1.Research progress on mechanism of curcumin in treatment of depression
Lin WANG ; Qi-fei PAN ; Wen-juan LONG ; Jia-rong DU ; Zhong-yang HU ; Xin-yao LI ; Yi-shu CHEN ; Dong-dong QIN ; Xiao-man LYU
Chinese Pharmacological Bulletin 2025;41(9):1618-1623
Depression is a prevalent mental and emotional disor-der that often results in significant emotional disturbances,cog-nitive dysfunction,and memory impairments.It is characterized by a high incidence rate,a substantial disability burden,and limited therapeutic efficacy.Currently,the long-term use of medications for the treatment of depression can result in a range of adverse reactions,highlighting the urgent need to explore no-vel approaches that can effectively alleviate depressive symptoms while minimizing side effects.Curcumin,a natural polyphenolic compound derived from the rhizome of turmeric,demonstrates considerable potential in the prevention and treatment of depres-sion,owing to its diverse array of biological activities.In recent years,numerous studies have investigated the use of curcumin for the treatment of depression.This article aims to provide a comprehensive review of the mechanisms of action underlying curcumin's efficacy in treating depression.Specifically,it focu-ses on its ability to improve neurotransmitter imbalances,restore neural plasticity,alleviate neural damage,mitigate dysfunction of the hypothalamic-pituitary-adrenal(HPA)axis,regulate in-flammatory factors and neuroinflammatory signaling pathways,and inhibit oxidative stress.This review is intended to offer in-sights and methodological references for basic research on curcu-min,as well as for the development of novel therapeutic agents for the treatment of depression.
2.Effects of fangchinoline derivative LYY-32 on biological properties of BLM DNA helicase
Wang-ming ZHANG ; Qin-ying FENG ; Xiao-yu SONG ; Xin-zhong ZHOU ; Juan LU ; Wan-qing XIE ; Zhi-wen LAI ; Wei-dong PAN ; Jie-lin LIU
Chinese Pharmacological Bulletin 2025;41(9):1680-1686
Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17%.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49%.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3%at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100%.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.
3.Research progress on mechanism of curcumin in treatment of depression
Lin WANG ; Qi-fei PAN ; Wen-juan LONG ; Jia-rong DU ; Zhong-yang HU ; Xin-yao LI ; Yi-shu CHEN ; Dong-dong QIN ; Xiao-man LYU
Chinese Pharmacological Bulletin 2025;41(9):1618-1623
Depression is a prevalent mental and emotional disor-der that often results in significant emotional disturbances,cog-nitive dysfunction,and memory impairments.It is characterized by a high incidence rate,a substantial disability burden,and limited therapeutic efficacy.Currently,the long-term use of medications for the treatment of depression can result in a range of adverse reactions,highlighting the urgent need to explore no-vel approaches that can effectively alleviate depressive symptoms while minimizing side effects.Curcumin,a natural polyphenolic compound derived from the rhizome of turmeric,demonstrates considerable potential in the prevention and treatment of depres-sion,owing to its diverse array of biological activities.In recent years,numerous studies have investigated the use of curcumin for the treatment of depression.This article aims to provide a comprehensive review of the mechanisms of action underlying curcumin's efficacy in treating depression.Specifically,it focu-ses on its ability to improve neurotransmitter imbalances,restore neural plasticity,alleviate neural damage,mitigate dysfunction of the hypothalamic-pituitary-adrenal(HPA)axis,regulate in-flammatory factors and neuroinflammatory signaling pathways,and inhibit oxidative stress.This review is intended to offer in-sights and methodological references for basic research on curcu-min,as well as for the development of novel therapeutic agents for the treatment of depression.
4.Effects of fangchinoline derivative LYY-32 on biological properties of BLM DNA helicase
Wang-ming ZHANG ; Qin-ying FENG ; Xiao-yu SONG ; Xin-zhong ZHOU ; Juan LU ; Wan-qing XIE ; Zhi-wen LAI ; Wei-dong PAN ; Jie-lin LIU
Chinese Pharmacological Bulletin 2025;41(9):1680-1686
Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17%.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49%.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3%at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100%.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.
5.Safety analysis of different types of influenza vaccines in Fujian Province from 2019 to 2023
Zhiqiang LIN ; Jianxiong XIAO ; Ruihong WU ; Weiyi PAN ; Zhifei CHEN ; Qin WANG
Adverse Drug Reactions Journal 2025;27(4):225-231
Objective:To analyze and compare the reporting data of adverse events following immunization (AEFI) of influenza vaccines in Fujian Province from 2019 to 2023.Methods:Using the National Immunization Program Information Management System, the AEFI reports and vaccination data of influenza vaccines in Fujian Province from 2019 to 2023 were collected, and the reporting rates and clinical characteristics of AEFI of 6 types of influenza vaccines were compared. The 6 types of vaccines in the analysis were as follows: trivalent inactivated influenza vaccines (IIV3) for 6-35 months old people, IIV3 for ≥3 years old people, trivalent live attenuated nasal spray vaccine (LAIV3) for 3-17 years old people, quadrivalent inactivated influenza vaccines (IIV4) for 6-35 months old people, IIV4 for ≥6 months old people, and IIV4 for ≥3 years old people.Results:From 2019 to 2023, a total of 87 687.21 million doses of influenza vaccine were vaccinated in Fujian Province, and 510 cases of AEFI were reported, with a reporting rates of 5.82 per 100 000 doses. Among the 510 cases, 443 (86.86%) were general reactions, 56 (10.98%) were abnormal reactions, 1 (0.20%) was psychogenic reactions, and 10 (1.96%) were coincidence. There were no reports of vaccination accidents and vaccine quality accidents. The reporting rates of AEFI were relatively higher in 2019 and 2020 (18.38 and 18.00 per 100 000 doses, respectively), and lower in 2021, 2022 and 2023 (8.91, 10.68 and 2.30 per 100 000 doses, respectively); the differences were statistically significant (all P<0.05). The differences of reporting rates of AEFI between IIV3 for 6-35 months old people and IIV4 for 6-35 months old people, the injectable vaccines and nasal spray vaccines were not statistically significant. However, the reporting rates of overall AEFI, general reactions and abnormal reactions of IIV3 for ≥3 years old people were all higher than those of IIV4 for ≥3 years old people (7.77 per 100 000 doses vs. 3.88 per 100 000 doses, 6.18 per 100 000 doses vs. 3.59 per 100 000 doses, 1.41 per 100 000 doses vs. 0.19 per 100 000 doses). The reporting rates of overall AEFI and general reaction of IIV3 for 6-35 months old people were both higher than those of IIV3 for ≥3 years old (16.47 per 100 000 doses vs. 7.77 per 100 000 doses, 13.05 per 100 000 doses vs. 6.18 per 100 000 doses), and the differences were statistially significant (all P<0.05). The reporting rates of general abnormal reactions of IIV4 for 6-35 months old and ≥ 6 months old people were both higher than those of IIV4 for ≥3 years old people (14.73 per 100 000 doses and 9.52 per 100 000 doses vs. 3.88 per 100 000 doses); the reporting rates of general reactions and abnormal reactions of IIV4 for ≥6 months old people were both higher than those of IIV4 for ≥3 years old people (12.94 per 100 000 doses vs. 3.59 per 100 000 doses, 1.34 per 100 000 doses vs. 0.19 per 100 000 doses), the differences were statistcially significant (all P<0.05). In terms of clinical features, the reporting rates of fever (37.6-38.5 ℃ and ≥ 38.5 ℃), local redness and swelling (diameter 2.6-5.0 cm), and local induration (diameter ≤2.5 cm and 2.6-5.0 cm) after vaccination of IIV3 for ≥3 years old people were higher than those of IIV4 for ≥ 3 years old people (1.41 per 100 000 doses vs. 0.64 per 100 000 doses, 3.00 per 100 000 doses vs. 1.16 per 100 000 doses); the reporting rates of allergic rash and angioedema of IIV3 for ≥ 3 years old people were higher than those of IIV4 for ≥3 years old people (0.53 per 100 000 doses vs. 0.12 per 100 000 doses, 0.35 per 100 000 doses vs. 0); the differences were statistically significant (all P<0.016 7). Conclusions:The reporting rates of AEFI for influenza vaccines in Fujian Province from 2019 to 2023 was showing a downward trend. The AEFI was mainly general reactions. The reporting rates of AEFI were different among different influenza vaccines, but the overall safety was good.
6.Intelligent handheld ultrasound improving the ability of non-expert general practitioners in carotid examinations for community populations: a prospective and parallel controlled trial
Pei SUN ; Hong HAN ; Yi-Kang SUN ; Xi WANG ; Xiao-Chuan LIU ; Bo-Yang ZHOU ; Li-Fan WANG ; Ya-Qin ZHANG ; Zhi-Gang PAN ; Bei-Jian HUANG ; Hui-Xiong XU ; Chong-Ke ZHAO
Ultrasonography 2025;44(2):112-123
Purpose:
The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations.
Methods:
This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits.
Results:
Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01).
Conclusion
Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.
7.Optimization of Surgical Procedure and Efficacy Evaluation of Aortic Calcification Model in Rats with Chronic Kidney Disease
Yicong PAN ; Wenhong JIANG ; Ming HU ; Xiao QIN
Laboratory Animal and Comparative Medicine 2025;45(3):279-289
Objective To establish a chronic kidney disease-associated aortic calcification model in SD rats using different nephrectomy surgical methods, and to compare and evaluate surgical duration and survival time to explore a more optimized modeling method. Methods According to different surgical methods, the SD rats were divided into four groups: Group A: intraperitoneal resection of 2/3 of the left kidney followed by right total nephrectomy in the second stage; Group B: intraperitoneal resection of 2/3 of the left kidney and simultaneous right total nephrectomy; Group C: dorsal approach right total nephrectomy followed by resection of 2/3 of the left kidney in the second stage; Group D: dorsal approach resection of 2/3 of the left kidney followed by right total nephrectomy in the second stage. After comparing survival curves of SD rats undergoing intraperitoneal versus dorsal approaches, and staged versus single-stage nephrectomy, the optimal nephrectomy surgical method was determined. Then, twenty-four 8-week-old SPF-grade male SD rats were selected for nephrectomy combined with calcitriol-induced calcification. Experimental group (12 rats): the dorsal approach left 2/3 nephrectomy followed by right total nephrectomy, with intraperitoneal injection of 1 μg/kg calcitriol administered one week later to induce aortic calcification. Control group (12 rats): the intraperitoneal injection of 250 μL/kg physiological saline containing 1% DMSO one week after sham surgery. After intraperitoneal injection of drugs for 3 months, the survival status of rats in each group was observed. Under anesthesia, blood samples were collected from each group to measure serum phosphorus and calcium ion concentrations, as well as serum urea nitrogen and creatinine levels. After euthanizing the rats, a post-mortem examination was performed to observe the residual kidney morphology, and HE staining was used to observe the pathological changes in the coronal section of the kidney. Additionally, the entire aorta of each group was taken, and the degree of aortic calcification was observed by staining with Alizarin red S and von Kossa. Real-time fluorescence quantitative PCR was used to detect the gene expression of smooth muscle actin-associated protein alpha (Sm22), Runt-related transcription factor 2 (Runx2), and osteopontin (OPN) in rat aortic tissue to evaluate the effectiveness of the model. Results The exploratory optimization experiment of different surgical procedures found that the survival rate of group D rats,which underwent 2/3 left kidney resection followed by right whole kidney resection via the dorsal approach, was the highest, indicating that this surgical procedure was the best method for establishing a chronic kidney disease model with renal dysfunction. The experimental group rats treated with this surgical procedure combined with high-dose calcitriol injection had significantly lower serum calcium ion concentration than those in the sham-operated control group (P<0.05), while serum phosphorus ion concentration, serum creatinine, and serum urea nitrogen levels were significantly higher than those of the control group (P<0.05). HE staining of the kidneys showed significant organic changes in the kidneys of the experimental group rats, with a significant decrease in glomerular count compared to that of the control group (P<0.05), indicating the successful establishment of a renal failure model. Alizarin red S staining showed significant pigment deposition in the aortic media of the experimental group rats, while von Kossa staining showed significant silver nitrate deposition in the aortic media of the experimental group rats, which was consistent with the manifestation of aortic calcification in renal failure. Real-time fluorescence quantitative PCR showed that the expression level of Sm22 in the aortic tissue of the experimental group rats decreased (P<0.05), while the expression levels of OPN and Runx2 increased (P<0.05), indicating a transition of aortic smooth muscle cells from smooth muscle phenotype to bone-like phenotype and successful induction of an aortic calcification model. Conclusion The method of establishing an aortic calcification model of chronic kidney disease in SD rats by first removing two-thirds of the left kidney via the dorsal approach followed by right total nephrectomy, combined with high-dose calcitriol administration, shortens the surgical time, improves the success rate of modeling, and increases the animal survival rate.
8.Optimization of Surgical Procedure and Efficacy Evaluation of Aortic Calcification Model in Rats with Chronic Kidney Disease
Yicong PAN ; Wenhong JIANG ; Ming HU ; Xiao QIN
Laboratory Animal and Comparative Medicine 2025;45(3):279-289
Objective To establish a chronic kidney disease-associated aortic calcification model in SD rats using different nephrectomy surgical methods, and to compare and evaluate surgical duration and survival time to explore a more optimized modeling method. Methods According to different surgical methods, the SD rats were divided into four groups: Group A: intraperitoneal resection of 2/3 of the left kidney followed by right total nephrectomy in the second stage; Group B: intraperitoneal resection of 2/3 of the left kidney and simultaneous right total nephrectomy; Group C: dorsal approach right total nephrectomy followed by resection of 2/3 of the left kidney in the second stage; Group D: dorsal approach resection of 2/3 of the left kidney followed by right total nephrectomy in the second stage. After comparing survival curves of SD rats undergoing intraperitoneal versus dorsal approaches, and staged versus single-stage nephrectomy, the optimal nephrectomy surgical method was determined. Then, twenty-four 8-week-old SPF-grade male SD rats were selected for nephrectomy combined with calcitriol-induced calcification. Experimental group (12 rats): the dorsal approach left 2/3 nephrectomy followed by right total nephrectomy, with intraperitoneal injection of 1 μg/kg calcitriol administered one week later to induce aortic calcification. Control group (12 rats): the intraperitoneal injection of 250 μL/kg physiological saline containing 1% DMSO one week after sham surgery. After intraperitoneal injection of drugs for 3 months, the survival status of rats in each group was observed. Under anesthesia, blood samples were collected from each group to measure serum phosphorus and calcium ion concentrations, as well as serum urea nitrogen and creatinine levels. After euthanizing the rats, a post-mortem examination was performed to observe the residual kidney morphology, and HE staining was used to observe the pathological changes in the coronal section of the kidney. Additionally, the entire aorta of each group was taken, and the degree of aortic calcification was observed by staining with Alizarin red S and von Kossa. Real-time fluorescence quantitative PCR was used to detect the gene expression of smooth muscle actin-associated protein alpha (Sm22), Runt-related transcription factor 2 (Runx2), and osteopontin (OPN) in rat aortic tissue to evaluate the effectiveness of the model. Results The exploratory optimization experiment of different surgical procedures found that the survival rate of group D rats,which underwent 2/3 left kidney resection followed by right whole kidney resection via the dorsal approach, was the highest, indicating that this surgical procedure was the best method for establishing a chronic kidney disease model with renal dysfunction. The experimental group rats treated with this surgical procedure combined with high-dose calcitriol injection had significantly lower serum calcium ion concentration than those in the sham-operated control group (P<0.05), while serum phosphorus ion concentration, serum creatinine, and serum urea nitrogen levels were significantly higher than those of the control group (P<0.05). HE staining of the kidneys showed significant organic changes in the kidneys of the experimental group rats, with a significant decrease in glomerular count compared to that of the control group (P<0.05), indicating the successful establishment of a renal failure model. Alizarin red S staining showed significant pigment deposition in the aortic media of the experimental group rats, while von Kossa staining showed significant silver nitrate deposition in the aortic media of the experimental group rats, which was consistent with the manifestation of aortic calcification in renal failure. Real-time fluorescence quantitative PCR showed that the expression level of Sm22 in the aortic tissue of the experimental group rats decreased (P<0.05), while the expression levels of OPN and Runx2 increased (P<0.05), indicating a transition of aortic smooth muscle cells from smooth muscle phenotype to bone-like phenotype and successful induction of an aortic calcification model. Conclusion The method of establishing an aortic calcification model of chronic kidney disease in SD rats by first removing two-thirds of the left kidney via the dorsal approach followed by right total nephrectomy, combined with high-dose calcitriol administration, shortens the surgical time, improves the success rate of modeling, and increases the animal survival rate.
9.Intelligent handheld ultrasound improving the ability of non-expert general practitioners in carotid examinations for community populations: a prospective and parallel controlled trial
Pei SUN ; Hong HAN ; Yi-Kang SUN ; Xi WANG ; Xiao-Chuan LIU ; Bo-Yang ZHOU ; Li-Fan WANG ; Ya-Qin ZHANG ; Zhi-Gang PAN ; Bei-Jian HUANG ; Hui-Xiong XU ; Chong-Ke ZHAO
Ultrasonography 2025;44(2):112-123
Purpose:
The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations.
Methods:
This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits.
Results:
Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01).
Conclusion
Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.
10.Intelligent handheld ultrasound improving the ability of non-expert general practitioners in carotid examinations for community populations: a prospective and parallel controlled trial
Pei SUN ; Hong HAN ; Yi-Kang SUN ; Xi WANG ; Xiao-Chuan LIU ; Bo-Yang ZHOU ; Li-Fan WANG ; Ya-Qin ZHANG ; Zhi-Gang PAN ; Bei-Jian HUANG ; Hui-Xiong XU ; Chong-Ke ZHAO
Ultrasonography 2025;44(2):112-123
Purpose:
The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations.
Methods:
This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits.
Results:
Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01).
Conclusion
Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

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