1.Clinical study of CT-guided hematoma puncture drainage surgery combined with high-dose urokinase in treating hypertensive intracerebral hemorrhage
Xiaoxuan MA ; Weisheng RUAN ; Biao SHI ; Chunlong ZHAO ; Chao LYU
China Medical Equipment 2025;22(2):43-46,53
Objective:To observe the clinical effect of computed tomography(CT)-guided hematoma puncture drainage surgery combined with high-dose(≥50 000 U)urokinase in treating hypertensive intracerebral hemorrhage.Methods:The case data of a total of 90 patients with hypertensive intracerebral hemorrhage who underwent treatment in Zhangjiakou First Hospital from January 2022 to January 2023 were retrospectively selected as the study subjects.They were divided into a control group and an observation group using the average method,with 45 cases in each group.The conventional group received CT-guided hematoma puncture drainage surgery combined with conventional dose urokinase(20 000 U),while the observation group received CT-guided hematoma puncture drainage surgery combined with high-dose urokinase(50 000 U),with a 6-month follow-up for all patients.The changes of hematoma volume,length of hospital stay,levels of inflammatory indicators,the levels of hemodynamics,clinical efficacy,and incidence of postoperative complications after treatment between two groups were analyzed and compared.Results:After treatment,the hematoma volume at the 1st day[(34.64±5.53)mm3]and the 7th day[(34.64±5.53)mm3]post surgery of observation group were significantly lower than those[(44.57±6.85)mm3 and(16.64±3.24)mm3]of conventional group,and the differences of them between the two groups were statistically significant(t=7.567,10.570,P<0.05),respectively.The length of hospital stay of observation group[(16.86±6.63)d]was significantly lower than that of the control group[(23.47±10.34)d](t=3.610,P<0.05).The levels of matrix metalloproteinase-9(MMP-9),interleukin-6(IL-6),C-reactive protein(CRP),tumor necrosis factor-α(TNF-α)at 7th days post surgery of observation group were significantly lower than those of conventional group,and the differences of them between the two groups were statistically significant(t=5.826,10.202,7.661,2.724,P<0.05),respectively.The blood flow levels of middle cerebral artery(MCA),anterior cerebral artery(ACA),and posterior cerebral artery(PCA)after surgery in observation group were significantly higher than those in conventional group(t=2.833,3.329,3.973,P<0.05),respectively.The effective rate of treatment in observation group(95.56%)was significantly higher than that in conventional group(80.00%),and the difference was significant(x2=5.075,P<0.05).There was no significant difference in the incidence of postoperative complications between the two groups(P>0.05).Conclusion:CT-guided hematoma puncture drainage surgery combined with high-dose urokinase can significantly increase the dissolution rate of hematoma,and reduce the body's inflammatory response,and improve cerebral hemodynamic indicators,and effectively enhance clinical efficacy in treating hypertensive intracerebral hemorrhage,which have better treatment safety.
2.Comparison of electroacupuncture and dexamethasone on lung development impairment in offspring rats induced by prenatal nicotine exposure
Tingting GUO ; Bo JI ; Yang FANG ; Yitian LIU ; Hewen LI ; Xiaoxuan LIU ; Liyu LIU ; Ling ZHANG ; Wenxuan LIU ; Ye QUAN ; Bohan MA ; Sakurai REIKO ; Virender Kumar REHAN
Journal of Beijing University of Traditional Chinese Medicine 2025;48(8):1167-1175
Objective To investigate and compare the effects of electroacupuncture and dexamethasone on lung function and histomorphology and behavior in the offspring of perinatal nicotine exposure(PNE)rats.Methods Twenty-four pregnant Sprague-Dawley rats were randomly divided into control,model,electroacupuncture shallow needling,and dexamethasone groups using the random number table method(n=6 rats per group).A pulmonary dysplasia model in offspring rats with PNE was prepared by cervicodorsal subcutaneous injection with nicotine,and successful establishment of the model was confirmed by demonstrating statistically significant differences in growth parameters,lung function,and lung morphology compared to the control group.From the sixth day of maternal conception,the control group received cervicodorsal subcutaneous injection with 0.9%sodium chloride solution(1 mg/kg once per day),and the remaining groups were similarly injected with nicotine(1 mg/kg once per day).Concurrent with the nicotine injections,the electroacupuncture shallow needling group received electroacupuncture interventions at the"Zusanli"(ST 36)acupoint on both sides once a day for 20 min.In contrast,the offspring rats in the dexamethasone group received intraperitoneal dexamethasone injections from postnatal day 8(1.5 mg/kg once per day for 3 days),with a later dose of 0.75 mg/kg once per day for 4 days.Following successful model establishment,four offspring per rat were retained in each group using the random number table method.Until the 21st day after the birth of the offspring,using the random number table method,one offspring randomly selected from the four retained offspring per rat in each group was assigned to growth parameter assessment including body weight,lung weight,and lung index;simultaneously,one offspring was randomly selected for pulmonary function which was detected by a small animal pulmonary function machine,with the parameters of forced vital capacity(FVC),functional residual capacity(FRC),dynamic lung compliance(Cdyn),peak expiratory flow(PEF),peak inspiratory flow(PIF),and airway resistance(RL);concurrently,one offspring was randomly selected for hematoxylin and eosin staining to observe the histomorphology of the lung tissue,alveolar numbers,and mean alveolar septal thickness;additionally,one offspring was randomly selected for Morris water maze testing to evaluate the effects of the two intervention methods on learning and memory capabilities in offspring rats with PNE.Results Compared with the control group,the body weight,lung weight,lung index,FVC,PEF,FRC,Cdyn,alveolar number,platform crossing times,target quadrant time percentage,and target quadrant path percentage in the Morris water maze experiment were significantly decreased in the offspring rats of the model group(P<0.01).In contrast,PIF,RL,average thickness of alveolar septa,and latency of the Morris water maze experiment were significantly increased in the offspring rats of the model group(P<0.01).Compared with the model group,both electroacupuncture shallow needling group and dexamethasone group exhibited significant increases in body weight,lung weight,lung index,FVC,PEF,FRC,Cdyn,and alveolar numbers(P<0.05,P<0.01),along with significant decreases in PIF,RL values,and mean alveolar septal thickness(P<0.01).However,in the Morris water maze experiment,compared with the model group,the electroacupuncture shallow needling group demonstrated significantly more platform crossing times and a higher target quadrant time percentage and target quadrant path percentage(P<0.01),coupled with reduced latency period(P<0.01),whereas the dexamethasone group showed no significant differences compared to the model group.Compared to the electroacupuncture shallow needling group,the dexamethasone group showed significantly less platform crossing times and a lower target quadrant time percentage and target quadrant path percentage,coupled with increased latency period(P<0.01).Conclusion Both electroacupuncture and dexamethasone demonstrated protective effects on lung development in PNE offspring rats by ameliorating lung histomorphology and pulmonary function.However,offspring receiving late,small-dose,short-course dexamethasone exhibited inferior learning and memory capabilities,whereas the electroacupuncture group showed significantly superior cognitive performance compared to the dexamethasone group.
3.Identification of influencing factors for falls in hospitalized patients with cardiovascular diseases and construction of a prediction model based on machine learning technology
Jing TAO ; Lei TAO ; Xiaoxuan GONG ; Bingsen HUANG ; Yueting LIU ; Min ZHANG ; Yujiao MA ; Keyu CHEN
Chinese Journal of Practical Nursing 2025;41(33):2607-2612
Objective:To assess the fall risk of hospitalized patients with cardiovascular diseases, analyze the related influencing factors, and construct a prediction model based on machine learning technology, so as to provide a basis for the fall management of hospitalized patients with cardiovascular diseases.Methods:This study was a retrospective cohort study. A total of 450 patients admitted to the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University from June 2017 to June 2024 were selected as the research objects by convenience sampling method. By reviewing electronic medical records, trained nurses extracted the patients' general information and Activities of Daily Living Scale (ADL) scores during hospitalization. Lasso regression was used to screen risk factors, and machine learning libraries were used to construct support vector machine (SVM), decision tree, XGBoost, and neural network models. Bootstrap resampling method and area under the curve (AUC) were used to verify the model performance.Results:Among the 450 patients, there were 261 males and 189 females, with a mean age of (66.0 ± 8.4) years. Among them, 90 patients fell during hospitalization and 360 patients did not fall. The results of Lasso regression showed that ADL score ≤60 points, use of hypnotics, hypokalemia, nighttime toilet visits≥2 times, use of antihypertensive drugs, no caregiver, and history of atrial fibrillation were all risk factors for falls in hospitalized patients with cardiovascular diseases (regression coefficients ranging from 0.61 to 1.20, all P<0.01). Among the machine learning models, XGBoost had the best comprehensive performance (AUC=0.98), which was better than decision tree (AUC=0.66), SVM (AUC=0.95), and neural network (AUC=0.87). Conclusions:The fall risk of hospitalized patients with cardiovascular diseases is jointly affected by physiological, medication and behavioral factors, and the XGBoost model can effectively identify high-risk groups. In actual clinical work, nursing strategies can be optimized in combination with risk factors, and the application of intelligent fall prediction and assessment tools can be promoted.
4.Summary of the best evidence for frailty management during postoperative chemotherapy in gastric cancer patients
Chunxue MA ; Xiaoxuan CHEN ; Yanqiong ZHANG ; Xiaojing CHEN ; Zhangshuang LIN ; Yaoyao ZHU ; Wenjun LIN ; Limin XIA
Chinese Journal of Modern Nursing 2025;31(16):2160-2168
Objective:To summarize the best evidence for frailty management in patients undergoing postoperative chemotherapy for gastric cancer, so as to provide reference for alleviating patient frailty.Methods:Guidelines, expert consensus, evidence summaries, systematic reviews, and randomized controlled trials and other articles on the frailty management of patients with postoperative chemotherapy for gastric cancer were electronically searched in computerized decision-making systems such as UpToDate, BMJ Best Practice, and Guidelines International Network, in comprehensive databases such as PubMed, Embase, and Web of Science, and in the websites of professional societies. The search period was from database establishment to September 15, 2024. Two researchers independently screened the literature and evaluated the quality of the included literature, combining professional judgment to extract and summarize the best evidence.Results:A total of 18 papers were included, including two clinical decisions, one evidence summary, eight guidelines, two expert consensus, one systematic review, one randomized controlled trial, two quasi-experimental studies, and one observational study. The best evidence included a total of 34 pieces in seven aspects of comprehensive screening, nursing plan construction, preoperative prehabilitation, nutritional interventions, Chinese medicine interventions, exercise interventions, and psychological interventions for frailty.Conclusions:The summary of the best evidence for frailty management in patients undergoing postoperative chemotherapy for gastric cancer may provide an evidence-based basis for frailty interventions by clinical medical and staff.
5.Comparison of electroacupuncture and dexamethasone on lung development impairment in offspring rats induced by prenatal nicotine exposure
Tingting GUO ; Bo JI ; Yang FANG ; Yitian LIU ; Hewen LI ; Xiaoxuan LIU ; Liyu LIU ; Ling ZHANG ; Wenxuan LIU ; Ye QUAN ; Bohan MA ; Sakurai REIKO ; Virender Kumar REHAN
Journal of Beijing University of Traditional Chinese Medicine 2025;48(8):1167-1175
Objective To investigate and compare the effects of electroacupuncture and dexamethasone on lung function and histomorphology and behavior in the offspring of perinatal nicotine exposure(PNE)rats.Methods Twenty-four pregnant Sprague-Dawley rats were randomly divided into control,model,electroacupuncture shallow needling,and dexamethasone groups using the random number table method(n=6 rats per group).A pulmonary dysplasia model in offspring rats with PNE was prepared by cervicodorsal subcutaneous injection with nicotine,and successful establishment of the model was confirmed by demonstrating statistically significant differences in growth parameters,lung function,and lung morphology compared to the control group.From the sixth day of maternal conception,the control group received cervicodorsal subcutaneous injection with 0.9%sodium chloride solution(1 mg/kg once per day),and the remaining groups were similarly injected with nicotine(1 mg/kg once per day).Concurrent with the nicotine injections,the electroacupuncture shallow needling group received electroacupuncture interventions at the"Zusanli"(ST 36)acupoint on both sides once a day for 20 min.In contrast,the offspring rats in the dexamethasone group received intraperitoneal dexamethasone injections from postnatal day 8(1.5 mg/kg once per day for 3 days),with a later dose of 0.75 mg/kg once per day for 4 days.Following successful model establishment,four offspring per rat were retained in each group using the random number table method.Until the 21st day after the birth of the offspring,using the random number table method,one offspring randomly selected from the four retained offspring per rat in each group was assigned to growth parameter assessment including body weight,lung weight,and lung index;simultaneously,one offspring was randomly selected for pulmonary function which was detected by a small animal pulmonary function machine,with the parameters of forced vital capacity(FVC),functional residual capacity(FRC),dynamic lung compliance(Cdyn),peak expiratory flow(PEF),peak inspiratory flow(PIF),and airway resistance(RL);concurrently,one offspring was randomly selected for hematoxylin and eosin staining to observe the histomorphology of the lung tissue,alveolar numbers,and mean alveolar septal thickness;additionally,one offspring was randomly selected for Morris water maze testing to evaluate the effects of the two intervention methods on learning and memory capabilities in offspring rats with PNE.Results Compared with the control group,the body weight,lung weight,lung index,FVC,PEF,FRC,Cdyn,alveolar number,platform crossing times,target quadrant time percentage,and target quadrant path percentage in the Morris water maze experiment were significantly decreased in the offspring rats of the model group(P<0.01).In contrast,PIF,RL,average thickness of alveolar septa,and latency of the Morris water maze experiment were significantly increased in the offspring rats of the model group(P<0.01).Compared with the model group,both electroacupuncture shallow needling group and dexamethasone group exhibited significant increases in body weight,lung weight,lung index,FVC,PEF,FRC,Cdyn,and alveolar numbers(P<0.05,P<0.01),along with significant decreases in PIF,RL values,and mean alveolar septal thickness(P<0.01).However,in the Morris water maze experiment,compared with the model group,the electroacupuncture shallow needling group demonstrated significantly more platform crossing times and a higher target quadrant time percentage and target quadrant path percentage(P<0.01),coupled with reduced latency period(P<0.01),whereas the dexamethasone group showed no significant differences compared to the model group.Compared to the electroacupuncture shallow needling group,the dexamethasone group showed significantly less platform crossing times and a lower target quadrant time percentage and target quadrant path percentage,coupled with increased latency period(P<0.01).Conclusion Both electroacupuncture and dexamethasone demonstrated protective effects on lung development in PNE offspring rats by ameliorating lung histomorphology and pulmonary function.However,offspring receiving late,small-dose,short-course dexamethasone exhibited inferior learning and memory capabilities,whereas the electroacupuncture group showed significantly superior cognitive performance compared to the dexamethasone group.
6.Clinical study of CT-guided hematoma puncture drainage surgery combined with high-dose urokinase in treating hypertensive intracerebral hemorrhage
Xiaoxuan MA ; Weisheng RUAN ; Biao SHI ; Chunlong ZHAO ; Chao LYU
China Medical Equipment 2025;22(2):43-46,53
Objective:To observe the clinical effect of computed tomography(CT)-guided hematoma puncture drainage surgery combined with high-dose(≥50 000 U)urokinase in treating hypertensive intracerebral hemorrhage.Methods:The case data of a total of 90 patients with hypertensive intracerebral hemorrhage who underwent treatment in Zhangjiakou First Hospital from January 2022 to January 2023 were retrospectively selected as the study subjects.They were divided into a control group and an observation group using the average method,with 45 cases in each group.The conventional group received CT-guided hematoma puncture drainage surgery combined with conventional dose urokinase(20 000 U),while the observation group received CT-guided hematoma puncture drainage surgery combined with high-dose urokinase(50 000 U),with a 6-month follow-up for all patients.The changes of hematoma volume,length of hospital stay,levels of inflammatory indicators,the levels of hemodynamics,clinical efficacy,and incidence of postoperative complications after treatment between two groups were analyzed and compared.Results:After treatment,the hematoma volume at the 1st day[(34.64±5.53)mm3]and the 7th day[(34.64±5.53)mm3]post surgery of observation group were significantly lower than those[(44.57±6.85)mm3 and(16.64±3.24)mm3]of conventional group,and the differences of them between the two groups were statistically significant(t=7.567,10.570,P<0.05),respectively.The length of hospital stay of observation group[(16.86±6.63)d]was significantly lower than that of the control group[(23.47±10.34)d](t=3.610,P<0.05).The levels of matrix metalloproteinase-9(MMP-9),interleukin-6(IL-6),C-reactive protein(CRP),tumor necrosis factor-α(TNF-α)at 7th days post surgery of observation group were significantly lower than those of conventional group,and the differences of them between the two groups were statistically significant(t=5.826,10.202,7.661,2.724,P<0.05),respectively.The blood flow levels of middle cerebral artery(MCA),anterior cerebral artery(ACA),and posterior cerebral artery(PCA)after surgery in observation group were significantly higher than those in conventional group(t=2.833,3.329,3.973,P<0.05),respectively.The effective rate of treatment in observation group(95.56%)was significantly higher than that in conventional group(80.00%),and the difference was significant(x2=5.075,P<0.05).There was no significant difference in the incidence of postoperative complications between the two groups(P>0.05).Conclusion:CT-guided hematoma puncture drainage surgery combined with high-dose urokinase can significantly increase the dissolution rate of hematoma,and reduce the body's inflammatory response,and improve cerebral hemodynamic indicators,and effectively enhance clinical efficacy in treating hypertensive intracerebral hemorrhage,which have better treatment safety.
7.Identification of influencing factors for falls in hospitalized patients with cardiovascular diseases and construction of a prediction model based on machine learning technology
Jing TAO ; Lei TAO ; Xiaoxuan GONG ; Bingsen HUANG ; Yueting LIU ; Min ZHANG ; Yujiao MA ; Keyu CHEN
Chinese Journal of Practical Nursing 2025;41(33):2607-2612
Objective:To assess the fall risk of hospitalized patients with cardiovascular diseases, analyze the related influencing factors, and construct a prediction model based on machine learning technology, so as to provide a basis for the fall management of hospitalized patients with cardiovascular diseases.Methods:This study was a retrospective cohort study. A total of 450 patients admitted to the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University from June 2017 to June 2024 were selected as the research objects by convenience sampling method. By reviewing electronic medical records, trained nurses extracted the patients' general information and Activities of Daily Living Scale (ADL) scores during hospitalization. Lasso regression was used to screen risk factors, and machine learning libraries were used to construct support vector machine (SVM), decision tree, XGBoost, and neural network models. Bootstrap resampling method and area under the curve (AUC) were used to verify the model performance.Results:Among the 450 patients, there were 261 males and 189 females, with a mean age of (66.0 ± 8.4) years. Among them, 90 patients fell during hospitalization and 360 patients did not fall. The results of Lasso regression showed that ADL score ≤60 points, use of hypnotics, hypokalemia, nighttime toilet visits≥2 times, use of antihypertensive drugs, no caregiver, and history of atrial fibrillation were all risk factors for falls in hospitalized patients with cardiovascular diseases (regression coefficients ranging from 0.61 to 1.20, all P<0.01). Among the machine learning models, XGBoost had the best comprehensive performance (AUC=0.98), which was better than decision tree (AUC=0.66), SVM (AUC=0.95), and neural network (AUC=0.87). Conclusions:The fall risk of hospitalized patients with cardiovascular diseases is jointly affected by physiological, medication and behavioral factors, and the XGBoost model can effectively identify high-risk groups. In actual clinical work, nursing strategies can be optimized in combination with risk factors, and the application of intelligent fall prediction and assessment tools can be promoted.
8.Summary of the best evidence for frailty management during postoperative chemotherapy in gastric cancer patients
Chunxue MA ; Xiaoxuan CHEN ; Yanqiong ZHANG ; Xiaojing CHEN ; Zhangshuang LIN ; Yaoyao ZHU ; Wenjun LIN ; Limin XIA
Chinese Journal of Modern Nursing 2025;31(16):2160-2168
Objective:To summarize the best evidence for frailty management in patients undergoing postoperative chemotherapy for gastric cancer, so as to provide reference for alleviating patient frailty.Methods:Guidelines, expert consensus, evidence summaries, systematic reviews, and randomized controlled trials and other articles on the frailty management of patients with postoperative chemotherapy for gastric cancer were electronically searched in computerized decision-making systems such as UpToDate, BMJ Best Practice, and Guidelines International Network, in comprehensive databases such as PubMed, Embase, and Web of Science, and in the websites of professional societies. The search period was from database establishment to September 15, 2024. Two researchers independently screened the literature and evaluated the quality of the included literature, combining professional judgment to extract and summarize the best evidence.Results:A total of 18 papers were included, including two clinical decisions, one evidence summary, eight guidelines, two expert consensus, one systematic review, one randomized controlled trial, two quasi-experimental studies, and one observational study. The best evidence included a total of 34 pieces in seven aspects of comprehensive screening, nursing plan construction, preoperative prehabilitation, nutritional interventions, Chinese medicine interventions, exercise interventions, and psychological interventions for frailty.Conclusions:The summary of the best evidence for frailty management in patients undergoing postoperative chemotherapy for gastric cancer may provide an evidence-based basis for frailty interventions by clinical medical and staff.
9.Establishment of C57/B6-L and A549 cell lines stably expressing circLAMP3
Fuzai CHEN ; Conghui ZHAO ; Xiaoxuan ZHANG ; Chunping ZHANG ; Jiacheng HUANG ; Jilong CHEN ; Shujie MA
Chinese Journal of Veterinary Science 2024;44(9):2010-2016
This study aims to construct C57/B6-L and A549 cell lines that stably overexpress circu-lar RNA LAMP3(circLAMP3),laying the foundation for further research on the biological func-tions of circLAMP3.Total RNA was extracted and reverse transcripted into cDNA from C57/B6-L and A549 cells to amplify the full-length sequence of circLAMP3.Then,the fragments of cir-cLAMP3 were ligated into pLC5-ciR vector to obtain pLC5-Mouse-circLAMP3 and pLC5-Human-circLAMP3 recombinant plasmids.The lentiviruses expressing circLAMP3 were packaged on tran-sient transfected HEK293T cells.C57/B6-L and A549 cells were infected with lentiviruses to gen-erate cell lines overexpressing circLAMP3 through puromycin screening.To verify the overexpres-sion efficiency of circLAMP3 of cell lines,we performed the fluorescence microscopy,PCR amplifi-cation,quantitative PCR(qPCR),and Sanger sequencing experiments.The results indicated that the overexpression plasmids of pLC5-Mouse-circLAMP3 and pLC5-Human-circLAMP3 were suc-cessfully constructed.Strong green fluorescence was observed under a fluorescence microscopy.C57/B6-L and A549 cell lines showed a significant increase in the expression of circLAMP3 by PCR and qPCR methods.Sanger sequencing results showed that the junction site of circLAMP3 was correct.This study successfully constructed C57/B6-L and A549 cell lines overexpressing circLAMP3,providing biomaterials for further exploration of the biological function of circLAMP3 in influenza virus replication.
10.Analysis of CT imaging features and causes of miss diagnosis of ectopic pancreas based on endoscopy
Yuqi WANG ; Dinghao LUO ; Xiaoyuan CHAI ; Peng SUN ; Xiaoxuan MA
Basic & Clinical Medicine 2024;44(8):1162-1164
Objective To explore the imaging manifestations of ectopic pancreas based on endoscopic findings in order to find out the causes of miss diagnosis and to improve the diagnostic accuracy.Methods The clinical and CT imaging data of ectopic pancreas patients who underwent CT examination and confirmed by endoscopy and pathology microscopy at Air Force Medical Center from July 2018 to March 2023 were collected.Their im-aging characteristics were analyzed according to the endoscopic findings and the miss diagnosis was analyzed.Results There were 13 patients with ectopic pancreas and 3 of them had no obvious symptoms.Ten patients presented with gastrointestinal symptoms,including epigastric discomfort and pain,incomplete obstruction,and melena.Lesion sites:8 cases were located in the gastric antrum and 5 cases were located in the small in-testine.In this group,two patients showed apical erosions and glandular opening-like depressions on endoscop-ic results,but only one patient showed a"ductal sign"shown by CT scanning.None of the 13 patients in this group made ectopic pancreatic diagnosis on imaging,of which 4 were diagnosed as thickening of the gastroin-testinal tract wall,3 were diagnosed as gastrointestinal stromal tumor,3 were diagnosed as benign tumors and 3 had no obvious abnormalities.Conclusions The imaging diagnosis of ectopic pancreas should be made by closely combinating with the results of endoscopy to improve the accuracy of imaging diagnosis.CT is of great significance for the diagnosis of ectopic pancreas,and adequate preparation before gastrointestinal examination is an important step to avoid misdiagnosis.

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