Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

AIM To study the chemical constituents from the ethanol precipitated sediment of Radix Isatidis and their anti-inflammatory activities.METHODS The effects of ethanol precipitated sediment on IL-6 and TNF-α levels were detected by LPS-induced RAW264.7 cell inflammation model and enzyme-linked immunosorbent assay.The chemical constituents were analyzed by UPLC-QTOF-MS/MS and high performance molecular exclusion method.RESULTS When the concentration of Radix Isatidis ethanol sediment were 200 and 400 μg/mL,it could significantly inhibit the release of IL-6 and TNF-α.The ethanol sediment of Radix Isatidis was mainly composed of polysaccharides and proteins,including trace amounts of lipopeptides,indoles and amino acids,among which polysaccharides were mainly glucans.CONCLUSION The constituents from the ethanol sediment of Radix Isatidis are sugars,alkaloids(indoles),amino acids,and organic acids(fatty acids),and they may exert anti-inflammatory effects by synergistic manner.

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines

OBJECTIVE: To utilized the baseline data of the Beijing Fangshan Family Cohort Study, and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects. METHODS: Probands and their relatives from 9 rural areas in Fangshan district, Beijing were included in this study. We developed a healthy lifestyle score based on five lifestyle behaviors: smoking, alcohol consumption, body mass index (BMI), dietary pattern, and physical activity. The measurements of arterial stiffness were brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). A variance component model was used to determine the heritability of arterial stiffness. Genotype-environment interaction effects were performed by the maximum likelihood methods. Subsequently, 45 candidate single nucleotide polymorphisms (SNPs) located in the glycolipid metabolism pathway were selected, and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles. RESULTS: A total of 6 302 study subjects across 3 225 pedigrees were enrolled in this study, with a mean age of 56.9 years and 45.1% male. Heritability of baPWV and ABI was 0.360 (95%CI: 0.302-0.418) and 0.243 (95%CI: 0.175-0.311), respectively. Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed. Following the findings of genotype-environment interaction analysis, we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness, indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness. Three SNPs in CDKAL1, ATP8B2 and SLC30A8 were shown to interact with BMI, implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness. CONCLUSION The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness. Furthermore, we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness. Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness. This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.
Humans ; Male ; Middle Aged ; Female ; Ankle Brachial Index ; Cohort Studies ; Gene-Environment Interaction ; Vascular Stiffness/genetics* ; Pedigree ; Pulse Wave Analysis/methods* ; Genotype

Objective:To investigate COVID-19 vaccination status and relevant adverse reactions in patients with psoriasis treated with biological agents, and to explore the effect of COVID-19 vaccination on psoriatic lesions.Methods:Clinical data were collected from 572 psoriasis patients aged 18 - 60 years, who were registered in the management system of psoriasis patients treated with biological agents in the University of Hong Kong-Shenzhen Hospital from May 2019 to June 2021. The COVID-19 vaccination status was investigated by telephone interviews, and the vaccination-related information was obtained by fixed healthcare workers during a fixed time period according to a predesigned questionnaire. Measurement data were compared between two groups by using t test, and enumeration data were compared by using chi-square test or Fisher′s exact test. Results:The COVID-19 vaccination coverage rate was 43.13% (226 cases) among the 524 patients who completed the telephone interview, and was significantly lower in the biological agent treatment group (30.79%, 105/341) than in the traditional drug treatment group (66.12%, 121/183; χ2 = 60.60, P < 0.001) . The main reason for not being vaccinated was patients′ fear of vaccine safety (49.66%, 148/298) , followed by doctors′ not recommending (26.51%, 79/298) . In the biological agent treatment group after vaccination, the exacerbation of psoriatic lesions was more common in patients receiving prolonged-interval treatment (42.86%, 6/14) compared with those receiving regular treatment (4.40%, 4/91; Fisher′s exact test, P < 0.001) . Skin lesions were severely aggravated in two patients after COVID-19 vaccination, who ever experienced allergic reactions and whose skin lesions did not completely subside after the treatment with biological agents. Conclusions:The COVID-19 vaccination coverage rate was relatively low in the psoriasis patients treated with biological agents, and no serious adverse reaction was observed after vaccination. Prolonged-interval treatment due to COVID-19 vaccination ran the risk of exacerbation of skin lesions.

The Ministry of Education and other four departments jointly issued the Notice on the Construction of high-level schools of public Health, proposing that "it will take ten years to build a number of high-level schools of public health, and form a high-quality education development system to adapt to the construction of modern public health system". At present, the construction of high-level public health schools in various universities in China is in full swing. The high-level School of Public Health and the CDC have played an important role in constructing the national public health system and the human health community. The high-level public health schools are of strategic significance and important value to the development of the CDC. The review presents reflections and insights on the role of high-level public health schools in the development of the CDC and the challenges they might face.
Humans ; United States ; Schools, Public Health ; Schools ; Universities ; Public Health ; Centers for Disease Control and Prevention, U.S.

【Objective】 To explore the recruitment and retention strategy of blood donors by investigating the age composition of blood donors in some areas of China, so as to promote blood donation and enhance clinical blood supply. 【Methods】 Through the working platform of Practice Comparison Working Group of China’s Mainland Blood Collection and Supply Institutions, the average age and age composition of blood donors from 22 blood centers were collected, and statistical analysis was conducted after eliminating invalid data. 【Results】 The median average age of blood donors during the survey year was 30.02.The median age in 2.89% of the blood centers was lower than 25. The average age of different genders was statistically significant only in 2018(P<0.05). Fot first-time blood donors, the median constituent ratio of donors <25 and ≥25 years old was 54.53% and 44.28%, with median retention rate at 10.30% and 9.61%, respectively. The median overall participation rate of blood donors was 2.7%, with median participation rate of blood donors <25 years old at 5.1%. 【Conclusion】 The recruitment and retention of blood donor is crucial to enhance clinical blood supply. Blood donors <25 years old, with a longer period for future donation, should be the main target of blood donation recruitment. Meanwhile, the revision of upper age limit for blood donation is another important initiative to grow the blood donor pool.

OBJECTIVE: Through showing the full picture of double-arm controlled clinical research and systematic review evidence in the field of orally administrated Chinese herbal medicine (CHM) for treatment of lung cancer, to provide a reference for future clinical research and to indicate a direction for future systematic reviews. METHODS: A comprehensive search of clinical controlled studies was performed regarding orally administered CHM treatment for lung cancer published from January 1970 to September 2020. The language was restricted to Chinese and English. Relevant data were extracted, the quality of systematic reviews was evaluated, and the research evidence was visually displayed. RESULTS: Randomized controlled trials were the most common type of research design. The research sample sizes were typically small. Oral CHM showed certain curative advantages in treating lung cancer. The key stages in oral CHM intervention for lung cancer are chemotherapy, radiotherapy, and late palliative treatment. The advantageous outcomes of oral CHM treatment of lung cancer are the short-term efficacy, quality of life, and adverse reactions. The perioperative stage, overall survival, pharmacoeconomic evaluation, and Chinese medicine decoctions are weak research areas. CONCLUSIONS CHM has staged and therapeutic advantages in treating lung cancer. The overall methodological quality is poor, and the level of evidence requires improvement. It is necessary to carry out large-scale, standardized, and higher-quality research in the superior and weak areas of CHM treatment of lung cancer.
Drugs, Chinese Herbal/adverse effects* ; Humans ; Lung Neoplasms/drug therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Systematic Reviews as Topic

Objective: To investigate the clinicopathological characteristics of reactive epithelial hyperplasia and dysplasia in the stomach, as well as the clinical value of mucin special staining and proliferating cell nuclear antigen (Ki-67) in distinguishing the two gastric lesions. Methods: The clinical pathological data of 63 patients with gastric reactive epithelial hyperplasia, 54 patients with low-grade dysplasia, and 63 patients with high-grade dysplasia diagnosed from May 2018 to May 2021 in Beijing Chaoyang Hospital, Capital Medical University, Beijing, China were analyzed. Alcian blue periodic acid Schiff (AB-PAS) and Ki-67 staining were performed to examine the mucin staining pattern, number of Ki-67 positive cells, Ki-67 staining patterns in the three groups of lesions, and histopathologic characteristics. Results: The positive rates of AB-PAS in the reactive epithelial hyperplasia and gastric dysplasia groups were 87.3%(55/63) and 10.3%(12/117), respectively. The expression of AB-PAS in the reactive epithelial hyperplasia was gradually increased from the base to the surface of the epithelium. In low-grade dysplasia and high-grade dysplasia, there was no mucin present in the dysplasia epithelium. The difference between the two groups was statistically significant (P<0.01). The positive rate of Ki-67 in the epithelial reactive hyperplasia (>10%) was 81.0% (51/63), and the positive cells were mainly located in the neck and middle parts of the mucosal glands (58/63, 92.1%). In the low-grade dysplasia group, the positive rate of Ki-67 (>10%) was 90.7%(49/54); the positive cells were mainly located in the upper mucosa (33/54, 61.1%), showing a banded distribution pattern; in the high-grade dysplasia group, the positive rate (>10%) was 95.2%(60/63), and the positive cells were mainly located in the whole mucosa (49/63, 77.8%), showing a diffuse/diffuse scattered distribution pattern. The three groups had statistically different rates and distribution patterns of Ki-67 expression (P<0.01). Conclusion: The gastric epithelial reactive hyperplasia and dysplasia can be differentiated using clinicopathological features, AB-PAS staining and Ki-67 expression pattern.
Alcian Blue ; Humans ; Hyperplasia ; Ki-67 Antigen/metabolism* ; Periodic Acid ; Staining and Labeling ; Stomach Neoplasms/diagnosis*

OBJECTIVE: To investigate the correlation between drinking habits and pathological characteristics of patients with upper tract urothelial carcinoma (UTUC). METHODS: A preoperative questionnaire survey was conducted to understand the drinking habits of UTUC patients who were admitted to the Department of Urology, Peking University First Hospital for radical nephroureterectomy within one year from August 2020 to July 2021, and statistical analysis was performed in combination with their postoperative pathological characteristics. The statistical procedure was performed using SPSS 22.0 software, and firstly, the preliminary analysis was performed one by one using the columnar χ² test on the pathological characteristics of UTUC tumors as the dependent variable and the factors related to patients' general information, past history and drinking habits as the independent variables, and the independent variables that met P < 0.2 between the case and control groups for each dependent variable were specified for screening. The screened variables were included in the binary Logistic regression analysis. A difference of P < 0.05 was used to indicate a statistically significant difference. RESULTS: A total of 239 patients, 134 males and 105 females, with a mean age of (68.1±9.98)years and a median disease duration of 4.8 months, were included in this study. Multifactorial Logistic regression results suggested that after adjusting for the effects of other variables, UTUC patients who had the habit of drinking at least once every hour during the daytime had a significantly increased risk of high grade (G3) tumors(OR=1.941, 95%CI: 0.352-1.029, P < 0.01); these patients also had a significantly decreased risk of multifocal UTUC tumors (OR=0.344, 95% CI: 1.18-5.582, P=0.004). The patients who had the habit of drinking over 100 mL water each time had a significantly decreased risk of mutifocal UTUC incidence (OR=0.477, 95%CI: 0.225-1.012, P=0.046). Patients who pay attention to daily water intakes had a significantly increased risk of renipelvic carcinoma (OR=2.530, 95%CI: 1.434-4.463, P=0.001) and a significantly decreased risk of ureteral carcinoma (OR=0.314, 95%CI: 0.172-0.573, P < 0.01). Other variables included in the regression model did not differ significantly in their effects on the occurrence of tumor pathological characteristics. CONCLUSION Having the awareness of drinking water every 1 h during the day, drinking over 100 mL water each time, having the awareness of daily drinking habits correlated significantly with pathological characteristics of UTUC such as the presence of G3 tumor, multifocal tumors and location of the tumor. This conclusion still needs to be verified by subsequent trials with higher levels of evidence.
Carcinoma, Transitional Cell/surgery* ; Female ; Habits ; Humans ; Male ; Neoplasm Recurrence, Local/epidemiology* ; Retrospective Studies ; Ureteral Neoplasms/surgery* ; Urinary Bladder Neoplasms/surgery* ; Water