Acute pancreatitis is a common and critical disease in clinical practice, and clinical treatment has formed a multidisciplinary and collaborative model of traditional Chinese and Western medicine. However, its etiology and pathogenesis are complex and varied, and immune response is crucial in the occurrence and development of the disease. Therefore, based on the thinking of the pathological and physiological basis of immune response in the different stages of acute pancreatitis disease progression and related complications, and based on the biological characteristics and laws of the disease, this article summarizes a reasonable and phased implementation of Chinese and Western medicine collaborative management strategy, which is proposed to achieve optimal and precise treatment of the disease.
Objective To investigate the development and significance of the expression of early growth response gene-1 （EGR-1） in autogenous vein graft in rats and detect the role of it in intimal hyperplasia. Methods Autogenous vein graft model was established in 90 Wistar rats, transplanting the right jugular vein to infra renal abdominal aorta by microsurgical technique. The vein graft samples were harvested at hour 1, 2, 6 and 24, day 3, 7,14, 28 and 42 after procedure. Normal vein as control group. Egr-1 mRNA was measured by reverse transcription-PCR and in situ hybridization. Western blot and immunohistochemistry were used to detect the protein expression of Egr-1. Results Intimal hyperplasia reached peak at day 28 after autogenous vein graft surgery. Egr-1 mRNA and Egr-1 protein hadn’t been found in the normal vein. The expressions of Egr-1 mRNA and Egr-1 protein had biphasic changes. By reverse transcription-PCR and in situ hybridization, we found that the level of Egr-1 mRNA rose at 1 hour after graft, the expression of Egr-1 mRNA was (35±7)%. Decline at hour 6， 24 and day 3, the positive rates of Egr-1 mRNA were (8±2)%, (8±6)% and (8±4)% respectively. Reincrease at day 7, a peak at day 28, the positive rate of Egr-1 mRNA was (45±6)% (compared with other phase, P＜0.01). At day 42, the expression of Egr-1 mRNA declined again. Immunohistochemical staining and Western blot revealed Egr-1 protein had expressed at hour 2 early phase, the expression of Egr-1 protein was (30±5)%, and until to hour 6. The level of Egr-1 protein was decrease at hour 24 and day 3, the positive rates were (7±3)% and (7±8)% respectively. A peak at day 28, the positive rate of Egr-1 protein was (40±9)% (compared with other phase, P＜0.01). We found that immu-noreative Egr-1 located vascular smooth muscle cells （VSMCs） and monocytes/macrophages in tunica media at the early phase of day 7 and 14, and in neointimal and medial VSMCs at later phase of day 28. Egr-1 was also present in the endoluminal endothelial cells. Conclusion In autogenous vein graft, Egr-1 plays an important role in the proliferation of VSMCs. Egr-1 may become a new target for the prevention and therapy of intimal hyperplasia, stenosis and emphraxis after vein graft.
ObjectiveTo summarize the therapeutic targets of pancreatic cancer (PC).
MethodsThe related literatures about the therapeutic targets of PC were reviewed.
ResultsPC was one of the most challenging tumor in worldwide, and was characterized as a highly aggressive disease with poor overall prognosis and a high mortality rate. The hallmark of PC was its poor response to radio-and chemo-therapy. Current chemotherapeutic regimens could not provide substantial survival benefit with a clear increase in overall survival. Recently, several new approaches which could significantly improve the clinical outcome of PC had been described, involving signal-transduction pathways, immune response, stroma reaction, and epigenetic changes.
ConclusionsMany therapeutic targets are involved in the treatment of PC. As current therapies failed to significantly improve the progression and the survival of PC, new therapeutic approaches and clinical studies are strongly required.
ObjectiveTo study the clinical value of procalcitonin (PCT), WBC count, and C-reactive protein (CRP) in diagnosis of common bile duct stones with acute bile duct infection and systemic inflammatory response syndrome (SIRS).MethodsA total of 80 patients with bile duct stones were retrospectively analyzed, which were divided into two groups, SIRS group (n=40) and non-SIRS group (n=40). The numerical value of PCT, WBC count, and CRP were detected on 1, 4, and 7 day after admission, and calculated the score of acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) on 1 day after admission. Then analyzed the clinical value of PCT, WBC count, and CRP in diagnosis of common bile duct stones with acute bile duct infection and SIRS.ResultsEach area under the ROC curve of PCT, CRP, and WBC count were 0.81, 0.78, and 0.72, respectively, with significant difference (P<0.05). The PCT, CRP, and WBC count had a certain accuracy in diagnosis of common bile duct stones with acute bile duct infection and SIRS. The positive-relationship between PCT, CRP, WBC count and APACHE Ⅱ score was significant (r=0.91, P<0.01; r=0.88, P<0.01; r=0.69, P<0.01).ConclusionTo detect the numerical value of PCT, WBC count, and CRP had significant clinical value in diagnosis of common bile duct stones with acute bile duct infection and SIRS.
Objective To investigate the relationship of small airway function with airway sensitivity and reactivity and assess the factors influencingairway hyperresponsiveness (AHR).Methods Data of consecutive subjects with suspected asthma who had a≥20% reduction in FEV1 after ≤12.8 mmol/L cumulative doses of methacholine were analyzed from January 2005 to April 2006.Airway sensitivity was assessed by the cumulative dose of methacholine required to cause 20% reduction in FEV1 (PD20).Airway reactivity was analyzed using the slope of the dose-response curve (DRS).The DRS was defined as the reduction in FEV1 from baseline after the final dose of methacholine inhaled divided by the cumulative dose inhaled.Because of their highly skewed distribution，DRS was logarithmically transformed (log10) for all analysis.Results A total of 184 consecutive subjects aged 16 to 80 years was enrolled.There were 70 male (38.0%) and 114 female (62.0%) subjects.Subjects with higher airway sensitivity，indicated by lower PD20，also had a lower Vmax50% and Vmax25%，and vise versa.PD20 was negatively correlated wit log10DRS (r=-0.874，Plt;0.01).In a simple linear regression model，log10DNS was significantly correlated with FEV1%，Vmax50% or Vmax25% respectively (the determinant r2 were 0.062，0.097 and 0.085，respectively，all Plt;0.01).In a multiple linear regression model that included age，height，and percentage of predicted FEV1，Vmax50% and Vmax25% accounted for 3.9% and 2.6%，respectively，of variability in airway reactivity.The association between Vmax50% and log10DNS was significant in both male and female subjects.The r2 was higher in male subjects.The subjects were divided into three age groups and the association between Vmax50% or Vmax25% and log10DNS was higher in female than in male for age≤25 years，higher in male than in female for 25 -45 years.No association was found for agegt;45 years in both males and females.Conclusions Impaired small airway function is associated with higher airway sensitivity and reactivity to methacholine in subjects with suspected asthma.
Objective To assess the effect and safety of clinical nutritional supplementation with different patterns for treating systematic inflammatory response syndrome (SIRS). Methods Randomized controlled trials (RCTs) were identified from MEDLINE (1996 to Nov. 2004), EMBASE (1984 to Nov. 2002), Cochrane Controlled Trials Register (Issue 4, 2004), Chinese Cochrane Centre Database (Issue 4, 2004), CBMdisc (1978 to Nov. 2004). We handsearched related published and unpublished data and their references. All RCTs of nutritional interventions for SIRS were included. Data were extracted and evaluated by two reviewers independently with designed extraction form. RevMan 4.2.7 software was used for data analysis. Results Six RCTs involving 353 patients were included. All the results of meta-analysis were listed as the following: ① Mortality: compared with routine nutrition, one study showed that glutamine had a statistical difference with RR 0.67 and 95%CI 0.31 to 1.32. Compared with no treatment, one study showed selenium had a statistical difference with RR 1.19, 95%CI 0.59 to 2.41. ② Compared with routine nutrition, one study showed that glutamine had a statistical difference on reducing the ratio of nasocomial infection of SIRS with RR 0.5, 95%CI 0.27 to 0.91, but had no statistical difference on reducing the ratio of multiple organ dysfunction syndrome with RR 1.53, 95%CI 0.64 to 3.66. ③ Improvement of the critical condition of SIRS: compared with routine nutrition, one study showed that glutamine had a statistical differences with WMD 4.0, 95%CI 2.36 to 5.64; compared with high calorie intake, two studies showed low calorie intake had a statistical difference with WMD 4.9, 95%CI 1.76 to 8.04. ④ Reduction of the complication of hyperglycemia and hypertriglyceridemia: compared with high calorie intake, one study showed low calorie intake had statistical difference with WMD －0.70, 95%CI －1.20 to －0.20 and WMD －1.80, 95% CI －2.42 to －1.16 respectively and all P≤0.01. ⑤ Increasing of the plasma IgG concentration: compared with routine nutrition, two studies showed that glutamine had a statistical difference with WMD 4.20, 95% CI 2.23 to 6.16. ⑥ Increasing of the nitrogen balance, intestinal permeability, the level of plasma concentration of anlbumin, prealbumin and TRF: compared with control interventions, glutamine, low calorie intake, selenium supplementation and fructose-glucose-xylitol mixture showed no statistical difference. Conclusions Glutamine, low calorie intake, selenium supplementation, FGX mixture may decrease the complication of infection or metabolism and be better than the controlled interventions; but there is no benefit on reducing the rate of death result from SIRS compared with controlled interventions. The evidence of most RCTs with poor quality is too weak to draw a conclusion. More high quality trials are required.
Objective To explore the accuracy of contrast-enhanced magnetic resonance imaging (MRI) in predicting pathological complete remission (pCR) in breast cancer patients after neoadjuvant therapy (NAC). Methods The clinicopathological data of 245 patients with invasive breast cancer who had completed the surgical resection after NAC in the Affiliated Hospital of Southwest Medical University from March 2020 to April 2022 were collected retrospectively. According to the results of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) detected by immunohistochemistry, all patients were divided into four subgroups: HR+/HER2–, HR+/HER2+, HR–/HER2+ and HR–/HER2–. The value of MRI in evaluating the efficacy of NAC was analyzed by comparing the postoperative pathological results as the gold standard with the residual tumor size assessed by preoperative MRI. Meanwhile, the sensitivity, specificity and positive predictive value (PPV) of pCR predicted by the evaluation results of enhanced MRI were analyzed, and further analyzed its predictive value for pCR of different subtypes of breast cancer. Results There were 88 cases (35.9%) achieved radiological complete response (rCR) and 106 cases (43.3%) achieved pCR in 245 patients. Enhanced MRI in assessing the size of residual tumors overestimated and underestimated 12.7% (31/245) and 9.8% (24/245) of patients, respectively. When setting rCR as the MRI assessment index the specificity, sensitivity and PPV were 84.2% (117/139), 62.3% (66/106) and 75.0% (66/88), respectively. When setting near-rCR as the MRI assessment index the specificity, sensitivity and PPV were 70.5% (98/139), 81.1% (86/106), and 67.7% (86/127), respectively. The positive predictive value of both MRI-rCR and MRI-near-rCR in evaluating pCR of each subtype subgroup of breast cancer was the highest in the HR–/HER2+ subgroup (91.7% and 83.3%, respectively). In each subgroup, compared with rCR, the specificity of near-rCR to predict pCR decreased to different degrees, while the sensitivity increased to different degrees. Conclusions Breast contrast-enhanced MRI can more accurately evaluate the efficacy of localized breast lesions after NAC, and can also more accurately predict the breast pCR after NAC. The HR–/HER2+ subgroup may be a potentially predictable population with pCR exemption from breast surgery. However, the accuracy of the evaluation of pCR by breast enhancement MRI in HR+/HER2– subgroup is low.
The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy combined with surgery, but patients after the same treatment regimen show a large difference in outcomes. For patients with good response to neoadjuvant therapy, the waiting & observation scheme can be selected to avoid surgery and other complications. Therefore, accurate assessment of the response of patients with locally advanced rectal cancer after neoadjuvant therapy can better develop personalized treatment strategies. Current studies have found that blood sample detection, endoscopy, imaging examination and artificial intelligence have their own advantages and disadvantages in evaluating the response of neoadjuvant therapy. Therefore, this article reviews the application of different clinical tools in evaluating and predicting the response of neoadjuvant therapy for locally advanced rectal cancer, and looks forward to the future development direction.
Objective To investigate the regulatory effects of miR-26a-5p on the osteogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs) by regulating cAMP response element binding protein 1 (CREB1). Methods The adipose tissues of four 3-4 weeks old female C57BL/6 mice were collected and the cells were isolated and cultured by digestion separation method. After morphological observation and identification by flow cytometry, the 3rd-generation cells were subjected to osteogenic differentiation induction. At 0, 3, 7, and 14 days after osteogenic differentiation induction, the calcium deposition was observed by alizarin red staining, ALP activity was detected, miR- 26a-5p and CREB1 mRNA expressions were examined by real-time fluorescence quantitative PCR, and CREB1 protein and its phosphorylation (phospho-CREB1, p-CREB1) level were measured by Western blot. After the binding sites between miR-26a-5p and CREB1 was predicted by the starBase database, HEK-293T cells were used to conduct a dual-luciferase reporter gene experiment to verify the targeting relationship (represented as luciferase activity after 48 hours of culture). Finally, miR-26a-p inhibitor (experimental group) and the corresponding negative control (control group) were transfected into ADSCs. Alizarin red staining, ALP activity, real-time fluorescent quantitative PCR (miR-26a-5p) and Western blot [CREB1, p-CREB1, Runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN)] were performed at 7 and 14 days after osteogenic induction culture. Results The cultured cells were identified as ADSCs. With the prolongation of osteogenic induction culture, the number of calcified nodules and ALP activity significantly increased (P<0.05). The relative expression of miR-26a-5p in the cells gradually decreased, while the relative expressions of CREB1 mRNA and protein, as well as the relative expression of p-CREB1 protein were increased. The differences were significant between 7, 14 days and 0 day (P<0.05). There was no significant difference in p-CREB1/CREB1 between different time points (P>0.05). The starBase database predicted that miR-26a-5p and CREB1 had targeted binding sequences, and the dual-luciferase reporter gene experiment revealed that overexpression of miR-26a-5p significantly suppressed CREB1 wild-type luciferase activity (P<0.05). After 7 and 14 days of osteogenic induction, compared with the control group, the number of calcified nodules, ALP activity, and relative expressions of CREB1, p-CREB1, OCN, and RUNX2 proteins in the experimental group significantly increased (P<0.05). There was no significant difference in p-CREB1/CREB1 between the two groups (P>0.05). Conclusion Knocking down miR-26a-5p promoted the osteogenic differentiation of ADSCs by up-regulating CREB1 and its phosphorylation.
