OBJECTIVE To evaluate the effect of antimicrobial stewardship scientific(AMS)of antimicrobial agents on special antibiotics so as to provide evidence-based bases for reasonable use of antibiotics.METHODS A retro-spective survey was conducted for the status of use of special antibiotics in Zhongnan Hospital,Wuhan University.The utilization rate of intravenous infusion of antibiotics,antimicrobials use density(AUD)of special grade antibi-otics,defined daily doses(DDDs),etiological submission rate of microorganisms before use of antibiotics and drug resistance rates of major gram-negative bacteria to special grade antibiotics were observed and compared be-fore and after the AMS was carried out.RESULTS There were no significant differences in gender,severity of dis-ease and spectrum of infectious diseases before and after the AMS was carried out.The utilization rate of intrave-nous infusion of antibiotics was(55.64±1.63)％among the hospitalized patients after the AMS was carried out,the AUD of special grade antibiotics was 2.08±0.57,and the DDDs was 2406.53±292.16,showing generally downward trends(P＜0.05).The drug resistance rates of Acinetobacter baumannii strains to cefepime and imi-penem were 89.15％and 90.21％,respectively,showing upward trends(P＜0.05).CONCLUSION The AUD and DDDs of the special grade antibiotics can be remarkably reduced through powerful means such as carrying out AMS,setting up AMS task group for special grade antibiotics,developing guidance documents for scientific use of special antibiotics,taking full advantage of reasonable drug administration surveillance system,implementing closed-loop management of the special antibiotics,and completing early warning mechanisms for bacterial drug re-sistance as well as information construction to boost management.

Objective To understand the distribution characteristics of fungi on object surface in hospital environ-ment,and provide reference for the scientific and precise formulation of environment control strategies based on fun-gal in clinic.Methods From December 7 to 23,2023,a total of 60 environmental specimens of 19 categories in 6 departments of a large tertiary first-class hospital were collected and divided into water-related environmental speci-men group,complete facade environmental specimen group,and sanitary ware environmental specimen group.18S rRNA sequencing was performed on specimens with fungi detected.Results Fungal detection rate of environmental specimens was 20.00％(12/60).Sink in the department of endocrinology had the highest fungal colony count(15 CFU/cm2),followed by the air outlet of air disinfection device in the department of thoracic surgery and the in-ternal part of a faucet in the department of endocrinology(both 10 CFU/cm2).The water-related environmental specimen group detected most diverse fungal genera(14 species),with high relative abundances of Aspergillus(100％),Meyerozyma(99.06％),Ophiocordyceps genus(95.63％),and Kodamaea(87.86％).The air outlet of air disinfection device was detected with a high abundance of Chaetomium(44.08％)and Corollospora(39.71％).There was no statistically significant difference in the α-diversity(Shannon and Simpson indices,P values of 0.661 and 0.568,respectively)and β-diversity(P=0.712)among the three environmental specimens.Conclusion Under the routine implementation of basic environmental cleaning and disinfection in medical institutions,fungi are in a low prevalence in the environment.However,moist surfaces and air disinfection device are prone to fungal colonization,and it is necessary to strengthen daily monitoring and take corresponding intervention measures to reduce the risk of infection.

Objective To investigate the effects and mechanisms of fatty acid binding protein 4(FABP4)on ferroptosis in human renal tubular epithelial cells(HK-2)treated with hypoxia/reoxygenation(H/R).Methods HK-2 cells were cultured in vitro and subjected to hypoxia for 24 hours followed by reoxygenation for different durations(1,3,6 h).The messenger RNA(mRNA)and protein levels of FABP4 in HK-2 cells were detected at each time point using real-time fluorescent quantitative polymerase chain reaction and Western blotting.Small interfering RNA(siRNA)technology was used to silence the expression of FABP4 gene in HK-2 cells,which were then treated with H/R(24 h of hypoxia and 6 h of reoxygenation)or treated with the Nrf2 inhibitor ML385.Cell proliferation activity was assessed using cell counting kit-8(CCK-8).Lactate dehydrogenase(LDH)levels were measured by enzyme-linked immune absorbent assay.Malondialdehyde(MDA),glutathione(GSH)and ferrous ion(Fe2+)levels were determined by biochemical technology.Reactive oxygen species(ROS)levels were detected using the 2',7'-dichlorodihydrofluorescein diacetate fluorescence probe.Protein expression levels of FABP4,nuclear factor E2-related factor 2(Nrf2),heme oxygenase-1(HO-1),glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)were measured by Western blotting.Results The mRNA and protein levels of FABP4 in HK-2 cells increased with prolonged reoxygenation time(all P<0.05).H/R treatment reduced cell proliferation activity,increased LDH levels in the cell supernatant,and elevated MDA,Fe2+and ROS levels in HK-2 cells while decreasing GSH levels and the protein levels of Nrf2,HO-1,GPX4 and SLC7A11(all P<0.05).Silencing FABP4 enhanced the proliferation activity of H/R-treated HK-2 cells(P<0.05),reduced MDA,Fe2+and ROS levels,increased GSH levels,and elevated the protein levels of Nrf2,HO-1,GPX4 and SLC7A11(all P<0.05).However,these beneficial effects of FABP4 silencing on H/R-induced ferroptosis in HK-2 cells were reversed by co-treatment with ML385.Conclusions Silencing FABP4 alleviated H/R-induced ferroptosis in HK-2 cells,possibly by activating the Nrf2/GPX4 axis.

Objective To understand the distribution characteristics of fungi on object surface in hospital environ-ment,and provide reference for the scientific and precise formulation of environment control strategies based on fun-gal in clinic.Methods From December 7 to 23,2023,a total of 60 environmental specimens of 19 categories in 6 departments of a large tertiary first-class hospital were collected and divided into water-related environmental speci-men group,complete facade environmental specimen group,and sanitary ware environmental specimen group.18S rRNA sequencing was performed on specimens with fungi detected.Results Fungal detection rate of environmental specimens was 20.00％(12/60).Sink in the department of endocrinology had the highest fungal colony count(15 CFU/cm2),followed by the air outlet of air disinfection device in the department of thoracic surgery and the in-ternal part of a faucet in the department of endocrinology(both 10 CFU/cm2).The water-related environmental specimen group detected most diverse fungal genera(14 species),with high relative abundances of Aspergillus(100％),Meyerozyma(99.06％),Ophiocordyceps genus(95.63％),and Kodamaea(87.86％).The air outlet of air disinfection device was detected with a high abundance of Chaetomium(44.08％)and Corollospora(39.71％).There was no statistically significant difference in the α-diversity(Shannon and Simpson indices,P values of 0.661 and 0.568,respectively)and β-diversity(P=0.712)among the three environmental specimens.Conclusion Under the routine implementation of basic environmental cleaning and disinfection in medical institutions,fungi are in a low prevalence in the environment.However,moist surfaces and air disinfection device are prone to fungal colonization,and it is necessary to strengthen daily monitoring and take corresponding intervention measures to reduce the risk of infection.

Objective To investigate the effects and mechanisms of fatty acid binding protein 4(FABP4)on ferroptosis in human renal tubular epithelial cells(HK-2)treated with hypoxia/reoxygenation(H/R).Methods HK-2 cells were cultured in vitro and subjected to hypoxia for 24 hours followed by reoxygenation for different durations(1,3,6 h).The messenger RNA(mRNA)and protein levels of FABP4 in HK-2 cells were detected at each time point using real-time fluorescent quantitative polymerase chain reaction and Western blotting.Small interfering RNA(siRNA)technology was used to silence the expression of FABP4 gene in HK-2 cells,which were then treated with H/R(24 h of hypoxia and 6 h of reoxygenation)or treated with the Nrf2 inhibitor ML385.Cell proliferation activity was assessed using cell counting kit-8(CCK-8).Lactate dehydrogenase(LDH)levels were measured by enzyme-linked immune absorbent assay.Malondialdehyde(MDA),glutathione(GSH)and ferrous ion(Fe2+)levels were determined by biochemical technology.Reactive oxygen species(ROS)levels were detected using the 2',7'-dichlorodihydrofluorescein diacetate fluorescence probe.Protein expression levels of FABP4,nuclear factor E2-related factor 2(Nrf2),heme oxygenase-1(HO-1),glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)were measured by Western blotting.Results The mRNA and protein levels of FABP4 in HK-2 cells increased with prolonged reoxygenation time(all P<0.05).H/R treatment reduced cell proliferation activity,increased LDH levels in the cell supernatant,and elevated MDA,Fe2+and ROS levels in HK-2 cells while decreasing GSH levels and the protein levels of Nrf2,HO-1,GPX4 and SLC7A11(all P<0.05).Silencing FABP4 enhanced the proliferation activity of H/R-treated HK-2 cells(P<0.05),reduced MDA,Fe2+and ROS levels,increased GSH levels,and elevated the protein levels of Nrf2,HO-1,GPX4 and SLC7A11(all P<0.05).However,these beneficial effects of FABP4 silencing on H/R-induced ferroptosis in HK-2 cells were reversed by co-treatment with ML385.Conclusions Silencing FABP4 alleviated H/R-induced ferroptosis in HK-2 cells,possibly by activating the Nrf2/GPX4 axis.

OBJECTIVE To evaluate the effect of antimicrobial stewardship scientific(AMS)of antimicrobial agents on special antibiotics so as to provide evidence-based bases for reasonable use of antibiotics.METHODS A retro-spective survey was conducted for the status of use of special antibiotics in Zhongnan Hospital,Wuhan University.The utilization rate of intravenous infusion of antibiotics,antimicrobials use density(AUD)of special grade antibi-otics,defined daily doses(DDDs),etiological submission rate of microorganisms before use of antibiotics and drug resistance rates of major gram-negative bacteria to special grade antibiotics were observed and compared be-fore and after the AMS was carried out.RESULTS There were no significant differences in gender,severity of dis-ease and spectrum of infectious diseases before and after the AMS was carried out.The utilization rate of intrave-nous infusion of antibiotics was(55.64±1.63)％among the hospitalized patients after the AMS was carried out,the AUD of special grade antibiotics was 2.08±0.57,and the DDDs was 2406.53±292.16,showing generally downward trends(P＜0.05).The drug resistance rates of Acinetobacter baumannii strains to cefepime and imi-penem were 89.15％and 90.21％,respectively,showing upward trends(P＜0.05).CONCLUSION The AUD and DDDs of the special grade antibiotics can be remarkably reduced through powerful means such as carrying out AMS,setting up AMS task group for special grade antibiotics,developing guidance documents for scientific use of special antibiotics,taking full advantage of reasonable drug administration surveillance system,implementing closed-loop management of the special antibiotics,and completing early warning mechanisms for bacterial drug re-sistance as well as information construction to boost management.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Tumor microenvironment contributes to poor prognosis of pancreatic adenocarcinoma (PAAD) patients. Proper regulation could improve survival. Melatonin is an endogenous hormone that delivers multiple bioactivities. Here we showed that pancreatic melatonin level is associated with patients' survival. In PAAD mice models, melatonin supplementation suppressed tumor growth, while blockade of melatonin pathway exacerbated tumor progression. This anti-tumor effect was independent of cytotoxicity but associated with tumor-associated neutrophils (TANs), and TANs depletion reversed effects of melatonin. Melatonin induced TANs infiltration and activation, therefore induced cell apoptosis of PAAD cells. Cytokine arrays revealed that melatonin had minimal impact on neutrophils but induced secretion of Cxcl2 from tumor cells. Knockdown of Cxcl2 in tumor cells abolished neutrophil migration and activation. Melatonin-induced neutrophils presented an N1-like anti-tumor phenotype, with increased neutrophil extracellular traps (NETs) causing tumor cell apoptosis through cell-to-cell contact. Proteomics analysis revealed that this reactive oxygen species (ROS)-mediated inhibition was fueled by fatty acid oxidation (FAO) in neutrophils, while FAO inhibitor abolished the anti-tumor effect. Analysis of PAAD patient specimens revealed that CXCL2 expression was associated with neutrophil infiltration. CXCL2, or TANs, combined with NET marker, can better predict patients' prognosis. Collectively, we discovered an anti-tumor mechanism of melatonin through recruiting N1-neutrophils and beneficial NET formation.

Objective:To study the efficacy and safety of EndoClot polysaccharide hemostatic system (EndoClot PHS) for heparinized arterial hemorrhage of upper digestive tract (Forrest Ⅰa) in animal model.Methods:Twelve experimental pigs were randomly divided into the test group ( n=6) and the control group ( n=6) by simple random grouping method. Gastric arterial hemorrhage models were established. Endoclot PHS and Hemospray were used to spray on the wound to stop bleeding in the test group and the control group respectively. The time of effective hemostasis, the amount of hemostatic particles used, and the blockage of the powder feeding tube and its replacement were compared between the two groups. The survival and complications of experimental pigs were observed after the operation. In 10 days after the operation, the experimental pigs were euthanized for pathological dissection. Results:Spurting or pulsatile bleeding was achieved in all experimental pigs. There were significant differences in the time of effective hemostasis (8.75±0.84 min VS 9.83±0.62 min, t=-2.53, P=0.030) and the amount of hemostatic particles used to achieve effective hemostasis (6.71±0.39 g VS 14.10±1.62 g, t=-10.86, P<0.001) between the test group and the control group. There was no significant difference in the occurence of clogging or the replacement of powder feeding pipes between the two groups (0.64±0.02 times VS 0.67±0.04 times, t=-1.64, P=0.131). In addition, the gas source of the test group was stable, and the visual field under the endoscope was clear. Neither the test group nor the control group had gastric lesions, perforation, or embolism. The blood glucose, blood routine, and liver and kidney functions were normal, and no thrombosis or embolism of the main organs occurred in either group. Conclusion:EndoClot PHS is safe and effective for heparinized upper gastrointestinal arterial hemorrhage (Forrest Ⅰa) in animal models.

Objective:To study the clinical characteristics and classification of gastric neuroendocrine neoplasm(NEN) and prognostic factors of mixed adenoneuroendocrine carcinoma (MANEC) and gastric neuroendocrine carcinoma(NEC).Methods:A total of 148 gastric NENs were divided into type Ⅰ, type Ⅱ and type Ⅲ based on the classification of European Neuroendocrine Tumor Society (ENETS). Kaplan-Meier test and Cox regression model were used in univariate and multivariate survival analysis in 108 cases with pathological G3 gastric NEN.Results:In this study, the percentages of type Ⅰ, type Ⅱ and type Ⅲ were 25.0%(37), 3.4%(5) and 71.6%(106) respectively. Among type Ⅰ patients, 28(75.7%) lesions were located in gastric fundus or body, 29(78.4%) had bumps. Lymph node involvement was found in 4 (10.8%) patients. Twenty-six (70.3%) patients received endoscopic treatment and 11 (29.7%) with surgery. All 5 type Ⅱ patients presented lesions in gastric fundus or body, including 4 with ulcers, who were all treated by endoscope. Three type Ⅱ patients had gastrinoma, and 2 combined with multiple endocrine neoplasmⅠ. In type Ⅲ patients, 56(52.8%) showed ulcerative lesions. The majority of patients (102, 96.2%) had a single lesion, 94(88.7%) with lymph node or other organ metastasis. In this study, no deaths were reported in gastric NEN with a pathological grade of G1 or G2. The mortality rate was 38.9%(42/108) in patients with G3 NEN. Survival analysis suggested that age, metastasis of tumor were associated with poor prognosis ( P=0.041, 0.025). Conclusions:Patients with gastric NEN have heterogenous clinical presentations according to gender, age, endoscopic features, infiltration and metastasis, and pathological grade. Aging and metastasis are negative prognostic factors of G3 gastric NEN.