1.Expression and significance of PD-L1,CD163 and CD8 in primary cancer and paired lymph node metastatic cancer of lymphocyte-predominant breast cancer
Miaoling CHEN ; Yue YANG ; Huifang ZHANG ; Yuzhen HAN
Chinese Journal of Clinical and Experimental Pathology 2024;40(5):520-525,530
Purpose To investigate the expression and prog-nostic value of programmed death-ligand 1(PD-L1),CD 163 and CD8 in lymphocyte-predominant breast cancer(LPBC),and to analyze the expression of PD-L1,CD 163 and CD8 in primary cancer and corresponding lymph node metastatic cancer.Meth-ods LPBC with complete pathological data were selected.Im-munohistochemical EnVision method was used to detect the ex-pression of PD-L1,CD163 and CD8 in 82 cases of primary cancer and 23 cases of corresponding lymph node metastatic cancer.Their relationships with clinicopathological features and prognosis were analyzed,and the difference of expression be-tween primary cancer and lymph node metastatic cancer.Results The positive rates of PD-L1 in tumor cell(TC)and immune cell(IC)in primary cancer were 25.61%(21/82)and 79.27%(65/82),respectively.The positive rates of TC-PD-L1 in grade Ⅱ and grade Ⅲ were 18.00%(9/50)and 37.50%(12/32),respectively.The expression of TC-PD-L1 was corre-lated with the histological grade(P<0.05).The positive rates of IC-PD-L1 in tumor maximum diameter ≤2 cm and>2 cm were 66.67%(18/27)and 85.45%(47/55),respectively.The positive rates of IC-PD-L1 in Ki67≤20%and>20%were 60.00%(12/20)and 85.48%(53/62),respectively.The ex-pression of IC-PD-L1 was related to tumor maximum diameter and Ki67(P<0.05).TC-PD-L1 expression was positively correlated with CD8+intratumoral tumor-infiltrating lymphocytes(iTILs)density(r=0.277,P<0.05),and IC-PD-L1 expression was positively correlated with CD163(r=0.259,P<0.05).High expression of CD163 was significantly correlated with shorter DFS(P<0.05).Between primary cancer and lymph node metastatic cancer,the co-expression rates of TC-PD-L1 and IC-PD-L1 were 82.61%(19/23)and 47.82%(11/23),respectively,and the difference was not statistically significant(P>0.05).There were statistically differences of CD163 expression and CD8+iTILs be-tween primary cancer and lymph node metastatic cancer(P<0.05).Conclusion PD-L1 expression in primary cancer is as-sociated with poor clinicopathologic features,and high expression of CD163 suggests poor prognosis.There are differences in tumor immune microenvironment between LPBC primary cancer and lymph node metastatic cancer,and re-evaluation of PD-L1 of lymph node metastatic cancer may provide valuable guidance for clinical immunotherapy.
2.Effects of different fractions of inspired oxygen during general anesthesia on postoperative recovery in patients undergoing laparoscopic hernia repair and hysterectomy in a sub-plateau region
Jiyuan HAN ; Lichun HUAI ; Minghui WANG ; Yuzhen LI ; Bo FANG
Journal of China Medical University 2024;53(8):719-724
Objective To investigate the effects of different fractions of inspired oxygen administered during general anesthesia on post-operative recovery in patients undergoing laparoscopic hernia repair and hysterectomy in a sub-plateau region.Methods Clinical data of 111 patients undergoing laparoscopic hernia repair and hysterectomy under general anesthesia were collected from the People's Hospital of Datong Hui and Tu Autonomous County between April 2022 and November 2023.Based on the concentration of inhaled oxygen during general anesthesia,patients were randomly divided into three groups:100%oxygen(n=36),80%oxygen(n=38),and 60%oxygen(n=37).Respiratory-related parameters,including arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2),and oxygenation index(OI),were compared among the three groups before anesthesia induction,30 min after pneumoperito-neum,and 1 d after surgery.Postoperative pulmonary complications,incision infections,first gastrointestinal exhaust time,and length of hospitalization were recorded.Postoperative delirium and cognitive function were also assessed.Results At 30 min after pneumoperi-toneum induction,the OI in the 60%oxygen group was higher than that in the 100%oxygen group(P=0.009),whereas there was no sta-tistical difference in OI between the 80%oxygen and 100%oxygen groups(P>0.05).PaO2 and OI were lower(P<0.05)and PaCO2 was higher(P<0.05)in all groups on the 1st day after surgery than before the induction of anesthesia.PaO2 and OI were higher in the 80%oxygen group than in the 100%oxygen group(all P<0.05).PaO2 and OI were higher in the 60%oxygen group than in the 100%oxygen and 80%oxygen groups(all P<0.05).PaCO2 was lower in the 60%oxygen group than in the 100%oxygen group(P<0.001).The first gastrointestinal exhaust time was shorter in the 60%oxygen group than in the 100%oxygen group(P=0.019).No postoperative incision infections were observed in any of the three groups,and there were no statistically significant differences in the incidence of postoperative pulmonary complications,length of hospitalization,incidence of postoperative delirium,and cognitive dysfunction among the three groups(all P>0.05).Conclusion During general anesthesia for patients undergoing laparoscopic hernia repair and hysterectomy in a sub-pla-teau region,appropriately reducing the concentration of inspired oxygen(60%)is beneficial for postoperative respiratory and gastrointes-tinal function recovery without increasing the incidence of incision infections,postoperative delirium,and cognitive dysfunction.
3.Feature pyramid network for automatic segmentation and semantic feature classification of spontaneous intracerebral hemorrhage hematoma on non-contrast CT images
Changfeng FENG ; Qun LAO ; Zhongxiang DING ; Luoyu WANG ; Tianyu WANG ; Yuzhen XI ; Jing HAN ; Linyang HE ; Qijun SHEN
Chinese Journal of Medical Imaging Technology 2024;40(10):1487-1492
Objective To observe the value of feature pyramid network(FPN)for automatic segmentation and semantic feature classification of spontaneous intracerebral hemorrhage(sICH)hematoma showed on non-contrast CT.Methods Non-contrast CT images of 408 sICH patients in hospital A(training set)and 103 sICH patients in hospital B(validation set)were retrospectively analyzed.Deep learning(DL)segmentation model was constructed based on FPN to segment the hematoma region,and its efficacy was assessed using intersection over union(IoU),Dice similarity coefficient(DSC)and accuracy.Then DL classification model was established to identify the semantic features of sICH hematoma.Receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of DL classification model for recognizing semantic features of sICH hematoma.Results The IoU,DSC and accuracy of DL segmentation model for 95%sICH hematoma in training set was 0.84±0.07,0.91±0.04 and(88.78±8.04)%,respectively,which was 0.83±0.07,0.91±0.05 and(88.59±7.76)%in validation set,respectively.The AUC of DL classification model for recognizing irregular shape,uneven density,satellite sign,mixed sign and vortex sign of sICH hematoma were 0.946-0.993 and 0.714-0.833 in training set and validation set,respectively.Conclusions FPN could accurately,effectively and automatically segment hematoma of sICH,hence having high efficacy for identifying semantic features of sICH hematoma.
4.3D Res2Net deep learning model for predicting volume doubling time of solid pulmonary nodule
Jing HAN ; Lexing ZHANG ; Linyang HE ; Changfeng FENG ; Yuzhen XI ; Zhongxiang DING ; Yangyang XU ; Qijun SHEN
Chinese Journal of Medical Imaging Technology 2024;40(10):1514-1518
Objective To observe the value of 3D Res2Net deep learning model for predicting volume doubling time(VDT)of solid pulmonary nodule.Methods Chest CT data of 734 patients with solid pulmonary nodules were retrospectively analyzed.The patients were divided into progressive group(n=218)and non-progressive group(n=516)according to whether lung nodule volume increased by ≥25%during follow-up or not,also assigned into training set(n=515)and validation set(n=219)at a ratio of 7∶3.Then a clinical model was constructed based on clinical factors being significantly different between groups,CT features model was constructed based on features of nodules on 2D CT images using convolutional neural network,and 3D Res2Net model was constructed based on Res2Net network using 3D CT images as input.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated.Taken actual VDT as gold standard,the efficacy of the above models for predicting solid pulmonary nodule'VDT≤400 days were evaluated.Results No significant difference of predicting efficacy for solid pulmonary nodule'VDT≤400 days was found among clinical model,CT feature model and 3D Res2Net model,the AUC of which was 0.689,0.698 and 0.734 in training set,0.692,0.714 and 0.721 in validation set,respectively.3D Res2Net model needed 5-7 s to predict VDT of solid pulmonary nodules,with an average time of(5.92±1.08)s.Conclusion 3D Res2Net model could be used to predict VDT of solid pulmonary nodules,which might obviously reduce manual interpreting time.
5.Visually amplification-free rapid detection of 2019-nCoV nucleic acid based on CRISPR/Cas13a
Nan ZHAO ; Yong QI ; Wei LI ; Yingqing MAO ; Wenjing LIU ; Yifang HAN ; Erxin ZHANG ; Yingjia XU ; Ruichen LYU ; Yuxin JIANG ; Yuzhen LAI ; Jiameng LI ; Wanpeng SHEN ; Yue SONG ; Yuexi LI
Chinese Journal of Laboratory Medicine 2024;47(6):658-666
Objective:Based on the specific cleavage and non-specific "trans-cleavage" activities of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein(CRISPR/Cas13), we established a visually amplification-free rapid detection technique of 2019-nCoV nucleic acid. This technique is easily processed with a low detection limit and good specificity.Methods:According to the 2019-nCoV gene sequence, specific CRISPR RNAs were screened and designed by bioinformatics analysis, and then synthesized as universal signal-strained RNA transcription targets in vitro to establish and optimize the reaction system. Moreover, the 2019-nCoV pseudoviral nucleic acid was used as a standard substance to evaluate the detection limit. A total of 65 positive samples were collected from various 2019-nCoV variants, while 48 negative samples included other clinically common respiratory pathogens, such as influenza A virus, influenza B virus, human parainfluenza virus, Klebsiella pneumonia, etc. All samples were tested by quantitative PCR (qPCR), digital PCR, and the method established in this study. The sensitivity and specificity of the newly established method were analyzed and evaluated. Results:With the newly established technique, the detection time for 2019-nCoV nucleic acid could be minimized to 6 minutes. In addition, the detection limit was 14 copies/μl when assisted by the displaying instrument, whereas it increased to 28 copies/μl with the naked eye. This technique had a sensitivity and specificity of 98.5% (66/67) and 100% (46/46) respectively, showing no statistically significant difference compared to the gold standard qPCR( P=1). Conclusions:This study has successfully established a CRISPR/Cas13a-based visually rapid detection technique for 2019-nCoV nucleic acid. This technique offers the advantages of a simple process, convenient operation, low environmental operating requirements, a detection limit close to qPCR, and a strong potential for on-site testing applications.
6.Risk factors for hypertensive disorders in pregnancy in women residing in high altitude areas and their impacts on maternal and infant outcomes
Tongying HAN ; Qiongbo YE ; Haiyun LONG ; Deji YUZHEN ; Chongchong YANG ; Zhen YU ; Yajuan WANG
Chinese Journal of Perinatal Medicine 2023;26(8):669-675
Objective:To investigate the incidence and risk factors of hypertensive disorders in pregnancy (HDP) in high altitude areas and their influence on maternal and infant outcomes.Methods:This was a retrospective case-control study. A total of 220 newborns were selected as the high altitude group, who were born to 216 mothers with HDP and admitted to the Neonatal Intensive Care Unit of the Lhasa People's Hospital from June 1, 2018, to June 1, 2020. The low altitude group consisted of 235 newborns born to 231 mothers with HDP and admitted to the Department of Neonatology of the Children's Hospital Affiliated to Beijing Capital Institute of Pediatrics from January 1, 2018, to December 31, 2021. Differences in the types of HDP between the two groups and the risk factors for the high incidence of preeclampsia-eclampsia and early-onset preeclampsia in high altitude area were analyzed. The influences of HDP in high and low altitude areas on maternal and infant outcomes were compared. Statistical analysis was performed using t-test, Mann-Whitney U test, Pearson Chi-square test, or continuous correction Chi-square test, and univariate and multivariate logistic regression analysis. Results:Maternal age and the proportions of primiparae and women of advanced age or having irregular prenatal examination were greater in the high altitude group than those in the low altitude group (all P<0.05). Besides, the incidence of early-onset preeclampsia, eclampsia, preeclampsia-eclampsia, and chronic hypertension complicated by preeclampsia were also higher in the high altitude group (all P<0.05). Multivariate logistic regression analysis showed that high altitude was a risk factor for the development of preeclampsia-eclampsia ( OR=4.437, 95% CI:2.582-7.626). Adverse pregnancy history ( OR=2.576, 95% CI:1.217-5.452) and irregular prenatal examination ( OR=2.862, 95% CI:1.412-5.800) were independent risk factors for early-onset preeclampsia in pregnant women in high altitude areas. Twin-pregnancy was a protective factor for early-onset preeclampsia in pregnant women in high altitude areas ( OR=0.183, 95% CI: 0.054-0.623). The incidence of maternal heart failure [7.9% (17/216) vs 0.4% (1/231), χ2=15.98], placental abruption [7.9% (17/216) vs 3.5% (8/231), χ2=4.11], hemolysis, elevated liver function and low platelet count syndrome [14.4% (31/216) vs 1.7% (4/231), χ2=24.64], premature delivery [86.1% (118/216) vs 73.6% (170/231), χ2=10.79], fetal growth restriction [52.3% (115/220) vs 18.7% (44/235), χ2=56.26], fetal distress [18.2% (40/220) vs 8.1% (19/235), χ2=10.26], neonatal asphyxia [29.5% (65/220) vs 11.1% (26/235), χ2=24.26], severe asphyxia [8.6% (19/220) vs 2.6% (6/235), χ2=8.10] and the proportion of neonates requiring mechanical ventilation within 24 h after birth [69.5% (153/220) vs 42.6% (100/235), χ2=33.54] as well as neonatal death within 7 d after birth [5.5% (12/220) vs 1.3% (3/235), χ2=6.22] in the high altitude group were significantly higher than those in the low altitude group (all P<0.05). Conclusion:High altitude is a risk factor for preeclampsia-eclampsia, and the adverse effects of HDP on mothers and infants are more severe in high altitude areas.
7.Predictors and influencing factors of poor prognosis of neonatal asphyxia in Tibet
Tongying HAN ; Yuzhen DEJI ; Chi PU ; Chongchong YANG ; Qiongbo YE ; Zhen YU
Journal of Chinese Physician 2022;24(5):696-699,706
Objective:To explore the prognostic indicators and influencing factors of neonatal asphyxia in Tibet.Methods:From March 2019 to March 2020, the clinical data of 126 asphyxiated newborns admitted to the neonatology department of Lhasa People's Hospital were retrospectively studied. According to the prognosis, they were divided into good prognosis group and poor prognosis group, and the clinical characteristics of the two groups were compared. The predictive value of Apgar score after birth, arterial blood gas analysis within 6 hours [pH, alkali residue (BE)] and their combined detection on the prognosis of asphyxiated newborns was analyzed. Logistic regression analysis was used to analyze the related factors affecting the prognosis of asphyxiated newborns.Results:31 cases (24.6%) in the poor prognosis group and 95 cases (75.4%) in the good prognosis group. The Apgar score at 1, 5 and 10 minutes after birth and pH and BE within 6 hours in the poor prognosis group were significantly lower than those in the good prognosis group (all P<0.05). The incidence of meconium stained amniotic fluid, fetal intrauterine distress, brain damage, lung damage, myocardial damage, kidney damage, abnormal coagulation function and multiple organ damage after asphyxia in the good prognosis group were significantly higher than those in the good prognosis group (all P<0.05). The Apgar score at the 1, 5 and 10 minutes after birth combined with arterial blood gas analysis (pH and BE) within 6 hours after birth had high predictive value for the prognosis of asphyxiated newborns, with the area under receiver operating characteristic (ROC) curve of 0.79, sensitivity of 68.4% and specificity of 90.3%. Multivariate regression analysis showed that meconium stained amniotic fluid ( OR=4.501, 95% CI: 1.262-16.056), lung damage ( OR=5.004, 95% CI: 1.007-24.866) and brain damage ( OR=10.786, 95% CI: 2.726-42.673) were independent risk factors affecting the prognosis of neonatal asphyxia ( P<0.05). Conclusions:In Tibet, there are many factors affecting the poor prognosis of neonatal asphyxia. High attention and intervention should be given to mothers in perinatal period and asphyxiated newborns in order to reduce the incidence of poor prognosis of neonatal asphyxia.
8.Clinical characteristics and risk factors of bronchopulmonary dysplasia in premature infants ≤32 weeks at high altitude and low altitude
Tongying HAN ; Yajuan WANG ; Qiongbo YE ; Yuzhen DEJI ; Haiyun LONG ; Zhen YU
Chinese Pediatric Emergency Medicine 2022;29(6):440-445
Objective:To analyze the risk factors and clinical features of premature infants with bronchopulmonary dysplasia(BPD)at high altitude in Tibet and low altitude in Beijing.Methods:A retrospective case-control study was conducted.The clinical data of children with gestational age ≤32 weeks admitted to the Department of Neonatology of Lhasa People′s Hospital(altitude of 3 600 m)and the Department of Neonatology of Children′s Hospital Affiliated to Capital Institute of Pediatrics(altitude of 50 m)from January 1, 2018 to December 31, 2021 were collected.Cases were divided into BPD group and non-BPD group.Premature infants with BPD were divided into high altitude group and low altitude group according to different altitudes.The clinical characteristics and high risk factors of BPD were analyzed.Results:There were 379 premature infants with gestational age ≤32 weeks, 351 were included in the study, including 110 cases in group and 241 cases in non-BPD group.There were 48 cases in high altitude group and 62 cases in low altitude group.The incidence of BPD in high altitude areas(Lhasa)was 38.7%(48/124), among which mild, moderate and severe BPD accounted for 75.0%(36 cases), 18.8%(9 cases)and 6.3%(3 cases), respectively.The incidence rates of BPD were 100%(2/2), 86.7%(13/15)and 38.7%(33/107) in gestational age <28 weeks, 28 to 29 + 6 weeks and 30 to 32 weeks, respectively.There was a statistically significant difference among different gestational age groups( χ2=19.696, P<0.001). The incidence of BPD in low altitude areas(Beijing)was 27.3%(62/227), among which mild, moderate and severe BPD accounted for 74.2%(46 cases), 4.8%(3 cases)and 21.0%(13 cases), respectively.The incidence rates of BPD in gestational age<28 weeks, 28 to 29 + 6 weeks and 30 to 32 weeks were 100%(15/15), 45.6%(36/79)and 8.3%(11/133), respectively.There was a statistically significant difference among different gestational age groups( χ2=77.474, P<0.001). The incidence of BPD in high altitude areas was significantly higher than that in low altitude areas( χ2=4.841, P=0.028). Multivariate regression analysis showed that high altitude( OR 146.893, 95% CI 19.044-1 133.064), birth weight( OR 0.996, 95% CI 0.993-0.999), asphyxia( OR 4.187, 95% CI 3.020-21.670), non-invasive mechanical ventilation( OR 1.171, 95% CI 1.106-1.240)and invasive mechanical ventilation( OR 1.198, 95% CI 1.065-1.347)were significantly correlated with the occurrence of BPD.The gestational age at birth, small for gestational age infant, the fraction of inspired oxygen and the incidence of pregnancy induced hypertension in pregnant women in high altitude group were higher than those in low altitude group( P<0.05). The incidence of patent ductus arteriosus, the use time of noninvasive and invasive mechanical ventilation, the length of hospital stay, the age of mother, the application of prenatal hormone and the twin ratio in high altitude group were significantly lower than those in low altitude group( P<0.05). Conclusion:High altitude in Tibet is a high-risk factor for the occurrence of BPD in preterm infants.Strengthening maternal health care in high altitude areas of Tibet and doing a good job in asphyxia resuscitation in delivery room may be important measures to reduce BPD in preterm infants.
9.The advantages of ulthera assisted resection of carotid body tumors
Yuzhen HE ; Yu LUN ; Han JIANG ; Xi LI ; Yuchen HE ; Shiyue WANG ; Shijie XIN ; Jian ZHANG
Chinese Journal of General Surgery 2022;37(7):496-498
Objective:To evaluate the use of ulthera in carotid body tumor resectionMethods:From Jun 2004 to Jun 2019 at the First Hospital of China Medical University. Forty-three shamblin grade Ⅱ or Ⅲ patients were retrospectively assigned to ulthera assisted carotid body tumor resection (26 cases) and traditional carotid body tumor resection (17 cases).Results:In ulthera assisted group, the average tumor diameter was (4.0±0.6) cm, compared to (3.9±0.9) cm in traditional carotid body tumor surgery group, P=0.875. The operation time of the two group was respectively (117.6±39.8) min and (149.4±55.0) min ( P=0.005), blood loss (145.7±70.6) ml vs. (194.1±80.7) ml ( P=0.006), hospital stay was (16.8±7.5) d vs. (22.7±13.0) d ( P=0.017), and following-up period was between 6 and 180 months. One patient relapsed in ulthera assisted group. The postoperative complications occurred in 8 and 7 cases respectively. Conclusion:Ulthera assisted carotid body tumor resection helps shorten operation time, hospital stay and decrease intraoperative blood loss.
10.Effects of lncRNA CDKN2B-AS1 targeting miR-98-5p on proliferation and invasion of lung cancer A549 cells
Siwei WANG ; Xiufang CAO ; Yuzhen XU ; Bo JIANG ; Han WANG ; Jie WEN
Chinese Journal of Endocrine Surgery 2021;15(3):299-303
Objective:To investigate the effects of long non-coding RNA (lncRNA) CDKN2B-AS1 targeting miR-98-5p on proliferation and invasion of lung cancer A549 cells.Methods:A549 cells cultured in vitro were divided into control group, pcDNA group (transfected with pcDNA) , CDKN2B-AS1 group (transfected with pcDNA CDKN2B-AS1) and double transfection group (transfected with pcDNA CDKN2B-AS1 and pcDNA miR-98-5p) . The expression of lncRNA CDKN2B-AS1, miR-98-5p and the protein expression of PCNA, MMP-9 in A549 cells were detected. The activity, clone number, cloning efficiency, and the number of invasive cells of A549 cells were detected.Results:Compared with pcDNA group, the expression level of lncRNA CDKN2B-AS1 [ (2.14±0.14) vs (1.03±0.10) ], OD value in each time points, clone number [ (314.60±18.13) vs (220.08±12.46) ], cloning efficiency [ (85.81±3.06) % vs (60.03±2.85) %], invasive cell number [ (233.30±18.98) vs (140.84±12.30) ], expression levels of PCNA [ (0.78±0.08) vs (0.48±0.07) ] and MMP-9 [ (0.75±0.06) vs (0.38±0.06) ] proteins in A549 cells in CDKN2B-AS1 group were significantly increased ( P<0.05) ; the expression level of miR-98-5p [ (0.23±0.03) vs (0.99±0.09) ] was significantly decreased ( P<0.05) ; compared with CDKN2B-AS1 group, there was no significant difference in the expression level of lncRNA CDKN2B-AS1 in A549 cells in double transfection group ( P>0.05) , while the expression level of miR-98-5p in A549 cells was significantly increased ( P<0.05) . The OD value in each time points, clone number, cloning efficiency, invasive cell number, expression levels of PCNA and MMP-9 proteins were significantly decreased ( P<0.05) . Conclusion:LncRNA CDKN2B-AS1 can promote the proliferation and invasion of lung cancer A549 cells by targetingly inhibiting the expression of miR-98-5p.

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