1.Expert consensus on visualized tele-round and quality control management based on the improvement of clinical practice ability
Wanhong YIN ; Xiaoting WANG ; Ran ZHOU ; Dawei LIU ; Yan KANG ; Yaoqing TANG ; Xiaochun MA ; Jianguo LI ; Zhenjie HU ; Haitao ZHANG ; Wei HE ; Lixia LIU ; Wenjin CHEN ; Ran ZHU ; Jun WU ; Hongmin ZHANG ; Lina ZHANG ; Wenzhao CHAI ; Shihong ZHU ; Wangbin XU ; Rongqing SUN ; Xiangyou YU ; Tianjiao SONG ; Ying ZHU ; Hong REN ; Ai SHANMU ; Qing ZHANG ; Wei FANG ; Xiuling SHANG ; Liwen LYU ; Shuhan CAI ; Xin DING ; Heng ZHANG ; Guang FENG ; Lipeng ZHANG ; Bo HU ; Dong ZHANG ; Weidong WU ; Feng SHEN ; Xiaojun YANG ; Zhenguo ZENG ; Qibing HUANG ; Xueying ZENG ; Tongjuan ZOU ; Milin PENG ; Yulong YAO ; Mingming CHEN ; Hui LIAN ; Jingmei WANG ; Yong LI ; Feng QU ; Gang YE ; Rongli YANG ; Xiukai CHEN ; Suwei LI ; Juxiang WANG ; Yangong CHAO
Chinese Journal of Internal Medicine 2025;64(2):101-109
Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.
2.Unilateral biportal endoscopy assisted bilateral decompression in the treatment of lumbar disc herniation with imaging herniation on one side and clinical symptoms on the contralateral side
Weiliang SU ; Yongfeng DOU ; Dong LIU ; Guohua DAI ; Min ZHANG ; Jianqiang XING ; Dawei WANG ; Peng HU ; Xiaopeng GENG
Chinese Journal of Orthopaedics 2025;45(1):44-50
Objective:To observe the clinical efficacy of unilateral biportal endoscopy (UBE) assisted bilateral decompression in the treatment of lumbar disc herniation with imaging herniation on one side and clinical symptoms on the contralateral side.Methods:A total of 20 patients with lumbar disc herniation with imaging herniation on one side and clinical symptoms on the contralateral side treated with UBE from January 2022 to January 2024 in the Affiliated Hospital of Binzhou Medical University were retrospectively analyzed. There were 9 males and 11 females, aged 50.4±14.0 years (range, 23-72 years). The intervertebral disc herniation level included L 3-4 in 1 case, L 4-5 in 15 cases, and L 5S 1 in 4 cases. There were 10 cases on the left side and 10 cases on the right side. The duration of symptoms was 24.1±33.7 months (range, 1-120 months). Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate postoperative pain relief and functional recovery. The clinical efficacy was evaluated by modified MacNab criteria at 6 months after operation. Results:All patients successfully completed the operation. The operation time was 90.3±24.6 min (range, 55-134 mins). The VAS scores of patients at 3 days, 1 month, 3 months and 6 months after operation were 3.6±0.9, 2.2±0.7, 1.2±0.5 and 1.0±0.6, respectively, which were lower than those before operation (6.4±0.8), and the differences were statistically significant ( F=668.728, P<0.001). The ODI at 3 days, 1 month, 3 months and 6 months after operation were 34.2%±4.7%, 28.7%±2.8%, 24.3%±2.1% and 20.5%±2.0%, respectively, which were lower than 69.4%±5.2% before operation, and the differences were statistically significant ( F=515.578, P<0.001). The clinical efficacy was evaluated by modified MacNab criteria at 6 months after operation. Among 20 patients, 18 cases were excellent, 1 case was good, and 1 case was fair. All patients were followed up for 9.1±2.1 months (range, 6-14 months). One patient had a dural tear during the operation, but the range was small and there was no defect, and no further treatment was performed. Numbness of the lower limbs occurred 1 day after operation, and the symptoms disappeared after symptomatic treatment. There was no recurrence of lower limb symptoms, lumbar instability, intervertebral space infection or other complications at the last follow-up. Conclusion:Bilateral decompression with UBE is effective in the treatment of lumbar disc herniation with imaging herniation on one side and clinical symptoms on the contralateral side, which can improve the lumbar pain and function of patients.
3.Prediction of anticoagulant treatment of portal vein thrombosis based on clinical and CT radiomics
Peng LIU ; Jingxuan ZHANG ; Hui XU ; Dawei YANG ; Zhenghan YANG
Journal of Practical Radiology 2025;41(7):1153-1157
Objective To establish and validate a machine learning model integrating abdominal contrast-enhanced CT radiomics features and clinical characteristics,and to construct a predictive model for the efficacy of anticoagulant treatment in portal vein thrombosis(PVT).Methods A retrospective selection was conducted on 94 PVT patients who received anticoagulant treatment.Patients were divided into effective and ineffective treatment groups based on the follow-up results.Clinical information was collected,and imaging features were evaluated.Univariate and multivariate logistic regression were performed to select clinical information and imaging fea-tures for constructing a clinical-imaging model.On CT venous phase images,the PVT mask was delineated and radiomics features were extracted,and the radiomics model was screened and established.A combined model was further developed using features from both the clinical-imaging and radiomics models.Receiver operating characteristic(ROC)curves were used to evaluate the predictive efficacy of different models.Results The area under the curve(AUC)for the clinical-imaging model,radiomics model,and com-bined model were 0.594,0.794,and 0.776,respectively.The radiomics and combined models demonstrated superior predictive efficacy for anticoagulant treatment in PVT compared to the clinical-imaging model.No significant difference in performance was observed between radiomics and combined models.Conclusion The radiomics model and combined model based on abdominal contrast-enhanced CT can effectively predict the efficacy of anticoagulant treatment for PVT.
4.Digital three-dimensional assisted unilateral biportal endoscopy in treatment of highly isolated lumbar disc herniation with translaminar approach.
Weiliang SU ; Suni LU ; Dong LIU ; Jianqiang XING ; Peng HU ; Yongfeng DOU ; Xiaopeng GENG ; Dawei WANG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(3):346-353
OBJECTIVE:
To investigate the effectiveness of digital three-dimensional (3D) assisted unilateral biportal endoscopy (UBE) in the treatment of highly isolated lumbar disc herniation (LDH) with translaminar approach.
METHODS:
The clinical data of 59 patients who met the selection criteria and underwent UBE treatment due to highly isolated LDH between January 2022 and December 2023 were retrospectively analyzed. Among them, 25 cases were treated with digital 3D assisted translaminar approach (observation group) and 34 cases were treated with interlaminar approach (control group). There was no significant difference in gender, age, disease duration, surgical segment, and preoperative visual analogue scale (VAS) score and Oswestry disability index (ODI) between the two groups ( P>0.05). The operation time, intraoperative blood loss, and lateral articular surface preservation rate were recorded and compared between the two groups. VAS score and ODI were used to evaluate the improvements of pain and function before operation and at 3 and 6 months after operation. The modified MacNab criteria was used to evaluate the effectiveness at last follow-up.
RESULTS:
One patient in the control group had dural tear, and the other patients had no nerve injury, infection, dural tear, or other related complications. There was no significant difference in operation time and intraoperative blood loss between the two groups ( P>0.05). Patients in both groups were followed up 6-13 months, with an average of 8.3 months. The lateral articular surface preservation rate in the observation group was significantly higher than that in the control group ( P<0.05). Three patients in the observation group and 2 patients in the control group had calf muscle venous thrombosis, which was cured after anticoagulant treatment with rivaroxaban and delayed exercise time. There was no recurrence or second operation during the follow-up period. The VAS score and ODI of the two groups at 3 and 6 months after operation significantly improved when compared with those before operation ( P<0.05). There was no significant difference between the two groups at each time point after operation ( P>0.05). At last follow-up, the effectiveness was evaluated according to the modified MacNab criteria, and there was no significant difference in the evaluation grade and excellent and good rate between the two groups ( P>0.05).
CONCLUTION
UBE via translaminar approach is safe and effective for the treatment of highly isolated LDH, which is beneficial to protect the facet joint, maintain spinal stability, and reduce soft tissue injury. With the assistance of digital 3D technique, preoperative planning can be performed accurately.
Humans
;
Intervertebral Disc Displacement/diagnostic imaging*
;
Lumbar Vertebrae/diagnostic imaging*
;
Male
;
Retrospective Studies
;
Female
;
Endoscopy/methods*
;
Treatment Outcome
;
Middle Aged
;
Adult
;
Imaging, Three-Dimensional
;
Operative Time
;
Pain Measurement
5.Construction of an in vitro simulated one compartment extravascular administration model and comparisons with a classic in vitro administration model in lanthanum nitrate induced HepG2 cell death
Dawei FU ; Yujin FU ; Lailai YAN ; Jie CHEN ; Zhiyu LIU ; Juanling FU ; Biyun YAO ; Weidong HAO ; Peng ZHAO
Chinese Journal of Pharmacology and Toxicology 2025;39(4):285-295,中插1-中插2
OBJECTIVE To establish an in vitro simulated one compartment extravascular adminis-tration model with lanthanum nitrate as the test substance,and explore the differences between this model and the classic in vitro administration model in lanthanum nitrate induced HepG2 cell death.METHODS An in vitro administration device was designed based on compartment model theories which consisted of four functional chambers:the liquid storage chamber,mixing chamber,toxicant exposure chamber,and waste liquid receiving chamber.The four chambers were connected by peristaltic pump hoses.The peristaltic pumps were employed to ensure unidirectional and constant speed trans-mission of liquid between these chambers.According to the preset toxicokinetic parameters such as T1/2a and T1/2,an in vitro simulated one compartment extravascular administration model of lanthanum nitrate was constructed using the device.The content of lanthanum nitrate in the toxicant exposure chamber at different time points was measured using inductively coupled plasma mass spectrometry.The concentration-time curves of lanthanum nitrate were analyzed using PKsolver and GraphPad Prism 8.0 software.The constructed in vitro simulated one compartment extravascular administration model was evaluated by comparing the measured and theoretical values of toxicokinetic parameters.HepG2 cells were treated with lanthanum nitrate in the in vitro simulated one compartment extravascular administration model and classic in vitro administration model,respectively,and cell death was measured using the Hoechst 33342/propidium iodide staining method.RESULTS Within the Cmax range of 3.91-1 000.00 μmol·L-1,the measured concentration-time curves of lanthanum nitrate in the toxicant expo-sure chamber almost conformed with the corresponding calculated theoretical curves(the correlation coefficients were all>0.998 0).The measured values of toxicokinetic parameters,including Ke,T1/2,Ka,T1/2a,Tmax,Cmax,CL and AUC0-∞,were close to the corresponding theoretical values.The fitting coeffi-cients(R2)of the concentration-time curves for each experimental group were all>0.990 0,which was consistent with one compartment model for extravascular administration.In the simulated one compart-ment extravascular administration model,no significant death of HepG2 cells was observed in any lanthanum nitrate dose group.In the classic in vitro administration model,the cell death rate of the 0.500 mmol·L-1 lanthanum nitrate group was higher than that of the solvent control group,but no significant cell death was observed in the 0.119 mmol·L-1 group or 0.243 mmol·L-1 group.When Cmax or Cadministration was 0.500 mmol·L-1,classic in vitro administration induced a higher cell death rate than simulated one compart-ment extravascular administration.However,there was no statistically significant difference in lanthanum nitrate induced HepG2 cell death between the two administration models when the AUC was equal.CONCLUSION The device designed in this study can be used to in vitro simulate one compartment extravascular administration,making in vitro toxicity testing more similar to in vivo scenarios,and providing data for optimizing administration methods of in vitro toxicity testing.There are differences in lanthanum nitrate induced HepG2 cell death between simulated one compartment extravascular administration and classic in vitro administration,indicating that different in vitro exposure modes can affect toxicity.
6.Unilateral biportal endoscopy assisted bilateral decompression in the treatment of lumbar disc herniation with imaging herniation on one side and clinical symptoms on the contralateral side
Weiliang SU ; Yongfeng DOU ; Dong LIU ; Guohua DAI ; Min ZHANG ; Jianqiang XING ; Dawei WANG ; Peng HU ; Xiaopeng GENG
Chinese Journal of Orthopaedics 2025;45(1):44-50
Objective:To observe the clinical efficacy of unilateral biportal endoscopy (UBE) assisted bilateral decompression in the treatment of lumbar disc herniation with imaging herniation on one side and clinical symptoms on the contralateral side.Methods:A total of 20 patients with lumbar disc herniation with imaging herniation on one side and clinical symptoms on the contralateral side treated with UBE from January 2022 to January 2024 in the Affiliated Hospital of Binzhou Medical University were retrospectively analyzed. There were 9 males and 11 females, aged 50.4±14.0 years (range, 23-72 years). The intervertebral disc herniation level included L 3-4 in 1 case, L 4-5 in 15 cases, and L 5S 1 in 4 cases. There were 10 cases on the left side and 10 cases on the right side. The duration of symptoms was 24.1±33.7 months (range, 1-120 months). Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate postoperative pain relief and functional recovery. The clinical efficacy was evaluated by modified MacNab criteria at 6 months after operation. Results:All patients successfully completed the operation. The operation time was 90.3±24.6 min (range, 55-134 mins). The VAS scores of patients at 3 days, 1 month, 3 months and 6 months after operation were 3.6±0.9, 2.2±0.7, 1.2±0.5 and 1.0±0.6, respectively, which were lower than those before operation (6.4±0.8), and the differences were statistically significant ( F=668.728, P<0.001). The ODI at 3 days, 1 month, 3 months and 6 months after operation were 34.2%±4.7%, 28.7%±2.8%, 24.3%±2.1% and 20.5%±2.0%, respectively, which were lower than 69.4%±5.2% before operation, and the differences were statistically significant ( F=515.578, P<0.001). The clinical efficacy was evaluated by modified MacNab criteria at 6 months after operation. Among 20 patients, 18 cases were excellent, 1 case was good, and 1 case was fair. All patients were followed up for 9.1±2.1 months (range, 6-14 months). One patient had a dural tear during the operation, but the range was small and there was no defect, and no further treatment was performed. Numbness of the lower limbs occurred 1 day after operation, and the symptoms disappeared after symptomatic treatment. There was no recurrence of lower limb symptoms, lumbar instability, intervertebral space infection or other complications at the last follow-up. Conclusion:Bilateral decompression with UBE is effective in the treatment of lumbar disc herniation with imaging herniation on one side and clinical symptoms on the contralateral side, which can improve the lumbar pain and function of patients.
7.Prediction of anticoagulant treatment of portal vein thrombosis based on clinical and CT radiomics
Peng LIU ; Jingxuan ZHANG ; Hui XU ; Dawei YANG ; Zhenghan YANG
Journal of Practical Radiology 2025;41(7):1153-1157
Objective To establish and validate a machine learning model integrating abdominal contrast-enhanced CT radiomics features and clinical characteristics,and to construct a predictive model for the efficacy of anticoagulant treatment in portal vein thrombosis(PVT).Methods A retrospective selection was conducted on 94 PVT patients who received anticoagulant treatment.Patients were divided into effective and ineffective treatment groups based on the follow-up results.Clinical information was collected,and imaging features were evaluated.Univariate and multivariate logistic regression were performed to select clinical information and imaging fea-tures for constructing a clinical-imaging model.On CT venous phase images,the PVT mask was delineated and radiomics features were extracted,and the radiomics model was screened and established.A combined model was further developed using features from both the clinical-imaging and radiomics models.Receiver operating characteristic(ROC)curves were used to evaluate the predictive efficacy of different models.Results The area under the curve(AUC)for the clinical-imaging model,radiomics model,and com-bined model were 0.594,0.794,and 0.776,respectively.The radiomics and combined models demonstrated superior predictive efficacy for anticoagulant treatment in PVT compared to the clinical-imaging model.No significant difference in performance was observed between radiomics and combined models.Conclusion The radiomics model and combined model based on abdominal contrast-enhanced CT can effectively predict the efficacy of anticoagulant treatment for PVT.
8.Construction of an in vitro simulated one compartment extravascular administration model and comparisons with a classic in vitro administration model in lanthanum nitrate induced HepG2 cell death
Dawei FU ; Yujin FU ; Lailai YAN ; Jie CHEN ; Zhiyu LIU ; Juanling FU ; Biyun YAO ; Weidong HAO ; Peng ZHAO
Chinese Journal of Pharmacology and Toxicology 2025;39(4):285-295,中插1-中插2
OBJECTIVE To establish an in vitro simulated one compartment extravascular adminis-tration model with lanthanum nitrate as the test substance,and explore the differences between this model and the classic in vitro administration model in lanthanum nitrate induced HepG2 cell death.METHODS An in vitro administration device was designed based on compartment model theories which consisted of four functional chambers:the liquid storage chamber,mixing chamber,toxicant exposure chamber,and waste liquid receiving chamber.The four chambers were connected by peristaltic pump hoses.The peristaltic pumps were employed to ensure unidirectional and constant speed trans-mission of liquid between these chambers.According to the preset toxicokinetic parameters such as T1/2a and T1/2,an in vitro simulated one compartment extravascular administration model of lanthanum nitrate was constructed using the device.The content of lanthanum nitrate in the toxicant exposure chamber at different time points was measured using inductively coupled plasma mass spectrometry.The concentration-time curves of lanthanum nitrate were analyzed using PKsolver and GraphPad Prism 8.0 software.The constructed in vitro simulated one compartment extravascular administration model was evaluated by comparing the measured and theoretical values of toxicokinetic parameters.HepG2 cells were treated with lanthanum nitrate in the in vitro simulated one compartment extravascular administration model and classic in vitro administration model,respectively,and cell death was measured using the Hoechst 33342/propidium iodide staining method.RESULTS Within the Cmax range of 3.91-1 000.00 μmol·L-1,the measured concentration-time curves of lanthanum nitrate in the toxicant expo-sure chamber almost conformed with the corresponding calculated theoretical curves(the correlation coefficients were all>0.998 0).The measured values of toxicokinetic parameters,including Ke,T1/2,Ka,T1/2a,Tmax,Cmax,CL and AUC0-∞,were close to the corresponding theoretical values.The fitting coeffi-cients(R2)of the concentration-time curves for each experimental group were all>0.990 0,which was consistent with one compartment model for extravascular administration.In the simulated one compart-ment extravascular administration model,no significant death of HepG2 cells was observed in any lanthanum nitrate dose group.In the classic in vitro administration model,the cell death rate of the 0.500 mmol·L-1 lanthanum nitrate group was higher than that of the solvent control group,but no significant cell death was observed in the 0.119 mmol·L-1 group or 0.243 mmol·L-1 group.When Cmax or Cadministration was 0.500 mmol·L-1,classic in vitro administration induced a higher cell death rate than simulated one compart-ment extravascular administration.However,there was no statistically significant difference in lanthanum nitrate induced HepG2 cell death between the two administration models when the AUC was equal.CONCLUSION The device designed in this study can be used to in vitro simulate one compartment extravascular administration,making in vitro toxicity testing more similar to in vivo scenarios,and providing data for optimizing administration methods of in vitro toxicity testing.There are differences in lanthanum nitrate induced HepG2 cell death between simulated one compartment extravascular administration and classic in vitro administration,indicating that different in vitro exposure modes can affect toxicity.
9.Expert consensus on visualized tele-round and quality control management based on the improvement of clinical practice ability
Wanhong YIN ; Xiaoting WANG ; Ran ZHOU ; Dawei LIU ; Yan KANG ; Yaoqing TANG ; Xiaochun MA ; Jianguo LI ; Zhenjie HU ; Haitao ZHANG ; Wei HE ; Lixia LIU ; Wenjin CHEN ; Ran ZHU ; Jun WU ; Hongmin ZHANG ; Lina ZHANG ; Wenzhao CHAI ; Shihong ZHU ; Wangbin XU ; Rongqing SUN ; Xiangyou YU ; Tianjiao SONG ; Ying ZHU ; Hong REN ; Ai SHANMU ; Qing ZHANG ; Wei FANG ; Xiuling SHANG ; Liwen LYU ; Shuhan CAI ; Xin DING ; Heng ZHANG ; Guang FENG ; Lipeng ZHANG ; Bo HU ; Dong ZHANG ; Weidong WU ; Feng SHEN ; Xiaojun YANG ; Zhenguo ZENG ; Qibing HUANG ; Xueying ZENG ; Tongjuan ZOU ; Milin PENG ; Yulong YAO ; Mingming CHEN ; Hui LIAN ; Jingmei WANG ; Yong LI ; Feng QU ; Gang YE ; Rongli YANG ; Xiukai CHEN ; Suwei LI ; Juxiang WANG ; Yangong CHAO
Chinese Journal of Internal Medicine 2025;64(2):101-109
Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.
10.Clinical predictive value of PD-1/PD-L1-induced electrocardiogram changes for cardiotoxicity
Nan XUE ; Lili PENG ; Dawei WU ; Xiaojiang LI
Chinese Journal of Oncology 2024;46(10):979-986
Objective:To observe the electrocardiogram (ECG) changes of programmed death receptor 1 (PD-1)/programmed death receptor-ligand 1 (PD-L1) immune checkpoint inhibitors before and after immunotherapy of patients during clinical antitumor process, and to explore the occurrence and influencing factors of cardiotoxicity of immune checkpoint inhibitors.Methods:A total of 93 patients with locally advanced or metastatic solid tumors confirmed by pathological diagnosis in Cancer Hospital of Chinese Academy of Medical Sciences from October 1, 2019 to September 30, 2020 were selected and treated with PD-1/PD-L1 inhibitor monotherapy. Groups were divided according to immunotherapy regimen: Group A (drug code: 609A), 16 patients were given 1 mg/kg of the drug for 21 days; Group B (drug code: HX008), 23 patients were treated with 200mg for 21 days; Group C (drug code: GB226), 28 patients were treated with 3mg/kg for 14 days; Group D (drug code: LP002), 26 patients were treated with 900mg for 14 days. The patients were monitored and followed up for 10 cycles. The ECG results of each group were recorded, and the correlation between ECG abnormality and cardiotoxicity was analyzed.Results:A total of 75 patients showed abnormal ECG that met the diagnostic criteria. There was no significant difference in abnormal ECG rate after immunotherapy in group A ( P>0.05), while the incidence of adverse cardiac events increased after immunotherapy in group B ( P<0.05), and the abnormal ECG rate increased significantly after chemotherapy in group C and group D. There was statistical difference before and after immunotherapy ( P<0.001). The number of abnormal cases in group A (8 cases, 50.0%, 8/16) was significantly lower than that of group B (20 cases, 87.0%, 20/23). The number of abnormal cases in group C and group D was 24 (85.7%) and 23 (88.4%), respectively, without statistical difference ( P>0.05), but their abnormal rates of ECG were higher than that in group A. The incidence of electrical adverse events in immunotherapy center of patients with underlying diseases was 1.93 times higher than that of patients without underlying diseases. The incidence of central electrical adverse events during immunotherapy in group B, C and D was 6.667, 6.000 and 7.667 times higher than that in group A, respectively. Conclusions:The high sensitivity of early ECG changes induced by immune checkpoint inhibitors enables early prediction of related cardiotoxicity. The presence or absence of comorbid underlying disease and drug dosage are correlated with the occurrence of adverse cardiac events, and these early changes provide a evidence for clinical treatment and prevention.

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