Objective:To explore the association of tumor associated macrophages (TAM) with tumor invasiveness, metastasis and prognosis in cardia carcinoma tissues.Methods:The cancer tissues and pericarcinomatous tissues of 100 patients with cardia carcinoma who underwent D2 radical operation in the First Hospital of Putian City from January 2014 to January 2015 were collected. M2-type TAM was marked with CD163. The tissue microarray was made and the expression of CD163 in microarray tissues was detected by using immunohistochemistry. The median number of CD163 positive cells in all cancer tissues was taken as the cut-off value. The patients with the mean number of CD163 positive cells ≥ the cut-off value were those with high TAM infiltration, and vice versa. The association of TAM infiltration with clinicopathological features and prognosis was analyzed, and Cox proportional hazards model was used for multivariate analysis of survival.Results:The positive cell median number of CD163 in cardia carcinoma tissues was higher than that in adjacent tissues [the median number ( P25, P75): 32/high power field (HP) (16/HP, 46/HP) vs. 6/HP (4/HP, 11/HP)], and the difference was statistically significant ( Z = -35.044, P < 0.01). There were 48 cases in low invasive group (< 32/HP) and 52 cases in high invasive group (≥32/HP). The proportion of patients with high TAM infiltration in serosa and extraserosa was higher than that in mucosa and muscle [60.9% (39/64) vs. 36.1% (13/36)], and the proportion of patients with high TAM infiltration for patients with lymph node metastasis was higher than that for patients without lymph node metastasis [61.8% (42/68) vs. 31.3% (10/32)], and the proportion of patients with high TAM infiltration for those with TNM stage Ⅲ-Ⅳ was higher than that for those with TNM stage Ⅰ-Ⅱ [64.4% (38/59) vs. 34.1% (14/41)], and the differences were statistically significant (all P < 0.05). The median overall survival time of high TAM group was shorter than that of low TAM group [24.00 months (95% CI 17.25-43.50 months) vs. 62.00 months (95% CI 34.00-68.00)], and the difference in overall survival was statistically significant (χ 2 = 18.137, P < 0.01). Lymph node metastasis ( HR = 0.301, 95% CI 0.105-0.862, P = 0.025), TNM staging ( HR = 8.404, 95% CI 2.810-25.133, P < 0.01) and TAM infiltration level in cancer tissues ( HR = 4.277, 95% CI 2.372-7.712, P < 0.01) were independent influencing factors for overall survival of patients. Conclusions:TAM plays an important role in the invasion and metastasis of cardia carcinoma and can be used as an independent predictor of biological behavior and prognosis in cardia carcinoma.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system, primarily affecting the optic nerve and spinal cord.In addition to aquaporin 4 antibody, more and more studies have shown that interleukins (IL) also play an important role in the progression of NMOSD.For example, among the most common CD4 + T cells, Th17 cells can destroy the blood-brain barrier to invade the central nervous system and then affect autoimmunity; Th2-mediated IL-4 and IL-10 regulate immune activities by activating macrophages; Tregs can suppress the immune response by restricting various immune cell functions.The levels of related IL in the cerebrospinal fluid and blood of NMOSD patients vary at different stages of the disease course.This article mainly reviews the role and a change characteristics of interleukins related to NMOSD, which helps us to understand its pathogenic mechanism in-depth, and discusses whether IL can be used as immunophysiological markers to diagnose NMOSD.

Objective To assess the methodology of papers on systematic reviews and meta-analysis of interventions published in Journal of Evidence-Based Medicine .Methods Basic data were extracted from 70 papers on systematic reviews and meta-analysis of interventions published in Journal of Evidence-Based Medicinefrom 2001 to 2011 .Methodology used in these papers was assessed according to the AMSTAR Scale.The data were input into the Excelland analyzed using the SPSS7.0 and Meta-Analyst software.Results The methodology used in 34 papers (48.6%) was assessed using the Cochrane bias risk assessment tools.Fund support, number of authors and their affiliated institutions did not sig-nificantly affect the total score of methodology used in the 70 papers .Conclusion The methodology used in papers on systematic reviews and meta-analysis of interventions published in Journal of Evidence-Based Medicine is not quite valid as its early design program and retrieval strategies are imperfect , and it does not provide the excluded literature list and the interest conflict.

Objective To investigate the feasibility and effectiveness of endovascular treatment of posterior communicating artery aneurysm (PcoAA)in keeping the fetal posterior cerebral artery (FPCA) patency. Methods Form January 2014 to December 2015,14 patients with ruptured PcoAA enrolled retrospectively were treated with endovascular embolization. Six of them were treated with simple coil embolization,3 with stent-assisted coil embolization,3 with double catheter-assisted coil embolization,1 with stent-assisted coil embolization + double catheter technique,and 1 with Y-stent in Yijishan Hospital, Wannan Medical College. The immediate embolization rate of PcoAA (using Raymond grade),prognosis of the patients (the modified Rankin scale score at 6 months after procedure),complications,and imaging follow-up results were analyzed. Results The success rate of coil and stenting was 100% . All the stents were accurately released in place without displacement. The immediate Raymond grading of the aneurysms displayed that Raymond grade Ⅰ was in 8 cases,Raymond grade Ⅱ was in 4 cases,and Raymond grade Ⅲ was in 2 cases. All FPCA were kept patent. A coil protruded into internal carotid artery in one case during the procedure. Others did not have any complications,such as intraoperative cerebral vasospasm,in-stent thrombosis,and rupture. All 14 patients were followed up for 3 -24 months after procedure. Two had recurrence. Both were aneurysms embolized with coils only. No rebleeding and ischemic
complications were observed. The modified Rankin scale scores in 13 cases were 0 -2 at 6 months after procedure,1 was 4. Conclusions Endovascular embolization for the treatment of PcoAA and keeping FPCA patency are safe and feasible. A variety of endovascular treatment modalities are necessary in order to keep FPCA patency.

Objective To investigate the risk factors for influencing recrudescence after endovascular embolization of posterior communicating artery aneurysms.Methods From January 2014 to December 2014,71 consecutive patients (a total of 74 aneurysms) with posterior communicating artery aneurysm treated with endovascular treatment at the Department of Neurosurgery,Yijishan Hosptial of Wannan Medical College were enrolled retrospectively.The aneurysms were calculated as the number of cases (n=74).The aneurysms were divided into two groups according to whether they had recrudescence or not,including recurrent group (n=18) and non-recurrent group (n=56).The differences of the clinical data and aneurysm characteristics between the two groups were compared.Multivariate logistic regression was used to analyze the risk factors for recrudescence after endovascular embolization of posterior communicating artery aneurysms.Results Of the 74 patients with aneurysm,51 were treated with simple coil embolization and 23 were treated with stent-assisted coil embolization.All the coils were released satisfactorily.There were significant difference in the size of aneurysms and Raymond grade between the two groups (all P<0.01).The incidence of aneurysms with daughter cysts (55.6% [10/18] and the rate of non-stent-assisted coil embolization (88.9% [16/18]) in the recurrent group were significantly higher than those in the non-recurrent group (23.2% [13/56],62.5% [35/56]).The difference between the two groups was statistically significant (all P<0.05).There was no significant difference in other aneurysm features between the two groups (all P>0.05).After variable selection,the Raymond grade was referred to Raymond gradeⅠ.Multivariate logistic regression analysis showed that the non-stent-assisted coil embolization (OR,4.789,95%CI 1.207-19.009,P=0.026),Raymond grade Ⅱ (OR,12.326,95%CI 3.838-39.592,P<0.01),Raymond grade Ⅲ (OR,36.884,95%CI 2.892-470.454,P=0.005) were the independent risk factors for recrudescence after embolization of posterior communicating artery aneurysms.Conclusion Non-stent-assisted coil embolization,Raymond Ⅱ and Ⅲ may cause recrudescence of posterior communicating artery aneurysms.

Objective:To analyze the clinical features and prognosis factors of aquaporin 4 (AQP4) antibody-positive neuromyelitis optica spectrum disorders related optic neuritis (NMOSD-ON).Methods:An ambidirectional cohort study. From June 1, 2015 to June 1, 2019, 103 patients with AQP4 antibody-positive NMOSD-ON in Department of Neuro-ophthalmology, The First Medical Center of PLA General Hospital were included. All patients of followed-up period were ≥24 months. According to the best corrected visual acuity (BCVA) at the last follow-up, the affected eyes were divided into the low vision group [log of minimum resolution angle (logMAR) BCVA≥1.0] and the non-low vision group (logMAR BCVA<1.0), 66 and 37 cases, respectively. The two groups of patients were compared the genernal clinical characteristics, and the logistic regression model and COX proportional hazard model were used to analyze the relevant factors affecting the patient's visual prognosis and recurrence.Results:Among the 103 cases, 96 cases (93.2%, 96/103) were female; 94 cases (91.3%, 94/103) had unilateral disease; 48 cases (46.6%, 48/103) were the first onset; 85 cases (82.5%, 85/103) were effected by eye pain or orbital pain; 21 cases (20.4%, 21/103) had optic disc edema; 51 cases (49.5%, 51/103) serologically autoimmune antibody test were positive. Orbital magnetic resonance imaging (MRI) was performed in 101 cases. There was no obvious abnormal signal in visual pathways except for 5 cases (5.0%, 5/101); 96 cases (95.0%, 96/101) had abnormal signal in the visual path, and the optic nerve was found in the orbit; 52 cases had abnormal optic nerve in orbital segment (51.5%, 52/101); 37 cases (35.9%, 37/103) recurred within 24 months. The recovery of logMAR BCVA after the first onset and the logMAR BCVA at the first onset, at 6 months of follow-up in two groups were 1.4±1.0, 0.3±0.4, 1.9±0.7 and 0.4±0.5, 2.1±0.6, 0.3±0.4, respectively; and there were statistically significant differences between the two groups of patients at different times ( Z=-4.967,-7.603,-8.027; P<0.001). Logistic regression multivariate analysis showed that recovery of BCVA≥1.0 logMAR after the first onset [odds ratio ( OR)=226.276, P<0.001 ] and the number of attacks ( OR=8.554, P=0.003) were independent risk factors for low vision. Multivariate analysis of the Cox proportional hazards model showed the higher the MRI score [hazard ratio ( HR)=0.588, P=0.007] and plasma exchange ( HR=0.124, P=0.049) in the acute phase were protective factors for recurrence. Conclusions:Vision loss accompanied by eye pain or orbital pain is the main symptom of onset AQP4 antibody-positive NMOSD-ON, a small number of patients have disc edema, 49.5% patients serologically autoimmune antibody test are positive. Abnormal optic nerve signals can be seen in 95.0% of patients in orbital MRI, and 51.5% patients have abnormalities in the orbital optic nerve. The worse the recovery of BCVA after the first onset and the greater the number of attacks are unfavorable factors affecting the prognosis of vision. High MRI scores and plasma exchange in the acute phase are favorable factors to prevent the recurrence of the disease.

Background::Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism.Methods::Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR. Results::Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter –42 bp to –28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor progression. Conclusions::This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

Objective:To explore the application of cognitive interview (CI) in intercultural adaptation of the Happiness Scale for Middle-Aged Women (HAS-MW) .Methods:This was a qualitative study. In January 2022, 20 middle-aged women in community of Yanji City were selected by purposive sampling for two rounds of CI, and 10 subjects participated in each round of CI. According to the interview outline, we understood the understanding of the subjects on the HAS-MW items that were preliminarily localized in Chinese. The expert group discussed and revised the items of the scale according to the interview results.Results:In this study, a total of 2 rounds of cognitive interviews were conducted, the age of 10 respondents (P1-P10) in the first round was (49.00±3.55) , and the age of 10 respondents (P11-P20) in the second round was (51.00±3.16) . After the first round, 6 items in HAS-MW were revised due to "imperfect language, grammar and expression". The second round of CI results showed that the respondents understood the contents of the revised scale items and believed that they were consistent with the original scale.Conclusions:Through CI, we can comprehensively understand middle-aged women's understanding of the content of the HAS-MW, effectively find out the cognitive bias caused by improper language expression in the process of the scale's localization, improve the understanding of the content of the scale by the interviewees, which is conducive to intercultural adaptation of the HAS-MW and provides a reference for the revision of the scale.

Objective:To explore the effect of Xingnao Kaiqiao acupuncture treatment on brain network reorganization for the patients with stroke recovery, and therefore understand the neural mechanism underlying Xingnao Kaiqiao acupuncture treatment.Methods:Prospective case series study. Thirteen acute ischemia stroke patients were recruited from the Department of Neurology, Shanghai Minhang Hospital of Integrated Traditional Chinese and Western Medicine from Aug 2018 to Oct 2019. They were treated with Xingnao Kaiqiao acupuncture once a day for 10 consecutive days in addition to routine treatments, and received clinical assessments before treatment and 14 days after treatment onset. EEG signals were recorded during the first acupuncture treatment, from before inserting the needles (the baseline), during needle retention, to after removal of the needles. The brain network was constructed using phase locking index, and its clustering coefficient (CC), characteristic path length (PL) and small-worldness (S) were analyzed using one-way repeated ANOVA.Results:Compared with the baseline, the CC of delta-band network (sparsity=0.10: t=3.306, P=0.006; 0.12: t=2.909, P=0.013; 0.14: t=2.331, P=0.038) and the PL of delta-band (sparsity=0.12: t=3.236, P=0.007; 0.14: t=2.754, P=0.017, 0.18: t=2.878, P=0.014) and alpha-band (sparsity=0.10: t=2.432, P=0.032) networks were significantly decreased during the needle retention stage. Clinical assessments demonstrated a significant treatment efficacy of Xingnao Kaiqiao acupuncture, and its efficacy which was indicated by improved NIHSS score, was significantly correlated with the CC changes in the delta band network from baseline to needle retention. The correlation was strongest when the network sparsity was 0.12 ( r=0.78, P=0.002). Conclusion:Xingnao Kaiqiao acupuncture can regulate the brain network of stroke patients in real time, and this immediate regulation maybe associated with its treatment effect.

Background::Cancer immunotherapy has emerged as a promising strategy against triple-negative breast cancer (TNBC). One of the immunosuppressive pathways involves programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), but many patients derived little benefit from PD-1/PD-L1 checkpoint blockades treatment. Prior research has shown that MYC, a master transcription amplifier highly expressed in TNBC cells, can regulate the tumor immune microenvironment and constrain the efficacy of immunotherapy. This study aims to investigate the regulatory relationship between MYC and PD-L1, and whether a cyclin-dependent kinase (CDK) inhibitor that inhibits MYC expression in combination with anti-PD-L1 antibodies can enhance the response to immunotherapy. Methods::Public databases and TNBC tissue microarrays were used to study the correlation between MYC and PD-L1. The expression of MYC and PD-L1 in TNBCs was examined by quantitative real-time polymerase chain reaction and Western blotting. A patient-derived tumor xenograft (PDTX) model was used to evaluate the influence of a CDK7 inhibitor THZ1 on PD-L1 expression. Cell proliferation and migration were detected by 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation and cell migration assays. Tumor xenograft models were established for in vivo verification. Results::A high MYC expression level was associated with a poor prognosis and could alter the proportion of tumor-infiltrating immune cells (TIICs). The positive correlation between MYC and PD-L1 was confirmed by immunostaining samples from 165 TNBC patients. Suppression of MYC in TNBC caused a reduction in the levels of both PD-L1 messenger RNA and protein. In addition, antitumor immune response was enhanced in the TNBC cancer xenograft mouse model with suppression of MYC by CDK7 inhibitor THZ1. Conclusions::The combined therapy of CDK7 inhibitor THZ1 and anti-PD-L1 antibody appeared to have a synergistic effect, which might offer new insight for enhancing immunotherapy in TNBC.