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 To retrospectively analyze of factors influencing early preterm birth(EPB)and late preterm birth(LPB)in pregnancy women with placenta previa complicated by placenta accreta spectrum disorders(PAS),and assess maternal and infant outcomes.Methods We included 590 cases of pregnancy women with placenta previa complicated by PAS who underwent cesarean sections at five hospitals in Wuhan and Xianning cities between January 2018 and June 2021.These patients were divided into three groups based on delivery gesta-tional age:EPB,LPB,and term birth(TB).A multiple logistic regression model was employed to analyze the risk factors associated with EPB and LPB.Additionally,differences in early maternal and infant outcomes among these groups were examined.Results Among 590 pregnancy women with placenta previa complicated by PAS,the proportions of EPB and LPB were 9.7%and 54.4%.The use of uterine contraction inhibitors prior to cesarean section,vaginal bleeding,and previous cesarean sections history were identified as risk factors for both EPB and LPB.The proportion of severe postpartum hemorrhage was comparable between the EPB group and the LPB group;however,the incidence of neonatal asphyxia,low birth weight infants,and the rate of newborns transferred to the Neonatal Intensive Care Unit(NICU)within 24 hours after cesarean delivery were significantly higher in the EPB group compared to the LPB group.Conclusions Placenta previa complicated by PAS predominantly leads to LPB.The history of prior cesarean sections,uterine contractions,and vaginal bleeding prior to cesarean section,are sig-nificantly associated with both EPB and LPB.During the perinatal period,efforts should be made to extend gesta-tional weeks under close monitoring to minimize the incidence of premature births and thereby improve early mater-nal and infant outcomes.

Objective:To compare the effects of citrate and heparin anticoagulation on coagulation function and efficacy in children with septic shock undergoing continuous blood purification (CBP), and to provide guidance for CBP anticoagulation in children with septic shock.Methods:A case control study was conducted. Thirty-seven children with septic shock admitted to the pediatric intensive care unit (PICU) of the First Affiliated Hospital of Gannan Medical University from July 2019 to September 2022 were enrolled as the research subjects. The patients were divided into citrate local anticoagulation group and heparin systemic anticoagulation group according to different anticoagulation methods. The baseline data, the level of coagulation indicators [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib), D-dimer] before treatment and 1 day after weaning from CBP, serum inflammatory mediators [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), hypersensitivity C-reactive protein (hs-CRP), procalcitonin (PCT)], bleeding complications during CBP and 7-day mortality were collected.Results:A total of 37 cases were enrolled finally, including 17 cases with citric acid local anticoagulation and 20 cases with heparin systemic anticoagulation. There was no statistically significant difference in general data such as gender, age, and body weight of children between the two groups. There were no statistically significant differences in baseline levels of coagulation indicators and inflammatory mediators before treatment of children between the two groups. One day after weaning from CBP, both groups showed varying degrees of improvement in coagulation indicators compared with those before treatment. Compared with before treatment, the PT of the heparin systemic anticoagulation group was significantly shortened after 1 day of weaning (s: 11.82±2.05 vs. 13.64±2.54), APTT and TT were significantly prolonged [APTT (s): 51.54±12.69 vs. 35.53±10.79, TT (s): 21.95±4.74 vs. 19.30±3.33], D-dimer level was significantly reduced (mg/L: 1.92±1.58 vs. 4.94±3.94), with statistically significant differences (all P < 0.05). While in the citrate local anticoagulation group, only APTT was significantly prolonged after treatment compared with that before treatment (s: 49.28±10.32 vs. 34.34±10.32, P < 0.05). There were no statistically significant differences in other coagulation indicators compared with before treatment. Compared with the citric acid local anticoagulation group, the PT of the heparin systemic anticoagulation group was significantly shortened after treatment (s: 11.82±2.05 vs. 13.61±3.05, P < 0.05), and the D-dimer level was significantly reduced (mg/L: 1.92±1.58 vs. 3.77±2.38, P < 0.01). The levels of inflammatory mediators in both groups were significantly reduced 1 day after CBP weaning compared with those before treatment [citric acid local anticoagulation group: hs-CRP (mg/L) was 12.53±5.44 vs. 22.65±7.27, PCT (μg/L) was 1.86±1.20 vs. 3.30±2.34, IL-6 (ng/L) was 148.48±34.83 vs. 202.32±48.62, TNF-α (ng/L) was 21.38±7.71 vs. 55.14±15.07; heparin systemic anticoagulation group: hs-CRP (mg/L) was 11.82±4.93 vs. 21.62±8.35, PCT (μg/L) was 1.90±1.08 vs. 3.18±1.97, IL-6 (ng/L) was 143.81±33.41 vs. 194.02±46.89, TNF-α (ng/L) was 22.44±8.17 vs. 56.17±16.92, all P < 0.05]. However, there was no statistically significant difference between the two groups (all P > 0.05). There was no statistically significant difference in bleeding complication during CBP and 7-day mortality in children between the citrate local anticoagulation group and the heparin systemic anticoagulation group (5.9% vs. 30.0%, 17.6% vs. 20.0%, both P > 0.05). Conclusions:Heparin for systemic anticoagulation and regional citrate anticoagulation can significantly reduce the levels of IL-6, TNF-α, hs-CRP and PCT in children with septic shock, and relieve inflammatory storm. Compared with citric acid local anticoagulation, heparin systemic anticoagulation can shorten the PT and reduce the level of D-dimer in children with septic shock, which may benefit in the prevention and treatment of disseminated intravascular coagulation (DIC).

AIM: In order to bridge the gap between pharmacogenomic research and its clinical application, we propose the concept of genetic electronic identity, named "GeneFace", and developed an electronic information system which integrated "drug-gene" interactions and recommendations for personalized medicine. METHODS: Based on the self-developed Precision Medicine knowledgebase, which concludes drug directions, guidelines or important literatures with high level of evidence, we developed GeneFace with Java-based open-resource application framework Spring Boot, further developed a mobile App with cross-platform framework Uni-APP. RESULTS: The App includes six modules: genetic testing appointment, genetic knowledge introduction, individualized medication advice, medication records, Geneface interpretation, and Precision Medicine knowledgebase. By detecting the genotype of more than 300 gene loci upon first use, users import the results to form a personal "drug-gene identity card". Then scan or enter the drug name in "GeneFace", the App would automatically give corresponding medication recommendations, including: risks for possible adverse drug reactions, risks for reducing the efficacy or even ineffectiveness, and possibility for dose adjustment, etc., which increase the safety of clinical drug use. People can obtain pharmacogenomics knowledge and basic drug information in the "GeneFace" app. CONCLUSION: Development as a digital therapeutic product, the expanded application of GeneFace can rapidly promote clinical applications of basic pharmacogenomics research and significantly improve drug use safety, which creating a new model for accelerating the clinical application of personalized medicine.

AIM: Describe the general situation of the First-In-Human trials of the drugs, and summarize the design and results of the First-In-Human trials. METHODS: We searched the literature of the First-In-Human trials in 2009-2020 on PubMed and screened out the literature that met the research purpose. The basic information of the literature was collected. Data analysis was conducted to summarize relevant outcomes. RESULTS: A total of 559 First-In-Human trials were included in this study. The types of drugs included small molecule drugs (52.42%, 293/559), macromolecule drugs (45.62%, 255/559), and a small amount of cells and viruses (1.97%, 11/559) and so on. Regarding the determination of the starting dose, whether it was in macromolecules (23.86%, 21/88) or small molecules (30.15%, 41/136), No Observed Adverse Effect Level (27.68%, 62/224) was mainly used as the main reference basis, followed by preclinical research (21.88%, 49/224) and Minimal Anticipated Biological Effect Level (8.48%, 19/224), etc. In the dose escalation test, 50.19%(135/269) of the studies used the traditional standard 3+3 dose escalation method, followed by the accelerated titration method (7.06%, 19/269), and the improved 3+3 method (6.69%, 18/269), etc. CONCLUSION: The design of First-In-Human clinical trials has certain regularity in the content and results of the research design. In the subsequent trials, it is important to scientifically design the First-In-Human trials, and promote the safe and effective development of the First-In-Human trials of the drugs.

Objective:To systematically evaluate the effect of hydrocortisone combined with vitamin C and vitamin B1 on the efficacy of patients with sepsis or septic shock.Methods:Databases including CNKI, Sino Med, VIP, Wanfang, PubMed, the Cochrane Library, and Embase were searched from inception to January 2021 for the randomized controlled trial (RCT) about hydrocortisone combined with vitamin C and vitamin B1 to treat sepsis or septic shock. The experimental group was given intravenous injection of hydrocortisone, vitamin B1 and vitamin C based on conventional treatment; the control group was given conventional treatment or placebo/hydrocortisone/hydrocortisone+vitamin B1 based on conventional treatment. Outcome indicators included sequential organ failure assessment (SOFA), mortality, the duration of vasoactive drugs, new acute kidney injury (AKI) patients, length of stay in intensive care unit (ICU) and in hospital. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. RevMan 5.3 software was then used to perform Meta-analysis. Funnel plot was used to test publication bias.Results:A total of 6 articles involving 816 patients were included, with 411 patients in the experimental group and 405 patients in the control group. The Meta-analysis results showed that the duration of vasoactive drugs in the experimental group was significantly shorter than that in the control group [mean difference ( MD) = -24.02, 95% confidence interval (95% CI) was -32.36 to -15.68, P < 0.000 01]. However, there were no significant differences in SOFA, mortality, new AKI patients, the length of ICU stay and hospital stay between the two groups [SOFA: MD = -0.14, 95% CI was -1.15 to 0.87, P = 0.79; mortality: relative risk ( RR) = 0.99, 95% CI was 0.81 to 1.21, P = 0.92; new AKI patients: RR = 1.10, 95% CI was 0.42 to 2.87, P = 0.84; length of ICU stay: MD = 1.33, 95% CI was -2.22 to 4.89, P = 0.46; length of hospital stay: MD = 1.02, 95% CI was -0.66 to 2.69, P = 0.23]. The funnel plot showed that most of the points were symmetrical and showed an inverted funnel shape, suggesting that the publication bias among the studies was small. There was no significant publication bias on this Meta-analysis. Conclusions:Hydrocortisone combined with vitamin C and vitamin B1 can shorten the duration of vasoactive drugs in patients with sepsis or septic shock, but it cannot effectively reduce the SOFA score, mortality, new AKI patients, length of stay in ICU and in hospital. Limited by the number and quality of the included studies, further large-scale, multi-center, blinded, RCT are still needed for verification.

AIM: To study the pharmacokinetic characteristics of single-dose oral moxifloxacin hydrochloride tablets under fasting and fed conditions, and use moxifloxacin hydrochloride tablets produced by Bayer Pharma AG as a reference to compare the pharmacokinetic parameters of the two preparations, and evaluate the human bioequivalence of the two preparations. METHODS: A single-center, randomized, open, two-period, and self-crossover design was adopted to conduct a fasting and fed bioequivalence study of 23 healthy subjects each. The 0.4 g dose preparations were taken orally per cycle on fasting or fed administration. The plasma concentrations of moxifloxacin at different times after administration were determined by HPLC-MS/MS. The main pharmacokinetic parameters were calculated, and the bioavailability of the test preparation relative to the reference preparation was evaluated. RESULTS: After subjects in the fasting group took the test preparation T and the reference preparation R, the main pharmacokinetic parameters of moxifloxacin hydrochloride were: C

Objective:To investigate the value of 18F-fluorodeoxy glucose ( 18F-FDG) positron emission tomography/computed tomography (PET-CT) in predicting the epidermal growth factor receptor (EGFR) mutations in patients with lung squamous cell carcinoma. Methods:We retrospectively analyzed the clinical data and 18F-FDG PET-CT imaging data of 206 patients with lung squamous cell carcinoma confirmed by pathology and underwent EGFR mutation test in the First Affiliated Hospital of Nanjing Medical University from June 2013 to October 2018. Receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of maximum standard uptake value (SUV max), metabolic tumor volume (MTV), total lesion glycolysis (TLG). The Chi- squared test was used to assess the difference in PET parameters. A multivariate Logistic regression analysis was performed to yield the parameters with statistic difference. Results:All of 206 patients with lung squamous cell carcinoma showed a high 18F-FDG uptake. The median of SUV max, MTV and TLG were 19.14, 37.69 cm 3 and 291.73, respectively. Among the 206 patients, EGFR mutations were identified in 14 cases, including 7 with exon 21 (L858R) mutation, 6 with exon 19 mutation and 1 with exon 20 mutation. ROC curve showed that the AUC of SUV max, MTV and TLG were 0.624 (95% CI=0.454-0.794, P=0.122), 0.892 (95% CI=0.811-0.973, P<0.001) and 0.860 (95% CI=0.768-0.952, P<0.001), respectively. The median SUV max (19.14) was used as the cutoff points due to the small value of AUC. The cutoff point of MTV was 20.09 cm 3, the cutoff point of TLG was 211.07. Univariate analysis showed that the sex, smoking history, M stage, MTV and TLG were associated with EGFR mutations (all P<0.05). Logistic multivariate analysis showed that the sex, smoking history and TLG were the independent predictors of EGFR mutation (all P<0.05). Conclusion:TLG detected by 18F-FDG PET/CT is an independent factor for predicting EGFR mutation in patients with lung squamous cell carcinoma, and has certain reference value for predicting EGFR mutation.

Objective:To investigate the value of 18F-fluorodeoxy glucose ( 18F-FDG) positron emission tomography/computed tomography (PET-CT) in predicting the epidermal growth factor receptor (EGFR) mutations in patients with lung squamous cell carcinoma. Methods:We retrospectively analyzed the clinical data and 18F-FDG PET-CT imaging data of 206 patients with lung squamous cell carcinoma confirmed by pathology and underwent EGFR mutation test in the First Affiliated Hospital of Nanjing Medical University from June 2013 to October 2018. Receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of maximum standard uptake value (SUV max), metabolic tumor volume (MTV), total lesion glycolysis (TLG). The Chi- squared test was used to assess the difference in PET parameters. A multivariate Logistic regression analysis was performed to yield the parameters with statistic difference. Results:All of 206 patients with lung squamous cell carcinoma showed a high 18F-FDG uptake. The median of SUV max, MTV and TLG were 19.14, 37.69 cm 3 and 291.73, respectively. Among the 206 patients, EGFR mutations were identified in 14 cases, including 7 with exon 21 (L858R) mutation, 6 with exon 19 mutation and 1 with exon 20 mutation. ROC curve showed that the AUC of SUV max, MTV and TLG were 0.624 (95% CI=0.454-0.794, P=0.122), 0.892 (95% CI=0.811-0.973, P<0.001) and 0.860 (95% CI=0.768-0.952, P<0.001), respectively. The median SUV max (19.14) was used as the cutoff points due to the small value of AUC. The cutoff point of MTV was 20.09 cm 3, the cutoff point of TLG was 211.07. Univariate analysis showed that the sex, smoking history, M stage, MTV and TLG were associated with EGFR mutations (all P<0.05). Logistic multivariate analysis showed that the sex, smoking history and TLG were the independent predictors of EGFR mutation (all P<0.05). Conclusion:TLG detected by 18F-FDG PET/CT is an independent factor for predicting EGFR mutation in patients with lung squamous cell carcinoma, and has certain reference value for predicting EGFR mutation.

The infectious disease outpatient service as a frontier is an important fulcrum of public health service. Its standardized construction is an important support for ensuring medical safety, reducing nosocomial infections, and controlling the epidemic of infectious diseases. The sub-specialty outpatient service of infection diseases includes fever outpatient service, intestinal outpatient service, tuberculosis outpatient service, AIDS outpatient service, liver disease outpatient service, etc. According to the characteristics of each subspecialty outpatient service and combining with clinical practice, we elaborated the setting norms of subspecialty outpatient service for common infectious diseases from the perspective of planning and design, building layout, equipment and facilities configuration, staffing, daily management and demonstration.