Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Ischemic stroke causes brain inflammation and multi-organ injury, which is closely associated with the peroxisome proliferator-activated receptor-gamma (PPARγ) signaling pathway. Recent studies have indicated that ginsenoside Rb1 (GRb1) can protect the integrity of the blood-brain barrier after stroke. In the current study, a mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established to determine whether GRb1 can ameliorate brain/lung/intestinal barrier damage via the PPARγ signaling pathway. Staining (2,3,5-triphenyltetrazolium chloride, hematoxylin, and eosin) and Doppler ultrasonography were employed to detect pathological changes. Endothelial breakdown was investigated with the leakage of Evans Blue dye and the expression of TJs (tight junctions) and AJs (adherent junctions). Western blot and immunofluorescence were used to determine the levels of cell junction proteins, PPARγ and NF-κB. Results showed that GRb1 significantly mitigated multi-organ injury and increased the expression of cerebral microvascular, pulmonary vascular, and intestinal epithelial connexins. In brain, lung, and intestinal tissues, GRb1 activated PPARγ, decreased the levels of phospho-NF-κB p65, and inhibited the production of proinflammatory cytokines, thereby maintaining barrier permeability. However, co-treatment with GRb1 and the PPARγ antagonist GW9662 reversed the barrier-protective effect of GRb1. These findings indicated that GRb1 can improve stroke-induced brain/lung/intestinal barrier damagevia the PPARγ pathway.
Animals ; Brain ; Brain Ischemia ; Ginsenosides ; Infarction, Middle Cerebral Artery ; Lung ; Mice ; NF-kappa B ; Neuroprotective Agents ; PPAR gamma ; Reperfusion ; Reperfusion Injury ; Signal Transduction

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.
Humans ; Retrospective Studies ; Esophageal Neoplasms/pathology* ; Carcinoma/drug therapy* ; Prognosis ; Treatment Outcome ; Chemoradiotherapy/methods* ; Radiotherapy Dosage

OBJECTIVE: To analyze the influence of serum homocysteine (Hcy) levels to the prognosis of newly diagnosed multiple myeloma (MM) patients, and to explore related factors affecting the prognosis of the patients. METHODS: The clinical pathological data of 180 newly diagnosed MM patients treated in our hospital from March 2013 to February 2015 were collected, and the patients were divided into high and low Hcy groups based on the median Hcy. The survival curves of the patients in the two groups were drawn to compare the differences of the survival; univariate and multivariate survival analysis was used to observe the influence of serum cysteine to the prognosis of newly diagnosed MM patients; the clinicopathological data of the patients with high and low Hcy in the two groups was compared, Pearson test was used to further analyzes the relationship between Hcy and different factors, and explores the related factors of Hcy affecting the prognosis of the patients. RESULTS: The median survival times of patients in the high and low Hcy groups were 32 (5-59) and 41 (7-71) months, respectively. The 3-year survival rate of the patients in high Hcy group was significantly lower than those in low Hcy group, and the difference shows statistically significant (P<0.05). The results of univariate survival analysis showed that the OS of newly diagnosed MM patients whom with advanced age, high bone disease grade, high-level bone marrow plasma cell count, LDH, C-reactive protein, Cr, β CONCLUSION Serum Hcy level has a correlation trend with the survival of newly diagnosed MM, which is affected by factors such as Hb.
Bone Marrow Cells ; Homocysteine ; Humans ; Multiple Myeloma ; Prognosis ; Risk Factors

Objective:To predict the therapeutic targets and related signaling pathways of quercetin in the treatment of heart failure （HF） by network pharmacology and molecular docking methods，and further clarify its mechanisms through in vitro cell model. Method:The pharmacological targets of quercetin were obtained by SwissTargetPrediction and Targetnet databases； the heart failure related targets were obtained by Online Mendelian Inheritance in Man（OMIM），GeneCards and Therapeutic Target Database（TTD） databases； the protein-protein interaction（PPI） network was analyzed by STRING database（Search Tool for Recurring Instances of Neighbouring Genes），and the PPI network diagram of quercetin for heart failure target was established. Cytoscape 3.7.2 software was used for analyzing and screening the anti-heart failure network nodes of quercetin，and the obtained targets were enriched with gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis by DAVID database. In order to explore the mechanism of quercetin in the treatment of heart failure，we used cell model to verify the function in heart failure treatment. Results:The predicted results showed that there were 23 targets for the treatment of heart failure，such as Matrix Metallopeptidase-9（MMP-9），androgen receptor（AR），coagulation factor 2（F2），insulin like growth factor 1 receptor（IGF1R），epidermal growth factor receptor（EGFR），janus kinase-2（JAK2），cytochrome P450 family 19 subfamily A member 1（CYP19A1），estrogen receptor-1（ESR1），tumor necrosis factor（TNF），protein tyrosine phosphatase receptor type C（PTPRC） and cytochrome P450 family 17 subfamily A member 1（CYP17A1） etc. The results suggest that quercetin may play a role in the treatment of heart failure by intervening in the physiological processes of cardiovascular cell proliferation and metabolism，regulating hypoxia-inducible factor 1 （HIF-1）signaling pathway and steroid hormone biosynthesis. Conclusion:Quercetin has the characteristics of multi-target，multi-channel and multi-channel in the treatment of heart failure. It may play a role in the treatment of heart failure by regulating MMP-9，EGFR and other key genes，participating in the biological process of cardiac and vascular cell proliferation and metabolism.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Medium- and long-chain triglyceride (MCT/LCT) propofol is widely used as an intravenous anesthetic, especially in the intensive care unit. The present study aimed to assess whether MCT/LCT propofol is safe in the hyperlipidemic population for long-term use. Free fatty acids (FFAs) were used to establish high-fat stimulation of HepG2 and Huh7 cells. Subsequently, these cells were treated with propofol at the concentration of 0, 4, or 8 µg/ml for 24 and 48 h. The results indicated that the cell viability was notably decreased when the cells were stimulated with 2 mmol/L FFAs and treated with 12 µg/ml MCT/LCT propofol. Accordingly, we chose 2 mmol/L FFAs along with 4 and 8 µg/ml MCT/LCT propofol for the subsequent experiments. Four and 8 µg/ml MCT/LCT propofol inhibited FFA-induced lipid accumulation in the cells and significantly reversed acetyl coenzyme A carboxylase (ACC) activity. In addition, MCT/LCT propofol not only significantly promoted the phosphorylation of AMPK and ACC, but also reversed the FFA-induced decreased phosphorylation of AMPK and ACC. In conclusion, MCT/LCT propofol reverses the negative effects caused by FFAs in HepG2 and Huh7 cells, indicating that MCT/LCT propofol might positively regulate lipid metabolism.
Acetyl-CoA Carboxylase ; AMP-Activated Protein Kinases ; Cell Survival ; Fatty Acids, Nonesterified ; Hepatocytes ; Intensive Care Units ; Lipid Metabolism ; Liver ; Metabolism ; Phosphorylation ; Propofol ; Triglycerides

Objective　Mini-invasive Carisolv is an aid to treat dental caries for patients with dental phobia. The article was to investigate the level of pain in caries removal using mini-invasive Carisolv III gel and mechanical methods with four psychological indicators.　Methods　We collected 120 primary molar tooth caries of 60 children treated in our hospital. Two primary molar tooth caries of each child were respectively treated with Carisolv III gel (Group A) and mechanical method (Group B) for caries removal. Psychological indicators including the visual analog scale (VAS), the Frank1 behavior rating scale (Frank1), the Kuttner law (Kuttner), and the Houpt behavior rating scale (Houpt) were used to assess the level of pain, degree of cooperation, pain tolerance and comfort. The clinical efficiency after six months and treatment time were compared between the two groups.　Results　There was no statistically significant difference before treatment between the two groups using the four psychological indicators (P>0.05) , while significant differences were found during and after the treatment between the two groups (P<0.05). Then, Carisolv III gel and mechanical groups for careis removal were compared before, during and after treatment themselves. In the Carisolv III gel group, there was no statistically significant difference using the four psychological indicators (P>0.05). In the mechanical group, there were statistically significant differences before and during treatment or before and after treatment using the four psychological indicators (P<0.05). The treatment time in Carisolv III gel group was longer than in mechanical group (P=0.001). There was no statistical difference between the two groups in filling examination after six months (P=0.082).　Conclusion　Carisolv III gel for caries removal can effectively avoid pain, improve comfort and decrease fear in children, which can be promoted in clinical application.