1.A multi-dimensional analysis of pollen broadcasting concerns in Chinese population: a large-scale multi-center cross-sectional survey
Chiyu XU ; Yanshu ZHANG ; Ning LUAN ; Xiangyi LIU ; Dayang QIN ; Hongmin WANG ; Xuping XIAO ; Shuihong ZHOU ; Jie ZHANG ; Ping ZHANG ; Yuqing BAI ; Pengpeng WANG ; Yan QI ; Zhongwu SUN ; Zhuang LIU ; Luo BA ; Wenchao WANG ; Xing LU ; Min WANG ; Rui GUO ; Deyi SUN ; Liyuan TAO ; Li ZHU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(1):2-11
Objective:To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors.Methods:From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions.Results:Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects ( χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients ( χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications ( χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment ( R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not ( OR=1.83, P<0.001). Conclusions:Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.
2.Analysis of the efficacy and safety of preoperative programmed death protein-1 inhibitor combined with chemotherapy in immunotherapy-sensitive patients with locally advanced gastric cancer or adenocarcinoma of the esophagogastric junction
Yingjie LI ; Peng YUAN ; Jianning ZHAI ; Yunfeng YAO ; Luxin TAN ; Zhongwu LI ; Xiaoyan ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2024;27(7):684-693
Objective:To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1 (PD-1) inhibitor with either oxaliplatin + capecitabine (CapeOx) or oxaliplatin + tegafur gimeracil oteracil potassium (SOX) in the treatment of locally advanced immunotherapy-sensitive gastric cancer (LAGC) or adenocarcinoma of the esophagogastric junction (AEG).Methods:The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy- sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024. Patients with any one of the following three characteristics were immunotherapy-sensitive: (i) PD-L1 combined positive score (CPS) ≥5; (ii) microsatellite instability-high (MSI-H) / mismatch repair deficiency (dMMR); or (iii) Epstein-Barr virus-encoded RNA (EBER) positivity. All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery. Patients with immune system diseases, distant metastases, or human epidermal growth factor receptor 2 positivity were excluded. Factors analyzed included pathological complete response, clinical complete response, major pathological response, R0 resection rate, surgical conversion rate, and safety of the treatment, including immune-related adverse events (irAEs) and surgical complications.Results:The study cohort comprised 39 patients (28 men and 11 women) of median age 62 (range 44–79) years. After the above-described preoperative treatment, radical resection of the 14 tumors that were initially considered unresectable was achieved (surgical conversion rate: 14/14). Twenty-three of the remaining 25 patients underwent radical resection. The last two patients achieved clinical complete responses and opted for a "non-surgical strategy" (watch and wait). Overall, 37 patients (94.9%) underwent radical resection, with an R0 resection rate of 100% (37/37), pathological complete response rate of 48.6% (18/37), and major pathological response rate of 62.2% (23/37). Of the 24 patients with CPS ≥ 5 (non-MSI-H/dMMR and non-EBER positive), 11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response. Of the eight patients with MSI-H/dMMR, six achieved pathological complete responses and one a clinical complete response. Of the seven patients with EBER positivity, one achieved a pathological complete response. After excluding patients with major pathological complete responses, there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients (7.769±5.570 vs. 15.538±16.870, t=2.287, P=0.041). All patients tolerated preoperative immunotherapy well; nine patients (9/39, 23.1%) had Grade I–II irAEs. There were no Grade III–IV irAEs. The five patients with pyloric obstruction before treatment tolerated normal diets after treatment. The incidence of postoperative complications among all patients who underwent surgery was 18.9% (7/37), including one case of Grade IIIA anastomotic leakage, one of Grade IIIA intestinal obstruction, one of Grade II abdominal hemorrhage, two of Grade II abdominal infection, one of Grade I intestinal obstruction. Additionally, one patient developed COVID-19 postoperatively. All patients recovered with symptomatic treatment. Conclusion:We found that preoperative treatment of patients with LAGC or AEG of one of three types (CPS≥5, dMMR+MSI-H, and EBER positivity) with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety, with high surgical conversion, R0 resection, and complete response rates.
3.Analysis of the efficacy and safety of preoperative programmed death protein-1 inhibitor combined with chemotherapy in immunotherapy-sensitive patients with locally advanced gastric cancer or adenocarcinoma of the esophagogastric junction
Yingjie LI ; Peng YUAN ; Jianning ZHAI ; Yunfeng YAO ; Luxin TAN ; Zhongwu LI ; Xiaoyan ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2024;27(7):684-693
Objective:To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1 (PD-1) inhibitor with either oxaliplatin + capecitabine (CapeOx) or oxaliplatin + tegafur gimeracil oteracil potassium (SOX) in the treatment of locally advanced immunotherapy-sensitive gastric cancer (LAGC) or adenocarcinoma of the esophagogastric junction (AEG).Methods:The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy- sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024. Patients with any one of the following three characteristics were immunotherapy-sensitive: (i) PD-L1 combined positive score (CPS) ≥5; (ii) microsatellite instability-high (MSI-H) / mismatch repair deficiency (dMMR); or (iii) Epstein-Barr virus-encoded RNA (EBER) positivity. All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery. Patients with immune system diseases, distant metastases, or human epidermal growth factor receptor 2 positivity were excluded. Factors analyzed included pathological complete response, clinical complete response, major pathological response, R0 resection rate, surgical conversion rate, and safety of the treatment, including immune-related adverse events (irAEs) and surgical complications.Results:The study cohort comprised 39 patients (28 men and 11 women) of median age 62 (range 44–79) years. After the above-described preoperative treatment, radical resection of the 14 tumors that were initially considered unresectable was achieved (surgical conversion rate: 14/14). Twenty-three of the remaining 25 patients underwent radical resection. The last two patients achieved clinical complete responses and opted for a "non-surgical strategy" (watch and wait). Overall, 37 patients (94.9%) underwent radical resection, with an R0 resection rate of 100% (37/37), pathological complete response rate of 48.6% (18/37), and major pathological response rate of 62.2% (23/37). Of the 24 patients with CPS ≥ 5 (non-MSI-H/dMMR and non-EBER positive), 11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response. Of the eight patients with MSI-H/dMMR, six achieved pathological complete responses and one a clinical complete response. Of the seven patients with EBER positivity, one achieved a pathological complete response. After excluding patients with major pathological complete responses, there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients (7.769±5.570 vs. 15.538±16.870, t=2.287, P=0.041). All patients tolerated preoperative immunotherapy well; nine patients (9/39, 23.1%) had Grade I–II irAEs. There were no Grade III–IV irAEs. The five patients with pyloric obstruction before treatment tolerated normal diets after treatment. The incidence of postoperative complications among all patients who underwent surgery was 18.9% (7/37), including one case of Grade IIIA anastomotic leakage, one of Grade IIIA intestinal obstruction, one of Grade II abdominal hemorrhage, two of Grade II abdominal infection, one of Grade I intestinal obstruction. Additionally, one patient developed COVID-19 postoperatively. All patients recovered with symptomatic treatment. Conclusion:We found that preoperative treatment of patients with LAGC or AEG of one of three types (CPS≥5, dMMR+MSI-H, and EBER positivity) with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety, with high surgical conversion, R0 resection, and complete response rates.
4.Tumor cell lysate with low content of HMGB1 enhances immune response of dendritic cells against lung cancer in mice.
Zhongwu PAN ; Siqi LI ; Yaohui WANG ; Haijun LIU ; Lin GUI ; Bohan DONG
Journal of Southern Medical University 2023;43(6):906-914
OBJECTIVE:
To assess the effect of tumor cell lysate (TCL) with low high-mobility group B1 (HMGB1) content for enhancing immune responses of dendritic cells (DCs) against lung cancer.
METHODS:
TCLs with low HMGB1 content (LH-TCL) and normal HMGB1 content (NH-TCL) were prepared using Lewis lung cancer (LLC) cells in which HMGB1 was inhibited with 30 nmol/L glycyrrhizic acid (GA) and using LLC cells without GA treatment, respectively. Cultured mouse DCs were exposed to different doses of NH-TCL and LH-TCL, using PBS as the control. Flow cytometry was used to detect the expressions of CD11b, CD11c and CD86 and apoptosis of the stimulated DCs, and IL-12 levels in the cell cultures were detected by ELISA. Mouse spleen cells were co-cultured with the stimulated DCs, and the activation of the spleen cells was assessed by detecting CD69 expression using flow cytometry; TNF-β production in the spleen cells was detected with ELISA. The spleen cells were then co-cultured with LLC cells at the effector: target ratios of 5:1, 10:1 and 20:1 to observe the tumor cell killing. In the animal experiment, C57/BL6 mouse models bearing subcutaneous LLC xenograft received multiple injections with the stimulated DCs, and the tumor growth was observed.
RESULTS:
The content of HMGB1 in the TCL prepared using GA-treated LLC cells was significantly reduced (P < 0.01). Compared with NH-TCL, LH-TCL showed a stronger ability to reduce apoptosis (P < 0.001) and promote activation and IL- 12 production in the DCs. Compared with those with NH-TCL stimulation, the DCs stimulated with LH-TCL more effectively induced activation of splenic lymphocytes and enhanced their anti-tumor immunity (P < 0.05). In the cell co-cultures, the spleen lymphocytes activated by LH-TCL-stimulated DCs showed significantly enhanced LLC cell killing activity (P < 0.01). In the tumor-bearing mice, injections of LH-TCL-stimulated DCs effectively activated host anti-tumor immunity and inhibited the growth of the tumor xenografts (P < 0.05).
CONCLUSION
Stimulation of the DCs with LH-TCL enhances the anti-tumor immune activity of the DCs and improve the efficacy of DCbased immunotherapy for LLC in mice.
Animals
;
Humans
;
Mice
;
Apoptosis
;
Dendritic Cells/immunology*
;
Glycyrrhizic Acid/pharmacology*
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HMGB1 Protein
;
Lung Neoplasms/immunology*
5.Effects of homocysteine on cerebral perfusion and cognitive function in patients with arteriosclerotic cerebral small vessel disease
Mingxu LI ; Chaojuan HUANG ; Wei ZHANG ; Xia ZHOU ; Jiabin YIN ; Wenhao ZHU ; Chenchen LI ; Zhongwu SUN
Chinese Journal of Neurology 2023;56(11):1244-1253
Objective:To investigate the effect of homocysteine (Hcy) on cerebral perfusion and cognitive function in patients with arteriosclerotic cerebral small vessel disease (aCSVD).Methods:A total of 117 patients with aCSVD who visited the First Affiliated Hospital of Anhui Medical University from June 2020 to September 2022 were enrolled and divided into the aCSVD cognitive impairment group (aCSVD-CI, n=57) and aCSVD non-cognitive impairment group (aCSVD-NCI, n=60) according to the Montreal Cognitive Assessment score. Serum Hcy measurement, cognitive function assessment, and three-dimensional pseudo-continuous arterial spin labeling perfusion imaging scan were performed in all patients, and multivariate Logistic regression analysis was used to explore risk factors for cognitive impairment in patients with aCSVD. The cerebral blood flow and perfusion differential brain regions of the whole brain, grey matter, and white matter were compared between the two groups. Partial correlation analyses were performed between the serum Hcy, overall cognitive function scores and cerebral blood flow in grey matter, as well as between the cerebral blood flow in the perfusion differential brain area and cognitive function scores. The mediating effect model was used to analyze the role of grey matter blood flow in the relationship between serum Hcy and overall cognition. Results:The serum Hcy level in the CSVD-CI group was higher than that in the CSVD-NCI group [16.38(14.02, 18.58) μmol/L vs 14.40 (11.93, 15.73) μmol/L, Z=-3.81, P<0.001]. In terms of cerebral perfusion, compared with the aCSVD-NCI group, the aCSVD-CI group had significantly lower cerebral blood flow in grey matter ( Z=-3.22, P=0.001), left middle frontal gyrus ( t=-4.91, P<0.05), right middle frontal gyrus ( t=-5.14, P<0.05), and right orbital medial frontal lobe ( t=-4.38, P<0.05). In contrast, the left hippocampus ( t=4.58, P<0.05) had increased cerebral blood flow. Multivariate Logistic regression analysis showed that serum Hcy level was independent risk factor for cognitive impairment in aCSVD after controlling for multiple risk factors. Partial correlation analysis showed that left middle frontal gyrus blood flow ( r=-0.39, P=0.006), right middle frontal gyrus blood flow ( r=-0.44, P=0.002), and right orbital medial frontal lobe cerebral blood flow ( r=-0.43, P=0.002) were negatively correlated with the Stroop Color Word Test-C results. Left hippocampal cerebral blood flow was negatively correlated with Auditory Word Learning Test-long-delayed recall ( r=-0.43, P=0.002). Further mediation analysis showed that the effect of Hcy on cognitive function was partly mediated by grey matter cerebral blood flow (indirect effect=-0.11, P<0.001). Conclusion:Hcy is an independent risk factor for cognitive impairment in aCSVD, and part of the effect of elevated Hcy on cognitive impairment in aCSVD may be mediated by decreased gray matter cerebral perfusion.
6.Clinical research progress on lymph node metastasis in gastric mixed adenoneuroen-docrine carcinoma
Kai ZHOU ; Anqiang WANG ; Yan WU ; Zhongwu LI ; Zhaode BU
Chinese Journal of Clinical Oncology 2023;50(24):1275-1279
Gastric mixed adenoneuroendocrine carcinomas(G-MANEC)are an infrequent variant of gastrointestinal tumors.Despite their relatively low occurrence,there has been a noticeable upward trend.G-MANEC exhibit a highly invasive nature,frequently leading to lymph-atic and distant metastases,which ultimately result in unfavorable prognosis.Consequently,this condition has garnered considerable in-terest among researchers.G-MANEC are characterized by the presence of adenocarcinoma and neuroendocrine carcinoma components,with each component comprising at least 30%of the tumor.In recent years,a growing body of knowledge regarding G-MANEC has led to a more comprehensive research approach towards this type of carcinoma.Nevertheless,there has been a notable deficiency to date in the ex-amination of lymph node metastatic aspects of G-MANEC,which poses several pressing challenges that demand immediate resolutions.This review aims to systematically analyze previous case reports and studies on mixed neuroendocrine-non-neuroendocrine neoplasms(MiNEN)while incorporating research on gastric cancer.This study focuses on various aspects of G-MANEC,including the epidemiology,biological ori-gin,diagnosis,patterns of lymph node metastasis,relationship with hematogenous metastasis,association between lymphatic and distant metastases,and treatment.The objective is to offer guidance for future research endeavors concerning G-MANEC.
7.Altered neurovascular coupling in arteriosclerotic cerebral small vessel disease and the correlation with cognitive function
Chaojuan HUANG ; Xin YUAN ; Wei ZHANG ; Mingxu LI ; Chenchen LI ; Xia ZHOU ; Zhongwu SUN
Chinese Journal of Neurology 2022;55(5):458-465
Objective:To investigate the global and local changes of neurovascular coupling in arteriosclerotic cerebral small vessel disease (aCSVD) and the correlation with cognitive function.Methods:Forty-three patients with confirmed aCSVD from the outpatient department or ward of the Department of Neurology, the First Affiliated Hospital of Anhui Medical University between June 2020 and June 2021 were enrolled in this study. Meanwhile, 48 healthy subjects were selected as controls. Cognitive evaluation, resting-state functional magnetic resonance imaging and 3D pseudo-continuous arterial spin labeling magnetic resonance imaging scanning were performed in all subjects. The global cerebral blood flow-regional homogeneity (ReHo) correlation coefficient and the cerebral blood flow/ReHo ratio were used to evaluate global and local neurovascular coupling. Meanwhile, correlations between the cerebral blood flow/ReHo ratio and neuropsychological assessments were explored in aCSVD patients.Results:Global cerebral blood flow-ReHo coupling was decreased in aCSVD patients compared to healthy controls [aCSVD patients: 0.942(0.933, 0.950), healthy controls: 0.947(0.939, 0.954), Z=-2.11, P=0.035]. aCSVD patients showed decreased cerebral blood flow/ReHo ratio in the right lingual gyrus ( t=-4.45, P<0.05) and increased cerebral blood flow/ReHo ratio in the left ( t=4.91, P<0.05) and right ( t=4.72, P<0.05) inferior parietal lobule. Cerebral blood flow/ReHo ratio of the right inferior parietal lobule was negatively correlated with total score ( r=-0.33, P=0.031) and praxis score ( r=-0.43, P=0.004) in Cambridge Cognitive Examination-Chinese Version subitems and positively correlated with scores of Stroop Color Word Test (SCWT)-color ( r=0.33, P=0.032), SCWT-word ( r=0.34, P=0.025) and Trail Making Test-B ( r=0.31, P=0.043) in aCSVD patients. While the cerebral blood flow/ReHo ratio of the right lingual gyrus was negatively correlated with Visual Replicate-Immediate Recall score ( r=-0.36, P=0.017). Conclusion:aCSVD patients showed abnormal global and local neurovascular coupling, which was associated with attention, executive function, and visual space function.
8.The effect of adjuvant radiotherapy on N 2 patients with non-small cell lung cancer
Wenze TIAN ; Li WAN ; Zhongwu HU ; Xuechun LENG ; Zhen ZHANG ; Zhenbing YOU
Chinese Journal of Radiological Medicine and Protection 2020;40(7):507-511
Objective:To investigate the effect of adjuvant radiotherapy on the prognosis of patients with N 2 stage non-small cell lung cancer (NSCLC) undergoing radical resection. Methods:The data of 1 208 patients with NSCLC who received radical lung cancer resection combined with chemotherapy or post-operative adjuvant radiotherapy and chemotherapy from SEER database of the United States from 2004 to 2016 were included in the study. 627 patients received radical lung cancer resection combined with chemotherapy (surgery + chemotherapy group), and 581 patients received radical lung cancer resection combined with radiochemotherapy (surgery + radiochemotherapy group). We analyzed and compared the effect of postoperative adjuvant radiotherapy on the prognosis of patients with N 2 stage NSCLC undergoing radical resection. The 1∶1 propensity matching method was used to analyze the prognosis of the two groups. Results:In the two groups of patients with stage N 2 NSCLC included in the study, the median survival time was 51 months in the operation + radiotherapy and chemotherapy group, and the 3- and 5-year cancer specific survival rates were 58.3% and 44.9%, respectively. The median survival time was 50 months in operation + chemotherapy group, and the 3- and 5-year cancer specific survival rates were 59.9% and 46.5%, respectively. There was no statistically significant difference between the two groups in cancer specific survival ( P>0.05). The result of subgroup analysis showed that the cancer specific survival of patients in operation + radiotherapy and chemotherapy group was significantly worse than that in operation + chemotherapy group ( χ2=5.085, P<0.05). Multivariate Cox regression analysis showed that age, gender, G stage, T stage and the number of lymph node metastasis were the important factors affecting the cancer specific survival of patients with N 2 NSCLC ( Wald =15.236, 7.039, 4.841, 10.155, 11.192, respectively, P<0.05). After propensity matching, there was no statistically significant difference in cancer specific survival ( P>0.05) between the two groups. However, in the T 1 NSCLC patients, the cancer specific survival of operation + radiochemotherapy group was significantly worse than that of operation + chemotherapy group ( χ2=5.364, P<0.05), while the cancer specific survival of operation + radiochemotherapy group was significantly better than that of operation + chemotherapy group in T 3-4 subgroup( χ2=4.486, P<0.05). According to the tendency matching of pathological subgroups, the cancer specific survival of surgery + radiochemotherapy group was significantly better than that of surgery + chemotherapy group ( χ2=6.279, P<0.05) in the non adenocarcinoma subgroup. And the multivariate Cox regression analysis indicated that postoperative radiotherapy was an important factor for cancer specific survival in patients with N 2 non adenocarcinoma non-small cell lung cancer ( Wald=7.300, P<0.05). However, before and after propensity matching in lung adenocarcinoma subgroup, there was no statistically significant difference in cancer specific survival between the surgery + radiochemotherapy group and the surgery + chemotherapy group ( P>0.05). Conclusions:Postoperative adjuvant radiotherapy can improve the prognosis of patients with T 3-4 or non-adenocarcinoma N 2 NSCLC. But, for other patients with N 2 non-small cell lung cancer, the choice of postoperative adjuvant radiotherapy should be cautious, especially for T 1 stage.
9.Changes in gray matter volume and their correlation with cognitive impairment in patients with subcortical vascular cognitive impairment
Yimei ZHANG ; Linlin LI ; Wei ZHANG ; Xia ZHOU ; Xiaoqun ZHU ; Zhongwu SUN
Chinese Journal of Neurology 2020;53(5):328-334
Objective:To analyze the changes of total gray matter volume in patients with subcortical vascular cognitive impairment (SVCI) and their correlation with cognitive impairment.Methods:Data of fifty patients with subcortical ischemic vascular disease (SIVD) who admitted to the outpatient department or ward of the Department of Neurology, the First Affiliated Hospital of Anhui Medical University from November 2017 to March 2019, were collected for the study, including 23 patients with SVCI and 27 patients with subcortical ischemic vascular disease without cognitive impairment (SIVD-NCI). All subjects were assessed using the Minimal Mental State Examination (MMSE), the Montreal Cognitive Assessment scale (MoCA), the Cambridge Cognitive Assessment scale for the elderly-Chinese version (CAMCOG-C), the Stroop test, the Geriatric Depression Scale, and the Activity of Daily Living scale (ADL). All subjects underwent 3.0 T magnetic resonance imaging scans to obtain T 1WI, T 2WI, fluid attenuated inversion recovery (FLAIR) images and 3D-T 1 structural image data. Voxel-based morphometry (VBM) was used to analyze and compare the differences in gray matter volume between SVCI group and SIVD-NCI group. Results:Compared with the SIVD-NCI group, the MMSE score (22.00 (20.00, 24.00) vs 28.00 (27.00, 29.00), Z=-6.073, P<0.001), MoCA score (15.00 (13.00,19.00) vs 24.00 (23.00, 26.00), Z=-5.233, P<0.001), total score of CAMCOG-C (67.65±13.35 vs 88.41±10.98, t=-6.032, P<0.001) and the directional (8.00 (5.00, 9.00) vs 10.00 (9.00, 10.00), Z=-4.133, P<0.001), language (24.00 (21.00, 26.00) vs 27.00 (24.00, 28.00), Z=-3.171, P=0.002), memory (11.00 (9.00, 15.00) vs 19.00 (17.00, 21.00), Z=-4.648, P<0.001), attention (4.00 (2.00, 6.00) vs 7.00 (6.00, 7.00), Z=-3.929, P<0.001), executive (8.00 (6.00, 10.00) vs 11.00 (9.00, 12.00), Z=-3.696, P<0.001), calculation (2.00 (2.00, 2.00) vs 2.00 (2.00, 2.00), Z=-2.528, P=0.011), thinking (6.00 (3.00, 6.00) vs 6.00 (6.00, 8.00), Z=-4.029, P<0.001), perception (6.00 (6.00, 7.00) vs 8.00 (7.00, 9.00), Z=-4.221, P<0.001) in the SVCI group were obviously decreased. ADL score (21.00 (20.00, 26.00) vs 20.00 (20.00, 20.00), Z=-2.634, P=0.008) and Stroop test score (28.61±4.53 vs 20.04±6.07, t=5.704, P<0.001) were significantly higher in the SVCI group than in the SIVD-NCI group. The total gray matter volume ((556.86±49.19) mm 3vs (618.13±51.73) mm 3, t=-3.572, P=0.001) and white matter volume ((479.35±48.17) mm 3vs (507.22±43.84) mm 3, t=-2.141, P=0.037) in the SVCI group were smaller than that in the SIVD-NCI group. VBM analysis showed that the SVCI group had significantly smaller gray matter volume in the left inferior temporal gyrus ( t=5.17, P<0.001, family wise error (FWE) correction), right middle temporal gyrus ( t=4.99, P<0.001, FWE correction), right orbital superior frontal gyrus ( t=5.02, P<0.001, FWE correction), left middle occipital gyrus ( t=5.67, P<0.001, FWE correction), right middle occipital gyrus ( t=5.77, P<0.001, FWE correction). MoCA score was positively correlated with the volume of gray matter in the left inferior temporal gyrus of patients with SIVD ( r=0.292, P<0.05), language function score was positively correlated with the volume of gray matter in the left inferior temporal gyrus ( r=0.322, P<0.05), and Stroop test score was negatively correlated with gray matter volume in the left inferior temporal gyrus ( r=-0.329, P<0.05). Conclusion:Gray matter atrophy exists in multiple brain regions in patients with SVCI, and these atrophic brain regions are associated with cognitive impairment of SIVD.
10.Total neoadjuvant therapy followed by watch and wait approach or organ preservation for MRI stratified low-risk rectal cancer: early result from a prospective, single arm trial
Lin WANG ; Yiming ZHAO ; Tingting SUN ; Yuanlian XU ; Shijie LI ; Xiaoyan ZHANG ; Yong CAI ; Yongheng LI ; Zhongwu LI ; Pengju CHEN ; Yifan PENG ; Weihu WANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2020;23(3):258-265
Objective:To explore the safety and efficacy of watch and wait strategy and organ preservation surgery after total neoadjuvant treatment for MRI stratified low-risk rectal cancer.Methods:A prospective single arm phase Ⅱ trial developed at Department of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute was preliminarily analyzed. Subjects were enrolled from August 2016 to January 2019. Low-risk rectal cancer with following MRI features were recruited: mid-low tumor, mrT2-3b, MRF (-), EMVI (-), CRM (-), differentiation grade 1-3. Patients received intensity-modulated radiotherapy (IMRT) 50.6 Gy/22f with concurrent capecitabine and 4 cycles of consolidation CAPEOX. Patients with cCR/near-cCR confirmed by physical examination, rectal MRI, endoscopy, and serum CEA were recommended for watch & wait approach or local excision (LE). The main study outcomes were 2-year organ preservation rate (OPR) and sphincter preservation rate (SPR).Results:Thirty-eight patients were eligible for analysis, including 24 males and 14 females with median age of 56 years; 9 cases of mrT2 (23.7%), 14 cases of mrT3a (36.8%) and 15 cases of mrT3b (39.5%); 5 cases of well differentiated adenocarcinoma (13.2%), 32 cases of moderately differentiated adenocarcinoma (84.2%) and 1 case of mucinous adenocarcinoma (2.6%). Carcinoemobryonic antigen (CEA) was elevated before treatment in 1 case. One case (2.6%) of grade 3 radiation dermatitis occurred during IMRT; 18 cases (47.4%) occurred grade 3 to 4 adverse events during consolidation chemotherapy. After total neoadjuvant treatment, the cCR and near-cCR rates were 42.1% (16/38) and 23.7% (9/38), respectively, while non-cCR rate was 34.2% (13/38). Twenty patients (20/38, 52.6%) of cCR or near-cCR underwent watch & wait approach, with a local regrowth rate of 20% (4/20). Four patients received LE, including one salvage LE. Thirteen patients (4 were ypCR) received radical resection, including 10 cases of initial low anterior resections (LAR), 1 cases of initial abdominal perineal resection (APR) and 2 cases of salvage LAR, four patients refused operation. The median follow-up time was 23.5 (8.5-38.3) months. At the last interview of follow-up, the OPR and SPR were 52.6% (20/38) and 84.2% (32/38), respectively. Only one patient developed lung metastasis and no local recurrence occurred after radical resection or LE.Conclusion:Total neoadjuvant treatment for low-risk rectal cancer achieves high cCR/near-cCR rate, with increased probability of receiving watch and wait approach and organ preservation in this subgroup.

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