OBJECTIVES: To investigate the clinical characteristics and prognosis of chronic disseminated candidiasis (CDC) in children with acute leukemia (AL) following chemotherapy. METHODS: A retrospective analysis was conducted on children diagnosed with CDC (including confirmed, clinically diagnosed, and suspected cases) after AL chemotherapy from January 2015 to December 2023 at Fujian Medical University Union Hospital, Zhangzhou Municipal Hospital, and Quanzhou First Hospital Affiliated to Fujian Medical University. Clinical characteristics and prognosis were analyzed. RESULTS: The incidence of CDC in children with AL following chemotherapy was 1.92% (32/1 668). Among the children with acute lymphoblastic leukemia, the incidence of CDC in the high-risk group was significantly higher than in the low-risk group (P=0.002). All patients presented with fever unresponsive to antibiotics during the neutropenic period, with 81% (26/32) involving the liver. C-reactive protein (CRP) levels were significantly elevated (≥50 mg/L) in 97% (31/32) of the patients. The efficacy of combined therapy with liposomal amphotericin B and caspofungin or posaconazole for CDC was 66% (19/29), higher than with caspofungin (9%, 2/22) or liposomal amphotericin B (18%, 2/11) monotherapy. The overall cure rate was 72% (23/32). The proportion of patients with CRP ≥50 mg/L and/or a positive β-D-glucan test for more than 2 weeks and breakthrough infections during caspofungin treatment was significantly higher in the treatment failure group compared to the successful treatment group (P<0.05). CONCLUSIONS CDC in children with AL after chemotherapy may be associated with prolonged neutropenia due to intensive chemotherapy. Combination antifungal regimens based on liposomal amphotericin B have a higher cure rate, while persistently high CRP levels and positive β-D-glucan tests may indicate poor prognosis.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Antifungal Agents/therapeutic use* ; Candidiasis/diagnosis* ; Chronic Disease ; Leukemia/complications* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications* ; Prognosis ; Retrospective Studies

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

Objective To investigate the effect of amygdalin on the permeability increase of microvascular endothelial cells(PMVEC)induced by influenza A virus FM1 and its mechanism.Methods The PMVEC cells were randomly divided into control group,model group(100 TCID50 FM1),amygdalin low-dose group(100 TCID50 FM1+4.0 mg·mL-1 amygdalin),amygdalin medium-dose group(100 TCID50 FM1+8.0 mg·mL-1 amygdalin),amygdalin high-dose group(100 TCID50 FM1+16.0 mg·mL-1 amygdalin)and 740Y-P group(100 TCID50 FM1+16.0 mg·mL-1 amygdalin+50 μmol·L-1 PI3K activator 740Y-P).Methyl thiazolyl tetrazolium(MTT)method,Transwell method,enzyme linked immunosorbent assay(ELISA)method and Western blot method were used to detect cell proliferation,cell permeability,inflammatory factor expression level and protein expression level in each group,respectively.Results Interleukin-6(IL-6)levels in control,model,amygdalin-L,amygdalin-M,amygdalin-H groups were(50.12±3.16),(93.12±5.61),(80.33±6.24),(70.05±5.46)and(61.03±4.68)pg·mL-1,respectively;the levels of tumor necrosis factor-α(TNF-α)in each group were(101.31±9.24),(167.05±10.31),(142.02±10.13),(125.34±9.87)and(112.44±8.05)pg·mL-1,respectively.The cell transepithelial resistance(TER)of control,model,amygdalin-L,amygdalin-M,amygdalin-H and 740Y-P groups were(53.01±4.17),(24.98±2.66),(30.01±3.49),(36.84±3.25),(46.23±4.31),(30.21±3.16)Ω × cm2;phosphorylated phosphatidylinositol-3 hydroxy kinase(p-PI3K)protein levels in each group were 0.34±0.04,1.01±0.09,0.80±0.08,0.61±0.07,0.43±0.05,0.87±0.09,respectively;phosphorylated mammalian target of repamycin(p-mTOR)levels in each group were 0.27±0.03,0.82±0.10,0.60±0.06,0.42±0.03,0.31±0.02 and 1.01±0.12,respectively.Compared model group with control group;compared amygdalinp-L,-M,-H groups with model group;compared amygdalinp-H group with 740Y-P group,the differences of the above indicators were all statistically significant(all P＜0.05).Conclusion Amygdalin may decrease the permeability of PMVEC cells induced by influenza virus FM1 by inhibiting PI3K/AKT/mTOR pathway.

Objective To investigate the effects of emodin on the healing of infected wound and the regulation of Toll-likereceptor 4(TLR4)/nuclear factor kappa-B(NF-κB)signaling pathway in rats.Methods The model of infectious wounds rats were constructed by the full-thickness skin defect method.The successful model rats were randomly divided into model group,control group and experimental-L,-M,-H groups with 12 rats per group;another 12 normal rats were taken as the normal group.Experimental-L,-M,-H groups was applied with emodin 150,300 and 600 μg·d-1 and 200 mg·kg-1 emodin by gavage,respectively.Control group was applied with mopirolacin cream 0.1 g·d-1 on rat wounds,once a day.Normal and model groups were treated with 0.9％NaCl.Six groups were treated for 21 days.The wound healing rates and dynamic blood flow were measured.The levels of tumor necrosis factor(TNF)-α and interleukin(IL)-1β in serum and the hydroxyproline(HYP)and catalase(CAT)in wound tissue were measured by enzyme linked immunosorbent assay.The protein levels of TLR4 and NF-κB in wound were determined by Western blot.Results The wound healing rates of experimental-M,-H groups,control group and model group were(50.70±1.26)％,(75.51±0.50)％,(69.44±1.65)％and(28.58±5.09)％,respectively.The dynamic blood flow values of experimental-M,-H groups,control group,model group and blank group were(123.71±3.71),(155.61±2.47),(146.29±2.04),(79.47±4.76)and(158.00±1.93)mL·min-1;the levels of TNF-α were(81.05±2.32),(56.69±1.59),(69.53±2.39),(139.46±2.46)and(46.49±5.71)ng·L-1;the levels of IL-1β were(59.87±0.83),(42.66±1.30),(48.37±3.34),(88.79±1.84)and(33.93±2.19)ng·L-1;the levels of HYP were(24.79±0.82),(31.12±1.16),(25.83±1.12),(16.88±2.20)and(32.95±1.18)pg·mg-1;the levels of CAT were(24.99±1.47),(34.52±1.26),(31.00±1.15),(13.70±2.09)and(34.23±0.70)U·mg-1;the relative expression levels of TLR4 protein were 0.74±0.05,0.53±0.05,0.55±0.04,1.09±0.07 and 0.23±0.05;the relative expression levels of NF-κB protein were 0.69±0.06,0.44±0.04,0.52±0.03,1.10±0.04 and 0.22±0.10,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups were statistically significant(all P＜0.05).Conclusion Emodin can improve the infectious wound healing and dynamic blood flow in rats,and inhibit the inflammatory levels and oxidative stress response in wound tissue,and the mechanism may be related to the regulation of TLR4/NF-κB pathway.

Objective To evaluate the bioequivalence of a single oral dose of ritonavir in fasted and fed conditions in healthy Chinese adult subjects with the test and reference formulations.Methods A single-center,open-label,randomized,single-dose,two-periods,two-sequence crossover design was used,and 64 subjects were enrolled in both the fasted and fed groups.The subjects received 100 mg of the test preparation or reference preparation orally per cycle,and the drug concentration of ritonavir in plasma was detected using the high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method.Pharmacokinetic parameters were estimated by a non-compartment model,and SAS 9.4 software was used for statistical analysis.Results Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of ritonavir tablets and the reference formulation in the fasting group:Cmax were(791.90±400.20)and(809.60±449.14)ng·mL-1;AUC0_t were(6 072.61±2 631.98)and(6 296.30±3 388.95)ng·h·mL-1;AUC0-∞ were(6 129.59±2 655.57)and(6 347.26±3 434.12)ng·h·mL-1,respectively.Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of ritonavir tablets and the reference formulation in the fed group:Cmax were(512.37±233.60)and(521.74±223.87)ng·mL-1;AUC0_t were(4 203.43±2 221.33)and(4 200.13±1 993.50)ng·h·mL-1;AUC0_∞ were(4 259.21±2 266.88)and(4 259.63±2 044.12)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of Cmax,AUC0_t and AUC0_∞ of the prototype drug ritonavir in plasma after oral administration of 100 mg of the test and reference formulations of ritonavir tablets under fasting and fed conditions fell within the 80.00％to 125.00％equivalence interval.Conclusion The test and reference formulations of ritonavir tablets were bioequivalent under fasting and postprandial conditions.

Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects in vitro, concurrently enhancing the transcriptional activity of farnesoid X receptor (FXR). FXR inversely modulates the transcriptional activity of NF-κB, which has an important role in regulating inflammatory responses. Consequently, the current study was to explore the safeguarding influence of schisandrin A on ulcerative colitis and delineate the mechanism by which it regulates this effect through the FXR signaling pathway. The effect of schisandrin A on the mRNA levels of inflammatory factors was evaluated in RAW264.7 cells. The dual luciferase reporter gene assay was used to verify the relationship between schisandrin A and FXR targeting. The animal experiments were performed in accordance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2304250005). Acute ulcerative colitis was induced in wild-type or FXR knockout C57BL/6 mice by drinking 3% dextran sodium sulfate (DSS) for 7 days, and schisandrin A was administered via gavage for a continuous treatment period of 7 days. The body weight and faecal were monitored daily. The mRNA levels of inflammatory factors in colon tissue and FXR target genes were measured by RT-qPCR. The findings revealed that schisandrin A, in vitro, impeded the lipopolysaccharide (LPS)-induced elevation in mRNA levels of inflammatory factors and schisandrin A could augment transcriptional activity of FXR. In wild-type mice, schisandrin A significantly improved weight loss, colon shortening, loose stools and blood in stools in mice with acute ulcerative colitis, and schisandrin A significantly reduced the expression of pro-inflammatory factors genes and significantly increased the expression of FXR target genes in colon tissues. In FXR knockout mice, the administration of schisandrin A failed to yield ameliorative effect on acute ulcerative colitis in mice. In conclusion, schisandrin A can reduce intestinal inflammation through the FXR signaling pathway to alleviate acute ulcerative colitis in mice. Implications arise that Schisandra lignans could serve as lead compounds for drug development aimed at inflammatory bowel disease.

Aim To investigate the effects of multi-gly-cosides of Tripterygium wilfordii(GTW)on mitochon-drial dynamics-related proteins and the mechanism of nephroprotective effects in IgA nephrophathy(IgAN)rats.Methods SPF grade male SD rats were random-ly divided into the Control group,modelling group,prednisone group(6.25 mg·kg·d-1)and GTW group(6.25 mg·kg·d-1).The IgAN rat model was established by the method of"bovine serum albumin(BSA)+carbon tetrachloride(CCl4)+lipopolysac-charide(LPS)".The total amount of urinary protein(24 h-UTP)and erythrocyte count in urine were meas-ured in 24 h urine.Blood biochemistry of serum albu-min(ALB),alanine aminotransferase(ALT),urea ni-trogen(BUN),and creatinine(Scr)were measured in abdominal aorta of the rats;immunofluorescence and HE staining were used to observe the histopathology of the kidneys;RT-PCR and Western blotting were used to detect the mRNA and protein expression levels of key proteins regulating mitochondrial division and fu-sion:dynamin-related protein 1(Drp1),mitochondrial fusion protein 1(Mfn1),and mitochondrial fusion pro-tein 2(Mfn2),and PTEN-induced putative kinase 1(Pink1),in the kidney tissue of rats.Results GTW significantly reduced urinary erythrocyte count and 24 h-UTP,decreased serum ALT,BUN and Scr levels,in-creased serum ALB levels,improved renal histopatho-logical status in IgAN rats,increased the protein and mRNA expression levels of Mfn1,Mfn2,and Pink1,and decreased the protein and mRNA expression levels of Drp1 in renal tissues.Conclusions GTW may regu-late mitochondrial structure and maintain the dynamic balance of mitochondrial dynamics by promoting the ex-pression of Mfn1,Mfn2,Pink1 and decreasing Drp1.This may result in a reduction in urinary erythrocyte counts and proteinuria,and an improvement in renal function.

Aim To explore the mechanism of action of Tripterygium glycosides tablets on kidney of rats with IgA nephropathy based on inflammation-related path-ways.Methods Forty-five male SD rats of SPF grade were randomly divided into control group and modeling group.In addition to the blank group,the modeling group used the combination of bovine serum albumin(BSA)+carbon tetrachloride(CC14)+lipopolysac-charide(LPS)to establish the IgA nephropathy rat model.Successfully modeled rats were randomly divid-ed into the model group,the prednisone group and Tripterygium glycosides tablets group,and the treat-ment group was given the drug by gavage from the 13 th week,and the 24 hours urine,blood and kidney tis-sues of the rats were collected and examined after 4 weeks of the administration of the drug.Urine erythro-cyte count,quantitative 24-h urine protein(24 h-UTP),urea nitrogen(BUN),and blood creatinine(Scr)were detected in each group;serum interleukin 1β(IL-1β)and tumor necrosis factor α(TNF-α)were detected by enzyme-linked immunosorbent assay(Elisa);the pathological changes in the renal tissues of the rats in each group were observed by horizontal hematoxylin-eosin(HE)staining;and the renal tis-sues in each group were observed by Western blotting.The expressions of LIGHT,HVEM,LTβR proteins and their mRNAs in rat kidney tissue were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction(RT-PCR).Results Tripterygium glycosides tablets significantly reduced the levels of urinary erythrocyte count,24 h-UTP,BUN,and Scr in IgA nephropathy rats(P＜0.01),improved renal histopathology,lowered the levels of se-rum inflammatory factors IL-1β and TNF-α(P＜0.01),and lowered the levels of LIGHT,HVEM,LTβR proteins and their mRNA expression in renal tis-sues(P＜0.01).Conclusions Tripterygium glyco-sides tablets may inhibit the immune response and re-duce the release of inflammatory factors by down-regu-lating the LIGHT-HVEM/LT(3R pathway,thus reduc-ing the inflammatory response,lowering the urinary e-rythrocytes and urinary proteins,improving the renal nephron pathologic injury,and protecting the renal function.

Objective:To explore the expressions of zinc homeostasis-related proteins,G protein-coupled receptor 39(GPR39)and ANO1 mRNA in the sperm of patients with asthenozoospermia(AS),and analyze their correlation with sperm motility.Methods:We collected semen samples from 82 male subjects with PR+NP＜40％,PR＜32％and sperm concentration＞15 × 106/ml(the AS group,n=40)or PR+NP≥40％,PR≥32％and sperm concentration＞15 × 106/ml(the normal control group,n=42).We analyzed the routine semen parameters and measured the zinc content in the seminal plasma using the computer-assisted sperm analysis system,detected the expressions of zinc transporters(ZIP13,ZIP8 and ZNT10),metallothioneins(MT1G,MT1 and MTF),GPR39,and calcium-dependent chloride channel protein(ANO1)in the sperm by real-time quantitative PCR(RT qPCR),examined free zinc distribution in the sperm by laser confocal microscopy,and determined the expressions of GPR39 and MT1 proteins in the sperm by immunofluorescence staining,followed by Spearman rank correlation analysis of their correlation with semen parameters.Results:There was no statistically significant difference in the zinc concentration in the seminal plasma between the AS and normal control groups(P＞0.05).Compared with the controls,the AS patients showed a significantly reduced free zinc level(P＜0.05),relative expressions of MT1G,MTF,ZIP13,GPR39 and ANO1 mRNA(P＜0.05),and that of the GPR39 protein in the AS group(P＜0.05).No statistically significant differences were observed in the relative expression levels of ZIP8,ZNT10 and MT1 mRNA between the two groups(P＞0.05).The relative expression levels of GPR39,ANO1,MT1G and MTF mRNA were positively correlated with sperm motility and the percentage of progressively motile sperm(P＜0.05).Conclusion:The expressions of zinc homeostasis proteins(MT1G,MTF and ZIP13),GPR39 and ANO1 mRNA are downregulated in the sperm of asthenozoospermia pa-tients,and positively correlated with sperm motility.

The purpose of this study was to understand the prevalence of Neoehrlichia mikurensis in rodents in Yunnan commensal rodent plague foci.Lianghe Country,Mangshi City,and Mile City in Yunnan Province were chosen as sampling sites,where rodents were captured with dead-traps.The N.mikurensis groEL gene in rodent spleen samples was detected with nested PCR,and the positive products were sequenced with Sanger bidirectional assays.The infection rate of N.mikurensis a-mong plague foci,habitats,species,and sexes was compared with Chi-square tests or Fisher's exact probability method.Of 656 rodent spleen samples,12 N.mikurensis positive samples were detected in R.tanezumi,R.sladeni,N.confucianus,and B.bowersi.The positivity rate was 1.83％.No significant difference in the N.mikurensis positivity rate was observed a-mong plague foci,habitats,species,and sexes(P＞0.05).Genetic evolution analysis of the groEL gene indicated that the se-quence similarity of nucleic acid sequences in 12 positive samples was 99.5％-100％,and the nucleic acid sequences of N.mikurensis were in the same branch,belonging to cluster Ⅳ.Thus,four species of rodents were found to have low frequency infection with N.mikurensis in Yunnan commensal rodent plague foci.