Neuronal reprogramming is an innovative technique for converting non-neuronal somatic cells into neurons that can be used to replace lost or damaged neurons, providing a potential effective therapeutic strategy for central nervous system (CNS) injuries or diseases. Transcription factors have been used to induce neuronal reprogramming, while their reprogramming efficiency is relatively low, and the introduction of exogenous genes may result in host gene instability or induce gene mutation. Therefore, their future clinical application may be hindered by these safety concerns. Compared with transcription factors, small-molecule compounds have unique advantages in the field of neuronal reprogramming, which can overcome many limitations of traditional transcription factor-induced neuronal reprogramming. Here, we review the recent progress in the research of small-molecule compound-mediated neuronal reprogramming and its application in CNS regeneration and repair.
Humans ; Cellular Reprogramming/drug effects* ; Neurons/cytology* ; Animals ; Transcription Factors ; Small Molecule Libraries/pharmacology* ; Nerve Regeneration

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

OBJECTIVE: To explore clinical effects of bone setting manipulation combined with pry reduction and Kirschner needle internal fixation in treating SandersⅡ-Ⅲ calcaneal fracture. METHODS: Clinical data of 52 patients with types Sanders Ⅱand Ⅲ calcaneal fracture (foot) treated with bone-setting manipulation combined with pry reduction and Kirscher needle internal fixation from July 2017 to July 2019 were retrospectively analyzed, including 43 males and 9 females, aged from 31 to 72 years old with an average of (50.83±10.48) years old; 15 patients with Sanders typeⅡ and 37 patients with Sanders type Ⅲ. The changes of Bühler angle, Gissane angle, calcaneus width and calcaneus height before operation and 24 months after operation were compared, and Maryland foot function score was performed to evaluate clinical effects. RESULTS: All patients were followed up from 24 to 60 months with an average of (41.50±9.86)months. The fracture healed normally and the healing time was (11.00±0.95) weeks. Bühler angle, Gissane angle, calcaneal bone width and calcaneal bone height were increased from (16.37±8.36)°, (96.27±9.62)°, (46.82±4.67) mm, (38.41±3.58) mm before operation to (31.48±8.24)°, (111.62±8.69)°, (42.06±4.83) mm, (44.21±3.82) mm at 24 months after operation, and the difference were statistically significant (P<0.01). Postoperative Maryland score at 24 months was (93.04±8.83), 40 patients got excellent result, 7 good and 5 fair. CONCLUSION Orthopedic manipulation combined with percutaneous reduction and Kirschner wire internal fixation could significantly improve Bühler angle, Gissane angle, width, and height of Sanders typeⅡ and Ⅲ calcaneal fractures, and the curative effect is satisfactory.
Humans ; Male ; Female ; Calcaneus/surgery* ; Middle Aged ; Fracture Fixation, Internal/methods* ; Adult ; Aged ; Fractures, Bone/therapy* ; Retrospective Studies ; Bone Wires ; Manipulation, Orthopedic/methods*

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

BACKGROUND: Medical informatics accumulated vast amounts of data for clinical diagnosis and treatment. However, limited access to follow-up data and the difficulty in integrating data across diverse platforms continue to pose significant barriers to clinical research progress. In response, our research team has embarked on the development of a specialized clinical research database for cardiology, thereby establishing a comprehensive digital platform that facilitates both clinical decision-making and research endeavors. METHODS: The database incorporated actual clinical data from patients who received treatment at the Cardiovascular Medicine Department of Chinese PLA General Hospital from 2012 to 2021. It included comprehensive data on patients' basic information, medical history, non-invasive imaging studies, laboratory test results, as well as peri-procedural information related to interventional surgeries, extracted from the Hospital Information System. Additionally, an innovative artificial intelligence (AI)-powered interactive follow-up system had been developed, ensuring that nearly all myocardial infarction patients received at least one post-discharge follow-up, thereby achieving comprehensive data management throughout the entire care continuum for high-risk patients. RESULTS: This database integrates extensive cross-sectional and longitudinal patient data, with a focus on higher-risk acute coronary syndrome patients. It achieves the integration of structured and unstructured clinical data, while innovatively incorporating AI and automatic speech recognition technologies to enhance data integration and workflow efficiency. It creates a comprehensive patient view, thereby improving diagnostic and follow-up quality, and provides high-quality data to support clinical research. Despite limitations in unstructured data standardization and biological sample integrity, the database's development is accompanied by ongoing optimization efforts. CONCLUSION The cardiovascular specialty clinical database is a comprehensive digital archive integrating clinical treatment and research, which facilitates the digital and intelligent transformation of clinical diagnosis and treatment processes. It supports clinical decision-making and offers data support and potential research directions for the specialized management of cardiovascular diseases.

OBJECTIVE: To investigate whether the G protein-coupled estrogen receptor (GPER) can attenuates acute lung injury in mice with exertional heat stroke (EHS) by inhibiting ferroptosis. METHODS: Sixty SPF-grade male C57BL/6 mice were randomly divided into four groups: normal control group (control group), EHS model group (EHS group), dimethyl sulfoxide (DMSO) solvent group (EHS+DMSO group), and GPER-specific agonist G1 group (EHS+G1 group), with 15 mice in each group. All mice underwent 14 days of adaptive training at 24-26 centigrade before modeling, and the EHS model was established using a high-temperature treadmill device. After successful modeling, the mice were allowed to cool naturally at room temperature. In the EHS+G1 group, 40 μg/kg of the GPER-specific agonist G1 was slowly injected intraperitoneally immediately after modeling. In the EHS+DMSO group, 40 μg/kg of DMSO was slowly injected intraperitoneally immediately after modeling. The control group received no treatment. Five hours after modeling, abdominal aortic blood was collected, and lung tissues were harvested after euthanasia. The lung coefficient was calculated to evaluate lung injury. Lung histopathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining, and a lung histopathological score was assigned. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), and Fe²⁺ in lung tissue. Immunofluorescence was used to detect the expression of glutathione peroxidase 4 (GPX4). Real-time polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of GPX4, ferroportin 1 (FPN1), and ferritin heavy chain 1 (FTH1). Western blotting was performed to detect the protein expression of GPX4, FPN1, and FTH1. RESULTS: Compared with the control group, the lung coefficient and lung histopathological score were significantly increased in the EHS group. HE staining showed significant thickening and unevenness of the alveolar septa and alveolar walls, partial alveolar collapse, and extensive erythrocyte, inflammatory cell, and plasma-like material extravasation in the alveolar spaces. Serum levels of TNF-α, IL-1β, MDA, and Fe²⁺ were significantly elevated. Immunofluorescence staining showed a significant decrease in GPX4-positive expression in lung tissue. Western blotting and RT-PCR showed significantly reduced protein and mRNA expression of GPX4, FPN1, and FTH1 in lung tissue. Compared with the EHS group, the EHS+G1 group showed a significant reduction in lung coefficient and lung histopathological score [lung coefficient (mg/g): 3.9±0.1 vs. 4.6±0.3, lung histopathological score: 4.2±0.2 vs. 6.9±0.2, both P < 0.05]. HE staining revealed reduced severity of lung tissue fluid extravasation, inflammatory infiltration, decreased hemorrhage, and less severe alveolar structural damage. Serum levels of TNF-α, IL-1β, MDA, and Fe²⁺ were significantly reduced [TNF-α (ng/L): 44.3±0.2 vs. 64.6±0.3, IL-1β (ng/L): 69.3±0.4 vs. 97.8±0.2, MDA (nmol/L): 2.8±0.3 vs. 3.6±0.5, Fe²⁺ (nmol/L): 0.021±0.004 vs. 0.028±0.004, all P < 0.05]. Immunofluorescence staining showed a significant decrease in GPX4-positive expression in lung tissue (fluorescence intensity: 35.53±2.41 vs. 16.45±0.31, P < 0.05). RT-PCR and Western blotting showed significantly increased mRNA and protein expression of GPX4, FPN1, and FTH1 in lung tissue [mRNA expression: GPX4 mRNA (2^-ΔΔCt): 0.44±0.05 vs. 0.09±0.01, FPN1 mRNA (2^-ΔΔCt): 0.77±0.17 vs. 0.42±0.14, FTH1 mRNA (2^-ΔΔCt): 0.75±0.04 vs. 0.58±0.01; protein expression: GPX4/β-actin: 0.96±0.11 vs. 0.24±0.04, FPN1/β-actin: 1.26±0.21 vs. 0.44±0.14, FTH1/β-actin: 0.27±0.12 vs. 0.15±0.07; all P < 0.05]. However, there were no statistically significant differences in any of the above indicators between the EHS+DMSO group and the EHS group. CONCLUSION Activation of GPER can attenuate EHS-related lung injury in mice, and its mechanism may be related to the activation of the GPX4 signaling pathway and inhibition of ferroptosis.
Animals ; Mice, Inbred C57BL ; Male ; Mice ; Heat Stroke/metabolism* ; Receptors, G-Protein-Coupled ; Ferroptosis ; Receptors, Estrogen ; Acute Lung Injury/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-1beta/metabolism* ; Lung Injury ; Lung/metabolism*

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective To analyze the incidence and risk factors of hypothermia in elderly patients with malnutrition during proximal femoral nail antirotation(PFNA)internal fixation under general anesthesia.Methods A total of 139 elderly patients underwent PFNA internal fixation under general anesthesia were selected,and the nutritional status scores 1 day before surgery ranged from 0 to 11 points.Univariate and multivariate Logistic binary regression analysis was performed to analyze the related factors that may lead to intraoperative hypothermia.Results Among 139 elderly patients with preoperative nutritional scores of 0 to 11 points,79 cases(56.83%)developed intraoperative hypothermia.The results of univariate and multivariate Logistic binary regression analysis suggested that age≥75 years old,mini nutritional assessment short form(MNA-SF)nutritional score 0 to 7 points,BMI<18.5 kg/m2,duration of general anesthesia≥2 hours,intraoperative flushing fluid volume≥1 000 mL and intraoperative fluid volume≥1 000 mL were the risk factors for the occurrence of intraoperative hypothermia in elderly patients(OR>1,P<0.05).The use of warm blanket insulation was the protective factor against the occurrence of intraoperative hypothermia(OR<1,P<0.05).Conclusion The incidence of intraoperative hypothermia during PFNA internal fixation under general anesthesia in elderly patients with mainutrition before operation is high,and patients with poor nutritional status are more likely to develop intraoperative hypothermia.Patients with older age,poor nutritional status,lower BMI,longer duration of general anesthesia,and more intraoperative flushing fluid volume and intraoperative fluid volume are likely to lead to intraoperative hypothermia.The use of warm blanket can reduce the incidence of intraoperative hypothermia.

Objective To compare regional pulmonary ventilation and perfusion and ventilation/perfusion(V/Q)matching in different body positions using electrical impedance tomography(EIT).Methods Ten healthy experimental pigs were selected to collect their EIT lung ventilation and perfusion data in supine,prone,left lateral and right lateral positions.The EIT data underwent analysis and image reconstruction using MATLAB R2022b and EIDORS v3.9.The effective regions with ventilation and perfusion were determined and the V/Q matching regions were computed with the maximum pixel value 20％as the threshold.Comparisons were carried out over the V/Q matching indexes including V/Q match％,dead space％and shunt％and ventilation and perfusion distribution in regions of interest(ROIs)including ROI1,ROI2,ROI3 and ROI4 in different body positions.Results The differences in V/Q match％,dead space％and shunt％of the experimental animals in varied positions were not statistically significant(P＞0.05).The regional distribution of pulmonary ventilation and perfusion changed in different positions,and the regional distributions differed in ROIl,ROI2 and ROI3 for ventilation(P＜0.05)and in ROI1 and ROI2 for perfusion(P＜0.05).The ventilation and perfusion regions were distributed consistently with the gravity-dependent areas in supine and prone positions whereas conversely in the right and left lateral positions.Conclusion The V/Q matching indexes of one subject have high test consistency in different body positions;gravity-dependent areas varied with the changes of the body positions,which affected the distribution of pulmonary ventilation and perfusion regions;EIT can be used for measuring the changed pulmonary ventilation and perfusion due to different positions and determining the influences of position changes on pulmonary ventilation and perfusion and V/Q matching.[Chinese Medical Equipment Journal,2024,45(5):1-7]

Objective With the widespread of transcatheter aortic valve replacement(TAVR)in patients with severe symptomatic aortic stenosis(AS),the life-cycle management has become a major determinant of prognosis.Methods A total of 408 AS patients who underwent successfully TAVR from June 2021 to August 2023 were consecutively enrolled in Hospital Valve Intervention Center.Patients were assigned to the Usual Care(UC)group between June 2021 and October 2022,while patients were assigned to the Heart Multi-parameter Monitoring(HMM)group between November 2022 and August 2023.The primary endpoint was defined as composite endpoint within 6 months post-TAVR,including all-cause death,cardiovascular death,stroke/transient ischemic attack,conduction block,myocardial infarction,heart failure rehospitalization,and major bleeding events.Secondary endpoints were the time interval(in hours)from event occurrence to medical consultation or advice and patient satisfaction.Statistical analysis was performed using Kaplan-Meier and multivariable Cox proportional hazards models.Results The incidence of primary endpoint in HMM group was significantly lower than that in UC group(8.9％vs.17.7％,P=0.016),the driving event was the rate of diagnosis and recognition of conduction block.The average time intervals from event occurrence to receiving medical advice were 3.02 h in HHM group vs.97.09 h in UC group(P＜0.001).Using cardiac monitoring devices and smart healthcare platforms provided significant improving in patients long-term management(HR 0.439,95％CI 0.244-0.790,P=0.006).Conclusions The utilization of cardiac monitoring devices and smart healthcare platforms effectively alerted clinical events and improved postoperative quality of life during long-term management post TAVR.