Correlates of stigma for patients with breast cancer: a systematic review and meta-analysis.

OBJECTIVE: This study was conducted to examine the factors associated with stigma in breast cancer women. METHODS: PubMed, Embase, the Cochrane Library, Web of Science, and two Chinese electronic databases were electronically searched to identify eligible studies that reported the correlates of stigma for patients with breast cancer from inception to July 2022. Two researchers independently performed literature screening, data extraction, and risk of bias assessment. R4.1.1 software was used for statistical analysis. RESULTS: Twenty articles including 4161 patients were included in the systematic review and meta-analysis. Results showed that breast cancer stigma was positively correlated with working status, type of surgery, resignation coping, depression, ambivalence over emotional expression, and delayed help-seeking behavior and negatively correlated with age, education, income, quality of life, social support, confrontation coping, psychological adaptation, self-efficacy, and self-esteem. Descriptive analysis showed that breast cancer stigma was positively correlated with intrusive thoughts, body image, anxiety, and self-perceived burden but negatively correlated with a sense of coherence, personal acceptance of the disease, sleep quality, cancer screening attendance and doctor's empathy. CONCLUSION: Many demographic, disease-related, and psychosocial variables are related to breast cancer stigma. Our view can serve as a basis for health care professionals to develop health promotion and prevention strategies for patients with breast cancer.

Protective Effects of Luteolin on Lipopolysaccharide-Induced Acute Renal Injury in Mice.

BACKGROUND Sepsis can cause serious acute kidney injury in bacterium-infected patients, especially in intensive care patients. Luteolin, a bioactive flavonoid, has renal protection and anti-inflammatory effects. This study aimed to investigate the effect and underlying mechanism of luteolin in attenuating lipopolysaccharide (LPS)-induced renal injury. MATERIAL AND METHODS ICR mice were treated with LPS (25 mg/kg) with or without luteolin pre-treatment (40 mg/kg for three days). The renal function, histological changes, degree of oxidative stress, and tubular apoptosis in these mice were examined. The effects of luteolin on LPS-induced expression of renal tumor necrosis factor-α (TNF-α), NF-κB, MCP-1, ICAM-1, and cleaved caspase-3 were evaluated. RESULTS LPS resulted in rapid renal damage of mice, increased level of blood urea nitrogen (BUN), and serum creatinine (Scr), tubular necrosis, and increased oxidative stress, whereas luteolin pre-treatment could attenuate this renal damage and improve the renal functions significantly. Treatment with LPS increased TNF-α, NF-κB, IL-1ß, cleaved caspase-3, MCP-1, and ICAM-1 expression, while these disturbed expressions were reversed by luteolin pre-treatment. CONCLUSIONS These results indicate that luteolin ameliorates LPS-mediated nephrotoxicity via improving renal oxidant status, decreasing NF-κB activation and inflammatory and apoptosis factors, and then disturbing the expression of apoptosis-related proteins.

[Chemical studieson hydrophilic constituents of toad skin].

Fifteen compounds were isolated from the toad skin by a combination of various chromatographic methods including macroporous resin, silica gel, ODS and semi-preparative HPLC. Their structures were identified as 4,5-dimethyl-1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-6-ol(1), serotonin(2), N-methyl serotonin(3), O-methyl bufotenine(4), 1,2,3,4-tetrahydro-6-hydroxy-ß-carboline(5), O-methylserotonin(6), glycinebetaine(7), caffeine(8), bufotenine(9), shepherdine(10), tryptophan(11), (5-hydroxy-1H-indol-3-yl)acetic acid(12), 5-hydroxy tryptophol(13), 2-methyl-6-hydroxy-1,2,3,4-tetrahydro-ß-carboline(14), bufothionine(15). Among them, compound 1 was a new compound,compound 5 was a new natural product. Compounds 4-8 and 10-14 were separated from toad skin for the first time.

Comparative metabolism of four limonoids in human liver microsomes using ultra-high-performance liquid chromatography coupled with high-resolution LTQ-Orbitrap mass spectrometry.

RATIONALE: Limonoids, characterized by a triterpenoid skeleton with a furan ring, are unique secondary metabolites widely distributed in the families of Rutaceae, particularly in Citrus species and Meliaceae. Studies on health benefits have demonstrated that limonoids have a range of biological activities. Dietary intake of citrus limonoids may provide a protective effect against the onset of various cancers and other xenobiotic related diseases. However, few studies about the metabolic profiles of limonoids have been carried out. METHODS: The objectives of this study were to investigate the metabolic profiles of four limonoids (limonin, obacunone, nominin and gedunin) in human liver microsomes (HLMs) using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC/HRMS) and to identify the cytochrome P450 (CYP) enzymes involved in the formation of their metabolites by recombinant human CYP enzymes. RESULTS: Based on the accurate HR-MS/MS spectra and the proposed MS/MS fragmentation pathways, four metabolites of limonin (M1-1, M1-2, M1-3 and M1-4), eight metabolites ofobacunone (M2-1, M2-2, M2-3, M2-4, M2-5, M2-6, M2-7 and M2-8), six metabolites of nominin (M3-1, M3-2, M3-3, M3-4, M3-5 and M3-6) and three metabolites of gedunin (M4-1, M4-2 and M4-3) in HLMs were tentatively identified and the involved CYPs were investigated. CONCLUSIONS: The results demonstrated that reduction at C-7 and C-16, hydroxylation and reaction of glycine with reduction limonoids were the major metabolic pathways of limonoids in HLMs. Among them, glycination with reduction was the unique metabolic process of limonoids observed for the first time. CYP2D6 and CYP3A4 played an important role in the isomerization and glycination of limonoids in HLMs, whereas other CYP isoforms were considerably less active. The results might help to understand the metabolic process of limonoids in vitro such as the unidentified metabolites of limonin glucoside observed in the medium of microbes and the biotransformation of limonin in juices. Moreover, it would be beneficial for us to further study the pharmacokinetic behavior of limonoids in vivo systematically.

Characteristics analysis of hepatitis B core-related antigen in children with hepatitis B e antigen-positive chronic viral hepatitis B infection.

BACKGROUND: The objective of antiviral therapy for chronic viral hepatitis B infection (CHB) is to achieve a functional cure. An important viral marker in the serum of patients with CHB is the serum hepatitis B core-related antigen (HBcrAg). However, there is limited research on HBcrAg in juvenile patients with CHB. In this study, we aimed to investigate the correlation between serum HBcrAg and other hepatitis B virus (HBV) markers in children with CHB and its predictive significance for prognosis during antiviral therapy. METHODS: A single-center retrospective study was conducted involving 79 children with CHB, aged between 0 and 16 years. All the children were treated with interferon [or combined nucleos(t)ide analogs] for 48 weeks. HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA were measured before treatment, and at 12 and 48 weeks after treatment. The enrolled children were classified into the seroclearance group and the nonseroclearance group based on the therapeutic outcome. RESULTS: HBsAg seroclearance was observed in 28 out of 79 patients and hepatitis B e antigen seroconversion without HBsAg seroclearance was observed in 14 out of 79 patients following the conclusion of the treatment, with baseline HBcrAg titer levels showing no statistical significance in both the seroclearance and nonseroclearance groups ( P  = 0.277). HBsAg and HBV DNA were positively correlated with HBcrAg in children with CHB ( R2  = 0.3289, 0.4388). The area under the receiver operating characteristic curve of the decrease in HBcrAg at 12 weeks of treatment as a predictor of seroclearance at 48 weeks of treatment, exhibited a value of 0.77. CONCLUSION: A decrease in serum HBcrAg levels in children with hepatitis B serves as a prognostic indicator.

[Relation between serum levels of high mobility group box 1 and hepatitis B virus-related acute-on-chronic liver failure].

OBJECTIVE: To evaluate the levels of high mobility group box 1 protein (HMGB1) in serum of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) and investigate its potential relation to the clinical features of these patients. METHODS: Sixty patients with HBV-related ACLF, 30 patients with chronic hepatitis B (CHB), and 24 healthy individuals (controls) were enrolled in the study. Markers of liver function, such as aspartate aminotransferase (AST), were measured by routine biochemical methods. Imaging studies, such as abdominal computed tomography or magnetic resonance imaging, were used for disease staging. Serum levels of HMGB1 were measured by ELISA. Deaths within the 2-month follow-up after serum collection were used for the survival analysis. Patients who developed peritonitis, pneumonia, or other bacterial and fungal infections during the 2-month follow-up after serum collection were classified as the infected group. Pairwise comparisons were carried out by t-test, and multiple comparisons were carried out by analysis of variance. RESULTS: Patients with HBV-related ACLF had significantly higher serum levels of HMGB1 than CHB patients or controls (P = 0.003). Among the patients with HBV-related ACLF, those in the late stage (n = 20) had significantly higher levels of HMGB1 than those in the early stage (n = 20) (P = 0.005). The serum levels of HMGB1 correlated well with AST level in patients with HBV-related ACLF (P = 0.006). In addition, patients with HBV-related ACLF who developed infection or died during follow-up also had significantly higher levels of HMGB1 (P = 0.028 or P = 0.017, respectively). CONCLUSION: Enhanced serum level of HMGB1 is associated with development of HBV-related ACLF in CHB patients. The strong correlation between HMGB1 and AST levels suggest that HMGB1 may be useful as a prognostic marker for development of ACLF.

[Orthogonal design based optimization of a mouse model of acute liver failure induced by D-galactosamine and lipopolysaccharide].

OBJECTIVE: To apply an orthogonal design optimization strategy to a mouse model of acute liver failure induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS) exposure. METHODS: A four-level orthogonal array design (L16(45)) was constructed to test factors with potential impact on successful establishment of the model (D-GalN and LPS dosages, and dilution rate of the D-GalN/LPS mixture). The mortality rate of mice within 24 hours of D-GalN/LPS administration was determined by the Kaplan-Meier method. The model outcome was verified by changes in serum alanine transferase level, liver histology, and hepatocyte apoptosis. RESULTS: The orthogonal array identified the optimal model technique as intraperitoneal injection of a combination of D-GalN and LPS at dosages of 350 mg/kg and 30 mug/kg, respectively, and using a dilution rate of 3. The dosages tested had no effect on survival. The typical signs of liver failure appeared at 6 hrs after administration of the D-GalN/LPS combination. CONCLUSION: The orthogonal design optimization strategy provided a procedure for establishing a mouse model of acute liver failure induced by D-GalN and LPS that showed appropriate disease outcome and survival, and which will serve to improve future experimental research of acute liver failure.

[Clinical and pathological analysis of 566 patients with cryptogenic liver diseases].

OBJECTIVE: To investigate the etiology, pathology, and clinical characteristics of cryptogenic liver diseases in order to develop a pathogenic profile for clinical diagnosis and therapeutic design. METHODS: The data of the 566 patients diagnosed with abnormal liver function and who had undergone liver biopsy at our institute between January 2006 to March 2010 were retrospectively analyzed. The Chi-squared (x²) test was used to assess disease correlation with sex and the rank sum test was used to assess disease correlation with continuous data since all data had asymmetric distribution. RESULTS: Among the 566 patients, abnormal liver function was attributed to alcoholic liver disease (n=175; 30.92%), drug-induced or environmentally-induced liver disease (n=101; 17.84%), hereditary and metabolic disease (n=93; 16.43%), infectious hepatitis disease (n=84; 14.84%), fatty liver disease (n=53; 9.36%), and autoimmune liver disease (n=30; 53.00%). Thirty patients had unknown etiology, despite liver biopsy analysis. Among these disease subgroups, there were distinct correlations with sex, age, and levels of alanine transaminase (ALT) and gamma-glutamyltransferase (GGT). The autoimmune liver disease group was correlated with sex (q=9.14, 7.435, 5.071, 9.529, and 12.5, respectively; P less than or equal to 0.01). The alcoholic liver disease group and autoimmune liver disease group were correlated with age (vs. genetic metabolic disease group: q=17.254 and 10.302; infectious hepatitis group: q=17.523 and 10.697); drug/environmentally-induced liver damage group: q=9.170 and 5.266); fatty liver group: q=7.118 and 4.661) (P less than or equal to 0.01). In addition, the alcoholic and autoimmune liver disease groups were correlated with GGT levels (vs. genetic metabolic disease group: q=8.003; infectious hepatitis group: q=4.793; drug/environmentally-induced liver damage group: q=4.404) (P less than or equal to 0.01). CONCLUSION: Liver pathology is important for the diagnosis of cryptogenic liver diseases. Patient age, sex, and biochemistry index may facilitate diagnosis and treatment in the absence of pathology.

Non-clinical pharmacology and toxicology studies of bevacizumab biosimilar LY01008.

LY01008 was a biosimilar of Avastin® developed by Shandong Boan Biotechnology. To support the clinical trial and marketing application of LY01008 as a biosimilar, a series of non-clinical pharmacodynamics (PD), pharmacokinetics (PK), and toxicological studies have been conducted. The PD study results showed that LY01008 had similar pharmacodynamic effects with Avastin in VEGF (vascular endothelial growth factor) binding activity, inhibitory effect on angiogenesis and vascular permeability, and anti-tumor activities in nude mouse models alone or combined with chemotherapeutic agents. PK study showed that LY01008 had similar PK parameters with Avastin at the same doses, and the relative bioavailability of LY01008 was 111.4%. The maximum tolerated dose of LY01008 in the single-dose toxicity study of cynomolgus monkeys was greater than 258 mg/kg. LY01008 had no effects on central nervous system, cardiovascular system and respiratory system in cynomolgus monkeys. LY01008 had no hemolytic effect in vitro and no local irritation in cynomolgus monkeys. The immunogenicity of LY01008 was no higher than that of Avastin in cynomolgus monkeys. In the one-month multiple-dose toxicity study in cynomolgus monkeys, the toxicokinetics profiles of LY01008 was similar with Avastin, the characteristics of the toxic reactions were the same and the extent was similar between LY01008 and Avastin, and no new toxic reactions were observed on LY01008. In conclusion, LY01008 had a good safety profile, and was biosimilar with Avastin in the comparative studies of pharmacodynamics, pharmacokinetics, toxicokinetics and toxicology, which supported the clinical trial and marketing application of LY01008 as a biosimilar of Avastin.

The Disassociation of the A20/HSP90 Complex via Downregulation of HSP90 Restores the Effect of A20 Enhancing the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents.

NF-κB (nuclear factor κB) is a regulator of hepatocellular cancer (HCC)-related inflammation and enhances HCC cells' resistance to antitumor therapies by promoting cell survival and anti-apoptosis processes. In the present work, we demonstrate that A20, a dominant-negative regulator of NF-κB, forms a complex with HSP90 (heat-shock protein 90) and causes the disassociation of the A20/HSP90 complex via downregulation of HSP90. This process restores the antitumor activation of A20. In clinical specimens, the expression level of A20 did not relate with the outcome in patients receiving sorafenib; however, high levels of HSP90 were associated with poor outcomes in these patients. A20 interacted with and formed complexes with HSP90. Knockdown of HSP90 and treatment with an HSP90 inhibitor disassociated the A20/HSP90 complex. Overexpression of A20 alone did not affect HCC cells. Downregulation of HSP90 combined with A20 overexpression restored the effect of A20. Overexpression of A20 repressed the expression of pro-survival and anti-apoptosis-related factors and enhanced HCC cells' sensitivity to sorafenib. These results suggest that interactions with HSP90 could be potential mechanisms of A20 inactivation and disassociation of the A20/HSP90 complex and could serve as a novel strategy for HCC treatment.

Clinical Course and Outcome Patterns of Acute-on-chronic Liver Failure: A Multicenter Retrospective Cohort Study.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is acute decompensation of liver function in the setting of chronic liver disease, and characterized by high short-term mortality. In this study, we sought to investigate the clinical course of patients at specific time points, and to propose dynamic prognostic criteria. METHODS: We assessed the clinical course of 453 patients with ACLF during a 12-week follow-up period in this retrospective multicenter study. The clinical course of patients was defined as disease recovery, improvement, worsening or steady patterns based on the variation tendency in prothrombin activity (PTA) and total bilirubin (TB) at different time points. RESULTS: Resolution of PTA was observed in 231 patients (51%) at 12 weeks after the diagnosis of ACLF. Among the remaining patients, 66 (14.6%) showed improvement and 156 (34.4%) showed a steady or worsening course. In patients with resolved PTA, the clinical course of TB exhibited resolved pattern in 95.2%, improved in 3.9%, and steady or worse in 0.8%. Correspondingly, in patients with improved PTA, these values for TB were 28.8%, 27.3%, and 43.9%, respectively. In patients with steady or worsening PTA, these values for TB were 5.7%, 32.3%, and 65.6%, respectively. Dynamic prognostic criteria were developed by combining the clinical course of PTA/TB and the clinical outcomes at 4 and 12 weeks after diagnosis in ACLF patients. CONCLUSIONS: We propose the following dynamic prognostic criteria: rapid progression, slow progression, rapid recovery, slow recovery, and slow persistence, which lay the foundation for precise prediction of prognosis and the improvement of ACLF therapy.

[Estimation of liver inflammation and necrosis in patients with chronic hepatitis B through different biochemical items].

OBJECTIVES: To establish a new grading system to evaluate liver inflammation and necrosis in patients with chronic hepatitis B through clinical biochemical assays. METHODS: Clinical and pathological data were collected from 255 cases with chronic hepatitis B. 19 biochemical items were analyzed and 5 items were selected for our grading system. Each of the five items was scored 0 to 4 based on the different values. The extent of liver inflammation and necrosis was evaluated according to the total score. RESULTS: ALT, AST, ChE, GGT and TBA were selected for our grading system. The grade of liver inflammation and necrosis was considered less than 2.0 if total score lower than 6, and higher grade was considered with higher total score. The estimated results shared an identity of 82.8% with the real grades of liver inflammation and necrosis. When this grading system was applied to patients with liver inflammation and necrosis equal to or higher than grade 2.0, it exhibited a sensitivity of 83.8%, a specificity of 81.2%, a positive prediction value of 88.6%, a negative prediction value of 74.2% in all cases, and 88.0%, 84.7%, 90.6%, 82.4% respectively in patients older than 12 years. CONCLUSION: Our data suggest that the grading system can be used to evaluate the extent of liver inflammation and necrosis in patients with chronic hepatitis B.

Hepatitis B virus infection contributes to oxidative stress in a population exposed to aflatoxin B1 and high-risk for hepatocellular carcinoma.

Biomarkers of hepatitis B virus (HBV) infection, aflatoxin B1 (AFB1) exposure and oxidative stress were detected in 71 hepatocellular carcinoma (HCC) patients and 694 controls from southern China. Plasma level of AFB1-albumin-adducts (AAA) and protein carbonyl content (PCC) were significantly higher in the 71 HCC cases than in any age/gender matched HBV sero-status groups (p<0.001). HCC patients positive for the p53-249 G-T mutation had a marginally higher level of PCC than those negative for the mutation (p=0.077). HBV infection had a prominent influence on the association between AFB1 exposure and oxidative stress biomarkers in the controls. Our study indicates a significant contribution from HBV infection to oxidative stress in a population with AFB1 exposure which might substantially increase risk for HCC in this region.

Clinical and pathological analysis of 19 patients with superficial CD34-positive fibroblastic tumor / 中华皮肤科杂志

Objective:To investigate clinical, histopathological, molecular genetic characteristics, and immunophenotypes of superficial CD34-positive fibroblastic tumor (SCPFT) .Methods:The pathological data were collected from 19 cases of SCPFT from January 2015 to July 2022 in the First Affiliated Hospital of Nanjing Medical University, and analyzed retrospectively.Results:In total, 19 cases of SCPET were enrolled, including 8 males and 11 females. Their age at onset ranged from 16 to 67 years, and the disease duration ranged from 3 months to 3 years. Tumors occurred in the thigh (6 cases), back (4 cases), shoulder (3 cases), abdominal wall (2 cases), popliteal fossa (1 case), lower leg (1 case), foot (1 case) and forehead (1 case). The tumor lengths were 0.8 - 4 (2.36 ± 0.76) cm, with relatively clear borders. Surgical excision was performed in all the 19 cases, and 1 case experienced recurrence. Histopathological examination showed that tumors were located in the dermis and subcutis, and infiltrated the peripheral fat tissues or the dermis; tumors were composed of abundant spindle cells and polygonal cells arranged in interlacing fascicles; cells with nuclear pleomorphism were observed in all cases, and were characterized by large, hyperchromatic and irregular nuclei, intranuclear pseudoinclusions, and prominent nucleoli; the mitotic figure was rare, and tumor necrosis was not found; inflammatory cell infiltration to different extents was observed in the tumor stroma, and lymphocyte sheaths were observed around the tumors in 2 cases. Immunohistochemical staining showed strong diffuse expression of CD34 in the tumor cells in all the 19 cases, the Ki-67 proliferation index was < 10% in 18 cases, and CKpan (2/12), desmin (2/15), and smooth muscle actin (1/19) were focally expressed. Fluorescence in situ hybridization for the detection of PRDM10 gene rearrangements was performed in 3 cases, and identified PRDM10 rearrangements in 2 cases, including 1 case of SCPFT accompanied by lymphocyte sheaths without EWSR1 rearrangements. Conclusion:SCPFT is an intermediate fibroblastic tumor with no characteristic clinical manifestations, often accompanied by PRDM10 rearrangements, and its diagnosis depends on histopathological patterns.

Glycogen Phosphorylase Isoenzyme Bb, Myoglobin and BNP in ANT-Induced Cardiotoxicity.

Anthracyline (ANT) has been demonstrated as a useful treatment for leukemia and solid tumors. However, ANT has previously reported cardiotoxic effects, which can reduce the therapeutic index for cancer treatment. This study aimed to investigate the associations of glycogen phosphorylase isoenzyme BB (GPBB), myoglobin (Mb), and brain natriuretic peptide (BNP) with anthracycline (ANT-induced cardiotoxicity (AIC)) amongst the Chinese population. Patients suffering from leukemia were recruited. Electrocardiogram and echocardiography were used along with chemotherapy to determine left ventricular ejection fraction (LVEF), mitral ratio of peak early to late diastolic filling velocity (E/A), E-wave deceleration time (EDT), and isovolumic relaxation time (IVRT). Double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) was employed to examine and compare serum GPBB, Mb, and BNP levels. Following chemotherapy, the patients presented higher levels of serum GPBB, Mb, and BNP than before chemotherapy treatment. The levels of LVEF (%), E/A, and IVRT were significantly decreased after chemotherapy, while EDT was markedly increased. The cumulative ANT dose was positively corelated to serum GPBB, Mb, and BNP levels while it was negatively corelated to LVEF levels. In conclusion, serum GPBB, Mb, and BNP levels in combination might provide higher diagnostic accuracy in the early detection of AIC compared with other single indicators.

Mining and analysis of ADE signals of romiplostim and eltrombopag based on FAERS database / 中国药房

OBJECTIVE To provide a reference for the safe use of thrombopoietin receptor agonists romiplostim and eltrombopag in clinic. METHODS FDA adverse event reporting system （FAERS） in the United States was adopted to collect adverse drug event （ADE） reports of romiplostim and eltrombopag from their launch in the United States to September 30， 2022； the ADE signals of the two drugs were analyzed using the reporting odds ratio （ROR） method and the comprehensive standard method of the UK Medicines and Healthcare Products Regulatory Agency. RESULTS A total of 14 021 and 4 431 ADE reports were collected about romiplostim and eltrombopag， respectively， with a gender composition of more females than males. After signal screening， 563 ADE signals were obtained about romiplostim， involving 25 system organ classes （SOC）； eltrombopag had 433 ADE signals， involving 26 SOC. The most frequently reported ADE for both drugs was platelet count decreased （2 060， 1 585 cases）， which was mentioned in their drug instructions. In terms of signal intensity， romiplostim exhibited the highest signal for abnormal thrombopoietin levels （ROR of 2 268.85）， while eltrombopag had the highest signal for positive dengue virus test （ROR of 954.50）， with neither of these signals mentioned in their respective drug instructions. CONCLUSIONS The ADE of romiplostim and eltrombopag mainly affects the blood and lymphatic system， and there are many new suspicious high-risk signals.

Investigation and analysis of nursing prevention and control of ventilator-associated pneumonia in ICUs of 194 tertiary hospitals / 中华护理杂志

Objective To investigate the nursing clinical practice of ICU ventilator-associated pneumonia(VAP)prevention and control of tertiary hospitals in China,and analyze relevant countermeasures.Methods A self-designed questionnaire consisted of 3 parts and 26 items.A questionnaire survey was conducted among nurses in 380 ICUs in 194 tertiary hospitals in 26 provinces from September 1 to 15,2021,using the convenient sampling method.Results A total of 380 valid questionnaires were collected,with an effective rate of 100%.In the system process,369(97.11%)ICUs had files to prevent VAP;291(76.58%)ICUs had a checklist of measures to prevent VAP clustering;274(72.11%)ICUs had continuous improvement projects about VAP in the last 3 years.In the aspect of body position management,semi-decubitus position was the first choice for the patients with invasive mechanical ventilation of 338(88.95%)ICUs.For nursing operation,224(58.95%)ICUs used Subglottic suction,and 128(33.68%)among them used air shock to remove the retention on the balloon;normal saline is still routinely injected before sputum aspiration in 72(18.95%)ICUs.In terms of balloon pressure monitoring,253(66.58%)ICUs did the oral care 3-4 times a day.In the balloon pressure monitoring,313(82.37%)ICUs use airbag pressure gauges to intermittently monitor airbag pressure;293(77.11%)ICUs replaced the ventilator pipeline once a week.There are significant differences in the current practice status of different types of ICUs in terms of compliance strategies for bed head lifting,subglottic secretion drainage,airbag pressure monitoring,and oral care(P<0.05).Conclusion At present,the relevant systems and procedures to prevent VAP have been improved,but the specific prevention and control measures need to be further unified.Therefore,it is suggested to analyze the weak links of VAP nursing prevention and control practice in various medical structures,carry out relevant training and quality control for the weak links,and further improve the working mechanism of continuous quality improvement,thus effectively reduce the incidence of VAP.

High-throughput transcriptional profiling of perturbations by Panax ginseng saponins and Panax notoginseng saponins using TCM-seq / 药物分析学报

Panax ginseng(PG)and Panax notoginseng(PN)are highly valuable Chinese medicines(CM).Although both CMs have similar active constituents,their clinical applications are clearly different.Over the past decade,RNA sequencing(RNA-seq)analysis has been employed to investigate the molecular mechanisms of extracts or monomers.However,owing to the limited number of samples in standard RNA-seq,few studies have systematically compared the effects of PG and PN spanning multiple conditions at the transcriptomic level.Here,we developed an approach that simultaneously profiles transcriptome changes for multiplexed samples using RNA-seq(TCM-seq),a high-throughput,low-cost workflow to molecularly evaluate CM perturbations.A species-mixing experiment was conducted to illustrate the accuracy of sample multiplexing in TCM-seq.Transcriptomes from repeated samples were used to verify the robustness of TCM-seq.We then focused on the primary active components,Panax notoginseng sa-ponins(PNS)and Panax ginseng saponins(PGS)extracted from PN and PG,respectively.We also char-acterized the transcriptome changes of 10 cell lines,treated with four different doses of PNS and PGS,using TCM-seq to compare the differences in their perturbing effects on genes,functional pathways,gene modules,and molecular networks.The results of transcriptional data analysis showed that the tran-scriptional patterns of various cell lines were significantly distinct.PGS exhibited a stronger regulatory effect on genes involved in cardiovascular disease,whereas PNS resulted in a greater coagulation effect on vascular endothelial cells.This study proposes a paradigm to comprehensively explore the differences in mechanisms of action between CMs based on transcriptome readouts.

Evaluation of oxidative stress in a group of adolescents exposed to a high level of aflatoxin B1--a multi-center and multi-biomarker study.

The association between aflatoxin B1 (AFB1) exposure and oxidative stress was extensively examined in 84 adolescents from an area at high risk for hepatocellular carcinoma in China. Plasma level of aflatoxin B1-albumin adducts (AAAs) was associated with AFB1 excretion in urine (r = 0.394, P < 0.001). Urinary AFB1 was also associated with both the urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG) (r > or = 0.479, P < 0.001) and 8-OHdG and hOGG1 levels in peripheral leukocytes (r > or = 0.308, P < or = 0.005). Similarly, AAA was significantly associated with both the urinary excretion of 8-OHdG (r > or = 0.259, P < or = 0.018) and the 8-OHdG and hOGG1 levels in peripheral leukocytes (r > or = 0.313, P < or = 0.004). In addition, urinary 8-OHdG was correlated with both the level of DNA 8-OHdG (r > or = 0.24, P < or = 0.05) and the expression of hOGG1 in peripheral leukocytes (r > or = 0.429, P < 0.001). Protein carbonyl content (PCC) level was significantly associated with not only the level of DNA 8-OHdG (r > or = 0.366, P < 0.001) and the urinary 8-OHdG (r > or = 0.258, P < or = 0.018) but also the expression of hOGG1 in peripheral leukocytes (r = 0.485, P < 0.001). A significant but weak association was found between high-performance liquid chromatograph-electrochemical detection (HPLC-ECD) and enzyme-linked immunosorbent assay (ELISA) for urinary 8-OHdG (r = 0.334, P = 0.002) and between HPLC-ECD and flow cytometry assays for 8-OHdG in leucocytes (r = 0.395, P < 0.001). Significant associations were observed between AAA and PCC and liver function indices (alanine aminotransferase and aspartate aminotransferase). These findings suggest significant contribution from AFB1 exposure to oxidative stress and subsequent repair among adolescents that may impose substantial risk for hepatocarcinogenesis in adulthood in this region.

[Immunologically-competent cells in liver infiltrating lymphocytes in patients with chronic severe hepatitis B].

OBJECTIVE: To investigate the frequencies of immunologically competent cells (ICCs) in the liver-infiltrating lymphocytes (LILs) and peripheral blood and their possible role in pathogenesis in patients with chronic severe hepatitis B (CSHB). METHODS: LILs were isolated from the liver tissue samples from 11 CSHB patients and 5 normal controls (NCs) by the method of combined grinding with semi-frosted microscopic slides and sedimentation of hepatic cells. The frequency of isolated ICCs, including CD3(+), CD4(+), and CD8(+) T-cells, NK cells, NKT cells, and B cells was examined and compared with that of the circulating ICCs in the CSHB patients. Comparison was conducted between the CSHB patients and the controls. RESULTS: (1) In the CSHB patients, the frequencies of CD4(+) T cells and B cells in LILs were 17% +/- 6% and 3.0% +/- 1.0% respectively, both significantly lower than those in the circulating blood (32% +/- 8% and 21.4% +/- 12.2% respectively, both P < 0.01); however, the frequencies of CD8(+) T cells, NK cells, and NKT cells in LILs were 38% +/- 13%, 34% +/- 18%, and 10% +/- 4% respectively, all significantly lower than those in the circulating blood (26% +/- 6%, 15% +/- 9%, and 6% +/- 4%, all P < 0.05). (2) The frequencies of infiltrating CD3(+) T cells and CD4(+) T cells of the CSHB patients were both significantly higher than those of the NCs (P = 0.042 and P = 0.001); and the frequency of infiltrating CD8(+) T cells of the CSHB patients was higher than that of the NCs, and the and the frequencies of infiltrating NK cells and NKT cells in LILs were lower than those of the NCs, however, not significantly. (3) Compared with the liver tissues from the NCs, the liver tissues from the CSHB patients exhibited a significantly higher ratio of liver-infiltrating CD4(+) T cells to peripheral blood CD4(+) T-cell subsets (P = 0.001), and significantly lower ratios of liver-infiltrating NKT cells and B cells to the peripheral blood NKT-cells and B cells (P = 0.029 and P = 0.001 respectively). CONCLUSION: The abundant infiltrating immune active cells, especially the CD4(+) T cells, CD8(+) T cells, and NK cells, may be the causal factors that drive the progressive development of CSHB.