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(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Background::Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection.Methods::A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2.Results::Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI= 1.263–2.818), and nonsystemic treatment (adjusted OR= 1.602, 95% CI= 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression analysis. Conclusions::A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension.

Objective This study aims to investigate the therapeutic effect and mechanism of Naoxinqing on non-alcohol fatty liver disease (NAFLD) induced by a high-fat diet through network pharmacology,molecular docking and in vitro and in vivo experiments. Methods ApoE-/-mice were given a high-fat diet for 12 weeks to establish the NAFLD model,followed by a 12-week Naoxinqing administration. To evaluate the therapeutic effect of Naoxinqing on NAFLD induced by a high-fat diet,biochemical and histopathological experiments were performed,including assessment of blood lipids,liver function,serum inflammatory factors,as well as Hematoxylin and eosin (HE),Oil red O,and Sirius red staining of liver. Subsequently,network pharmacology and molecular docking techniques were employed to predict the key targets of Naoxinqing. Finally,the mechanism of Naoxinqing was validated by Western Blot in HepG2 cells and liver tissue. Results The results of serum biochemistry and liver tissue pathology showed that Naoxinqing can significantly improve high-fat diet-induced hepatic lipid accumulation,hepatocellular injury,and inflammation. Network pharmacology and molecular docking analysis results suggested that Naoxinqing may affect lipid metabolism through the AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1) pathway. Finally,in vitro cell experiment confirmed that the main mechanism of Naoxinqing is to activative the AMPK/SIRT1 pathway,upregulate the expression of downstream carnitine palmitoyltransferase 1 (CPT1A),promote fatty acid oxidation,and ultimately improve NAFLD. Conclusion This study demonstrated that Naoxinqing improved NAFLD by promoting fatty acid oxidation through the activation of the AMPK/SIRT1 pathway.

Objective:To analyze the positioning error of vacuum pad and breast bracket in base note radiotherapy for breast cancer with breast conserving surgery based on cone beam CT (CBCT).Methods:A total of 120 patients who received IMRT after breast conserving surgery for breast cancer in the radiotherapy department of Nantong Cancer Hospital from April 2020 to April 2022 were retrospectively selected. According to the fixation method, the patients were divided into two groups: group A ( n=60) was fixed with a vacuum pad, and group B ( n=60) was fixed with a breast bracket. CBCT was used to evaluate the placement, and the placement errors and the occurrence of radiation dermatitis in each group were analyzed. Results:The translation errors of group A and group B in the left and right directions were (0.33±0.12)cm and (0.34±0.15)cm, respectively, and there was no statistically significant difference between the groups ( P>0.05). The errors in the direction of the abdomen and back were 0.32(0.11, 0.42)cm and 0.15(0.09, 0.21)cm, respectively, while the errors in the direction of the head and foot were 0.34(0.16, 0.34) cm and 0.23(0.15, 0.37)cm, respectively. The translation errors of the head, foot, and abdomen and back in group B were smaller than those in group A (all P<0.05). Patients in group B had significantly smaller translation errors in the left and right directions [group A: (0.31±0.13)cm, group B: (0.18±0.05)cm, P<0.05], and after rotation in the ventral and dorsal directions [group A: (0.31±0.11)cm, group B: (0.23±0.08)cm, P<0.05]. There was no statistically significant difference in translation errors after rotation in the head and foot directions ( P>0.05). The rotation error in the left and right directions of group B was smaller than that of group A [A: (0.98 0.12)°, group B: (0.67±0.31)°, P<0.05]. There was no statistically significant difference in the comparison of head foot and abdominal back rotation errors (all P>0.05). The planned center point (MIDM) of group B patients was located 10 cm to the left and right horizontally (MIDL, MIDR), with MIDM moving 8 cm to the head side (SM), MIDL moving 8 cm to the head side (SL), MIDR moving 8 cm to the head side (SR), MIDM moving 8 cm to the foot side (IM), MIDL moving 8 cm to the foot side (IL), and MIDR moving 8 cm to the foot side (IR). The thickness of the phantom was lower than that of group A (all P<0.05). At the completion of treatment, the total incidence of high-grade radiation dermatitis in group A was 61.67%(37/60), while the total incidence of high-grade radiation dermatitis in group B was 41.67%(25/60). The incidence of high-grade radiation dermatitis in group B was lower than that in group A ( P<0.05). Conclusions:Using breast bracket for breast fixation after breast conserving surgery for breast cancer can reduce the positioning error, the phantom thickness and the incidence of high-grade radiation dermatitis during intensity modulated radiotherapy, which is of high clinical value.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

Objective:To explore the value of color Doppler ultrasound (CDUS) combined with shear wave elastography (SWE) in the diagnosis of thyroid micropapillary carcinoma (PTMC).Methods:The clinical data were retrospectively collected including 51 patients with PTMC (study group) and 49 patients with benign thyroid nodules (control group) who treatment in Maanshan 17 Metallurgical Hospital from October 2020 to December 2022. The clinical data, serum tumor markers, CDUS quantitative parameters, and SWE quantitative parameters were compared between the two groups, the correlation between CDUS, SWE quantitative parameters and serum tumor markers were analyzed by Pearson test, and the diagnostic value of CDUS, SWE quantitative parameters were analyzed by receiver operating characteristic(ROC) curve.Results:The levels of serum carcinoembryonic antigen (CEA), thyroglobulin (TG), galactose hemagglutinin-3 (Gal-3), resistance index (RI), peak systolic flow velocity (PSV), elasticity modulus minimum (E min), elasticity modulus mean (E mean), and elasticity modulus maximum (E max) in the study group were higher than those in the control group: (28.76 ± 4.29) μg/L vs. (15.73 ± 2.96) μg/L, (117.53 ± 25.17) μg/L vs. (49.85 ± 9.64) μg/L, (8.31 ± 2.43) μg/L vs. (3.50 ± 0.82) μg/L, 0.85 ± 0.21 vs. 0.54 ± 0.13, (44.18 ± 8.26) cm/s vs. (22.05 ± 6.49) cm/s, (15.80 ± 1.94) kPa vs. (12.97 ± 1.58) kPa, (38.02 ± 10.39) kPa vs. (23.16 ± 7.83) kPa, (60.13 ± 19.41) kPa vs. (34.65 ± 11.87) kPa, there were statistical differences ( P<0.05). In patients with PTMC, the results of Pearson test showed that, RI, PSV, E min, E mean, and E max were positively correlated with serum CEA, TG, and Gal-3 levels ( P<0.05). The results of ROC curve analysis showed that the area under the curve (AUC) of the combined diagnosis of PTMC by RI, PSV, E min, E mean, and E max was 0.937. Conclusions:CDUS combined with SWE can provide reliable reference for clinical diagnosis of PTMC.

AIM:To explore the effect of polyphenolic compound 3,5-dihydroxy-4-methoxybenzyl alcohol(DHMBA)on hypoxia/reoxygenation(H/R)injury of human umbilical vein endothelial cells(EA.hy926 cells)and its po-tential mechanisms.METHODS:To construct an H/R model,the EA.hy926 cells were cultured in an acidic hypoxia buffer while in an anaerobic workstation.The cells were divided into control,H/R,H/R+different doses of DHMBA,H/R+edaravone(antioxidant)and H/R+reactive oxygen species(ROS)inducer oligomycin A+DHMBA groups.Cell viability was measured by CCK-8 assay,and tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)levels in cells were mea-sured by ELISA.Phosphorylation of endothelial nitric oxide synthase(eNOS)and nuclear factor-κB(NF-κB)p65 were measured by Western blot.Intracellular NO levels were determined by laser confocal microscopy.Glutathione(GSH)/glu-tathione disulfide(GSSG)oxidation balance was determined by the dinitrobenzoic acid chromogenic method.Intracellular ROS levels were measured by flow cytometry.Lactate dehydrogenase(LDH)leakage was determined using nitro blue tet-razolium staining.Scratch assays were performed to assess cell migration.RESULTS:DHMBA exhibited no significant cytotoxicity between 125 and 1 000 μmol/L.In H/R-injured human umbilical vein endothelial cells,DHMBA improved cell survival,inhibited phosphorylation of NF-κB p65,reduced the content of TNF-α and IL-6,and increased phosphory-lation of eNOS and NO levels.DHMBA also suppressed ROS overload and restored the ratio between GSH and oxidized GSH,decreased in LDH leakage and increased cell migration in H/R-injured human umbilical vein endothelial cells.CONCLUSION:DHMBA can alleviate H/R-induced oxidative stress,inflammation,cellular damage,and dysfunction,which are associated with the ability of DHMBA to inhibit ROS production in human umbilical vein endothelial cells.

Objective To investigate the expression of long non-coding RNA(LncRNA)nuclera-enriched autosomal transcript(NEAT1)in children with retinoblastoma(Rb)and the effect of down-regulation of NEAT1 in Rb cell Y79 on cell biological function.Methods A total of 83 children with Rb who were diagnosed and treated in Huangshi Central Hospital from March 2015 to March 2021 were collected as the research object.During the same period,50 healthy children(control group)were selected in the children's health center.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression of NEAT1 in serum.The differences in the expressions of NEAT1 in serum between Rb children and the control group,and the differences in the expressions of NEAT1 in serum among Rb children with different clinical indicators,were analyzed.Y79 cells were cultured and were divided into si-NEAT1 group(transfected with interference sequence of NEAT1),si-NC group(transfected with control sequence)and Ctl group(only add transfection reagent).The qRT-PCR,MTT,flow cytometry and Transwell were used to detect the NEAT1 expression,cell proliferation,apoptosis,migration and invasion.Results The expression level of NEAT1 in the serum of children with Rb(1.43±0.28)was higher than that in the control group(1.01±0.21),with significant difference(t=9.116,P＜0.001).The expression levels of NEAT1 in serum of children with Rb with Intraocular International Retinoblastoma classification(IIRC)stage CDE,poor differentiation,optic nerve infiltration and lymph node metastasis were higher than those in children with Rb with AB,medium to high differentiation,no optic nerve infiltration and lymph node metastasis,with significant differences(t=2.190～3.693,all P＜0.05).The area under the curve for diagnosing Rb based on NEAT1 expression in serum was 0.882(95％CI:0.826～0.937).When the expression level of NEAT1 was 1.20,the sensitivity and specificity were 80.00％and 79.52％,respectively.Compared with the si-NC group(1.03±0.09)and the Ctl group(1.02±0.15),the expression level of NEAT1 in the si-NEAT1 group(0.35±0.06)was decreased,with significant differences(t=14.829,9.994,all P＜0.001).The absorbance A values in the si-NEAT1 group at 24,48,72 and 96h were significantly lower than those in the si-NC group and the Ctl group(t=si-NC=2.796～4.362,tCtl=2.641～5.555,all P＜0.05),while the apoptosis rate in the si-NEAT1 group was significantly higher than those in the si-NC group and the Ctl group,and the differences were statistically significant(t=4.999,3.915,all P＜0.05).Compared with the si-NC group and the Ctl group,the number of migrating cells(116.50±9.35 vs 132.00±7.32,134.00±7.95)and the number of invasive cells(96.33±8.94 vs 117.67±12.39,119.17±10.05)in the si-NEAT1 group were reduced,and the differences were statistically significant(tsi-NC=3.196,3.421,tCtl=3.492,4.159,all P＜0.05).Conclusion The expression level of NEAT1 in the serum of children with Rb was elevated,which may have a certain diagnostic value for children with Rb.Silencing the expression of NEAT1 in Y79 cells could reduce cell proliferation,accelerate cell apoptosis,and inhibit cell migration and invasion.