The construction of a training system for visiting physicians in the department of rare diseases in China is an important measure to improve the overall diagnosis and treatment capacity for rare diseases and address the critical challenge of insufficient knowledge and skills among clinicians in practice. This article systematically describes the visiting physician training system established by the Department of Rare Diseases at Peking Union Medical College Hospital. It summarizes the training objectives and positioning, design logic, and learning modules of the system, aiming to provide a reference for the construction of the specialized talent team for rare diseases in China.

OBJECTIVE:Patients with osteoporotic vertebral compression fractures still have residual back pain after vertebral augmentation.The current research is characterized by limited sample size,complex confounding factors,and inconsistent research results.To gain a deeper understanding of this phenomenon,the aim of this study was to identify and evaluate the risk factors for residual back pain after surgery through a systematic review and meta-analysis.METHODS:A comprehensive search was conducted in CNKI,VIP,WanFang,CBMdisc,PubMed,The Cochrane Library,Embase,and Web of Science for case-control studies on residual back pain after vertebral body augmentation for osteoporotic vertebral compression fractures from database inception to July 2024.The search terms were a combination of subject terms and free terms.The basic information,patient characteristics,surgical-related indicators,and risk factors for surgical back pain of the included studies were extracted.After evaluating the bias risk of all included studies,a meta-analysis was conducted using Stata 14.0 software on the relevant indicators.RESULTS:(1)21 case-control studies with a total of 8 043 patients were included.Among them,965 patients developed back pain.The quality score of all 21 studies was ≥7.(2)The meta-analysis results showed that age(WMD=0.98,95％CI:0.40-1.56,P=0.010),bone mineral density(WMD=-0.28,95％CI:-0.34 to-0.21,P=0.000),the number of vertebral fractures(OR=3.50,95％CI:2.65-4.62,P=0.000),thoracolumbar fracture index(OR=3.65,95％CI:2.61-5.11,P=0.000),cement volume(OR=6.89,95％CI:2.62-18.17,P=0.000),and cement distribution(OR=2.38,95％CI:1.93-2.93,P=0.000)were risk factors for the development of back pain after vertebral body augmentation in patients with osteoporotic vertebral compression fractures.CONCLUSION:Current evidence indicates that age,bone mineral density,the number of vertebral fractures,thoracolumbar fracture index,bone cement injection volume,and the distribution of bone cement are risk factors for low back pain.Specifically,bone mineral density,the number of vertebral fractures,thoracolumbar fracture index,and non-uniform distribution of bone cement are identified as independent risk factors for low back pain.Patients exhibiting these high-risk factors require vigilant monitoring and prompt intervention to mitigate the occurrence of clinical low back pain,thereby enhancing patient outcomes and quality of life.

OBJECTIVE:Patients with osteoporotic vertebral compression fractures still have residual back pain after vertebral augmentation.The current research is characterized by limited sample size,complex confounding factors,and inconsistent research results.To gain a deeper understanding of this phenomenon,the aim of this study was to identify and evaluate the risk factors for residual back pain after surgery through a systematic review and meta-analysis.METHODS:A comprehensive search was conducted in CNKI,VIP,WanFang,CBMdisc,PubMed,The Cochrane Library,Embase,and Web of Science for case-control studies on residual back pain after vertebral body augmentation for osteoporotic vertebral compression fractures from database inception to July 2024.The search terms were a combination of subject terms and free terms.The basic information,patient characteristics,surgical-related indicators,and risk factors for surgical back pain of the included studies were extracted.After evaluating the bias risk of all included studies,a meta-analysis was conducted using Stata 14.0 software on the relevant indicators.RESULTS:(1)21 case-control studies with a total of 8 043 patients were included.Among them,965 patients developed back pain.The quality score of all 21 studies was ≥7.(2)The meta-analysis results showed that age(WMD=0.98,95％CI:0.40-1.56,P=0.010),bone mineral density(WMD=-0.28,95％CI:-0.34 to-0.21,P=0.000),the number of vertebral fractures(OR=3.50,95％CI:2.65-4.62,P=0.000),thoracolumbar fracture index(OR=3.65,95％CI:2.61-5.11,P=0.000),cement volume(OR=6.89,95％CI:2.62-18.17,P=0.000),and cement distribution(OR=2.38,95％CI:1.93-2.93,P=0.000)were risk factors for the development of back pain after vertebral body augmentation in patients with osteoporotic vertebral compression fractures.CONCLUSION:Current evidence indicates that age,bone mineral density,the number of vertebral fractures,thoracolumbar fracture index,bone cement injection volume,and the distribution of bone cement are risk factors for low back pain.Specifically,bone mineral density,the number of vertebral fractures,thoracolumbar fracture index,and non-uniform distribution of bone cement are identified as independent risk factors for low back pain.Patients exhibiting these high-risk factors require vigilant monitoring and prompt intervention to mitigate the occurrence of clinical low back pain,thereby enhancing patient outcomes and quality of life.

BACKGROUND:Crosslinked sodium hyaluronate gel has good mechanical property,biocompatibility,and biodegradability,and can be used as an isolated protective material in tumor radiation therapy to protect endangered organs from damage caused by excess radiation dose. OBJECTIVE:To investigate the safety and efficacy of crosslinked sodium hyaluronate gel in reducing the dose of radiation to dangerous organs during brachytherapy. METHODS:A total of 16 specific pathogen-free Kunming mice of the same age and similar body weight were selected as experimental subjects and divided into experimental group and control group by the random number table method,with 8 mice in each group.125I seeds were implanted subcutaneously in the back of mice in the experimental group,and then crosslinked sodium hyaluronate gel was injected around the radioactive particles.Only 125I seeds were implanted subcutaneously in the back of mice in the control group.After injection,the distance between the radioactive particles and the epidermis was measured by spiral CT scan,and the surface radiation dose was measured by radiation dosimeter.Within 10 weeks after injection,the growth state,survival rate,skin radiation damage,and gel retention of mice were observed. RESULTS AND CONCLUSION:(1)Spiral CT scan showed that the implanted gel was relatively concentrated and created an effective distance between the radioactive seeds and the epidermis.The body surface radiation dose of the experimental group was significantly lower than that of the control group(P<0.01).(2)During the experimental observation period,mice in both groups survived;mice in the control group showed obvious irritability and other unstable behavior in the late experimental period,and some mice in the experimental group showed similar behavior.The daily food intake of mice in the two groups had no significant change,and the body mass showed the same increasing trend.After implantation of radioactive seeds,the two groups of mice showed different degrees of radioactive skin injury.From day 23 after injection to the end of the experiment,the skin radiation injury score of the experimental group was lower than that of the control group(P<0.01).At week 10 after implantation,6 mice in the experimental group had no obvious gel residue under their skin,and 2 mice had a very small amount of scattered gel-like samples under their skin.(3)Therefore,the crosslinked sodium hyaluronate injection technique can increase the space between the radioactive target area of 125I seeds and the organ at risk outside the target through physical space occupying,which can effectively reduce the dose of the organ at risk,and play a role in the isolation and protection of the organ at risk.

BACKGROUND:With the development of biomechanics,its research into cardiovascular diseases has become more and more extensive.By studying the mechanical properties of blood vessels,the pathogenesis of cardiovascular diseases such as atherosclerosis and restenosis can be effectively revealed and new ideas and methods can be developed for the treatment of cardiovascular diseases. OBJECTIVE:To review the research status of apoptosis of vascular smooth muscle cells induced by mechanical stress and search for potential target molecules and signaling pathways for clinical treatment,thereby improving the clinical treatment effect on cardiovascular diseases such as atherosclerosis and restenosis. METHODS:We searched the literature in CNKI,PubMed and ScienceDirect databases from January 1992 to May 2023.The search terms were"vascular smooth muscle cell,mechanical stress,shear stress,stretch stress,apoptosis"in Chinese and English.Finally,63 articles were included for review and analysis. RESULTS AND CONCLUSION:Physiological and pathological apoptosis of vascular smooth muscle cells is an adaptive remodeling in response to the changes in vascular mechanics.Vascular smooth muscle cells in different parts have different mechanical stimuli and their pathogenesis is also different.Low shear stress,physiological shear stress and high shear stress directly interact with surface molecules,receptors and proteins of vascular smooth muscle cells to regulate apoptosis-related signaling molecules and inhibit cell proliferation,thus regulating the apoptosis of vascular smooth muscle cells.In this part,the research on promoting proliferation is not summarized.Low stretch stress,physiological stretch stress and high stretch stress can all cause apoptosis of vascular smooth muscle cells,but it is still controversial.There are many mechanoreceptors(such as integrins and receptor tyrosine kinases)on the surface of vascular smooth muscle cells,which can transform mechanical signals into intracellular chemical signals(such as the Hippo pathway),activate the apoptosis signals of vascular smooth muscle cells and regulate the apoptosis of vascular smooth muscle cells.In short,different mechanical stimuli start a variety of signal pathways and regulate the apoptosis of vascular smooth muscle cells through various signal molecules.For example,shear stress affects Fas/FasL and Akt pathways mainly by stimulating prostaglandin secretion and transforming growth factors.Strech stress mainly regulates the YAP pathway and Notch pathway through Yes-related proteins.At different times or intensities,these molecules may play opposite two-way roles.For example,when mouse vascular smooth muscle cells are stretched at 10%physiological tension for 1 hour,cell proliferation increases.However,the proliferation of human vascular smooth muscle cells can decrease after 12 hours of stretching.Clinically,the key molecules of mechanical transduction can be disturbed by searching for key molecules that interfere with mechanical transduction at their critical time points of action.

OBJECTIVE: To observe the effects of electroacupuncture (EA) on improving motor function and regulating microglial activation based on Notch receptor 1 (Notch1)/Hes family bHLH transcription factor 1 (Hes1) pathway in mice with Parkinson's disease (PD). METHODS: Thirty-six male C57BL/6 mice were randomly divided into a control group, a model group and an EA group, 12 mice in each group. PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days in the model group and the EA group. From the 1st day of modeling, EA was applied at "Baihui" (GV20) and bilateral "Shenshu" (BL23) in the EA group, with continuous wave, in frequency of 2 Hz and current of 2 mA, 15 min a time, once a day for 14 days continuously. The behavioral performance was evaluated by gait test, pole climbing test and hanging test, the number of positive cells of tyrosine hydroxylase (TH) and the co-expression positive cells of Notch1/ionized calcium binding adaptor molecule 1 (Iba-1) in the substantia nigra of midbrain was assessed by immunofluorescence, the protein expression of TH, α-synuclein (α-syn), Notch1, Hes1, Iba-1, inducible nitric oxide synthase (iNOS), Arginase-1 (ARG1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 was detected by Western blot, the mRNA expression of Notch1 and Hes1 was detected by real-time PCR. RESULTS: Compared with the control group, in the model group, the stride frequency was accelerated (P<0.001) and the stride length was shortened (P<0.001) for the four limbs, the pole climbing test time was prolonged (P<0.01) and the grip level was reduced (P<0.01); in the substantia nigra of midbrain, the number of positive cells of TH was decreased (P<0.001), the number of co-expression positive cells of Notch1/Iba-1 was increased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-1βand IL-6 was increased (P<0.01, P<0.05, P<0.001), the protein expression of TH, ARG1 and IL-10 was decreased (P<0.01, P<0.001), the mRNA expression of Notch1 and Hes1 was increased (P<0.01). Compared with the model group, in the EA group, the stride frequency was decelerated (P<0.001) and the stride length was increased (P<0.05, P<0.01, P<0.001) for the four limbs, the pole climbing test time was shortened (P<0.05) and the grip level was increased (P<0.05); in the substantia nigra of midbrain, the number of positive cells of TH was increased (P<0.01), the number of co-expression positive cells of Notch1/Iba-1 was decreased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-6 and IL-1β was decreased (P<0.05, P<0.01), the protein expression of TH, ARG1 and IL-10 was increased (P<0.05, P<0.001, P<0.01), the mRNA expression of Notch1 and Hes1 was decreased (P<0.05). CONCLUSION EA can improve the behavioral performance and protect the dopaminergic neurons in PD mice, its mechanism may relate to the inhibition of Notch1/Hes1-mediated neuroinflammation, thus inhibiting the microglial activation.
Animals ; Electroacupuncture ; Microglia/metabolism* ; Male ; Receptor, Notch1/metabolism* ; Parkinson Disease/physiopathology* ; Transcription Factor HES-1/metabolism* ; Mice ; Mice, Inbred C57BL ; Humans ; Signal Transduction

Objective:To investigate the effect of chlorogenic acid on atherosclerosis (AS) in a mouse model.Methods:Twenty-four specific pathogen-free male ApoE-/- mice were adaptively fed for 1 week and then randomly divided into three groups ( n=8 per group): The model group, the atorvastatin group, and the chlorogenic acid group. All three groups were fed with a high-fat diet. Eight male C57BL/6N wild-type mice served as the control group and were fed with a standard diet. After 8 weeks, the atorvastatin group received intragastric administration of a solution containing 0.9% sodium chloride +2.6 mg/kg atorvastatin at 10 mL/kg, while the chlorogenic acid group received 0.9% sodium chloride +200 mg/kg chlorogenic acid at 10 mL/kg. The control and model groups were given an equal volume of 0.9% sodium chloride once a day. After 9 weeks of continuous treatment, the mice were anesthetized, and the aortas were collected for Oil Red O staining. Image J was used to measure plaque area and total vascular area, and the percentage was calculated. Liver tissues were subjected to hematoxylin-eosin (H&E) staining to observe pathological changes. Blood samples from the abdominal aorta were collected to measure lipid profiles [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)], liver function markers [aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)], and inflammatory cytokines [interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α)]. Non-HDL-C levels were calculated as TC minus HDL-C. Results:Aortic lipid plaque area: The model group exhibited a significantly higher plaque area than the control group [(44.91±1.91)% vs. (0.21±0.11)%]. Both the atorvastatin group [(15.00±1.29)%] and the chlorogenic acid group [(26.13±2.16)%] showed reduced plaque areas compared to the model group ( P<0.05). Liver pathology: The control group displayed intact hepatocyte structure with regular morphology, whereas the model group exhibited significant steatosis. Both the atorvastatin and chlorogenic acid groups showed alleviated liver damage compared to the model group. Blood lipid levels: The model group had higher TC, TG, HDL-C, LDL-C, and non-HDL-C levels than the control group [(30.3±4.0) mmol/L vs. (2.8±0.3) mmol/L, (1.26±0.32) mmol/L vs. (0.52±0.12) mmol/L, (3.02±0.39) mmol/L vs. (2.00±0.17) mmol/L, (14.87±5.23) mmol/L vs. (0.39±0.09) mmol/L, (27.3±4.0) mmol/L vs. (0.8±0.3) mmol/L, respectively]. Both the atorvastatin group [(24.0±3.1), (0.64±0.08), (2.04±0.41), (8.55±1.15), (22.0±3.2) mmol/L] and the chlorogenic acid group [(23.3±2.5), (0.88±0.14), (2.28±0.18), (8.90±0.29), (21.0±2.5) mmol/L] showed lower levels than the model group ( P<0.05). The model group had higher ALT, AST, and ALP levels than the control group [(274±43) U/L vs. (99±14) U/L, (130±66) U/L vs. (38±4) U/L, (86±15) U/L vs. (60±5) U/L, respectively]. Both the atorvastatin group [(139±12), (58±16), (69±5) U/L] and the chlorogenic acid group [(138±11), (55±16), (54±5) U/L] exhibited lower levels than the model group ( P<0.05). Inflammatory cytokines: The model group had higher IL-6, IL-1β, and TNF-α levels than the control group [(238±15) ng/L vs. (202±7) ng/L, (211±6) ng/L vs. (174±6) ng/L, (1 325±75) ng/L vs. (1 036±75) ng/L, respectively]. Both the atorvastatin group [(215±9), (191±4), (1 163±78) ng/L] and the chlorogenic acid group [(220±13), (195±7), (1 197±53) ng/L] showed reduced levels compared to the model group (all P<0.05). Conclusion:Chlorogenic acid may inhibit aortic lipid plaque deposition and ameliorate AS in mice by improving lipid metabolism and suppressing inflammatory responses.

Objective:To investigate the clinicopathological and molecular genetic features of high-grade astrocytomas with piloid features (HGAP).Methods:Clinical, histopathological and imaging data of 7 cases of HGAP diagnosed at the Neuropathology Center of Beijing Tiantan Hospital, Beijing, China from August 2023 to October 2024 were collected. The histopathological and molecular features for each case were analyzed.Results:Among the seven patients there were 4 males and 3 females, with the median age of 37 (34, 51) years. Patients exhibited various clinical symptoms and signs depending on the tumor′s location. Four tumors were located in the cerebellum, 2 in the supratentorial region, and 1 in the spinal cord. Magnetic resonance imaging showed that 6 of the 7 patients had cystic and solid lesions, with focal or nodular enhancement and relatively unclear boundaries. Histopathological features had a diverse morphological spectrum and extensive grading. Five cases displayed a pilocytic astrocytoma-like appearance with infiltrative growth patterns, while two cases presented glioblastoma-like morphology, containing locally anaplastic pleomorphic xanthoastrocytoma with minor pilocytic components. All tumors were diffusely positive for GFAP and Olig2, while 4 tumors exhibited partial or complete loss of ATRX. The Ki-67 proliferation index ranged from 2% to 40%. Next-generation sequencing showed that tumor cells most commonly harbored MAPK pathway gene mutations, and/or homozygous deletions of CDKN2A/B, and/or ATRX mutations. Among the 7 HGAP models, 3 cases showed the three types of molecular genetic variations, 1 case showed MAPK mutations and homozygous deletions of CDKN2A/B, 1 case had MAPK mutations and ATRX mutations, 1 case had only MAPK mutations, and 1 case showed no detectable molecular changes. DNA methylation clustering analyses showed that the median model prediction score was 0.94 (range, 0.85-0.99) for the 7 HGAP models. Five cases showed the MGMT promoter hypermethylation. Four patients received radiotherapy and concomitant temozolomide treatment after surgery, while three patients received no known treatments. At the last follow-up, seven patients were alive without any tumor, two patients had recurrence, and one patient was alive with the tumor.Conclusions:HGAP is relatively rare and predominantly occurs in adults. It has a wide histopathological spectrum and various histological grades, characterized by piloid astrocytoma-like and glioblastoma-like histological features. Its diagnosis relies on methylation clustering analysis. Most tumors harbor gene alterations in the MAPK signaling pathway, along with homozygous deletions of CDKN2A/B or ATRX mutations. The biological behavior is typically aggressive, while imaging and histological findings can be misleading. Therefore, clinicians need to increase their diagnostic awareness of this tumor and prevent missed diagnoses.

Objective:To explore the application of the suspension culture method in pancreatic cancer organoid construction.Methods:Cell suspensions obtained from 8 pancreatic cancer tissue samples at the Second Hospital of Lanzhou University between July 2023 and March 2024, were prepared by digested pancreatic cancer tumor tissues using mixed enzymes, inoculated into ultra-low adsorption culture plates for suspension culture, and when the organoids were cultured to a certain size, passaging and freezing were initiated, and their structural morphology was observed by inverted microscope. Hematoxylin-eosin (HE) staining showed that pancreatic cancer organoids were lumpy or irregularly tubular, with obvious nuclear atypia, and were remarkably similar in tissue structure to pancreatic cancer tissue.Results:Among the 8 pancreatic cancer tissue samples, pancreatic cancer organoids were successfully constructed in three patients, and HE staining showed that pancreatic cancer organoids had a high degree of structural similarity with tumor tissues. Immunohistochemistry suggested that CK7, CK19, P53, and Ki-67 were expressed in the pancreatic cancer organoids and tumor tissues of case origin in more or less the same way.Conclusion:The suspension culture method is able to construct pancreatic cancer-like organs that are approximately the same as the originating tumor tissues at the tissue level.

Periodontitis is a globally prevalent inflammatory oral disease, affecting approximately 50% of the population worldwide and imposing a substantial burden on patients′ health and quality of life. Early and accurate diagnosis is critical for preventing disease progression; however, conventional diagnostic approaches often rely on subjective clinical assessments, which only primarily evaluate the cumulative state of the disease, thus limiting their ability to achieve precise early detection. In recent years, the rapid advancement of artificial intelligence (AI) in medical diagnostics has demonstrated significant promise, particularly through the integration of multimodal data to enable more comprehensive information capture and analysis. Multimodal data fusion, which combines diverse inputs such as imaging, clinical parameters, and biomarkers, offers transformative potential for AI-powered periodontitis diagnostics. This innovative approach aims to overcome the limitations of traditional methods, significantly enhancing diagnostic accuracy and predictive capabilities. This manuscript reviews the primary diagnostic techniques for periodontitis, explores recent advances in AI applications within this domain, and emphasizes the potential of multimodal data in facilitating precision diagnosis. Furthermore, it provides new insights and supports for personalized treatment strategies.