Locomotion, a fundamental motor function encompassing various forms such as swimming, walking, running, and flying, is essential for animal survival and adaptation. The mesencephalic locomotor region (MLR), located at the midbrain-hindbrain junction, is a conserved brain area critical for controlling locomotion. This review highlights recent advances in understanding the MLR’s structure and function across species, from lampreys to mammals and birds, with a particular focus on insights gained from optogenetic studies in mammals. The goal is to uncover universal strategies for MLR-mediated locomotor control. Electrical stimulation of the MLR in species such as lampreys, salamanders, cats, and mice initiates locomotion and modulates speed and patterns. For example, in lampreys, MLR stimulation induces swimming, with increased intensity or frequency enhancing propulsive force. Similarly, in salamanders, graded stimulation transitions locomotor outputs from walking to swimming. Histochemical studies reveal that effective MLR stimulation sites colocalize with cholinergic neurons, suggesting a conserved neurochemical basis for locomotion control. In mammals, the MLR comprises two key nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). Both nuclei contain glutamatergic and GABAergic neurons, with the PPN additionally housing cholinergic neurons. Optogenetic studies in mice by selectively activating glutamatergic neurons have demonstrated that the CnF and PPN play distinct roles in motor control: the CnF drives rapid escape behaviors, while the PPN regulates slower, exploratory movements. This functional specialization within the MLR allows animals to adapt their locomotion patterns and speed in response to environmental demands and behavioral objectives. Similar to findings in lampreys, the CnF and PPN in mice transmit motor commands to spinal effector circuits by modulating the activity of brainstem reticular formation neurons. However, they achieve this through distinct reticulospinal pathways, enabling the generation of specific behaviors. Further insights from monosynaptic rabies viral tracing reveal that the CnF and PPN integrate inputs from diverse brain regions to produce context-appropriate behaviors. For instance, glutamatergic neurons in the PPN receive signals from other midbrain structures, the basal ganglia, and medullary nuclei, whereas glutamatergic neurons in the CnF rarely receive inputs from the basal ganglia but instead are strongly influenced by the periaqueductal grey and inferior colliculus within the midbrain. These differential connectivity patterns underscore the specialized roles of the CnF and PPN in motor control, highlighting their unique contributions to coordinating locomotion. Birds exhibit exceptional flight capabilities, yet the avian MLR remains poorly understood. Comparative studies suggest that the pedunculopontine tegmental nucleus (PPTg) in birds is homologous to the mammalian PPN, which contains cholinergic neurons, while the intercollicular nucleus (ICo) or nucleus isthmi pars magnocellularis (ImC) may correspond to the CnF. These findings provide important clues for identifying the avian MLR and elucidating its role in flight control. However, functional validation through targeted experiments is urgently needed to confirm these hypotheses. Optogenetics and other advanced techniques in mice have greatly advanced MLR research, enabling precise manipulation of specific neuronal populations. Future studies should extend these methods to other species, particularly birds, to explore unique locomotor adaptations. Comparative analyses of MLR structure and function across species will deepen our understanding of the conserved and evolved features of motor control, revealing fundamental principles of locomotion regulation throughout evolution. By integrating findings from diverse species, we can uncover how the MLR has been adapted to meet the locomotor demands of different environments, from aquatic to aerial habitats.

Objective:To explore the intervention effects of repetitive transcranial magnetic stimulation on cognitive function of schizophrenia patients with methods using meta-analysis.Methods:CNKI,Wanfang Data,VIP,PubMed,Web of Science,the Cochrane Library and Embase were searched for randomized controlled trials of repetitive transcranial magnetic stimulation on cognitive function in schizophrenia.Quality assessment was per-formed with the Cochrane Handbook for Systematic Reviews.Effect sizes and heterogeneity were assessed using RevMan 5.3.Results:A total of 31 randomized controlled trials(2 421 patients)were included in this study.Meta-analysis showed that rTMS improved cognitive function in schizophrenia patients(SMD=0.73).Subgroup analyses showed that intervention intensity was less than or equal to 100％RMT,the intervention frequency was 1 Hz,the intervention time was lasted at least 20 min/time,and the intervention period was four weeks,the effect of rTMS was better.Subgroup analyses showed that rTMS was more effective in improving for patients with durations of 5 to 10 years.Conclusion:rTMS has more significant improvement effects on cognitive function in schizophrenia pa-tients.It is recommended to set the intervention intensity 100％RMT,the intervention frequency of 1 Hz,the in-tervention time ≥20 min,and the intervention period of 4 weeks in the clinic.

Sleep-wake disorder is one of the most common nonmotor symptoms of Parkinson's disease (PD). Melatonin has the potential to improve sleep-wake disorder, but its mechanism of action is still unclear. Our data showed that melatonin only improved the motor and sleep-wake behavior of a zebrafish PD model when melatonin receptor 1 was present. Thus, we explored the underlying mechanisms by applying a rotenone model. After the PD zebrafish model was induced by 10 nmol/L rotenone, the motor and sleep-wake behavior were assessed. In situ hybridization and real-time quantitative PCR were used to detect the expression of melatonin receptors and lipid-metabolism-related genes. In the PD model, we found abnormal lipid metabolism, which was reversed by melatonin. This may be one of the main pathways for improving PD sleep-wake disorder.
Animals ; Zebrafish ; Melatonin/pharmacology* ; Lipid Metabolism/drug effects* ; Disease Models, Animal ; Rotenone/pharmacology* ; Sleep Wake Disorders/metabolism* ; Parkinson Disease/metabolism* ; Motor Activity/drug effects* ; Sleep/drug effects*

Objective:To explore the tracking accuracy of the surface optically guided tracking system (OGTS) in radiotherapy.Methods:Phantom verification and clinical trial verification were adopted. Specialized equipment was employed for the phantom verification. Specifically, the displacement of the optical markers as they moved from a predetermined position to the target position on the reflector ball platform was captured using the OGTS, and then the obtained displacement was compared with the fixed distance within the phantom to calculate the accuracy and repeatability of the OGTS. For the clinical trial verification, 45 patients treated with radiotherapy, which consisted of 15 cases with head, breast, and rectal tumors each, were selected to investigate the tracking accuracy and repeatability of the OGTS. For each patient, the values derived from the image-guided positioning system (IGPS) and the OGTS before and after image-guided setup error correction during three times of fractionated radiotherapy were randomly obtained. The translational errors of each error correction were also recorded. Before radiotherapy, patients′ setup errors were corrected and relevant data were obtained using the IGPS. The correction result of translation errors obtained using the IGPS served as a gold standard to verify the accuracy of the OGTS in monitoring the translational motion of patients. Finally, the comprehensive translational deviation of both method was calculated.Results:The phantom measurements showed that the comprehensive translational deviation for tracking accuracy and tracking repeatability of the OGTS had a maximum deviation and a standard deviation of 0.18 mm and 0.03 mm, respectively. The clinical trial result indicated that the tracking accuracy of IGPS and OGTS exhibited statistically significant differences only for the head in the z direction ( t = 2.21, P < 0.05). Conversely, no statistically significant differences were observed for the head in the remaining directions or for the breast and rectum in the three translational directions ( P > 0.05). The analysis showed that comprehensive translational deviations for the head, breast, and rectum derived from OGTS and IGPS were (0.91±0.62), (1.64±1.30), and (1.52±1.29) mm, respectively, satisfying the requirement that the deviations should be below 2 mm. Conclusions:The OGTS, featuring easy operation and high tracking accuracy, can assist the IGPS in real-time respiratory monitoring during radiotherapy.

Objective:To investigate the clinical value of dynamic detection of lymphocyte subsets and blood cell counts in management of patients with lupus nephritis (LN).Methods:The clinical data of 65 patients with primary LN admitted in Affiliated Hospital of Qingdao University from January 2015 to April 2021 were retrospectively analyzed. According to the stage of disease progression and medications used,LN patients were classified into primary active phase,post-induction therapy phase,and maintenance therapy phase. The changes in lymphocyte subsets were monitored,and the relationship of lymphocyte subsets and blood cell count ratios with lupus activity and infection events was evaluated.Results:The decrease of CD4 +T lymphocyte and NK cell counts were negatively correlated with the activity of systemic lupus erythematosus (SLE)( r=-0.67,-0.33, P<0.01),while CD8 +T lymphocyte,B cell counts,neutrophil/lymphocyte ratio (NLR),platelet/lymphocyte ratio (PLR),and monocyte/lymphocyte ratio (MLR) were positively correlated with the SLE activity( r=0.38,0.26,0.34,0.26,0.29, P<0.05). The area under ROC curve (AUC) of CD4 +T lymphocyte count in predicting the occurrence of infection in LN patients was the highest (0.89); taking 247.50 cell/μl as cutoff value,the sensitivity and specificity were 81.25% and 87.50%,respectively. The combination of CD4 +T lymphocyte with CRP increased the predicting value for the occurrence of infection. Conclusion:Dynamic detection of blood lymphocyte subsets and blood cell counts can reflect SLE activity and the occurrence of infection in LN patients. Among these indicators the CD4 +T lymphocyte has the highest predictive value for the occurrence of infection,and the combination of the CD4 +T lymphocyte count with CRP level can further improve the predicting value.

[Abstract] Objective To establish an inflammation model by stimulating BV2 microglia by lipopolysaccharide, and to explore the regulation effect of ginsenoside Rg1 on inflammation by activating peroxisome proliferator activated receptor γ(PPARγ) receptor protein. Methods BV2 microglia were randomly divided into control group, model group, ginsenoside Rg1 group, rosiglitazone group and GW9662 group. The control group did not do any treatment, the model group was treated with 1 mg/ L lipopolysaccharide, and the other groups were treated with lipopolysaccharide added with 0. 4 mmol/ L ginsenoside Rg1, 10 μmol/ L rosiglitazone or 10 μmol/ L respectively. GW9662. The proliferation of BV2 microglia in each group was detected by CCK-8 method; PPAR-γ, phospho-NF-κB p65 (p-NF-κB p65), induced expression of inducible nitric oxide synthase(iNOS) and human arginase 1(ARG-1) proteins. ELISA was used to detect the inflammatory factors interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-8(IL-8) and the content of tumor necrosis factor-α (TNF-α). Results Compared with the control group, the cell proliferation rate in the model group was significantly increased, and the contents of IL-1β, IL-6, IL-8 and TNF-α increased significantly. The result of immunofluorescence and Western blotting showed that iNOS and p-NF-κB p65 increased significantly, and the positive expressions of PPARγ and ARG-1 decreased significantly(both P<0. 01). The expression level of TNF-α decreased, the positive expressions of iNOS and p-NF-κB p65 decreased significantly, and the positive expressions of PPARγ and ARG-1 increased significantly(all P<0. 01). Conclusion Ginsenoside Rg1 inhibits the inflammatory response of BV2 microglia after lipopolysaccharide stimulation, and its mechanism may be related to the regulation of PPARγ/ NF-κB pathway to promote the M2-type polarization of microglia.

Objective:To improve the quality assurance (QA) skills of radiotherapy personnel and medical students and reduce the radiation risk of training by developing a remote training system for QA of medical electronic linear accelerators.Methods:This training system was built based on radiotherapy technology and quality control contents of medical electronic linear accelerators, and a virtual reality interactive software was developed using extended reality (XR) technology Unity 3D. A remote control module of multi-terminal platform was also developed. A multi-perspective evaluation system was adopted and a questionnaire was designed to analyze the application value of this system.Results:The training system reproduced the live environment and physical objects of medical electronic linear accelerator treatment room. It built a multi-terminal virtual simulation training system with radiotherapy technology as well as QA knowledge system. This system could provide 5G remote control of medical electronic linear accelerator for off-site quality control demonstration and guidance. By March 1, 2022, a total number of 133 people had been trained using this system, 76 valid questionnaires had been taken, of which 90.79% (69/76) of the respondents trusted the experimental results shown by the system and 88.16% (67/76) of the respondents considered the training system necessary.Conclusions:The training effect of this system is widely recognized. It fundamentally reduces the training radiation hazard and provides reference for the reform and progress of QA training mode of medical electronic linear accelerators.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Objective To design a full-chain teaching platform for oral and maxillofacial surgery to solve the problems of the traditional teaching mode in medical students'clinical thinking ability,practical operation and evaluation.Methods A full-chain teaching platform for oral and maxillofacial surgery was developed with B/S architecture and front-end and back-end separation mode.The server end was programmed with Java language and the browser was realized with TypeScript language.The teaching platform developed was composed of three functional modules for basic training,practical operation and examination and evaluation.Results The platform developed enabled medical students to observe the whole process of oral and maxillofacial surgery in an immersive environment,and facilitated the practical operation and the evaluation for teaching effects.Conclusion The platform developed effectively standardizes the training of medical students in oral and maxillofacial surgery,improves their theoretical level,thinking ability and practical operation and enhances teaching effects for oral and maxillofacial surgery.[Chinese Medical Equipment Journal,2023,44(10):44-48]

To investigate the clinical and immunological features of dermatomyositis (DM) complicated with macrophage activation syndrome (MAS). The demographic and clinical characteristics of five patients diagnosed with DM complicated with MAS hospitalized in the Department of Rheumatology and Immunology, Peking University People ' s Hospital from 2011 to 2021 were collected. The results of clinical manifestations, laboratory tests, immunological features, treatments and prognosis were analyzed and summarized. In this study, five female patients in Peking University People's Hospital with an average age of 63.8 (44.0-83.0) years and an average disease duration of 16.1 (1.5-48.0) months. All the patients had typical DM rash (such as heliotrope sign, V/shawl sign or Gottron's sign/papules). They all had muscle involvement (including myalgia or muscle weakness). Two patients had positive myositis-specific antibodies (MSAs), in which case 1 had anti-TIF1-γ antibody and case 5 had anti-NXP-2 antibody. Four patients had interstitial lung disease except case 3. All of the cases developed MAS in the active stage of DM. Common manifestations of MAS in these five patients included high-grade fever, cytopenia, decreased fibrinogen, elevated ferritin and increased soluble CD25. Case 1 presented with neutropenia (0.6×10⁹ /L), thrombocytopenia (26.0×10⁹ /L), hypofibrinogenemia (0.9 g/L), markedly elevated ferritin (26 331.0 μg/L), decreased NK cell activity. Case 2 had anaemia (hemoglobin 81.0 g/L), thrombocytopenia (55.0×10⁹ /L), hypertriglyceridemia (4.7 mmol/L), hypofibrinogenemia (1.2 g/L), elevated ferritin (>100 000.0 μg/L), hemophagocytosis in bone marrow. Case 3 had anaemia (hemoglobin 88 g/L), decreased fibrinogen (1.9 g/L), increased ferritin (>27 759.0 μg/L), splenomegaly, hemophagocytosis in bone marrow. Case 4 suffered from neutropenia(0.3×10⁹ /L), anaemia(hemoglobin 78 g/L), hypertriglyceridemia (4.2 mmol/L), hypofibrinogenemia (0.9 g/L), increased ferritin (>100 000.0 μg/L), and decreased NK cell activity. Case 5 presented anaemia (hemoglobin 60.0 g/L), thrombocytopenia (67.0×10⁹ /L), hypertriglyceridemia (12.7 mmol/L), decreased fibrinogen (1.1 g/L), and elevated ferritin (>923.0 μg/L). All the patients were treated with methylprednisone pulse therapy (200-500 mg) combined with cyclosporine while case 5 received rituximab after methylprednisone pulses. In addition, case 3 also received the combination of mycophenolate mofetil. Case 1 was given etoposide while case 4 was treated with cyclophosphamide and repeated plasmapheresis at the same time. Moreover, intravenous immunoglobulin was added meantime apart from case 3. The condition of four patients improved significantly, nevertheless case 4 experienced recurred pulmonary symptoms and died of respiratory failure. As for complications about infection, case 2 had bacterial infection with high level procalcitonin (PCT) before MAS treatment and condition was improved after empiric antibacterial therapy. Case 3 had cytomegalovirus DNAemia before diagnosis of MAS and viral titer turned negative after ganciclovir therapy. After treatment of MAS, four patients developed cytomegalovirus DNAemia except case 3, in which case 5 was co-infected with bacteria. To sum, DM complicated with MAS is relatively rare, and its patients are of ten in life-threatening condition. Early detection, treatment and prevention of infection during treatment are critical to improve the prognosis.
Humans ; Female ; Middle Aged ; Dermatomyositis/complications* ; Macrophage Activation Syndrome/complications* ; Afibrinogenemia/complications* ; Autoantibodies ; Neutropenia ; Thrombocytopenia/complications* ; Ferritins/therapeutic use* ; Hypertriglyceridemia/complications* ; Fibrinogen/therapeutic use*