The significance of inflammatory markers in prognosticating the effectiveness and safety of immunotherapy in conjunction with chemotherapy during the primary intervention of advanced non-small cell lung carcinoma.

OBJECTIVE: The aim of this study is to scrutinize the prognostic significance of inflammatory biomarkers concerning the effectiveness and safety of combining PD-1 inhibition with chemotherapy in the management of advanced NSCLC. METHODS: We conducted a retrospective analysis involving 206 NSCLC patients who received treatment at Qingdao Municipal Hospital. The study encompassed the acquisition of baseline clinical attributes and hematological parameters of these patients. The optimal threshold values for PLT and NLR were ascertained based on pre-treatment evaluations, with a particular focus on their association with PFS. Variables linked to PFS were subject to scrutiny through Kaplan-Meier analysis and logistic regression. The Receiver Operating Characteristic (ROC) curve served as the means to determine the ideal cut-off values for categorizing levels of inflammatory markers into high and low classifications. We employed Chi-square tests to evaluate the relationship between elevated and reduced baseline levels of inflammatory markers and irAE. RESULTS: Kaplan-Meier analysis disclosed that patients in the low baseline PLT group and the low NLR group exhibited a substantially more favorable prognosis in contrast to their counterparts in the high baseline PLT and high NLR groups. Multivariate analysis indicated that diminished baseline PLT and NLR levels before treatment independently foretell extended PFS. Chi-square analysis underscored a substantial correlation between baseline WBC, NEUT, LYMPH, MONO, and NLR levels and irAE. CONCLUSION: Subdued baseline PLT and NLR levels may serve as indicators of a more auspicious prognosis in patients contending with advanced NSCLC undergoing the combination of PD-1 inhibition and chemotherapy. Elevated baseline levels of inflammatory markers antedating PD-1 therapy in advanced NSCLC may be intimately interrelated with the occurrence of irAE.

Indole alkaloids isolated from the Nicotiana tabacum-derived Aspergillus fumigatus 0338 as potential inhibitors for tobacco powdery mildew and their mode of actions.

To explore active natural products against tobacco powdery mildew caused by Golovinomyces cichoracearum, an extract from the fermentation of endophytic Aspergillus fumigatus 0338 was investigated. The mechanisms of action for active compounds were also studied in detail. As a result, 14 indole alkaloid derivatives were isolated, with seven being newly discovered (1-7) and the remaining seven previously described (8-14). Notably, compounds 1-3 are rare linearly fused 6/6/5 tricyclic prenylated indole alkaloids, with asperversiamide J being the only known natural product of this kind. The isopentenyl substitutions at the 5-position in compounds 4 and 5 are also rare, with only compounds 1-(5-prenyl-1H-indol-3-yl)-propan-2-one (8) and 1-(6-methoxy-5-prenyl-1H-indol3-yl)-propan-2-one currently available. In addition, compounds 6 and 7 are new framework indole alkaloid derivatives bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. The purified compounds were evaluated for their activity against G. cichoracearum, and the results revealed that compounds 7 and 9 demonstrated obvious anti-G. cichoracearum activities with an inhibition rate of 82.6% and 85.2%, respectively, at a concentration of 250 µg/mL, these rates were better than that of the positive control agent, carbendazim (78.6%). The protective and curative effects of compounds 7 and 9 were also better than that of positive control, at the same concentration. Moreover, the mechanistic study showed that treatment with compound 9 significantly increased the structural tightness of tobacco leaves and directly affect the conidiospores of G. cichoracearum, thereby enhancing resistance. Compounds 7 and 9 could also induce systemic acquired resistance (SAR), directly regulating the expression of defense enzymes, defense genes, and plant semaphorins, which may further contribute to increased plant resistance. Based on the activity experiments and molecular dockings, the indole core structure may be the foundation of these compounds' anti-G. cichoracearum activity. Among them, the indole derivative parent structures of compounds 6, 7, and 9 exhibit strong effects. Moreover, the methoxy substitution in compound 7 can enhance their activity. By isolating and structurally identifying the above indole alkaloids, new candidates for anti-powdery mildew chemical screening were discovered, which could enhance the utilization of N. tabacum-derived fungi in pesticide development.

Predictive modeling for postoperative delirium in elderly patients with abdominal malignancies using synthetic minority oversampling technique.

BACKGROUND: Postoperative delirium, particularly prevalent in elderly patients after abdominal cancer surgery, presents significant challenges in clinical management. AIM: To develop a synthetic minority oversampling technique (SMOTE)-based model for predicting postoperative delirium in elderly abdominal cancer patients. METHODS: In this retrospective cohort study, we analyzed data from 611 elderly patients who underwent abdominal malignant tumor surgery at our hospital between September 2020 and October 2022. The incidence of postoperative delirium was recorded for 7 d post-surgery. Patients were divided into delirium and non-delirium groups based on the occurrence of postoperative delirium or not. A multivariate logistic regression model was used to identify risk factors and develop a predictive model for postoperative delirium. The SMOTE technique was applied to enhance the model by oversampling the delirium cases. The model's predictive accuracy was then validated. RESULTS: In our study involving 611 elderly patients with abdominal malignant tumors, multivariate logistic regression analysis identified significant risk factors for postoperative delirium. These included the Charlson comorbidity index, American Society of Anesthesiologists classification, history of cerebrovascular disease, surgical duration, perioperative blood transfusion, and postoperative pain score. The incidence rate of postoperative delirium in our study was 22.91%. The original predictive model (P1) exhibited an area under the receiver operating characteristic curve of 0.862. In comparison, the SMOTE-based logistic early warning model (P2), which utilized the SMOTE oversampling algorithm, showed a slightly lower but comparable area under the curve of 0.856, suggesting no significant difference in performance between the two predictive approaches. CONCLUSION: This study confirms that the SMOTE-enhanced predictive model for postoperative delirium in elderly abdominal tumor patients shows performance equivalent to that of traditional methods, effectively addressing data imbalance.

Interpretation of histiocytic/dendritic cell neoplasms and stromal-derived neoplasms of lymphoid tissues in the 5th edition of WHO classification of haematolymphoid tumors / 中华病理学杂志

The 5th edition of the World Health Organization classification of hematolymphoid tumors (WHO Blue Book) is soon to be published. Significant revisions have been made in the chapters on histiocytic/dendritic cell neoplasms and stroma-derived neoplasms of lymphoid tissues, leading to the reclassification and renaming of specific diseases. This article provides a concise interpretation and summary of these updates, highlighting the differences from the fourth edition. Pertinent changes from clinical pathological diagnosis to treatment and prognosis are explored, with an emphasis on recent advancements in molecular genetics. Newly introduced disease classifications are discussed, and the section on follicular dendritic cell sarcoma contributed by the author is detailed to assist readers in quickly understanding and assimilating the new classification standards.

Effect of salvianolic acid B on inflammatory responses of vascular smooth muscle cells in septic mice: role of circACTA2 / 中华麻醉学杂志

Objective:To evaluate the effect of Salvianolic acid B (Sal B) on the inflammatory responses of vascular smooth muscle cells (VSMCs) in septic mice and the role of circACTA2.Methods:In vivo experiment Eighty-one healthy male C57BL/6 mice, aged 6-8 weeks, were divided into 3 groups ( n=27 each) by a random number table method: sham operation group, sepsis group and Sal B group. Sepsis model was developed by cecal ligation and puncture. After sucessful preparation of the model, Sal B 7 mg/kg/d was intraperitoneally injected once a day for 2 consecutive days in Sal B group. Twenty mice in each group were randomly selected to measure systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and whole blood lactic acid (Lac) and to record the survival within 7 days after developing the model. Seven mice in each group were randomly selected at 48 h after developing the model, and the arterial vascular tissues were collected for determination of the expression of interleukin-1beta (IL-1β) (by immunofluorescence staining), expression of IL-1β, tumor necrosis factor-alpha (TNF-α) and IL-6 protein and mRNA (by Western blot and quantitative real-time polymerase chain reaction, respectively), and expression of circACTA2 (by quantitative real-time polymerase chain reaction). Cell experiment Mouse VSMCs were cultured and divided into 6 groups ( n=3 each) by a random number table method: control group (C group), lipopolysaccharide (LPS) group, Sal B group, si-circACTA2+ C group, si-circACTA2+ LPS group, and si-circACTA2+ Sal B group. The cells were incubated for 24 h with LPS (final concentration 1 μg/ml) in LPS group and with LPS (final concentration 1 μg/ml) and Sal B (final concentration 5 μmol/L) in Sal B group. VSMCs were transfected with si-circACTA2 only in si-circACTA2+ C group. At 24 h after transfection of si-circACTA2 into VSMCs, the cells were incubated with LPS (final concentration 1 μg/ml) in si-circACTA2+ LPS group and with LPS (final concentration 1 μg/ml) and Sal B (final concentration 5 μmol/L) for 24 h in si-circACTA2+ Sal B group. The expression of IL-1β, TNF-α and IL-6 protein and mRNA was detected using Western blot and quantitative real-time polymerase chain reaction, and the expression of circACTA2 was determined by the quantitative real-time polymerase chain reaction. Results:In vivo experiment Compared with sham operation group, SBP, DBP and MAP were significantly decreased, the concentrations of whole blood Lac were increased, 7-day survival rate was decreased, the expression of IL-1β, TNF-α and IL-6 protein and mRNA in arterial vascular tissues was up-regulated, circACTA2 expression was down-regulated ( P<0.05), and the fluorescence of IL-1β was enhanced in sepsis group. Compared with sepsis group, SBP, DBP and MAP were significantly increased, whole blood Lac concentrations were decreased, 7-day survival rate was increased, the expression of IL-1β, TNF-α and IL-6 protein and mRNA in arterial vascular tissues was down-regulated, the expression of circACTA2 was up-regulated ( P<0.05), and the fluorescence of IL-1β was weakened in Sal B group. Cell experiment Compared with group C, the expression of IL-1β, TNF-α and IL-6 protein and mRNA was significantly up-regulated, and the expression of circACTA2 was down-regulated in LPS group ( P<0.05). Compared with LPS group, the expression of IL-1β, TNF-α and IL-6 protein and mRNA was significantly down-regulated, and the expression of circACTA2 was up-regulated in Sal B group ( P<0.05). Compared with si-circACTA2+ C group, the expression of IL-1β, TNF-α and IL-6 protein and mRNA was significantly up-regulated in si-circACTA2+ LPS group ( P<0.05). There were no significant differences in the expression of IL-1β, TNF-α and IL-6 protein and mRNA between si-circACTA2+ LPS group and si-circACTA2+ Sal B group ( P>0.05). Conclusions:Sal B can reduce the inflammatory responses of VSMCs, and the mechanism may be related to promoting the expression of circACTA2 in septic mice.

Comprehensive analysis of prognosis of cuproptosis-related oxidative stress genes in multiple myeloma.

Introduction: Multiple myeloma (MM) is a highly heterogeneous hematologic malignancy. The patients' survival outcomes vary widely. Establishing a more accurate prognostic model is necessary to improve prognostic precision and guide clinical therapy. Methods: We developed an eight-gene model to assess the prognostic outcome of MM patients. Univariate Cox analysis, Least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression analyses were used to identify the significant genes and construct the model. Other independent databases were used to validate the model. Results: The results showed that the overall survival of patients in the high-risk group was signifificantly shorter compared with that of those in the low-risk group. The eight-gene model demonstrated high accuracy and reliability in predicting the prognosis of MM patients. Discussion: Our study provides a novel prognostic model for MM patients based on cuproptosis and oxidative stress. The eight-gene model can provide valid predictions for prognosis and guide personalized clinical treatment. Further studies are needed to validate the clinical utility of the model and explore potential therapeutic targets.

Correlation of elevated serum uric acid with coronary artery disease in Xinjiang, China: A retrospective case-control study.

Elevated serum uric acid (SUA) levels are associated with coronary artery disease (CAD). However, whether this association is independent of traditional cardiovascular risk factors remains controversial. Our study aimed to determine the concentration of SUA in the presence and severity of CAD in multi-ethnic patients in Xinjiang, China. For this study, 412 consecutive patients with percutaneous coronary intervention (PCI) and 845 individuals with normal coronary angiograms were included in the study. CAD severity was evaluated using the Gensini score index. The SUA concentrations and the levels of various cardiometabolic risk factors were investigated. We assessed the relationship between SUA levels and other cardiometabolic risk factors. Logistic regression was used to evaluate risk factors for PCI patients. SUA levels were significantly elevated in PCI patients compared to those in control subjects (P < .01). With increased UA levels, we found that the risk factors for CAD increased. SUA concentration had a significant positive relationship with total cholesterol (P < .01), triglycerides (P < .01), low-density lipoprotein cholesterol (P < .01), and creatinine (P < .01) in both sexes. In the PCI group, there was no significant correlation between UA levels. SUA levels are not an independent risk factor for CAD. It can be concluded that in Xinjiang, China, SUA is related to multiple risk factors for CAD, but not related to the severity of CAD.

Clonotypic analysis of immunoglobulin heavy chain sequences among 44 patients with Waldenström macroglobulinemia / 中华医学遗传学杂志

OBJECTIVE@#To analyze the correlation between the mutational status of immunoglobulin heavy chain variable (IGHV) gene with the prognosis of patients with Waldenström macroglobulinemia (WM).@*METHODS@#Immunoglobulin heavy chain gene (IGH) clonotypic sequence analysis was carried out to assess the mutational status of IGHV in the blood and/or bone marrow samples from 44 WM patients. The usage characteristics of IGHV-IGHD-IGHJ gene was explored.@*RESULTS@#The most common IGHV subgroup was IGHV3, which was similar to the data from the Institute of Hematology of Chinese Academy of Medical Science. IGHV3-23 (20.45% vs. 15.44%) and IGHV3-74 (11.36% vs. 7.35%) were the main fragments used, which was followed by IGHV4 gene family (15.91% vs. 24.26%). However, no significant correlation was found between the IGHV4 usage and the prognosis of the patients. Should 98% be taken as the cut-off value for the IGHV mutation status, only 5 patients had no IGHV variant, and there was no correlation with the prognosis. Based on the X-tile analysis, 92.6% was re-selected as the cut-off value for the IGHV variant status in such patients. LDH was increased in 26 patients (59.1%) without IGHV variant (P < 0.05), whilst progression-free survival (P < 0.05) and overall survival (P < 0.05) were significantly shorter compared with those with IGHV variants.@*CONCLUSION@#The usage characteristics of IGHV-IGHD-IGHJ in our patients was similar to reported by the Institute of Hematology of Chinese Academy of Medical Science, albeit that no correlation was found between the IGHV4 usage and the prognosis of the patients. Furthermore, 98% may not be appropriate for distinguishing the IGHV variant status in WM patients.

Analysis of the prevalence of dyslipidemia and correlative factors in Tajik population in Pamir Plateau of Xinjiang / 中华心血管病杂志

Objective: To investigate the prevalence of dyslipidemia and the level of blood lipids among Tajik people in Pamir Plateau, Xinjiang, and explore the related factors of dyslipidemia. Methods: It is a retrospective cross-sectional study. A multi-stage cluster random sampling survey was conducted among 5 635 Tajiks over 18 years old in Tashkorgan Tajik Autonomous County, Xinjiang Province from May to October 2021. Data were collected through questionnaire survey (general information, medical history, and personal history), physical examination (height, weight, waist, and blood pressure) and blood test (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density cholesterol (HDL-C)) to analyze the dyslipidemia and its risk factors among Tajiks. Results: The age of Tajik participants was (41.9±15.0) years, including 2 726 males (48.4%). The prevalence of borderline high TC, high LDL-C and high TG levels were 17.2%, 14.7% and 8.9%, respectively. The prevalence of high TC, high LDL-C, high TG and low HDL-C were 4.1%, 4.9%, 9.4% and 32.4%, respectively, and the prevalence of dyslipidemia was 37.0%. There is a positive correlation between male,higher education level, higher body mass index (BMI) value,waist circumference, living in town, smoking and dyslipidemia. Conclusions: The low prevalence of high TC, high LDL-C, high TG and high prevalence of low HDL-C was a major characteristic of Tajik people in Pamir Plateau of Xinjiang. The lower rates of overweight and obesity may be one of the reasons for the lower prevalence of dyslipidemia among Tajik.

Analysis of the prevalence of dyslipidemia and correlative factors in Tajik population in Pamir Plateau of Xinjiang / 中华心血管病杂志

Objective: To investigate the prevalence of dyslipidemia and the level of blood lipids among Tajik people in Pamir Plateau, Xinjiang, and explore the related factors of dyslipidemia. Methods: It is a retrospective cross-sectional study. A multi-stage cluster random sampling survey was conducted among 5 635 Tajiks over 18 years old in Tashkorgan Tajik Autonomous County, Xinjiang Province from May to October 2021. Data were collected through questionnaire survey (general information, medical history, and personal history), physical examination (height, weight, waist, and blood pressure) and blood test (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density cholesterol (HDL-C)) to analyze the dyslipidemia and its risk factors among Tajiks. Results: The age of Tajik participants was (41.9±15.0) years, including 2 726 males (48.4%). The prevalence of borderline high TC, high LDL-C and high TG levels were 17.2%, 14.7% and 8.9%, respectively. The prevalence of high TC, high LDL-C, high TG and low HDL-C were 4.1%, 4.9%, 9.4% and 32.4%, respectively, and the prevalence of dyslipidemia was 37.0%. There is a positive correlation between male,higher education level, higher body mass index (BMI) value,waist circumference, living in town, smoking and dyslipidemia. Conclusions: The low prevalence of high TC, high LDL-C, high TG and high prevalence of low HDL-C was a major characteristic of Tajik people in Pamir Plateau of Xinjiang. The lower rates of overweight and obesity may be one of the reasons for the lower prevalence of dyslipidemia among Tajik.

Isochromenes from the Nicotiana tabacum-derived endophytic fungus Aspergillus versicolor and their anti-tobacco mosaic virus activities.

Three new isochromenes, (5-methoxy-7-prenyl-1H-isochromen-3-yl)methanol (1), 3-(3-(hydroxymethyl)-5-methoxy-1H-isochromen-7-yl)propan-1-ol (2), and (5-methoxy-7-methyl-1H-isochromen-3-yl)methanol (3), along with three known analogues (4-6) were isolated from the fermentation products of a Nicotiana tabacum-derived endophytic fungus Aspergillus versicolor. Their structures were elucidated by spectroscopic methods, including extensive 1 D and 2 D NMR techniques. Compounds 1-3 and 6 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that compound 2 exhibited high anti-TMV activity with inhibition rate of 46.4%, and this rate is higher than that of positive control. Compounds 1, 3, and 6 also showed potential anti-TMV activity with inhibition rates of 28.6, 30.5, and 26.2%, respectively. The IC50 of compounds 1-3 and 6 were also tested, and showed IC50 values of 49.3, 22.4, 42.2, and 54.1 µM, respectively.

Efficacy of goal-directed analgesia/sedation for improvement in preoperative management of patients with aortic dissection / 中华麻醉学杂志

Objective:To evaluate the efficacy of goal-directed analgesia/sedation for improvement in the preoperative management of the patients with aortic dissection.Methods:One hundred and ten patients of either sex, aged≥18 yr, diagnosed with arterial dissection by aortic CTA in our hospital, were divided into 2 groups ( n=55 each) using a random number table method: conventional group and goal-directed analgesia/sedation group. Routine preoperative management was performed in both groups. Fentanyl 0.13 μg/min was intravenously infused, and the infusion rate of fentanyl was adjusted to maintain the numerical rating scale (NRS) score at 0-3 at rest in conventional group. Midazolam 0.02 mg·kg -1·h -1 and fentanyl 0.13 μg/min were intravenously infused, and the infusion rates of midazolam and fentanyl were adjusted to maintain Richmond agitation-sedation score at -2 to 0 and NRS score at rest 0-3 in goal-directed analgesia/sedation group. Nicardipine was intravenously injected and the administration rate was adjusted to maintain systolic blood pressure at 100-120 mmHg, and metoprolol was taken orally to maintain the heart rate 60-70 beats/min. The time to reach the target blood pressure and consumption of fentanyl and nicardipine within 24 h were recorded, and the occurrence of drug-related adverse reactions during analgesia and sedation and perioperative death were recorded. Results:Compared with conventional group, the time to reach the target blood pressure was significantly shortened, and the consumption of fentanyl and nicardipine within 24 h was decreased in goal-directed analgesia/sedation group ( P<0.05). No adverse reactions or perioperative death was observed in two groups. Conclusions:Goal-directed analgesia/sedation (Richmond Agitation-Sedation Scale score -2-0, NRS score at rest 0-3) is helpful in controlling blood pressure and heart rate, thus improving the quality of preoperative management of patients with aortic dissection.

Influence of surfactant on the permeability at different positions of a leaching column.

To solve the problems of poor permeability and low leaching rate in ore heap leaching, solid surface physical chemistry, seepage mechanics theory for porous media, CT scanning and SEM were used to carry out column leaching tests with a homemade segmented removable plexiglass column; the variation law for the permeability coefficients of each segment of the leaching column before and after leaching was analyzed. The experimental results showed that there was little difference in the permeability coefficient of ore at different heights before leaching. After leaching, the permeability coefficients were unevenly distributed along the column height, and the lowest value was located at the bottom of the leaching column. The addition of surfactant provided an obvious improvement in the permeability of the leaching column. The permeability coefficient at the bottom of the leaching column was 6% higher than that of the control group. At the same time, the addition of surfactant increased the leaching rate of ore by nearly 10%. A theoretical analysis showed that the surfactant improved the permeability of ore heaps mainly by preventing physical blockage by fine particles and inhibiting deposition of chemical products.

Sequence Type 5 (ST5) as a Possible Predictor of Bacterial Persistence in Adult Patients with Methicillin-Resistant Staphylococcus aureus Pneumonia Treated with Vancomycin.

Vancomycin remains the mainstay of treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. This study assessed risk factors for vancomycin failure in 63 patients with MRSA pneumonia through detailed clinical, microbiological, pharmacokinetic/pharmacodynamic, and genetic analyses of prospective multicenter studies conducted from February 2012 to July 2018. Therapeutic drug monitoring was performed during vancomycin treatment, and the 24-h area under the curve (AUC0-24) was calculated. All baseline strains were collected for MIC determination, heterogeneous vancomycin-intermediate S. aureus (hVISA) screening, and biofilm determination. Whole-genome sequencing was performed on the isolates to analyze their molecular typing and virulence and adhesion genes. Clinical signs and symptoms improved in 44 patients (44/63, 69.8%), with vancomycin daily dose (P = 0.045), peak concentration (P = 0.020), and sdrC (P = 0.047) being significant factors. Isolates were eradicated in 51 patients (51/63, 81.0%), with vancomycin daily dose (P = 0.009), cardiovascular disease (P = 0.043), sequence type 5 (ST5; P = 0.017), tst (P = 0.050), and sec gene (P = 0.044) associated with bacteriological failure. Although the AUC0-24/MIC was higher in the groups with bacterial eradication, the difference was not statistically significant (P = 0.108). Multivariate analysis showed that no variables were associated with clinical efficacy; ST5 was a risk factor for bacterial persistence (adjusted odds ratio, 4.449; 95% confidence interval, 1.103 to 17.943; P = 0.036). ST5 strains had higher frequencies of the hVISA phenotype, biofilm expression, and presence of some adhesion and virulence genes such as fnbB, tst, and sec than non-ST5 strains. Our study suggests that ST5 is a possible predictor of bacterial persistence in MRSA pneumonia treated with vancomycin. IMPORTANCE Few studies have simultaneously examined the influence of clinical characteristics of patients with pneumonia, the vancomycin pharmacokinetic/pharmacodynamic (PK/PD) index, and the phenotypic and genetic characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains. We assessed risk factors for vancomycin failure in patients with MRSA pneumonia by analyzing these influences in a prospective multicenter study. Sequence type 5 (ST5) was a possible predictor of bacterial persistence in adult patients with MRSA pneumonia (adjusted odds ratio, 4.449). We found that this may be related to ST5 strains having higher levels of vancomycin heterogeneous resistance, biofilms, and the presence of adhesion and virulence genes such as fnbB, tst, and sec.

Hormone replacement therapy is associated with reduced hepatocellular carcinoma risk and improved survival in postmenopausal women with hepatitis B: A nationwide long-term population-based cohort study.

Postmenopausal women with hepatitis B virus (HBV) infection are more likely to have accelerated liver fibrosis, eventually advancing to liver cirrhosis or hepatocellular carcinoma (HCC). The association between sex hormones and HBV-related HCC risk is unclear. We investigated whether hormone replacement therapy (HRT) is beneficial to postmenopausal women with HBV infection. This retrospective study selected the data of 44,465patients with HBV infection between January 2000 and December 2018 from Taiwan's National Health Insurance Research Database. After excluding patients with preexisting liver diseases, liver cirrhosis, or liver malignancies, we grouped the remaining 10,474 patients by whether they had undergone HRT for at least 3 months (n = 5,638) and whether they had not received HRT (n = 4,836). After propensity score matching, we assigned 3080 patients to an HRT cohort and matched them (1:1) with those in a non-HRT cohort. The incidence of HCC (P < 0.022) and all-cause mortality rate (P < 0.001) were lower in the HRT cohort than in the non-HRT cohort. The liver cirrhosis risk was not significantly higher in the HRT cohort (P = 0.355). HRT is associated with reduced HCC risk and improved survival outcomes but is unrelated to liver cirrhosis development in postmenopausal women.

Identification of in vitro angiotensin-converting enzyme and dipeptidyl peptidase IV inhibitory peptides from draft beer by virtual screening and molecular docking.

BACKGROUND: Hypertension and diabetes are two kinds of senile diseases which often occur simultaneously. The commonly used drugs in clinic may produce certain side effects. Food-derived polypeptide is a kind of polypeptide with great development potential, which has many functions of regulating human physiological function. Beer is rich in nutrition but there are few researches on bioactive peptides in beer. RESULTS: In this study, a rapid virtual screening method was established to obtain bioactive peptides from Tsingtao draft beer. The peptide sequence was analyzed by ultra-performance liquid chromatography-quadrupole-Orbitrap-tandem mass spectrometry (UPLC-Q-Orbitrap-MS2 ), and 50 peptides were identified. Eight peptides with potential biological activities were screened by using Peptide Ranker software and previous literature references. On the basis of absorption prediction, toxicity prediction, and molecular docking analysis, LNFDPNR and LPQQQAQFK were finally confirmed. The molecular docking results showed that two peptides could bind angiotensin-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV) tightly by hydrogen bonding and hydrophobic interaction. The in vitro activity evaluation results showed that two peptides had obvious ACE and DPP-IV inhibitory activity. CONCLUSION: This study established a method for rapidly screening bioactive peptides from Tsingtao draft beer, screened two ACE and DPP-IV inhibitory peptides in beer and analyzed their active action mechanism. This article may have great theoretical significance and practical value to further explore the health function of beer. © 2021 Society of Chemical Industry.

The silencing of FNDC1 inhibits the tumorigenesis of breast cancer cells via modulation of the PI3K/Akt signaling pathway.

Fibronectin type III domain­containing protein 1 (FNDC1) is a protein that contains a major component of the structural domain of fibronectin. Although many studies have indicated that FNDC1 serves vital roles in the development of various diseases, the role of FNDC1 in the progression of breast cancer (BC) remains elusive. The aim of the present study was to investigate the biological functions of FNDC1 in BC cells and the associated mechanisms. The expression levels of FNDC1 in BC tissues and normal breast tissues were analyzed using The Cancer Genome Atlas database (TCGA). Kaplan­Meier curves were mined from TCGA to examine the clinical prognostic significance of FNDC1 mRNA in patients with BC. The expression of FNDC1 was knocked down by transfection with shRNA in BC cells. Cell viability, colony formation ability, migration and invasion were assayed following the silencing of FNDC1 in BC cells. The expression of proteins was measured using a western blotting assay. The bioinformatic data indicated that the FNDC1 mRNA expression levels were significantly upregulated in BC tissues compared with normal breast tissues, and the high mRNA expression levels of FNDC1 were associated with a lower overall survival in patients with BC. The downregulation of FNDC1 inhibited the proliferation, colony formation, migration and invasion of BC cells. Investigation of the mechanisms revealed that the silencing of FNDC1 decreased the protein expression levels of MMPs and epithelial­to­mesenchymal markers. Furthermore, the silencing of FNDC1 led to the inactivation of the PI3K/Akt signaling pathway. FNDC1 was highly upregulated and acted as an oncogene in BC. Therefore, targeting FNDC1 may be a potential strategy for the treatment of BC.

Automatic Framework Acquisition and Visualization Analysis of Ancient Chinese Medicine Literature Relating to Tumor / 中国实验方剂学杂志

Objective:To obtain ancient traditional Chinese medicine（TCM）literatures relating to tumor and visual analysis by an automatic framework tool， in order to systematically sort out the development of ancient Chinese medicine oncology. Method:Based on the database platform of ancient TCM books，names of tumor-related diseases in ancient TCM books were retrieved by Selenium WebDriver， an automation framework tool under Python 3.8. Lxml's etree library was used to parse the data. Statistics was made for "classification"， "authors"， "completion time" and "summary" of relevant ancient books automatically. After the data was checked and processed， Tableau 2019.2 software was used for data visualization analysis. And ancient Chinese medicine literatures relating to tumor were consulted at the database manually，with the dynasties as the clue，and the symptoms，etiology，pathogenesis and prognosis as the emphasis，this paper explores the development process of TCM oncology. Result:A total of 774 349 bytes of text data of 1 128 entries in 242 ancient books were included automatically. According to the findings， there were simple classification and time distribution of tumor diseases in ancient TCM books in the pre-Qin period， with a simple view on the pathogenesis of tumor diseases. From the Han dynasty to the Tang dynasty， the number of relevant literature records and the types and disease names had gradually increased，which further enriched the cognition of tumor nature，signs，classification methods，differential diagnosis；in Song and Ming dynasties，the proportion of Chinese prescription books and surgery books had increased gradually，with the largest number of abdominal organ tumor names among all dynasties；from Qing dynasty to the Republic of China，literatures relating to tumor name and classification were the most improved，and then the TCM tumor syndrome differentiation and treatment system had been formed. Conclusion:It was found that TCM oncology originated in the pre-Qin dynasty，and was improved in the Han and Tang dynasties， mature in the Song and Ming dynasties and completed in the Qing dynasty and the Republic of China. The data visualization method with integrated automation framework and parsing tools is helpful to analyze the subdivision characteristics of ancient TCM literatures，which is convenient，efficient and innovative，in the expectation to provide a classic reference for contemporary TCM studies.

Preimplantation Genetic Diagnosis of α/β Complex Thalassemia by Next Generation Sequencing / 中国实验血液学杂志

OBJECTIVE@#To explore the application value of next generation sequencing (NGS) in preimplantation genetic diagnosis of α/β complex thalassemia couple.@*METHODS@#The coding regions of α-globin genes (HBA1, HBA2) and β-globin gene (HBB) were selected as the target regions. The high-density and closely linked single nucleotide polymorphism (SNP) sites were selected as the genetic linkage markers in the upstream and downstream 2M regions of the gene. After NGS, the effective SNP sites were selected to construct the haplotype of the couple, and the risk chromosome of the mutation carried by the couple was determined. The NGS technology was used to sequence the variations of HBA1, HBA2 and HBB directly and construct haplotype linkage analysis for preimplantation genetic diagnosis.@*RESULTS@#Direct sequencing and haplotype linkage analysis of HBA1, HBA2 and HBB showed that two of the six blastocysts were α/β complex thalassemia, one was β-thalassemia heterozygote, two were α-thalassemias heterozygotes, and one was intermediate α-thalassemia. A well-developed embryo underwent preimplantation genetic diagnosis was implanted into the mother's uterus, and a healthy infant was born at term.@*CONCLUSION@#Preimplantation genetic diagnosis can be carried out by NGS technology in α/β complex thalassemia couples, and abortion caused by aneuploid embryo selection can be avoided.

Advances in the microbial synthesis of aromatic fragrance molecules / 生物工程学报

Aromatic compounds make up a large part of fragrances and are traditionally produced by chemical synthesis and direct extraction from plants. Chemical synthesis depends on petroleum resources and has disadvantages such as causing environment pollutions and harsh reaction conditions. Due to the low content of aromatic compounds in plants and the low yield of direct extraction, plant extractions require large amounts of plant resources that occupy arable land. In recent years, with the development of metabolic engineering and synthetic biology, microbial synthesis of aromatic compounds from renewable resources has become a promising alternative approach to traditional methods. This review describes the research progress on the synthesis of aromatic fragrances by model microorganisms such as Escherichia coli or yeast, including the synthesis of vanillin through shikimic acid pathway and the synthesis of raspberry ketone through polyketide pathway. Moreover, this review highlights the elucidation of native biosynthesis pathways, the construction of synthetic pathways and metabolic regulation for the production of aromatic fragrances by microbial fermentation.