Objective To explore the dynamic changes and mechanisms of neurological and cognitive functions in mice with traumatic brain injury (TBI). Methods Totally 60 12⁃month⁃old Balb/ c mice were divided into control group (10 in group) and TBI group (50 in group). TBT model mice were divided into 5 subgroups according to the time of model construction, including model 1 day, model 1 day, model 3 day, model 7 day, model 14 days and model 28 days group with 10 in each group. At the 29th day of the experiment, neurological scores and step down tests were carried out. After the test, the mice were sacrificed for brains which were detected by immunohistochemistry staining, inflammatory cytokine tests and Western blotting. Results Compared with the control group, the neurological scores of mice in TBI group increased, and then decreased after the 7th day when the scores reached the peak. However, the latency of step down errors was lower than control group, and the number of step down errors was higher than control group which had no changes. Compared with the control group, the expression of lonized calcium⁃binding adapter molecule 1(IBA1), chemokine C⁃X3⁃C⁃motif ligand1 (CX3CL1), C⁃X3⁃C chemokine receptor 1(CX3CR1), NOD⁃like receptor thermal protein domain associated protein 3 (NLRP3), and phosphorylation nuclear factor(p⁃NF)⁃κB in TBI group increased and reached to the peak at the 7th day, and then started to decrease. At the same time, the levels of inflammatory cytokines interleukin⁃6(IL⁃6) and tumor necrosis factor⁃α(TNF⁃α) first increased to the peak, and then began to decrease. However, compared with the control group, the expression of amyloid β(Aβ) protein and p⁃Tau protein in the model group continued to increase at all time. Conclusion The TBI model caused continuous activation of microglia along with inflammatory response, which first increased and then decreased, resultsing in neurological scores changes. In addition, the inflammatory response may act as a promoter of Aβ protein deposition and Tau protein phosphorylation, leading to cognitive impairment in mice.

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides (MOIG) on bone loss of rheumatoid arthritis (RA) rats, and the mechanism of osteoclast function and activity induced by lipopolysaccharide (LPS). RA rats were established by injecting bovin type II collagen. The Bio-ethic Committee of Zhejiang Chinese Medical University approved all experimental protocols associated with this study (IACUC-20180410-03). The collagen-induced arthritis (CIA) rats were administered drug by gavage for 8 weeks; the femoral trabecular micro-structure changes were observed in CIA rats by micro-CT; the LPS-induced osteoclasts model further observed the effect and mechanism of anti-inflammatory osteoporosis in vitro. The results indicated that MOIG could markedly increase bone mineral density (BMD) in CIA rats, improve trabecular micro-structure. In vitro studies demonstrated that MOIG could significantly inhibit osteoclastogensis and differentiation, suppress tartrate resistant acid phosphatase (TRAP) activity, F-actin ring formation, TNF receptor associated factor 6 (TRAF6) recruitment, and inhibitor of nuclear factor kappa-Bα (IκBα) degradation as well as p65 phosphorylation, thereby repressing nuclear factor kappa-B (NF-κB) signaling pathway activation. Subsequently, MOIG effectively inhibited osteoclast nuclear factor of activated T-cells c1 (NFATc1) and cellular oncogene Fos (c-Fos) expression, as well as bone resorption related protein activity including matrix metalloprotein 9 (MMP-9) and cathepsin K (CtsK). Meanwhile, MOIG also repressed the phosphorylation expression of Janus activating kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), thereby inhibiting JAK2/STAT3 signaling pathway activation. Moreover, further studies found that MOIG could suppress glycogen synthase kinase-3β (GSK-3β) activity, and GSK-3β gene silencing could markedly inhibit oetsoclast F-actin ring formation as well as the phosphorylation expression of p65 and STAT3. Of note, compared with GSK-3β gene silencing group, there was no significant difference in the group treated with both MOIG with GSK-3β gene silencing simultaneously. Thus, the results suggested that MOIG may inhibit NF-κB signaling pathway and JAK2/STAT3 signaling pathway activation via regulating GSK-3β, thereby alleviating bone destruction in RA.

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 analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

OBJECTIVE: To explore the mechanism of proteasome inhibitor MG132 in improving osteoporosis. METHODS: Total of 32 female SD rats, weighing 220 to 250 g and 8 weeks old, were selected. They were randomly divided into 4 groups(n=8). Rats of group A and group B were cut off ovaris on both sides to make model of osteoporosis, and then they were given proteasome inhibitors MG132 and dimethyl sufoxide (DMSO) respectively. Group C was a sham group and rats were given MG132. Group D was a normal group and rats were given MG132 too. The rats were killed in batches at 6 and 12 weeks after administration, and the femoral neck tissues were obtained. Relevant data were analyzed, such as pathomorphological observation, micro-CT analysis, detection of 20S proteasome activity in tissues, and expression of Wnt and β-catenin. RESULTS: Morphological observation showed that the trabecular were slightly thinner, reticulated, and occasionally interrupted in group A, while the trabecular were obviously thinner and discontinuous in group B. And the trabecular were intact and arranged reticulated in group C and D. The analysis results of bone mineral density(BMD), bone surface(BS), bone volume/total volume(BV/TV) and trabecular thickness(Tb.Th) showed that group B was worse than other groups in all parameters at different time points(P<0.05), and group A was worse than group C and group D in BS(P<0.05), there was no significant difference in all parameters between group C and group D. RFU value of 20S proteasome in group B was significantly higher than that in other groups(P<0.05). According to the results of Western blot, the gray values of Wnt protein and β-catenin protein in group A were significantly higher than those in other groups (P<0.05). CONCLUSION MG-132, a ubiquitin proteasome inhibitor, can regulate Wnt/β-catenin signaling pathway by inhibiting the degradation of β-catenin protein, and delaying the occurrence and development of osteoporosis.
Animals ; Bone Density ; Female ; Leupeptins ; Osteoporosis/drug therapy* ; Proteasome Inhibitors/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Wnt Signaling Pathway ; beta Catenin/metabolism*

OBJECTIVE: To investigate the clinical characteristics, laboratorial and bone marrow pathological features of primary thrombocytopenia (ET) patients with different mutations of CALR, JAK2 and MPL genes. METHODS: The chinical data of 120 cases of ET in Jiangsu provincial people's hospital/ The First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2017 were collected and analyzed, including 76 cases with JAK2 gene mutation, 40 cases with CALR gene mutation, 2 cases with MPL gene mutations, 2 cases without gene mutation. RESULTS: Among the ET patients, compared with the JAK2 gene mutation, CALR gene mutation showed statistically significant deareament of white blood cells and hemoglobin (P=0.001, P=0.01) and the male platelets in CALR group showed significant increament (P=0.04). Fourthermore, the average number of megakaryocytes and its cluster numbers in each hight power field of vision showed statistically significant decreament in CALR group as compared with JAK2 group (P=0.001, P=0.001), and thrombotic events in CALR group were signicantly lower than those in JAK2 group (7.5% vs 18.4%) (P=0.03). CONCLUSION Mutations of CALR, JAK2 have different clinical characteristics and blood pathological changes of Chinese ET patients, and their clinical significance is worth to explore.
Bone Marrow ; Calreticulin ; genetics ; China ; Humans ; Janus Kinase 2 ; genetics ; Male ; Mutation ; Receptors, Thrombopoietin ; genetics ; Thrombocythemia, Essential

Objective: To prepare oxymatrine phospholipid complex solid lipid nanoparticles(OMT-PC-SLN) lyophilized powder and evaluate its pharmaceutical properties. Method: Pseudo-ternary phase diagram was employed to optimize the formula of microemulsion;single factor experiments were adopted to optimize the formulation process of OMT-PC-SLN lyophilized powder with encapsulation efficiency as index;the morphology of this preparation was observed by transmission electron microscope(TEM).The particle size was measured by particle size analyzer and the in vitro release performance of OMT-PC-SLN lyophilized powder was examined. Result: Optimal formulation process was as following:taking soybean phospholipid and polyethylene glycol 15-hydroxystearate(Kolliphor HS 15) as the emulsifier,ethanol as co-emulsifier,ratio of emulsifier to co-emulsifier(K_m)=3:2,oil phase:(emulsifier+co-emulsifier)=1:9,oxymatrine phospholipid complex-stearic acid-soybean phospholipid-Kolliphor HS 15-ethanol(30:100:180:360:360);taking 50 mL of 4%mannitol solution as the external aqueous phase,ice bath stirring at 1 000 r·min^-1 and solidifying for 1 h,precooled at -20℃ for 24 h,took out and dried for 24 h.OMT-PC-SLN lyophilized powder was spherical in appearance with encapsulation efficiency of (38.09±1.24)%,average particle size of 785.5 nm,polydispersity coefficient(PDI) of 0.456 and the Zeta potential of -24.82 mV.The cumulative release rates of OMT-PC-SLN lyophilized powder were 72.63%at 2 h and 98.42%at 12 h;the cumulative release rate of oxymatrine(crude drug) was 98.60%at 2 h. Conclusion: This optimized formulation process of OMT-PC-SLN lyophilized powder is stable with good repeatability;compared with oxymatrine,OMT-PC-SLN lyophilized powder has a certain sustained-release effect.

Objective To understand infection status of human immunodeficiency virus (HIV) and analyze the influencing factors among men who have sex with men (MSM) in Guangzhou. Methods Men who have sex with men (MSM) were recruited from 2014 to 2017. Face-to-face questionnaire survey was conducted to collect information of characterisitc and behaviors. Blood samples were used to detect HIV antibodie. Data were analyzed using SPSS 19.0. Results Among 2 419 MSM, 200(8.27%) participants were confirmed positive for HIV. Multivariate Logistic regression analysis showed that with Guangzhou and monthly economic income >0.5 million as reference, non-Guangzhou (OR=1.712, 95% CI: 1.176-2.492，P=0.005) and monthly economic income ≤0.5 million (OR=1.998, 95% CI: 1.409-2.833，P<0.001) were associated with HIV infection among MSM. Diagnosed syphilis (OR=2.461, 95% CI: 1.375-4.405,P=0.002) , undetected syphilis (OR=2.333, 95% CI: 1.635-3.331,P<0.001), anal sex role passive (OR=2.015, 95% CI: 1.244-3.267,P=0.004), both active and passive (OR=2.115, 95% CI: 1.374-3.251,P=0.001), non-using condoms every time during anal sex (OR=1.955, 95% CI: 1.374-2.781,P<0.001), non-fixed anal sex objects (OR=2.150, 95% CI: 1.463-3.160,P<0.001) were major risk factors for HIV infection among MSM. Conclusions The prevalance of HIV infection and high-risk sexual behavior were high among MSM in Guangzhou. It is urgent to expand the scope of HIV testing and advocate safe sexual behaviors among MSM.

Objective: To compare the effect of insulin-like growth factor-1 receptor (IGF-1R) inhibitor and insulin on renal interstitial macrophage infiltration in mice with type 2 diabetic kidney disease (DKD) mice. Methods: Twenty-four male C57BL/6 mice were selected. After 1 week of adaptive feeding, 6 rats were randomly selected as the control group. The other mice were intraperitoneally injected with streptozotocin (30 mg/kg) after 8 weeks of high-fat and high-sugar feeding. After 72 h, the type 2 diabetes mellitus (DM) models were successfully established if random blood glucose was greater than 16.7 mmol/L. After 8 weeks, if the proteinuria of DM mice increased, the DKD models were successful. DKD mice were divided into 3 groups by random number remainder method: DKD group (n=6), DKD+insulin group (insulin group, n=6, subcutaneous injection of 1-2 U/d insulin) and DKD+IGF-1R inhibitor (IGF-1R inhibitor group, n=6, administered with 30 mg·kg^-1·d^-1 IGF-1R inhibitor). They were continuously treated for 8 weeks. Random blood glucose was tested by glucometer. Blood and urine were collected, and biochemical indicators, such as serum creatinine, urea nitrogen and urine protein were measured by biochemical analyzer. Renal pathological changes were detected by hematoxylin-eosin staining (HE) and periodic acid-schiff staining (PAS). Suppressor of cytokine signaling 2 (SOCS2) mRNA and insulin-like growth factor-1 (IGF-1) mRNA were detected by in situ hybridization. The protein expressions of SOCS2, F4/80, Toll-like receptor 4 (TLR4) and CD68 were detected by immunohistochemistry. Results: Compared with the control group, blood glucose, serum creatinine, serum urea nitrogen and urinary protein excretion rate were significantly higher in DKD mice (all P<0.05), and CD68⁺ cells number, F4/80⁺ cells number and the expression of TLR4 in the tubulointerstitial of DKD mice were significantly higher (all P<0.05). After intervention with insulin or IGF-1R inhibitor, serum creatinine, serum urea nitrogen and urinary protein excretion rate of DKD mice were significantly reduced (all P<0.05). Insulin intervention could significantly reduce blood glucose in mice (P<0.05), but had no significant effect on macrophages. Although IGF-1R inhibitor did not significantly reduce blood glucose, it could significantly reduce the number of CD68, F4/80 positive cells and the expression of TLR4 protein in renal interstitium of DKD mice (all P<0.05). Compared with the DKD group, insulin intervention significantly reduced the expression of IGF-1 protein and mRNA (both P<0.01), and increased the expression of SOCS2 mRNA and protein (both P<0.01). And the expression of SOCS2 protein was correlated with the number of F4/80⁺ cells in insulin group (R²=0.8461, P=0.005). However, IGF-1R inhibitors had no significant effect on SOCS2 expression, but had better inhibition of macrophage infiltration. Conclusion IGF-1R inhibitor has a better inhibitory effect on DKD renal interstitial macrophage infiltration than insulin. The mechanism may be related to the fact that IGF-1R inhibitor does not up-regulate SOCS2 expression, whereas insulin up-regulates SOCS2 expression to activate some potential pathways.

OBJECTIVETo evaluate the clinical outcome of intelligent inflated reduction combined with percutaneous pedicle screw fixation in treating thoracolumbar burst fractures.

METHODSThe clinical data of 22 patients with thoracolumbar burst fractures of single segment treated from January 2013 to December 2015 were retrospectively analyzed. There were 12 males and 10 females, aged from 32 to 56 years old with an average of (42.4±8.6) years. Self-made intelligent pneumatic reset instrument was applied to 22 cases under anaesthesia reduction, and then percutaneous pedicle screw fixation was performed. Clinical features were observed and the clinical effects were evaluated by VAS, ODI, kyphotic angle (Cobb angle) and the injured vertebral anterior border height before and after operation.

RESULTSAll the patients were followed up from 1 to 2.5 years with an average of 18 months. All fractures obtained bone healing, no complications such as loosening, displacement, breakage of pedicle screw and kyphosis were found. Preoperative, 1 week postoperative, and final follow-up, VAS scores of lumbar pain were 7.82±0.85, 3.09±0.92, 1.05±0.72;ODI scores were 84.2±11.2, 46.3±9.0, 12.2±4.3;Cobb angle were (16.3±5.4)°, (3.7±2.2)°, ( 5.5±2.6)°; the injured vertebral anterior border heights were (59.5±7.8)%, (86.9±6.0)%, (83.5±5.5)%, respectively. There was significant differences in VAS, ODI scores between any two times(<0.05). At 1 week postoperative and final follow-up, Cobb angle, injuried vertebral anterior border height were obviously improved (<0.05), and there was no significant difference between postoperative 1 week and final follow-up (>0.05).

CONCLUSIONSIt is safe and feasible surgical technique that intelligent inflated reduction combined with percutaneous pedicle screw fixation for thoracolumbar burst fractures. It has advantage of little trauma, reliable fixation, and less complication, etc. Therefore, it is a better choice for single-segment thoracolumbar burst fractures.