High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

Analysis of Perinatal Outcomes of Twin Pregnancy in a Referral Hospital for High Risk

Introduction: The incidence of twin pregnancies has increased significantly in recent decades. These pregnancies require more attention due to their worse outcomes than singleton pregnancies. Objective: To analyze the characteristics and perinatal outcomes of twin pregnancies at the Caxias do Sul General Hospital. Methods: This is a descriptive and retrospective study that included all births related to twin pregnancies between March 1998 and June 2018. Maternal and perinatal variables were analyzed. Descriptive analyses were carried out using measures of central tendency and dispersion for continuous variables (mean and standard deviation or median and interquartile range), according to a prior assessment of distribution using the Shapiro-Wilk test, and absolute (n) and relative (n%) frequencies for categorical variables. Results: 172 pairs of twins/21,972 births (0.8%) were identified. There was a high percentage of interpartum interval of less than 12 months, adherence and prenatal visits, body mass index, and need for neonatal intensive care. Stillbirth and neomortality rates were within acceptable parameters. Conclusion: The sample studied showed a percentage similar to that in the literature, a high rate of maternal and perinatal complications, characterizing it as a high-risk fetal pregnancy.

Hmo1:A versatile member of the high mobility group box family of chromosomal architecture proteins

Eukaryotic chromatin consisting of nucleosomes connected by linker DNA is organized into higher order structures,which is facilitated by linker histone H1.Formation of chromatin compacts and protects the genome,but also hinders DNA transactions.Cells have evolved mechanisms to modify/remodel chromatin resulting in chromatin states suitable for genome functions.The high mobility group box(HMGB)proteins are non-histone chromatin architectural factors characterized by one or more HMGB motifs that bind DNA in a sequence nonspecific fashion.They play a major role in chromatin dynamics.The Saccharomyces cerevisiae(yeast hereafter)HMGB protein Hmo1 contains two HMGB motifs.However,unlike a canonical HMGB protein that has an acidic C-terminus,Hmo1 ends with a lysine rich,basic,C-terminus,resembling linker histone H1.Hmo1 exhibits characteristics of both HMGB proteins and linker histones in its multiple functions.For instance,Hmo1 promotes transcription by RNA polymerases I and II like canonical HMGB proteins but makes chromatin more compact/stable like linker histones.Recent studies have demonstrated that Hmo1 destabilizes/disrupts nucleosome similarly as other HMGB proteins in vitro and acts to maintain a common topological architecture of genes in yeast genome.This minireview reviews the functions of Hmo1 and the underlying mechanisms,highlighting recent discoveries.

Prevalence of Precancerous Lesions Based on Digital Cervicography with VIA/VILI among Women Positive for High-Risk Human Papillomavirus Serotypes: A Screening Center-Based Study in Cameroon

Background: Since 2021, high-risk Human Papilloma Virus (HR-HPV) testing has been the recommended screening test for cervical cancer for all settings;either used alone in a “test and treat” strategy, or with a triage test, with or without biopsy, before treatment. Cameroon has rolled out immunization against HPV 16 and 18, but studies show a higher prevalence of non-16/18 HR-HPV types. Objectives: Determine the prevalence of precancerous lesions, in women with HR-HPV infection and evaluate association of digital cervicography (DC) VIA/VILI positivity with HPV serotype, as a measure of their contribution to precancer and cancer incidence. Methodology: The study was cross-sectional, descriptive, and analytic. It took place at the Etoug-Ebe and Ekoudoum Baptist Hospitals in Yaoundé, during the period April-September 2022. We reviewed the records of women screened for cervical cancer between February 2020 and December 2021 and evaluated the prevalence of lesions on digital cervicography (DC) with VIA/VILI for women positive for HR-HPV serotypes. The data were analyzed using SPSS version 20.0 for Windows. P values Results: We identified 315 cases with a positive HR-HPV deoxyribonucleic acid (DNA) test, 224 (71.1%) had a DC VIA/VILI triage test done. Of these, 30 (13.4%) women had a positive DC VIA/VILI, with five women (2.2%) having lesions suggestive of cancer. Out of 11 cases positive for HPV 16 alone, 05 (45.5%) had a positive DC VIA/VILI test. Of the 14 cases positive for HPV 18 alone, 03 (21.4%) had a positive VIA/VILI, meanwhile only 19 (10.7%) of the 177 cases positive for non-16/18 HPV had a positive VIA/VILI test. Conclusion: A high proportion of women (13.4%) with HR HPV had a positive DC VIA/VILI, with a significant proportion (2.2%) having lesions suggestive of invasive cervical cancer HR-HPV serotype was associated with DC VIA/VILI positivity;HPV 16 had the strongest association (45.5%), followed by HPV 18 (21.4%), and non-16/18 HR-HPV (10.7%), suggesting a decreasing order of oncogenicity.

Effects of Health Education with Problem-Based Learning Approaches on the Knowledge, Attitude, Practice and Coping Skills of Women with High-Risk Pregnancies in Plateau Areas

Objective: Given the unique cultural background, way of life, and physical environment of the Tibetan Plateau, this study aims to investigate the effects of health education using problem-based learning (PBL) approaches on the knowledge, attitude, practice, and coping skills of women with high-risk pregnancies in this region. Methods: 76 high-risk pregnancy cases were enrolled at Tibet’s Linzhi People’s Hospital between September 2023 and April 2024. 30 patients admitted between September 2023 and December 2023 were selected as the control group and were performed with regular patient education. 46 patients admitted between January 2024 and April 2024 were selected as the observation group and were performed regular patient education with problem-based learning approaches. Two groups’ performance on their health knowledge, attitude, practice and coping skills before and after interventions were evaluated, and patient satisfaction were measured at the end of the study. Results: There was no statistical significance (P P P Conclusions: Health education with problem-based learning approaches is worth promoting as it can help high-risk pregnant women in plateau areas develop better health knowledge, attitude and practice and healthier coping skills. Also, it can improve patient sanctification.

Current molecular methods for the detection of hepatitis C virus in high risk group population:A systematic review

Hepatitis C virus(HCV) is an emerging infection worldwide and the numbers of persons infected are increasing every year. Poor blood transfusion methods along with unsafe injection practices are potential sources for the rapid spread of infection. Early detection of HCV is the need of the hour especially in high riskgroup population as these individuals are severely immunocompromised. Enzyme Immunoassays are the most common detection techniques but they provide no evidence of active viremia or identification of infected individuals in the antibody-negative phase and their efficacy is limited in individuals within high risk group population. Molecular virological techniques have an important role in detecting active infection with utmost specificity and sensitivity. Technologies for assessment of HCV antibody and RNA levels have improved remarkably, as well as our understanding of how to best use these tests in patient management. This review aims to give an overview of the different serological and molecular methods employed in detecting HCV infection used nowadays. Additionally, the review gives an insight in the new molecular techniques that are being developed to improve the detection techniques particularly in High Risk Group population who are severely immunocompromised.

Seroprevalence of <i>Brucella</i>Antibodies and Risk Factors Associated with Human Brucellosis in High-Risk Occupational Groups of the Noun Division in the West Region of Cameroon

Brucellosis is an anthropozoonotic disease with an important public health impact. Although the transmission of Brucella from animals to humans can occur in different epidemiological settings of sub-Saharan African countries, little data has been published on human brucellosis. This study aimed to detect Brucella antibodies and the risk factors associated to brucellosis among high-risk occupational groups of people in the Noun Division of Cameroon. For this study, a structured questionnaire was used to assess risk factors associated with human brucellosis. Thereafter, blood samples were collected from high-risk occupational groups of people in four villages. Plasma was extracted from each sample and Brucella antibodies were detected using Rose Bengal Plate Test (RBPT) and indirect Enzyme-Linked Immunosorbent Assay (i-ELISA). Of the 273 participants enrolled, the overall seroprevalence of Brucella antibodies was 12.45% with RBPT and 10.26% with i-ELISA test. This seroprevalence was significantly (P = 0.04;X2 = 9.73) higher among livestock herdsmen (15.8%), slaughterhouse workers (9.8%), butchers (4.8%), participants having no educational level (14.3%) and those experiencing above 5 years of risky activity (15%). Raw milk consumption (OR: 4.8;P = 0.001), no formal education (OR: 6.4;P = 0.03) and assistance of animal during parturition (OR: 7.2;P < 0.0001) appeared as factors that may increase the risk of Brucella infections. The detection of Brucella antibodies indicates the risk of human brucellosis in some groups of people of the Noun division. Consuming unpasteurized milk, participating in parturition and lacking knowledge on brucellosis appeared as risk factors associated with human brucellosis in western Cameroon. It raises the need of developing and implementing control measures for human and animal brucellosis.

Phenolic Profile,Antioxidant,Antihyperlipidemic and Cardiac Risk Preventive Effect of Pigmented Black Rice Variety Chakhao poireiton in High-Fat High-Sugar Induced Rats

The present study aimed to investigate the hypolipidemic,antioxidant and cardiac risk-suppressing effects of Chakhao poireiton(CP),a GI-tagged pigmented black rice from India.In vitro and ex vivo studies confirmed that whole rice extracts of CP have potent antioxidant,3-hydroxy-3-methylglutaryl-CoA reductase,cholesterol esterase inhibitory,and antilipase effects.An in vivo study was conducted to evaluate the effects of the ethanol extracts of CP on high-fat high-sugar induced hyperlipidemic rats.The ethanol extract significantly ameliorated lipid parameters and liver enzymes to normal.Levels of lactate dehydrogenase,creatine kinase-N-acetyl cysteine,C-reactive protein,and lipoprotein a were significantly lower in the extract-treated groups than those in the disease control group.A marked reduction of ApoB/ApoA1 and other atherogenic indices were observed in extract-treated groups.Twelve phenolic compounds,i.e.rosamarinic acid,gallic acid,protocatechuic acid etc.,were quantified in CP.This study provided the first evidence of the antihyperlipidemic and cardiac risk inhibitory effects of CP,which would be beneficial in preventing and managing hyperlipidemia,associated oxidative stress,and cardiac complications.

Clinical Significance of Serum Uric Acid Combined with Cystatin C Detection in Patients with Different Levels of Hypertension with High Risk Degree and Above

Objective: To explore the clinical significance of serum uric acid combined with cystatin C detection in high risk degree of hypertension of different grades. Methods: The patients who were treated in the Department of Cardiovascular Medicine of our hospital from January to December 2022 were selected as the study subjects, and the high risk and extremely high risk groups of grade I, II and III hypertension were selected for comparative analysis to explore their clinical significance. Results: There was a statistically significant difference in the number of patients with extremely high risk of grade II hypertension between men and women (P 0.05), which showed that there was no specificity in the concentration detection of serum uric acid and cystatin C in different grades of hypertension;there was no significant difference in serum uric acid concentration between grade II and grade III of hypertension with high risk grade and cystatin C concentration between grade I and grade III of hypertension with high risk grade (P > 0.05), but there was significant difference in the concentration detection of serum uric acid and cystatin C between the other groups (P < 0.05), which indicates that the detection of serum uric acid and cystatin C has important clinical significance in the high risk degree of hypertension. Conclusion: In the comparison of the detection of blood uric acid and cystatin C in different levels of hypertension with extremely high risk, the difference of cystatin C in grade I and grade III was not statistically significant, and the rest were statistically significant;therefore, the detection of serum uric acid and cystatin C can provide reliable laboratory data for clinical diagnosis and treatment of the extremely high risk degree of different levels of hypertension.

Enterprise Internal Control Based on Risk Management with Moutai Group as an Example

Focusing on the two themes of"internal control"and"risk management",this paper makes an in-depth analysis of the current situation of risk management and internal control of Moutai Group.It analyzes the current situation of risk management and internal control of Moutai Group.It is found that the risk management of Moutai Group is not perfect,the information exchange is not smooth,and the internal control assessment is not perfect.Finally,it puts forward some corresponding countermeasures,including establishing an effective information communication mechanism,perfecting the risk assessment system,and strengthening the construction of the professional talent team.

Suppressing high mobility group box-1 release alleviates morphine tolerance via the adenosine5'-monophosphate-activated protein kinase/heme oxygenase-1 pathway

Opioids,such as morphine,are the most potent drugs used to treat pain.Long-term use results in high tolerance to morphine.High mobility group box-1(HMGB1) has been shown to participate in neuropathic or inflammatory pain,but its role in morphine tolerance is unclear.In this study,we established rat and mouse models of morphine tolerance by intrathecal injection of morphine for 7 consecutive days.We found that morphine induced rat spinal cord neurons to release a large amount of HMGB1.HMGB1 regulated nuclear factor κB p65 phosphorylation and interleukin-1β production by increasing Toll-like receptor 4receptor expression in microglia,thereby inducing morphine tolerance.Glycyrrhizin,an HMGB1 inhibito r,markedly attenuated chronic morphine tole rance in the mouse model.Finally,compound C(adenosine 5’-monophosphate-activated protein kinase inhibitor) and zinc protoporphyrin(heme oxygenase-1 inhibitor)alleviated the morphine-induced release of HMGB1 and reduced nuclear factor κB p65 phosphorylation and interleukin-1β production in a mouse model of morphine tolerance and an SH-SY5Y cell model of morphine tole rance,and alleviated morphine tolerance in the mouse model.These findings suggest that morphine induces HMGB1 release via the adenosine 5’-monophosphate-activated protein kinase/heme oxygenase-1 signaling pathway,and that inhibiting this signaling pathway can effectively reduce morphine tole rance.

Level of Acceptance of COVID-19 Vaccine and Its Determinants among High Risk Groups for Severe COVID-19 Infection Living in Mogadishu Somalia

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which is widely referred to as “COVID-19”, has been infecting more than 5.5 million over 144 countries. A vaccine is considered to be the most awaiting intervention and hundreds of global R&D institutions engaged in unprecedented speed to develop the vaccine. The availability of COVID-19 vaccines may not translate into its uptake. Although governments will provide the vaccines, their uptake is voluntary. Objective: This study was carried out to evaluate the level of acceptance of COVID-19 vaccine and it’s determinants among high risk groups for severe COVID-19 infection living in Mogadishu Somalia. Methods: The study was cross-sectional, descriptive analysis conducted to obtain reliable information about the acceptance of COVID-19 vaccine and it is determinants among high-risk groups living in Mogadishu, Somalia. The calculated sample size was 404 using Cochran’s formula = Z2p(1 − p)/d2 and addition of 5% non-respondent rate. According to PESS population estimate in 2020, there are 17 districts. We grouped them into 2 strata and through simple random sampling one district was selected from each strata. After randomly selecting the two districts, three sub districts were randomly selected from each and then every second house (1, 3, 5) in the main roads will be selected. If target population were not found in the second selected house, the next house will be taken until sample size is obtained. Results: 59.4% of respondents were willing to accept and take vaccination while 40.6% of them were not accepting the vaccination. Being afraid of the side effect was the most common reason for not accepting the vaccine Conclusion: More than one third of respondents (40.6%) were not willing to accept the vaccination, knowledge towards COVID-19 was strongly associated with acceptance level of COVID-19 vaccine. Recommendation: Multi-sector organized awareness campaigns involving FMH as well as local authorities and civil society to enhance level of knowledge of community towards COVID-19.

Application Analysis of High Risk HPV Detection Combined with Cervical Cytology, Colposcopy and Pathology in Cervical Lesions of Women in Tiandeng County

Purpose: To understand the application of high-risk HPV detection combined with cervical cytology, colposcopy and pathology in cervical lesions of women in Tiandeng County. Method: Women in the outpatient and inpatient departments of our hospital from January 2021 to October 2022 were collected for high-risk HPV testing, TCT, colposcopy and pathological examination according to their personal wishes, to understand the application of relevant examinations in cervical lesions. Result: In 2021, the number of patients was 5801, among whom 1743 patients had received cervical cancer examination in the past, accounting for 30.05% of the total number of patients, and 5795 who had volunteered for TCT examination this time, accounting for 99.90% of the total;A total of 289 cases of atypical squamous cells with unclear significance (ASC-US) were detected, excluding 11 cases of high-grade squamous intraepithelial lesions (ASC-H), 122 cases of low-grade squamous intraepithelial lesions (LSIL), 16 cases of high-grade squamous intraepithelial lesions (HSIL), 2 cases of squamous cell carcinoma (SCC), and 4 cases of atypical adenocyte (AGC);Atypical cervical adenocytosis and cervical carcinoma in situ were not detected. The number of people who volunteered for high-risk HPV testing was 4237, and the number of positive cases was 740, accounting for 17.47% of the screening population;Among 740 HPV-positive patients, 488 high-risk HPV-positive patients were selected for TCT examination, and 87 patients were found to be TCT positive;From 401 high-risk HPV-positive and TCT negative patients, 287 patients with possible lesions were screened out for colposcopy;The results showed that 60 patients may have certain cervical lesions and need further pathological examination and the results showed that 28 patients had CTN1 and 18 patients had CIN2 - 3. In 2022, 8840 patients received medical treatment, among which 3188 patients had received cervical cancer examination in the past, accounting for 36.06% of the total number of patients, and 8314 patients voluntarily underwent TCT examination, accounting for 94.05% of the total number of patients. 434 cases of atypical squamous cells with ambiguous meaning (ASC-US) were detected, excluding 13 cases of high-grade squamous intraepithelial lesions (ASC-H), 217 cases of low-grade squamous intraepithelial lesions (LSIL), 35 cases of high-grade squamous intraepithelial lesions (HSIL), 1 case of squamous cell carcinoma, and 4 cases of atypical adenocarcinoma (AGC);Atypical cervical adenocytosis and cervical carcinoma in situ were not detected. The number of volunteers for high-risk HPV testing was 3871 cases, and the number of positive cases was 654 cases, accounting for 16.89% of the screening number. 527 high-risk HPV-positive patients were selected from 654 HPV-positive patients for TCT examination, and the number of TCT-positive patients was found to be 49. From 478 high-risk HPV-positive patients with TCT negative, 276 patients with possible lesions were screened out for colposcopy;The results showed that 66 patients may have certain cervical lesions and need further pathological examination;and then the results showed that 31 cases of CTN1 and 6 cases of CIN2 - 3. Conclusion: Gynecological high-risk HPV examination can provide better etiological sources for cervical cancer screening;Cervical cytology examination has high sensitivity;Colposcopy examination has high specificity;Pathological examination can be used as an effective supplement for cervical cytology examination and colposcopy;So high-risk HPV combined with cytology examination, colposcopy examination and pathological examination has high clinical application value;It is worth popularizing and applying.

Distribution of High-Risk Human Papillomavirus Genotypes among Women with Colposcopic Diagnosis of Cervical Intraepithelial Neoplasia in Bangladesh

Background: The incidence of cervical cancer is high in Bangladesh and there is a high prevalence of preinvasive lower genital tract disease among women of reproductive age. Persistent high-risk Human Papilloma Virus (HPV) infection is the main underlying cause of cervical cancer and its precursor, cervical intraepithelial neoplasia (CIN). Objective: The aim of the study was to identify the subtypes of high-risk HPV infection among women with the colposcopic diagnosis of cervical intraepithelial neoplasia in Bangladesh. Methods: This cross-sectional observational study was conducted in the colposcopy clinic of Dhaka Medical College Hospital over a six-month period. A total of 100 participants were enrolled. Married women, between 30 - 60 years of age with colposcopically diagnosed cervical intra epithelial neoplasia were enrolled. Women with chronic illness, pregnancy, and women unable to consent were excluded from this study. After counselling, colposcopically directed punch biopsies were taken from each CIN case concurrently with high-risk HPV testing by polymerase chain reaction (PCR). Results: The mean age of the patients was 38.69 (SD ±7.76) years. CIN 1 was diagnosed in 57% of participants, while 24% had CIN II and 19% had CIN III lesions. High-risk HPV was present in 52 patients. HPV 16 was the most common identified in 28 (53.84%) and HPV 18 was the second most common with 20 (38.46%) either singly or in combination with other high-risk subtypes. The other HPV strains, HPV 31, 33, 35, 52, 56 and 58, were also detected either as mono or co-infections. Out of the 52 HPV positive cases, 29 (55.8%) had mono infection and 23 (44.2%) had co-infection with several subtypes. The highest incidence (50%) of oncogenic HPV infections was present among women aged 35 - 45 years. Risk factors associated with HPV positive cases were high parity (P 0.05), early age at marriage (P = 0.754) and early age of first child. Conclusion: This study identified a high prevalence of HPV 16 and 18 genotypes. HPV vaccination with the current 9-valent HPV vaccine, which contains HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Will be an effective public health measure to eradicate cervical cancer in Bangladesh.

Effects of High Risk Pregnancy Factors on Pelvic Floor Muscle Weakness and Changes of PG, ACTH and CRP

Objective: To investigate the effects of different delivery modes on perinatal pelvic floor muscle strength, PG, ACTH and CRP of high-risk pregnant women. Methods: 380 high-risk pregnant women who gave birth in our hospital from March 2021 to February 2022 were selected as subjects, including 100 vaginal natural delivery, 156 forceps assisted delivery and 124 cesarean section. Pelvic floor pressure, PG, ACTH, CRP, IL-6, TNF-α and IL-4, IL-10 levels were evaluated and compared. The perinatal occurrence of pelvic floor functional disease (PFD) in high-risk pregnant women in each group was analyzed and evaluated. Results: There were statistical differences in the amount of postpartum blood loss (P 0.0001, F = 99.01), postpartum blood loss 24 h (P = 0.0004, F = 19.54) and hospital stay (P 0.0001, F = 70.81) among the three groups of high-risk women in natural vaginal delivery, forceps delivery and cesarean section. In addition, there were 72, 134 and 70 cases of abnormal pelvic floor fatigue in natural vaginal delivery, forceps assisted delivery and cesarean section (P 0.0001, χ2 = 30.16). There were 36, 79 and 21 cases of muscle injury, respectively (P 0.0001, χ2 = 34.16). There were 49, 98 and 43 cases of dysmuscular contraction, respectively (P 0.0001, χ2 = 21.94). There were 65, 120 and 41 cases with vaginal dynamic pressure 80 cm H2O (P 0.0001, χ2 = 56.86), respectively. The.

High-mobility group box 1 protein and its role in severe acute pancreatitis

The high mobility group box 1(HMGB1),which belongs to the subfamily of HMG-1/-2,is a highly conserved single peptide chain consisting of 215 amino acid residues with a molecular weight of approximately 24894 Da.HMGB1 is a ubiquitous nuclear protein in mammals and plays a vital role in inflammatory diseases.Acute pancreatitis is one of the most common causes of acute abdominal pain with a poor prognosis.Acute pancreatitis is an acute inflammatory process of the pancreas(duration of less than six months),for which the severe form is called severe acute pancreatitis(SAP).More and more studies have shown that HMGB1 has a bidirectional effect in the pathogenesis of SAP.Extracellular HMGB1 can aggravate the pancreatic inflammatory process,whereas intracellular HMGB1 has a protective effect against pancreatitis.The mechanism of HMGB1 is multiple,mainly through the nuclear factor-κB pathway.Receptors for advanced glycation endproducts and toll-like receptors(TLR),especially TLR-2 and TLR-4,are two major types of receptors mediating the inflammatory process triggered by HMGB1 and may be also the main mediators in the pathogenesis of SAP.HMGB1 inhibitors,such as ethyl pyruvate,pyrrolidine dithiocarbamate and Scolopendra subspinipes mutilans,can decrease the level of extracellular HMGB1 and are the promising targets in the treatment of SAP.

A survey of high risk factors affecting retinopathy in full-term infants in China

AIM: To investigate the possible relationship between the influencing factors occurring before and during birth in full-term infants and the outcome of retinopathy. METHODS: Totally 816 full-term infants admitted in the neonate intensive unit of Boai Hospital of Zhongshan between 1 May, 2008 and 30 June, 2011 were included in the study. Fundus examination was performed and evaluated individually on them at the age of 48 hours after delivery, 2 weeks and 1 month. Some possible risk factors happening prenatally or during delivery such as pregnant related hypertension, placenta previa, placental abruption etc, as well as some neonatal risk factors such as neonatal asphyxia, hypoxic-ischemic encephalopathy (HIE), low birth weight etc, were recorded and evacuated. Then the effect of the risk factors of full-term infants on retinopathy was studied. RESULTS: The incidence of retinal hemorrhage of full-term infants with prenatal pregnant related hypertension (PRH) of the mother (43.6%) was significantly higher than that of full-term infants without (8.0%). (P<0.001). The incidence of retinal hemorrhage of full-term infants with neonatal asphyxia and /or hypoxic-ischemic encephalopathy (HIE)(29.3%) was significantly higher than that of those without (15.7%), but correlation was not found between the severity of retina hemorrhage and the degree of hypoxic disease. A pale color of optic disc was associated with a low birth weight of full-term infant. Full-term infants with birth weigh-less than 2500g had a significant higher incidence of retinopathy than those with birth weight equal or more than 2500g( P<0.001). CONCLUSION: The main influencing factors which lead to retinopathy of high risk full-term infants are prenatal factors such as PRH, and some neonatal risk factors such as asphyxia, hypoxic-ischemic encephalopathy, and low birth weight.

High mobility group box-1 protein inhibits regulatory T cell immune activity in liver failure in patients with chronic hepatitis B

BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMGB1) protein is involved in the process of endotoxemia. Regulatory T (Treg) cells maintain immune tolerance and contribute to the immunological hyporesponsiveness against HBV infection. However, the roles of HMGB1 and Treg cells in the pathogenesis of liver failure in CHB patients, and whether HMGB1 affects the immune activity of Treg cells are poorly known at present, and so were explored in this study. METHODS: The levels of HMGB1 expression were detected by ELISA, real-time RT-PCR, and Western blotting, and the percentage of CD4(+)CD25(+)CD127(low) Treg cells among CD4(+) cells was detected by flow cytometry in liver failure patients with chronic HBV infection, CHB patients, and healthy controls. Then, CD4(+)CD25(+)CD127(low) Treg cells isolated from the peripheral blood mononuclear cells from CHB patients were stimulated with HMGB1 at different concentrations or at various intervals. The effect of HMGB1 on the immune activity of Treg cells was assessed by a suppression assay of the allogeneic mixed lymphocyte response. The levels of forkhead box P3 (Foxp3) expression in Treg cells treated with HMGB1 were detected by RT-PCR and Western blotting. RESULTS: A higher level of HMGB1 expression and a lower percentage of Treg cells within the population of CIA(+) cells were found in liver failure patients than in CHB patients (82.6+/-20.1 mu g/L vs. 34.2+/-13.7 mu g/L; 4.55+/-1.34% vs. 9.52+/-3.89%, respectively). The immune activity of Treg cells was significantly weakened and the levels of Foxp3 expression were reduced in a dose- or time-dependent manner when Treg cells were stimulated with HMGB1 in vitro. CONCLUSIONS: The high level of HMGB1 and the low percentage of Treg cells play an important role in the pathogenesis of liver failure in patients with chronic HBV infection. Moreover, HMGB1 can weaken the immune activity of Treg cells. It is suggested that effectively inhibiting HMGB1 expression could be a feasible way to treat liver failure by suppressing endotoxemia and enhancing Treg cell activity.

Risk Factors of Precancerous Gastric Lesions in A Population at High Risk of Gastric Cancer

Objective： In cancer prevention, the targeting of precancerous lesions has been recognized as the most promising method. However, little attention has been paid to the risk factors of precancerous gastric lesions, especially in rural China where there is high prevalence of precancerous gastric lesions. We therefore conducted a cross-sectional study in Liaoning province, China, to investigate the potential risk and protective factors of these precancerous gastric lesions. Methods： A total of 1,179 subjects with high risk of gastric cancer from Zhuanghe County were included in this study. Standard questionnaires were used in collecting epidemiological factors and the data were then analyzed by the unconditional logistic regression model. Results： Smoking and drinking were the risk factors for the precancerous gastric lesions among rural subjects, and the association of smoking or drinking and the precancerous gastric lesions increased in strength with the daily consumption and duration. As the factors such as age, gender, smoking, alcohol were controlled, a multivariable analysis revealed that there was a significant correlation between the deep-fry food intake and the gastric epithelial dysplasia with the odds ratio （OR） of 1.78 [95% confidence interval （CI）： 1.01-3.12]. Garlic eating was shown to confer protection against the development of gastric ulcer （OR=0.55, 95% CI： 0.33-0.92）. Conclusion： Smoking and drinking were the risk factors for the precancerous gastric lesions among rural subjects. Deep-fry food intake might be one of the risk factors for the precancerous gastric lesions and garlic eating was shown to confer protection against the development of gastric ulcer among rural Chinese population.

High mobility group box 1 protein (HMGB1) as an immune-modulating factor for polarization of human T lymphocytes

Objective This study was performed to investigate the effect of high mobility group box-1 protein (HMGB1) on immune function of human T lymphocytes in vitro and explore its potential role in cell-mediated immune dysfunction. Methods Fresh blood was obtained from healthy adult volunteers and peripheral blood mononuclear cells (PBMCs) were isolated, then rhHMGB1 was added to PBMCs. Four-color flow cytometric (FCM) analysis was used for the measurement of intracellular cytokine including interleukin IL-4 and interferon IFN- ? ELISA kits were employed for the determination of IL-2 and sIL-2R protein levels in cell culture supernatants. Results (1) Different stimulating time and dosage of rhHMGB1 did not alter the number of IFN- αpositive cells (Th1). rhHMGB1 stimulation provoked a dose-dependent and time-dependent increase in Th2 subset and decrease in ratio of Th1 to Th2. (2) Compared with the untreated cells, when the cells were coincubated with rhHMGB1 (10-100ng/ml) for 12 hrs, protein release of IL-2 and sIL-2R were significantly up-regulated. At 48 hrs, in contrast, protein production was relatively lower in cells after exposure to 100-1000 ng/ ml rhHMGB1. Conclusions These findings demonstrated that HMGB1 has a dual influence on immune functions of human T lymphocytes.