Objective:To investigate the drug resistance status and genomic characterization of Proteus mirabilis (PM) isolated from outpatient cases with diarrhea in Tai′an City and Laizhou City, Shandong Province. Methods:A total of 510 fecal samples were collected from 510 patients with acute diarrhea admitted to 43 sentinel hospitals in Tai′an City and Laizhou City, Shandong Province, between January 2021 and December 2022. The samples were cultured and isolated to identify Proteus spp. by direct inoculation, the drug susceptibility testing was performed by microbroth dilution method, and resistance genes and virulence genes were obtained by whole genome sequencing and bioinformatic analysis, thereby revealing the genetic environment surrounding the blaOXA-1 and blaCTX-M-65 genes. Single nucleotide polymorphism (SNP) analysis and core genome multilocus sequence typing (cgMLST) were conducted on the current strains and 100 PM isolates downloaded from the National Center for Biotechnology Information (NCBI) database via customizable methods utilizing RidomSeqSphere+ software, with the objective of exploring the phylogenetic relationships among the strains. Results:A total of 35 strains of Proteus were isolated from 510 fecal samples, including 31 strains of PM with a detection rate of 6.08% (31/510) and four strains of Proteus vulgaris.The multidrug resistance rate of PM was 100.00% (31/31).The 35 isolates carried a total of 43 resistance genotypes.Thirteen strains of PM carried blaOXA-1, six strains carried both blaOXA-1 and blaCTX-M-65, and 15 PM strains carried at least 15 antibiotic resistance genes (ARGs). The virulence genes included ureA, mrpA, ZapA, hpmA and so on. blaOXA-1 and blaCTX-M-65 genes were surrounded by mobile elements such as Tn3, ISL3 and IS6. cgMLST showed consistency with the SNP clustering results. Isolate 2022LZ41 from Laizhou City clustered with isolates 2022TA018, 2022TA017 and 2022TA019 from Tai′an City, with the number of allelic differences ranging from zero to two, and the Laizhou City isolate 2022LZ40 was highly genetically related to strain CRK0056 (human, USA, 2015). Conclusions:PM isolated from patients with diarrhea is multidrug-resistant, carrying many resistance and virulence genes.The presence of mobile genetic elements can lead to horizontal transfer of resistance genes.

Objective:To investigate the popularization of non-iodized salt among residents in water-borne high iodine areas and the iodine nutrition status of key populations in Shandong Province.Methods:In 2021, monitoring was conducted on a county-by-county basis in 47 counties (cities, districts, hereinafter referred to as counties) in 9 cities of Shandong Province, in accordance with the newly designated high iodine areas in the "Definition of Water Source High Iodine Areas and High Iodine Disease Areas" (GB/T 19380-2016) and historical high iodine areas. In each monitoring county, administrative villages with a median water iodine level greater than 100 μg/L were sorted by water iodine value, and a systematic sampling method was used to select 5 administrative villages as monitoring sites to investigate the water improvement situation and the iodine level of residents' drinking water. Totally 40 non boarding students aged 8 to 10 from one primary school and 20 pregnant women were selected in each village location to collect household edible salt samples and random urine samples for testing salt iodine and urine iodine levels, and the B-ultrasound method was used for thyroid examination in children.Results:A total of 364 high iodine administrative villages had been monitored, all of which had completed water improvement with a water improvement rate of 100.0%. The median iodine content in residential drinking water was 20.3 μg/L, ranging from 0.1 to 869.1 μg/L; and 11 464 edible salt samples were collected from residents' homes, with a non-iodized salt rate of 82.7% (9 481/11 464). A total of 9 197 urine samples from children and 2 335 urine samples from pregnant women were tested, with median urinary iodine levels of 219.0 and 139.0 μg/L, respectively. A total of 9 197 children were examined for thyroid, with 262 cases detected and a goiter rate of 2.8%.Conclusions:The rate of non-iodized salt in high iodine areas of Shandong Province still needs to be improved. Children's iodine nutrition is above the appropriate level, while pregnant women are at an iodine deficiency level.

Objective:To explore the ventilation strategy of using pressure controlled ventilation-volume guaranteed (PCV-VG) mode combined with personalized positive end expiratory pressure (PEEP) during surgery, and its impact on oxygenation function and incidence of postoperative pulmonary complications (PPCs) in patients undergoing brain tumor surgery.Methods:Sixty patients who underwent elective brain tumor surgery at the Linyi People′s Hospital from January 2023 to June 2023 were selected. The patients were randomly divided into PCV-VG ventilation mode group (T group) and volume controlled ventilation (VCV) mode group (C group) using a random number table method, with 30 patients in each group. One patient was excluded from group T due to changes in the condition, and 29 patients were actually included. Group T adopted PCV-VG ventilation mode and searched for the maximum dynamic lung compliance (Cdyn) by titrating PEEP. The PEEP corresponding to the maximum Cdyn value was the optimal PEEP, which was maintained until the end of mechanical ventilation. Group C adopted a ventilation mode of VCV plus 5 cmH 2O fixed value PEEP. All patients underwent arterial blood gas analysis before anesthesia induction (T 1), 15 minutes after setting ventilation mode (T 2), and 15 minutes after extubation (T 3), recording arterial oxygen partial pressure (PaO 2), carbon dioxide partial pressure (PaCO 2), lactate (Lac), and blood glucose (Glu), and calculating oxygenation index (PaO 2/FiO 2). The levels of white blood cells (WBC), C-reactive protein (CRP), and procalcitonin (PCT) were recorded before and 72 hours after surgery. The incidence of postoperative PPCs at 72 hours was observed. Results:There was a statistically significant difference in the grouping effect and time effect of PaO 2 and PaCO 2 between group C and group T (all P<0.05), while there was no statistically significant difference in the interaction effect (all P>0.05); The differences in grouping effects, time effects, and interaction effects of PaO 2/FiO 2 between group C and group T were statistically significant (all P<0.05); The average value of the optimized PEEP obtained by T-group titration was 7.48 cmH 2O, corresponding to an average platform pressure (Pplat) of 14.90 cmH 2O, and an average value of 53.37 ml/cmH 2O corresponding to the maximum Cdyn value. Compared with the Pplat and Cdyn corresponding to the fixed value of 5 cmH 2O PEEP in Group C, the Pplat corresponding to the optimized PEEP in Group T was lower than that in Group C ( P<0.05), and the Cdyn was higher than that in group C ( P<0.05). The CRP level and incidence of PPCs in group T after 72 hours of surgery were significantly lower than those in group C (all P<0.05). Conclusions:Compared with VCV, the ventilation mode of PCV-VG combined with personalized PEEP can improve intraoperative lung ventilation and oxygenation function in patients with brain tumors, reduce the occurrence of pulmonary inflammation 72 hours after surgery, and lower the incidence of PPCs.

Myocarditis is an inflammatory disease of myocardium caused by a variety of factors.The most common etiology is enterovirus, followed by respiratory viruses, especially the new coronaviruses, mycoplasma, rickettsia, and toxoplasma, etc.The probability of arrhythmia is relatively high in myocarditis due to increased myocardial susceptibility, and its type may be suggestive of disease progression and prognosis.Electrophysiological changes in the cardio-myocytes are observed by electrocardiography and ambulatory electrocardiography.Echocardiography and cardiac magnetic resonance are used to detect specific changes in the internal structure of the myocardium and left ventricular systolic function and to assist in the diagnosis.For the treatment of myocarditis, in addition to general treatment, according to the needs of the condition, intravenous immunoglobulin, glucocorticoids, and receptor antagonists of some cytokines can be used.The prognosis of pediatric myocarditis is related to the type of myocarditis, the speed of progression, the degree of myocardial damage, the electrophysiological changes and the structural changes of the heart.

Objective To explore risk factors of poor early prognosis in the treatment of COVID-19 by nematevir and ritonavir tablets Paxlovid and establish the prediction model to provide reference for improving the effect of such patients. Methods 92 inpatients of COVID-19 treated with Paxlovid in three military tertiary hospital in southern Fujian from January 2023 to March 2023 were retrospectively analyzed. The clinical indicators of 92 inpatients were collected for univariate and multivariate analysis by single factor and multiple factors and the independent risk factors of poor early prognosis in Paxlovid were screened out. Logistic model equation was transformed to construct the combined predictors, and ROC curve was used to determine the area under the curve (AUC) and the optimal critical value of the combined predictors. Results Among 92 patients, 31 (33.70%) developed poor early prognosis, including 11 deaths (35.48%), 17 critical cases (54.84%) and 3 severe cases (9.68%). Multi-factor Logistic regression analysis showed that the disease days, lymphocyte count, aspartate aminotransferase(AST), C reactive protein(CRP) and ventilator-assisted ventilation were independent risk factors for poor early prognosis in Paxlovid. A formula for calculating the combined predictors (Y) was established as Y_{combinedpredictors}=7.875X_{disease days}+126.188X_{lymphocyte count}+1.438X_AST+X_CRP+220.500X_{ventilator-assisted ventilation} based on the above independent risk factors, and the ROC curve was drawn. With the maximum area under the ROC curve of the combined predictors being 0.939, the prediction value was best, and the optimal critical value of the ROC curve corresponding to the maximum Youden index (0.756) was 447.920.Theoretical accuracy of the model was 89.10%. Conclusion The disease days, lymphocyte count, AST, CRP and ventilator-assisted ventilation were independent risk factors for poor early prognosis in Paxlovid. Combined predictors could be calculated by the above risk factors before medication. The efficiency should be improved by taking more active treatment, including combining with other anti-COVID-19 drugs when the prediction result exceeds 447.920.

ObjectiveTo observe the therapeutic effect of Yiyuan Qiwei pills （YYQW） on diabetes mellitus-induced induced erectile dysfunction （DMED） in rats and explore its regulation on the nitric oxide （NO）-cyclic guanosine monophosphate （cGMP） signaling pathway. MethodFifty-five healthy SD male rats of clean grade aged 2-3 months underwent intraperitoneal injection of streptozotocin （STZ） to induce the DMED model， and another 10 healthy SD male rats of clean grade aged 2-3 months were assigned to the control group. The model rats were randomly divided into a model group， a sildenafil group （5 mg·kg^-1， ig）， and low-， medium-， and high-dose YYQW groups （1.5， 3.0， 6.0 g·kg^-1， ig）. The rats in the model group and the control group were given normal saline by gavage at 10 mL·kg^-1， once a day for two months. After intervention， the penile erectile function of rats in each group was measured by a pressure detection system. The pathological changes and ultrastructure of penile corpus cavernosum were observed by hematoxylin-eosin （HE） staining and transmission electron microscopy， respectively. The level of NO in the corpus cavernosum was detected by nitrate reductase. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of cGMP and advanced glycation end products （AGEs）. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of endothelial nitric oxide synthase （eNOS）， neurogenic nitric oxide synthase （nNOS）， total nitric oxide synthase （NOS）， and phosphodiesterase type5 （PDE5） in rat penile tissues. The expression of above proteins was detected by Western blot. ResultCompared with the control group， the model group showed decreased intracavernous pressure （ICP）， NO， and cGMP levels， reduced mRNA and protein expression of nNOS and NOS， and increased PDE5 mRNA and protein expression （P<0.05）. Compared with the model group， the sildenafil group and the YYQW groups displayed increased ICP， NO， and cGMP levels， elevated mRNA and protein expression levels of nNOS and NOS， and reduced PDE5 mRNA and protein expression levels （P<0.05）. There were no pathological changes in the tissues and cell ultrastructure of the corpus cavernosum in the control group， while serious pathological changes were observed in the model group. Additionally， the sildenafil group and the YYQW groups were superior to the model group， the optimal effect was observed in the high-dose YYQW group. ConclusionYYQW can improve the penile erectile function of DMED rats and reduce the pathological damage of corpus cavernosum. The mechanism may be related to the promotion of nNOS and NOS expression， the inhibition of PDE5 expression， and the activation of the NO/cGMP signaling pathway.

Objective:Evidence on potential cardiovascular benefits of personal-level intervention among the elderly exposed to high levels of particulate matter(PM)remains limited.We aimed to assess improvements in surrogate markers of cardiovascular injury in vulnerable populations at risks by using indoor air filtration units.Methods:We conducted a randomized crossover trial for 2 separate 2-week air filtration interventions in 20 households of patients with stable chronic obstructive pulmonary disease and their partners in the winter of 2013,with concurrent measurements of indoor PM.The changes in biomarkers indicative of cardiac injury,atherosclerosis progression and systemic inflammation following intervention were evaluated using linear mixed-effect models.Results:In the analysis,average levels of indoor PM with aerodynamic diameters＜2.5 μm(PM2.5)decreased significantly by 59.2％(from 59.6 to 24.3 μg/m3,P＜0.001)during the active air filtration.The reduction was accompanied by improvements in levels of high-sensitivity cardiac troponin I by-84.6％(95％confidence interval[CI]:-90.7 to-78.6),growth differentiation factor-15 by-48.1％(95％CI:-31.2 to-25.6),osteoprotegerin by-65.4％(95％CI:-56.5 to-18.7),interleukin-4 by-46.6％(95％CI:-62.3 to-31.0)and myeloperoxidase by-60.3％(95％CI:-83.7 to-3.0),respectively.Conclusion:Indoor air filtration intervention may provide potential cardiovascular benefits in vulnerable popu-lations at risks.

Background The increasing threats of air pollution and extreme weather have been widely recognized in recent years in China, but their individual and joint effects on cardio-cerebrovascular mortality are unclear. Objective This study aims to investigate the individual effects of and potential interactions between oxidant pollutants and ambient temperature on cardio-cerebrovascular mortality risks. Methods We collected daily data on death counts of cardio-cerebrovascular diseases, concentrations of ambient air pollutants, and meteorological parameters in Guangzhou, Chinabetween 1 January 2006 and 31 December 2016. A generalized additive model with a Poisson distribution was conducted to assess the associations of oxidant pollutants and ambient temperature with cardio-cerebrovascular mortality risks. Bivariate response surface models and stratified analyses were further adopted to qualitatively and quantitatively examine the potential interactions between oxidant pollutants and ambient temperature on cardio-cerebrovascular mortality risks. Results During the study period, the daily averages were 60.3 μg·m⁻³ for ozone (O₃), 50.9 μg·m⁻³ for combined atmospheric oxidant capacity (O_x), 32.5 μg·m⁻³ for nitrogen dioxide (NO₂), and 22.3℃ for ambient temperature. The average daily death counts of coronary and stroke diseases were 20 and 15, respectively. Per 10 μg·m⁻³ increment in O₃, O_x, and NO₂ were associated with increased coronary mortality risks (excess risk, ER) of 1.26% (95%CI: 0.79%-1.74%), 1.61% (95%CI: 0.99%-2.23%), and 1.33% (95%CI: 0.59%-2.07%), and with increased stroke mortality risks of 1.56% (95%CI: 1.04%-2.09%), 2.30% (95%CI: 1.60%-3.01%), and 2.93% (95%CI: 2.07%-3.79%) over cumulative lags of 2-5 days, respectively. The exposure-response relationships between ambient temperature and coronary and stroke mortality risks exhibited an inverse "J" shape, with the minimum mortality at temperatures of 25.7℃ for coronary disease and 27.3℃ for stroke. Our results further showed potentially synergic effects of higher temperatures and higher levels of O₃ and O_x exposures on coronary mortality risks, and the relative ER due to interactions was 0.103 (95%CI: 0.028-0.178) for O₃ and 0.079 (95%CI: 0.004-0.154) for O_x. We didn't find evidence of an interaction between oxidant pollutants and low temperature. Conclusion Short-term exposures to oxidant pollutants are associated with increased cardio-cerebrovascular mortality risks, and the interactive effects of high temperature and oxidant pollutants are synergistic in relation to cardio-cerebrovascular mortality risks.

The capacity for thermal tolerance is critical for industrial enzyme. In the past decade, great efforts have been made to endow wild-type enzymes with higher catalytic activity or thermostability using gene engineering and protein engineering strategies. In this study, a recently developed SpyTag/SpyCatcher system, mediated by isopeptide bond-ligation, was used to modify a rumen microbiota-derived xylanase XYN11-6 as cyclized and stable enzyme C-XYN11-6. After incubation at 60, 70 or 80 ℃ for 10 min, the residual activities of C-XYN11-6 were 81.53%, 73.98% or 64.41%, which were 1.48, 2.92 or 3.98-fold of linear enzyme L-XYN11-6, respectively. After exposure to 60-90°C for 10 min, the C-XYN11-6 remained as soluble in suspension, while L-XYN11-6 showed severely aggregation. Intrinsic and 8-anilino-1-naphthalenesulfonic acid (ANS)-binding fluorescence analysis revealed that C-XYN11-6 was more capable of maintaining its conformation during heat challenge, compared with L-XYN11-6. Interestingly, molecular cyclization also conferred C-XYN11-6 with improved resilience to 0.1-50 mmol/L Ca²⁺ or 0.1 mmol/L Cu²⁺ treatment. In summary, we generated a thermal- and ion-stable cyclized enzyme using SpyTag/SpyCatcher system, which will be of particular interest in engineering of enzymes for industrial application.
Animals ; Cyclization ; Endo-1,4-beta Xylanases ; chemistry ; metabolism ; Enzyme Stability ; Industrial Microbiology ; methods ; Microbiota ; Protein Engineering ; Rumen ; enzymology ; microbiology ; Temperature

Objective: To explore the effect of mindfulness traits on sleep quality of college students, and to investigate the mediating mechanism of cognitive emotion regulation and anxiety for mindfulness trait factors, and sleep quality in college students. Methods: Totally 397 college students from five colleges were investigated using Five Facet Mindfulness Questionnaire, Cognitive Emotion Regulation Questionnaire, Self-Rating Anxiety Scale and Pittsburgh Sleep Quality Index.SPSS 22.0 version and Bootstrap method were used to analysis data and test intermediate effect. Results: (1)The total score of mindfulness trait and the score of describe, act with awareness and non-judge factors in mindfulness traits were(118.44±9.38), (24.82±3.87), (27.41±5.53) and (25.07±4.60), respectively.The total score of sleep quality was (5.57±2.62), and it was negatively related to the above three factors (r=-0.13--0.37, all P<0.05). (2)Anxiety played a complete mediating role between describe factor and sleep quality.Negative cognitive emotion regulation and anxiety played multiple mediating roles between the total score of mindfulness trait, the act with awareness factor and sleep quality.Negative cognitive emotion regulation and anxiety played a complete chain mediated role between non-judge factor and sleep quality. Conclusion The describe, act with awareness and non-judge factors in mindfulness traits can affect sleep quality through mediation of negative cognitive emotion regulation and / or anxiety.