Objectives:To observe the effect of repetitive trans-spinal magnetic stimulation(rTSMS)on the activation of spinal cord derived neural stem cells(NSCs)through Notch1.Methods:The complete spinal cord of fetal C57BL/6 mice at 16 weeks of gestation was promptly extracted following euthanasia.NSCs obtained from the spinal cord were cultured in vitro.Subsets and rate changes of NSCs were analyzed using single cell sequencing and RNA profiling.The cultured NSCs were divided into control group,intervention(rTSMS)group and experiment(rTSMS+Notch 1 shRNA)group.The control group was treated with sham stimulation.The rTSMS group was treated with 20Hz high frequency stimulation with 1500 pulses.The rTSMS+Notch1 shRNA group received the same rTSMS intervention after transfection with Notch1 shRNA lentivirus.The expression of Notch1 was detected by Western blot,and the activation of NSCs was detected by immunofluorescence staining and sphere formation test.Results:Spinal cord derived NSCs cultured in vitro could differentiate into neurons,astrocytes and oligodendrocytes.Single cell sequencing showed that NSCs could be divided into 6 subgroups with special heterogeneity,and Notch1 mainly expressed in the subgroups of dNSCs and pNSCs.The expression of Notch1 in the cells decreased significantly on the 5th day after transfection with Notch1 shRNA lentivirus(Control group:1.080±0.086 vs Experiment group:0.520±0.041,P＜0.05).rTSMS intervention could significantly up-regulate the expression of Notchl(Control group:1.030±0.068 vs Intervention group:1.480±0.087,P＜0.05).The diameter of the neurosphere(Control group:88.5±7.5 vs Intervention group:106.2±8.8 vs Experiment group:89.2±8.1,P＜0.05)and the rate of BrdU positive cells were significantly increased(Control group:38.6±3.7 vs Intervention group:50.3±4.6,P＜0.05)after rTSMS intervention.After Notch1 shRNA,the neurosphere diameter and BrdU positive cell rate(Intervention group:50.3±4.6 vs Experiment group:35.1±3.5,P＜0.05)significantly decreased in the experiment group.Conclusions:rTSMS can promote activation of NSCs through Notch1 in vitro.

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

The mechanisms underlying exercise-induced neuroprotective effects after traumatic brain injury (TBI) remained elusive, and there is a lack of effective treatments for TBI. In this study, we investigated the effects of an integrative approach of exercise and Yisaipu (TNFR-IgG fusion protein, TNF inhibitor) in a mouse TBI model. Male C57BL/6J mice were randomly assigned to a sedentary group or a group that followed a voluntary exercise regimen. The effects of 6-week prophylactic preconditioning exercise (PE) alone or in combination with post-TBI Yisaipu treatment on moderate TBI associated deficits were examined. The results showed that combined treatments of PE and post-TBI Yisaipu were superior to single treatments on reducing sensorimotor and gait dysfunctions in mice. These functional improvements were accompanied by reduced systemic inflammation largely via decreased serum TNF-α, boosted autophagic flux, and mitigated lesion volume after TBI. Given these neuroprotective effects, composite approaches such as a combination of exercise and TNF inhibitor may be a promising strategy for facilitating functional recovery from TBI and are worth further investigation.
Animals ; Brain Injuries, Traumatic/pathology* ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents/pharmacology* ; Recovery of Function ; Tumor Necrosis Factor Inhibitors

BACKGROUND: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. METHODS: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD. RESULTS: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05). CONCLUSION Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
Birth Weight ; Bronchopulmonary Dysplasia ; China/epidemiology* ; Delivery Rooms ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Extremely Premature ; Infant, Newborn ; Male ; Pregnancy

Cochlear Implantation ; Genes, Neurofibromatosis 2 ; Humans ; Neurofibromatosis 2/surgery* ; Neuroma, Acoustic/surgery* ; Sequence Deletion

Objective:To explore the improvement effect of total flavonoids of Mori Cortex combined with total saponins of Anemarrhena Asphodeloide on hyperlipidemia rats with osteoporosis and its possible mechanism. Method:The 40 SPF male SD rats were adaptively fed for 7 days， and then randomly divided into normal group， model group， calcitriol group （45 ng·kg^-1）， total flavonoids of Mori Cortex and total saponins of Anemarrhena Asphodeloide 1∶2 group （0.6 g·kg^-1+0.4 g·kg^-1） and 2∶1 group （1.2 g·kg^-1+0.2 g·kg^-1）. Except for the normal group， rats in the other groups were fed with high fat for 9 weeks， the normal group and the model grouotal flavonoids of total flavonoids of Mori Cortex and total saponins of Anemarrhena Asphodeloip were given normal saline by gavage， and the other groups were given corresponding drugs by gavage， after 12 weeks of administration， except for the normal group ， the other groups were given intramuscular injection of glucocorticoids at the same time. After 22 weeks of administration， the weight of rats with total flavonoids from Mori Cortex combined with total saponins of Anemarrhena Asphodeloide was measured. Serum levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， osteocalcin （BGP） and bone alkaline phosphatase （BALP） were determined by biochemical assay. Hematoxylin-eosin （HE） staining to observe the pathological changes of rat tibia. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression levels of peroxisomal proliferators activate the receptor gamma（PPARγ） and Runt-related transcription factor 2 （Runx2） mRNA in rat bone tissue， immunofluorescence was used to detect the expression of PPARγ and Runx2 in rats. Result:Compared with normal group， the body mass of rats in model group was significantly increased （P<0.01）， and the contents of TC， TG， and LDL-C in the serum were significantly increased （P<0.01）. Compared with model group， the body weight of rats in thet total flavonoids of Mori Cortex and total saponins of Anemarrhena Asphodeloide 1∶2 group and 2∶1 group were significantly reduced （P<0.01）， and the contents of TC， TG， and LDL-C in the serum were significantly reduced （P<0.01）， the content of BGP and BALP increased （P<0.01）. HE staining results showed that compared with the normal group， the tibia fat vacuoles of the model group increased， and the number of osteoblasts decreased， compared with the model group， the total flavonoids of the Mori Cortex and the flavonoids-total saponins of Anemarrhena Asphodeloide 1∶2 group and 2∶1 group decreased in tibia fat vacuoles and increased the number of osteoblasts， the results of immunofluorescence and Real-time PCR showed that， compared with normal group， the expression of Runx2 in the model group decreased and the expression of PPARγ increased （P<0.01）. Compared with model group， the total flavonoids of Mori Cortex-total saponins 1∶2 group and the total flavonoids of Mori Cortex-total saponins 2∶1 Group up-regulated the expression of Runx2 and down-regulated the expression of PPARγ （P<0.05，P<0.01）. Conclusion:The total flavonoids of Mori Cortex combined with the total saponins of Anemarrhena Asphodeloide up-regulated Runx2 and down-regulated the expression of PPARγ mRNA and protein， thereby affecting the metabolism of TG and TC in the blood， achieving a therapeutic effect on osteoporosis， provides experimental basis for the clinical prevention and treatment of hyperlipidemia with osteoporosis.

Hepatitis B virus (HBV) capsid protein plays an important role in the life cycle, thus becoming an ideal target for drug design. Capsid protein inhibitors can exert a synergistic antiviral effect with nucleoside drugs by inhibiting the replication of HBV. This paper reviews the research progress of capsid protein inhibitors with different structural types from the perspective of medicinal chemistry.

Hepatitis B has become one of the major diseases which seriously affect people's health and social development. Hepatitis B, with high incidence and long disease course, cannot be cured by approved drugs such as the nucleoside analogues. Therefore, the discovery of safe and efficient novel HBV inhibitors is of great significance. From the point of view of medicinal chemistry, we summarized and discussed current endeavours towards the discovery and development of anti-HBV agents of RNase H and other novel target inhibitors with various scaffolds or distinct mechanisms of action, besides the existing capsid protein inhibitors.

Ebola virus is extremely virulent and highly contagious. Ebola virus causes outbreaks of severe hemorrhagic fever, with human mortality rates of up to 90%. There is currently no preventive or therapeutic treatment in the form of vaccines, biological or small molecular agents. Currently, a lot of anti-Ebola virus agents have been reported. Here, we review the latest advances in this field.

OBJECTIVE: To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China. METHODS: According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017. RESULTS: A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66). CONCLUSIONS Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.
China ; Female ; Humans ; Infant, Newborn ; Meconium Aspiration Syndrome ; Pregnancy ; Respiratory Distress Syndrome, Newborn ; Retrospective Studies