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.

Hepatotoxicity is a common side effect for patients treated with gefitinib, but the related pathogenesis is unclear and lacks effective predictor and management strategies. A multi-omics approach integrating pharmacometabolomics, pharmacokinetics and pharmacogenomics was employed in non-small cell lung cancer patients to identify the effective predictor for gefitinib-induced hepatotoxicity and explore optional therapy substitution. Here, we found that patients with rs4946935 AA, located in Forkhead Box O3 (FOXO3) which is a well-known autophagic regulator, had a higher risk of hepatotoxicity than those with the GA or GG variant (OR = 18.020, 95%CI = 2.473 to 459.1784, P = 0.018) in a gefitinib-concentration dependent pattern. Furthermore, functional experiments identified that rs4946935_A impaired the expression of FOXO3 by inhibiting the promotor activity, increasing the threshold of autophagy initiation and inhibiting the autophagic activity which contributed to gefitinib-induced liver injury. In contrast, erlotinib-induced liver injury was independent on the variant and expression levels of FOXO3. This study reveals that FOXO3 mutation, leading to autophagic imbalance, plays important role in gefitinib-induced hepatotoxicity, especially for patients with high concentration of gefitinib. In conclusion, FOXO3 mutation is an effective predictor and erlotinib might be an appropriately and well-tolerated treatment option for patients carrying rs4946935 AA.

Objective: To estimate the effectiveness of the primary screening strategy for liver cancer in rural areas to provide basic information for the optimization and perfection of the technical program for the early detection and treatment of liver cancer. Methods: Residents including males aged 35-64 and females aged 45-64 from 9 counties in rural China between 2013 and 2015 were selected as the target population. The participant was classified into a high-risk and non-high-risk group based on the standardized questionnaire or HBsAg, and the Chi-squared test was applied to compare differences between the two groups. The Cox proportional hazard regression models were applied to assess hazard ratio (HR) and its 95% confidence interval (CI). Results: 358 348 participants were recruited from 2013 to 2015. 1 196 individuals were identified with liver cancer until December 31, 2021, with an incidence density of 52.0/10(5) person-years. Of the participants, 54 650 were assessed as high risk (15.3%) based on the questionnaire and the status of HBsAg. The high-risk population had a higher incidence density (168.3/10(5) person-years vs 31.5/10(5) person-years) and higher risk of developing liver cancer (HR=2.98, 95% CI=2.64-3.35), compared to the non-high-risk group. Based on the questionnaire-based high-risk assessment system, 47 884 (13.4%) individuals were identified as high risk, who showed statistical differences in terms of incidence density and incidence risk, in comparison to the low-risk population (all P<0.05). HBsAg can screen out a higher proportion of high-risk individuals who are women, non-smokers, non-drinkers, and individuals without a family history of liver cancer (all P<0.05). The sensitivity analysis of the effectiveness of the whole primary screening method is stable, and high-risk individuals still had a higher risk of liver cancer. Conclusions: The primary screening method of the questionnaire-based risk assessment system and HBsAg can achieve satisfactory effectiveness. The questionnaire-based risk assessment system could identify high-risk individuals to some extent, however, it still needs to be improved to meet the actual requirements.
China/epidemiology* ; Early Detection of Cancer ; Female ; Hepatitis B Surface Antigens ; Humans ; Incidence ; Liver Neoplasms/epidemiology* ; Male ; Mass Screening ; Risk Factors

Objective: To investigate the effects of non-muscle myosin Ⅱ (NMⅡ) gene silenced bone marrow-derived mesenchymal stem cells (BMMSCs) on pulmonary extracellular matrix (ECM) and fibrosis in rats with acute lung injury (ALI) induced by endotoxin/lipopolysaccharide (LPS). Methods: The experimental research methods were adopted. Cells from femur and tibial bone marrow cavity of four one-week-old male Sprague-Dawley rats were identified as BMMSCs by flow cytometry, and the third passage of BMMSCs were used in the following experiments. The cells were divided into NMⅡ silenced group transfected with pHBLV-U6-ZsGreen-Puro plasmid containing small interference RNA sequence of NMⅡ gene, vector group transfected with empty plasmid, and blank control group without any treatment, and the protein expression of NMⅡ at 72 h after intervention was detected by Western blotting (n=3). The morphology of cells was observed by an inverted phase contrast microscope and cells labeled with chloromethylbenzoine (CM-DiⅠ) in vitro were observed by an inverted fluorescence microscope. Twenty 4-week-old male Sprague-Dawley rats were divided into blank control group, ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group according to the random number table, with 5 rats in each group. Rats in blank control group were not treated, and rats in the other 3 groups were given LPS to induce ALI. Immediately after modeling, rats in ALI alone group were injected with 1 mL normal saline via tail vein, rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were injected with 1×10⁷/mL BMMSCs and NMⅡ gene silenced BMMSCs of 1 mL labelled with CM-DiⅠ via tail vein, and rats in blank control group were injected with 1 mL normal saline via tail vein at the same time point, respectively. At 24 h after intervention, the lung tissue was collected to observe intrapulmonary homing of the BMMSCs by an inverted fluorescence microscope. Lung tissue was collected at 24 h, in 1 week, and in 2 weeks after intervention to observe pulmonary inflammation by hematoxylin eosin staining and to observe pulmonary fibrosis by Masson staining, and the pulmonary fibrosis in 2 weeks after intervention was scored by modified Ashcroft score (n=5). The content of α-smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), and MMP-9 was detected by immunohistochemistry in 2 weeks after intervention (n=3), the activity of superoxide dismutase (SOD), malondialdehyde, myeloperoxidase (MPO) was detected by enzyme-linked immunosorbent assay at 24 h after intervention (n=3), and the protein expressions of CD11b and epidermal growth factor like module containing mucin like hormone receptor 1 (EMR1) in 1 week after intervention were detected by immunofluorescence staining (n=3). Data were statistically analyzed with one-way analysis of variance, Bonferroni method, and Kruskal-Wallis H test. Results: At 72 h after intervention, the NMⅡprotein expression of cells in NMⅡ silenced group was significantly lower than those in blank control group and vector group (with P values <0.01). BMMSCs were in long spindle shape and grew in cluster shaped like vortexes, which were labelled with CM-DiⅠ successfully in vitro. At 24 h after intervention, cell homing in lung of rats in ALI+NMⅡ silenced BMMSC group was more pronounced than that in ALI+BMMSC group, while no CM-DiⅠ-labelled BMMSCs were observed in lung of rats in blank control group and ALI alone group. There was no obvious inflammatory cell infiltration in lung tissue of rats in blank control group at all time points, while inflammatory cell infiltration in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly less than that in ALI alone group at 24 h after intervention, and alveolar wall turned to be thinner and a small amount of congestion in local lung tissue appeared in rats of the two groups in 1 week and 2 weeks after intervention. In 1 week and 2 weeks after intervention, collagen fiber deposition in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group was significantly aggravated compared with that in blank control group, while collagen fiber deposition in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly improved compared with that in ALI alone group. In 2 weeks after intervention, modified Ashcroft scores for pulmonary fibrosis of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were 2.36±0.22, 1.62±0.16, 1.06±0.26, respectively, significantly higher than 0.30±0.21 in blank control group (P<0.01). Modified Ashcroft scores for pulmonary fibrosis of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly lower than that in ALI alone group (P<0.01), and modified Ashcroft score for pulmonary fibrosis of rats in ALI+NMⅡ silenced BMMSC group was significantly lower than that in ALI+BMMSC group (P<0.01). In 2 weeks after intervention, the content of α-SMA in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly decreased compared with that in ALI alone group (P<0.05 or P<0.01). The content of MMP-2 in lung tissue of rats in the 4 groups was similar (P>0.05). The content of MMP-9 in lung tissue of rats in ALI alone group was significantly increased compared with that in blank control group (P<0.01), and the content of MMP-9 in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01). At 24 h after intervention, the activity of malondialdehyde, SOD, and MPO in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in blank control group (P<0.01), the activity of malondialdehyde in lung tissue of rats in ALI+NMⅡ silenced BMMSC group and the activity of SOD in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in ALI alone group (P<0.05 or P<0.01), and the activity of SOD in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). The activity of MPO in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01), and the activity of MPO in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). In 1 week after intervention, the protein expression of CD11b in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly increased compared with those in the other three groups (P<0.05 or P<0.01), while the protein expressions of EMR1 in lung tissue of rats in the four groups were similar (P>0.05). Conclusions: Transplantation of NMⅡ gene silenced BMMSCs can significantly improve the activity of ECM components in the lung tissue in LPS-induced ALI rats, remodel its integrity, and enhance its antioxidant capacity, and alleviate lung injury and pulmonary fibrosis.
Acute Lung Injury/therapy* ; Animals ; Bone Marrow ; Collagen/metabolism* ; Endotoxins ; Extracellular Matrix ; Lipopolysaccharides/adverse effects* ; Lung ; Male ; Malondialdehyde/metabolism* ; Matrix Metalloproteinase 2/metabolism* ; Matrix Metalloproteinase 9/metabolism* ; Mesenchymal Stem Cells/metabolism* ; Myosin Type II/metabolism* ; Pulmonary Fibrosis ; Rats ; Rats, Sprague-Dawley ; Saline Solution/metabolism* ; Superoxide Dismutase/metabolism*

OBJECTIVE: To analyze and predict the effect of coronavirus infection on hematopoietic system and potential intervention drugs, and explore their significance for coronavirus disease 2019 (COVID-19). METHODS: The gene expression omnibus (GEO) database was used to screen the whole genome expression data related with coronavirus infection. The R language package was used for differential expression analysis and KEGG/GO enrichment analysis. The core genes were screened by PPI network analysis using STRING online analysis website. Then the self-developed apparent precision therapy prediction platform (EpiMed) was used to analyze diseases, drugs and related target genes. RESULTS: A database in accordance with the criteria was found, which was derived from SARS coronavirus. A total of 3606 differential genes were screened, including 2148 expression up-regulated genes and 1458 expression down-regulated genes. GO enrichment mainly related with viral infection, hematopoietic regulation, cell chemotaxis, platelet granule content secretion, immune activation, acute inflammation, etc. KEGG enrichment mainly related with hematopoietic function, coagulation cascade reaction, acute inflammation, immune reaction, etc. Ten core genes such as PTPRC, ICAM1, TIMP1, CXCR5, IL-1B, MYC, CR2, FSTL1, SOX1 and COL3A1 were screened by protein interaction network analysis. Ten drugs with potential intervention effects, including glucocorticoid, TNF-α inhibitor, salvia miltiorrhiza, sirolimus, licorice, red peony, famciclovir, cyclosporine A, houttuynia cordata, fluvastatin, etc. were screened by EpiMed plotform. CONCLUSION SARS coronavirus infection can affect the hematopoietic system by changing the expression of a series of genes. The potential intervention drugs screened on these grounds are of useful reference significance for the basic and clinical research of COVID-19.
COVID-19 ; Computational Biology ; Follistatin-Related Proteins ; Hematopoietic System ; Humans ; Pharmaceutical Preparations ; SARS-CoV-2

Objective To investigate the prevalence and influencing factors of intestinal protozoan infections among rural children in Henan Province. Methods A total of 104 survey sites were sampled from 35 counties (cities) in Henan Province using the stratified cluster sampling method to investigate the prevalence of intestinal protozoan infections among rural children from 2014 to 2015. The trophozoites and cysts of intestinal protozoa were identified using the iodine staining method and the physiological saline direct smear method (one detection for one stool sample). The prevalence of intestinal protozoan infections was compared among rural children with different characteristics, and the factors affecting intestinal protozoan infections among rural children were identified. Results The overall prevalence of intestinal protozoan infections was 0.60% (40/6 771) among rural children in Henan Province from 2014 to 2015. There were 7 species of intestinal protozoa identified, and there was no species-specific prevalence (χ² = 37.732, P = 0.000). No significant differences were found in prevalence of intestinal protozoan infections among rural children in terms of gender (χ² = 1.793, P = 0.181), age (χ² = 1.443, P = 0.486), occupation (χ² = 0.219, P = 0.896) or ecological region (χ² = 1.700, P = 0.637). In addition, terrain (χ² = 2.311, P = 0.510), economic level (χ² = 4.322, P = 0.229), source of drinking water (χ² = 0.731, P = 0.393), eating raw vegetables (χ² = 1.134, P = 0.287) and deworming (χ² = 1.089, P = 0.297) had no remarkable effects on the prevalence of intestinal protozoan infections among rural children in Henan Province; however, the prevalence of intestinal protozoan infections varied significantly among rural children living in regions with different coverage of non-harmless toilets (χ² = 10.050, P = 0.018). Conclusion The prevalence of intestinal protozoan infections is low among rural children in Henan Province.

The indication of bloodletting therapy was determined based on the multi-dimensional evidence assessment, which could provide guidance for the clinical application of bloodletting therapy. The literature of bloodletting therapy was comprehensively collected by retrieval in CNKI, Wanfang and VIP databases (until February 23, 2019), modern books in Library of Tianjing University of TCM and the (Fifth Edition). The disease spectrum of bloodletting therapy was determined by self-designed questionnaire survey e-mailed to relevant experts. The indication of bloodletting therapy was determined by Delphi expert meeting. As a result, 746 pieces of ancient literature and 32 775 modern literature were included. The indications of bloodletting therapy based on the multi-dimensional evidence assessment include herpes zoster, acne, acute tonsillitis, vascular headache, varicose veins of lower extremities, acute lumbar sprain, early erysipelas, wheat swelling, exogenous fever of children, stroke, which are mainly the syndromes of blood stasis, toxin, excess and heat.
Bloodletting ; Humans ; Medicine, Chinese Traditional

【Objective】 To investigate the expression of estrogen receptor beta(ERβ) and methylation status of 5'-untranslated region in papillary thyroid carcinoma(PTC) and explore the reason for the low expression of ERβ in PTC. 【Methods】 Western blot and immunohistochemical staining were used to analyze the protein expression of ERβ in human normal thyroid Nthy-ori3-1 cells, thyroid papillary carcinoma BCPAP cells and tissues of normal thyroid, nodular hyperplasia and PTC. qRT-PCR was employed to detect the expression levels of ERβ mRNA(0K-1), ERβ mRNA(0N-1) and total ERβ mRNA in cells and tissues. Bisulfite genomic sequencing was performed to evaluate the methylation status of CpG islands in promoter 0K, promoter 0N and exon 0N in cells and tissues. After Nthy-ori3-1 cells and BCPAP cells were treated with 5-aza-2'-deoxycytidine(5-aza-dC), a DNA methyltransferase(DNMT) inhibitor, qRT-PCR was used to examine the expression levels of ERβ mRNA(0K-1), ERβ mRNA(0N-1) and total ERβ mRNA in the treated cells. 【Results】 The protein expression of ERβ in PTC cells was significantly lower than that in normal thyroid cells(P<0.01). The cases with positive ERβ expression in tissues of normal thyroid, nodular hyperplasia and PTC were 5, 3 and 0, respectively(all n=10). The protein expression of ERβ in PTC tissues was significantly lower than that in normal thyroid tissues(P<0.05). Compared with those in normal thyroid cells and tissues, the expression levels of ERβ mRNA(0N-1) and total ERβ mRNA in PTC were significantly reduced(P<0.01), while ERβ mRNA(0K-1) expression showed no significant difference(P>0.05). The methylation degrees of ERβ promoter 0N and exon 0N were gradually increased in the development of PTC, while promoter 0K was unmethylated or hypomethylated in normal thyroid, nodular hyperplasia and PTC cells and tissues. 5-aza-dC treatment resulted in reexpression of ERβ mRNA(0N-1) and total ERβ mRNA in BCPAP cells but brought no change in ERβ mRNA(0K-1) expression. 【Conclusions】 Methylation in ERβ 5'-untranslated region is correlated to the low expression of ERβ gene in PTC, especially aberrant methylation of promoter 0N and exon 0N.

Objective To explore the infection distribution and drug resistance of pathogens in patients with severe liver disease,and provide reference for clinical medication.Methods Retrospective analysis of the microbiological specimens from patients with severe liver disease in Department of Infection of our hospital from August 2014 to November 2016 and the drug susceptibility testing were carried out by means of K-B disc diffusion method after bacterial culturing,and the distribution and drug resistance of pathogens were analyzed.Results Totally 17 of 73 patients with severe liver disease developed hospital infection (23.3％).104 strains of bacteria were isolated and 78 strains out of them were multidrug-resistant bacteria (75.0％).Among them,28(26.9％) strains were gram-positive coccus,mainly consisting of Staphylococcus aureus and Staphylococcus epidermidis,and 58(55.8％) were gram-negative coccus,mainly composed of Escherichia coli,Klebsiella pneumonia and Acinetobacter baumannii,and 18(17.3％) strains fungi.S.aureus and enterococci were resistant to penicillin,erythromycin and levofloxacin,the resistance rates were above 80.0％,but had low resistance rates to vancomycin,teicoplanin and tigecycline.The resistance rates of E.coli and K.pneumoniae to piperacillin,cefazolin and cefuroxime sodium were above 85.0％,but they had lower resistance rates to tigecycline and amikacin.Acinetobacter baumannii was 100％ resistant to piperacillin and tazobactam,ceftazidime,imipenem and amikacin,but had low resistance to tigecycline and minocycline.Conclusions Multi-drug resistant bacteria are the main bacterial pathogens in patients with severe liver disease and have a high resistance rate to commonly used antibiotics,empirical treatment in the population at high risk of multidrug-resistant bacteria infections requires the use of broad-spectrum or high-grade antibiotics (e.g.carbapenems or tigecycline) and drugs against specific pathogenic bacteria (glycopeptides,linezolid,and amikacin etc).Early de-escalation policies are recommended to prevent the spread of multidrug-resistant bacteria in cirrhosis.

BACKGROUND: Elastic intramedullary nail is commonly used in the treatment of fractures of children, but few studies concern the elastic intramedullary nail for treating fractures in adults. OBJECTIVE: To investigate the repair effect of elastic intramedullary nail in the treatment of 22-A fracture in forearm of adults. METHODS: From January 2015 to April 2016, a total of 21 adult patients with the 22-A fracture (35 fractures) were treated with manipulative reduction and elastic intramedullary nail fixation in the First Affiliated Hospital of Guangzhou University of Chinese Medicine. The follow-up time was 12-18 months. Radiographs were taken and the guidance of the limb function training was given at regular intervals. The Andserson scoring system was used to evaluate the patients' forearm limb function. Fracture healing, elbow, wrist joint activity and forearm rotation were recorded. The satisfactory questionnaires were recorded. The patients were divided into three grades as satisfaction, general satisfaction and dissatisfaction; simultaneously, reasons were recorded. RESULTS AND CONCLUSION: (1) The Andserson scoring was satisfactory in 16 cases accounted for 76%, general satisfaction in 3 cases accounted for 14%, dissatisfaction in 2 cases accounted for 10%. (2) Wrist joint activity increased from (172±4)° before the operation to (181±3)° at the end of the follow-up. Elbow joint activity increased from (102±18)° before the operation to (124±13)° at the end of the follow-up. Forearm rotation activity increased from (84±11)° before the operation to (155±13)° at the end of the follow-up (P < 0.05). (3) In the follow-up of the 21 patients, 13 patients were satisfied with the result of surgery; 5 patients were generally satisfied; 2 patients were dissatisfied because the limited limb functions; and 1 patient was dissatisfied because of the nail irritability; the dissatisfaction rate accounted for 14%. (4) Elastic intramedullary nail can obtain affirmative effect in the treatment of adult 22-A fracture of the forearm; and clinical application should be based on the type of fracture.