[Study on the risk factors of coal workers' pneumoconiosis and the mechanism of pyroptosis in peripheral blood].

Objective: To explore the risk factors of coal workers' pneumoconiosis, reveal the molecular mechanism of pyroptosis in peripheral blood of coal workers' pneumoconiosis patients, and provide new strategies and potential diagnostic biomarkers for the treatment of the disease. Methods: From January 1, 2020 to December 31, 2022, workers with suspected occupational diseases who were diagnosed with coal workers' pneumoconiosis in the Third People's Hospital of Xinjiang Uygur Autonomous Region were included in the study, including 77 patients with coal workers' pneumoconiosis stage Ⅰ, 10 patients with stage Ⅱ, 6 patients with stage Ⅲ, and 49 workers with dust-free lung disease as the control group. General information of the subjects was collected, blood samples were collected for routine blood and blood biochemical results, and plasma levels of interleukin (IL) -1ß and IL-18 were measured. Combined with the results of clinical examination, multi-factor ordered logistic regression analysis was carried out to evaluate the influencing factors of coal workers' pneumoconiosis. At the same time, the expression of pyroptosis related proteins in blood cells was detected to reveal the molecular mechanism of coal workers' pneumoconiosis. Results: All 142 subjects were male, with an average age of (51.65±6.31) years old and an average working age of (15.94±9.38) years. There were significant differences in smoking age (F=4.95, P=0.003) and lunch break distribution (H=8.84, P=0.031) among all groups. The hemoglobin content of stage Ⅰ patients was higher than that of stage Ⅱ patients, and the neutrophil percentage of stage Ⅲ patients was higher than that of the other 3 groups (P<0.05). The levels of total bilirubin and indirect bilirubin in stage Ⅰ patients were higher than those in control group, while the erythrocyte sedimentation rate in stage Ⅱ patients was higher than that in the other 3 groups (P<0.05). The levels of IL-18 and IL-1ß in stage Ⅲ of coal workers' pneumoconiosis were higher than those in the other 3 groups (P<0.05). Multiple logistic regression analysis showed that smoking age (OR=1.03, 95%CI: 1.00-1.06) and IL-1ß level (OR=4.61, 95%CI: 1.59-13.32) were independent risk factors for coal workers' pneumoconiosis (P<0.05). Compared with the control group, the expression levels of nucleotide-binding of oligomeric domain-like receptor protein 3 (NLRP3), Caspase-1, GSDMD, Caspase-4 and other proteins in stage Ⅲ of coal workers' pneumoconiosis were significantly increased (P<0.05) . Conclusion: Smoking age is a risk factor for coal workers' pneumoconiosis, IL-1ß may be a potential biomarker for the diagnosis of coal workers' pneumoconiosis, and pyroptosis may play a role in the development of peripheral inflammation of coal workers' pneumoconiosis.

Similar programmed death ligand 1 (PD-L1) expression profile in patients with mild COPD and lung cancer.

Programmed Death Ligand 1 (PD-L1) is crucial in regulating the immunological tolerance in non-small cell lung cancer (NSCLC). Alveolar macrophage (AM)-derived PD-L1 binds to its receptor, PD-1, on surveilling lymphocytes, leading to lymphocyte exhaustion. Increased PD-L1 expression is associated with cigarette smoke (CS)-exposure. However, the PD-L1 role in CS-associated lung diseases associated with NSCLC, such as chronic obstructive pulmonary disease (COPD), is still unclear. In two different cohorts of ever smokers with COPD or NSCLC, and ever and never smoker controls, we evaluated PD-L1 expression: (1) via cutting-edge digital spatial proteomic and transcriptomic profiling (Geomx) of formalin-fixed paraffin-embedded (FFPE) lung tissue sections (n = 19); and (2) via triple immunofluorescence staining of bronchoalveolar lavage (BAL) AMs (n = 83). PD-L1 mRNA expression was also quantified in BAL AMs exposed to CS extract. PD-L1 expression was increased in the bronchiolar wall, parenchyma, and vascular wall from mild-moderate (GOLD 1-2) COPD patients compared to severe-very severe (GOLD 3-4) COPD patients and controls. Within all the COPD patients, PD-L1 protein expression was associated with upregulation of genes involved in tumor progression and downregulation of oncosuppressive genes, and strongly directly correlated with the FEV1% predicted, indicating higher PD-L1 expression in the milder vs. more severe COPD stages. In bronchioles, PD-L1 levels were strongly directly correlated with the number of functionally active AMs. In BAL, we confirmed that AMs from patients with both GOLD 1-2 COPD and NSCLC had the highest and similar, PD-L1 expression levels versus all the other groups, independently from active cigarette smoking. Intriguingly, AMs from patients with more severe COPD had reduced AM PD-L1 expression compared to patients with mild COPD. Acute CS extract stimulation increased PD-L1 mRNA expression only in never-and not in ever-smoker AMs. Lungs from patients with mild COPD and NSCLC are characterized by a similar strong PD-L1 expression signature in bronchioles and functionally active AMs compared to patients with severe COPD and controls. Active smoking does not affect PD-L1 levels. These observations represent a new resource in understanding the innate immune mechanisms underlying the link between COPD and lung cancer onset and progression and pave the way to future studies focused on the mechanisms by which CS promotes tumorigenesis and COPD.

[The necessity and importance of standardized management of acromegaly: from the perspective of development of expert consensuses and clinical guidelines].

Acromegaly is a rare disease, and multidisciplinary collaboration is essential for its diagnosis, treatment, and follow-up.In recent years, a series of novel findings have been echieved in clinical studies on acromegaly.Therefore, the China Pituitary Adenoma Specialist council has convened Chinese specialists in neurosurgery, endocrinology, radiology, and radiotherapy to release the Chinese Consensus for the Diagnosis and Treatment of Acromegaly (2021), which aims to promote the standardized and individualized management of acromegaly.Looking back to the past, the consensuses and guidelines have played vital roles in establishing the widely recognized biochemical remission criteria, promoting new drugs and novel therapeutic strategies which are of significance for standardized treatment, and emphasizing the need to focus on the systemic complications of acromegaly and the long-term quality of life. In this editorial, we briefly reviewed the expert consensuses and clinical guidelines on acromegaly at home and abroad, and discussed their important roles in promoting standardized disease management from three aspects including biochemical remission standards, medical treatment, and the diagnosis and treatment of systemic complications.

[Differential circRNA expression profiles in peripheral blood mononuclear cells among mild and severe influenza-associated pneumonia patients].

Objective: To explore the difference in the expression profile of circular RNA in peripheral blood mononuclear cells between patients with mild and severe influenza pneumonia. Methods: From December 2018 to March 2019, 10 inpatients with mild and 10 inpatients with severe influenza pneumonia admitted to the Department of Infection and Clinical Microbiology of Beijing Chaoyang Hospital were included. Clariom™ D gene chip was used to explore the circRNA expression profiles of peripheral blood mononuclear cells (PBMC) isolated from the patients. The absolute value of the fold change (FC value)>2 and P<0.05 were used as the criteria to screen the differentially expressed circRNA, and the gene ontology (GO) enrichment analysis and the Kyoto Encyclopedia of Gene and Genome database (Kyoto Encyclopedia of Genes and Genomes, KEGG) signal pathway enrichment analysis were also performed. Results: The age of mild patients [M (P25, P75)] was 62.0 (34.5, 69.8) years old, including 4 males; the age of severe patients [M (P25, P75)] was 50.0 (37.0, 60.0) years old, all were males. A total of 137 differentially expressed circRNAs in PBMCs of mild and severe patients were screened. The numbers of up-regulated and down-regulated circRNAs in mild patients were 101 and 36, respectively. Among them, hsa_circ_0091073 (FC value=160.898, P<0.05) was the most significantly up-regulated circRNA and hsa_circ_0092219 (FC value =-17.630, P<0.05) was the most significantly down-regulated circRNA. GO enrichment analysis showed that a total of 111 secondary GO items were significantly associated with related differential expression of circRNA (P<0.05). The GO terms associated with upregulated circRNAs included DNA-templated transcription, regulation of DNA-templated transcription, regulation of transcription from RNA polymerase Ⅱ promoter, etc.; The GO terms associated with downregulated circRNAs included neutrophil degranulation, killing of cells of other organism, defense response to fungus, etc. KEGG signaling pathway analysis showed that there were 37 metabolic pathways related to differentially expressed circRNAs (P<0.05). Signaling pathways related to up-regulated circRNAs included nuclear factor-κB (NF-κB) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, tumor necrosis factor (TNF) signaling pathway, etc. Signaling pathways related to down-regulation of circRNAs included cancer transcription disorders, folate carbon pool, and other types of O-glycan biosynthesis. Conclusion: The expression of circRNA in PBMC of mild and severe influenza pneumonia patients is significantly different, and it may play a role in the pathogenic mechanism of influenza pneumonia through multiple signal pathways.

The inhibitory effects of class I histone deacetylases on hippocampal neuroinflammatory regulation in aging mice with postoperative cognitive dysfunction.

OBJECTIVE: Neuroinflammation in the hippocampus has been determined to contribute to postoperative cognitive dysfunction (POCD) occurrence in elderly individuals. Histone deacetylases (HDACs) have been identified as important regulators of inflammation. However, the roles of different types of HDACs in POCD have never been fully explored. MATERIALS AND METHODS: POCD mouse models were established using isoflurane and validated by the Morris water maze test. The mice were pretreated with UF010 [a Class I HDAC inhibitor (HDACi)], MC1568 (a Class II HDACi) and SAHA (a Class I and II HDACi) before POCD establishment. HDAC protein levels and the activity of the NF-κB/p65, JAK/STAT and TLR/MyD88 signaling pathways in the hippocampus were investigated by Western blot (WB). The enrichment of HDACs on the promoters of genes was detected using ChIP-qPCR. RESULTS: Class I HDACs, including HDAC2 and HDAC8, and Class II HDACs, including HDAC4, HDAC7 and HDAC10, were all upregulated in the POCD group compared to the control group. Furthermore, compared to the MC1568 pretreatment group and the control group, the groups pretreated with UF010 and SAHA exhibited amelioration of the effects of anesthesia/surgery induced POCD and compromised inflammatory reactions in the hippocampus. Likewise, the NF-κB/p65, JAK/STAT and TLR/MyD88 signaling pathways were inactivated upon pretreatment with UF010 and SAHA compared to MC1568. Finally, the transcription of the genes negatively regulating these three pathways declined, and the enrichment of HDAC1, HDAC2 and HDAC8 was significantly elevated in the context of POCD. CONCLUSIONS: Class I HDACs, especially HDAC1, HDAC2 and HDAC8, play crucial roles in enhancing neuroinflammation in the hippocampus and causing POCD. Class I HDACs are potential therapeutic targets for POCD prevention and treatment via neuroinflammation inhibition.

LncRNA ST8SIA6-AS1 promotes colorectal cancer cell proliferation, migration and invasion by regulating the miR-5195/PCBP2 axis.

OBJECTIVE: Long non-coding RNAs (lncRNAs) have been reported to play a vital role in the development and progression of various cancers, including colorectal cancer (CRC). Although the dysregulation of lncRNA ST8SIA6-AS1 participates in the development of multiple malignancies, the underlying molecular mechanisms of ST8SIA6-AS1 in regulating CRC progression remain to be fully discovered. PATIENTS AND METHODS: The expression level of lncRNA ST8SIA6-AS1 was examined in the tumor tissues and paracancerous tissues of CRC patients. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was utilized to examine the expression levels of ST8SIA6-AS1, miR-5195, and Poly-(C) Binding Protein 2 (PCBP2). The protein expression level of PCBP2 was detected by Western blotting. MTT assay was performed to measure the proliferation of HCT-116 and SW480 cells. Cell migration and invasion abilities were measured by transwell assay. Luciferase reporter assay was used to examine the interaction between miR-5195 and ST8SIA6-AS1 or PCBP2. RESULTS: This study revealed that lncRNA ST8SIA6-AS1 was upregulated in CRC tissues and cells. Knockdown of ST8SIA6-AS1 inhibited proliferation, migration, and invasion of CRC cells. Moreover, ST8SIA6-AS1 was proved to inhibit miR-5195 expression by directly targeting miR-5195. In addition, it was demonstrated that overexpression of miR-5195 inhibited CRC progression. Furthermore, PCBP2 was shown to enhance sh-ST8SIA6-AS1 and miR-5195 mimics-attenuated cell proliferation, migration, and invasion by directly binding to miR-5195. CONCLUSIONS: Our study revealed that ST8SIA6-AS1 promoted CRC progression via the miR-5195/PCBP2 axis. This study may provide an improved understanding of the pathogenesis of CRC.

[Economic evaluation of fifteen cervical cancer screening strategies in rural China].

Objective: To evaluate the feasible cervical cancer screening strategies in rural China. Methods: The study was based on the health industry scientific research project of National Health Commission in 2015, cervical cancer screening technology and demonstration research suitable for rural areas in China, we collected health economics and epidemiological parameters and established the unscreening model and screening model with Treeage Pro 2011 software. Combining with the data acquired from site investigation, including population screening, treatment-related clinical materials and cost data, we simulated the occurrence and the development of cervical cancer of rural women in China under different screening and intervention programs and predicted the screening effects [cumulative incidence, cumulative risk of disease, life years and quality adjusted life years (QALY) , gains] and costs after 20 years, and using health economic evaluation analysis (cost-effectiveness analysis, cost-utility analysis, cost-benefit analysis). Screening programs included five screening strategies [visual inspection with acetic acid/lugol's iodine (VIA/VILI), careHPV, ThinPrep cytology test (TCT), careHPV+TCT, careHPV+VIA/VILI] and three screening intervals (1-year, 3-year, 5-year), a total of fifteen screening programs. Results: Compared with no screening, fifteen screening programs reduced the cumulative incidence by 22.65%-51.76%. Compared with TCT or VIA/VILI, for the same screening interval, the reduced cumulative incidence, the amounts of life-year saved and QALY and benefits gained of careHPV were the highest. The cost-effectiveness ratios of these screening programs ranged (0.44-3.24)×10(4) Yuan per life-year saved, cost-utility ratios ranged (0.15- 1.01)×10(4) Yuan per QALY, benefit-cost ratios ranged 7.73-59.10. The results of incremental costeffectiveness ratios showed that VIA/VILI every five years, VIA/VILI every three years, careHPV every five years, careHPV every three years and careHPV every year were dominant programs. Conclusions: VIA/VILI screening is cost-effective, careHPV is slightly more expensive but more effective. In rural China, careHPV screening every five years could be recommended. This study provides a basis for the determination of cervical cancer screening methods feasible for rural areas in China.

[Cost-effectiveness analysis of cervical cancer screening strategies in urban China].

Objective: To explore the most economically feasible cervical cancer screening strategies in urban China. Methods: A series of Markov models were constructed to evaluate health and economic outcomes of different screening strategies. There were 24 screening strategies including four screening methods: liquid-based cytology (LBC), human papillomavirus (HPV) DNA genotyping, HPV DNA genotyping with LBC triage (HPV DNA+ LBC), HPV DNA genotyping and LBC co-testing (HPV DNA-LBC), along with three intervals (every 1, 3 or 5 years) and two starting age for screening (30 or 35 years old) were compared. Models parameters were obtained from a cervical cancer screening study in urban China and literature reviews. Results: The cumulative incidence and mortality risk of cervical cancer declined over 69% and 82% respectively for each screening strategy as compared with the no screening scenario. LBC every five years starting from 35 years old strategy cost the least (RMB 690 per capita) and could save life years compared with no screening. The cost effectiveness ratios of 24 strategies ranged from -10 903 to 117 992 RMB per life year saved. All strategies were cost-effective compared to no screening. In the incremental cost-effectiveness analysis, LBC every 5 years starting from 30 strategy, HPV DNA genotyping every 3 years starting from 30 strategy, LBC every 3 years starting from 30 strategy and LBC every year starting from 30 strategy were dominant strategies. Conclusions: Screening can effectively prevent cervical cancer. In urban Chinese areas with insufficient socioeconomic resources, LBC every 5 years from 35 years old strategy is recommended. In relatively more affluent areas, LBC every 5 years from 30 years old strategy, LBC every 3 years from 30 years old strategy, HPV DNA genotyping every 3 years from 30 years old strategy, and LBC every year from 30 years old strategy are recommended successively.

[Study on direct economic burden and influencing factors in patients with cervical cancer and precancerous lesions].

Objective: To account the direct cost of uterine cervix carcinoma treatment in China and to explore the related factors which influence the direct financial burden of the disease. Methods: Data was collected through the medical record system and telephone interviews in 14 county-level hospitals and 9 provincial and municipal hospitals from 14 provinces/municipalities enrolled in the Chinese National Health Industry Research Project in 2015. The direct financial burden of uterine cervix carcinoma treatment consisted of the direct medical cost and the direct non-medical cost of treatment in different pathological cervical cancer stages and precancerous lesions. Multiple liner regression method was used to analyze the factors affecting the costs. Results: The age of the 3 246 patients was (46.40±10.43) years, including 2 423 patients from provincial and municipal hospitals and 823 patients from county-level hospitals. The direct financial burden for one patient of pathological uterine cervix carcinoma stage or precancerous lesion ranged from 10 156.3 yuan to 75 716.4 yuan in provincial and municipal hospitals, and for patients from county-level hospitals, the cost was between 4 927.9 yuan and 47 524.8 yuan per person. There was a wide gap between the direct financial burden of patients in different disease stages. The direct financial burden of patients with precancerous lesions ranged from 4 927.9 yuan per person to 11 243.0 yuan per person, as for patients of pathological uterine cervix carcinoma stages, the direct financial burden was between 29 274.6 yuan and 75 716.4 yuan per person. The factors which influence direct financial burden would include: the levels of the hospital, pathological period, medicare reimbursement, days of treatment, and the methods of treatment (P<0.001). Conclusion: The direct financial burden of diseases in patients with pathological uterine cervix carcinoma stage or precancerous lesion differed in different levels of hospital and pathological periods. In addition, medicare reimbursement, days of treatment, and the methods of treatment all had impact on it.

[Effects and safety of quadratus lumborum block in analgesia after hip arthroplasty].

Objective: To evaluate the efficacy of ultrasound guided quadratus lumborum block combined with non-steroidal anti-inflammatory drugs for postoperative analgesia in patients undergoing total hip arthroplasty. Methods: From January to June 2017, sixty American Society of Anesthesiologists (ASA) physical status Ⅰ to Ⅲ patients, aged 55-75 yr, scheduled for total hip arthroplasty, were randomly divided into control group(group N) and quadratus lumborum block (group R). Ultrasound guided quadratus lumborum block was implemented on the affected side at the end of operation.Then 30 ml 0.33% ropivacaine were administrated in group R, while the control group did not receive the same block. A sufentanil patient-controlled analgesia pump was connected to the patient. The rest visual analogue score (VAS) were recorded at 0 h(T(0)), 3 h(T(1)), 6 h (T(2)), 12 h(T(3)), 24 h (T(4)), 36 h (T(5)) and 48 h(T(6)) after sugery, the VAS scores on movement were evaluated at T(4), T(5) and T(6) time points.The consumption of sufentanil within each period time were recorded.The maximal flexion and abduction degrees of the hip joint were evaluated at 12, 24, 36 and 48 h after operation. The number of patients for rescue pain relief by intravenous analgesia pump during 24 h and 48 h after surgery were counted in both groups. The postoperative adverse effects and overall satisfaction in the two groups were recorded. Results: The VAS at rest in group R were 0.8±0.4, 1.0±0.3, 1.2±0.5, 2.0±0.5, 1.7±0.4 , 1.6±0.5 at T(1), T(2), T(3), T(4), T(5), T(6) respectively, and those in group N were 3.0±0.7, 3.5±0.9, 3.8±0.9, 3.3±1.1, 3.3±0.7, 3.0±0.7 at the same time points. The VAS at rest were lower in group R than those in control group at all time points (F=203.090, 216.354, 203.956, 35.548, 96.332, 80.577, all P<0.01). The VAS on movement in group R were 2.7±0.9, 2.9±0.7 , 2.0±0.6 at T(4), T(5), T(6) respectively , and those in group N were 6.0±1.5, 5.8±1.1, 4.5±1.0. The VAS on movement were also lower in group R than those in control group(F=154.561, 143.224, 141.479, all P<0.01). The maximum flexion degrees in group R were (61±12)degrees, (64±10)degrees, (69±15)degrees and(78±19)degrees at 12, 24, 36, 48 h after operation, and those were (45±11) degrees, (49±10)degrees, (52±12)degrees and(60±14)degrees at the same time points. The maximum flexion degrees in group R were increased more than control group at 12, 24, 36, 48 h after operation(F=34.981, 35.575, 52.106, 41.681, all P<0.01). The abduction degrees in group R were(22±6)degrees, (26±6)degrees, (27±8)degrees and(28±7)degrees at 12, 24, 36, 48 h after surgery, and those in group N were (14±5) degrees, (17±6)degrees, (20±6)degrees and(20±5)degrees. The abduction degrees in group R were increased more than those in group N(F=58.974, 33.402, 19.151, 20.575, all P<0.01). The rates of rescue analgesia for pain relief were 10% and 16.7% at 24 h and 48 h after operation respectively in group R, and those were 100% and 100% in group N. Compared to group N, the rates of rescue analgesia for pain relief in group R were significantly decreased (χ(2)=49.091, 42.857, all P<0.01). The incidences of postoperative nausea and vomiting, pruritus in group R were 3.3% and 3.3% respectively, and those in group N were 23.3% and 20.0%. The incidences of nausea and vomiting, pruritus in group R were lower than those in group N (χ(2)=5.192, 4.875, all P<0.01). The overall satisfaction scores in group R (3.7 ± 1.0 ) were higher than those (1.9±0.7) in the group N(t=7.841, P<0.01). Conclusion: The quadratus lumborum block combined with parecoxib sodium for multimodal analgesia after total hip arthroplasty is effective and provides satisfactory analgesia.

Dexmedetomidine protects against cisplatin-induced acute kidney injury in mice through regulating apoptosis and inflammation.

OBJECTIVE AND DESIGN: Cisplatin-based chemotherapy has been widely used in the perioperative period of cancer surgery, which exacerbates the risk of renal injury. In this study, we examined whether dexmedetomidine (DEX), a commonly used anesthetic adjuvant, shows a protective effect against cisplatin-induced acute kidney injury. MATERIALS: Acute kidney injury in mice was induced by cisplatin. TREATMENTS: Mice were administered with DEX 25 µg/kg or atipamezole 250 µg/kg (once a day, for 3 days) after cisplatin treatment. METHODS: The renal function and tubular damage score were evaluated at 72 h following cisplatin administration. Apoptotic tubular cells were detected by TUNEL assay. Caspase-3, p53, Bax, F4/80+ macrophages, CD3+ T cells, and NF-κB were examined by immunohistochemistry staining or Western blot. Tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and monocyte chemoattractant protein (MCP)-1 in kidney were measured using real-time polymerase chain reaction. RESULTS: DEX treatment preserved renal function and reduced tubular damage score of mice after cisplatin administration. Mice treated with DEX exhibited less apoptotic tubular cells in response to cisplatin insult, which was associated with decreased Bax and reduced activation of p53 and caspase-3. DEX suppressed the infiltration of macrophages and T cells into the kidneys following cisplatin treatment, which was involved in the inhibition of NF-κB activation and decreased expression of TNF-α, IL-1ß, IL-6, and MCP-1. Furthermore, we showed that the renoprotective effect conferred by DEX may be related to α2 adrenoceptor-dependent pathway. CONCLUSION: We demonstrate that DEX protects the kidney against cisplatin-induced AKI by the regulation of apoptosis and inflammatory response.

[Predictive value of C-reactive protein in emerging non-alcoholic fatty liver disease].

Objective: To investigate the predictive value of C-reactive protein (CRP) in emerging non-alcoholic fatty liver disease (NAFLD). Methods: A prospective cohort study was performed. A total of 101510 employees of Kailuan Group Company who underwent physical examination from July 2006 to October 2007 were enrolled as study subjects. The employees with a history of drinking, fatty liver disease, myocardial infarction, stroke, and malignant tumors and incomplete data were excluded. Finally 25843 employees were enrolled in the cohort study. According to the baseline CRP level, these employees were divided into CRP < 1 mg/L group, CRP 1-3 mg/L group, and CRP > 3 mg/L group. The detection rate of emerging NAFLD was compared between groups, and the multivariate logistic regression model was used to analyze the risk of NAFLD in each group. Results: With the increasing CRP level, age, systolic pressure, diastolic pressure, waist circumference, body mass index, fasting blood glucose, total cholesterol, serum uric acid, and the proportion of male patients tended to increase (P< 0.01). The detection rate of emerging NAFLD was 24.6% in the CRP < 1 mg/L group, 29.6% in the CRP 1-3 mg/L group, and 30.6% in the CRP > 3 mg/L group (χ 2= 92.10,P< 0.01). The results of the logistic regression analysis showed that after the confounding factors such as age, sex, and waist circumference were corrected, the risk of NAFLD in the CRP 1-3 mg/L group and CRP > 3 mg/L group was 1.09 (95%CI1.01-1.17) and 1.24 (95%CI1.13-1.35) times that in the CRP < 1 mg/L group. Conclusion: CRP is the independent risk factor for the development of NAFLD.

[The influence of lumbar sympathetic ganglion radiofrequency thermocoagulation on the activation of microglia in rats with diabetic neuropathic pain].

OBJECTIVE: To observe the influence of lumbar sympathetic ganglion radiofrequency thermocoagulation on the activation of spinal microglia in rats with diabetic neuropathic pain (DNP). METHODS: Thirty-six painful diabetic Sprague-Dawley rats induced by 60 mg/kg streptozotocin (STZ) intraperitoneal injection were randomly divided into diabetic neuropathic pain group (group DNP, n=12), Sham operation group (group Sham, n=12) and radiofrequency thermocoagulation group (group R, n=12). Meanwhile another 12 age-matched rats were allocated as normal control group (group N), rats in group N received intraperitoneal injection of equal volume of normal saline. Twenty-eight days after STZ injection, rats in group R received L3 lumbar sympathetic ganglia radiofrequency thermocoagulation on the left side under X-ray guideline after anesthesia with damage time 60 s and damage temperature 60 ℃. Rats in group Sham received puncture positioning, but not thermocoagulation therapy. The mechanical paw withdrawal threshold (PWT) were performed before STZ injection, 7, 14, 21, 28 days after STZ injection and 1, 3, 5, 7, 14 days after radiofrequency thermocoagulation, respectively. Blood glucose were performed before STZ injection, 3, 28 days after STZ injection and 1, 14days after radiofrequency thermocoagulation. After the final behavioral testing, L3-L5 spinal cord tissues were removed to exam the expression of microglia marker OX42 by Western blotting and immunofluorescence technique, and the changes in the expression of inflammation factor IL-1ß, IL-6, TNF-α were detected by ELISA technique. RESULTS: Compared with group N, after 14, 21, 28 days of STZ injection and 1, 3, 5, 7, 14 days of radiofrequency thermocoagulation, the PWT of group DNP and group Sham decreased significantly (P<0.05); Before radiofrequency thermocoagulation, the PWT of rats in group DNP was (3.84±0.83) g, the PWT of rats in group R was (4.45±0.88) g, there was no statistically significant difference between group DNP and group R (t=1.514, P>0.05), but after radiofrequency thermocoagulation, compared with DNP group, the PWT of rats in group R increased significantly (P<0.05), and lasted to 14 d after radiofrequency thermocoagulation. The ratio of spinal microglia marker OX42 and GAPDH, the expression of inflammation factor IL-1ß, IL-6, and TNF-α in group N were 0.074±0.023, (35.93±6.16) pg/ml, (92.11±13.23) pg/ml, and (169.50±22.64) pg/ml, respectively. The ratio of spinal microglia marker OX42 and GAPDH, the expression of inflammation factor IL-1ß, IL-6, and TNF-α in group DNP were 1.023±0.185, (73.82±9.25) pg/ml, (155.33±21.82) pg/ml, and (298.30±33.21) pg/ml, respectively. The ratio of spinal microglia marker OX42 and GAPDH, the expression of inflammation factor IL-1ß, IL-6, and TNF-α in group Sham were 0.951±0.103, (73.00±7.54) pg/ml, (151.02±24.26) pg/ml, and (294.01±36.37) pg/ml, respectively. The ratio of spinal microglia marker OX42 and GAPDH, the expression of inflammation factor IL-1ß, IL-6, and TNF-α in group R were 0.563±0.019, (51.81±7.36) pg/ml, (123.24±16.13) pg/ml, and (229.23±29.16) pg/ml, respectively. Compared with group N, the expression of spinal microglia marker OX42 and inflammation factor IL-1ß, IL-6, and TNF-α in group DNP, group Sham and group R increased significantly (F=7.501, 348.698, 568.021, 145.110, all P<0.05). Compared with DNP group, the expression of spinal microglia marker OX42 and inflammation factor IL-1ß, IL-6, and TNF-α of group R reduced significantly (all P<0.05). CONCLUSION: The lumbar sympathetic ganglion radiofrequency thermocoagulation can alleviate diabetic neuropathic pain. The mechanism may relate with the inhibition of spinal microglia activation and the lower expression of inflammation factor.

Curcumin promotes the apoptosis of human endometrial carcinoma cells by downregulating the expression of androgen receptor through Wnt signal pathway.

OBJECTIVE: The current study aimed to explore the effect ofcurcumin on androgen receptor (AR) expression in endometrial carcinoma cells, as well as the underlying mechanisms. MATERIALS AND METHODS: Endometrial carcinoma cells were treated with curcumin (10, 50, and 100 micromol/l) for 12, 24, and 48 hours. Their growth curves were drawn using MTT assays and their apoptotic rates were determined using flow cytometry. The mRNA and protein expression of AR was detected using PCR and that of the Wnt signal related nucleopro- tein beta-cantenin was observed using western blot analysis. The influence of beta-cantenin on the action of curcumin was observed. RESULTS: Curcumin downregulated the proliferation and apoptosis of human endometrial carcinoma cells in concentration and time-dependent manners. It downregulated the expression of AR and beta-cantenin in the cells. rWnt3a partially cancelled the effects of curcumin on the proliferation and apoptosis of human endometrial carcinoma cells as well as the AR expression-downregulating effect of curcumin. CONCLUSION: Curcumin inhibits the proliferation and apoptosis of human endometrial carcinoma cells by downregulating their AR expression through the Wnt signal pathway.

Toll-like receptor 4 genetic variants and prognosis of breast cancer.

Despite the knowledge of many genetic alterations present in breast cancer, the complexity of this disease precludes placing its biology into a simple conceptual framework. Toll-like receptor 4 (TLR4) plays important roles in regulating innate immunity and may affect the development of cancers. Polymorphisms in TLR4 gene have been shown to be associated with impaired immune responses. Here, we investigated the association of TLR4 polymorphisms with breast cancer. Four functional TLR4 polymorphisms (-2242T/C, Asp299Gly, Thr399Ile, and +3725G/C) were genotyped in a total of 665 breast cancer patients and 768 healthy controls. Data were analyzed using the chi-squared test. Results showed that the prevalence of TLR4 +3725GC and CC genotypes were significantly increased in breast cancer cases when compared with controls [odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.08-1.73, P = 0.008 and OR = 2.34, 95% CI = 1.66-3.35, P < 0.0001, respectively]. Also, the frequency of TLR4 +3725C allele was significantly higher in breast cancer patients (P < 0.0001). The -2242T/C polymorphism did not show any significant differences between cases and controls. In addition, when analyzing the survival time of breast cancer patients with TLR4 +3725G/C polymorphism, cases with +3725C allele had significantly shorter survival time overall (P = 0.006). These results suggested that polymorphism in TLR4 gene was associated with increased susceptibility to breast cancer and could be used as a prognostic marker for this malignancy.

Sodium valproate inhibits MDA-MB-231 breast cancer cell migration by upregulating NM23H1 expression.

Breast cancer is a common cancer in women, with a highly variable course, from inoffensive to lethal. To find a more effective strategy for its treatment, sodium valproate has been tested as an anti-cancer drug; it is the only clinically available histone deacetylase inhibitor. However, data about the effects of sodium valproate on breast cancer are insufficient in both animals and humans; studies have yielded conflicting conclusions. In particular, little is known about the association between expression of the metastasis suppressor Nm23H1 gene and breast cancer. We hypothesized that sodium valproate regulates NM23H1 expression, and affects migration and/or invasion. We found that sodium valproate at concentrations of 0.8-3.2 mM inhibits migration and modulates Nm23H1 gene expression in a concentration-dependent manner. Confluent MDA-MB-231 cells were scratched by a micropipette tip after VPA treatment for 24 h; 24 h later, the scratch was almostly closed in the 0 mM VPA-treated cells, while the 3.2 mM VPA-treated cells migrated the slowest. The cell migration ratio exposed to 0.8, 1.6 and 3.2 mM VPA was about 66.67, 30.67 and 26.67% (P < 0.05). We also found evidence that sodium valproate upregulates NM23H1 expression, which is a clue to its anti-cancer mode of action. The NM23H1 gene expression was relative fold increased determined by Western blotting at 3.2 mM VPA. Collectively, these observations indicate that sodium valproate has potential for use in breast cancer treatment.

Neuroprotective effect of grafting GDNF gene-modified neural stem cells on cerebral ischemia in rats.

Previous studies indicated the beneficial effects of glial cell line-derived neurotrophic factor (GDNF) and transplanted neural stem cells (NSCs) on stroke. Here, we explored whether transplantation of neural stem cells (NSCs) modified by GDNF gene provides a better therapeutic effect than native NSCs after stroke. Primary rat NSCs were transfected with GDNF plasmid (GDNF/NSCs, labeled by green fluorescent protein from AdEasy-1, GFP). Adult rats were subjected to two-hour middle cerebral artery occlusion and reperfusion, followed by infusion of NSCs (labeled with5-bromo-2'-deoxyuridine before infusion, BrdU), GDNF/NSCs and saline at 3 days after reperfusion (NSCs group, GDNF/NSCs group, control group), respectively. All rats were sacrificed at 1, 2, 3, 5, and 7 weeks after reperfusion. Modified Neurological Severity Scores (mNSS) test and H and E staining were respectively performed to evaluate neurological function and lesion volume. Immunohistochemistry was used to identify implanted cells and observe the expressions of Synaptophysin (Syp) and postsynaptic density-95 (PSD-95) and caspase-3. TdT-mediated dUTP-biotin nick-end labeling (TUNEL) was employed to observe apoptotic cells. Western blotting was used to detect brain-derived neurotrophic factor (BDNF) and NT-3 protein expression. Significant recovery of mNSS was found in GDNF/NSCs rats at 2 and 3 weeks after reperfusion compared with NSCs rats. Lesion volume in the NSCs and GDNF/NSCs groups was reduced significantly compared with control group. The number of NSCs in the GDNF/NSCs group was significantly increased in comparison with NSCs group. Moreover, Syp-immunoreactive product at 2 and 3 weeks after reperfusion and PSD-95 immunoreactive product in the GDNF/NSCs group were significantly increased compared with NSCs group. In contrast, caspase-3 positive cells and TUNEL-positive cells in the GDNF/NSCs group were significantly decreased compared with NSCs group. Significant increase of BDNF protein in the GDNF/NSCs and NSCs groups was observed compared to the control group at different time points of reperfusion, and GDNF/NSCs grafting significantly increased BDNF protein expression compared to NSCs grafting. In addition, significant increase of NT-3 protein in GDNF/NSCs and NSCs groups was detected only at 1 week of reperfusion compared to control group. The results demonstrate that grafting NSCs modified by GDNF gene provides better neuroprotection for stroke than NSCs grafting alone.

First Report of Ageratum yellow vein virus Causing Tobacco Leaf Curl Disease in Fujian Province, China.

A leaf curling disease was observed on 7% of tobacco plants during December 2005 in research plots in the Cangshan District of Fuzhou, Fujian, China. Tobacco plants were infested with Bemisia tabaci, suggesting begomovirus etiology. To identify possible begomoviruses, total DNA was extracted from four symptomatic leaf samples (F1, F2, F3, and F4). The degenerate primers PA and PB were used to amplify part of the intergenic region and AV2 gene of DNA-A-like molecules (3). A 500-bp DNA fragment was amplified by PCR from all four samples. The PCR products were cloned and sequenced (GenBank Accession Nos. EF531601-EF531603 and EF527823). Alignment of the 500-bp sequences for the four isolates indicated that they shared 98.5 to 99.6% nt identity, suggesting that the plants were all infected by the same virus. Overlapping primers TV-Full-F (5'-GGATCCTCTTTTGAACGAGTTTCC-3') and TV-Full-R (5'-GGATCCCACATGTTTAAAATAATAC-3') were then designed to amplify the full-length DNA-A from sample F2. The sequence was 2,754 nucleotides long (GenBank Accession No. EF527823). A comparison with other begomoviruses indicated the F2 DNA-A had the highest nucleotide sequence identity (95.7%) with Ageratum yellow vein virus (AYVV; GenBank Accession No. X74516) from Singapore. To further test whether DNAß was associated with the four viral isolates, a universal DNAß primer pair (beta 01 and beta 02) was used (4). An amplicon of approximately 1.3 kb was obtained from all samples. The DNAß molecule from F2 was then cloned and sequenced. F2 DNAß was 1,345 nucleotides long (GenBank Accession No. EF527824), sharing the highest nucleotide sequence identity with the DNAß of Tomato leaf curl virus (97.2%) from Taiwan (GenBank Accession No. AJ542495) and AYVV (88.8%) from Singapore (GenBank Accession No. AJ252072). The disease agent was transmitted to Nicotiana tabacum, N. glutinosa, Ageratum conyzoides, Oxalis corymbosa, and Phyllanthus urinaria plants by whiteflies (B. tabaci) when field infected virus isolate F2 was used as inoculum. In N. tabacum and N. glutinosa plants, yellow vein symptoms were initially observed in young leaves. However, these symptoms disappeared later during infection and vein swelling and downward leaf curling symptoms in N. tabacum and vein swelling and upward leaf curling in N. glutinosa were observed. In A. conyzoides, O. corymbosa, and P. urinaria plants, typical yellow vein symptoms were observed. The presence of the virus and DNAß in symptomatic plants was verified by PCR with primer pairs TV-Full-F/TV-Full-R and beta 01/beta 02, respectively. The above sequence and whitefly transmission results confirmed that the tobacco samples were infected by AYVV. In China, Tobacco leaf curl Yunnan virus, Tobacco curly shoot virus, and Tomato yellow leaf curl China virus were reported to be associated with tobacco leaf curl disease (1,3). To our knowledge, this is the first report of AYVV infecting tobacco in China. A. conyzoides is a widely distributed weed in south China and AYVV was reported in A. conyzoides in Hainan Island, China (2). Therefore, this virus may pose a serious threat to tobacco production in south China. References: (1) Z. Li et al. Phytopathology 95:902, 2005. (2) Q. Xiong et al. Phytopathology 97:405, 2007. (3) X. Zhou et al. Arch. Virol. 146:1599, 2001. (4) X. Zhou et al. J. Gen. Virol. 84:237, 2003.