Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.

Objective To establish an individualized nomogram model and evaluate its efficacy to provide a possible evaluation basis for the prognosis of lower third and abdominal part of oesophageal adenocarcinoma (EAC). Methods Lower third and abdominal part of EAC patients from 2010 to 2015 were chosen from the SEER Research Plus Database (17 Regs, 2022nov sub). The patients were randomly allocated to the training cohort and the internal validation cohort with a ratio of 7∶3 using bootstrap resampling. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) in EAC patients, which would be elected to construct the nomogram prediction model. C-index, calibration curve and receiver operating characteristic (ROC) curve were performed to evaluate its efficacy. Finally, the efficacy to evaluate the OS of EAC patients was compared between the nomogram prediction model and TNM staging system. Results In total, 3945 patients with lower third and abdominal part of EAC were enrolled, including 3475 males and 470 females with a median age of 65 (57-72) years. The 2761 patients were allocated to the training cohort and the remaining 1184 patients to the internal validation cohort. In the training and the internal validation cohorts, the C-index of the nomogram model was 0.705 and 0.713, respectively. Meanwhile, the calibration curve also suggested that the nomogram model had a strong capability of predicting 1-, 3-, and 5-year OS rates of EAC patients. The nomogram also had a higher efficacy than the TNM staging system in predicting 1-, 3-, and 5-year OS rates of EAC patients. Conclusion This nomogram prediction model has a high efficiency for predicting OS in the patients with lower third and abdominal part of EAC, which is higher than that of the current TNM staging system.

Objective To evaluate the value of postoperative radiotherapy (PORT) in patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy. Methods Patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy were chosen from the SEER Research Plus Database [17 Registries, November 2012 Submission (2000-2019)]. The patients were divided into a PORT group and a non-PORT group according to whether the PORT was used. To balance baseline characteristics between non-PORT and PORT groups, R software was used to conduct a propensity score matching (PSM) with a ratio of 1 : 1 and a matching tolerance of 0.01. Both the Cox regression analysis and Kaplan-Meier survival analysis were conducted to evaluate the value of PORT in terms of overall survival (OS) and disease-specific survival (DSS). Results In total, 2468 patients with stage ⅢA-N2 non-small cell lung cancer were enrolled, including 1078 males and 1390 females with a median age of 65 (58-71) years. There were 1336 patients in the PORT group, and 1132 patients in the non-PORT group. Cox regression analysis showed that PORT was not significantly associated with OS (multivariate analysis: HR=1.051, 95%CI 0.949-1.164, P=0.338) and DSS (multivariate analysis: HR=1.094, 95%CI 0.976-1.225, P=0.123). No statistical difference was found in the OS or DSS between non-PORT group and PORT group after PSM analysis (P＞0.05). Conclusion PORT does not have a survival benefit for patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy.

【Objective】 To investigate the effects of biomimetic bone trabecular with the same porosity and pore size and regular porous structure on the adhesion, proliferation, and differentiation of osteoblasts, so as to provide theoretical basis for the improvement of osseointegration performance of titanium alloy implants. 【Methods】 The biomimetic bone trabecular and regular porous structures with the same porosity and pore size were generated by computer-aided software, and then processed into disc-shaped Ti6Al4V scaffolds with a diameter of 10 mm and a height of 3 mm by selective laser melting technology. MC3T3-E1 cells, the precursor cells of mouse osteoblasts in the logarithmic growth phase, were seeded on two kinds of scaffolds and divided into biomimetic bone trabecular group and regular porous structure group. After 3 hours of culture, acridine orange staining and phalloidin /DAPI staining were used to evaluate the number of cell adhesion. After 3 days of culture, the scaffolds were examined by scanning electron microscopy to evaluate the adhesion state of cells. After 1, 3, and 5 days of culture, the scaffolds were taken for CCK8 detection to observe the proliferation of cells. After 7 and 14 days of differentiation, alkaline phosphatase (ALP) activity was detected. After 14 days of differentiation, the expressions of osteogenesis-related genes (ALP, OCN, RUNX2) were detected by RT-PCR. After 30 days of differentiation, the scaffolds were stained with alizarin red and 100 g/L cetylpyridinium chloride was used to dissolve mineralized nodules. Calcium salt deposition was qualitatively and quantitatively detected to evaluate cell differentiation. 【Results】 The results of acridine orange and phalloidin /DAPI staining showed that the biomimetic trabecular Ti6Al4V scaffold adhered to more MC3T3-E1 cells than the regular porous structure, and the cytoskeleton of the former scaffold was more densely distributed. The results of scanning electron microscopy showed that the pseudopodia of MC3T3-E1 cells on the biomimetic bone trabecular Ti6Al4V scaffold were longer and the extension state was better than that of the regular porous structure. CCK8 test showed that the proliferation of MC3T3-E1 cells on the biomimetic trabecular bone titanium alloy scaffold was significantly higher than that on the regular porous structure on the 3rd and 5th day, and the difference gradually increased with the increase of time, with statistical significance (P<0.05). The results of cell differentiation test showed that ALP activity on the bionic trabecular scaffold was higher than that on the regular porous structure (P<0.05). The expressions of osteogenic genes (ALP, OCN, RUNX2) in MC3T3-E1 cells on the biomimetic bone trabecular titanium alloy scaffold were significantly higher than those on the regular porous structure (P<0.05). After 30 days of induction, the amount of calcium salt deposited in the bionic trabecular titanium alloy scaffold was significantly larger than that in the regular porous structure (P<0.05). 【Conclusion】 The biomimetic bone trabecular with a porosity of 65% and an equivalent pore size of 600 μm is more conducive to the adhesion, proliferation and differentiation of mouse osteoblast precursor cells MC3T3-E1 on the titanium alloy scaffold than the regular porous structure with the same porosity and pore size. It is theoretically more conducive to improving the osseointegration performance of titanium alloy implants.

Ischemic stroke is one of the leading causes of death and disability worldwide. In Han dynasty， HUA Tuo proposed the original preventive medicine idea that "with good blood circulation， the disease cannot be born"， which opened a broad space for the cross-research of blood-related mechanical factors and pharmacology. In the pathogenesis of ischemic stroke， mechanical factors comprehensively affect the function and crosstalk of platelets and endothelial cells. In recent years， as the well-known effects on thrombosis and stroke， more attention has been paid to hemodynamic factors as the participants involved in pathological mechanisms and potential therapeutic targets of ischemic stroke. The mechanical force ion channel Piezo1 widely exists on the surface of many types of cells. Besides being regulated by chemical and endogenous substances， Piezo1 responds to different mechanical conditions， regulates the opening and closing of channels， and activates different downstream signaling pathways. Piezo1 is now regarded as an important connection between mechanical and biochemical signals. A variety of Chinese medicine can affect the activity of Piezo1 protein， which may prevent and treat thrombotic diseases such as ischemic stroke through Piezo1 protein. In this paper， the effects of Piezo1 protein on the physiological and pathological functions of endothelial cells and platelet under different mechanical conditions and the role of Piezo1 in the process of thrombosis were reviewed， as well as the effects of Chinese medicine， chemical medicine， and endogenous substances targeting Piezo1 channel. These could provide new ideas for further exploring the mechanisms of Chinese medicines in activating blood circulation， developing new drugs， and deepening biomechanical-pharmacology research.

Objective:To investigate the effect of lymph node metastasis on the prognosis of patients with G2 phase stage pancreatic neuroendocrine neoplasm(pNEN).Methods:A retrospective case control study was conducted to analyze the case data of 368 patients with pancreatic neuroendocrine tumors in G2 phase stage from January 1, 2010 to December 31, 2016 in SEER database, including 174 males and 194 females. According to whether lymph nodes were metastatic, they are divided into lymph node non metastatic (N0) group ( n=272) and lymph node metastatic (N1) group ( n=96). The Kaplan-Meier method and Log-rank test were used to compare the overall survival rate (OS) of patients in the N0 and N1 groups. The COX proportional risk model was used to evaluate whether N stage was an independent risk factor affecting prognosis. Count data were expressed as cases and percentage(%), and Chi-square test was used for comparison between the groups. Results:Among all patients, the OS of patients in the N0 group was better than that of patients in the N1 group. The OS of N0 patients at 1, 3, and 5 years was 96.3%, 92.7%, and 85.6%, respectively, while the OS of N1 patients at 1, 3, and 5 years was 92.6%, 82.1%, and 82.1%, respectively ( P=0.014). Multivariate analysis showed that age ( HR=2.245, 95% CI: 1.126-4.475, P=0.022) and N stage ( HR=0.457, 95% CI: 0.237-0.883, P=0.020) were independent prognostic factors for G2 phase pNEN patients. Conclusion:Lymph node metastasis is one of the independent prognostic factors in patients with G2 phase stage pNEN.

Mechanical allodynia (MA), including punctate and dynamic forms, is a common and debilitating symptom suffered by millions of chronic pain patients. Some peripheral injuries result in the development of bilateral MA, while most injuries usually led to unilateral MA. To date, the control of such laterality remains poorly understood. Here, to study the role of microglia in the control of MA laterality, we used genetic strategies to deplete microglia and tested both dynamic and punctate forms of MA in mice. Surprisingly, the depletion of central microglia did not prevent the induction of bilateral dynamic and punctate MA. Moreover, in dorsal root ganglion-dorsal root-sagittal spinal cord slice preparations we recorded the low-threshold Aβ-fiber stimulation-evoked inputs and outputs of superficial dorsal horn neurons. Consistent with behavioral results, microglial depletion did not prevent the opening of bilateral gates for Aβ pathways in the superficial dorsal horn. This study challenges the role of microglia in the control of MA laterality in mice. Future studies are needed to further understand whether the role of microglia in the control of MA laterality is etiology-or species-specific.
Mice ; Animals ; Hyperalgesia/metabolism* ; Microglia/metabolism* ; Disease Models, Animal ; Spinal Cord/metabolism* ; Spinal Cord Dorsal Horn/metabolism* ; Ganglia, Spinal/metabolism*

Objective To investigate the guiding role of quantitative evaluation system of immune status in the individualized management of immunosuppressants for the recipients after liver transplantation. Methods Clinical data of 239 liver transplant recipients were retrospectively analyzed. MingDao Immune Cell Analysis (MICA) was established. All recipients were divided into two groups according to the adjustment regimens of immunosuppressants. The immunosuppressant regimen was adjusted according to MingDao Immune System Score (MISS) in the MISS group (n=84), and the medication plan was empirically adjusted during the same period in the control group (n=155). According to the time of postoperative detection (t), the recipients in the MISS group were divided into subgroup A (t ≤ 28 d, n=78), subgroup B (28 d < t ≤ 6 months, n=68), subgroup C (6 months < t ≤ 12 months, n=18), subgroup D (12 months < t ≤ 24 months, n=18) and subgroup E (t > 24 months, n=19). In the MISS group, postoperative MISS scores of recipients in subgroups A-E were analyzed. The incidence of acute rejection and opportunistic infection and the overall survival rate were statistically compared between the MISS and control groups. Results The MISS scores in subgroups A-E were -7.0 (-13.2, -2.0), -2.0 (-5.8, 1.8), -0.5 (-7.3, 2.8), -2.0 (-4.5, 3.3) and -3.0 (-6.0, 1.0), respectively. The immune status of the recipients was gradually improved over postoperative time, and the difference between two groups was statistically significant (P < 0.05). In the MISS group, 15% (13/84) of the recipients developed acute rejection, and 27% (42/155) in the control group, and the difference was statistically significant (P < 0.05). In the MISS group, the MISS score of the recipients with acute rejection was 0 (-2.5, 3.5), and -5.0 (-12.0, -1.0) for their counterparts without acute rejection, and the difference was statistically significant (P < 0.05). In the MISS group, 2% (2/84) of the recipients presented with postoperative opportunistic infection, and 9% (14/155) in the control group, and the difference was statistically significant (P < 0.05). In the MISS group, the 1- and 3-year overall survival rates were 86.9% and 79.8%, and 83.2% and 76.8% in the control group, and no significant difference was observed between two groups (P > 0.05). Conclusions MICA and MISS score may reflect the immune status of liver transplant recipients, and guide the individualized management of administration of immunosuppressants after liver transplantation.