Paraquat-induced convulsion and death: a report of five cases.

Paraquat (PQ) is a potent toxicant for humans, and poisoning with PQ is associated with high mortality. Patients with severe PQ-induced poisoning may die of multiple organ failure involving the circulatory and respiratory systems. Death resulting from epilepsy-like convulsions, which are infrequently noted reported with PQ poisoning, is observed clinically with this condition. This study presents the clinical data of five patients with severe PQ-induced poisoning who died of epilepsy-like convulsions, and related publications were reviewed in order to investigate the pathogenesis, clinical manifestations, and prognosis of these convulsions. Our results may help prevent this event and improve the success of treatment.

[Meta-analysis of leg length discrepancy after robot-assisted and traditional total hip arthroplasty].

Objective: To systematically evaluate the difference in leg length discrepancy (LLD) between robot-assisted total hip arthroplasty (THA) and traditional THA. Methods: The Cochrane Library, PubMed, Web of Science, EMbase, CNKI, Wanfang, VIP, and CBM databases were searched by computer to collect cohort studies of robot-assisted and traditional THAs from inception to August 11th, 2021. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias of the included studies. Meta-analysis was performed using RevMan 5.3 software. Results: A total of 10 high-quality cohort studies were included. The results of Meta-analysis showed that compared with traditional THA, LLD after robot-assisted THA was smaller [ MD=-1.64, 95% CI (-2.25, -1.04), P<0.001], Harris scores at 3 and 12 months after operation were higher [ MD=1.50, 95% CI (0.44, 2.57), P=0.006; MD=7.60, 95% CI (2.51, 12.68), P=0.003]. However, the operative time was longer [ MD=8.36, 95% CI (4.56, 12.17), P<0.000 1], and the postoperative acetabular anteversion angle was larger [ MD=1.91, 95% CI (1.43, 2.40), P<0.001]. There was no significant difference in Harris score at 6 months, amnesia index (Forgotten joint score, FJS), postoperative acetabular abduction angle, and incidence of complication between the two groups ( P>0.05). Conclusion: Robot-assisted THA is superior to traditional THA in postoperative LLD.

Celecoxib prevents tumor necrosis factor-α (TNF-α)-induced cellular senescence in human chondrocytes.

Osteoarthritis (OA) is a cartilage degenerative disease commonly observed in the elderly population and significantly impacts the normal life of OA patients. It has been reported that the development of pathological cell senescence in chondrocytes is involved in the pathogenesis of OA. Celecoxib is a common non-steroidal anti-inflammatory drug, and it has been recently reported to exert therapeutic effects on OA. However, its underlying mechanism is still unclear. The present study intends to explore its mechanism and provide fundamental evidence for the application of Celecoxib in the treatment of clinical OA. Tumor necrosis factor-α (TNF-α) was utilized to establish an in vitro model of chondrocytes senescence. The elevated reactive oxygen species (ROS) generation, increased cell cycle arrest in G0/G1 phase, reduced telomerase activity, and upregulated senescence-associatedß-galactosidase (SA-ß-Gal) staining were all observed in TNF-α-treated chondrocytes, which were then dramatically reversed by 10 and 20 µM Celecoxib. In addition, the upregulated DNA damage biomarkers, p-ATM, and p-CHK2, observed in TNF-α-treated chondrocytes were significantly downregulated by 10 and 20 µM Celecoxib. Lastly, the expression level of p21 and p53 was greatly elevated in chondrocytes by stimulation with TNF-α which was then pronouncedly repressed by treatment with Celecoxib. Taken together, our data reveal that Celecoxib ameliorated TNF-α-induced cellular senescence in human chondrocytes.

Exposure characterization and risk assessment of ultrafine particles from the blast furnace process in a steelmaking plant.

OBJECTIVES: This study aimed to clarify the exposure characteristics and risks of ultrafine particles from the blast furnace process and to provide a reasonable control strategy for protecting the health of workers. METHODS: The blast furnace location of a steelmaking plant was selected as a typical investigation site. A membrane-based sampling system was used to collect ultrafine particles to analyze their morphology and elemental compositions. A real-time system was used to monitor the total number concentration (NC), total respirable mass concentration (MC), surface area concentration (SAC), and size distribution by number. The risk level of ultrafine particles was analyzed using the Stoffenmanager-Nano model. RESULTS: The total NC, total MC, and SAC increased significantly relative to background concentrations after slag releasing started and decreased gradually after the activity stopped. The three highest total concentrations during slag releasing were 3-10 times higher than those of the background or non-activity period. The ultrafine particles were mainly gathered at 10.4 or 40 nm, and presented as lump-like agglomerates. The metal elements (Al and Pt) in the ultrafine particles originated from slag and iron ore. The risk level of the ultrafine particles was high, indicating the existing control measures were insufficient. CONCLUSIONS: The blast furnace workers are at high risk due to exposure to high levels of ultrafine particles associated with working activity and with a bimodal size distribution. The existing control strategies, including engineering control, management control, and personal protection equipment need to be improved.

[Study of ALAD and VDR gene polymorphisms associated with lead nephrotoxicity susceptibility].

OBJECTIVE: To explore lead nephrotoxicity associated with delta-aminolevulinic acid dehydratase, vitamin D receptor gene polymorphism as well as joint effect of gene-gene, gene-environment. METHODS: 233 occupational lead-exposed workers were involved in this study. Then blood lead was detected as lead exposure biomarker. Urinary N-acetyl-beta-D-glucosamindase and beta2-microglobin of those workers were measured as biomarkers of nephrotoxicity. PCR-RFLP method was used for gene polymorphism analysing. RESULTS: Lead exposure concentration was higher than national limit, NAG acticity were (2.12 +/- 0.07) U/mmol Cr in workers with ALAD1-2/ALAD2-2 genotype and (1.73 +/- 0.03) U/mmol Cr in workers with ALAD1-1 genotype (P < 0.05). In the same condition, beta2-MG were (20.94 +/- 1.12) microg/mmol Cr in workers with VDR-Bb genotype and (15.28 +/- 0.09) microg/mmol Cr in workers with VDR-bb genotype (P = 0.01). Analysis of logistic regression confirmed that lead exposure and high blood lead as well as combined effect of gene-environment were responsible for lead nephrotoxicity in workers (OR = 6.58, 2.41, 3.01). CONCLUSION: Polymorphisms of ALAD and VDR gene may play an important role in lead nephrotoxicity in high lead-exposed workers. Joint effect of gene-environment could be involved in lead nephrotoxicity in workers.

The Circadian Gene Per1 Plays an Important Role in Radiation-Induced Apoptosis and DNA Damage in Glioma.

Objective: Period1 (PER1), a core circadian gene, not only modulates circadian rhythm but may also play an important role in other biological processes, including pathways involved in the proliferation and apoptosis of tumor cells. In this study, we investigated the mechanism by which the downregulated expression of PER1 promotes the apoptosis of wild-type P53 human glioma U343 cells exposed to X-rays. Methods:U343 cells were exposed to 6 mV 10 Gy X-ray irradiation after infection with an shRNA lentivirus to reduce the expression of PER1 and were analyzed by SCGE analysis, flow cytometry, qRT-PCR, and western blotting. Result: SCGE analysis revealed that compared with the controls, U343 cells expressing low levels of PER1 showed minor DNA damage when exposed to X-ray irradiation (P<0.05), and the flow cytometry assay showed lower death rates (P<0.05). RT-PCR and western blot analysis both revealed decreased expression of CHK2 and P53, which regulate DNA damage and repair via the CHK2-P53 pathway, and decreased expression of C-MYC, which is related to cell apoptosis. Conclusion:Our research suggests that PER1 may play an important role in tumor radiotherapy, which is attributable to enhanced chk2-P53 signaling and proapoptotic processes. These findings provide a new target for the clinical treatment of glioma and a reliable basis for postradiation therapy and gene therapy for glioma and other cancers.

Exposure-lag-response association between sunlight and schizophrenia in Ningbo, China.

Previous studies found that mental disorders such as bipolar disorder, seasonal affective disorder and schizophrenia, often show seasonal variability, which usually be attributed to the variations in the number of natural sunlight. However, few studies have been conducted on the acute effects of exposure to sunlight on the onset of these disease. The aim of this study was to evaluate the exposure-response relationship between sunshine duration and the hospital admissions for schizophrenia. We obtained data on hospital admissions for schizophrenia from the largest psychiatric hospital in Ningbo, China, during 2012-2016. A Distributed lag non-linear model was used to estimate the exposure-lag-response relationship between sunlight and schizophrenia. We calculated the effects of short and long sunshine duration, defined using the cutoffs at the 1st and 99th sunshine duration percentiles. We detected significant and non-linear associations between sunlight and schizophrenia, and the overall estimated relative risk (RR) for a lag of 0-21 days was 1.45 (95% CI: 1.07, 1.97) and 1.41(95% CI: 0.72, 2.75) for short and long sunshine duration, respectively. The burden of schizophrenia was greater during periods with short sunshine duration than during periods with long sunshine duration, with the AFs of 19.94% (95% CI: 8.65%, 28.24%) and 2.12% (95% CI: -2.70%, 5.57%), respectively. The female and people more than 45 years old were most susceptible to these effects. We repeated our analysis by using global solar radiation as a continuous exposure variable of sunlight intensity in the model, and the result shows that the female and middle-aged and eldly patients were also susceptible to the effects of low levels of global solar radiation. Our findings suggest that there may be a relationship between lack of exposure to sunlight and increased risk of hospital admissions for schizophrenia. Policymakers and doctors should promote further understanding of the health benefits of sunlight and take effective measures to prevent schizophrenia.

Role of taurine upregulated gene 1 as a predictor of poor outcome in osteosarcoma.

AIMS: Previous studies have found that long noncoding RNA taurine upregulated gene 1 (TUG1) can regulate osteosarcoma cells apoptosis and proliferation; the aim of this study was to investigate the clinical significance of TUG1 in osteosarcoma. SUBJECTS AND METHODS: The expression of TUG1 was detected by real-time and quantitative polymerase chain reaction assay in 94 pairs of tumor tissues and corresponding noncancerous bone tissues of osteosarcoma patients. Its correlations with clinicopathologic features were analyzed, and the significance of TUG1 as a prognostic factor was determined. RESULTS: This study shows that the expression of TUG1 in osteosarcoma tissues was significantly higher than that in adjacent normal bone tissues. Upregulation of TUG1 was significantly correlated with the larger tumor size and advanced tumor-node-metastases stage of osteosarcoma patients. Kaplan-Meier curve showed a decreased overall survival time of osteosarcoma patients with high TUG1 expression. Moreover, univariate and multivariate analyses suggested that low-expression level of TUG1 was an independent poor prognostic indicator for osteosarcoma patients. CONCLUSIONS: In conclusion, our data support TUG1 as a potential prognostic predictor and gene therapy target with its high expression in tumor tissues and its association with carcinogenesis and progression in osteosarcoma.

Inhibition of long noncoding RNA BDNF-AS rescues cell death and apoptosis in hypoxia/reoxygenation damaged murine cardiomyocyte.

BACKGROUND: Hypoxia/reoxygenation (H/R)-induced cardiomyocyte damage in vitro bears many similarities to myocardial infraction in vivo. In this study, we investigated whether long noncoding RNA (lncRNA) BDNF-AS has functional role in rescuing H/R-induced damage in cardiomyocyte in vitro. METHOD: Murine neonatal cardiomyocytes were cultured in vitro, and treated with either long (Hypoxia (L)) or short (Hypoxia (S)) H/R conditions. Viability and TUNEL assays were conducted to assess cardiomyocyte death or apoptosis. QRT-PCR was used to examine BDNF-AS mRNA expression. Endogenous BDNF-AS was downregulated by siRNA in cardiomyocyte. Its effect on H/R-induced cardiomyocyte damage was then examined. In addition, survival-associated proteins, including BDNF, VEGF and Akt were examined by western blot in siRNA-transfected cardiomyocytes. RESULTS: Hypoxia (S) induced apoptosis whereas Hypoxia (L) induced cell death in murine neonatal cardiomyocyte in vitro. Under both conditions, endogenous cardiomyocyte BDNF-AS was significantly upregulated. SiRNA-mediated BDNF-AS downregulation rescued cardiomyocyte death under Hypoxia (L) condition, and reduced cardiomyocyte apoptosis under Hypoxia (L) condition. Moreover, BDNF-AS downregulation activated BDNF and VEGF through upregulation, and activated Akt through phosphorylation in H/R-damaged cardiomyocyte. CONCLUSION: Inhibition of lncRNA BDNF-AS may be an efficient way to rescue cardiomyocyte from H/R-induced apoptosis or cell death.

[Optical, scanning electron and atomic force microscopic observation of the microstructure of human humeral bone].

OBJECTIVE: To observe the microstructure of human long bone with scanning electron and atomic force microscopes to understand the ultrastructural organization and the composition and the morphology of the bone collagen and minerals. METHOD: Fresh human cadaveric humeral bone were fixed and dehydrated to prepare the ground sections and thin slices, respectively, which were observed for bone microstructure using optical, scanning electron and atomic force microscopy, respectively. RESULTS: Under optical microscope, the bone lacunae were in circular permutation around the Haversian canal, and the canaliculi communicated the lacunae and Haversian canal or between the lacunae. Atomic force microscopy represented distinct morphology of the large clusters of collagen, and the collagen fibers thickened in the mineralized zone and appeared in the shape of overlapping discs, whereas the calcium-phosphorus crystal displayed ellipse cylinders. The size, shape and relation of the canaliculi and lacunae were observed clearly. The bone matrix was observed in circular arrangement along the Haversian canal and the calcium-phosphorus crystal was in regular alignment under scanning electron microscope. CONCLUSION: Atomic force microscopy can help analyze the three-dimensional configuration of calcium-phosphorus crystal and bone collagen as well as the canaliculi and lacuna. The canaliculi serve as the channels mediating alimentation and molecular signals into the lacuna.

[In vitro biocompatibility of novel absorbable hydroxyapatite and AO artificial bone beta-tricalcium phosphate with rhesus bone marrow stromal cells].

OBJECTIVE: To study the in vitro biocompatibility of novel hydroxyapatite (HA) and AO artificial bone beta-tricalcium phosphate (beta-TCP) with rhesus bone marrow stromal cells (rBMSCs) . METHODS: The third passage of rBMSCs were cultured with HA and beta-TCP respectively, with the cells cultured without the materials as the control. The morphology and proliferation of cells were observed by inverted phase-contrast microscope and scanning electron microscope (SEM). MTT assay was used to semiquantitatively evaluate the cell proliferation. RESULTS: The rBMSC cocultured with HA exhibited good growth as observed under inverted phase-contrast microscope, without significant difference from the cells in the control group. Some small particles were seen pealing off from beta-TCP, and some of the cells died. Under SEM, rBMSCs showed good adhesion to HA with obvious proliferation, but the ratio of adhesive cells was not as high as that in beta-TCP group. MTT assay showed no significant difference in the cell number between HA and the control groups, but the cell number in beta-TCP group was notably less than that of control group. CONCLUSION: Novel HA has good biocompatibility with rBMSCs for bone tissue engineering, and AO artificial bone still needs improvement to serve as scaffold material for BMSCs.

Effect of pretreatment with adenosine, diazoxide or ischemic preconditioning on ischemia- reperfusion injury in the limbs of rats.

OBJECTIVE: To study the effect of ischemic preconditioning (PC) and pharmacological preconditioning with adenosine or diazoxide on ischemia-reperfusion (IR) injury in the limbs of rats. METHODS: According to different treatment received before ischemic-reperfusion injury, 66 SD rats were divided into 6 groups including a normal control and a ischemia-reperfusion control group, IP10 group in which the rats received 10-min ischemia followed by 10-min interval for reperfusion for 3 times before IR, IP5 group in which the rats were subjected to 5-min ischemia with 5-min reperfusion intervals for 3 times before IR, adenosine (Ade) pretreatment group and diazoxide (Dia) pretreatment group. Except the normal control group, which consisted of 6 rats, each group contained 12 rats, and IR injury was induced by blocking the blood flow in bilateral limbs for 4 h, followed by reperfusion for 2 or 24 h when twitch and spastic contractility of the tibialis anterior muscle and serum creatine phosphokinase (CPK) were measured. RESULTS: In IP5 and Ade pretreatment group, the twitch tension of the tibialis anterior muscle of the rats was significantly enhanced after 2 and 24 h of reperfusion, achieving the level of the normal control. The twitch tension was also enhanced in rats of IP10 group at 24 h, but at 2 h, though with less effectiveness than that in IP5 and Ade group. Dia pretreatment reduced twitch and tetanic contraction forces of the tibialis anterior muscle after 2 h of reperfusion, but obviously improved twitch tension at 24 h. Improvement in the tetanic tension, however, was seen in none of the groups. Serum CPK of IP5, IP10 and Ade groups after 2 and 24 h while Dia at only 24 h of reperfusion was obviously lower than that of IR group. CONCLUSIONS: Ischemic and Ade preconditioning can protect the limbs of rats from ischemia-reperfusion injury, and Dia has delayed protective effect. IP5 is superior than IP10 and Ade PC can produce similar effect to that of ischemic PC.

Crocetin induces cytotoxicity in colon cancer cells via p53-independent mechanisms.

OBJECTIVE: Crocin has been proposed as a promising candidate for cancer chemoprevention. The purpose of this investigation was to investigate the chemopreventive action and the possible mechanisms of crocin against human colon cancer cells in vitro. METHODS: Cell proliferation was examined using MTT assay and the cell cycle distribution fractions were analyzed using flow cytometric analysis after propidium iodide staining. Apoptosis was detected using the TUNEL Apoptosis Detection Kit with laser scanning confocal microscope. DNA damage was assessed using the alkaline single-cell gel electrophoresis assay, while expression levels of p53, cdk2, cyclin A and P21 were examined by Western blot analysis. RESULTS: Treatment of SW480 cells with crocetin (0.2, 0.4, 0.8 mmol/L) for 48 h significantly inhibited their proliferation in a concentration-dependent manner. Crocetin (0.8 mmol/L) significantly induced cell cycle arrest through p53-independent mechanisms accompanied by P21 induction. Crocetin (0.8 mmol/L) caused cytotoxicity in the SW480 cells by enhancing apoptosis and decreasing DNA repair capacity in a time-dependent manner. CONCLUSIONS: This report provides evidence that crocetin is a potential anticancer agent, which may be used as a chemotherapeutic drug.

A potential calcium antagonist and its antihypertensive effects.

Imperatorin (Imp) as a hypotensive active ingredient, its hypotensive effect was evaluated in the SHRs, its calcium antagonism and affinity to L-type calcium channel was also confirmed. The results showed that the blood pressure was decreased in the SHRs treated with Imp, the aortic ring was relaxed with Imp, L-type calcium channel currents and intracellular calcium free ion rise was nearly disappeared when adding Imp. In addition, Imp displayed a chromatographic peak similar to nitrendipine and verapamil by the cell membrane chromatography, same results from protein-drug docking approaches. Hence, Imp target the L-type calcium channel, and may be used as a novel antihypertensive drug.

[Green fluorescent protein as a tracer of bone marrow stromal cells in bone tissue engineering in rhesus].

OBJECTIVE: To observe the role of green fluorescent protein (GFP) in tracing rhesus bone marrow stromal cells (rBMSCs) during tissue-engineered bone formation in vivo. METHODS: Ad5.CMV-GFP was amplified by infecting QBI-293A cells, and the bone marrow was harvested from the ilium of adult male rhesus to obtain rBMSCs, which were cultured and passaged in vitro. GFP was transfected into the third-passage rBMSCs via adenovirus vector and the labeled cells were inoculated into absorbable HA scaffold and cultured for 3 days, with untransfected rBMSCs as control, before the cell-matrix compounds were implanted into the latissimus dorsi muscles of rhesus. Samples were harvested at 6 week and embedded in paraform, and ground sections of the bone tissue were prepared to observe green fluorescence under laser scanning confocal microscope. Propidium iodide staining of the sections was also performed for observation. RESULTS: The rBMSCs grew well after GFP transfection, and green fluorescence could be seen 24 h after the transfection and became stronger till 48 h, with a positive transfection rate beyond 80%. Six weeks after cell implantation, the rBMSCs labeled by GFP-emitted green fluorescence were detected in the bone tissue under laser scanning confocal microscope. CONCLUSION: GFP can effectively trace BMSCs during bone tissue engineering, and the transplanted BMSCs constitute the main source of bone-forming cells in bone tissue engineering.