Cryptococcus neoformans are most common Fungi in central nervous system infection.Incidence of cryptococcal meningitis is on the rise in recent years.The use of antifungal drugs must control majority of cryptoeoccosis,and at least one-third of patients have experienced failure of antifungal therapy,and mortality and disable rate are on the rise.Long-term heavy use of antifungal drugs cause cryptococcus resistance phenomenon,and it is the main cause of treatment failure.Therefore,the study of cryptococcus resistance mechanism is imminent.This review summarizes the research progresses of cryptococcus resistance mechanism in recent years,aiming to provide theoretical guidance for the research of new antifungal drugs and providing basis for individual treatment.

OBJECTVE:To investigate the clinical effect and safety of pregabalin combined with gabapentin in the treatment of central pain after cerebral infarction.METHODS:One hundred and fifty patients with central pain after cerebral infarction in our hospital from Jan.2010 to Dec.2015 in our department were randomly divided into group A,B,C,with 50 cases in each group.Group A was given Pregabalin capsule 75 mg,bid combined with Gabapentin capsule 0.1 g,tid;group B was given Pregabalin capsule 75 mg,bid;group C was given Gabapentin capsule 0.1 g,tid;3 groups were treated for 4 weeks.VAS score,NRS score,PSQI and SF-36 score were observed among 3 groups before and after treatment to evaluate clinical efficacies of 3 groups;the occurrence of ADR were recorded in 3 groups.RESULTS:The clinical total response rate of group A,B,C were separately 94.00％,74.00％,70.00％.The clinical total response rate of group A was significantly better than that of group B and C,with statistical significance (P＜0.05).After treatment,VAS score of group A,B,C were separately(3.87 ± 0.74),(5.10 ± 1.26),(5.03 ± 1.23);NRS score were separately (3.91 ± 0.88),(5.29 ± 1.25),(5.37 ± 1.30);VAS score and NRS score of group A were signifi cantly lower than group B,C and before treatment,with statistical significance (P＜0.05);PSQI score of group A,B,C were separately(4.03 ± 0.85),(5.92 ± 1.16),(5.83 ± 1.11);SF-36 score were separately (372.84 ± 73.25),(348.07 ± 60.54),(345.67 ± 59.72);PSQI score and SF-36 score of group A were significantly better than group B,C and before treatment,with statistical sig nificance (P＜0.05).There was no statistical significance in the incidence of ADR among 3 groups (P＞0.05).CONCLUSIONS:Compared with pregabalin and gabapentin alone,pregabalin combined with gabapentin in the treatment of central pain after cerebral infarction can efficiently relieve the perceived pain,improve sleep quality and daily life quality and not increase the risk of ADR;therefore,drug combination plan is recommended for patient with central pain after cerebral infarction,especially with poor effect of two single drug.

Objective To purify native and recombinant heparin-binding hemagglutinin(HBHA)protein,and investigate the activity of HBHA polyclonal antibody against aggregation of Bacillus CalmetteGuerin(BCG)induced by HBHA.Methods After growing BCG to the stationary phase in the 7H9 liquid medium,the native HBHA protein(nHBHA)was obtained by CL-6B column chromatography.At the same time,the HBHA gene fragment was cloned and expressed by transforming Escherichia coli BL-21.Then the polyclonal antibody against rHBHA was prepared by immunizing rabbit.Different comcentration of the HBHA protein was added to the BCG liquid medium,and the aggregation of the BCG was observed.Then,add the HBHA protein that incubated with anti-HBHA antibodies to the BCG culture medium and observe the aggregation of BCG.Results The purity of native HBHA was 99% and the concentration was 1.016 mg/ml.The expressed product contained 36% of total somtic protein.After purified,the purity of the recombinant HBHA protein was 97.1% and the concentration was 10.98 mg/ml.Both the rHBHA and nHBHA could induce the aggregation of BCG.When then concentration of nHBHA is 0.2μg/ml,BCG could be induced to aggregate,while the rHBHA concentration is 2μg/ml could induce the aggregation.Both aggregations could be suppressed by the polyclonal antibody against rHBHA.Conclusions The native and recombinant HBHA are successfully obtained.It is proved that the rHBHA could induce the aggregation of BCG similar as nHBHA,and polyclonal antibody against rHBHA could also suppress the activity of nHBHA.It suggested that rHBHA could be further used in clinical diagnosis and vaccination.

Objective To evaluate the application effect of nursing management in the follow-up of patients with recurrent acute pancreatitis (RAP).Methods During January 2016 and January 2017,the clinical data of RAP patients admitted in Changhai Hospital of Navy Medical University was collected.Selfcontrol method was used to establish a prospective cohort study.Meticulous nursing management mode was applied to follow up the patients for 12 months.Patients' compliance,symptom improvement,patients' satisfaction and other markers are evaluated using questionnaires to assess the effect of meticulous nursing management once every 3 months.The data over 12 months were collected.Results Sixty-four RAP patients were finally included.The average follow-up period was 19.7 ±3.4 months.Before admission,the average disease course was(4.21 ± 3.95) years.30 patients (46.9％)had a history of drinking;33 patients (51.6％)had a history of smoking.25 patients (39.1％) had abnormal blood lipid and 40 patients (62.5％) had the dietary habit of high lipid and high protein.The etiology included alcohol (n =10,15.6％),high lipid (n =7,10.9％),biliary diseases (n =1,1.6％),idiopathic causes (n =46,71.9％) and abnormal BMI (n =49,76.6％).After the meticulous nursing management,the frequency of pancreatitis,VAS score of pain and alcohol intake situation was obviously lower than before intervention [(0.50 ±0.85) times/year vs(2.77 ±2.52)times/year;(1.84 ±2.54)vs(6.47 ±2.15);2 cases vs 30 cases].The number of patients who took medicine on time and BMI were obviously decreased[(52 cases vs 13 cases;(23.26 ± 3.85) kg/m2 vs (21.92 ± 4.27)kg/m2)],and the differences were statistically significant (P ＜0.01).Patients' satisfaction with this nursing model was 4.90 ± 0.56.Conclusions The implementation of the new meticulous nursing management model can effectively alleviate patient's symptom condition and improve the compliance behavior and life quality of the patients.

Objective:To explore whether the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) is involved in the inflammatory signaling pathway of endothelial cells.Methods:Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. Results:Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2 -ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2 -ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2 -ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2 -ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2 -ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2 -ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2 -ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2 -ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. Compared with the blank control group, the phosphorylation level of Akt in the LPS group was increased. Compared with the LPS group, both OGT expression and O-GlcNAc modification were down-regulated after pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor. Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2 -ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2 -ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2 -ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2 -ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2 -ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2 -ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2 -ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. Conclusions:The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. AKT may be involved in the effect of LPS on the inhibition of O-GlcNAc modification.

Objective:To evaluate the clinical characteristics and prognosis of febrile convulsions (FS) in children during the epidemic period of novel coronavirus Omicron variant.Methods:A retrospective analysis was conducted on the clinical data of pediatric patients diagnosed with FS at Changsha Central Hospital Affiliated to University of South China from February 1, 2022 to January 31, 2023. The clinical characteristics and prognosis of FS patients caused by Omicron variant infection (observation group) were compared with those caused by non Omicron variant infection (control group).Results:A total of 131 cases in the observation group and 341 cases in the control group; The proportion of children aged 12-36 months in the observation group was lower than that in the control group ( P<0.05), and the proportion of children aged ≥60 months was higher than that in the control group ( P<0.05). Most of the FS in the observation group occurred within 24 hours of fever (128/131, 97.7%), with a statistically significant difference compared to the control group ( P<0.05), and most of them were generalized tonic clonic seizures (127/131, 96.9%), with only one seizure during the course of the disease (114/131, 87.0%), consistent with the characteristics of simple FS. The main clinical symptoms of FS patients in the observation group were upper respiratory tract infections (108/131, 82.5%), which were significantly higher than those in the control group (164/341, 48.1%), while the incidence of lower respiratory tract infections was lower than that in the control group ( P<0.05). 369 pediatric patients were followed up by phone or outpatient visits, with 98 cases in the observation group and 2 cases experiencing recurrence. There was no recurrence in the group aged ≥60 months; A total of 271 cases were followed up in the control group, with 9 cases experiencing recurrence. Conclusions:The number of children with FS caused by novel coronavirus Omicron variant has increased sharply, and the proportion of late onset FS patients has increased significantly. Most of them are upper respiratory tract infections. Convulsions usually occur within 24 hours of fever, and the prognosis is good.

Background and objectiveSerum carcinoembryonic antigen (CEA) and the soluble fragment of cyto-keratin 19 (CYFAR21-1) are important tumor markers (TMs) in the preoperative examination of patients with non-small cell lung cancer (NSCLC). However, the prognostic role of these markers in NSCLC patients remains controversial. hTe aim of the study was to investigate the clinical signiifcance of serum CEA variances and CYFAR21-1 levels for the prognosis of NSCLC patients following surgery.MethodshTis retrospective study investigated the clinical records and follow-up sessions of 175 patients with NSCLC who accepted surgery and adjuvant chemotherapy. Patients were subdivided into groups based on serum CEA and CYFAR21-1 levels. Survival analysis was conducted usingKaplan-Meier method for each group. hTe prognostic fac-tor was evaluated usingCox proportional hazards model.Results hTe overall survival (OS) of patients with high preopera-tive CEA or CYFAR21-1 levels was lower than that of patients with normal preoperative CEA or CYFAR21-1 levels. hTe OS displayed a signiifcant difference (P=0.001) between groups with high and normal preoperative CYFAR21-1. Compared with groups exhibiting normal preoperative and postoperative levels of CEA or CYFAR21-1, the OS was shorter for groups with high preoperative and postoperative levels of CEA or CYFAR21-1. hTe difference of the paired groups was signiifcant (P<0.05). Compared with the groups with normal preoperative and postoperative levels of CEA and CYFAR21-1, the OS was lower for the groups with high preoperative and postoperative levels of CEA and CYFAR21-1, which indicated a signiifcant difference (P<0.001). hTe CEACYFAR211 (HHHH), CEACYFAR211 (NNHH), CYFAR21-1 (HH), CEA (HH), and male genderwere identiifed as independent prognostic factors (P<0.05).ConclusionhTis study suggested that the prognosis of NSCLC patients was not signiifcantly satisfactory if preoperative and postoperative level of serum CEA or CYFAR21-1 was higher than standard value, especially if the preoperative and postoperative levels of CYFAR21-1 and CEA were higher than the standard values. hTe measurement of preoperative and postoperative levels of CYFAR21-1 and CEA proved helpful for the prognosis of patients with NSCLC.

Objective:To explore the value of laparoscopic and endoscopic cooperative surgery with the patient lying on supine position under general anesthesia in the operation of type I Mirizzi syndrome with choledocholithiasis.Methods:From Jan 2018 to Jan 2020, 53 cases of Mirizzi syndrome with choledocholithiasis undergoing laparoscopic and endoscopic cooperative surgery (preLC+ ERCP+ EST) at the Second Affiliated Hospital of Kunming Medical University were retrospectively analyzed.Results:53 patients successfully underwent LC without conversion to open surgery, and 2 patients failed in ERCP + EST attempt, with a success rate of 96.2%. One patient developed pancreas pseudocyst as a result of post-operative hemorrhagic necrotizing pancreatitis. Two patients suffered from chronic pancreatitis. Three patients complaining postoperative upper abdominal discomfort were finally diagnosed as stump cystic duct inflammation by MRCP, and no abnormalities were found in the follow-up of the remaining cases.Conclusion:Laparoscopic and endoscopic cooperative surgery in the treatment of patients with type I Mirizzi syndrome combined with choledocholithiasis is minimally invasive and effective.

Objective:The research was aimed to investigate the association between serum total homocysteine (tHcy) and subacute combined degeneration of the spinal cord (SCD).Methods:A retrospective survey of 106 newly diagnosed patients with SCD were enrolled in this research who were treated in the department of neurology of Xijing Hospital from January 2008 to February 2019, meanwhile, 121 patients with spinal cord lesion (not SCD) and 104 neurology mild outpatients were selected as controls. Serum tHcy level was determined by using the chemiluminescent immunoassay assay. A multivariate logistic regression model was used to analyze the risk factors for SCD. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, sensitivity, specificity and Youden index were used to evaluate the diagnostic efficacy of tHcy. Spearman correlation analysis was used to observe the correlation between tHcy and SCD severity. The SCD patients were categorized into normal or mild tHcy group, moderate tHcy group, and severe tHcy group based on tHcy levels. Clinical symptoms, nerve conduction velocity, magnetic resonance imaging (MRI) findings from the patients were studied.Results:The serum tHcy levels in SCD patients were 64.3(26.5, 98.8) μmol/L, while in patients with spinal cord lesion (not SCD) group were 13.7(10.8, 19.2) μmol/L, neurology mild outpatients were 10.6(8.2, 13.0) μmol/L, which was higher in SCD group ( H=112.020, P<0.001), ( H=165.525, P<0.001).The multivariate logistic regression model showed tHcy is the impact factor of SCD ( OR=1.107, 95% CI:1.077-1.139, P<0.001). At ROC analysis, tHcy showed diagnostic value with an optimal cut-off value of 24.9 μmol/L (AUC 0.913, 95% CI: 0.875-0.951, sensitivity 79.2%, specificity 91.6%). Spearman correlation analysis showed that tHcy was positively correlated with functional disability rating scale ( r=0.254, P=0.009). Conclusions:Serum tHcy is the risk factor for SCD and related to its disability. Focus on the increased level of tHcy plays a positive role in the diagnosis of SCD.

Objective:The research was aimed to investigate the association between serum total homocysteine (tHcy) and subacute combined degeneration of the spinal cord (SCD).Methods:A retrospective survey of 106 newly diagnosed patients with SCD were enrolled in this research who were treated in the department of neurology of Xijing Hospital from January 2008 to February 2019, meanwhile, 121 patients with spinal cord lesion (not SCD) and 104 neurology mild outpatients were selected as controls. Serum tHcy level was determined by using the chemiluminescent immunoassay assay. A multivariate logistic regression model was used to analyze the risk factors for SCD. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, sensitivity, specificity and Youden index were used to evaluate the diagnostic efficacy of tHcy. Spearman correlation analysis was used to observe the correlation between tHcy and SCD severity. The SCD patients were categorized into normal or mild tHcy group, moderate tHcy group, and severe tHcy group based on tHcy levels. Clinical symptoms, nerve conduction velocity, magnetic resonance imaging (MRI) findings from the patients were studied.Results:The serum tHcy levels in SCD patients were 64.3(26.5, 98.8) μmol/L, while in patients with spinal cord lesion (not SCD) group were 13.7(10.8, 19.2) μmol/L, neurology mild outpatients were 10.6(8.2, 13.0) μmol/L, which was higher in SCD group ( H=112.020, P<0.001), ( H=165.525, P<0.001).The multivariate logistic regression model showed tHcy is the impact factor of SCD ( OR=1.107, 95% CI:1.077-1.139, P<0.001). At ROC analysis, tHcy showed diagnostic value with an optimal cut-off value of 24.9 μmol/L (AUC 0.913, 95% CI: 0.875-0.951, sensitivity 79.2%, specificity 91.6%). Spearman correlation analysis showed that tHcy was positively correlated with functional disability rating scale ( r=0.254, P=0.009). Conclusions:Serum tHcy is the risk factor for SCD and related to its disability. Focus on the increased level of tHcy plays a positive role in the diagnosis of SCD.