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 determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Objective:To investigate the influencing of preoperative total bilirubin (TBil) on perioperative complications of hepatolithiasis receiving liver resection.Methods:The retrospective cohort study was conducted. The clinical data of 300 patients with hepatolithiasis who were admitted to 2 medical centers from January 2010 to January 2022 were collected. There were 115 males and 185 females, aged (54±13)years. Measurement data with normal distribution were represented as Mean± SD, and the independent sample t test was used for comparison between groups. Measurement data with skewed distribution were represented as M( Q1, Q3), and the Mann-Whitney U test was used for comparison between groups. Count data were expressed as absolute numbers, and the chi-square test was used for comparison between groups. Variables with P<0.10 in the univariate analysis were included into the multivariate analysis. Univariate analysis was conducted using the Logistic regression model,and multivariate analysis was conducted using the Logistic stepwise regression model with backward Wald method. Continuous variables were converted into categorical variables based on commonly reported cutoff values when conducting Logistic regression analysis. Results:(1) Comparison of clinical data of patients with different preoperative TBil. Of 300 patients with hepatolithiasis, there were 252 cases with low level of preoperative TBil as 14.4(11.1,19.7)μmol/L, and there were 48 cases with high level of preoperative TBil as 44.0(31.3,59.8)μmol/L. Of the pati-ents with low level of preoperative TBil, neutrophils percentage was 62%±10%, cases with intra-operative blood transfusion was 29, and cases undergoing anatomical liver resection was 166. Of the patients with high level of preoperative TBil, neutrophils percentage was 70%±11%, cases with intraoperative blood transfusion was 22, and cases undergoing anatomical liver resection was 15. There were significant differences in cases classified as>grade 2 of ASA classification, neutrophils percentage, cases with intraoperative blood transfusion and cases undergoing anatomical liver resection between patients with low and high level of preoperative TBil ( t=5.182, χ2=33.669, 18.775, P<0.05). (2) Comparison of perioperative complications of patients with different preoperative TBil. Of the 252 patients with low level of TBil, there were 151 cases with complications including 35 cases of serious complications, there was 1 case with postoperative liver failure, the duration of postoperative hospital stay was 13.0(10.0,16.0)days. Of the 48 patients with high level of TBil, there were 32 cases with complications including 17 cases of serious complications, there were 6 cases with postoperative liver failure, the duration of postoperative hospital stay was 14.0(10.0,18.8)days. There were significant differences in cases with serious complications and cases with postoperative liver failure between patients with low and high level of preoperative TBil ( χ2=13.041, 20.879, P<0.05). (3) Analysis of factors influencing postoperative serious complications in patients undergoing liver resection. Results of multivariate analysis showed that age, body mass index (BMI), preoperative TBil and volume of intraoperative blood loss were independent factors influencing postoperative serious complications in patients undergoing liver resection for hepatolithiasis ( odds ratio=3.852, 2.358, 2.935, 5.135, 95% confidence interval as 1.478?9.979, 1.110?5.009, 1.398?6.158, 2.088?12.626, P<0.05). Conclusions:Patients with high level of preoperative TBil have a significantly increased risk of postoperative serious complications and liver failure who receive liver resection for hepatolithiasis. Age, preoperative BMI, TBil and volume of intraoperative blood loss are independent factors influencing postoperative serious complications in patients undergoing liver resection for hepatolithiasis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the role of p-AKT-mTOR-P70S6K signaling pathway in radiation therapy for polyploid cervical cancer cells.Methods:Human cervical cancer HeLa cell lines were selected and HeLa cells were radiated under 7 Gy of 6 MV X-ray. The morphological changes of the cells were observed with an inverted microscope on day 5 after radiation induction. All cells were divided into the 7 Gy group (7 Gy X-ray radiation but not transfected polyploidy HeLa cells) and the control group (the non-radiation-induced and not transfected HeLa cells). In addition, the plasmid carrying pcDNA3 negative control sequence and the plasmid carrying pcDNA3-TT-AKT sequence were transfected into HeLa cells, respectively, which were induced by 7 Gy X-ray radiation after 48 h of transfection, and then they were recorded as the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group. Cell proliferation ability was detected by using CCK-8 assay, cell cycle was detected by using flow cytometry, cell apoptosis was detected by using mitochondrial membrane potential assay, the relative expression levels of cell proliferation, cell cycle, apoptosis and autophagy related proteins were tested by using Western blot.Results:Most of the normal HeLa cells in the 7 Gy group died on day 5 after radiation induction, and only a few surviving cells increased in size with multiple nuclei. The results of Western blot showed that the relative expression levels of p-AKT, p-mTOR and p-P70S6K in HeLa cells of the 7 Gy group were lower than those of the control group (all P < 0.05). CCK-8 assay showed that the absorbance ( A) values were 0.45±0.06, 0.65±0.06 after 48 h of culture and 0.75±0.05, 1.05±0.02 after 72 h of culture, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the differences were statistically significant (all P < 0.05), and the A values in the pcDNA3-TT-AKT + 7 Gy group were all higher than those in the pcDNA3 +7 Gy group. Flow cytometry results showed that the proportion of cells was (29.2±3.6)%, (26.7±1.7)% in G 0/G 1 phase and (29.6±1.6)%, (30.3±0.6)% in G 2/M phase, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the differences were not statistically significant (all P > 0.05); the proportion of cells in S phase was (10.2±0.9)% and (14.6±1.5)%, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the differences were statistically significant ( t = 2.86, P = 0.043). Mitochondrial membrane potential assay showed that the green fluorescence proportion was (23.1±2.5)% and (14.3±1.9)%, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the different was statistically significant ( t = 4.82, P = 0.009). Western blot results showed that the relative expression level of p-cdc25c (Ser216) in the pcDNA3-TT-AKT+7 Gy group was higher than that in the pcDNA3+7 Gy group ( P < 0.001); and the relative expression levels of Bak and LC3-Ⅱ/Ⅰ in the pcDNA3-TT-AKT+7Gy group were lower than those in the pcDNA3 +7 Gy group, respectively (all P < 0.05). Conclusions:The p-AKT-mTOR-P70S6K signaling pathway may be involved in the regulation of radiation-induced polyploidy HeLa cell proliferation, cell cycle and cell apoptosis.

OBJECTIVE: To analyze and compare the characteristics and causes of F wave changes in patients with Charcot-Marie-Tooth1A (CMT1A) and chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Thirty patients with CMT1A and 30 patients with CIDP were enrolled in Peking University Third Hospital from January 2012 to December 2018. Their clinical data, electrophysiological data(nerve conduction velocity, F wave and H reflex) and neurological function scores were recorded. Some patients underwent magnetic resonance imaging of brachial plexus and lumbar plexus, and the results were analyzed and compared. RESULTS: The average motor conduction velocity (MCV) of median nerve was (21.10±10.60) m/s in CMT1A and (31.52±12.46) m/s in CIDP. There was a significant difference between the two groups (t=-6.75, P < 0.001). About 43.3% (13/30) of the patients with CMT1A did not elicit F wave in ulnar nerve, which was significantly higher than that of the patients with CIDP (4/30, 13.3%), χ²=6.65, P=0.010. Among the patients who could elicit F wave, the latency of F wave in CMT1A group was (52.40±17.56) ms and that in CIDP group was (42.20±12.73) ms. There was a significant difference between the two groups (t=2.96, P=0.006). The occurrence rate of F wave in CMT1A group was 34.6%±39%, and that in CIDP group was 70.7%±15.2%. There was a significant difference between the two groups (t=-5.13, P < 0.001). The MCV of median nerve in a patient with anti neurofascin 155 (NF155) was 23.22 m/s, the latency of F wave was 62.9-70.7 ms, and the occurrence rate was 85%-95%. The proportion of brachial plexus and lumbar plexus thickening in CMT1A was 83.3% (5/6) and 85.7% (6/7), respectively. The proportion of brachial plexus and lumbar plexus thickening in the CIDP patients was only 25.0% (1/4, 2/8). The nerve roots of brachial plexus and lumbar plexus were significantly thickened in a patient with anti NF155 antibody. CONCLUSION The prolonged latency of F wave in patients with CMT1A reflects the homogenous changes in both proximal and distal peripheral nerves, which can be used as a method to differentiate the CIDP patients characterized by focal demyelinating pathology. Moreover, attention should be paid to differentiate it from the peripheral neuropathy caused by anti NF155 CIDP. Although F wave is often used as an indicator of proximal nerve injury, motor neuron excitability, anterior horn cells, and motor nerve myelin sheath lesions can affect its latency and occurrence rate. F wave abnormalities need to be comprehensively analyzed in combination with the etiology, other electrophysiological results, and MRI imaging.
Humans ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/pathology* ; Median Nerve/pathology* ; Ulnar Nerve/pathology* ; Brachial Plexus/pathology* ; Magnetic Resonance Imaging/methods*

Objective:To investigate the characteristics related to proliferation, migration and invasion of radiation-induced polyploid colon cancer SW1116 cells and their progeny.Methods:Colon cancer SW1116 cells were conventionally cultured in Leibovitz's L-15 medium containing 10% fetal bovine serum. SW1116 cells at logarithmic growth stage were irradiated with 7 Gy X-ray, and the morphological changes of the cells were observed by inverted microscope on days 3, 5, 10 and 19 after radiation induction. According to the morphological changes of the cells, the cells at day 3 after radiation induction were labeled as polyploid giant cancer cell (PGCC) group, and the cells at day 19 were recorded as PGCC progeny group. SW1116 cells without radiation induction were used as control group. Flow cytometry was used to detect cell ploidy in the control, PGCC and PGCC progeny groups, CCK-8 assay was used to detect the proliferation ability of the three groups, cell migration and invasion abilities of the three groups were detected by cell scratch assay and Transwell assay, and Western blotting was used to detect the expressions of cell cycle and proliferation-related proteins and epithelial-mesenchymal transition (EMT) marker N-cadherin (N-cad) in the three groups.Results:The volume of SW1116 cells gradually became larger on days 3, 5 and 10 after radiation induction, and returned to normal on day 19. The proportions of polyploid (DNA content >4N) cell subsets in the control group, PGCC group and PGCC progeny group were (2.3±1.1)%, (23.1±8.1)% and (3.2±0.5)%, the difference was statistically significant ( F = 18.52, P < 0.05), and the proportion of polyploid cell subpopulations in the PGCC group was higher than that in the control group ( t = 5.38, P < 0.01), but the differences between the PGCC progeny group and the control group were not statistically significant ( t = 0.22, P > 0.05). After 72 h of culture, the cell proliferation rates of the control, PGCC and PGCC progeny groups were (100.0±4.1)%, (73.5±0.7)% and (123.9±3.5)%, and the difference was statistically significant ( F = 190.27, P < 0.001). After 48 h of cell scratching, the scratch healing rates in the control, PGCC and PGCC progeny groups were (38.0±2.7)%, (41.5±4.0)% and (63.7±4.2)%, and the difference was statistically significant ( F = 43.05, P < 0.001). After 24 h of culture, the number of invasive cells in the control, PGCC and PGCC progeny groups was 12.9±1.2, 3.4±0.6 and 23.7±1.5, and the difference was statistically significant ( F = 63.64, P < 0.001). The expression levels of cell cycle-related proteins P-cdc25c, cdc25c and cdc2 in the PGCC group were lower than those in the control group (all P < 0.05), and the expression levels of transcription factor-related proteins E2F-2, E2F-3 and EMT marker N-cad were downregulated compared with the control group (all P < 0.05); the expression levels of P-cdc25c, cdc25c, cdc2, E2F-2, E2F-3 and N-cad proteins in the PGCC progeny group were higher than those in the control group (all P < 0.05). Conclusions:Radiation can induce colon cancer SW1116 cells to produce polyploid, which may then generate daughter cells through asymmetric mitosis and gain new life, and then promote the recurrence and metastasis of colon cancer.

Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3^rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB₁, vitaminB₂, vitaminB₆, vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.
Humans ; Male ; Acidosis, Lactic ; Brain ; Brain Stem ; Dystonia ; Dystonic Disorders ; Mitochondrial Diseases ; Infant

Peripheral bacterial infections without impaired blood-brain barrier integrity have been attributed to the pathogenesis of Parkinson's disease (PD). Peripheral infection promotes innate immune training in microglia and exacerbates neuroinflammation. However, how changes in the peripheral environment mediate microglial training and exacerbation of infection-related PD is unknown. In this study, we demonstrate that GSDMD activation was enhanced in the spleen but not in the CNS of mice primed with low-dose LPS. GSDMD in peripheral myeloid cells promoted microglial immune training, thus exacerbating neuroinflammation and neurodegeneration during PD in an IL-1R-dependent manner. Furthermore, pharmacological inhibition of GSDMD alleviated the symptoms of PD in experimental PD models. Collectively, these findings demonstrate that GSDMD-induced pyroptosis in myeloid cells initiates neuroinflammation by regulating microglial training during infection-related PD. Based on these findings, GSDMD may serve as a therapeutic target for patients with PD.

Objective To explore the clinical effect of amniotic membrane transplantation combined with entropion correction for ocular surface and eyelid burns.Methods A total of 80 patients with ocular surface injury and lower eyelid entropion caused by chemical or thermal burns who received surgical treatment in our hospital were selected as the research objects.All patients received amniotic membrane transplantation combined with entropion correction.All patients were examined by slit-lamp microscope and photographed before and 8 weeks after surgery.The visual acuity changes,tear film rupture time and serum levels of vascular endothelial growth factor(VEGF),trans-forming growth factor β1(TGF-β1)and insulin growth factor 1(IGF-1)were compared before and 8 weeks after surgery.Eight weeks after surgery,exfoliated epithelial cells of the central cornea and limbus were collected and analyzed by PAS staining and immunofluorescence staining.Results At 8 weeks after surgery,the patient's ocular surface condition recovered well,eyelid entropion was successfully corrected,postoperative visual acuity was significantly better than that before surgery(P<0.05).Compared with before surgery,the tear film rupture time 8 weeks after surgery was significantly prolonged(P<0.05),and the serum VEGF,TGF-β1 and IGF-1 levels 8 weeks after surgery were significantly increased(P<0.05).PAS staining showed that there was no goblet cell in the central cornea and limbus.Immunofluorescence staining showed that cytokeratin 12(CK12)was highly expressed in the corneal epithelial cells,and low expressed in corneal limbal epithelial cells near the cornea.Conclusion Amniotic membrane transplantation combined with entropion correction has a significant therapeutic effect on patients with ocular burn,which can promote ocular surface repair,correct entropion,improve postoperative visual acuity,and achieve self-amplification of cornea stem cells.It is a safe and effective treatment method.