italic>Candida albicans (C. albicans) stands as the primary opportunistic fungal pathogen responsible for fungal infections. The formation of biofilms constitutes a key virulence trait of C. albicans and a pivotal factor in drug resistance. Consequently, the development of antifungal drugs possessing biofilm inhibitory properties holds importance in the treatment of fungal infectious diseases. This study conducted in-depth research of the novel biofilm inhibitor named 1-(cyclopentylamino)-3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propan-2-ol (IMB-H12). IMB-H12 showed good inhibitory activity on the formation of biofilms and a certain scavenging effect on mature biofilms. Preliminary research on the mechanism of action has found that IMB-H12 can inhibit the transformation from yeast to hyphal phase, inhibit the formation of mycelium, and reduce the adhesion activity and hydrophobicity of Candida albicans. IMB-H12 could also induce changes in the content of cell wall components, downregulate the expression of multiple genes related to adhesion and hyphal formation. Therefore, further research on this compound is expected to discover new lead compounds with antifungal activity.

Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.

Aim To investigate the effect of polyphyl-lin Ⅱ(PP Ⅱ)on autophagy of osteosarcoma(OS)cells and its related molecular mechanism.Methods U2OS and HOS cells were cultured in vitro and treated with different concentrations of PP Ⅱ(5,10,15,20 μmol·L-1)for 24 h.The changes of acid vesicles were detected by AO staining,the autophagosomes was ob-served by transmission electron microscopy,the ex-pressions of LC3B-Ⅱ/LC3B-Ⅰ,p62,caspase-3,cleaved caspase-3 were detected by Western blot,the intracellular reactive oxygen species(ROS)was detec-ted by DCFH-DA fluorescence probe,cell viability was detected by CCK-8,cell apoptosis rate was detected by Annexin V-FITC/PⅠ staining.Results PP Ⅱ signifi-cantly increased the number of acidic vesicles(P＜0.05,P＜0.01)and autophagosomes.PP Ⅱ signifi-cantly up-regulated the ratio of LC3B-Ⅱ/LC3B-Ⅰ,and down-regulated the expression level of p62 protein in a concentration-and time-dependent manner(P＜0.05,P＜0.01).PP Ⅱ significantly increased intra-cellular ROS levels(P＜0.01).Autophagy inhibitor 3-MA and CQ could reverse the regulation of cell via-bility,autophagy and apoptosis related proteins by PP Ⅱ in U2OS cells,endoplasmic reticulum stress inhibi-tor 4-PBA could also reverse the regulation of autoph-agy related proteins by PP Ⅱ in U2OS cells.Conclu-sion PP Ⅱ promotes OS cell autophagy by mediating ROS and endoplasmic reticulum stress.

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Objective To explore the effect of high altitude exposure and short-term acclimation on the platelet-associated parameters by studying the changes of platelet-associated parameters in healthy young man.Methods Four hundred and sixtytwo young men were recruited from Chengdu (the elevation of 500m) during Jun.2012 to Aug.2013 according to the inclusion and exclusion criteria,of which 193 had been living in Chengdu (plain group),and 269 flew from Chengdu to Lhasa (3700m) in 2 hours,and then 147 of them were exposed in the high altitude for 1 day (acute high altitude exposure group),and another 122 for 7 days (short-term acclimation group).The demographic data were collected and the blood routine and platelet-associated parameters were measured of all the participants,and then the information collected were compared between the 3 groups.Results Compared to the plain group,the platelet count (PLT),platelet distribution width (PDW) and plateletcrit (PCT) reduced and the mean platelet volume (MPV) increased significantly (P＜0.05) in the acute high altitude exposure group;while all the indexes in short-term acclimation group returned to approach the levels in the plain group,but statistical differences still existed in PLT,PDW and PCT (P＜0.05).The platelet activating factor (PAF) and epinephrine (Epi) decreased markedly in acute high altitude exposure group than in plain group (P＜0.05);while in short-term acclimation group,the PAF returned to approach the level in plain group,and the Epi was further down (P＜0.05).In addition,no marked difference of 5-HT level was observed in the 3 groups (P＞0.05).Pearson correlation analysis indicated that high altitude-induced reduction of oxygen saturation (SpO2) was positively related to the changes of PLT.Conclusions Acute high altitude exposure may reduce PLT,PDW and PCT levels,but elevate MPV and enhance the platelet activity.The reduction of SpO2 might be associated with the changes of PLT,PDW and PCT.Platelet-associated parameters may be recovered to normal with a compensatory effect after short-term acclimation.

Objective: To examine the sex-specific associations between tobacco smoking and risk of cardiovascular diseases in Chinese adults. Methods: The present analysis included 487 373 participants from the China Kadoorie Biobank after excluding those with cancer, heart diseases, stroke at baseline survey. The baseline survey was conducted from June 2004 to July 2008. The number of follow-up years was calculated from the time that the participants completed baseline survey to the time of any event: CVD incidence, death, loss of follow-up, or December 31, 2015, whichever occurred first. We used Cox proportional hazards regression models to estimate the HRs and 95%CI of incident cardiovascular diseases with tobacco smoking. Results: During a median follow-up of 8.9 years(a total of 4.1 million person years), we documented 33 947 cases of ischemic heart diseases, 6 048 cases of major coronary diseases, 7 794 cases of intracerebral hemorrhage, and 31 722 cases of cerebral infarction. The prevalence of smoking was much higher in men (67.9%) than in women (2.7%). Smoking increased risk of all subtypes of cardiovascular diseases. Compared with nonsmokers, the multivariable-adjusted HRs (95% CI) for current smokers were 1.54 (1.43-1.66) for major coronary event, 1.28 (1.24-1.32) for ischemic heart disease, 1.18 (1.14-1.22) for cerebral infarction, and 1.07 (1.00-1.15) for intracerebral hemorrhage, respectively. Female smokers tended to have greater risk of developing major coronary event associated with amount of tobacco smoked daily (interaction P=0.006) and age when smoking started (interaction P=0.011). There was no sex difference in these two effects for ischemic heart diseases, intracerebral hemorrhage and cerebral infarction (all interaction P>0.05). Conclusions: This prospective study confirmed increased risk of all subtypes of cardiovascular diseases in current smokers. Smoking was more harmful to women than to men for major coronary event.
Adult ; Asian People/statistics & numerical data* ; Cardiovascular Diseases/epidemiology* ; China/epidemiology* ; Female ; Humans ; Incidence ; Male ; Neoplasms/epidemiology* ; Prevalence ; Prospective Studies ; Risk Factors ; Smoking/ethnology* ; Smoking Cessation ; Stroke/epidemiology* ; Tobacco Smoking/adverse effects*

Objective To investigate the clinical value of preoperative nutritional support (PNS) therapy in the hepatectomy of patients with nutritional risk.Methods The prospective study was conducted.The clinical data of 133 patients with nutritional risk who were admitted to the Drum Tower Hospital Affiliated to Nanjing University Medical School from August 2012 to June 2016 were collected.All the patients undergoing PNS and traditional therapy were divided into the PNS group and the control group by random number table method,respectively.Observation indicators:(1) comparisons of laboratory indexes between groups;(2) comparisons of postoperative situations between groups;(3) comparisons of postoperative complications between groups.Measurement data with normal distribution were represented as-x±s.Comparisons between groups were evaluated with the independent-sample t test.Comparisons of count data were analyzed using the chi-square test,and repeated measures data were analyzed by the repeated measures ANOVA.Results All the 133 patients were screened for eligibility,including 68 in the PNS group and 65 in the control group.(1) Comparisons of laboratory indexes between groups:alanine transaminase (ALT),aspartate transaminase (AST),total bilirubin (TBil),cholinesterase,albumin (Alb),prealbumin,transferrin and C-reactive protein (CRP) in the PNS group were respectively (36± 13) U/L,(29± 10) U/L,(18.5±2.4) mmol/L,(5 738± 1 824) U/L,(37.4±5.1) g/L,(155±48) mg/L,(2.2±0.5)g/L,(10±4) g/L at admission and (33 ± 9) U/L,(27 ± 8) U/L,(17.9± 1.8) mmol/L,(5 796± 2 016) U/L,(38.5 ± 4.7) g/L,(181 ± 40) mg/L,(2.4± 0.5) g/L,(8± 4) g/L before operation and (285±100)U/L,(218±93)U/L,(33.5±6.3)mmol/L,(4 847±1 044)U/L,(32.6±3.8)g/L,(105±34)mg/L,(1.3±0.4) g/L,(55±28) g/L at 1 day postoperatively and (149±84) U/L,(76±42) U/L,(22.7±4.9) mmol/L,(3 866±893) U/L,(34.2±2.4) g/L,(125±30) mg/L,(1.6±0.4) g/L,(51±34) g/L at 3 days postoperatively and (64±33) U/L,(44±18) U/L,(19.4±2.8) mmol/L,(4 257± 1 032) U/L,(37.0±2.1) g/L,(148±42) mg/L,(1.9±0.4)g/L,(16±11)g/L at 7 days postoperatively;ALT,AST,TBil,cholinesterase,Alb,prealbumin,transferrin and CRP in the control group were respectively (36± 15)U/L,(31± 12)U/L,(18.3±2.9)mmol/L,(5 762±1 693)U/L,(37.3±6.1)g/L,(162±51)mg/L,(2.3±0.5)g/L,(10±4)g/L at admission and (36±11)U/L,(30±11)U/L,(18.2±2.8)mmol/L,(5 789±1 673)U/L,(37.8±7.1)g/L,(166±57) mg/L,(2.3±0.6) g/L,(9±5) g/L before operation and (305±127) U/L,(246± 104) U/L,(34.2±7.8) mmol/L,(4 842±1 173)U/L,(32.0±4.1) g/L,(83±32) mg/L,(1.2±0.4) g/L,(61 ±31) g/L at 1 day postoperatively and (163±104)U/L,(82±62)U/L,(23.1±6.0)mmol/L,(3 672±937) U/L,(33.8±3.6) g/L,(106±30)mg/L,(1.4±0.4)g/L,(61±40)g/L at 3 days postoperatively and (77±48) U/L,(52±27) U/L,(20.2±3.5) mmol/L,(3 925±987) U/L,(36.6±2.8) g/L,(125±40) mg/L,(1.7±0.4) g/L,(22± 12) g/L at 7 days postoperatively,showing no statistically significant difference in changing trends of above indicators between groups (F =1.007,2.223,0.579,0.014,0.235,3.533,2.970,2.143,P＞0.05).Results of further analysis showed that there were statistically significant differences in the levels of ALT,AST and cholinesterase at 7 days postoperatively between groups (t=1.832,2.073,1.899,P＜0.05),and in the levels of prealbumin before operation and at 1,3 and 7 days postoperatively between groups (t =1.698,3.738,3.625,3.178,P＜0.05) and in the levels of transferrin and CRP at 3 and 7 days postoperatively between groups (t=2.917,2.709,1.667,2.990,P＜0.05).(2) Comparisons of postoperative situations between groups:time to initial exsufflation,time of initial defecation,infused volume of exogenous albumin and duration of postoperative hospital stay were respectively (46± 15)hours,(64±16)hours,(23±10)g,(9.2±2.6)days in the PNS group and (55±18)hours,(78±21)hours,(39±25)g,(11.7±5.3) days,with statistically significant differences in the above indicators between groups (t =2.830,4.157,5.044,3.497,P＜0.05).(3) Comparisons of postoperative complications between groups:23 and 33 patients in the PNS and control groups had postoperative complications,showing a statistically significant difference between groups (x2=3.915,P＜0.05).Eight and 17 patients in the PNS and control groups were respectively complicated with peritoneal effusion,with a statistically significant difference between groups (x2 =4.508,P＜ 0.05).Conclusion PNS therapy in the hepatectomy of patients with nutrition risk can effectively improve pre-and post-operative nutrition statuses,reduce liver damage,accelerate recoveries of liver and gastrointestinal functions,reduce complications,shorten duration of postoperative hospital stay and accelerate patients' recovery.

Objective To investigate the efficacy of biphasic insulin aspart 50(BIAsp50)twice daily(bid) versusbiphasichumaninsulin50(BHI50)(bid)plusmetforminonbloodglucosecontrolfollowingastandardmealtest in Chinese patients with type 2 diabetes mellitus(T2DM). Methods A randomized, open-label, 2-sequence, crossover trial for two 4-week treatment periods was conducted in 14 Chines institutes. Eligible subjects inadequately controlled with BHI50(bid)plus metformin were randomized to two sequences in a 1 : 1 ratio(A:BIAsp50-BHI50, B:BHI50-BIAsp50 ) . Standard meal tests were performed at baseline and the ends of two periods within 4 weeks. Primary endpoint was 2h postprandial plasma glucose ( PPG) increment following standard meal test, with insulin dose standardized at 0. 3 IU/kg. Results A total of 161 subjects were randomized into two sequences(81 to sequence A, and 80 to sequence B) and finally analysed. After 4 weeks of treatment, mean 2h PPG increment with BIAsp50 was lower than that with BHI50 [ treatment difference of BIAsp50 vs BHI50: -1. 12 mmol/L ( 95% CI-1. 66,-0. 58), P<0. 01], suggesting superiority of BIAsp50 over BHI50. Incremental area under the curve for PPG(0-2 h)with BIAsp50 was lower than that with BHI50 [treatment difference:-38. 8 mmol·L-1·min-1(95%CI-77. 3,-0. 26), P=0. 049], as was the mean 2h PPG [treatment difference:-0. 58 mmol/L(95% CI -1. 13,-0. 03), P=0. 040]. The FPG value with BIAsp50 was higher than that with BHI50 [treatment difference:0. 52 mmol/L(95%CI 0. 18, 0. 86), P=0. 003]. The rate of nocturnal hypoglycemia with BIAsp50 was lower than that with BHI50(1. 13 vs 2. 86 events per subject year, P<0. 01). Conclusion In patients with T2DM inadequately controlled with BHI50 plus metformin, BIAsp50 was proven to be well-tolerated with improved postprandial glucose control compared with BHI50.

OBJECTIVETo develop and evaluate a mouse model of nonalcoholic steatohepatitis (NASH) induced by a high-fat and high-fructose (HFHFr) diet.

METHODSSix-week-old C3H mice were randomly divided into groups for HFHFr diet experimental modeling, high fat-only (HF) diet controls, high fructose-only (HFr) diet controls, and standard chow (SC) diet controls. The standard HFHFr diet was modified so that it consisted of 76.5% standard chow, 12% lard, 1% cholesterol, 5% egg yolk powder, 5% whole milk powder, and 0.5% sodium cholate, along with 20% fructose drinking water. At the end of experimental weeks 4, 8, and 16, measurements were taken for the NASH-related parameters of body mass, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), lipid profile, and wet liver weight (upon sacrifice). In addition, histological changes in the liver were evaluated by hematoxylin-eosin (HE) and oil red O staining. The significance of differences between groups was assessed by statistical analysis, using the

METHODSof t-test, Wilcoxon rank sum test, x2 test, F test or Fisher's test as appropriate.

RESULTSAs compared to the mice in the SC group at the corresponding time points, the mice in the HFHFr and HF groups showed significantly higher body mass and wet liver weight, as well as more extensive and robust lipid disposition in hepatic tissues as evidenced by oil red O staining. However, HE staining indicated that the HFHFr and HF groups had different degrees of macrosteatosis accompanied with intralobular inflammatory foci, with the former showing more remarkable NASH-related histological changes. Analysis at the end of week 16 showed that about 80% of the mice in the HFHFr group had developed NASH [nonalcoholic fatty liver disease (NAFLD) activity score (NAS): less than 5]. The levels of low-and high-density lipoprotein (LDL and HDL) cholesterol, as well as the levels of ALT and AST, were increased from the end of week 4 to the end of week 8 for the HFHFr and HF groups. At the end of week 16, the two groups differed in the extent of increase in total cholesterol and LDL and HDL cholesterol, with only the HFHFr group showing statistically significant changes. Specifically, at the end of week 16, the HFHFr group showed ALT levels of 108.5 +/- 93.34 U/L (F=5.099, P =0.005 vs. HF group: 44.30 +/- 35.71 U/L, HFr group: 46.70 +/- 17.95 U/L, SC group: 24.70 +/- 6.57 U/L), AST levels of 316.30 +/- 208.98 U/L (F=6.654, P=0.001 vs. HF: 132.12 +/- 75.43 U/L, HFr: 143.30 +/- 38.53 U/L, SC: 122.60 +/- 12.76 U/L), total cholesterol levels of 5.18 +/- 0.58 mmol/L (F=72: 470, P =0.000 vs. HF: 3.94 +/- 0.75 mmol/L, HFr: 2.30 +/- 0.50 mmol/L, SC: 2.02 +/- 0.24 mmol/L), HDL cholesterol levels of 3.05 +/- 0.49 mmol/L (F=25.413, P =0.000 vs. HF: 2.65 +/- 0.54 mmol/L HFr: 1.77 +/- 0.47 mmol/L, SC: 1.58 +/- 0.16 mmol/L), LDL cholesterol levels of 1.11 +/- 0.23 mmol/L (F =83.297, P =0.000 vs. HF: 0.72 +/- 0.17 mmol/L, HFr: 0.27 +/- 0.04 mmol/L, SC: 0.20 +/- 0.05 mmol/ L).

CONCLUSIONThe present study suggests that a mouse model of NASH can be successfully induced by a 16-week modified HFHFr diet.

BACKGROUND:CT-guided percutaneous intervention and rehabilitation techniques are both classic programs for diagnosis and treatment of lumbar disc herniation. Is the combination of CT-guided percutaneous intervention and rehabilitation techniques preferential y used for treatment of lumbar disc herniation?
OBJECTIVE:To evaluate the curative effect of CT-guided interventional injection combined with rehabilitation integration treatment for lumbar disc herniation and to analyze prognostic factors.
METHODS:Eighty-eight patients with lumbar disc herniation were subjected to CT-guided interventional injection combined with rehabilitation integration treatment from May 2010 to May 2013. Injection medicine consisted of betamethasone, tanshinone Ⅱ A sulfonate, neurotropin, normal saline and iohexol. Rehabilitation integration treatment included traction, manipulation, acupuncture, transcutaneous electrical nerve stimulation and thermal magnon. Macnab criteria and Chinese version of Oswestry low back pain disability questionnaire were used to assess the curative effects in comparison with the 112 patients receiving only CT-guided interventional injection that were reported previously. The prognostic factors, such as age, disease course time and herniation type of target segment were testified by correlation analysis.
RESULTS AND CONCLUSION:Total y 77 patients were completely fol owed up for 1 year. There were excellent outcomes in 64 cases, while favorable outcomes in 7 cases, fair outcomes in 5 case, poor outcome in 1 case, with a better outcome rate of 92%.There was a significantly decreased trend in Oswestry disability Index scores at 1, 6, 12 months during the fol ow-ups (P<0.01). No severe complications occurred in al the included patients. The curative effects were improved in term of better outcomes rate compared with the 112 patients receiving only CT-guided interventional injection, but there was no significant difference (P>0.05). The young group (≤ 45 years) had better outcomes than the older group (>45 years;P<0.01). In addition, disease course time and herniation type of target segment were not statistical y significant risk factors predicting clinical results (P>0.05). These findings indicate that CT-guided interventional injection combined with rehabilitation integration treatment could relieve lower back pain and radical leg pain effectively and decrease life disability level.