ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

Objective:To investigate the expression levels and clinical significance of serum microRNA (miR) -155 and miR-135b-5p in patients with peptic ulcer complicated with Helicobacter pylori ( Hp) infection. Methods:A prospective study was conducted, and 263 patients with peptic ulcer were selected consecutively from July 2021 to February 2023 at the Affiliated Hospital of Jining Medical College. Among them, 146 cases were confirmed as Hp infection ( Hp infection group) and 117 cases were not complicated with Hp infection (non Hp infection group) by 14C breath test; type Ⅰ Hp infection was in 110 cases, and type Ⅱ Hp infection was in 36 cases by immunoblotting method. The serum expression levels of miR-155 and miR-135b-5p were detected by real-time fluorescence quantitative polymerase chain reaction, serum gastrin level was detected by radioimmunoassay method, and the serum pepsinogen (PG) Ⅰ and PG Ⅱ were detected by enzyme linked immunosorbent assay. The clinical data were recorded. Multivariate Logistic regression analysis was used to analyze the independent risk factors of Hp infection in patients with peptic ulcer; receiver operating characteristic (ROC) curve was used to analyze the efficacy of serum miR-155 and miR-135b-5p in diagnosis the Hp infection in patients with peptic ulcer. Results:The gastrin, PG Ⅰ, PG Ⅱ, ulcer bleeding rate and recurrence rate in Hp infection group were significantly higher than those in non Hp infection group: (108.47 ± 15.35) ng/L vs. (79.63 ± 10.58) ng/L, (295.41 ± 37.26) pg/L vs. (236.75 ± 29.17) pg/L, (44.08 ± 8.52) pg/L vs. (39.29 ± 6.74) pg/L, 25.34% (37/146) vs. 15.38% (18/117) and 21.92% (32/146) vs. 11.97% (14/117), and there were statistical differences ( P<0.01 or <0.05). The serum miR-155 and miR-135b-5p in Hp infection group were significantly higher than those in non Hp infection group (1.94 ± 0.63 vs. 0.95 ± 0.29 and 1.86 ± 0.57 vs. 1.03 ± 0.31), and there were statistical differences ( P<0.01). The serum miR-155 and miR-135b-5p in patients with typeⅠ Hp infection were significantly higher than those in patients with type Ⅱ Hp infection (2.05 ± 0.66 vs. 1.60 ± 0.54 and 1.97 ± 0.61 vs. 1.52 ± 0.45), and there were statistical differences ( P<0.01). Multivariate Logistic regression analysis result showed that serum miR-155, miR-135b-5p, gastrin and PG Ⅰwere independent risk factors of Hp infection in patients with peptic ulcer ( OR = 1.443, 1.436, 1.452 and 1.438; 95% CI 1.165 to 1.787, 1.146 to 1.799, 1.187 to 1.777 and 1.150 to 1.798; P<0.01). ROC curve analysis result showed that the area under the curve of serum miR-155 combined with miR-135b-5p in the diagnosis of Hp infection in patients with peptic ulcer was significantly greater than that of serum miR-155 and miR-135b-5p alone (0.907 vs. 0.839 and 0.836, Z = 2.57 and 2.81, P = 0.010 and 0.005). Conclusions:The serum levels of miR-155 and miR-135b-5p are high in patients with peptic ulcer complicated with Hp infection, and the combination of the two has high diagnostic value for Hp infection in patients with peptic ulcer.

Exposure to ionizing radiation intervenes in genomic stability and gene expression,resulting in the disruption of normal metabolic processes in cells and organs by causing complex biolog-ical responses.Altered genomic variations,gene expression and metabolite concentrations in blood or tissue samples reflect systemic radiation damage.With the application of new techniques and exten-sive study on the mechanisms for ionizing radiation damage,related indicators such as chromosomal variation,gene expression,lipid and metabolism are being recognized and promise to be the markers for early diagnosis and prognosis of radiation exposure.Therefore,this article reviews recent progress in and potential applications of biomarkers related to ionizing radiation injury.

Objective:To construct a special training program for oncology nurses on immunotherapy, and to lay the foundation for the promotion of standardized care of immunotherapy.Methods:The first draft of the immunotherapy training program for oncology nurses was initially constructed through literature review and semi-structured interviews; the final draft of the immunotherapy training program for oncology nurses was determined by using the Delphi expert correspondence method from October to December, 2023.Results:Two rounds of expert correspondence were conducted, and the effective recovery rates of the questionnaires were 15/15, with the expert authority coefficients of 0.847 and 0.867, and Kendall harmony coefficients of 0.207 and 0.212, respectively (both P<0.01). The final established special training program for immunotherapy for oncology nurses included 3 primary indicators, 17 secondary indicators, and 58 tertiary indicators. Conclusions:The construction process of the special training program for oncology nurses′immunotherapy is rigorous and scientific, with obvious speciality characteristics, which can provide a feasible program for the training of oncology nurses′immunotherapy nursing.

Objective:To understand the status, evaluation methods and risk factors of economic toxicity in patients with head and neck cancer, in order to provide reference for the construction of follow-up intervention programs.Methods:This scoping review was conducted under the Joanna Briggs Institute in Australia guidelines. Relevant studies were searched in PubMed, Embase, Web of Science, Cochrane Library, Scopus, CINAHL, China National Knowledge Infrastructure, Wanfang Database, VIP Database and Chinese Biomedical Literature Database. Chinese and English literature was screened and summarized from inception to September 21, 2023.Results:A total of 14 articles were included, and the economic toxicity of patients with head and neck cancer was more serious.The evaluation methods were mainly divided into scale evaluation and database data calculation. The risk factors of economic toxicity in patients with head and neck cancer included three aspects: demographic factors such as young age, low education and low income; disease and treatment-related factors such as tumor location in larynx/hypopharynx, current/past use of tube feeding, advanced tumor/distant metastasis; social support factors such as insufficient social security, and so on.Conclusions:Future studies should pay more attention to economic toxicity in patients with head and neck cancer, standardize the selection of assessment tools to reduce heterogeneity, and develop individualized intervention measures for the risk factors of economic toxicity in patients with head and neck cancer, in order to reduce the occurrence of economic toxicity in patients with head and neck cancer.

Objective To provide a longitudinal evaluation tool based on the frequency of aggressive be-havior for the aggression assessment of schizophrenia patients.Methods The Life History of Aggression was translated and revised to form the Life History of Aggression-Chinese Version(LHA-CV)based on 369 patients diagnosed with schizophrenia in the Chengdu community and compulsory medical insti-tution.The reliability of LHA-CV was analyzed by means of split-half reliability,test-retest reliability and inter-evaluator consistency.The validity was analyzed by item analysis,construct validity and crite-rion validity.Results Item analysis found that LHA-CV had good homogeneity and discriminant validity.Exploratory factor analysis found that the Kaiser-Meyer-Olkin(KMO)test value was 0.80,and the Bartlett's sphericity test χ2=1203.46(P<0.05),and it revealed four factors including non-physical ag-gression,physical aggression,self-directed aggression and antisocial behavior/consequences.The factor loadings for all 11 items were greater than 0.40.Confirmatory factor analysis was performed on the factor model,Chi-square degree of freedom(χ2/df)was 3.61,root mean square error of approxima-tion(RMSEA)was 0.07,goodness-of-fit index(GFI)was 0.92,comparative fit index(CFI)was 0.90,incremental fit index(IFI)was 0.90,and the discriminant validity of each factor was good.The criterion validity test showed the total score of LHA-CV was positively correlated with the aggressive behavior level of MacArthur Community Violence Instrument,the total score of Buss-Perry Aggression Scale,and the score of Antisocial Personality Disorder Subscale of Personality Diagnostic Question-naire-4th Edition Plus(PDQ-4+_ASPD,P<0.05).The Cronbach's α coefficient of non-physical aggres-sion,physical aggression,self-directed aggression,antisocial behavior/consequences and LHA-CV total score were 0.82,0.73,0.74,0.56 and 0.79,respectively.The test-retest reliability,Spearman-Brown split-half reliability and intra-class correlation coefficient of LHA-CV total score were 0.82(P<0.05),0.66 and 0.99,respectively.Conclusion LHA-CV has good reliability and validity,and can be used as an evaluation tool for longitudinally assessing aggressive behavior in schizophrenia patients.

This study aimed to explore the relationship between comorbidity factors and in-hospital mortality related to factors in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) pneumonia. This study collected clinical data from 218 patients with CRKP pneumonia in Beijing hospital from November 2011 to December 2023, analyzed the number of comorbidities carried by CRKP pneumonia patients, comorbidity patterns, Charlson Comorbidity Index (CCI) scores, and comorbidity of underlying diseases, and explored the relationship between various indicators and comorbidity factors and in-hospital mortality in CRKP pneumonia patients. The Ward.D cluster analysis was performed on the comorbidities of patients and used to draw heatmaps. Using a multiple logistic regression model, a nomogram model was constructed to predict in-hospital mortality in patients with CRKP pneumonia. This study included 218 patients with CRKP pneumonia. The results showed that there were significant differences in the age ( P=0.003), comorbidities such as heart failure ( P<0.001), arrhythmia ( P=0.002), chronic liver disease ( P=0.003), chronic kidney disease ( P=0.002), CCI score ( P=0.007), total number of comorbidities ( P<0.001), and comorbidity patterns (respiratory/immune/psychiatric disease patterns and cardiovascular/tumor/metabolic disease patterns, P=0.003) between the survival and death groups of CRKP pneumonia patients. The multiple logistic regression showed that cardiovascular/tumor/metabolic disease patterns ( P=0.030), CCI score ( P=0.040), concomitant heart failure ( P=0.011), and concomitant arrhythmia ( P=0.025) were independent risk factors for in-hospital mortality in patients with CRKP pneumonia. The nomogram model for predicting the risk of in-hospital mortality in patients with CRKP pneumonia, constructed based on the identified risk factors, had an area under the ROC curve of 0.758. Both the ROC curve and validation curve indicated that the nomogram model had stable performance in predicting in-hospital mortality in patients with CRKP pneumonia. In summary, comorbidity factors are risk factors for predicting in-hospital mortality in patients with CRKP pneumonia, and the role of comorbidity factors in in-hospital mortality in patients with CRKP pneumonia should be taken seriously.

Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

Tropane alkaloids (TAs) are a class of anticholinergic drugs widely used in clinical practice and mainly extracted from plant, among which Atopa belladonna is the main commercial drug source. It is of great industrial value to obtain TAs in large quantities by plant metabolic engineering. In TAs pathway, cytochrome oxidase CYP82M3 catalyze the synthesis of tropinone and then tropinone reductase I (TRI) compete with TRII for tropinone to form tropine leading to the TAs synthesis (drainage). In this study, based on the "increasing flow and drainage" metabolic engineering strategy, two genes, namely HnCYP82M3 and DsTRI from Hyoscyamus niger and Datura stramonium, respectively, were overexpressed in the hair roots of A. belladonna, with a view to promote the TAs accumulation. The HnCYP82M3 gene was cloned from the root of H. niger, and it encoded amino acid with 91.7% sequence identity with AbCYP82M3 from A. belladonna. Overexpression of HnCYP82M3 alone did not affect the content of TAs in hair roots of A. belladonna, indicating that CYP82M3 was not a key enzyme in TAs biosynthesis. Simultaneous overexpression of HnCYP82M3 and DsTRI greatly promoted the accumulation of the three TAs, and the contents of hyoscyamine, anisodamine and scopolamine were 4.97 times, 2.83 times and 2.19 times that of the control, respectively, and the increase amplitude was greater than that of single overexpression of DsTRI. This study showed that the "increasing flow and drainage" strategy of enzyme genes co-expression at branch points was a promising metabolic engineering method to effectively improve the biosynthesis of TAs in A. belladonna, and laid a theoretical and technical foundation for the large-scale industrial acquisition of TAs.