1.Clinical value of bone morphogenetic protein antagonist GREM1 as an immuno-active indicator in tumor microenvironment of gastric cancer
Xudong ZHANG ; Xiaoning LI ; Haikang CUI ; Xi YANG ; Lan YANG ; Wenjie ZHANG
Chinese Journal of Immunology 2024;40(4):741-751
Objective:To screen prognostic genes as indicators for predicting immunoactive in tumor microenvironment(TME)of gastric cancer(GC).Methods:Paraffin tissue specimens and corresponding paracancer tissues were collected from 55 patients with GC.Total 976 GC transcriptome RNA-Seqs and clinical datasets were obtained from TCGA and GEO databases.Infiltra-tion status of immune cells and Immune/Stormal scores were calculated using the ESTIMATE and CIBERSORT algorithm.R package"limma"was performed to selected differentially expressed genes(DEGs).Univariate Cox regression analysis was used to determine prognostic factors of DEGs.qRT-PCR was demonstrated to detect mRNA expression of the hub genes.Potential biological functions of GREM1 were investigated by GSEA.Correlations of GREM1 with immune signature molecules and drug susceptibility were investigated by TISIDB and CellMiner database.Results:Immune Score was positively correlated with improved outcomes of GC patients.A total of 40 shared TME-related DEGs were selected in the high and low groups of Immune Score and Stromal Score.Four survival-related DEGs were obtained by Cox analysis,which were GREM1,SFRP2,CYP1B1 and MGP.By comparing the difference of gene expres-sion in tumor and adjacent tissues and the degree of affinity with immune microenvironment,it was found that GREM1 was most likely to play a role in immune remodeling in TME;expression of GREM1 was positively correlated with clinicopathological features(TNM),while negatively correlated with survival time of GC patients.GSEA results showed that GREM1 high-expression group were mainly enriched in immune-related active genomes.Besides,GREM1 expression was positively correlated to M2 macrophages,while negatively correlated to CD8+T cells.GREM1 was also positively associated with immunosuppressor TGF-β1,immunopotentiator ENT-PD1,chemokine CCL14 as well as receptor CCR2.Moreover,GC patients with high expression of GREM1 might more sensitive to drug Vismodegib therapy.Conclusion:GREM1 can regard as an immunosuppressive clinical indicator in TME of GC.
2.Predictive model of endocrine drug resistance in hormone receptor-positive breast cancer based on ultrasound radiomics
Xiaoxue LIU ; Lei ZHANG ; Xudong ZHANG ; Wei FAN ; Qingxiang LI ; Xinran FANG ; Zihao QIN ; Junjia WANG ; Jiawei TIAN ; Hao CUI
Chinese Journal of Ultrasonography 2024;33(11):1000-1009
Objective:To establish an ultrasound radiomics model by integrating clinical, pathological, and conventional ultrasound features with radiomics characteristics, and to explore its clinical value in predicting endocrine resistance in hormone receptor(HR)-positive breast cancer.Methods:A retrospective analysis was performed on 478 patients with HR-positive breast cancer from January 2017 to December 2021 in the Second Affiliated Hospital of Harbin Medical University, of which 430 were resistant and 48 were sensitive. The clinical, pathological and immunohistochemical data and ultrasound images were collected.Firstly, the propensity score was used to process and match the data. Secondly, Logistic regression was used to screen clinical, pathological, and conventional ultrasound features associated with endocrine resistance. Then, PyRadiomics was used to extract the radiomic features of grayscale ultrasound images, and a series of methods such as Lasso regression were used to screen the radiomic features related to endocrine resistance. Seven machine learning methods such as random forest were used to build a radiomics model. Finally, clinical, pathological and ultrasound features were added to establish a clinical pathological model, a clinical pathological ultrasound model, a clinical pathological radiomics model and a combined model of the four features, and the model effectiveness was evaluated.Results:①Propensity score matching: 96 patients were matched, including 48 patients in the drug-resistant group and 48 patients in the sensitive group. ②Screening clinical pathological conventional ultrasound features related to endocrine resistance: lymph node metastasis, tumor diameter, posterior echo attenuation, and growth orientation were independent predictors of endocrine resistance (all P<0.05). ③Screening radiomics features related to endocrine resistance: 18 features such as Dependence Entropy. ④Establishing radiomics model: the machine learning model of random forest method (AUC=0.80) performed best. ⑤Radiomics model integrating clinical, pathological and conventional ultrasound features: the AUC of the clinical pathological model was 0.70, the AUC of the clinical pathological ultrasound model was 0.78, the AUC of the clinical pathological radiomics model was 0.82, and the AUC of the combined model was 0.86. Conclusions:The radiomics model established by the random forest method performs best in predicting endocrine resistance in HR-positive breast cancer. The model that integrates multiple features performs best in assessing endocrine resistance.which is expected to provide an objective basis for clinicians to predict endocrine resistance in HR-positive breast cancer.
3.Clinical analysis of 8 cases of transverse testicular ectopia
Gonglong LI ; Haoyu YAO ; Huali WANG ; Xudong SUN ; Qingdong QIAO ; Xichun CUI
Chinese Journal of Applied Clinical Pediatrics 2023;38(6):461-464
Objective:To study the clinical manifestations, diagnostic methods and therapeutic outcomes of transverse testicular ectopia (TTE).Methods:Clinical data of 8 cases of TTE treated in the Department of the First Urologic Surgery, Xinxiang Central Hospital and Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University from May 2004 to November 2018 were retrospectively analyzed.Clinical manifestations, diagnostic methods, surgical treatment and follow-up results of TTE were summarized.Results:The age of 8 cases of TTE was 1 year 5 months to 5 years.Among the 8 cases of TTE, 6 cases were involved with the left side and 2 cases with the right side.All patients were admitted due to scrotal emptiness.Three cases were combined with persistent Müllerian duct syndrome (PMDS) and 1 case combined with hypospadias.Preoperative diagnosis of TTE was definitely made in 5 cases, involving 4 cases diagnosed by ultrasound and 1 case diagnosed by magnetic resonance imaging.Laparoscopy was performed in 2 cases, including 1 case treated with laparoscopic scrotopexy, and the other one transferred to an open surgery of trans-septal orchiopexy due to poor development of the spermatic cord.Open surgery was performed in 6 cases, including 1 case with bilateral testicular fixation in the ipsilateral scrotum due to adhesion of spermatic cord closely, and 5 cases with trans-septal orchiopexy.Müllerian ducts residues were excised during surgery in 3 cases combined with PMDS.Postoperative wound infection or hematoma was not reported in all cases.Orchiepididymitis and the involvement of contralateral testes occurred in 1 case treated with trans-septal orchiopexy at 11 months postoperatively, which were relieved after anti-inflammatory treatment.All cases were postoperatively followed up for 3-48 months, and the development and blood supply of bilateral testes were detected normal by ultrasonography.Postoperative testicular atrophy was not reported.Conclusions:The possibility of TTE should be considered in patients with unilateral cryptorchidism combined with contralateral inguinal mass.Ultrasonography is preferred to the diagnosis of TTE.Laparoscopic surgery plays an important role in the diagnosis and treatment of TTE, which is helpful to identify abnormalities in the Müllerian duct structure.
4.Design and analysis of shoulder type exoskeleton stretcher for individual soldier.
Yunxiao MAO ; Haipo CUI ; Zhan ZHAO ; Xudong GUO ; Xin ZHANG ; Qian MA
Journal of Biomedical Engineering 2023;40(6):1200-1208
For the transportation process of rescuing wounded personnel on naval vessels, a new type of shoulder type exoskeleton stretcher for individual soldier was designed in this paper. The three-dimensional model of the shoulder type exoskeleton stretcher for individual soldier was constructed using three dimensional modeling software. Finite element analysis technique was employed to conduct statics simulation, modal analysis, and transient dynamics analysis on the designed exoskeleton stretcher. The results show that the maximum stress of the exoskeleton stretcher for walking on flat ground is 265.55 MPa, which is lower than the allowable strength of the fabrication material. Furthermore, the overall deformation of the structure is small. Modal analysis reveals that the natural frequency range of the exoskeleton stretcher under different gait conditions is 1.96 Hz to 28.70 Hz, which differs significantly from the swing frequency of 1 Hz during walking. This indicates that the designed structure can effectively avoid resonance. The transient dynamics analysis results show that the maximum deformation and stress of exoskeleton stretcher remain within the safety range, which meets the expected performance requirements. In summary, the shoulder type exoskeleton stretcher for individual soldier designed in this study can solve the problem of requiring more than 2 people to carry for the existing stretcher, especially suitable for narrow spaces of naval vessels. The research results of this paper can provide a new solution for the rescue of wounded personnel on naval vessels.
Humans
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Stretchers
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Military Personnel
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Shoulder
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Exoskeleton Device
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Walking
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Gait
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Biomechanical Phenomena
5.Preparation of specific yolk immunoglobulin against Fusarium and evaluation of its anti- Fusarium effect
Jing LIN ; Xing LIU ; Xudong PENG ; Cui LI ; Jianxin SUI ; Guiqiu ZHAO
Chinese Journal of Experimental Ophthalmology 2022;40(2):110-117
Objective:To prepare specific anti- Fusarium yolk immunoglobulin (IgY) and investigate its tolerance to temperature and pH and verify its antifungal effect against Fusarium. Methods:Eighteen 22-week-old Leghorn laying hens were selected and randomized into negative control group and experimental group according to the random number table method, with 9 hens in each group.The 2×10 7 colony forming units (CFU)/ml suspension of inactivated hyphae of Fusarium and Freund complete adjuvant was mixed in a 1∶1 ratio and emulsified.The hens in the experimental group were injected with 1 ml of the mixture to immunize and received 1 ml of Freund incomplete adjuvant as booster injection at two weeks after the initial injection.The egg yolk was collected from the 5th to 16th week after immunization.Specific anti- Fusarium IgY protein was prepared by salting out method using ammonium sulfate.The obtained protein solution was put into a freeze dryer and made into freeze-dried powder stored at 4 ℃.The hens in the negative control group were injected with 0.9% sodium chloride to prepare the non-specific antibody as the negative control.Bradford method was used to determine the concentration of specific egg IgY protein and the indirect enzyme-linked immunosorbent assay (ELISA) was employed to measure its titer.The 1×10 5 CFU/ml and 1×10 3 CFU/ml Fusarium suspension were cultured with different concentrations of IgY and phosphate buffered saline (PBS) for 4 days, and the absorbance value at 600 nm was measured.The co-incubated PBS/negative IgY with Fusarium solution was set as blank control/negative control accordingly.The concentration-killing curve of anti- Fusarium IgY against Fusarium was obtained.The specific IgY solution was diluted to 0.02 mg/ml with PBS pH 7.4, and the diluted specific IgY solution was placed into the water bath for 30 minutes at 30, 40, 50, 60, 70, 80, 90 ℃, respectively, and was cooled down to room temperature.The specific IgY solution was diluted to 0.02 mg/ml with PBS pH 1, pH 2, pH 3, pH 4, pH 5, pH 6, pH 7, pH 8, pH 9, pH 10, pH 11, pH 12, respectively, and the diluted specific IgY solution was placed at 4 ℃ for one hour.The activity of diluted specific IgY solution by different methods was measured by indirect ELISA, and the tolerance of IgY to various temperatures and pH was evaluated.Twelve 8-week-old SPF female C57BL/6 mice were selected and randomized into the PBS control group and specific IgY treatment group according to the random table method, with 6 mice in each group.The right eyes of the 12 mice were infected with Fusarium to establish mice model of fungal keratitis.One day after modeling, 200 mg/ml of anti- Fusarium IgY was dropped to the right eyes of mice in the specific IgY treatment group, and PBS was dropped to the right eyes of mice in the PBS control group.The corneas of mice in the two groups were observed under the slit lamp microscope at 1, 3 and 5 days following modeling, and the corneal ulcer was scored according to the grading scale for inflammation score.The use and care of experimental animals followed the Association for Research in Vision and Ophthalmology statement.This study protocol was approved by an Ethics Committee of The Affiliated Hospital of Qingdao University (No.QYFYWZLL26168). Results:The IgY protein concentration from the 5th to 16th week after immunization was 1.57, 2.89, 24.98, 25.09, 23.89, 25.78, 21.57, 21.37, 18.98, 15.78, 14.67, 12.67 mg/ml, respectively.The titer of IgY was increased from the 5th week, and it reached the highest titer 1∶10 000 at the 7th week, which could be maintained until the 12th week after immunization before it dropped gradually.The concentration-killing curve showed that compared with the blank control group and negative control group, Fusarium grew slowly in the specific IgY treatment group.The specific IgY with a titer greater than 1∶10 000 had thermal stability below 60 ℃.The activity of specific IgY was highest at pH 4 to 6, which could be maintained above 70% at pH 3 to 9 and was further reduced with the decrease or increase of pH.At 1, 3 and 5 days after Fusarium infection, the inflammation scores were 3.50±0.55, 7.33±0.82, 4.00±0.63 in the PBS control group, and 3.33±0.82, 4.17±0.75, 2.50±0.55 in the specific IgY treatment group.There was a statistically significant overall difference in inflammation scores at various time points between the two groups ( Fgroup=247.35, P<0.05; Ftime=23.19, P<0.05). At 3 and 5 days after Fusarium infection, there was a smaller ulcer area and decreased inflammation scores in the specific IgY treatment group compared with the PBS control group, and the differences were statistically significant (all at P<0.05). Conclusions:The high titer specific IgY can be successfully prepared by salting out method using ammonium sulfate, which is with high stability, tolerance to temperature and pH.Moreover, it can alleviate the severity of corneal ulcers and reduce inflammation scores in the mouse model of fungal keratitis.
6.Status of HVPG clinical application in China in 2021
Wen ZHANG ; Fuquan LIU ; Linpeng ZHANG ; Huiguo DING ; Yuzheng ZHUGE ; Jitao WANG ; Lei LI ; Guangchuan WANG ; Hao WU ; Hui LI ; Guohong CAO ; Xuefeng LU ; Derun KONG ; Lin SUN ; Wei WU ; Junhui SUN ; Jiangtao LIU ; He ZHU ; Dongliang LI ; Wuhua GUO ; Hui XUE ; Yu WANG ; Jiancuo GENGZANG ; Tian ZHAO ; Min YUAN ; Shirong LIU ; Hui HUAN ; Meng NIU ; Xin LI ; Jun MA ; Qingliang ZHU ; Wenbo GUO ; Kunpeng ZHANG ; Xiaoliang ZHU ; Birun HUANG ; Jianan LI ; Weidong WANG ; Hongfeng YI ; Qi ZHANG ; Long GAO ; Guo ZHANG ; Zhongwei ZHAO ; Kai XIONG ; Zexin WANG ; Hong SHAN ; Mingsheng LI ; Xueqiang ZHANG ; Haibin SHI ; Xiaogang HU ; Kangshun ZHU ; Zhanguo ZHANG ; Hong JIANG ; Jianbo ZHAO ; Mingsheng HUANG ; Wenyong SHEN ; Lin ZHANG ; Feng XIE ; Zhiwei LI ; Changlong HOU ; Shengjuan HU ; Jianwei LU ; Xudong CUI ; Ting LU ; Shaoqi YANG ; Wei LIU ; Junping SHI ; Yanming LEI ; Jinlun BAO ; Tao WANG ; Weixin REN ; Xiaoli ZHU ; Yong WANG ; Lei YU ; Qiang YU ; Huiling XIANG ; Wenqiang LUO ; Xiaolong QI
Chinese Journal of Hepatology 2022;30(6):637-643
Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.
7.Persistence and adherence to secondary preventive medication in ischemic stroke patients and its influence on prognosis
Wenjian LI ; Xudong PAN ; Jing WANG ; Guangli CUI ; Aijun MA
Chinese Journal of Neurology 2017;50(3):178-183
Objective To investigate the status of medication adherence of secondary prevention after acute ischemic stroke and influence on prognosis in Qingdao area , including antithrombotic drugs , lipid-lowering drugs , antihypertensive drugs and glucose-lowering drugs , to provide the basis for making medical policy.Methods We examined patients with acute cerebral infarction and transient ischemic attack in the Department of Neurology of Affiliated Hospital of Qingdao University from December 2014 to January 2016.Patients′medication status and recurrence of stroke events were registered by using telephone and clinic follow-up within six months after the patients discharged from hospital .The standard of good and bad drug adherence was as follows:good adherence was defined as proportion of days covered ( PDC) ≥80%, bad adherence was defined as PDC <80%.SPSS 19.0 statistical software was used to analyze the influence factors of medication adherence and the influence of medication adherence on prognosis .Results Finally, 444 cases (88.62%) were analyzed.A total of 352 cases (79.28%) had high medication adherence at six months after discharging from hospital .The following factors can improve the adherence of drug treatment:history of diabetes (108 cases (30.68%) in good medication adherence group , 16 cases (17.39%) in poor medication adherence group,χ2 =6.401, P=0.011), having employee health insurance (186 cases (52.84%) in good medication adherence group , 33 cases (35.87%) in poor medication adherence group ,χ2 =8.405, P=0.004), endovascular stent implantation (29 cases(8.24%) in good medication adherence group, 0 case in poor medication adherence group ,χ2 =8.109, P=0.004), staying in hospital more than 10 days ( 230 cases ( 65.34%) in good medication adherence group , 49 cases ( 53.26%) in poor medication adherence group ,χ2 =4.558, P=0.033).Six months later , the modified Rankin Scale ( mRS) score of poor medication adherence group was significantly higher than that in good adherence group ( mRS score≥3,50 cases (14.20%) in good medication adherence group , 22 cases (23.91%) in poor medication adherence group,χ2 =5.060, P=0.024) .After six months, a total of 13 cases had recurrent cerebral infarction, with two cases ( 0.57%) in good adherence group , 11 cases ( 11.96%) in poor adherence group.High medication adherence was an independent protective factor of recurrent stroke ( OR=0.042, 95%CI 0.008 -0.210, P<0.01 ) .At one, three, six months after discharging from hospital , the medication adherence of antihypertensive and glucose-lowering drugs was better than that of antiplatelet agents and lipid-lowering drugs (all P<0.05).Conclusions The persistence and adherence to secondary preventive medication in ischemic stroke patients was generally well at 6th month after discharging from hospital.History of diabetes , having employee health insurance , stent implantation and longer hospital stay are the influencing factors to high medication adherence .High medication adherence is an independent protective factor for ischemic stroke recurrence .The medication adherence of antihypertensive and glucose-lowering drugs is better than that of antithrombotic drugs and lipid-lowering drugs.
8.Action observation therapy can improve upper extremity motor function after stroke
Fang SHEN ; Hu LIU ; Xudong GU ; Ming ZENG ; Jianming FU ; Jing WANG ; Yao CUI ; Meihong ZHU
Chinese Journal of Physical Medicine and Rehabilitation 2017;39(3):184-188
Objective To explore the effects of action observation therapy on upper-extremity motor function after ischemic stroke and on the motor cortex using functional magnetic resonance imaging (fMRI).Methods Forty patients with ischemic stroke were randomly assigned to an observational group (n =20) or a control group (n =20).Both groups received conventional rehabilitation,while the observational group was additionally provided with action observation therapy for 8 weeks.Both groups were assessed using the Fugl-Meyer assessment (FMA) and the Barthel index (BI) before and after the 8 weeks of treatment and functional magnetic resonance imaging was performed before treatment.Two months after the treatment,nine patients of the experimental group and 8 of the control group who continued to receive their respective treatments after discharge were again assessed using functional magnetic resonance imaging.Results After the treatment the average FMA score and BI score of both the observational group and the control group had increased significantly.The increase in the average FMA score of the observational group was significantly greater than that of the control group.However,there was no significant difference between the two groups in the increases in BI score after 8 weeks of treatment.The fMRI results showed that there was a significantly greater rise in activity in the bilateral precentral gyrus,parietal lobe and the supplementary motor area of the patients in the observational group after the treatment compared with the control group.Conclusion Action observation therapy can improve upper extremity motor function and performance in the activities of daily living after ischemic stroke and induce changes in the excitability of the cerebral motor cortex.
9.A finite element model of the knee joint for total knee arthroplasty: Construction and biomechanic analysis
Yuefu DONG ; Zhifang MOU ; Shengbo JIANG ; Xudong LIU ; Weidong HE ; Bing WANG ; Jian LIU ; Jizheng CUI
Journal of Medical Postgraduates 2017;30(8):839-843
Objective Few studies are reported on the construction of a finite element model of human complex knee joint using multimodality CT and MRI images.In this study, we developed a finite element model of the knee joint for total knee arthroplasty (TKA) using matched and fused CT and MRI data, hoping to provide a useful tool for the simulation study of knee joint biomechanics of TKA.Methods The CT and MRI image data about an intact knee of a 26-year-old male volunteer were imported into the Mimics software for the establishment of 3D models of bony and soft-tissue structures.A complete knee model was developed following the registration and fusion of the constructed 3D models based on the external landmarks.After the simulated implantation of TKA components, a finite element model of the TKA knee was constructed with the Hypermesh software.Then the finite element model was analyzed following the definition of its material behavior, boundary conditions and loading.Results The finite element model of the TKA knee, which was composed of bones, ligaments, components, polyethylene insert and bone cement, was developed from CT-MRI image registration and fusion and maintained its important spatial relationship among different structures in the TKA knee.The results obtained from the finite element analysis showed the characteristics of stress distribution in the TKA knee.Conclusion The finite element model of the knee joint for TKA can be established by matching and fusing CT and MRI image data, which can be employed as a useful tool for the study of knee joint biomechanics of TKA.
10.Action observation therapy improves upper extremity motor function after stroke
Jing WANG ; Ming ZENG ; Minmin JIN ; Meixia YANG ; Yao CUI ; Meihong ZHU ; Ming SHI ; Liang LI ; Xudong GU
Chinese Journal of Physical Medicine and Rehabilitation 2017;39(7):503-506
Objective To explore the effects of action observation therapy on upper-extremity motor function and ability in the activities of daily living after cerebral infarction.Methods Forty-one cerebral infarction survivors were randomly assigned to an observation group (n =21) or a control group (n =20).Both groups were given the conventional rehabilitation treatment,while the observation group additionally received action observation therapy 20 mins per day,6 times per week for 8 weeks.Before and after the 8 weeks of treatment,both groups were assessed using the Fugl-Meyer assessment (FMA),Wolf's motor function test (WMFT) and the modified Barthel index (MBI).Results Before the intervention there was no significant difference between the groups in any of the measurements.After the 8 weeks of treatment,all of the results in the treatment group were significantly better,on average,than those of the control group.Conclusions Action observation therapy can improve upper-extremity motor function and ability in the activities of daily living after stroke.

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