Objective To report a case of Elizabethkingia anopheles(E.anopheles)-associated sepsis and menin-gitis,review the relevant literatures,and provide reference for the diagnosis and treatment of this infection.Methods Treatment process of a pediatric patient aged 11-year-7-month old who developed post-neurosurgery E.anophe-les-associated sepsis and meningitis was analyzed retrospectively.Relevant literature was reviewed to summarize clinical characteristics of patients with E.anopheles-associated sepsis or meningitis.Results The main clinical manifestations of this pediatric patient were fever and abnormal cerebrospinal fluid routine.The cerebrospinal fluid and blood cultures showed E.anopheles.Patient recovered after vancomycin treatment.Including this case,a total of 33 cases were analyzed,with 16 males and 1 unreported gender.The median age of patients was 49 years old(range:1 day-84 years).Most cases were healthcare-associated infections(62.5％,n=20)with underlying disea-ses,and 24 cases were cured.Conclusion E.anopheles-associated infections are rare in clinic,but can cause severe infections such as sepsis and meningitis,warranting clinical attention.

Objective:To investigate the effect of natural plant compound puerarin(PUE)on expression of NLRP3 inflamma-some in macrophages and its effect in ulcerative colitis(UC)in mice.Methods:A mouse model of UC was established using dextran sulfate sodium(DSS).Mice received PUE via gavage for 7 consecutive days,body weight,disease activity index and colon length were measured.HE staining was performed to assess tissue pathological damage.Flow cytometry was used to determine the proportion of peripheral blood mononuclear cells in colonic lamina propria.Immunofluorescence was employed to assess the colocalization of NLRP3 inflammasome and macrophages.qRT-PCR was conducted to measure mRNA expression levels of pro-inflammatory cytokines and NLRP3-related genes in colonic tissues.Protein expression levels of ZO-1,Occludin,cleaved caspase-1 and IL-1β in colonic tissues were detected by Western blot.A cell model was established using lipopolysaccharide(LPS)and adenosine triphosphate(ATP).mRNA expression levels of genes related to NLRP3 inflammasome were detected by qRT-PCR.Western blot was used to detect effects of PUE on expression levels of proteins related to NLRP3 inflammasome and NF-κB signaling pathway.Results:PUE treatment signifi-cantly improved symptoms of DSS-induced UC in mice,including body weight,disease index,colon length and pathological damage.Following PUE intervention,infiltration of Ly6C+MHC Ⅱ-monocyte derived macrophages in the colonic lamina propria was reduced.Expression levels of pro-inflammatory cytokines and NLRP3 inflammasome related molecules in colonic tissues were decreased.PUE treatment increased expression levels of ZO-1 and Occludin in intestinal epithelial cells.In vitro experiments confirmed that PUE reduced expression levels of NLRP3 inflammasome-related molecules in macrophages induced by LPS combined with ATP,as well as protein expression level of p-NF-κB p65.Conclusion:PUE significantly alleviates the symptoms of UC by reducing intestinal tissue inflamma-tion and repairing the epithelial barrier.The mechanism may involve regulating NF-κB signaling pathway,thereby reducing the forma-tion and activation of NLRP3 inflammasome in macrophages.

Objective To report a case of Elizabethkingia anopheles(E.anopheles)-associated sepsis and menin-gitis,review the relevant literatures,and provide reference for the diagnosis and treatment of this infection.Methods Treatment process of a pediatric patient aged 11-year-7-month old who developed post-neurosurgery E.anophe-les-associated sepsis and meningitis was analyzed retrospectively.Relevant literature was reviewed to summarize clinical characteristics of patients with E.anopheles-associated sepsis or meningitis.Results The main clinical manifestations of this pediatric patient were fever and abnormal cerebrospinal fluid routine.The cerebrospinal fluid and blood cultures showed E.anopheles.Patient recovered after vancomycin treatment.Including this case,a total of 33 cases were analyzed,with 16 males and 1 unreported gender.The median age of patients was 49 years old(range:1 day-84 years).Most cases were healthcare-associated infections(62.5％,n=20)with underlying disea-ses,and 24 cases were cured.Conclusion E.anopheles-associated infections are rare in clinic,but can cause severe infections such as sepsis and meningitis,warranting clinical attention.

Objective:To investigate the effect of natural plant compound puerarin(PUE)on expression of NLRP3 inflamma-some in macrophages and its effect in ulcerative colitis(UC)in mice.Methods:A mouse model of UC was established using dextran sulfate sodium(DSS).Mice received PUE via gavage for 7 consecutive days,body weight,disease activity index and colon length were measured.HE staining was performed to assess tissue pathological damage.Flow cytometry was used to determine the proportion of peripheral blood mononuclear cells in colonic lamina propria.Immunofluorescence was employed to assess the colocalization of NLRP3 inflammasome and macrophages.qRT-PCR was conducted to measure mRNA expression levels of pro-inflammatory cytokines and NLRP3-related genes in colonic tissues.Protein expression levels of ZO-1,Occludin,cleaved caspase-1 and IL-1β in colonic tissues were detected by Western blot.A cell model was established using lipopolysaccharide(LPS)and adenosine triphosphate(ATP).mRNA expression levels of genes related to NLRP3 inflammasome were detected by qRT-PCR.Western blot was used to detect effects of PUE on expression levels of proteins related to NLRP3 inflammasome and NF-κB signaling pathway.Results:PUE treatment signifi-cantly improved symptoms of DSS-induced UC in mice,including body weight,disease index,colon length and pathological damage.Following PUE intervention,infiltration of Ly6C+MHC Ⅱ-monocyte derived macrophages in the colonic lamina propria was reduced.Expression levels of pro-inflammatory cytokines and NLRP3 inflammasome related molecules in colonic tissues were decreased.PUE treatment increased expression levels of ZO-1 and Occludin in intestinal epithelial cells.In vitro experiments confirmed that PUE reduced expression levels of NLRP3 inflammasome-related molecules in macrophages induced by LPS combined with ATP,as well as protein expression level of p-NF-κB p65.Conclusion:PUE significantly alleviates the symptoms of UC by reducing intestinal tissue inflamma-tion and repairing the epithelial barrier.The mechanism may involve regulating NF-κB signaling pathway,thereby reducing the forma-tion and activation of NLRP3 inflammasome in macrophages.

Neurofibromatosis(NF)as an autosomal dominant disease usually involves multiple sys-tems throughout the body and is classified as type 1 or type 2 NF.Neurofibromatosis scoliosis(NFS)is main-ly type 1,and severe neurofibromatosis scoliosis type 1(NF1-S)is manifested by abnormalities in spinal anat-omy and morphology,such as rotation of the parietal vertebrae and abnormal morphology of the pedicles,which leads to the difficulty and maximal risk of pedicle screw placement in scoliosis orthopedic surgery.In or-der to improve the safety of surgery,this paper discusses the morphology and anatomical structure of the pedi-cles in the patients with NF1-S,and analyzes the accuracy and safety of different pedicle-assisted screw place-ment techniques to provide reference for clinical surgery and promote the improvement of treatment level.

Objective:To investigate the predictive value of preoperative blood parameters on the efficacy of microscopic varicocele ligation in the treatment of infertility patients with varicocele.Methods:The clinical data of 110 patients with varicocele admitted to Xi′an People′s Hospital and Tangdu Hospital of Air Force Military Medical University from June 2016 to January 2021 were analyzed retrospectively. Successful operation was defined as the restoration of all semen parameters (sperm concentration, forward motility, morphology, etc.) to normal values 6 months after operation. The patients were divided into effective treatment group (group A, 78 cases) and ineffective treatment group (group B, 32 cases). The blood parameters of the two groups were compared before operation. Spearman correlation analysis was used to determine the relationship between blood parameters [neutrophil/lymphocyte ratio (NLR) and mean platelet volume (MPV)] and the success of microscopic varicocele ligation. The predictive value of blood parameters (NLR and MPV) to the success of microscopic varicocele ligation was analyzed by receiver operating characteristic (ROC) curve.Results:There was no significant difference in clinical characteristics, and sex hormone levels between the two groups before operation (all P>0.05); There were statistically significant differences in NLR and MPV in blood parameters between the two groups (both P<0.05), and there was no significant differences in other blood parameters (both P>0.05). There was no significant difference in semen parameters between the two groups before operation (all P>0.05). After operation, the semen volume, semen concentration, forward movement and sperm morphology of patients in group A were significantly improved compared with those before operation (all P<0.05), while the parameters of patients in group B had no significant difference compared with those before operation (all P>0.05). There was a negative correlation between preoperative NLR and the success rate of spermatic vein ligation ( r=-0.719, P<0.01), and a positive correlation between MPV and the success rate of spermatic vein ligation ( r=0.522, P<0.01). The ROC curve was used to analyze the threshold of predictive variables for the success of spermatic vein ligation. The optimal critical value of NLR was 2.01 ( P<0.01), and the optimal critical value of MPV was 11.45 ( P<0.01). Conclusions:Low NLR (<2.01) and high MPV (>11.45) may be useful preoperative predictive tools for identifying the group of infertile varicocele patients who would benefit most from microscopic spermatic vein ligation.

Objective:To explore the effect of Xuanbai-Chengqi Decoction combined with conventional western medicine therapy for the coma patients with acute cerebral infarction. Methods:A total of 72 patients with acute cerebral infarction in Huaibei Hospital of Traditional Chinese Medicine from March 2019 to January 2020 were randomly divided into two groups with 36 in each group. The control group was treated with conventional western medicine therapy, and the treatment group was given Xuanbai-Chengqi Decoction by nasal feeding on the basis of the control group. Both groups were treated for 7 days. The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the degree of neurological deficit, and the Full Outline of Unresponsiveness Scale (FOUR) was used to evaluate the degree of consciousness disorder of patients. Three-dimensional reconstruction of head CT was performed to identify and mark the edema area. The levels of serum high-sensitivity C-reactive protein (hs-CRP), homocysteine (Hcy) and vascular endothelin-1 (ET-1) were measured by double antibody sandwich enzyme-linked immunosorbent assay. The adverse events during treatment were observed and the clinical effective rate was evaluated. Results:The total effective rate was 100% (36/36) in the treatment group and 86.1% (35/36) in the control group, and the difference between the two groups was statistically significant ( Z=-0.242, P=0.015). On the 3rd and 7th day after treatment, the NIHSS scores of the treatment group were significantly lower than those in the control group ( t values were 26.567 and 17.982, all Ps<0.01). On the 3rd and 7th day after treatment, the eye opening response, motor response, brainstem response, brain stem response and total scores (3 days after treatment, t=15.235 , 14.892, 18.452, 11.232, 16.235; 7 days after treatment, t=19.5 68, 16.232, 10.356, 9.546, 11.098) of the treatment group were significantly lower than those in the control group. The levels of serum hs-CRP, Hcy, ET-1 and CT threshold of brain edema in the treatment group were significantly lower than those in the control group after treatment ( t=22.352, 17.789, 11.908 and 19.652, all Ps<0.01). There were no adverse drug reactions, no abnormal changes in blood routine tests, liver function and electrocardiogram in both groups. Conclusion:The Xuanbai-Chengqi Decoction combined with conventional western medicine therapy can improve the neurological function and promote awakening of coma patients with acute cerebral infarction, which may be related to reducing the levels of inflammatory cytokines related to hs-CRP, Hcy and ET-1, improving microcirculation and relieving brain edema.

Objective:To investigate the correlation of blood pressure variability within 24 h after thrombolysis with symptomatic intracerebral hemorrhage (sICH) and 90 d outcome in patients with acute ischemic stroke.Methods:Patients with acute ischemic stroke treated with recombinant tissue plasminogen activator in the Department of Neurology, Jinshan Branch, Shanghai Sixth People's Hospital from January 2017 to May 2019 were enrolled prospectively. The baseline data of the patients were collected. The patients were divided into sICH group and non-sICH group according to the changes of head CT and the National Institutes of Health Stroke Scale (NIHSS) score after thrombolysis. At 90 d after thrombolysis, the modified Rankin scale was used to evaluate the outcomes, and the patients were divided into a good outcome group (0-2) and a poor outcome group (3-6). The blood pressure within 24 h after thrombolysis was monitored and the parameters related to blood pressure variability in 5 time periods (0-2 h, 2-6 h, 6-12 h, 12-18 h, and 18-24 h) were calculated, including systolic blood pressure (SBP) and diastolic blood pressure (DBP) maximum (max), minimum (min), maximum and minimum difference (max-min) and mean (mean). The differences between the adjacent blood pressures were calculated, the standard deviation (SD), successive variation (SV), rise successive variability (SVrise), drop successive variability (SVdrop), the maximum squared difference in blood pressure rise (SVrisemax), the maximum squared difference in blood pressure drop (SVdropmax) were calculated and recorded, respectively. Multivariate logistic regression analysis was used to evaluate the effect of various blood pressure variability parameters on sICH and the outcomes after intravenous thrombolysis. Results:A total of 112 patients receiving intravenous thrombolysis were included in the study. Their median age was 71 years (range, 38-92 years), 66 were males (58.9%); median baseline NIHSS score was 10. Seventeen patients (15.2%) developed hemorrhagic transformation, 10 of them (8.9%) were sICH. The 90-d follow-up showed that 73 patients (65.2%) had a good outcome, 39 (34.8%) had a poor outcome and 7 of them (6.3%) died. There were significant differences in hypertension ( P=0.029), ischemic heart disease ( P=0.012), total cholesterol ( P=0.033), baseline NIHSS score ( P=0.003) between the sICH group and the non-sICH group. There were significant differences in age ( P=0.025), gender ( P=0.005), atrial fibrillation ( P=0.003), etiologic classification of stroke ( P=0.003), baseline NIHSS score ( P<0.001) and sICH ( P=0.003) between the poor outcome group and the good outcome group. In addition, there were significant differences in multiple blood pressure variability parameters among the above groups (all P<0.05). Multivariate logistic regression analysis showed that DBP SVdropmax, 6-12 h DBP SV, 12-18 h DBP SV, 6-12 h DBP SVdrop, 12-18 h DBP SVdrop were the independent risk factors for sICH after intravenous thrombolysis (all P<0.05); 2-6 h SBP SV, 2-6 h SBP SVrise, 2-6 h SBP SVdrop, 2-6 h DBP SV, 2-6 h DBP SVrise and 2-6 h DBP SVdrop were the independent risk factors for poor outcome after intravenous thrombolysis (all P<0.05). Conclusions:Early blood pressure and some blood pressure variability parameters are closely related to sICH and outcomes after intravenous thrombolysis in acute ischemic stroke. Closely monitoring of blood pressure and its variability can help clinical management and outcome prediction after intravenous thrombolysis.

Objective:To investigate the influences of SCN3A gene polymorphism(c.905A>G/p.N302S and c. 1441C>T/p.L481L) on the efficacy of valproic acid sodium in the treatment of Zhuangzu epilepsies.Methods:Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)technique and the way of direct sequence, the SCN3A gene c. 905A>G/p.N302S and c. 1441C>T/p.L481L genotypes in peripheral blood were detected in 244 epileptic patients (85 cases in effective group and 139 cases of ineffective group) in the standardized treatment of valproic acid sodium.The blood concentration of valproic acid sodium was detected by LC-MS.Evaluating the correlation between the genotype and alleles of two groups of patients and the efficacy of valproic acid sodium and analyzing the difference of valproic acid sodium's blood concentration between different genotypes.The linkage disequilibrium of c. 905A>G/p.N302S and c. 1441C>T/p.L481L were analyzed by software SHEsis.Results:The allele and genotype distribution in c. 905A>G/p.N302S loci between effective group(A, G allele: 50.6%, 49.4%, AA, AG, GG genotype: 27.1%, 47.1%, 25.8%) and ineffective group(A, G allele: 37.4%, 62.6%, AA, AG, GG genotype: 16.6%, 41.7%, 41.7%) had statistically significant difference(χ 2=7.501, P=0.006; χ 2=7.907, P=0.019). There was no significant difference in allele and genotype distribution of c. 1441C>T/p.L481L loci between effective group(C, T allele: 47.1%, 52.9%, CC, CT, TT genotype: 23.5%, 47.1%, 29.4%) and ineffective group(C, T allele: 38.8%, 61.2%, CC, CT, TT genotype: 18.7%, 40.3%, 41.0%)(χ 2=2.920, P=0.088; χ 2=3.099, P=0.212). Compared with the AA + AG genotype, the GG genotype at c. 905A>G/p.N302S locus significantly reduced the efficacy of valproic acid sodium ( OR=2.051, 95% CI=1.136-3.703). Compared with genotypes AA+ AG, there were no significant differences in blood concentration of genotype GG of c. 905A>G/p.N302S ( t=3.256, P=0.137). Compared with genotypes CC+ CT, there were no significant differences in blood concentration of genotype TT of c. 1441C>T/p.L481L( t=4.628, P=0.082). c.905A>G/p.N302S and c. 1441C>T/p.L481L were without linkage disequilibrium. Conclusion:These results suggest that the single nucleotide polymorphisms of c. 905A>G/p.N302S in SCN3A genes may play a role in the resistivity of valproic acid sodium in Zhuangzu epilepsies.

OBJECTIVE: To design and synthesize folate-modified pH-responsive chitosan-based nanomicelles and investigate the anti-tumor activity of the drug-loaded micelles. METHODS: CHI-DMA was obtained by reductive amination reaction of aldehyde-based chitosan and hydrophilic amine compounds, and CHI-DMA-LA was obtained by condensation reaction with lauric acid; FA-CHI-DMA-LA was obtained after modification with folic acid (FA). The drug-loaded nanomicelles FA-CHI-DMA-LA/DOX were assembled by solvent change method. The physicochemical properties of polymers were characterized by hydrogen nuclear magnetic resonance and transmission electron microscope. The particle size and surface potential were determined by dynamic light scattering method. Folic acid access rate, doxorubicin (DOX) loading rate and entrapped efficiency were measured by UV-vis spectrophotometer. The drug release properties of DOX-loaded micelles were monitored by fluorescence spectrophotometer at different pHs (7.4, 6.5, 5.0). The cytotoxicity against human oral cancer KB cells was detected by MTT assay. Fluorescence microscope and flow cytometry were applied to investigate the phagocytosis of DOX-loaded micelles on KB cells. RESULTS: FA-CHI-DMA-LA was synthesized. The particle sizes of FA-CHI-DMA-LA-1 and FA-CHI-DMA-LA-2 micelles which used for the subsequent experiments were (73±14) nm and (106±15) nm, zeta potential were (15.59±1.98) mV and (21.20±2.35) mV, respectively. The drug loading rates of drug-loaded micelles FA-CHI-DMA-LA-1/DOX and FA-CHI-DMA-LA-2/DOX are (4.08±1.12)%and (4.12±0.44)%, respectively. drug release is pH-responsive, with cumulative release of DOX up to 37%and 36%at pH 5.0, which is about 1.5 times higher than that of pH 7.4. For FA-CHI-DMA-LA micelles with 1.25 to 125 μg/mL concentration, the survival rate of KB cells is more than 70%after incubation for 24 hours. The cell uptake of FA-CHI-DMA-LA/DOX micelles was enhanced compared to CHI-DMA-LA/DOX, and the cell uptake was higher in incubation without FA medium than that with FA. Compared with free DOX or CHI-DMA-LA/DOX, FA-CHI-DMA-LA/DOX nanomicelles showed higher cyctoxicity to KB cells, especially the FA-CHI-DMA-LA-2/DOX nanomicelles, the cell survival rate was about 17% after incubation for 24 hours. CONCLUSIONS FA-modified chitosan-based nanomicelle with good biocompatibility was successfully prepared, which exhibits tumor microenvironmental pH responsive drug release and tumor targeting.
Antineoplastic Agents ; Chitosan ; Doxorubicin ; Drug Carriers ; Folic Acid ; Humans ; Micelles ; Nanostructures ; Polymers