Natural pyrethrins induce cytotoxicity in SH-SY5Y cells and neurotoxicity in zebrafish embryos (Danio rerio).

Natural pyrethrins are widely used in agriculture because of their good insecticidal activity. Meanwhile, natural pyrethrins play an important role in the safety evaluation of pyrethroids as precursors for structural development of pyrethroid insecticides. However, there are fewer studies evaluating the neurological safety of natural pyrethrins on non-target organisms. In this study, we used SH-SY5Y cells and zebrafish embryos to explore the neurotoxicity of natural pyrethrins. Natural pyrethrins were able to induce SH-SY5Y cells damage, as evidenced by decreased viability, cycle block, apoptosis and DNA damage. The apoptotic pathway may be related to the involvement of mitochondria and the results showed that natural pyrethrins induced a rise in Capase-3 viability, Ca2+ overload, a decrease in adenosine triphosphate (ATP) and a collapse of mitochondrial membrane potential in SH-SY5Y cells. Natural pyrethrins may mediate DNA damage in SH-SY5Y cells through oxidative stress. The results showed that natural pyrethrins induced an increase in reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and catalase (CAT) activity, and induced a decrease in glutathione peroxidase (GPx) activity in SH-SY5Y cells. In vivo, natural pyrethrins induced developmental malformations in zebrafish embryos, which were mainly characterized by pericardial edema and yolk sac edema. Meanwhile, the results showed that natural pyrethrins induced damage to the Huc-GFP axis and disturbed lipid metabolism in the head of zebrafish embryos. Further results showed elevated ROS levels and apoptosis in the head of zebrafish embryos, which corroborated with the results of the cell model. Finally, the results of mRNA expression assay of neurodevelopment-related genes indicated that natural pyrethrins exposure interfered with their expression and led to neurodevelopmental damage in zebrafish embryos. Our study may raise concerns about the neurological safety of natural pyrethrins on non-target organisms.

[Cangxi Tongbi Capsules promote chondrocyte autophagy by regulating circRNA＿0008365/miR-1271/p38 MAPK pathway to inhibit development of knee osteoarthritis].

To investigate the mechanism by which Cangxi Tongbi Capsules promote chondrocyte autophagy to inhibit knee osteoarthritis(KOA) progression by regulating the circRNA＿0008365/miR-1271/p38 mitogen-activated protein kinase(MAPK) pathway. The cell and animal models of KOA were established and intervened with Cangxi Tongbi Capsules, si-circRNA＿0008365, si-NC, and Cangxi Tongbi Capsules combined with si-circRNA＿0008365. Flow cytometry and transmission electron microscopy were employed to determine the level of apoptosis and observe autophagosomes, respectively. Western blot was employed to reveal the changes in the protein levels of microtubule-associated protein light chain 3(LC3)Ⅱ/Ⅰ, Beclin-1, selective autophagy junction protein p62/sequestosome 1, collagen Ⅱ, a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS-5), and p38 MAPK. The mRNA levels of circRNA＿0008365, miR-1271, collagen Ⅱ, and ADAMTS-5 were determined by qRT-PCR. Hematoxylin-eosin staining was employed to reveal the pathological changes of the cartilage tissue of the knee, and enzyme-linked immunosorbent assay to measure the levels of interleukin-1ß(IL-1ß) and tumor necrosis factor-alpha(TNF-α). The chondrocytes treated with IL-1ß showed down-regulated expression of circRNA＿0008365, up-regulated expression of miR-1271 and p38 MAPK, lowered autophagy level, increased apoptosis rate, and accelerated catabolism of extracellular matrix. The intervention with Cangxi Tongbi Capsules up-regulated the expression of circRNA＿0008365, down-regulated the expression of miR-1271 and p38 MAPK, increased the autophagy level, decreased the apoptosis rate, and weakened the catabolism of extracellular matrix. However, the effect of Cangxi Tongbi Capsules was suppressed after interfering with circRNA＿0008365. The in vivo experiments showed that Cangxi Tongbi Capsules dose-dependently inhibited the p38 MAPK pathway, enhanced chondrocyte autophagy, and mitigated articular cartilage damage and inflammatory response, thereby inhibiting the progression of KOA in rats. This study indicated that Cangxi Tongbi Capsules promoted chondrocyte autophagy by regulating the circRNA＿0008365/miR-1271/p38 MAPK pathway to inhibit the development of KOA.

High failure rate after Beta-tricalcium phosphate grafting for the treatment of femoral head osteonecrosis: a retrospective analysis.

BACKGROUND: Non-vascularized bone grafting is a promising head-preserving technique for younger patients diagnosed as non-traumatic osteonecrosis of the femoral head (NONFH). Among the various types of bone grafting techniques, "light-bulb" procedure grafting with synthetic bone substitute is an attractive option. We aimed to assess the effectiveness of using beta-tricalcium phosphate (ß-TCP) for the treatment of pre-collapse and early post-collapse lesions NONFH. METHODS: From April 2010 to June 2014, 33 patients (47 hips) with NONFH were treated using the afore-mentioned technique. The clinical and radiological outcomes were recorded and compared statistically between pre- and post-operation. Harris hip score (HHS) was used to evaluate the clinical results, and Association Research Circulation Osseous (ARCO) stage was applied to assess the radiological outcomes. RESULTS: The 5-years survival rate of using ß-TCP grafting was accounting for 25.5%. HHS was decreased from 78.47 to 52.87 points, and a very significant worsening of radiological results were revealed (P <  0.05). Two hips collapsed more than 2 mm were awaiting for THA, and 33 of the 47 hips had converted to THAs in an average time to failure of 24.24 months postoperatively. Meanwhile, only 4 hips survived without collapse, and 8 hips collapsed less than 2 mm. After surgery, the time onset of head collapse was 3.65 months on average, and the first conversion to THA was performed at 5 months postoperative. CONCLUSIONS: Our results suggest that "light-bulb" procedure grafting with ß-TCP sticks presented with a high failure rate in the early postoperative period. It is not proposed for the treatment of pre-collapse and early post-collapse lesions NONFH.

Incidence of and Risk Factors and Reinterventions for Post-Pancreatoduodenectomy Hemorrhage: Retrospective Analysis.

AIMS: To analyze the incidence of and risk factors for post-pancreatoduodenectomy (PD) hemorrhage (PPH) and to evaluate the outcomes of reinterventions for PPH. METHODS: All PDs between January 2009 and December 2014 were retrospectively evaluated. PPH was evaluated according to the criteria of the International Study Group of Pancreatic Surgery. Both univariate and multivariate analyses of risk factors for PPH and mortality were performed. Reinterventions were also evaluated. RESULTS: Of the 1,056 PDs during the study period, 78 (7.4%) developed PPH, including 36 with grade B and 42 with grade C. Of these 78 patients, 24 (30.8%) died of PPH-related causes. Multivariate analysis showed that older age, higher total bilirubin concentration, and postoperative pancreatic fistula (POPF) were independent risk factors for PPH. Patients who died of PPH were significantly older and had lower preoperative hemoglobin and albumin concentrations than patients who did not die of PPH. Of the 78 patients with PPH, 58 underwent reintervention, including 27 who underwent angiography, 24 who underwent endoscopy, 24 who underwent re-laparotomy, and 15 who underwent more than one reintervention. CONCLUSIONS: Older age, total bilirubin, and POPF are independent risk factors for PPH. Higher mortality are associated with advanced PPH and poor nutritional conditions.

The tumor suppressive role of RASSF1A in osteosarcoma through the Wnt signaling pathway.

Ras-association domain family 1 isoform A (RASSF1A) is a tumor suppressor gene and its expression is lost in numerous types of cancer cells, including primary osteosarcoma cells. However, its functional significance in osteosarcoma has not been well defined. The messenger RNA (mRNA) expression of RASSF1A in osteosarcoma tissues and corresponding non-tumoral tissues was measured by real-time PCR. Overexpression of RASSF1A was established by an adenoviral vector expressing RASSF1A. Cell migration and invasion were analyzed in transwells. Apoptosis and cell cycle were analyzed using flow cytometry. Wnt/ß-catenin activity was measured by TCF reporter dual-luciferase assay. Cell viability was measured by MTT assay. Protein expression was detected by Western blot. RASSF1A mRNA expression was significantly lower in osteosarcoma tissues than that in the corresponding non-tumoral tissues. The lowered RASSF1A expression correlated with the clinical severity of osteosarcoma. rAd-RASSF1A injection significantly inhibited the growth of xenograft MNNG/HOS tumors in mice. Overexpression of RASSF1A resulted in significant inhibition of the proliferation, migration, and invasion; induced apoptosis; and arrested cell cycle at G0/G1 phase in both the MNNG/HOS and SaOS2 cells. Overexpression of RASSF1A inhibited the Wnt/ß-catenin activity, decreased phosphorylation of Akt/glycogen synthase kinase-3-ß (GSK3-ß), and increased phosphorylation of mammalian sterile 20-like kinase 1 (MST1). Overexpression of RASSF1A downregulated the cyclin D1, c-Myc, and matrix metalloproteinase-7 (MMP-7) protein levels. RASSF1A functions as a tumor suppressor in osteosarcoma and exerts anti-cancer roles through regulating Akt/GSK-3-Wnt/ß-catenin signaling.

Chronic pancreatic inflammatory granuloma caused by foreign body presenting as a pancreatic pseudotumor: A case report and literature review.

In clinical practical work, a rare kind of chronic pancreatic inflammatory granuloma which is caused by the foreign body of gastrointestinal perforation could be misdiagnosed and treated as pancreatic neoplasm sometimes, and even brings irreparable harm to patients. Here, we depict a male presenting recurrent upper abdominal pain and gradual weight loss, besides, the computer tomography suggested pancreatic tumor strongly. Fortunately, it has been proved to be a chronic pancreatic inflammatory granuloma caused by fish bone through laparotomy finally. To our knowledge, this case is the first case about the chronic pancreatic inflammatory granuloma caused by foreign body which successfully avoids unnecessary pancreatectomy.

Protective effects of Vitamin C against spinal cord injury-induced renal damage through suppression of NF-κB and proinflammatory cytokines.

Spinal cord injury [SCI] leads to complex cellular and molecular interactions which affects various organ systems. The present study focused on determining the protection offered by Vitamin C against spinal injury-induced kidney damage in wistar rats. The experimental protocol was performed with three groups; Sham, SCI and Vitamin C [20 mg/kg/bw] followed by SCI. The kidney tissue was investigated for oxidative stress parameters [reactive oxygen species, protein carbonyl, sulphydryl content, thiobarbituric acid reactive species [TBARS], and myeloperoxidase activity] and antioxidant status [glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase activity]. Further, inflammation studies were performed by analyzing expression of NF-κB, cycloxygenase-2, iNOS through western blot analysis and inflammatory cytokines by TNF-α and IL-1ß levels. The present study shows clear evidence that Vitamin C treatment abrogated spinal injury-induced oxidative stress and inflammatory responses and enhanced the antioxidant status. Thus, the protection offered by Vitamin C against spinal cord injury-induced kidney damage is attributed to its anti-oxidant and anti-inflammatory effects.

NO oxidation catalysis on copper doped hexagonal phase LaCoO3: a combined experimental and theoretical study.

Cobalt-based perovskite catalysts showed excellent performance towards NO-NO2 oxidation. We systematically investigated the influence of different levels of Cu-doping on the catalytic performance of hexagonal phase LaCoO3 (LaCo1-xCuxO3 (x = 0.1, 0.2, 0.3)) for NO oxidation. The catalytic activities of the oxide catalysts followed the sequence: LaCo0.9Cu0.1O3 > LaCoO3 > LaCo0.8Cu0.2O3 > LaCo0.7Cu0.3O3 where the highest NO conversion for LaCo0.9Cu0.1O3 was 82% at 310 °C. The relevant structural characterizations were conducted by XRD, BET, FTIR and TEM. The interaction between Co and Cu promoted the conversion of NO to NO2. Upon increasing the Cu doping content, a decrease of the performance resulted from the generation of isolated CuO on the surface of the oxides, confirmed using H2-TPR and XPS. Combined with first-principle calculations, we explored the reaction mechanism of NO oxidation on the surface and found that Cu doping would facilitate the reaction by decreasing the energy of oxygen vacancy formation and the NO2 desorption barrier from Co- or Cu-nitrite.

Avermectin induced vascular damage in zebrafish larvae: association with mitochondria-mediated apoptosis and VEGF/Notch signaling pathway.

Avermectin is a highly effective insecticide that has been widely used in agriculture since the 1990s. In recent years, the safety of avermectin for non-target organisms has received much attention. The vasculature is important organs in the body and participate in the composition of other organs. However, studies on the vascular safety of avermectin are lacking. The vasculature of zebrafish larvae is characterized by ease of observation and it is a commonly used model for vascular studies. Therefore, zebrafish larvae were used to explore the potential risk of avermectin on the vasculature. The results showed that avermectin induced vascular damage throughout the body of zebrafish larvae, including the head, eyes, intestine, somite, tail and other vasculature. The main forms of damage are reduction in vascular diameter, vascular area and vascular abundance. Meanwhile, avermectin induced a decrease in the number of endothelial cells and apoptosis within the vasculature. In addition, vascular damage may be related to impairment of mitochondrial function and mitochondria-mediated apoptosis. Finally, exploration of the molecular mechanisms revealed abnormal alterations in the expression of genes related to the VEGF/Notch signaling pathway. Therefore, the VEGF/Notch signaling pathway may be an important mechanism for avermectin-induced vascular damage in zebrafish larvae. This study demonstrates the vascular toxicity of avermectin in zebrafish larvae and reveals the possible molecular mechanism, which would hopefully draw more attention to the safety of avermectin in non-target organisms.

[AI-HIP system for prosthesis size, global femoral offset and osteotomy in total hip arthroplasty].

OBJECTIVE: To explore planning effect of AI-HIP assisted surgical planning system in primary unilateral total hip arthroplasty (THA) and its influence on clinical outcomes. METHODS: A retrospective analysis was conducted on clinical data of 36 patients who underwent their first unilateral THA from March 2022 to November 2022 and continuously used AI-HIP system (AI-HIP group), including 16 males and 20 females, aged from 43 to 81 years old with an average of (62.2±10.9) years old. According to the matching principle, 36 patients who were planned by the traditional template method at the same period were selected as the control group, including 16 males and 20 females, aged from 40 to 80 years old with an average of (60.9±12.1) years old. The accuracy between two groups of prostheses were compared, as well as the combined eccentricity difference between preoperative planning and postoperative practice, lower limb length difference, osteotomy height from the upper edge of the lesser trochanter and top shoulder distance to evaluate planning effect. Harris score and visual analogue scale (VAS) were used to evaluate clinical efficacy. RESULTS: Both groups were followed up for 12 to 18 months with an average of (14.5±2.1) months. The complete accuracy and approximate accuracy of acetabular cup and femoral stalk prosthesis in AI-HIP group were 72.2%, 100%, 58.3%, 88.9%, respectively, which were better than 44.4%, 83.3%, 33.3%, 66.7% in control group (P<0.05). There was no statistical significance in planning of femoral head prosthesis size (P>0.05). The actual combined eccentricity difference and combined eccentricity difference (practical-planning) in AI-HIP group were 1.0(0.2, 2.4) mm and 1.1(-2.1, 3.2) mm, respectively;which were better than 3.0 (1.4, 4.9) mm and 3.5 (-1.6, 6.5) mm in control group (P<0.05). There was no significant difference between two groups in actual osteotomy height of the upper margin of the lesser trochanter (P>0.05). In AI-HIP group, the actual difference of lower extremity length after surgery, the difference of lower extremity length (practical-planning), osteotomy height from the upper margin of lesser trochanter (practical-planning), actual topshoulder distance after surgery, and topshoulder distance (practical-planning) were 1.5 (0.2, 2.8), 1.1 (-0.3, 2.2), 2.1(-2.3, 4.1), (15.3±4.1), 2.2(-4.8, 0.3) mm, respectively;which were better than control group of 2.6(1.3, 4.1), 2.5 (0.3, 3.8), 5.8(-2.4, 7.7), (13.0±4.3), -5.7(-9.4, -2.2) mm(P<0.05). At final follow-up, there were no significant differences in Harris scores of pain, function, deformity, total scores and VAS between two groups (P>0.05). The range of motion score was 4.8±0.6 in AI-HIP group, which was higher than that in control group (4.4±0.8)(P<0.05). CONCLUSION: Compared with traditional template planning, AI-HIP assisted surgical planning system has good accuracy in predicting the prosthetic size of the acetabular cup and femoral stalk, restoring joint eccentricity, planning lower limb length, osteotomy height and top shoulder distance on the first unilateral THA, and the clinical follow-up effect is satisfactory.

Does modified Braun enteroenterostomy improve alkaline reflux gastritis and marginal ulcer after pancreaticoduodenectomy?

BACKGROUND: The safety of pancreaticoduodenectomy has improved significantly. However, alkaline reflux gastritis and marginal ulcer are two substantial problems after pancreaticoduodenectomy. AIMS: To identify whether Child reconstruction with a modified Braun enteroenterostomy decreases the incidence of alkaline reflux gastritis and marginal ulcer after pancreaticoduodenectomy better than Roux-en-Y reconstruction. METHODS: Data on 57 consecutive patients who underwent standard pancreaticoduodenectomy between January 1, 2008 and January 31, 2012 were collected prospectively. Data on early and late complications of the Child reconstruction with a modified Braun enteroenterostomy and Roux-en-Y were gathered. The risk factors of alkaline reflux gastritis and marginal ulcer were also investigated by using univariate and multivariate analyses. RESULTS: Twenty-five patients received Roux-en-Y and 32 underwent Child reconstruction with a modified Braun enteroenterostomy. Early complications after the two reconstruction methods were insignificant. Significant differences in terms of later postoperative morbidity (P = 0.01) and change in body mass index (P = 0.03) were found 12 months after pancreaticoduodenectomy. No significant difference for alkaline reflux gastritis was observed between the two methods (14.8 vs. 28.6 %, P = 0.24). Marginal ulcer occurred significantly lower in patients with the modified reconstruction than in those with Roux-en-Y reconstruction (11.1 vs. 47.6 %, P = 0.01). Peptic ulcer history, diabetes mellitus, and reconstruction type had a significant effect on marginal ulcer formation. CONCLUSIONS: Child reconstruction with a modified Braun enteroenterostomy offers an advantage with respect to marginal ulcer after standard pancreaticoduodenectomy, potentially decreasing the incidence of alkaline reflux gastritis as effectively as Roux-en-Y reconstruction.

A new fixation method for stick-shaped specimens in microtensile tests: laboratory tests and FEA.

PURPOSE: To introduce a new fixation method for stick-shaped specimens for use in microtensile tests and to evaluate the effect of this new method on microtensile bond strength, failure modes, and stress distribution. MATERIALS AND METHODS: Flat mid-coronal dentin surfaces were prepared on 12 caries-free human third molars and randomly divided into two groups for testing with two dental adhesives (Adper Single Bond 2 [SB2] and Clearfil SE Bond [SEB]). Following adhesive application and composite buildups, the bonded teeth were sectioned into beams. Sticks from each tooth were then equally divided into two subgroups for microtensile bond testing according to the utilized gripping devices (a flat Ciucchi's jig and the experimental setup). Failure modes were examined with a field-emission scanning electron microscope (FESEM). Three-dimensional models of each gripping device and specimen were developed, and stress distributions were analyzed by finite element analysis (FEA). Statistical significance was set at α = 0.05 RESULTS: Compared to those fixed using a flat Ciucchi's jig, sticks fixed with the experimental setup yielded lower bond strength values (p = 0.021 for SB2 and p = 0.007 for SEB) and more mixed failure patterns (p = 0.036 for both SB2 and SEB). In addition, the experimental setup guaranteed a uniaxial tensile force that was perpendicular to the bonding interface and produced a more uniform stress distribution at the bonding interface. CONCLUSION: An experimental setup for fixing microtensile sticks was proposed that was designed to provide a uniform stress distribution at the adhesive interface. FEA and failure mode analysis confirmed such uniform distribution, thus supporting the validity of the bond strength results obtained with this new fixture design.

A modified reduction malarplasty utilizing 2 oblique osteotomies for prominent zygomatic body and arch.

The shape of the zygomatic body and arch have great influences to the facial contour of Orientals. The prominent zygoma makes the appearance look more fierce. Nowadays in China, the number of patients who underwent reduction malarplasty is increasing rapidly. Therefore, it is important to develop a reliable surgical procedure with small wound and good effects. Included in this report were 46 patients with prominent zygomatic body and arch treated between October 2007 and November 2010. Combined intraoral and extraoral approaches were used, and 2 oblique osteotomies were performed to anterior and posterior part of malar complex, respectively. The isolated zygoma segment was then internalized utilizing z-plasty for the posterior end and inward sliding and internal fixation for the anterior end. The extraoral approach was made through a small temple incision. All patients were subjectively satisfied with the postoperative appearance. Their face contours were effectively improved by the modified procedure. One patient had short-term numbness of the medial zygomatic region skin; no other complications were observed during the follow-up period. This surgical procedure was carried out using combined intraoral and extraoral approaches. No visible scars left on the face. After 2 oblique osteotomies were made, the anterior inward sliding and posterior z-plasty could be easily performed to the isolated zygomatic bone. No segmental bone removal was required. The natural curve of the face contour was maintained while the malar complex was reshaped. We concluded that it is an effective and safe reduction malarplasty technique for Orientals.

[Effects of posterior tibial slope on non-contact anterior cruciate ligament rupture and stability of anterior cruciate ligament rupture knee].

OBJECTIVE: To retrospectively explore the correlation between anterior cruciate ligament (ACL)-ruptured knees, stability of ACL-rupture knee and posterior tibial slope (PTS). METHODS: From January 2008 to October 2012, 150 knees with ACL rupture underwent arthroscopic surgery for ACL reconstruction. A control group was established for subjects undergoing arthroscopic surgery without ACL rupture during the same period. PTS was measured on a digitalized lateral radiograph. Lachman and mechanized pivot shift tests were performed for assessing the stability of knee. RESULTS: There was significant difference (P = 0.007) in PTS angle between the patients with ACL rupture (9.5 ± 2.2 degrees) and the control group (6.6 ± 1.8 degrees). Only among females, increased slope of tibial plateau had effect on the Lachman test. There was a higher positive rate of pivot shift test in patients of increased posterior slope in the ACL rupture group. CONCLUSION: Increased posterior tibial slope (>6.6) appears to contribute to non-contact ACL injuries in females. And the changes of tibial slope have no effect upon the Lachman test. However, large changes in tibial slope affect pivot shift.

Association Between Serum Copper Levels and Urinary Incontinence in Adult Men.

Urinary incontinence (UI) is a major health burden to aging patients. The function of the trace element copper in male UI is unclear. To elaborate on the impact of serum copper levels on UI, we investigated the association between serum copper levels and UI using data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional survey of male participants aged 20 years old and older in the United States from 2011 to 2016. We performed weighted multivariable logistic and linear regression models to evaluate the association between serum copper levels and UI. Compared with serum copper levels in quartile 1 (Q1), serum copper levels in Q2 and Q3 were associated with stress urinary incontinence (SUI) after adjusting for all potential confounders (Q2, odds ratio [OR] = 0.292, 95% confidence interval [CI] = 0.093-0.920, P = 0.047; Q3, OR = 0.326, 95% CI = 0.113-0.937, P = 0.049). No significance was found between serum copper levels and other types of UI. Our findings revealed that the serum copper levels were inversely related to SUI in adult males. Race and education level might modulate this relationship. Further studies are warranted for validation.

Bioinformatic analysis of biological changes involved in pelvic organ prolapse.

The molecular mechanisms involved in the pathogenesis of pelvic organ prolapse (POP) remain unclear. This study aimed to identify key molecules involved in the pathogenesis and progression of POP. Differentially expressed genes (DEGs) were identified based on gene expression data extracted from the GSE53868, GSE28660, and GSE12852 datasets in the gene expression omnibus database. The R software was used for data mining, and gene ontology functional annotation and Kyoto encyclopedia of genes and genomes enrichment analyses were performed to explore the biological functions of DEGs. A protein-protein interaction network (PPI) was constructed using the Search Tool for the Retrieval of Interacting Genes database, and hub genes were identified by the Cytoscape plug-in cytoHubba. In addition, the CIBERSORT algorithm was used to analyze and evaluate immune cell infiltration in POP tissues. A total of 92 upregulated DEGs were identified and subjected to enrichment analysis. Gene ontology analysis revealed that these DEGs were associated with response to hormones, positive regulation of cell death, collagen-containing extracellular matrix, and extracellular matrix. Kyoto encyclopedia of genes and genomes pathway analysis showed that the upregulated genes were mainly enriched in the phosphatidylinositol 3-kinase-AKT signaling pathway. The PPI network was structured. Nodes in the PPI network were associated with structural molecular activity and collagen-containing extracellular matrix. A total of 10 hub genes were identified, namely, CDKN1A, IL-6, PPARG, ADAMTS4, ADIPOQ, AREG, activating transcription factor 3, CCL2, CD36, and Cell death-inducing DNA fragmentation factor-like effector A. Furthermore, patients with POP were found to have a higher abundance of CD8-positive T cells in the 3 gene expression omnibus datasets. The abundance of CD8-positive T cells was negatively correlated with that of follicular helper T cells (Pearson correlation coefficient = -0.34, P < .01) or gamma delta T cells (Pearson correlation coefficient = -0.33, P < .01). But was positively correlated with that of M2 macrophages (Pearson correlation coefficient = 0.35, P < .01) and activated memory CD4 T cells (Pearson correlation coefficient = 0.34, P < .01). Altogether, PPARG, ADAMTS4, ADIPOQ, AREG, CD36, and Cell death-inducing DNA fragmentation factor-like effector A genes were discovered in the POP process for the first time, which should be intensively investigated.

The health risk of acetochlor metabolite CMEPA is associated with lipid accumulation induced liver injury.

Liver injury may cause many diseases, such as non-alcoholic fatty liver disease (NAFLD). Acetochlor is one of the representative chloroacetamide herbicides, and its metabolite 2-chloro-N-(2-ethyl-6-methyl phenyl) acetamide (CMEPA) is the main form of exposure in the environment. It has been shown that acetochlor can cause mitochondrial damage of HepG2 cells and induce apoptosis by activating Bcl/Bax pathway (Wang et al., 2021). But there has been less research on CMEPA. we explored the possibility of CMEPA and liver injury through biological experiments. In vivo, CMEPA (0-16 mg/L) induced liver damage in zebrafish larvae, including increased lipid droplets, changes in liver morphology (>1.3-fold) and increased TC/TG content (>2.5-fold). In vitro, we selected L02 (human normal liver cells) as the model, and explored its molecular mechanism. We found that CMEPA (0-160 mg/L) induced apoptosis (similar to 40%), mitochondrial damage and oxidative stress in L02 cells. CMEPA induced intracellular lipid accumulation by inhibiting AMPK/ACC/CPT-1A signaling pathway and activating SREBP-1c/FAS signaling pathway. Our study provides evidence of a link between CMEPA and liver injury. This raises concerns regarding the health risks of pesticide metabolites to liver health.

The effects of Spinosad on zebrafish larvae and THP-1 cells: Associated with immune cell damage and NF-kappa B signaling pathway activation.

Spinosad is a highly effective macrolide insecticide with a wide range of applications. However, few studies have been reported on the effects of Spinosad on immune cells. The immune system is an important line of defense in the human body and plays an important role in maintaining the normal functioning of the organism. Meanwhile, macrophages, neutrophils and Thymic T cells are an important component of the immune system. We studied the immunotoxicity of Spinosad using zebrafish and THP-1 cells. In vivo, Spinosad (0-20 µM) did not cause developmental toxicity in zebrafish, but induced damage to immune cells. In vitro, Spinosad (0-20 µM) inhibited THP-1 cells viability and induced mitochondrial damage and oxidative stress production. In further studies, it impaired phagocytosis of THP-1 cells and interfered with lipid metabolism. In addition, we found that Spinosad can promote the formation of the inflammatory body NLRP3 (NLR family, pyrin domain-containing 3) and activate the NF-kappa B (NF-κB) signaling pathway. These results suggest that Spinosad has a potential risk for inducing immunotoxicity. This study has drawn attention to Spinosad-induced immunotoxicity.

[Expression of multiple tumor suppressor gene p16 and its relationship with prognosis of gastric cancer patients].

OBJECTIVE: To investigate the relationship between p16 expression and cell proliferation and prognosis in gastric cancer patients. METHODS: Gastric cancer cell lines SGC-7901, MKN45, MKN28, human embryonic kidney cell line HEK293, human fibroblast cell line MRC-5, and surgical specimens of gastric carcinoma and adjacent normal gastric mucosa from 65 patients were included in this study. RT-PCR, MTT and FCM assays were used to detect p16 expression in gastric cancer cell lines and surgical specimens of gastric cancer. MTT assay was used to determine cancer cell viability and FCM to detect cell cycle. Kaplan-Meier survival curve and Log-Rank statistics were used to analyze the relationship between p16 expression and survival of petients with gastric cancer. RESULTS: Gastric cancer cell lines were mostly negative for p16 expression, and p16 was re-expressed after the cells transfected with p16 gene by adenovirus AdCMV-p16. p16 re-expression resulted in the decrease of cancer cell viability and cancer cell cycle arrest with increased G(1) phase and decreased S phase. p16 expression in cancer specimens was 32.3% (21/65), significantly lower than the 81.5% (53/65) in normal mucosa (χ(2) = 32.124, P < 0.001). The disease-free survival was significantly shorter in p16-negative patients than that in p16-positive patients (P < 0.01), but not the overall survival (P > 0.05). p16 expression was significantly correlated with differentiation and lymph node metastasis, but not significantly correlated with sex, age, tumor size or invasion depth of the gastric cancer. CONCLUSIONS: p16 gene is important for cancer cell proliferation. The inactivation gives cancer cells a high activity for proliferation and metastasis, and then influences the disease-free survival of gastric cancer patients.