Purpose::Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.Methods::C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. Results::Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.Conclusions::Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Mechanical allodynia (MA), including punctate and dynamic forms, is a common and debilitating symptom suffered by millions of chronic pain patients. Some peripheral injuries result in the development of bilateral MA, while most injuries usually led to unilateral MA. To date, the control of such laterality remains poorly understood. Here, to study the role of microglia in the control of MA laterality, we used genetic strategies to deplete microglia and tested both dynamic and punctate forms of MA in mice. Surprisingly, the depletion of central microglia did not prevent the induction of bilateral dynamic and punctate MA. Moreover, in dorsal root ganglion-dorsal root-sagittal spinal cord slice preparations we recorded the low-threshold Aβ-fiber stimulation-evoked inputs and outputs of superficial dorsal horn neurons. Consistent with behavioral results, microglial depletion did not prevent the opening of bilateral gates for Aβ pathways in the superficial dorsal horn. This study challenges the role of microglia in the control of MA laterality in mice. Future studies are needed to further understand whether the role of microglia in the control of MA laterality is etiology-or species-specific.
Mice ; Animals ; Hyperalgesia/metabolism* ; Microglia/metabolism* ; Disease Models, Animal ; Spinal Cord/metabolism* ; Spinal Cord Dorsal Horn/metabolism* ; Ganglia, Spinal/metabolism*

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Ulcerative colitis (UC) is a chronic refractory non-specific intestinal inflammatory disease that is difficult to be cured. The discovery of new ulcerative colitis-related metabolite biomarkers may help further understand UC and facilitate early diagnosis. It may also provide a basis for explaining the mechanism of drug action in the treatment of UC. Compound Sophorae Decoction (CSD) is an empirical formula used in the clinical treatment of UC. Although it is known to be efficacious, its mechanism of action in the treatment of UC is unclear. The purpose of this study was to investigate the changes in endogenous substances in UC rats and the effects of CSD on metabolic pathways using the metabonomics approach. Metabolomics studies in rats with UC and normal rats were performed using LC-MS/MS. Rats with UC induced using TNBS enema were used as the study models. Metabolic profiling and pathway analysis of biomarkers was performed using statistical and pathway enrichment analyses. 36 screened potential biomarkers were found to be significantly different between the UC and the normal groups; it was also found that CSD could modulate the levels of these potential biomarkers. CSD was found to be efficacious in UC by regulating multiple metabolic pathways.

Betacoronavirus ; China ; epidemiology ; Coronavirus Infections ; prevention & control ; Disease Outbreaks ; Emergencies ; Hospitals, General ; Humans ; Internet ; Pandemics ; prevention & control ; Pneumonia, Viral ; prevention & control

Cryptosporidiosis ; drug therapy ; Cryptosporidium ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Humans ; Parasitic Sensitivity Tests ; Phytotherapy ; Salicylates ; chemistry ; therapeutic use

OBJECTIVETo evaluate the clinical effects of modified lamina osteotomy replantation versus traditional lamina osteotomy replantation in the treatment of lumbar disc herniation with lumbar instability.

METHODSThe clinical data of 146 patients with unilateral lumbar disc herniation with lumbar instability underwent surgical treatment from March 2008 to March 2013 were retrospectively analyzed. Patients were divided into two groups according to osteotomy replantation pattern. There were 77 patients in the traditional group (underwent traditional lamina osteotomy replantation), including 42 males and 35 females with an average age of (49.4±18.5) years;the lesions occurred on L₄,₅ in 46 cases, on L₅5S₁ in 31 cases. There were 69 patients in modified group (underwent modified lamina osteotomy replantation), including 37 males and 32 females with an average age of (49.8±17.9) years;the lesions occurred on L₄,₅ in 40 cases, on L₅S₁ in 29 cases. The operation time, intraoperative blood loss, complication rate during operation, lamina healing rate, recurrence rate of low back and leg pain were compared between two groups. Visual analogue scales (VAS) and Japanese Orthopadic Association (JOA) scores were used to evaluate the clinical effects.

RESULTSThe operation time and intraoperative blood loss were similar between two group (>0.05). There was significantly different in nerve injury rate(5.80% vs 16.9%) and dural injury rate(1.45% vs 9.09%) between modified group and traditional group(<0.05). The recurrent rate of low back pain of modified group was higher (91.30%, 63/69) than that of traditional group (76.62%, 59/77), and the intervertebral fusion rate of modified group was lower(8.70%, 6/69) than that of traditional group (29.9%, 23/77) at 3 years after operation. Postoperative VAS scores of all patients were significantly decreased at 6 months, 1, 2, 3 years, and JOA scores were obviously increased (<0.05). At 1, 2, 3 years after operation, VAS scores of modified group were significantly lower than that of traditional group(<0.05), and JOA scores of modified group were higher than that of traditional group(<0.05).

CONCLUSIONSModified lamina osteotomy replantation has better long-term efficacy(in the aspect of recurrent rate of low back pain, intervertebral fusion rate, VAS and JOA score at three years follow-up) in treating lumbar disc herniation with instability.

The aim of this research is to investigate the inhibitory effects of calpain inhibitors (ALLN and calpain inhibitor IV) on mammary epithelial-mesenchymal transition (EMT) of MCF-10A cells induced by fibronectin (FN). After FN treatment of MCF-10A cells for 48 h, cell migration and invasion were determined by scratch repair assay and matrigel coated transwell assay, respectively. Vimentin, E-cadherin, snail and calpain-2 protein expression were measured by Western blot. The results suggest that FN induced morphological changes in MCF-10A cells, significantly increased the migration and invasion abilities of MCF-10A cells, upregulated the expression of calpain-2, vimentin and snail, and downregulated the expression of E-cadherin. All such changes by FN were reversed with ALLN and calpain inhibitor IV. In conclusion, the upregulation of calpain-2 was involved in FN-induced EMT of MCF-10A mammary epithelial cells, which may be inhibited by ALLN and calpain inhibitor IV.

One of the mechanisms of endometriosis-dysmenorrhea is closely related to the changes of pelvic anatomy and hemodynamics. TCM holds that cold-coagulation and blood-stasis that alternate and resist the cell palace is one of the main pathogenesis of dysmenorrheas.Dunhuang Liao Fengxu Shouruo Formula(P.3930),a precise and appropriate formulating prescription, plays an important role in activating blood, dispelling cold, tonifying qi and nourishing blood, which can warm the maridians and disperse cold, nourish blood and dissolve stasis and it achieves significant results. And in this prescription, the method of decocting herbs in mutton soup embodies the local characteristic of foodtherapy combined with medication of ancient Dunhuang medical prescriptions.