OBJECTIVE: To investigate the current status of clinical genetics specialization development and the diagnostic and therapeutic capabilities for hereditary diseases across medical institutions in Shanghai, and to assess the necessity and feasibility of establishing training bases for clinical genetics specialists. METHODS: By employing a cross-sectional survey design, the Clinical Genetics Committee of Shanghai Medical Association has conducted questionnaire surveys from March to April 2025 across 54 healthcare institutions in Shanghai (including 33 tertiary hospitals and 21 secondary hospitals). The survey involved administrative departments and medical personnel from 15 clinical specialties. The survey has covered current genetic disease diagnosis and treatment practices, relevant and specialised disease types, genetic department establishment, testing capabilities, personnel teams, and training requirements. RESULTS: The results revealed that 78.0% of clinical departments surveyed had treated patients with hereditary disorders. Shanghai possesses diagnostic and therapeutic expertise for over 95% of hereditary diseases listed in its rare disease catalogue, reflecting both the practical clinical demand for such conditions and the city's overall diagnostic and therapeutic strengths in this field. Nevertheless, significant disparities exist in the development of genetics departments across different tiers of healthcare institutions. Resources for genetic testing capabilities (including molecular, cellular, and biochemical testing) are also unevenly distributed across different tiers of hospitals. The survey further revealed that only 26.0% of departments believe that their current physician structure fully meets the diagnostic and treatment demands. Over 90% of departments consider standard training for clinical genetic specialists necessary, with 74.0% expressing willingness to participate in establishing training bases. Based on above findings and thorough deliberation, the Clinical Genetics Committee of the Shanghai Medical Association proposes advancing specialist training and discipline development through establishing a standard training system. The committee has drafted a three-year training protocol featuring a "joint training"-centered model, recommending a pilot-first, dynamically optimized strategy for steadily advancing training base development. CONCLUSION Shanghai faces substantial demand for genetic disease diagnosis and treatment, yet exhibits shortcomings in clinical genetics specialization development, resource allocation, and talent pipeline cultivation. To establish a standard training system holds significant practical importance and is underpinned by a broad demand.
Humans ; China ; Surveys and Questionnaires ; Genetic Diseases, Inborn/genetics* ; Cross-Sectional Studies ; Genetics, Medical/education* ; Genetic Testing

Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective:To investigate the effects of repetitive transcranial magnetic stimulation(rTMS) on learning memory and abnormal Aβ deposition in cerebral amyloid angiopathy(CAA) model mice, and further to investigate whether the mechanism involves the transport function of glymphatic system.Methods:Eight-month-old SPF grade Tg-SWDI mice were randomly divided into the CAA group and the rTMS group according to the random number table method with 7 in each group.Seven wild-type mice of the same genetic background and age served as the control group. The mice in rTMS group received two weeks of high-frequency rTMS intervention, and the mice in CAA group and control group were only restrained without rTMS intervention.Learning and memory functions were evaluated using the Morris water maze test.Amyloid-beta deposition, glymphatic system clearance, and aquaporin-4(AQP4) polarization were assessed using immunofluorescence, and AQP4 expression levels were measured by Western blot.Statistical analysis of the data was conducted using SPSS 25.0 and GraphPad Prism 9.5 softwares.Repeated-measures ANOVA was used for data on escape latency, and one-way ANOVA was used for comparisons between multiple groups for other data.Results:(1)In the novel object recognition test, there were statistically significant differences in recognition indices among the three groups of mice ( F=22.59, P<0.05). Compared with the control group, the mice in the CAA group showed a significant decrease in the new object recognition index ( P<0.05).Compared with the CAA group, the mice in the rTMS group showed a significant increase in the new object recognition index ( P<0.05).(2)In the Y-maze, there were statistical differences in the spontaneous alternation rates among the three groups ( F=5.00, P<0.05). Compared with the control group, the spontaneous alternation rate in the CAA group was significantly lower ( P<0.05).And compared with the CAA group, the spontaneous alternation rate in the rTMS group was significantly higher ( P<0.05).(3)In the Morris water maze test, there were significant interactions in escape latency among the three groups ( F=4.05, P=0.02), significant main effects of time ( F=713.22, P<0.01), and significant main effects of group ( F=421.55, P<0.01). There was no significant statistical difference in swimming speed among the three groups ( F=0.19, P>0.05), while the difference of the number of entries into the inner zone and the proportion of time spent were statistically significant( F=71.67, 294.14, both P<0.05).Compared with the control group, the CAA group mice significantly decreased in the number of entries into the inner zone and the proportion of time spent in the middle zone (both P<0.01).(4)Compared with the CAA group, the rTMS group significantly increased in the number of entries into the inner zone and the proportion of time spent in the middle zone (both P<0.01).The result of immunofluorescence test showed that there was a statistically significant difference in the levels of Aβ in the cerebral vessels among the three groups( F=385.76, P<0.01).The levels of Aβ in the cerebral vessels of the CAA group (62.00±2.65) were significantly higher than those in the control group (9.00±1.00, P<0.01).The levels in the rTMS group (51.33±3.21) were significantly lower than those in the CAA group (62.00±2.65, P<0.01). Using the residual fluorescence tracer levels of the control group as a baseline, there were statistically significant differences in the tracer intensities in the corpus callosum and cerebral cortex( F=258.97, 46.44, both P<0.05), the tracer intensities in the corpus callosum (3.57±0.21) and cerebral cortex (4.96±0.79) of the CAA group mice were significantly higher than those in the rTMS group (1.45±0.14, 1.78±0.47, P<0.01). The polarization of AQP4 in the cerebral cortex of rTMS group (0.51±0.07) was significantly higher than that in the CAA group (0.30±0.02, P<0.01). Conclusion:rTMS can alleviate learning memory and abnormal Aβ deposition in CAA model mice by modulating AQP4 polarisation and promoting transport function of glymphatic system.

Objective:To investigate the effects of repetitive transcranial magnetic stimulation(rTMS) on learning memory and abnormal Aβ deposition in cerebral amyloid angiopathy(CAA) model mice, and further to investigate whether the mechanism involves the transport function of glymphatic system.Methods:Eight-month-old SPF grade Tg-SWDI mice were randomly divided into the CAA group and the rTMS group according to the random number table method with 7 in each group.Seven wild-type mice of the same genetic background and age served as the control group. The mice in rTMS group received two weeks of high-frequency rTMS intervention, and the mice in CAA group and control group were only restrained without rTMS intervention.Learning and memory functions were evaluated using the Morris water maze test.Amyloid-beta deposition, glymphatic system clearance, and aquaporin-4(AQP4) polarization were assessed using immunofluorescence, and AQP4 expression levels were measured by Western blot.Statistical analysis of the data was conducted using SPSS 25.0 and GraphPad Prism 9.5 softwares.Repeated-measures ANOVA was used for data on escape latency, and one-way ANOVA was used for comparisons between multiple groups for other data.Results:(1)In the novel object recognition test, there were statistically significant differences in recognition indices among the three groups of mice ( F=22.59, P<0.05). Compared with the control group, the mice in the CAA group showed a significant decrease in the new object recognition index ( P<0.05).Compared with the CAA group, the mice in the rTMS group showed a significant increase in the new object recognition index ( P<0.05).(2)In the Y-maze, there were statistical differences in the spontaneous alternation rates among the three groups ( F=5.00, P<0.05). Compared with the control group, the spontaneous alternation rate in the CAA group was significantly lower ( P<0.05).And compared with the CAA group, the spontaneous alternation rate in the rTMS group was significantly higher ( P<0.05).(3)In the Morris water maze test, there were significant interactions in escape latency among the three groups ( F=4.05, P=0.02), significant main effects of time ( F=713.22, P<0.01), and significant main effects of group ( F=421.55, P<0.01). There was no significant statistical difference in swimming speed among the three groups ( F=0.19, P>0.05), while the difference of the number of entries into the inner zone and the proportion of time spent were statistically significant( F=71.67, 294.14, both P<0.05).Compared with the control group, the CAA group mice significantly decreased in the number of entries into the inner zone and the proportion of time spent in the middle zone (both P<0.01).(4)Compared with the CAA group, the rTMS group significantly increased in the number of entries into the inner zone and the proportion of time spent in the middle zone (both P<0.01).The result of immunofluorescence test showed that there was a statistically significant difference in the levels of Aβ in the cerebral vessels among the three groups( F=385.76, P<0.01).The levels of Aβ in the cerebral vessels of the CAA group (62.00±2.65) were significantly higher than those in the control group (9.00±1.00, P<0.01).The levels in the rTMS group (51.33±3.21) were significantly lower than those in the CAA group (62.00±2.65, P<0.01). Using the residual fluorescence tracer levels of the control group as a baseline, there were statistically significant differences in the tracer intensities in the corpus callosum and cerebral cortex( F=258.97, 46.44, both P<0.05), the tracer intensities in the corpus callosum (3.57±0.21) and cerebral cortex (4.96±0.79) of the CAA group mice were significantly higher than those in the rTMS group (1.45±0.14, 1.78±0.47, P<0.01). The polarization of AQP4 in the cerebral cortex of rTMS group (0.51±0.07) was significantly higher than that in the CAA group (0.30±0.02, P<0.01). Conclusion:rTMS can alleviate learning memory and abnormal Aβ deposition in CAA model mice by modulating AQP4 polarisation and promoting transport function of glymphatic system.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Liver Cancer is a prevalent malignant tumor worldwide,with various treatment options available. Among these, ablation therapy holds a significant role in liver cancer treatment due to its minimally invasive nature and lower complication rate. This article reviews the indications and contraindications of liver cancer ablation,the basic principles of different ablation techniques,and their advantages and limitations in clinical applications for liver cancer. Each ablation technique possesses unique characteristics regarding therapeutic efficacy,application scope,and complication profiles,necessitating the selection of the most appropriate approach tailored to the patient′s specific condition and tumor attributes. Furthermore,this article also discusses the potential role of ablation therapy in multidisciplinary treatment,highlighting its synergistic application with liver transplantation,interventional therapy,and immunotargeted therapy to significantly improve outcomes for unresectable liver cancer. Specifically,ablation therapy can induce an anti-tumor immune response by locally destroying the tumor,offering a potential application prospect for combining ablation with immunotherapy. Looking forward,with advances in nanotechnology,artificial intelligence,and image-guided techniques,ablation therapy is expected to progress towards higher precision,personalization,and safety,offering optimized treatment options for liver cancer patients.