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Abstract Objective To explore whether Cyclic Adenosine Monophosphate (cAMP)-Epac1 signaling is activated in 1-Desamino-8-D-arginine-Vasopressin-induced Endolymphatic Hydrops (DDAVP-induced EH) and to provide new insight for further in-depth study of DDAVP-induced EH. Methods Eighteen healthy, red-eyed guinea pigs (36 ears) weighing 200-350 g were randomly divided into three groups: the control group, which received intraperitoneal injection of sterile saline (same volume as that in the other two groups) for 7 consecutive days; the DDAVP-7d group, which received intraperitoneal injection of 10 mg/mL/kg DDAVP for 7 consecutive days; and the DDAVP-14d group, which received intraperitoneal injection of 10 μg/mL/kg DDAVP for 14 consecutive days. After successful modeling, all animals were sacrificed, and cochlea tissues were collected to detect the mRNA and protein expression of the exchange protein directly activated by cAMP-1 and 2 (Epac1, Epac2), and Repressor Activator Protein-1 (Rap1) by Reverse Transcription (RT)-PCR and western blotting, respectively. Results Compared to the control group, the relative mRNA expression of Epac1, Epac2, Rap1A, and Rap1B in the cochlea tissue of the DDAVP-7d group was significantly higher (p< 0.05), while no significant difference in Rap1 GTPase activating protein (Rap1gap) mRNA expression was found between the two groups. The relative mRNA expression of Epac1, Rap1A, Rap1B, and Rap1gap in the cochlea tissue of the DDAVP-14d group was significantly higher than that of the control group (p< 0.05), while no significant difference in Epac2 mRNA expression was found between the DDAVP-14d and control groups. Comparison between the DDAVP-14d and DDAVP-7d groups showed that the DDAVP-14d group had significantly lower Epac2 and Rap1A (p< 0.05) and higher Rap1gap (p < 0.05) mRNA expression in the cochlea tissue than that of the DDAVP-7d group, while no significant differences in Epac1 and Rap1B mRNA expression were found between the two groups. Western blotting showed that Epac1 protein expression in the cochlea tissue was the highest in the DDAVP-14d group, followed by that in the DDAVP-7d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); Rap1 protein expression in the cochlea tissue was the highest in the DDAVP-7d group, followed by the DDAVP-14d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); no significant differences in Epac2 protein expression in the cochlea tissue were found among the three groups. Conclusion DDAVP upregulated Epac1 protein expression in the guinea pig cochlea, leading to activation of the inner ear cAMP-Epac1 signaling pathway. This may be an important mechanism by which DDAVP regulates endolymphatic metabolism to induce EH and affect inner ear function. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Level 5.
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OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Subject(s)
Mice , Animals , Receptors, Tumor Necrosis Factor/physiology , Receptors, OX40 , Membrane Glycoproteins , Ligands , Antibodies, Monoclonal/pharmacology , Antineoplastic Agents/pharmacologyABSTRACT
This study aims to investigate the effect of Bombyx Batryticatus extract(BBE) on behaviors of rats with global cerebral ischemia reperfusion(I/R) and the underlying mechanism. The automatic coagulometer was used to detect the four indices of human plasma coagulation after BBE intervention for quality control of the extract. Sixty 4-week-old male SD rats were randomized into sham operation group(equivalent volume of normal saline, ip), model group(equivalent volume of normal saline, ip), positive drug group(900 IU·kg~(-1) heparin, ip), and low-, medium-, and high-dose BBE groups(0.45, 0.9, and 1.8 mg·g~(-1)·d~(-1) BBE, ip). Except the sham operation group, rats were subjected to bilateral common carotid artery occlusion followed by reperfusion(BCCAO/R) to induce I/R. The administration lasted 7 days for all the groups. The behaviors of rats were examined by beam balance test(BBT). Morphological changes of brain tissue were observed based on hematoxylin-eosin(HE) staining. Immunofluorescence method was used to detect common leukocyte antigen(CD45), leukocyte differentiation antigen(CD11b), and arginase-1(Arg-1) in cerebral cortex(CC). The protein expression of interleukin-1β(IL-1β), interleukin-4(IL-4), interleukin-6(IL-6), and interleukin-10(IL-10) was detected by enzyme-linked immunosorbent assay(ELISA). The non-targeted metabonomics was employed to detect the levels of metabolites in plasma and CC of rats after BBE intervention. The results of quality control showed that the BBE prolonged the activated partial thromboplastin time(APTT), prothrombin time(PT), and thrombin time(TT) of human plasma, which was similar to the anticoagulation effect of BBE obtained previously. The results of behavioral test showed that the BBT score of the model group increased compared with that of the sham operation group. Compared with the model group, BBE reduced the BBT score. As for the histomorphological examination, compared with the sham operation group, the model group showed morphological changes of a lot of nerve cells in CC. The nerve cells with abnormal morphology in CC decreased after the intervention of BBE compared with those in the model group. Compared with the sham operation group, the model group had high average fluorescence intensity of CD45 and CD11b in the CC. The average fluorescence intensity of CD11b decreased and the average fluorescence intensity of Arg-1 increased in CC in the low-dose BBE group compared with those in the model group. The average fluorescence intensity of CD45 and CD11b decreased and the average fluorescence intensity of Arg-1 increased in medium-and high-dose BBE groups compared with those in the model group. The expression of IL-1β and IL-6 was higher and the expression of IL-4 and IL-10 was lower in the model group than in the sham operation group. The expression of IL-1β and IL-6 was lower and the expression of IL-4 and IL-10 was higher in the low-dose, medium-dose, and high-dose BBE groups than in the model group. The results of non-targeted metabonomics showed that 809 metabolites of BBE were identified, and 57 new metabolites in rat plasma and 45 new metabolites in rat CC were found. BBE with anticoagulant effect can improve the behaviors of I/R rats, and the mechanism is that it promotes the polarization of microglia to M2 type, enhances its anti-inflammatory and phagocytic functions, and thus alleviates the damage of nerve cells in CC.
Subject(s)
Humans , Rats , Male , Animals , Interleukin-10 , Rats, Sprague-Dawley , Interleukin-4/metabolism , Bombyx , Interleukin-6/metabolism , Microglia/metabolism , Saline Solution/metabolism , Reperfusion Injury/metabolism , Brain Ischemia/metabolism , Cerebral Infarction , Reperfusion , NeuronsABSTRACT
OBJECTIVE@#To explore the clinical efficacy of percutaneous vertebroplasty(PVP) combined with nerve block in the treatment of lumbar osteoporotic vertebral compression fractures under the guidance of traditional chinese medicine "theory of equal emphasis on muscle and bone".@*METHODS@#Total of 115 patients with lumbar osteoporotic vertebral compression fractures were treated by percutaneous vertebroplasty from January 2015 to March 2022, including 51 males and 64 females, aged 25 to 86 (60.5±15.9) years. Among them, 48 cases were treated with PVP operation combined with erector spinae block and joint block of the injured vertebral articular eminence (intervention group), and 67 cases were treated with conventional PVP operation (control group). The visual analogue scale(VAS) and Oswestry disability index(ODI) before operation, 3 days, 1 month and 6 months after operation between two groups were evaluated. The operation time, number of punctures and intraoperative bleeding between two groups were compared.@*RESULTS@#The VAS and ODI scores of both groups improved significantly after operation compared with those before operation(P<0.05). Moreover, the VAS and ODI scores of 3 days and 1 month after operation of the intervention group improved more significantly than that of the control group(P<0.05). The difference of VAS and ODI scores before operation and 6 months after operation between two groups had no statistical significances(P>0.05). There was no statistically significant difference in the number of punctures and intraoperative bleeding between the two groups (P>0.05).@*CONCLUSION@#Based on the theory of "equal emphasis on muscles and bones", PVP combined with nerve block can effectively relieve paravertebral soft tissue spasm and other "muscle injuries", which can significantly improve short-term postoperative low back pain and lumbar spine mobility compared to conventional PVP treatment, and accelerate postoperative recovery, resulting in satisfactory clinical outcomes.
Subject(s)
Male , Female , Humans , Fractures, Compression/surgery , Vertebroplasty/methods , Spinal Fractures/surgery , Spinal Puncture , Lumbar Vertebrae/injuries , Muscles , Treatment Outcome , Osteoporotic Fractures/surgery , Retrospective Studies , Bone CementsABSTRACT
Objective To investigate the causes of infertility and its pathological mechanism in female SD rats with spontaneous dwarfism(short stature rat,SSR).Methods Adult wildtype and SSR female SD rats were used in this study.A vaginal smear was used to observe changes in the motile cycle.Ovulation promotion was compared using the simultaneous estrus supernumerary ovulation method.Ovarian and uterine weight and body weight,and ovarian and uterine indices were measured.AMH,E2,FSH,LH,and FSH/LH levels in serum were measured.Transcriptome sequencing of ovarian tissues was performed to analyze gene expression differences.Results No abnormalities were observed in the estrous cycle of SSR female rats.The body weight of SSR female rats was significantly lower than that of wildtype rats,and their ovarian and uterine indices were significantly higher than that of wildtype rats.The mean number of ovulations was significantly higher in wildtype rats than in SSR female infertile rats(P<0.001).Serum AMH(P<0.01)and E2(P<0.05)levels were significantly higher in wildtype rats than in SSR female infertile rats,and serum levels of FSH,LH,and FSH/LH(P<0.05)were significantly lower in SSR infertile females than in SSR infertile rats,while PROG showed no significant difference.Transcriptome sequencing yielded 250 differentially expressed genes,including 190 upregulated and 60 downregulated genes.p53 signaling pathway and cytokine-cytokine receptor interaction.The MCC,MNC,EPC,and degree calculations of the CytoHubba plug-in were used to screen the top 10 significant nodes.The intersection was used to finally obtain nine hub genes,namely Cxcl1,Cxcl2,IL1a,IL1b,Cd80,Mmp13,Mmp8,Fgf3,and Ptgs2.Conclusions Infertility in SSR female rats may be related to a decreased ovarian reserve function and poor ovarian response.Cxcl1,Cxcl2,IL1a,IL1b,Cd80,Mmp13,Mmp8,Fgf3,and Ptgs2 were associated with infertility,laying a theoretical foundation to further explore infertility mechanisms.
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Objective To observe the 18F-FDG PET/CT manifestations of primary systemic anaplastic large cell lymphoma(ALCL).Methods A total of 21 patients with primary systemic ALCL were enrolled,and PET/CT manifestations were observed.Results Among 21 cases of ALCL,there were 15 cases of ALK+and 6 cases of ALK-.Affected lymph nodes in multiple site were observed in 19 cases,mainly located in the neck(n=13),mediastinum(n=12 cases)or retroperitoneum(n=12),while single site affected lymph node was notice in 2 cases.Extranodal organs/site involvements were found in 12 cases,including 6 cases of soft tissue(such as skin,muscles,etc.),4 cases of bone,14 cases of organs,including 4 cases of lung,3 cases of liver,2 cases of pancreas,2 cases of kidney,2 cases of gastrointestinal tract and 1 case of thyroid.Among 21 cases of ALCL,19 with irregular lymph node morphology and fused into clusters,17 with uniform density,3 with necrosis and 1 with calcification.All ALCL lesions in 21 cases showed hypermetabolism,the maximum standard uptake value(SUVmax)and the mean standard uptake value(SUVmean)of the affected lymph node was 17.04±9.94 and 9.96±6.15,respectively,while the metabolic tumor volume(MTV)and total lesion glycolysis(TLG)of all lesions was 92.54(67.61,249.21)cm3 and 723.46(419.78,1 461.17)g,respectively.The maximum diameter of the affected lymph node was not significantly correlated with SUVmax nor SUVmean(both P>0.05),but positively correlated with MTV and TLG of all lesions(r=0.696,0.767,both P<0.001).Ann Arbor staging was positively correlated with the maximum diameter,SUVmax and SUVmean of the affected lymph node,also MTV and TLG of all lesions(r=0.467,0.458,0.702,0.780,0.664,all P<0.05).Conclusion 18F-FDG PET/CT manifestations of primary systemic ALCL were characteristic,with significant changed metabolic parameters,including SUVmax,SUVmean,MTV and TLG.
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The anatomy of the shoulder joint is complex. Glenoid fractures, intra-articular fractures of the shoulder, are relatively rare and often accompanied by serious injury. At present, there has been no consensus on the optimal strategies for their treatment. Insufficient knowledge and improper treatment of the surgeons may seriously affect the shoulder function of the patients to harm their quality of life. Therefore, proper handling of such fractures is a major challenge in clinic. In recent years when high-energy injuries are increasing and functional recovery after shoulder fracture is emphasized by more and more patients, great efforts have been put into the research into such fractures by orthopedic surgeons. This reviews expounds on the anatomy, diagnosis, classification and treatment of glenoid fractures, aiming to provide useful reference for the orthopaedic surgeons who deal with glenoid fractures.
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@#Abstract: Objective To investigate the distribution characteristics of HCV genotypes and subtypes in patients with HIV (human immunodeficiency virus, HIV)/HCV co-infection in Kunming based on the nucleocapsid protein gene sequence of HCV (hepatitis C virus). Methods Serum was collected from HIV/HCV co-infected patients with household registration in 14 county-level cities, districts and counties under the jurisdiction of Kunming, who admitted to Yunnan Provincial Infectious Disease Hospital from March to August 2019. The viral RNA was extracted from the serum, reverse transcribed to synthesize cDNA, and the HCV nucleocapsid protein gene-specific primers were used for nested PCR amplification. The positive amplification products were sequenced, bioinformatics software such as DNAstar and MEGAX were used for sequence analysis. Results A total of 64 samples from co-infected patients with clinical diagnosis of suspected HIV/HCV were collected and amplified by HCV nucleocapsid protein gene-specific primers, of which 17 samples were amplified positively. The results of sequence analysis showed that the sequences of 9 cases were located in the same evolutionary branch as the HCV 3b subtype sequence, and the nucleotide homology was 93.3%-95.2%; the sequences of 5 cases were located in the same evolutionary branch as the HCV 1b subtype sequence, and the nucleotide homology was 96.8%-97.6%; the sequence of one case and the subtype sequence of HCV 3a gene were located in the same evolutionary branch, and the nucleotide homology was 95.2%; the sequence of one case and HCV 6n gene subtype sequence were located in the same evolutionary branch, and the nucleotide homology was 97.9%; One case was located in the same evolutionary branch as the HCV 6u gene subtype sequence, and the nucleotide homology was 98.4%. Conclusions HCV 1b, HCV 3a, HCV 3b, HCV 6n and HCV 6u genotypes or subtypes of HCV are prevalent in Kunming, and HCV 3b is the most prevalent genotype.
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This paper summarizes the status of application and research of Fu's subcutaneous needling for peripheral facial paralysis, and the characteristics of different stages of peripheral facial paralysis treated with Fu's subcutaneous needling are analyzed from the aspects of intervention timing, protocol design, needle insertion point, sweeping and reperfusion activity, tube retaining time and acupuncture frequency. It is found that there are no norms and standards in sweeping and reperfusion, tube retention and acupuncture frequency in clinical application,and the exploration of staged treatment is insufficient in the research. In the future, it is necessary to form standardized operation to promote clinical promotion, and improve the research on treatment rules and mechanism according to the characteristics of disease stage.
Subject(s)
Humans , Facial Paralysis/therapy , Vascular Surgical Procedures , Acupuncture Therapy , NeedlesABSTRACT
Objective:To study the clinical results of robot-assisted laparoscopic resection for choledochal cysts.Methods:From October 2020 to June 2022, clinical data on 20 patients who underwent choledochal da Vinci robot-assisted laparoscopic choledochal cyst resection at Fujian Provincial Hospital were retrospectively analyzed. Forty-two children with choledochal cysts were included in this study. There were 16 males and 26 females, aged 25 (range 15.0 to 45.0) months. The operations were carried out by the same team of surgeons. These patients were divided into two groups based on the surgical methods: children who underwent da Vinci robot-assisted laparoscopic surgery were in the robotic group ( n=20) and children who underwent single-port (transumbilical) laparoscopic surgery were in the laparoscopic group ( n=22). The general clinical data, operation time, intraoperative blood loss, fasting time, hospital stay, total medical costs and complications were collectd and analysed. Follow-up was performed in outpatient visits. Results:Both the 2 groups underwent surgery successfully, and no patient was converted to laparotomy. When compared with the laparoscopic group, intraoperative blood loss [(10.65±3.75) vs. (14.86±3.75) ml], indwelling time of abdominal drainage tube [(5.45±2.21) vs. (7.05±1.94) d] and fasting time [(4.00±1.49) vs. (6.05±1.43) d] in the robotic group were significantly less, while the operation time [394(299, 422) vs. 351(269, 380) min] and hospitalization cost [(79 200±4 000) vs. (31 100±3 000) yuan] were significantly increased (all P<0.05). The differences in postoperative complication rates and pain score between the two groups showed no significant differences (all P>0.05). On follow-up, no patients developed complications such as cholangitis, jaundice, intestinal obstruction and cholangiocarcinoma, except for one patient in the laparoscopic group who developed cholangitis after surgery. Conclusion:Robot-assisted laparoscopic choledochal cystectomy was effective and safe in treatment of children with choledochal cysts.
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Objective@#To analyze the childhood blood pressure (BP) trajectory and its relationship with overweight and obesity, to provide evidence regarding prevention and control of childhood elevated BP.@*Methods@#A total of 1 177 children who participated in five surveys of Zigong school based cardiometabolic risks survey. Elevated BP was defined by using National BP reference for Chinese children. Groupbased trajectory model was used to identify distinct BP trajectories. Logistic models were conducted to investigate the association of number of overweight/obesity across surveys with BP trajectory.@*Results@#In the five consecutive waves, the corresponding prevalence of elevated BP was 1.9%, 6.6%, 7.0%, 12.5% and 11.2%. Childhood BP trajectory were classified into constant low and high increasing risk of elevated BP groups. The risk of elevated BP increased at a steady rate with age in constant low risk of elevated BP groups, while the risk of elevated BP increased dramatically with age in high increasing risk of elevated BP groups. Logistic regression analysis showed that those with increasing number of occurrence of overweight/obesity tended to be classified into high increasing risk of elevated BP group( OR=1.34, 95%CI=1.17-1.53, P <0.01).@*Conclusion@#Blood pressure trajectory during childhood varies. The risk of elevated BP increased dramatically with age in overweight and obese children. Attention should be paid to the BP trajectory of overweight and obese children to prevent elevated BP.
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Objective:To analyze the plasma levels of soluble immune checkpoint molecules in patients with primary liver cancer and their prognostic significance.Methods:The levels of sCD28, sCD80, sCD137, sCD27, sGITR, sTIM3, sCTLA4, sHVEM, IDO, sLAG3, sBTLA, sPD1, sPDL1 and sPDL2 in plasma samples of 58 patients with primary liver cancer and 30 healthy controls were detected by liquid chip technology and compared between different groups. The relationship between the plasma levels of soluble immune checkpoint molecules and tumor recurrence was analyzed.Results:The levels of sCD28 and sCD80 were higher in patients in Barcelona Clinic Liver Cancer (BCLC) stage 0/A and B than in healthy controls and patients in BCLC-C stage ( P<0.05). However, the levels of sCD27 and sHVEM in BCLC-C patients were significantly lower than those in BCLC-0/A and BCLC-B patients, and even lower than healthy control group. The levels of sCD137, IDO and sPD1 in BCLC-0/A and BCLC-B patients were higher than those in healthy controls. The levels of sPDL1 and sPDL2 in different BCLC stages were all higher than those in healthy controls, and maintained at high level in the three stages, but there was no significant difference between different stages. After 24 months of interventional treatment, the preoperative sCD28 level was lower in patients with recurrent tumor recurrence than in patients without recurrence ( t=2.843, P=0.007). The optimal cut-off value of sCD28 based on the receiver operating characteristic (ROC) curve for predicting tumor recurrence was 101.42 pg/ml and the area under the ROC curve was 0.771 (95%CI: 0.611-0.931) with a sensitivity of 0.889 and a specificity of 0.666. The cumulative recurrence rate in patients with high sCD28 level (≥101.41 pg/ml) was 57.9% at 24 months after surgery, which was lower than the rate (95.5%) in patients with low sCD28 level (<101.41 pg/ml). The difference in the cumulative recurrence rate between the two groups was statistically significant (χ 2=15.777, P=0.000). Conclusions:The expression patterns of soluble immune checkpoint molecules varied in patients at different stages of primary liver cancer, suggesting that there were differences in their immune status and sCD28 could be used as a prognostic marker for postoperative recurrence of liver cancer.
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Cellular metabolism in tumor is an important biological process to promote the occurrence and development of tumor, and the genes related to cellular metabolism are gradually becoming the targets of tumor treatment. However, more researches are still needed to explore the abnormal metabolism in tumor progression and its prognostic value. BDH2 gene is a multifunctional gene, participates in a variety of metabolic pathways, plays an important catalytic role in iron metabolism, participates in ketone metabolism and is related to lipid metabolism. In recent years, researchers have found that BDH2 plays distinct roles in various types of tumors. The occurrence and development of a variety of tumors are closely related to BDH2. This paper analyzes, summarizes and prospects the role and mechanism of BDH2 in metabolism and tumorigenesis.
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@#Objective - To analyze the effect of using vibration tools on the prevalence of work related musculoskeletal disorders ( ) Methods , - WMSDs in automobile factory workers. By judgment sampling method front line workers with more than one year of working experience in an automobile factory were selected as the research subjects. Musculoskeletal Disorders Questionnaire was used for investigation. The workers were divided into the control group and the vibration tool group. The propensity score ∶ , matching method was used to balance the confounding factors of the two groups of workers by 1 1 and 568 people were Results included in each group. The prevalence of WMSDs was compared between the two groups after matching. After , , , , , , matching the prevalence of WMSDs in the shoulder elbow hand/wrist upper back waist hip/buttock and knee of workers in , ( P ) the vibration tool group was higher than that in the control group and the differences were statistically significant all <0.05 ., The prevalence of WMSDs in different body parts of workers in the vibration tool group ranking from high to low was waist , , , , , , , , , , neck shoulder hand/wrist upper back knee ankle/foot elbow and hip/buttock with the rate of 74.3% 61.3% 54.2% , , , , , (P ) Conclusions 54.0% 50.9% 39.4% 35.2% 31.0% and 27.1% respectively <0.01 . The use of vibration tools can , , , , , increase the risk of WMSDs in shoulder elbow hand/wrist upper back waist hip/buttock and knee of automobile factory workers. Corresponding measures should be taken to reduce vibration intensity and reduce contact time to protect workers'
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ObjectiveTo investigate the effect of modified Xiaoyaosan on central dopamine transporter (DAT)/protein kinase C (PKC)-dependent signaling pathway in hyperprolactinemia (HPRL) rats. MethodHPRL rat model was established by chronic combined stress combined with intraperitoneal injection of metoclopramide. Ninety-six rats were randomly divided into six groups, namely, the blank group, model group, western medicine (bromocriptine, 0.001 g·kg-1·d-1) group, and high-, medium-, and low-dose (60, 30, 15 g·kg-1·d-1) modified Xiaoyaosan groups. After 14 days of administration, the serum prolactin (PRL) content was detected by enzyme-linked immunosorbent assay, the expression of tyrosine hydroxylase (TH) in rat hypothalamus by immunohistochemistry, and the protein expression of DAT and PKC in hypothalamus by Western blot. ResultCompared with the blank group, the model group exhibited significantly increased PRL and DAT (P<0.01), but decreased TH and PKC (P<0.01). Compared with the model group, bromocriptine and modified Xiaoyaosan at the medium dose significantly lowered the content of PRL (P<0.01). The modified Xiaoyaosan at the medium and high doses elevated the expression of TH (P<0.05, P<0.01). The expression levels of PKC in the medium- and low-dose modified Xiaoyaosan groups and the western medicine group were significantly increased (P<0.01), while the DAT expression levels in the high-, medium-, and low-dose modified Xiaoyaosan groups and the western medicine group were decreased (P<0.01). ConclusionThe modified Xiaoyaosan is able to up-regulate the expression of TH and down-regulate the level of DAT through PKC-dependent signaling pathway, thereby regulating the PRL.
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Objective: To investigate the effects of PM2.5 exposure at different stages of early life on the prefrontal cortex of offspring rats. Methods: Twelve pregnant SD rats were randomly divided into four groups: Control group (CG), Maternal pregnancy exposure group (MG), Early postnatal exposure group (EP) and Perinatal period exposure group (PP), 3 rats in each group. The pregnant and offspring rats were exposed to clean air or 8-fold concentrated PM2.5. MG was exposed from gestational day (GD) 1 to GD21. EP was exposed from postnatal day (PND) 1 to PND21, and PP was exposed from GD1 to PND21. After exposure, the prefrontal cortex of 6 offspring rats in each group was analyzed. HE staining was used to observe the pathological damage in the prefrontal cortex. ELISA was employed to detect neuroinflammatory factors, and HPLC/MSC was applied to determine neurotransmitter content. Western blot and colorimetry were applied for detecting astrocyte markers and oxidative stress markers, respectively. Results: Compared with MG and CG, the pathological changes of prefrontal cortex in PP and EP were more obvious. Compared with MG and CG, the neuroinflammatory factors (IL-1, IL-6, TNF-α) in PP and EP were increased significantly (P<0.01), the level of MT were decreased significantly (P<0.05), and the level of oxytocin (OT) showed a downward trend; the level of neurotransmitter ACh was also increased significantly (P<0.01). Compared with MG and CG, the GFAP level of PP and EP showed an upward trend, the level of oxidative stress index SOD in PP and EP was decreased significantly (P<0.01), and the level of ROS was increased significantly (P<0.01). Compared with the offspring rats of CG and MG, the CAT level of PP was decreased significantly (P<0.01, P<0.05). Compared with the offspring rats of CG, the CAT level of EP was decreased significantly (P<0.05). There was no significant difference in IL-1, IL-6, TNF-α, MT, OT, ACh, GFAP, SOD, ROS and CAT levels between PP and EP, or MG and CG. Conclusion: PM2.5 exposure in early life has adverse effects on the prefrontal cortex of offspring male rats, and early birth exposure may be more sensitive.
Subject(s)
Animals , Female , Male , Pregnancy , Rats , Interleukin-1/pharmacology , Interleukin-6 , Neurotransmitter Agents , Particulate Matter/toxicity , Prefrontal Cortex , Rats, Sprague-Dawley , Reactive Oxygen Species , Superoxide Dismutase , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
OBJECTIVES@#To investigate the prevalence of diabetes mellitus (DM) among Uygur children in Hotan Prefecture of Xinjiang, China, as well as the factors influencing the development of DM.@*METHODS@#The cluster random sampling method was used to select 5 308 children, aged 4-18 years, from the middle and primary schools and kindergartens in Hotan Prefecture of Xinjiang. The survey methods included questionnaire survey and the measurement of height and weight. All subjects were tested for fasting fingertip blood glucose to investigate the prevalence of DM and impaired fasting glucose (IFG).@*RESULTS@#A total of 5 184 valid questionnaires were collected. Fourteen children (0.27%) were found to have DM, among whom 8 had type 1 DM, 2 had type 2 DM, and 4 had unclassified DM. Twenty-nine children (0.56%) were found to have IFG. There was no significant difference in the prevalence rate of DM and IFG between boys and girls (P>0.05). The prevalence rate of DM was 0.18% in the 4-<10 years group, 0.47% in the 10-<15 years group, and 0.07% in the 15-18 years group (P=0.072).The prevalence rate of IFG in the above three age groups was 0.18%, 0.94%, and 0.42%, respectively, with a significant difference among groups (P=0.007). The proportion of family history of DM and the proportion of overweight/obesity in children with DM were significantly higher than those in children without DM (P<0.05), while the proportion of children with DM who preferred coarse grains was significantly lower than that in children without DM (P<0.05).@*CONCLUSIONS@#The prevalence of DM and IFG in Uyghur children in Hotan Prefecture of Xinjiang is relatively low. There is no significant difference in the prevalence of DM among children of different genders or age groups, but the prevalence of IFG in children of different age groups is different. A family history of DM, overweight or obesity, and low intake of coarse grains might be associated with the development of DM.
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Male , Blood Glucose , China/epidemiology , Pediatric Obesity , Prediabetic State/epidemiology , Prevalence , Risk FactorsABSTRACT
Objective:To investigate the relationship between fragment size of ulnar coronoid process fracture and patient prognosis.Methods:A retrospective study was conducted of the 34 patients who had been treated at Department of Orthopaedics, The Second Hospital Affiliated to Lanzhou University for fracture of ulnar coronoid process combined with elbow dislocation from July 2016 to December 2020. They were assigned into 2 groups according to their different treatments. In the surgery (internal fixation) group of 23 cases, there were 15 males and 8 females, aged from 22 to 71 years; in the conservative treatment group of 11 cases, there were 8 males and 3 females, aged from 38 to 78 years. Preoperatively, the sizes of coronoid process and fracture fragments were measured by elbow CT scan and 3D reconstruction, and a size-weighted ratio Z (%) corresponding to the fragment of coronoid process fracture was calculated. At the last follow-up, American Hospital for Special Surgery total elbow scoring system (HSS2) score was used to assess their therapeutic efficacy, the correlation between the ratio Z and HSS2 score for elbow function was calculated, and complications were recorded.Results:There were no significant differences between the surgery and conservative treatment groups in gender or age ( P>0.05). All the 34 patients were followed up for 18 to 54 months (average, 36.7 months). At the last follow-up, the HSS2 score was 93.77±0.84 (from 82 to 98) for the surgery group and 86.00±1.42 (from 78 to 90) for the conservative treatment group; the complications rate was 13.04% (3/23) for the former and 63.64% (7/11) for the latter. There was a linear relationship between the size-weighted ratio Z of the coronoid fracture fragment and the HSS2 elbow function score in the surgery group ( P<0.01). The linear regression equation between them was: y=99.44-0.121x ( r2=0.86, P<0.01). There was a linear relationship between the size-weighted ratio Z of the coronoid fracture fragment and the HSS2 elbow function score in the conservative treatment group ( P<0.01). The linear regression equation between them was: y=89.46-0.144x ( r2=-0.91, P<0.01). When a HSS2 elbow joint function score 90 was substituted into both linear regression equations, the results were x=78.02 for the surgery group and x=3.75 for the conservative treatment group. Conclusions:Conservative treatment may not lead to a satisfactory prognosis for the patients with coronoid process fracture whose size-weighted ratio of fracture fragment is larger than 3.75. Open reduction and internal fixation usually leads to a satisfactory prognosis for those whose size-weighted ratio of fracture fragment is smaller than 78.02.
ABSTRACT
BACKGROUND@#Nucleolar protein 6 (NOL6) is a nucleolar RNA-associated protein that is highly conserved between species. It has been proved to be associated with the prognosis of liver cancer. However, the underlying mechanism has not been fully established. This study aimed to assess the relationship between NOL6 and liver cancer prognosis.@*METHODS@#We constructed an NOL6-short hairpin RNA (shRNA)-expressing lentivirus. Through viral transfection, cell growth assay and fluorescence-activated cell sorting, we evaluated the effect of shRNA-mediated NOL6 knockdown on the proliferation, colony formation, and apoptosis of hepatocellular carcinoma (HCC) cells. The relationship between NOL6 expression and HCC patient survival has been established through bioinformatics analysis. We also explored the downstream molecular regulatory network of NOL6 in HCC by performing an Ingenuity Pathway Analysis in the database.@*RESULTS@#Increased NOL6 expression was detected in HCC cells compared to normal controls; HCC patients with high NOL6 expression had poorer prognoses than those with low expression. NOL6 knockdown inhibited HCC cell proliferation, apoptosis, and colony formation. Also, MAPK8, CEBPA, and FOSL1 were selected as potential downstream genes of NOL6.@*CONCLUSIONS@#NOL6 up-regulates HCC cell proliferation and affects downstream expression of related genes. Moreover, NOL6 is considered to be associated with poor prognosis in HCC patients.
Subject(s)
Humans , Apoptosis/genetics , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/genetics , Nuclear Proteins , PrognosisABSTRACT
Methyltransferase like 13 (METTL13), a kind of methyltransferase, is implicated in protein binding and synthesis. The upregulation of METTL13 has been reported in a variety of tumors. However, little was known about its potential function in head and neck squamous cell carcinoma (HNSCC) so far. In this study, we found that METTL13 was significantly upregulated in HNSCC at both mRNA and protein level. Increased METTL13 was negatively associated with clinical prognosis. And METTL13 markedly affected HNSCC cellular phenotypes in vivo and vitro. Further mechanism study revealed that METTL13 could regulate EMT signaling pathway by mediating enhancing translation efficiency of Snail, the key transcription factor in EMT, hence regulating the progression of EMT. Furthermore, Snail was verified to mediate METTL13-induced HNSCC cell malignant phenotypes. Altogether, our study had revealed the oncogenic role of METTL13 in HNSCC, and provided a potential therapeutic strategy.