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 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

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 investigate the relationship between the single nucleotide polymorphisms of SCN1A genes and the therapeutic effects of carbamazepine in Zhuang population with epilepsies. Methods We used Mass ARRAY-IPLEX and matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) technology to detect the SCN1A gene rs4667869 and rs10497275 genotypes in peripheral blood of186 Zhuang individuals with epileptic (66 cases in effective group and 120 cases of ineffective group) who received the standardized treatment of carbamazepine in Baise Region. The reversed phase high-performance liquid chromatography was used to determine blood drug level of carbamazepine. The correlations between the genotypes, alleles and the carbamazepine efficacy of the two groups were evaluated, respectively. We also analyzed the difference of carbamazepine's blood concentration between different genotypes. Results Three genotypes of GG, GC and CC were detected in rs4667869 locus. There were 3 genotypes of GG, GA and AA found in rs 10497275 locus.The differences in the allele distribution (χ2 = 11.790, P = 0.001) and genotype distribution (χ2= 10.655, P =0.005) of the rs4667869 locus were statistically significant between the two groups (ineffective group vs. effective group). However, there was no significant difference in allele distribution (χ2 = 3.335, P= 0.068) and genotype (χ2= 3.046, P = 0.218) for rs 10497275 locus in these two groups. Compared with the GG + GC genotype, the CC genotype of rs4667869 locus significantly reduced the antiepileptic efficacy of carbamazepine (OR = 2.800, 95％CI : 1.495～5.244). W hile there were no significant differences in blood concentration of genotype CC (t=1.273, P = 0.083) comparing with genotypes GG + GC in rs4667869. No significant differences were found in blood concentration between genotype AA and genotypes GG + GA of rs 10497275 (t= 0.963, P = 0.064). Conclusions These results suggest that the single nucleotide polymorphisms of rs4667869 in SCN1A genes could be associated with the drug resistance of carbamazepine in Zhuang population with epilepsies.

Objective: To establish and evaluate a microfluidic chip platform for the rapid diagnosis of post-neurosurgical bacterial infection. Methods: The pathogens isolated from patients with post-neurosurgical bacterial infection in Beijing Tiantan Hospital Affiliated to Capital Medical University during 2007 and 2016 and the epidemiological data from China drug resistance monitoring network CHINET were analyzed retrospectively. Based on the retrospective data and the molecular epidemiological information of drug-resistant bacteria reported in the literature, target pathogens and drug resistance gene parameters were selected. The microbial identification parameters from 10 different bacteria, including Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus epidermidis, Enterobacter cloacae, Staphylococcus aureus, Escherichia coli, Enterococcus faecium, Enterococcus faecalis, Stenotrophomonas maltophilia and Pseudomonas aeruginosa, and the parameters of 15 drug resistance genes, including mecA, vanA, vanB, aacC1, aadA1, bla CTX-M-1 , bla CTX-M-9 , bla GES-1 , bla OXA-23 , bla OXA-24 , bla OXA-58 , bla OXA-66 , bla KPC-2 , bla IMP-4 and bla VIM-2 , were selected for designing a microfluidic chip platform. Using MAIDI-TOF MS for bacterial identification, multiplex PCR for the detection of drug resistance genes, micro-broth dilution method for the detection of drug resistance phenotypes and ESBLs screening test as reference methods, 13 known bacteria were used to evaluate the preliminary performance of the established microfluidic chip platform, and 108 cerebrospinal fluid bacterial culture positive specimens were used to evaluate the clinical application value of the microfluidic chip platform. Results: The identification rates of 13 known strains and the coincidence rate of drug resistance genes were 100%. The coincidence rate of identification results for 108 cerebrospinal fluid bacterial culture positive specimens between the microfluidic chip platform and the MALDI-TOF MS method was as high as 94.44%. The coincidence rates of drug resistance phenotype of carbapenems, oxacillin, vancomycin, ESBLs and genotype between the microfluidic chip platform and the micro-broth dilution method or ESBLs screening test were above 90%. Conclusion The established microfluidic chip platform is fast and accurate, and has application value in microbial identification and the prediction of drug resistance, which may be used as an important supplementary method in the diagnosis of post-neurosurgical bacterial infection.

Objective To investigate the diagnostic value of procalcitonin ( PCT) and lactate in cerebrospinal fluid (CSF) combined with conventional biomarkers for post-neurosurgical bacterial meningitis (PBM).Methods Clinical data of 213 patients with post-neurosurgical meningitis admitted in Beijing Tiantan Hospital, Capital Medical University from March 2017 to December 2017 were retrospectively analyzed, including 85 cases of PBM and 128 cases of post-neurosurgical aseptic meningitis ( PAM).The diagnostic value of CSF procalcitonin , lactate and other 12 conventional biomarkers for PBM was analyzed by multivariate logistic regression.A prediction algorithm was generated and its diagnostic value for PBM was assessed with receiver operating characteristic curve (ROC).Results The univariate analysis showed that CSF cell count, CSF leukocyte count , CSF protein concentration , CSF glucose concentration, CSF glucose／blood glucose ratio, CSF PCT and CSF lactate were significantly associated with PBM.Multivariate logistic regression analysis showed that CSF PCT , CSF lactate, CSF protein concentration and CSF glucose ／blood glucose ratio were independent predictive factors for PBM.The predictive algorithm score ＝4.315 ×CSF PCT+0.822×CSF Lactate+0.009×CSF protein concentration -5.480×CSF glucose／blood glucose ratio-3.074.The predictive algorithm has the largest area under the ROC curve ( AUC ＝0.947), and the sensitivity and specificity of the predictive algorithm score were 90.60% and 85.10%, respectively.The positive predictive value , negative predictive value and the accurate rate of the algorithm in diagnosis of PBM were 84.06%, 94.44% and 90.40%, respectively.Conclusion The predictive algorithm based on the combination of CSF PCT and CSF lactate with CSF protein concentration and CSF glucose ／blood glucose ratio has a good diagnostic value for PBM.It can shorten the diagnosis time of PBM and improve the clinical outcomes.

OBJECTIVE: To assess the association of single nucleotide polymorphisms of SCN1A gene with therapeutic effect of carbamazepine among ethnic Zhuang Chinese patients with epilepsy. METHODS: Peripheral blood samples were taken from 186 epileptic patients for whom 66 cases standard regime of carbamazepine treatment was effective. Genotypes of rs3812718 and rs1813502 loci of the SCN1A gene were determined by Mass ARRAY-IPLEX and matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Correlation between genotypes of patients and efficacy of carbamazepine treatment was analyzed. RESULTS: Three genotypes (GG, GA and AA) were detected at both rs3812718 and rs1813502 loci of the SCN1A gene. A significant difference was found in allelic distribution (chi-square=17.810, P=0.000) and genotypic distribution (chi-square=17.873, P=0.000) of the rs3812718 locus between the effective group and ineffective group. No such difference was found with the rs1813502 locus (chi-square=1.606, P=0.206; chi-square=1.546, P=0.462, respectively). Compared with the GG+GA genotype, the AA genotype at rs3812718 locus significantly reduced the antiepileptic efficacy of carbamazepine (OR=3.776, 95%CI: 2.007-7.105). Among the 66 patients who were responsive to carbamazepine treatment, those with the AA genotype for rs3812718 or rs1813502 shown no significant difference in their blood concentration of carbamazepine compared with those with the GG+GA genotype (t=1.562, P=0.125; t=0.843, P=0.562, respectively). rs3812718 and rs1813502 were not in strong linkage disequilibrium. CONCLUSION Polymorphisms of rs3812718 of the SCN1A gene is associated with carbamazepine resistance among ethnic Zhuang Chinese epilepsy patients from Baise region.
Anticonvulsants ; Carbamazepine ; Epilepsy ; Genotype ; Humans ; NAV1.1 Voltage-Gated Sodium Channel ; Polymorphism, Single Nucleotide

Objective To explore the differences in antibiotic resistance among pathogenic bacteria isolated from respiratory tract and cerebrospinal fluid specimens in neurosurgery wards .Methods Antibiotic resist-ance tests were performed to analyze the antibiotic sensitivities of pathogenic bacteria isolated from respiratory tract and cerebrospinal fluid specimens in the neurosurgery wards at Beijing tiantan hospital affiliated to cap-ital medical university ,from January 2012 to December 2016 .Statistical analysis was performed using the t test or M-W test to determine the differences between the two independent samples were statistically significant . Results From January 2012 to December 2016 ,6 091 strains isolated from respiratory tract and 1 597 strains isolated from CSF specimens were obtained from patients in the neurosurgery wards of a hospital .Based on the results of the t test ,differences in the antibiotic sensitivities of pathogenic bacteria isolated from these two specimens were statistically significant .Three Gram-negative bacteria ,Pseudomonas aeruginosa ,Klebsiella pneumoniae and Acinetobacter baumannii ,showed statistically significant differences in antibiotic sensitivities between respiratory tract and cerebrospinal fluid specimens (P＜0 .05) ,but this difference was not statistically significant in Staphylococcus aureus (P＞0 .05) .Pathogenic bacteria isolated from two specimens showed sta-tistically significant differences in sensitivity to β-lactam antibiotics ,polymyxin B ,vancomycin and linezolid (P＜0 .05) .Conclusion The sensitivity differences between bacteria isolated from respiratory tract and cere-brospinal fluid specimens are statistically significant .Several reasons ,such as antibiotic-induced antibiotic re-sistance ,horizontal gene transfer are responsible for this result .