Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*

Objective:To explore the association between weight status and early changes in blood pressure, cardiac structure and function in children at 4 years of age.Methods:A cross-sectional study of the relationship between weight status and cardiovascular parameters was performed on the platform of "Shanghai Birth Cohort" in Shanghai Xinhua Hospital between 2017 and 2020. Height, weight, blood pressure and echocardiography were measured in 1 477 children at 4 years of age. According to body mass index (BMI), participants were classified into five groups: underweight, lean, normal weight, overweight and obese. Blood pressure, cardiac structure and function indexes were compared among different groups using one-way ANOVA. The associations between blood pressure, cardiac structure and function and weight status in children were analyzed by linear regression models. Multivariate logistic regression models were used to analyze whether weight status was an independent risk factor for elevated blood pressure or left ventricular hypertrophy (LVH) in children.Results:A total of 1 477 children including 772 boys and 705 girls were included in this study. There were 115 overweight and obese boys (14.9%) and 68 overweight and obese girls (9.6%). The majority of children had normal weight (916 cases, 62.0%), followed by underweight (303 cases, 20.5%), overweight (130 cases, 8.8%), lean (75 cases, 5.1%), and obese (53 cases, 3.6%). With the increase of BMI, systolic blood pressure, diastolic blood pressure, left ventricular mass index (LVMI), left ventricular posterior wall thickness in systole, left ventricular posterior wall thickness in diastole, left ventricular diameter in end-systole, left ventricular diameter in end-diastole, interventricular septum thickness in systole and left ventricular ejection fraction showed significantly positive trend, and the differences among the groups were significant (F=31.73, 6.59, 14.22, 4.96, 3.01, 31.50, 39.79, 5.91, 3.09, all P<0.05). Multiple linear regression showed that overweight and obese were all positively associated with systolic blood pressure (β=5.2, 95% CI 3.6-6.8), LVMI (β=1.9, 95% CI 0.8-3.1), left ventricular diameter in end-systole (β=1.3, 95% CI 0.9-1.8), and left ventricular diameter in end-diastole (β=1.6, 95% CI 1.0-2.2). In the Logistic regression model, compared with normal weight children, overweight ( OR=2.37, 95% CI 1.37-4.41) and obese children ( OR=10.90, 95% CI 4.47-26.60) both had significantly increased risk of elevated blood pressure. However, the risk of LVH did not significantly increased. Conclusions:Overweight and obesity in 4-year-old children are associated with increased blood pressure, increased left ventricle diameter and LVMI. Overweight and obesity are independent risk factors for elevated blood pressure in children at 4 years of age.

Objective:To study the variation in activity in patient′s body with differentiated thyroid cancer (DTC) treated with 131I and external dose level, analyze the relationship between the both, and estimate the correction factor for the dose equivalent rate for the patients with residual activity of 400 MBq. Methods:A total of 43 DTC patients who received 131I therapy for the first time after total thyroidectomy were studied. The dose was 1 850-3 700 MBq and average dose was (2 405±777) MBq. The measurements of residual activity in patient′s body and of dose equivalent rate at 0.3, 1 and 3 m in front of the patients were performed at 2, 6, 20, 22, 24, 27, 30, 44, 46, 48, 54, 68 and 72 h after administration of 131I. Results:The residual activity in patient′s body after 131I therapy varied with time as a function of A= A0 (1.033 16e -0.062 4t+ 0.017 17). It can be estimated that the effective half-life of DTC patients treated with thyroid remnant 131I ablation therapy is 12.19 h. It needs only 26.4-38.9 h to reduce the internal activity to the 400 MBq. The functions of variation with time of normalized dose equivalent rate at 0.3, 1, and 3 m away from patients were: H· 0.3=127.220 7e -0.054 8t+ 3.765 71; H· 1=30.225 8e -0.064 4t+ 0.824 67; and H· 3=4.161 9e -0.061 5t+ 0.167 97, respectively. There was a positive correlation between residual activity and dose equivalent rate at 1 m ( r=0.982, P<0.05), and the function is H· 1=0.025 A+ 1.245. When residual activities in DTC patient′s body were 1 000, 700 and 400 MBq, the corresponding dose equivalent rates at 1 m from patients were 26.2, 18.7 and 11.2 μSv/h, respectively. The correction factors for dose equivalent rate at 0.3, 1 and 3 m from patients with 400 MBq were 0.25, 0.49 and 0.70, respectively. Conclusions:DTC patients with administration of 131I activity below 3 700 MBq need only to be hospitalized for two days to reach the discharge standards. When the residual activity in DTC patient′s body drops to 400 MBq, the dose equivalent rate at 1 m is far less than 25 μSv/h. Simply using the point source formula to estimate the dose equivalent rate around the patient will result in overestimation. Therefore, the correction factor used in the estimation of radiation doses to patients by using the formula needs to be further studied so as to make the model-based estimated result more consistent with the actual situation.

This article reviews the common bowel preparation programs, influencing factors and intervention strategies before colonoscopy in elderly subjects, with a view to provide reference for improving the quality of bowel preparation in elderly colonoscopy subjects in the future.

OBJECTIVE:To observe therapeutic efficacy and safety of cefoperazone sodium and sulbactam sodium combined with Shenmai injection in the treatment of elderly stroke associated pneumonia(SAP). METHODS:A total of 84 SAP patients in Dazhou Municipal Central Hospital during Mar. 2016-Mar. 2017 were divided into control group(42 cases)and observation group (42 cases)according to random number table. Based on routine treatment,control group was additionally given Cefoperazone sodium and sulbactam sodium for injection 3 g added into 5% Glucose injection 100 mL,intravenously,twice a day;suitable antibiotics were selected according to the results of pathogenic examination and drug sensitivity test. Observation group was additionally given Shenmai injection 100 mL added into 5% Glucose injection 250 mL intravenously,once a day,on the basis of control group. Both groups were treated for consecutive 2 weeks. Clinical efficacies of 2 groups were observed,and the levels of T-lymphocyte subsets(CD4+,CD8+,CD4+/CD8+)and inflammatory markers(TNF-α,hs-CRP,PCT),length of hospital stay before and after treatment. The ADR was recorded. RESULTS:The total response rate(95.24%)and marked response rate (47.62%)of observation group were significantly higher than those of control group(83.33%,23.81%);length of hospital stay in observation group [(15.24±3.53)d] was significantly shorter than control group [(18.43±4.21)d],with statistical significance (P<0.05).After treatment,the levels of CD4+and CD4+/CD8+in 2 groups were significantly higher than before treatment,and the observation group was significantly higher than the control group;the levels of CD8 +,TNF-α,hs-CRP and PCT in 2 groups were significantly lower than before treatment;the observation group was significantly lower than the control group,with statistical significance(P<0.05);there was no statistical significance in the incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:Based on routine treatment,cefoperazone sodium and sulbactam sodium combined with Shenmai injection treat SAP significantly,can effectively improve immune function, reduce inflammation level and shorten the length of hospital stay without increasing the occurrence of ADR.

Objective To investigate the effect of transient receptor potential M4 (TRPM4) on autonomous regulation disorder of cerebral blood flow following subarachnoid hemorrhage (SAH) in rats.Methods A total of 120 clean grade male SD rats were selected.They were divided into sham operation,SAH,negative control,and treatment groups according to the random number table.The dead rats were excluded.A SAH model was induced by using the suprasellar cistern injection method with a stereotaxic apparatus.Isotonic saline 0.2 ml was injected into the rats of the sham operation group and negative control group respectively,and autologous tail arterial blood 0.2 ml was injected into the rats of the SAH group and the treatment group respectively.The isotonic saline solution was continuously pumped into lateral ventricle of rats via implantable micro-pump in the sham operation group and the SAH group respectively,and the concentration of 0.03 mol/L of TRPM4 blocking agent was continuously pumped into the lateral ventricles of rats in the control group and the treatment group respectively.The 4 groups of rats received the regional cerebral blood flow and whole cerebral blood flow detection on day 3,5,and 7,respectively.Results One hundred and six (88.3%) of the 120 SD rats survived to the time point of study,data analyses were performed in the 4 groups (with 21 rats in each group) respectively (n=7 in each time point).There were significant differences in cerebral cortex local and whole cerebral blood flow at day 3,5,and 7 in the sham operation,SAH and negative control groups (all P<0.05).Cerebral cortex local cerebral blood flow (141±18,148±24,and 168±19 PU,respectively at day 3,5,and 7) and whole cerebral blood flow (93±5,85±5,and 85±6 ml/[100 g·min],respectively at day 3,5,and 7 in the SAH group) were decreased significantly compared with the sham operation group (cortex local cerebral blood flow:235±17,220±24,and 224±20 PU),whole cerebral blood flow (141±10,147±8,and 143±8 ml/[100 g·min]),all P<0.05).Cerebral cortex local and whole cerebral blood flow (cortical local cerebral blood flow:183±26,173±26,and 187±15 PU,whole brain:114±10,104±9,and 119±5 ml/(100 g·min) in the treatment group were significantly increased compared with the SAH group (all P<0.05).Conclusion TRPM4 has an obvious effect on improving the autonomous regulation disorder of cerebral blood flow after SAH.

Objective To modify the purified water analysis methods in the Chinese Pharmacopoeia (Vol .Ⅱ ,Edition 2010) ,and mainly focus on the pH value determination ,analysis of nitrate and nitrite ,and the inspection of microorganism . Methods The usage of regents and colorimetric tubes in the analysis of nitrate and nitrite were inquired ,the feasibility of plat-ing culture used in the inspection of microorganism were proposed ,and the suggestion of using more instrumental analysis in-stead of titrimetric analysis in the purified water inspection wasraised .Results The choice of colormetric apparatus and the precision of the regents were explicit .The plating method was better in convenience and reliability than membrane-filter proce-dure during the microorganism inspection .Instrumental analysis is the trend of purified water inspection and deserved to be rec-ommended .Conclusion Based on our own and others′studies ,the methods of impurity analysis are improved ,which might be accepted in the revision of Chinese Pharmacopoeia in future .

Objective To investigate the influence of MgSO4 with different concentrations on cell survival and γ-H2AX expression in HUVEC irradiated with X-rays.Methods Cell proliferation rate was assayed by CCK-8,γ-H2AX foci formationwas observed with a laser confocal microscope,and γ-H2AX protein expression was detected by flow cytometer and Western blot assay.Results MgSO4 with a concentration of 1.25 mg/ml could improve the survival rate of IHUVEC treated with X-rays (t =-6.34,P ＜ 0.05).After irradiation,γ-H2AX loci approached to the highest level from 30 min to 1 h after radiation and then decreased.MgSO4 significantly reduced the foci formation at 0.5,1,2,6 and 12 h postirradiation (t =12.62,6.36,11.93,5.75,9.43,P ＜ 0.05).Both flow cytometry,and Western blot assays showed that MgSO4 inhibited γ-H2AX protein expression at 0.5,1 and 2 h post-irradiation (t =6.07,5.32,11.85,P ＜ 0.05).Conclusions MgSO4 could improve the survival rate and reduced γ-H2AX expression in HUVEC irradiated with X-ray.

Objective To study the effect of spontaneous subarachnoid hemorrhage (SAH)on transient receptor potential melastatin 4 (TRPM4)channel activity. Methods Seventeen SD rats of clean grade were selected. They were randomly divided into either a SAH (n = 10)or a sham operation group (n = 7) according to the random number table. At day 5 after SAH modeling,the cerebral arteries were harvested and the cerebral arterial smooth muscle cells were isolated using enzymatic digestion method. Western blot was used to detect TRPM4 expression and translocation rate. Patch-clamp techniques were used to study the maximum current intensity of the TRPM4 single channel in cerebral arterial smooth muscle cells. Results The fluorescent-stained TRPM4 were observed in cerebral arterial smooth muscle cells in the 2 groups of rats. The relative quantities of TRPM4 in the total protein of the sham operation group and the SAH group were 24 ± 3% and 32 ± 4% respectively. There was significant difference between the 2 groups (t = 4. 47,P < 0. 01). The translocation rates of TRPM4 in the sham operation group and the SAH group were 44. 0 ± 1. 9% and 60. 1 ± 2. 3% respectively,and the SAH group was higher than the sham operation group (χ2 = 4. 48,P < 0. 05). When the clamping voltages were - 100 mV,- 80 mV,- 60 mV,and - 40 mV,the maximum current intensity of TRPM4 single channel of the sham operation group was more than that of the SAH group. There were significant differences between the 2 groups (- 1. 90 ± 0. 10 mV vs. - 2. 23 ± 0. 08 mV,- 1. 68 ± 0. 12 mV vs. - 1. 99 ± 0. 12 mV,- 0. 89 ± 0. 09 mV vs. - 1. 24 ± 0. 09 mV,and - 0. 69 ± 0. 12 mV vs. - 0. 92 ± 0. 11 mV;all P < 0. 01). When the clamping voltages were - 20,0,20,40,60,80,and 100 mV,there was no significant difference in the maximum current intensity of TRPM4 single channel between the 2 groups (all P > 0. 05). Conclusion SAH has the induced effect for TRPM4 activity.