while the total rest time in the model group was increased(P<0.05).After treatment,the total distance and average speed in the acupotomy group were greater than those in the model group(P<0.05),while the total rest time in the acupotomy group was shorter than that in the model group(P<0.05).The pathological changes of the splenius capitis muscles indicated damage to the cervical muscle,and acupotomy improved cervical muscle strain.Compared with the normal group,The mRNA and protein expressions of fibroblast growth factor 7,fibroblast growth factor 9,fibroblast growth factor 10,fibroblast growth factor 18,and kinase insert domain protein receptor in the splenius capitis muscles were increased in the model group compared with the normal group(P<0.05).In contrast,acupotomy treatment could downregulate the above indicators(P<0.05).Thus,acupotomy may repair cervical muscle strain by regulating the expression of fibroblast growth factor 7,fibroblast growth factor 9,fibroblast growth factor 10,fibroblast growth factor 18,and kinase insert domain protein receptor,thereby improving intervertebral disc degeneration,which may be the key target for acupotomy treatment of cervical spondylosis.

Objective To investigate the feasibility of simultaneous multi-slice(SMS)acquisition combined with single-shot echo-planar imaging(SSEPI)multi-model diffusion weighted imaging(DWI)for breast lesions.Methods Totally 108 cases of breast lesions were retrospectively enrolled and divided into malignant group(n=66)and benign group(n=42)based on pathology.3.0T MR scanner was used to acquire SSEPI and SMS-SSEPI multi-b values DWI,7 derived parameters were obtained through post-processing with mono-exponential,fractional-order calculus(FROC)and continuous-time random walk(CTRW)models.Then the imaging quality and derived parameters of SMS-SSEPI and SSEPI DWI were compared between groups.Spearman correlation analysis was performed to explore the relationships of corresponding parameters between SMS-SSEPI DWI and SSEPI DWI.Diagnostic performance of each parameter for distinguishing malignant and benign lesions was evaluated according to the area under the receiver operating characteristic curve(AUC).Results Background noise score of SMS-SSEPI DWI was lower than that of SSEPI DWI(P＜0.05),whereas no significant difference of overall imaging quality,normal anatomical structure depiction,lesion conspicuity,geometric distortion,signal-to-noise ratio(SNR)nor contrast-to-noise ratio(CNR)was found between SMS-SSEPI DWI and SSEPI DWI(all P＞0.05).Parameters derived from SMS-SSEPI DWI were all moderately to highly positively correlated with those from SSEPI DWI(rs=0.66-0.98).Malignant lesions exhibited significantly lower apparent diffusion coefficient(ADC),diffusion coefficient based on FROC(DFROC),fractional order derivative in space(βFROC),diffusion coefficient based on CTRW(DCTRW),temporal diffusion heterogeneity index(αCTRW)and spatial diffusion heterogeneity index(βCTRW)values,but higher spatial parameter(μFROC)value than benign lesions(all P＜0.05).AUC of SMS-SSEPI DWI derived parameters for differentiating malignant from benign lesions were 0.699-0.900,of those from SSEPI DWI were 0.654-0.887,while in both SMS-SSEPI DWI and SSEPI DWI,DFROC had the highest diagnostic efficacy(AUC=0.900,0.887).Conclusion SMS-SSEPI DWI could be used to effectively differentiate malignant and benign breast lesions.

Objective:To evaluate the short-term and long-term efficacy of Heidelberg triangle dissection in surgical treatment for pancreatic head cancer.Methods:The clinicopathological data of 97 patients with pancreatic head cancer who underwent pancreaticoduodenectomy at Cangzhou Central Hospital from Jan 2017 to Jan 2020 were retrospectively analyzed. After propensity score matching, 33 patients were included into the Heidelberg group and 36 patients in the control group.Results:There were no significant difference between Heidelberg group and control group in preoperative general conditions and postoperative major complications, while there were more cases with safe surgical margin > 1 mm (81.8% vs. 58.3%, P=0.034) and a significantly higher total number of lymph node dissection (11.24±2.35 vs. 9.50±2.76, P=0.006). In the survival analysis, the cumulative recurrence rate at 12 months (0.182±0.067 vs. 0.444±0.083, P=0.023) and 18 months (0.424±0.086 vs. 0.667±0.079, P=0.024) were better off in the Heidelberg group, and the local recurrence rate in the Heidelberg group was significantly lower than that in the control group (15.3 % vs. 36.1 %, P=0.037). However, there was no statistical difference in the overall survival time between the two groups. Conclusion:Dissection of Heidelberg triangle in radical resection of pancreatic head cancer reduces tumor local recurrence ,while fails to provide survival benefit.

Objective:To investigate the effects of extracts of Rhizoma Sparganii and Rhizoma Curcumae on cartilage damage in osteoarthritis rats and NADPH oxidase 2 (NOX2)/reactive oxygen species (ROS)/nuclear factor-κB (NF-κB) signaling pathways. Methods:Rats (50 cases) were divided into the sham group, and model group, as well as the low, medium, and high dose groups of extracts of Rhizoma Sparganii and Rhizoma Curcumae, with 10 rats in each group. Except for sham group, the rat model of cartilage damage in knee osteoarthritis was established. On the second day after modeling, the rats in the low, medium, and high dose groups received intragastric extracts perfusion of Rhizoma Sparganii and Rhizoma Curcumae at the doses of 5, 10, and 20 g/kg respectively. The rats in the sham and model groups received intragastric equivalent 0.9% sodium chloride solution perfusion, once daily, for 20 days by continuous administration. The knee joint behavior, bone metabolism indicators, serum superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH) levels, inflammatory factors, NOX2, and NF-κB levels of each group were observed. Results:Compared with the model group, the behavioral abnormality scores, cartilage oligomeric matrix protein (COMP), MDA, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), NOX2, and NF-κB levels in the low, medium, and high dose groups were all gradually decreased (all P < 0.05), while proteoglycan, SOD, GSH, and interleukin-10 (IL-10) levels in the low, medium, and high dose groups were all gradually increased (all P < 0.05), and it was dose-dependent. Conclusions:Rhizoma Sparganii and Rhizoma Curcumae extracts can effectively improve cartilage damage in osteoarthritis rats, and it may be related to the inhibition of the NOX2/ROS/NF-κB signaling pathway.

Objective To explore the value of fractional order calculus(FROC)model diffusion weighted imaging(DWI)for evaluating pathological classification and differentiation degree of cervical cancer(CCA).Methods Totally 74 CCA patients were enrolled and divided into squamous cell carcinoma(SCC)group(n=54)and adenocarcinoma(ACA)group(n=20)based on pathological classification,also low differentiation group(n=33)and medium-high differentiation group(n=41)based on differentiation degree.Conventional MR examination and DWI with 12 b-values were performed,FROC model parameters(D,β,and p value)and the apparent diffusion coefficient(ADC)of mono-exponential model were obtained via software analysis.The parameters were compared between groups,and receiver operating characteristic curve of those being significantly different between groups were drawn,the area under the curves(AUC)were calculated to evaluate the diagnostic efficacy.Results Significant differences of ADC,D,and β values were found between SCC group and ACA group(all P＜0.05),and D value had the highest AUC(0.726)for distinguishing pathological classification CCA.Meanwhile,significant differences of D,β,p values and ADC were observed between low differentiation group and medium-high differentiation group(all P＜0.05),D value also had the highest AUC(0.865).AUC of the combined model constructed based on significant variables β and p values in logistic regression was 0.926,higher than that of each parameter alone(all P＜0.05).Conclusion FROC model DWI could be used to evaluate pathological classification and differentiation degree of CCA.

Objective:To investigate the characteristics and risk factors of local recurrence in resected pancreatic cancer.Methods:The clinicopathological data of 190 patients in whom recurrent sites can be identified after radical resection of pancreatic cancer from Sep 2013 to Aug 2020 at the Cangzhou Central Hospital were retrospectively analyzed. The survival time and clinicopathological characteristics of local recurrence were compared with those of other recurrence types. Cox risk regression model was used to analyze the risk factors of local recurrence.Results:The recurrence sites were local (49 cases, 25.8%), liver (53 cases, 27.9%), lung (35 cases, 18.4%), peritoneal (25 cases, 13.2%) and multiple sites (28 cases, 14.7%). Patients mRFS and mOS were 17.8 months and 30.9 months respectively. The clinicopathological features of patients with local recurrence were compared with those of other recurrence types [tumor diameter ( P=0.023), preoperative CA199 level ( P=0.021), peripancreatic nerve plexus invasion ( P=0.031), lymphovascular invasion ( P=0.004), surgical margin state ( P<0.001) and postoperative adjuvant chemotherapy ( P=0.038)]. Tumor diameter ( P=0.018), peripancreatic nerve plexus invasion ( P=0.002) and postoperative adjuvant chemotherapy ( P=0.004) were independent factors for local recurrence in resected pancreatic cancer, and only peripancreatic nerve plexus invasion was not associated with other recurrence types. Conclusions:Local recurrence in resected pancreatic cancer has important impact on the prognosis of patients. Peripancreatic nerve plexus invasion is an independent factor affecting local recurrence.

Objective:To investigate the short-term outcome of Heidelberg triangle dissection in laparoscopic pancreaticoduodenectomy (LPD) for pancreatic cancer.Methods:The clinical data of 84 patients with pancreatic head cancer who underwent LPD from July 2015 to September 2020 in the Department of Hepatobiliary and Pancreatic Surgery of the Cangzhou Central Hospital were retrospectively analyzed. According to the scope of surgical dissection, the patients were divided into the control group ( n=45) and the Heidelberg group ( n=39). In the control group, routine lymph node dissection was performed, and in the Heidelberg group, all blood vessels, lymphatic tissue and nerve tissue in the Heidelberg triangle area were dissected on the basis of routine lymph node dissection. Operation-related indicators (operation duration, intraoperative blood loss, cases of patients with intraoperative blood transfusion, fasting time and hospitalization duration after operation), postoperative complications (pancreatic fistula, biliary fistula, lymphatic fistula, bleeding and delayed gastric emptying) and postoperative pathological parameters (surgical margin, degree of differentiation, tumor size, cases of nerve invasion, number of dissected lymph nodes, lymph node metastasis and TNM stage) were compared between the two groups. Results:Compared with the control group, the operation time of the Heidelberg group was longer [ (334.85±24.95)min vs (305.09±24.54)min], theincidence of lymphatic fistula was higher (15.4% vs 2.2%), the rate of >1 mm at surgical margin was higher (76.9% vs 53.3%), and the total number of lymph nodes dissection was more [ (11.31±2.46) vs (9.49±2.28)]. All the differences between the two groups were statistically significant ( P<0.05). However, there were no significant differences on the intraoperative blood loss, cases of patients with intraoperative blood transfusion, postoperative hospital stay and fasting time, incidence of pancreatic fistula and biliary fistula, bleeding, delayed gastric emptying, degree of differentiation, tumor size, cases of nerve invasion, lymph node metastasis and TNM stage between the two groups. Conclusions:LPD combined with Heidelberg triangle dissection for pancreatic cancer was feasible and safe, which can increase the R 0 resection rate, remove more lymph nodes, reduce the local recurrence of pancreatic cancer and improve the prognosis of patients.