Dura mater is a tough collagen connective tissue attached to inner surface of skull and wrapped around brain.As a buffer bridge between brain tissue and skull,its physiological function and role in skull development and repair have always been a focus of research.Recent studies have found that dura mater not only directly participates in skull development during skull growth,but also secretes a variety of cytokines that control the development of central nervous system.There are abundant material exchange and cell communication between the two.This article reviews the role of dura in development and repair of skull,and provides clues for further discovery of the relevant mechanisms of dura in development and repair of skull.

Objective:To analyze whether involved-field irradiation (IFI) was associated with improved survival and reduced treatment-related adverse events compared with elective nodal irradiation (ENI) in Chinese patients with esophageal squamous cell carcinoma receiving radiotherapy.Methods:Literature review was conducted from CNKI, Wanfang Data, PubMed, Embase, Web of Science and Cochrane Central databases (until July 31, 2022). Relevant data were collected according to the inclusion and exclusion criteria. Primary outcomes included overall survival (OS) rate and treatment-related adverse events. Secondary outcomes included progression-free survival (PFS) rate and local control rate (LCR). Risk of bias was assessed using the Cochrane Risk of Bias tool. The quality of the results was assessed by using the meta analysis of Evidence Evaluation and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methods.Results:A total of 7 articles with 918 patients were included of which 465 received IFI and 453 received ENI. The 1-, 2-, 3-and 5-year OS rates in the IFI group were not significantly different from those in the ENI group (1-year OS rate: RR=1.00, 95% CI=0.94-1.07, P=0.97, high certainty; 2-year OS rate: RR=1.01, 95% CI=0.90-1.13, P=0.90, high certainty; 3-year OS rate: RR=0.86, 95% CI=0.71-1.05, P=0.14, high certainty; 5-year OS rate: RR=0.76, 95% CI=0.42-1.37, P=0.36, low certainty). In the IFI group, patients with ≥grade 2 acute radiation esophagitis ( RR=0.71, 95% CI=0.58-0.87, P=0.001, high certainty), ≥grade 3 acute radiation esophagitis ( RR=0.39, 95% CI=0.24-0.64, P<0.001, high certainty) and ≥grade 2 acute radiation pneumonitis ( RR=0.72, 95% CI=0.52-0.99, P=0.04, high certainty) were significantly lower compared with those in the ENI group. However, no significant differences were observed in the incidence of ≥grade 3 late radiation esophagitis, ≥grade 3 acute radiation pneumonitis and ≥grade 3 late radiation pneumonitis between two groups. No significant differences were noted in the 1-, 2-, 3-PFS rates and LCR between two groups. Conclusions:For Chinese patients with esophageal squamous cell carcinoma, IFI and ENI yield similar efficacy in terms of OS, PFS and LCR. However, IFI has a lower incidence of ≥grade 2 acute radiation esophagitis, ≥grade 3 acute radiation esophagitis and ≥grade 2 acute radiation pneumonitis than ENI.

Objective:To evaluate the efficacy and prognostic factors of radiotherapy combined with immunotherapy as the first-line treatment for patients with locally advanced or metastatic esophageal squamous cell carcinoma (LA/M ESCC).Methods:A single-center, retrospective analysis was conducted for the recent efficacy, survival, prognostic factors, post-treatment failure modes, and treatment-related adverse reactions of 57 LA/M ESCC patients eligible for enrollment.Results:The entire group of patients had 1-, 2-, and 3-year overall survival (OS) of 86.0%, 57.5%, and 53.9%, respectively and 1-, 2-, and 3-year progression-free survival (PFS) of 61.4%, 31.0%, and 31.0%, respectively. The median OS was not reached, and the median PFS was 15.0 (95% CI: 10.77-19.23) months. These patients had an overall response rate (ORR) of 80.7% (46/57) and a disease control rate (DCR) of 94.7% (54/57). As indicated by the result of the multivariate analysis, the independent prognostic factors affecting the OS of the patients included their age, clinical stage, number of immunotherapy cycles, and recent efficacy ( HR = 0.25, 2.58, 0.35, 4.05, P < 0.05), and the independent factors influencing the PFS of the patients included their clinical stage and recent efficacy ( HR = 2.27, 1.97, P < 0.05). There were no statistically significant differences in the effects of irradiation ranges and the combination modes of immunologic drugs and chemoradiotherapy on both OS and PFS of the patients ( P > 0.05). A total of 32 patients suffered post-treatment failure. After the second treatment, they had 1- and 2-year OS of 55.7% and 25.3%, respectively, with median OS of 14.0 (95% CI: 5.17-22.83) months. A total of 26 cases experienced treatment-associated adverse reactions of grades 2 or higher during and after treatment. Conclusions:The combination of radiotherapy and immunotherapy is effective and safe as the first-line treatment for LA/M ESCC patients. The post-treatment failure modes still include local recurrence and distant metastasis. Therefore, such combination merits further investigation.

Objective:To investigate the effects of the systemic immune-inflammation index (SII)on the long-term survival in esophageal cancer patients treated with radiotherapy.Methods:Aretrospective review was conducted for the clinical data of 303 patients with esophageal squamous cell carcinoma(ESCC)who received radical radiotherapy in the Fourth Hospital of Hebei Medical University from 2011 to 2017. These patients were divided into a high-SII group and a low-SII group according to their SII before radiotherapy. The correlation between SII and survival was determined using the Kaplan-Meier method and Cox regression model. Propensity score matching (PSM) was applied to reduce bias from measured confounding.Results:The SII of patients before radiotherapy was correlated significantly with T stage ( χ2=8.015, P=0.018) and TNM stage ( χ2=8.619, P=0.013). The 1-, 3-, 5-year overall survival (OS) rates in the high-SII group were 64.9%, 27.1%, and 19.4%, respectively. They were significantly lower than those in the low-SII group, which were 84.9%, 43.9%, and 30.5%, respectively (χ 2=13.443, P<0.001). The 1-, 3-, 5-year progression-free survival (PFS) rates in the high-SII group were 46.4%, 20.3%, and 13.3%, respectively. They were significantly lower than those in the low-SII group, which were 67.8%, 34.8%, and 26.5%, respectively (χ 2=12.383, P<0.001). The multivariate analysis indicated that the independent factors influencing the OS and PFS included T stage, lymph node metastasis, chemotherapy, and SII.After PSM was applied, the OS and PFS in the high-SII group were still lower than those in the low-SII group(χ 2OS=4.264, P=0.039; χ 2PFS=5.376, P=0.020), and the multivariate analysis showed that SII was a significant predictor for OS and PFS( HROS=1.357, P=0.037; HRPFS=1.393, P=0.022). Conclusions:SII is a significant independent influencing factor of the OS and PFS inESCC patients treated with received radiotherapy. Based on simple and inexpensive standard laboratory measurements, SII can be a promising marker for ESCC patients.

Objective:To investigate the long-term prognosis and failure mode of patients with esophageal squamous cell carcinoma who achieved clinical complete remission (cCR) after receiving radical radio (chemo) therapy.Methods:Clinical data of 183 patients with esophageal squamous cell carcinoma eligible for inclusion criteria who received treatment in our hospital from January 2009 to December 2012 were retrospectively analyzed. The factors that affected the long-term prognosis of patients were identified, and the failure mode of cCR patients and the prognosis after failure were analyzed. SPSS 19.0 statistical software was used for data analysis.Results:As of the follow-up date, the 1-, 3-, 5-, and 10-year overall survival (OS) rates and disease-free survival (DFS) rates of the entire group were 83.1%, 53.4%, 36.2%, 12.8% and 68.9%, 45.9%, 30.5%, 12.0%, respectively. The median OS and DFS were 41.3 months and 33.4 months. The results of multivariate analysis showed that cT staging, cN staging and prescribed dose were the independent factors affecting the OS ( P=0.001, <0.001, 0.003); hoarseness, lesion length, cT staging, cN staging and prescribed dose were the independent factors that affected the DFS ( P=0.002, 0.033, 0.009, <0.001, 0.003). In the whole group, 72 cases (39.3%) had local regional recurrence, 58 cases (31.7%) had distant metastasis, and 26 cases (14.2%) had local regional recurrence with distant metastasis. Among 104 patients after treatment failure, the prognosis of patients receiving salvage treatment was significantly better than that of their counterparts receiving maintenance treatment ( χ2=39.153, P<0.001). Conclusions:The long-term prognosis of patients with esophageal squamous cell carcinoma who achieved cCR after receiving radical radio (chemo) therapy is still unsatisfactory. Clinically, it is necessary to strengthen the clinical observation and follow-up of these patients. The main treatment failure mode of cCR patients is local regional recurrence. Active salvage treatment can significantly improve clinical prognosis of these patients.

Background::The risk for chronic kidney disease (CKD) is influenced by genetic predisposition, sex, and lifestyle. Previous research indicates that coffee is a potentially protective factor in CKD. The current study aims to investigate whether sex disparity exists in the coffee–CKD association, and whether genetic risk of CKD or genetic polymorphisms of caffeine metabolism affect this association.Methods::A total of 359,906 participants from the UK Biobank who were enrolled between 2006 and 2010 were included in this prospective cohort study, which aimed to estimate the hazard ratios for coffee intake and incident CKD using a Cox proportional hazard model. Allele scores of CKD and caffeine metabolism were additionally adjusted for in a subsample with qualified genetic data ( n = 255,343). Analyses stratified by genetic predisposition, comorbidities, and sex hormones were performed. Tests based on Bayesian model averaging were conducted to ascertain the robustness of the results. Results::Coffee was inversely associated with CKD in a dose-dependent manner. The effects of coffee did not differ across different strata of genetic risk for CKD, but were more evident among slower genetically predicted caffeine metabolizers. Significant sex disparity was observed ( P value for interaction = 0.013), in that coffee drinking was only associated with the risk reduction of CKD in females. Subgroup analysis revealed that testosterone and sex hormone-binding globulin (SHBG), but not estradiol, modified the coffee–CKD association. Conclusions::In addition to the overall inverse coffee–CKD association that was observed in the general population, we could also establish that a sex disparity existed, in that females were more likely to experience the benefit of the association. Testosterone and SHBG may partly account for the sex disparity.

Objective:To study the prognostic impact of prognostic nutritional index (PNI) before radiotherapy in clinical stage Ⅲ esophageal cancer patients.Methods:We retrospectively reviewed 125 esophageal cancer patients with clinical stage Ⅲ undergoing definitive radiotherapy in Fourth Hospital of Hebei Medical University from 2013 to 2017. The PNI and nutritional risk index (NRI) were calculated before radiotherapy. The optimal cutoff value of PNI was determined by time-dependent receiver operating characteristics (ROC) at 49.925.The patients were divided into low PNI group(PNI<49.925) and high PNI group (PNI≥49.925). Based on NRI, the patients were divided into normal NRI group (NRI≥100) and abnormal NRI group (NRI<100). Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS) and to perform univariate analysis. The mutlivariate analysis was performed by Cox regression model.Results:PNI was positively correlated with hemoglobin ( r=0.505, P<0.001) and NRI ( r=0.594, P<0.001). The 1-, 3- and 5-year OS rates in the low PNI group were significantly lower than those of the high PNI group (67.5%, 27.3%, 11.4% vs. 85.4%, 45.8%, 27.4%, respectively, χ2=8.569, P<0.05). Moreover, the 1-, 3- and 5-year PFS rates in the low PNI group were obviously higher than those in the high PNI group (59.7%, 23.2%, 4.9% vs. 79.2%, 35.4%, 24.9%, respectively, χ2=6.715, P<0.05). Univariate analysis showed that GTV, radiotherapy dose, chemotherapy, albumin, NRI and PNI were significantly correlated with OS and PFS (OS: χ2=6.822, 4.326, 4.474, 13.123, 8.846, 8.569, P<0.05: PFS: χ2=7.869, 4.636, 5.874, 10.911, 8.544, 6.715, P<0.05). Multivariate analysis showed that GTV, radiotherapy dose and PNI were independent prognostic factors for OS ( P<0.05). And GTV, radiotherapy dose, chemotherapy and PNI were independent prognostic factors for PFS ( P<0.05). Conclusions:The PNI before radiotherapy is a significant and independent predictor for survival of clinical stage Ⅲ esophageal cancer patients. Based on simple and inexpensive standard laboratory measurements, PNI could be a promising prognostic biomarker for esophageal cancer patients.

Objective:To analyze the therapeutic effects and prognosis after radiotherapy (chemotherapy) of patients with postoperative recurrent esophageal cancer.Methods:This study analyzed 501 patients with postoperative recurrent esophageal cancer who were treated in the Radiotherapy Department of the Fourth Hospital of Hebei Medical University and met enrollment conditions. Among them, 274 patients received concurrent chemotherapy and radiotherapy. The analyses in this study focused on the survival after the retreatment, postoperative recurrence patterns, prognosis of retreatment, and prognostic factors affecting the retreatment. Meanwhile, statistical analysis was conducted using the software SPSS Statistics 19.0.Results:The time of postoperative recurrence was 0.3-87.4 months, with a median number of 11.6 months. The median survival time was 12.1 months after the retreatment. Among all the patients, 344 patients suffered from only local recurrence, while the remaining 157 patients experienced distant metastasis. According to multivariate analysis result, independent prognostic factors included gender, pN stage, lymph node positive logarithmic ratio (LODDS), the number of chemotherapy cycles, time of recurrence, and distant metastasis ( P < 0.05). Meanwhile, prognostic factors affecting the 344 patients with only local recurrence included the time of recurrence, the number of chemotherapy cycles, and prescription dose ( χ2=22.605, 13.957, 10.446; P< 0.05). The remaining 157 patients suffered from distant metastasis. The 1-, 3-, and 5-year survival rates of them were 43.3%, 9.1%, and 5.5%, respectively, and those of the patients with only local recurrence were 53.6%, 22.6%, and 16.4%, respectively. The differences were statistically significant (χ 2=10.786, P< 0.05). Conclusions:Radiotherapy (chemotherapy) is safe and effective for the treatment of recurrent esophageal cancer. However, it features poor prognosis for male patients with a late pN stage, a high LODDS, the number of chemotherapy cycles ≤ 2, the time of recurrence≤ 24 months, and distant metastasis.

Objective:To evaluate the effects of different irradiation doses on postoperative local recurrence in patients with esophageal cancer after radio (chemo) therapy.Methods:Clinical data of 331 esophageal cancer patients presenting with postoperative local recurrence admitted to our hospital from 2009 to 2014 were collected. The recurrence site, the effects of different radiotherapy doses on the prognosis of patients and the independent prognostic factors were retrospectively analyzed. The survival rate was calculated by Kaplan-Meier method. Univariate prognostic analysis was performed by log-rank test. Multivariate prognostic analysis was conducted by Cox proportional hazard regression model.Results:The 1-, 3-and 5-year overall survival rates were 54.3%, 23.2% and 16.6%, respectively. The median overall survival was 13.4 months (95% CI: 11.7-15.0). The median survival of patients with radiotherapy doses< 60 Gy and ≥60 Gy was 10.8 and 13.9 months ( P=0.013). Stratified analysis showed that patients with age< 60 years, no smoking history, no drinking history, no family history, upper thoracic segment, left thoracotomy, N 0 staging, log odds of positive lymph nodes (LODDS)< 0.030, recurrence time ≥ 13.1 months and recurrence site ≥ 2 had better prognosis when receiving radiotherapy dose ≥ 60 Gy ( P=0.038, 0.033, 0.001, 0.003, 0.018, 0.010, 0.041, 0.039, 0.043 and 0.007). Moreover, the short-term clinical efficacy of patients treated with ≥60 Gy dose was significantly better than that of those with<60 Gy dose ( P<0.001), which did not increase the incidence of ≥grade 2 radiation-induced gastritis ( P=0.977) or radiation-induced pneumonitis ( P=0.444). Cox multivariate analysis showed that the LODDS size, prescription dose and short-term efficacy were the independent factors affecting clinical prognosis of patients ( P=0.006, 0.008 and<0.001). Conclusions:The recommended dose for esophageal cancer patients with local recurrence after radiotherapy (chemotherapy) is greater than or equal to 60 Gy. The results of this study need to be confirmed by prospective studies with a large sample size.

Objective:To study the effects of immunity index and blood inflammatory markers pre- and post-radiotherapy on prognosis of esophageal cancer patients with clinical stage Ⅲ.Methods:A total of 84 esophageal cancer patients with clinical stage Ⅲ (T 4N 1M 0) in Fourth Hospital of Hebei Medical University were analyzed, from May 2010 to April 2012. Intensity-modulated radiotherapy was delivered with a dose of 56-66 Gy/1.8-2.0 Gy per fraction. Flow cytometry was used to analyze the distribution of T-lymphocyte subsets (CD3, CD4, CD8, CD4/CD8) and natural killer cells (CD56) in the peripheral blood pre- and post- radiotherapy. Neutrophil-lymphocyte ratio (NLR) pre- and post- radiotherapy were also tested. The correlation of immunity index and blood inflammatory markers with prognosis was analyzed by univariate and multivariate analysis. Results:For all patients, the 1-, 3- and 5-year overall survival (OS) rates were 78.57%, 34.52% and 19.59%, respectively. The median OS time was 22.60 months. The 1-, 3- and 5-year progression free survival (PFS) rates were 69.05%, 27.38% and 12.09%, respectively. The median PFS time was 21.20 months. The objective response rate was 61.90%, with 11 patients of complete remission (CR) and 41 patients of partial remission (PR). Univariate analysis revealed that NLR before radiotherapy, T-lymphocyte subsets (CD3, CD4 and CD4/CD8) after radiotherapy were significantly associated with OS and PFS (OS: χ 2=7.851, 4.443, 8.381, 5.972, P<0.05, PFS: χ 2= 7.475, 6.290, 9.659, 8.738, P<0.05). Multivariate COX regression analysis showed that NLR before radiotherapy, T-lymphocyte subsets (CD4, CD4/CD8) after radiotherapy were independent prognostic factors for OS (χ 2=10.464, 4.292, 5.507, P<0.05). The NLR before radiotherapy and CD4/CD8 after radiotherapy were independent prognostic factors for PFS (χ 2=10.835, 8.545, P<0.05). Conclusions:Radiotherapy may influence the immune function. NLR before radiotherapy and CD4/CD8 after radiotherapy are of great value in predicting the prognosis of esophageal cancer patients.