Objective To investigate the inhibitory effects of high mobility group chromosomal protein N2 (HMGN2)on growth of human bladder cancer T24 cells and ectopic tumor growth of nude mice. Methods MTT and flow cytometry assay were conducted to detect cell growth of bladder epithelial cells(T24)cells in vitro. The transplantation tumor models in nude mice were constructed by injecting T24 cells in vivo. The para-tumorswere injected with PBS,HMGN2 protein and cisdichlorodiamineplatinum(DDP),respectively. Tumor volume and weight were calculated. The expression of cell proliferation-related proteins was detected by Western blot assay. Results MTT assay proved that HMGN2 could significantly inhibit the growth of T24 cells. Flow cytometry assay verified that HMGN2 could block T24 cells in S stage of the cell cycle. The average tumor volume and weight in the HMGN2 group and DDP positive control group were smaller than those in the PBS group(P<0.05,respectively), with the tumor inhibitory rate of 25% and 23%,respectively. The results of Westernblot showed that HMGN2 could decrease Bcl-2 expression and increase Bax expression in tumor. Conclusion HMGN2 has a significant antitumor effect on T24 cells and bladder carcinoma in nude mice,which may be associated with the induction of the apoptosis of carcinoma cells and the regulation of the cell cycle.

Objective To investigate the short-term clinical outcome of one-level degenerative diseases for a single surgeon during his initial phase of performing a minimally invasive surgery oblique lumbar interbody fusion (OLIF) on the basis of perioperative parameters and follow-up data.Methods A prospective analysis of 49 consecutive patients that underwent a OLIF between November 2014 and March 2016 by corresponding author was performed.Only those patients that were single level,index surgeries were included.Every patient had a diagnosis of degenerative lumbar diseases including lumbar spondylolisthesis (25 cases),discogenic low back pain (14 cases) or segmental instability (10 cases).Patients underwent an indirect decompression and fusion using an expandable tubular retractor and single intervertebral cage with bilateral percutaneous pedicle screw fixation.49 patients were divided into the A group (the first 24 patients) and the B group (25 patients after the initial 24 patients).The following data were compared between the two groups:surgical time for Skin-Skin (minutes),estimated blood loss (ml),radiograph exposure time (seconds),the clinical and radiographic results,and intra-/postoperative complications.All intraoperative parameters only included the measurement and findings related with the OLIF procedure.The short-term clinical outcome of single level degenerative lumbar diseases treated by OLIF was assessed on the basis of follow-up data.The learning curve was measured using a logarithmic curve-fit regression analysis.Results Average operative time was significantly longer in the A group 47.1±10.6 min compared with the B group 37.2± 10.0 min.In comparison with the B group,the A group had significantly more X-ray exposure time (25.3±6.1 s versus 17.1±6.9 s).The operative and X-ray exposure time gradually decreased as the series progressed,and an asymptote was reached after about 20 cases.There was no statistically significant difference in intraoperative blood loss between the A group (28.1± 18.2) ml and the B group 24.4± 10.9 ml.The most observed complication was donor site pain (11 cases,45.8％),followed by thigh numbness/pain (5 cases,20.8％) and psoas/quadriceps weakness (2cases,8.3％),paralytic ileus (one case,4.2％) and sympathetic nerve injury (one case,4.2％) in the A group.Donor site pain occurred in four patients (16.0％),thigh numbness/ pain in three patients (12.0％),psoas/quadrieeps weakness in one patient (4.0％) and sympathetic nerve injury in one patient (4.0％) in the B group.All complications were transient and resolved within 3 months.The incidence of complications excluding donor site pain in the early period (A group) and the later period (B group) was 37.5％ and 20.0％,respectively,although there were no significant differences in perioperative complications between both groups.Forty nine patients were followed up for more than 1 year,and the average follow-up period was 18.5±3.9 months.The back pain VAS and ODI scores decreased respectively from 6.4±2.3 before surgery to 1.5±0.9 in final follow-up and from 37.1 ±9.4 before surgery to 11.8±3.9 in the last follow-up time.Total fusion rate was 89.8％ (44/49 cases)in final follow-up.Radiographic evaluation showed similar bony fusion in the A group (22 of 24 cases) with the B group (22 of 25 cases) in the last follow-up time.Conclusion Single level degenerative lumbar diseases can safely and effectively be treated by using OLIF with a good short-term clinical outcome.The procedure presents a learning curve to the practicing spine surgeon with regards to operative time,X-ray exposure time and intra-/postoperative complications.Intraoperative parameters improved with understanding the minimally invasive technique.Close attention to details can minimize complications that may be associated with the learning curve.

OBJECTIVETo detect the embryo toxicity and the teratogenicity of DNAN in rats and provide basic data to occupational protection.

METHODS120 adult female SD rats and 60 male rats are mating for 1: 1, and the pregnant rats were randomly divided into five groups by the pregnant time. The negative control group are gavaged with 4% starch, and the three experiment groups are gavaged with DNAN suspension with the dose of 5 mg/kg, 15 mg/kg and 45 mg/kg respectively, while the positive control give aspirin of 280 mg/kg. All rats of the five groups are administrated gavage from gestation day 5 (GD5) to GD19 continuously. The rats are dislocated in GD20, and the toxicity of embryo and toetus are detected.

RESULTSThe net weight growth in all three dose group are less than that of negative group, while the dead foetus in high dose group is more than negative group. Moreover, the body weight, body lenghth, tail lenghth and the anal genital distance of foetus rats in high dose group are all less than that of negative group. The foetus external malformations of three dose groups appear no significant compared with negative group.However, the prevalences of skeleton malformation in high dose group and the internal organs malformation in the median and high dose group appear significant higher than that of negative group. There are significantly maternal reproductive toxicity, embryo toxicity and toetus toxicity in positive group.

CONCLUSIONDNAN can induced maternal reproductive toxicity, embryo toxicity and the teratogenicity to rats.

Animals ; Anisoles ; toxicity ; Female ; Male ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Teratogens ; toxicity ; Toxicity Tests

OBJECTIVETo detect the toxicity and teratogenicity of 2, 2-dinitroethene-1, 1-diamine (FOX-7) in rats.

METHODS125 adult SD rats were randomly divided into five groups, which are negative control (0 mg/kg) , positive control (280 mg/kg aspirin) , and three dose groups (5, 15, and 45 mg/kg) . They were administrated by gavage once a day from the 5th days to 19th days after pregnancy. The weight changes and toxicity of pregnant rats are recorded within the study, and the skeleton and internal organs malformations are detected by the recommended methods.

RESULTSAfter 5 or 6 days being poisoned, the pregnant rats appear significantly toxicity symptoms, such as exciting, irritability, and so on. The net weight raise in high dose group is less than the negative group, while the numbers of dead foetus in median and high dose groups are both more than that of negative group. Comparing with the negative group, the body weight and body lenghth of foetus rats in median and high dose groups, and the tail lenghth in high dose group are lower significantly. There are no external malformations in negative group and three dose groups. However, the foetus of high dose group appear significant skeleton and internal organs malformation prevalences that are significant more than negative group, including lateral cerebral ventricles enlarged, which accounts for 9.17%, occipital bone lost, which accounts for 2.59%.

CONCLUSIONFOX-7 can induced maternal reproductive toxicity, foetus toxicity and teratogenicity hazards to rats.

Animals ; Body Weight ; Female ; Nitro Compounds ; toxicity ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Teratogens ; toxicity ; Toxicity Tests

Objective: To investigate the effects of simulated-thermobaric explosive gas on the respiration and nervous system in rats. Methods: 70 of SPF SD rats were randomly divided into four thermobaric explosive gas groups, two restoration observation groups and control group from April to August in 2018. The exposure time of in four thermobaric explosive gas groups were 3.75, 7.5, 15.0 and 30 min, respectively. The restoration observation groups were designed to observe for 30 and 120 min after exposure thermobaric explosive gas 30 min. The bloods were collected and analyzed at the end of exposure and recovery observation. The endogenous carbon monoxide (CO) , nitric oxide (NO) , glutamic acid (GLU) , acetylcholinesterase (AchE) and dopamine (DA) were detected in brain tissues, respectively. Results: The blood gas index (pH, PCO₂, PO₂, COHb, O₂Hb, MeHbt) and blood electrolytes (Na⁺, K⁺, Ca²⁺ and Cl^-) in exposure groups have significant differences with these in control (P<0.05) . The pH value decreased with the exposure time longer. However, it basically returned to normal level when terminating exposure for 120 min. The concentration of PCO₂, MeHb and CoHb increased first and then decreased with the exposure time extension. Conversely, The PO₂ and O₂Hb decreased first and then increased with the exposure time longer. The concentration of endogenous CO, GLU, and AchE decreased and NO increased in exposure group 4 and the restoration observation group 1 compared with those in control (P<0.01) . In addition, there were pathological changes in lung and brain tissue of exposure group, such as inflammatory cell infiltration and edema. Conclusion The blood gas index, electrolytes, neurotransmitter, histopathology of lung and brain were changed to various degrees by thermobaric bomb gas exposure. These findings would provide some beneficial support for evaluating the damage effect of thermobaric bomb gas on organisms.

Objective:To establish a rapid, sensitive and specific detection method for important imported viruses based on the recombinase aided amplification (RAA) method and clustered regularly interspaced short palindromic repeats-associated protein 13a (CRISPR-Cas13a) system.Methods:In this study, we selected Japanese encephalitis virus (JEV), Yellow fever virus (YEV), West Nile virus (WNV), Middle East respiratory syndrome coronavirus (MERS-CoV)、Ebola virus (EBOV), Dengue virus (DENV), Rift Valley fever virus (RVFV), Zika virus (ZIKV) as subjects, and designed specific RAA primers and CRISPR RNA(crRNA). The sensitivity and specificity of the method were evaluated. We detected suspected clinical samples of dengue fever and compared with the fluorescent reverse transcriptase-polymerase chain reaction (RT-PCR) technology. Clinical simulation samples of the remaining seven viruses were also detected.Results:The RAA method combined with CRISPR-Cas13a can detect eight pathogens within 40-52 min at 39 ℃. The sensitivity was 1-10 copies/μl. There was no cross-reaction among eight viruses and all clinical samples could be detected by this method.Conclusions:The established RAA combined with CRISPR-Cas13a detection method can sensitively, specifically and quickly detect eight imported infectious disease pathogens.

Objective:To explore the association between insulin resistance (IR) and genome-wide DNA methylation based on Shanghai twin study.Methods:Monozygotic twins (MZ) from Shanghai were recruited during 2012-2013, 2017-2018, and 2022-2023. Data were collected by questionnaire survey, physical examination and laboratory tests. Genome-wide DNA methylation was quantified. Generalized linear mixed effect model was applied to analyze the association between methylation level at each site and homeostatic model assessment 2-insulin resistance (HOMA2-IR). Non-paired and paired designs were used to assess the association between DNA methylation and phenotype of IR. Cluster analysis was conducted to identify the clusters of top significant sites. Generalized linear regression was performed to examine the differential methylation patterns from clusters.Results:A total of 100 MZ pairs were included in this study. Hypermethylated cg10535199-2q23.1 ( β=0.74%, P=1.51×10 -7, OR=1.06, 95% CI: 1.03-1.09) and ch.17.49619327- SPOP ( β=0.23%, P=7.54×10 -7, OR=1.17, 95% CI: 1.08-1.28) were identified with suggestive significance. After correcting for multiple testing, no sites reached genome-wide significance. There was no statistical significance in the paired analysis. Two clusters with hypomethylated ( β=-0.39%, P<0.001) and hypermethylated ( β=0.47%, P<0.001) patterns were observed for HOMA2-IR. Conclusions:IR was significantly associated with DNA methylation, and genetic factors might contribute to the association.

Ovarian cancer is the most malignant gynecologic malignancy. In recent years, histone modifying enzymes (HMEs) have been widely studied as an important part of epigenetic modifi-cations in ovarian cancer. Histone modifying enzymes, including histone methyltransferases and demethylases, histone acetyltransferases and deacetylases, play an important role in the prolif-eration and migration of ovarian cancer cells by modifying histone and non-histone proteins, and can regulate the development of chemoresistance. Inhibitors of various histone modifying enzymes play good anti-tumor effects in ovarian cancer by promoting cell growth arrest and apoptosis, inhibi¬ting tumor cell invasion, and increasing chemo¬therapy sensitivity, and are expected to be a new strategy for precision treatment of ovarian cancer. Therefore, this paper will review the mechanism of action and therapeutic potential of histone modifying enzymes involved in methylation and acetylation processes in ovarian cancer.

OBJECTIVE: To explore the sub-chronic oral toxicity of 1,1-diamino-2,2-dinitroethene( FOX-7) in rats.METHODS: Ninety-six specific pathogen free healthy adult SD rats were randomly divided into control group,low-,medium-,and high-dose groups. Each group consisted of 24 rats,half of them were males and the other half were females.The low-,medium-,and high-dose groups of rats were exposed to 10,30,90 mg /( kg·d) body weigh of 1,1-diamino-2,2-dinitroethene by gavage for 90 days,once a day,6 days a week. The control group was given the same volume of 4%water starch solution. The toxic symptoms,the body weight,food utilization,routine blood,blood biochemical indicators,organ coefficients and histopathology changes of the rats were observed or tested. RESULTS: a) The body weights of male and female rats in the high-dose group in the 28 th day after exposure were lower than those of the control group for the same time and same sex( P < 0. 05). Food utilization in the male and female high-dose group in the 77 th and 90 th day after exposure were lower than those of the control group for the same time and same sex( P < 0. 05). b) Red blood cell counts,hemoglobin levels,hematocrit levels in the female rats of low-,medium-,and high-dose groups were lower than those of the female control group( P < 0. 05). Platelet counts in the female high-dose group was lower than that of the female control group( P < 0. 05). Red blood cell counts,hemoglobin level,hematocrit level and mean corpuscular hemoglobin concentration in the male high-dose group were lower than those of the male control group( P < 0. 05). The platelet counts in the male medium-,and high-dose group were lower than that of the male control group( P < 0. 05). c) Total cholesterol levels in female medium-,and high-dose group and blood urea nitrogen level in the female high-dose group were higher than those of the female control group( P < 0. 05). In high-dose group,the levels of total protein and uric acid were higher and lactate dehydrogenase level was lower than those of the control group( P < 0. 05). d) The spleen organ coefficients in the female high-dose group were higher and those in male medium- and high-dose groups were higher than those of the control group for same sex( P < 0. 05). The organ coefficients of liver and kidney in high-dose group were higher than those of the control group( P < 0. 05),the organ coefficients of testis and epididym in the male high-dose group were lower than those of the male control group( P < 0. 05). The testis convoluted tubule shrink and seminiferous cells decreased in the male high-dose group. e) The no observed adverse effect level of FOX-7 dinitroethene in female rats were less than10. 00 mg /( kg·d) and it was 10. 00 mg /( kg·d) in the male rats. CONCLUSION: FOX-7 could inhibit the growth of rats and damage the blood system and male reproductive system.

BACKGROUND: Congenital heart disease (CHD) is one of the most common congenital malformations in humans. Inconsistent results emerged in the existed studies on associations between air pollution and congenital heart disease. The purpose of this study was to evaluate the association of gestational exposure to air pollutants with congenital heart disease, and to explore the critical exposure windows for congenital heart disease. METHODS: The nested case-control study collected birth records and the following health data in Tianjin Women and Children's Health Center, China. All of the cases of congenital heart disease from 2013 to 2015 were selected matching five healthy controls for each case. Inverse distance weighting was used to estimate individual exposure based on daily air pollution data. Furthermore, the conditional logistic regression with distributed lag non-linear model was performed to identify the association between gestational exposure to air pollution and congenital heart disease. RESULTS: A total of 8,748 mother-infant pairs were entered into the analysis, of which 1,458 infants suffered from congenital heart disease. For each 10 µg/m³ increase of gestational exposure to PM_2.5, the ORs (95% confidence interval, 95%CI) ranged from 1.008 (1.001-1.016) to 1.013 (1.001-1.024) during the 1^st-2^nd gestation weeks. Similar weak but increased risks of congenital heart disease were associated with O₃ exposure during the 1^st week and SO₂ exposure during 6^th-7^th weeks in the first trimester, while no significant findings for other air pollutants. CONCLUSIONS This study highlighted that gestational exposure to PM_2.5, O₃, and SO₂ had lag effects on congenital heart disease. Our results support potential benefits for pregnancy women to the mitigation of air pollution exposure in the early stage, especially when a critical exposure time window of air pollutants may precede heart development.
Infant ; Pregnancy ; Child ; Humans ; Female ; Air Pollutants/analysis* ; Case-Control Studies ; Prenatal Exposure Delayed Effects/epidemiology* ; Heart Defects, Congenital/etiology* ; China/epidemiology* ; Particulate Matter/adverse effects* ; Maternal Exposure/adverse effects*