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The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed inde-pendently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endo-thelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.
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Objective To investigate the effect of recombinant Schistosoma japonicum egg ribonuclease SjCP1412 (rSjCP1412) on proliferation, cell cycle, apoptosis and activation of human hepatic stellate cells LX-2 in vitro, and explore the underlying mechanisms. Methods The rSjCP1412 protein was expressed in Escherichia coli BL21 by prokaryotic expression, and the highly purified soluble rSjCP1412 protein was prepared by Ni NTA affinity chromatography and urea gradient refolding dialysis. Yeast RNA was digested using 12.5, 25.0, 50.0 µg rSjCP1412 proteins at 37 °C for 2, 3, 4 h, and the enzymatic products were electrophoresed on 1.5% agarose gel to observe the RNAase activity of rSjCP1412 protein. The proliferation of LX-2 cells stimulated by different doses of rSjCP1412 protein for 48 hours was measured using CCK-8 assay, and the apoptosis of LX-2 cells stimulated by different doses of rSjCP1412 protein for 48 hours was detected using the Annexin V-FITC/PI double staining, while the percentage of LX-2 cells at G0/G1, S and G2/M phases of cell cycle following stimulation with different doses of rSjCP1412 protein for 48 h was detected by DAPI staining. The type I collagen, type III collagen and α-smooth muscle actin (α-SMA) mRNA expression was quantified using quantitative florescent real-time PCR (qPCR) assay and Western blotting at transcriptional and translational levels in LX-2 cells following stimulation with different doses of rSjCP1412 protein for 48 h, while soluble egg antigen (SEA) served a positive control and PBS without rSjCP1412 protein as a normal control in the above experiments. The expression of collagen I, α-SMA and Smad4 protein was determined using Western blotting in LX-2 cells following stimulation with rSjCP1412 protein, transforming growth factor-β1 (TGF-β1) alone or in combination, to examine the signaling for the effect of rSjCP1412 protein on LX-2 cells. Results The rSjCP1412 protein was successfully expressed and the highly purified soluble rSjCP1412 protein was prepared, which had a RNase activity. Compared with the normal group, the survival rates of LX-2 cells significantly decreased post-treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein and SEA for 48 h (F = 22.417 and 20.448, both P values < 0.05). The apoptotic rates of LX-2 cells significantly increased post-treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein for 48 h (F = 11.350, P < 0.05), and treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein for 48 h resulted in arrest of LX-2 cells in G0/G1 phase (F = 20.710, P < 0.05). Treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein for 48 h caused a significant reduction in relative expression levels of collagen I (F = 11.340, P < 0.05), collagen III (F = 456.600, P < 0.05) and α-SMA mRNA (F = 23.100, P < 0.05) in LX-2 cells, and both rSjCP1412 protein and SEA treatment caused a significant reduction in collagen I (F = 1 302.000, P < 0.05), α-SMA (F = 49.750, P < 0.05) and Smad4 protein expression (F = 52.420, P < 0.05) in LX-2 cells. In addition, rSjCP1412 protein treatment inhibited collagen I (F = 66.290, P < 0.05), α-SMA (F = 31.300, P < 0.05) and Smad4 protein expression (F = 27.010, P < 0.05) in LX-2 cells activated by TGF-β1. Conclusion rSjCP1412 protein may induce apoptosis of LX-2 cells and inhibit proliferation, cell cycle and activation of LX-2 cells through down-regulating Smad4 signaling molecules.
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@#Objective - （ ）- （ ） To observe the effects of renin angiotensin Ang aldosterone system RAAS in workers exposed to Methods - - occupational noise. Forty five workers with suspected occupational noise induced deafness were selected as noise ， ， exposure group using convenient sampling method. According to their tinnitus symptom noise exposure intensity and work age - ， ， they were divided into no tinnitus and tinnitus subgroups <90 dB and ≥90 dB subgroups work years <10 years and ≥10 years subgroups. Another 45 workers with no occupational noise exposure history were selected as control group. The levels of plasma （ ）， ， ， renin activity PRA AngⅠ AngⅡ and aldosterone of the two groups were detected and the aldosterone to renin activity Results ratio was calculated. The diastolic blood pressure of the noise exposure group was higher than that of the control group ［（ ）vs（ ） ，P ］ ， 80±7 76±8 mmHg <0.05 . However there was no significant difference in systolic blood pressure between the two （P ） （ ： groups >0.05 . The level of plasma AngⅡ in the noise exposure group was higher than that in the control group median vs ，P ） （ P ） 100.98 65.43 μg/L <0.05 . There was no statistical significance in other indexes between the two groups all >0.05 . The （ ： plasma AngⅡ level in < 90 dB subgroup in the noise exposure group was higher than that of the control group median 123.16 vs ，P ） 65.43 μg/L <0.05 . There was no statistical significance in other indexes among the two subgroups of tinnitus symptom or （ P ） work age in the noise exposure group and the control group all >0.05 . There were no significant differences in the abnormal ， （ P ） rates of PRA AngⅡ and aldosterone in plasma between the noise exposure group and the control group all >0.05 . Conclusion Occupational noise exposure may affect RAAS and lead to increased plasma AngⅡ levels in the workers. - Tinnitus and work age may not affect RAAS in occupational noise exposure workers.
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@#Objective - （ ）- （ ） To observe the effects of renin angiotensin Ang aldosterone system RAAS in workers exposed to Methods - - occupational noise. Forty five workers with suspected occupational noise induced deafness were selected as noise ， ， exposure group using convenient sampling method. According to their tinnitus symptom noise exposure intensity and work age - ， ， they were divided into no tinnitus and tinnitus subgroups <90 dB and ≥90 dB subgroups work years <10 years and ≥10 years subgroups. Another 45 workers with no occupational noise exposure history were selected as control group. The levels of plasma （ ）， ， ， renin activity PRA AngⅠ AngⅡ and aldosterone of the two groups were detected and the aldosterone to renin activity Results ratio was calculated. The diastolic blood pressure of the noise exposure group was higher than that of the control group ［（ ）vs（ ） ，P ］ ， 80±7 76±8 mmHg <0.05 . However there was no significant difference in systolic blood pressure between the two （P ） （ ： groups >0.05 . The level of plasma AngⅡ in the noise exposure group was higher than that in the control group median vs ，P ） （ P ） 100.98 65.43 μg/L <0.05 . There was no statistical significance in other indexes between the two groups all >0.05 . The （ ： plasma AngⅡ level in < 90 dB subgroup in the noise exposure group was higher than that of the control group median 123.16 vs ，P ） 65.43 μg/L <0.05 . There was no statistical significance in other indexes among the two subgroups of tinnitus symptom or （ P ） work age in the noise exposure group and the control group all >0.05 . There were no significant differences in the abnormal ， （ P ） rates of PRA AngⅡ and aldosterone in plasma between the noise exposure group and the control group all >0.05 . Conclusion Occupational noise exposure may affect RAAS and lead to increased plasma AngⅡ levels in the workers. - Tinnitus and work age may not affect RAAS in occupational noise exposure workers.
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This article elaborates the key points of the updated recommendations and the latest evidence of the important steps in China neonatal resuscitation guideline (revised in 2021), aiming to help clinicians better understand the guideline and guide training to achieve a standardized and efficient resuscitation and further to improve neonatal outcomes.
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Abstract@#Children were vulnerable groups in major public health emergencies. In 2020, the coronavirus disease 2019 (COVID-19) pandemic was widespread in the world. The mental health of school age children has become a worldwide concern. Herein, we conducted this review to evaluate the impact of COVID-19 on the mental health of general children and special children with a high risk of psychological problems, focusing on the prevalence of anxiety, depression, and post traumatic stress disorder among school age children in different countries and regions during the COVID-19 epidemic. Considering the susceptibility between individuals and the accessibility of social resources, we further explored the child, family, and social related factors affecting the mental health of school age children. Finally, some suggestions on the construction of children s mental health service system in major public health emergencies were put forward at the national, school family community, and individual levels. Building a safe and reliable child mental health protection network required the joint efforts of all sectors of society.
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OBJECTIVE@#To explore the clinical significance of magnetic resonance imaging water-fat separation (Dixon) technique in patients with multiple myeloma.@*METHODS@#A total of 41 newly diagnosed patients with multiple myeloma who underwent Dixon in The Affiliated Hospital of Qingdao University from April 2019 to April 2021 were included in this study. Patients were divided into observation group and control group according to whether Dixon performance was normal or not. The differences of clinical data and fat fraction (FF) between the two groups were compared. The correlation between FF and clinical data, disease stages and differences before and after treatment were also compared. The receiver operator characteristic curve of patients was drawn to analyze the diagnostic value of FF combined with serum alkaline phosphatase for bone destruction in patients with multiple myeloma.@*RESULTS@#Among the 41 patients, there were 12 cases in the control group and 29 cases in the observation group. There was no significant difference in age and sex between the two groups. In the observation group, β2-microglobulin concentration and M protein were significantly higher than those in the control group, while serum alkaline phosphatase and FF were lower (P<0.05). In all 41 patients included in the study, there was a significant negative correlation between FF value and β2-microglobulin concentration (r=-0.57), and a significant positive correlation between FF value and serum alkaline phosphatase (r=0.31). After treatment, FF value increased, while myeloma cell percentage, β2-microglobulin concentration and M protein decreased in 11 patients who completed 4 cycles of chemotherapy, and the differences before and after treatment were statistically significant (P<0.05). The value of serum alkaline phosphatase combined with FF value in predicting bone destruction is higher than that of FF value or serum alkaline phosphatase alone.@*CONCLUSION@#Dixon's different imaging manifestations can reflect the severity of the disease. FF value is correlated with clinical examination results and R-ISS staging, and there is a significant difference before and after treatment. Serum alkaline phosphatase combined with FF value is better than two indicators alone in predicting bone destruction.
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Humans , Magnetic Resonance Imaging , Multiple Myeloma/diagnostic imaging , Technology , WaterABSTRACT
Individualized treatment of prostate cancer depends on an accurate stratification of patients who are sensitive to various treatments. Interleukin-23 (IL-23) was reported to play a significant role in prostate cancer. Here, we aimed to explore the clinical value of IL-23-secreting (IL-23+) cells in prostate cancer patients. We evaluated interleukin-23A (IL-23A) expression in The Cancer Genome Atlas database and retrospectively enrolled 179 treatment-naïve metastatic prostate cancer patients diagnosed in our institute between June 2012 and December 2014. IL-23+ cells were stained and evaluated via immunohistochemistry. Further, survival and multivariate Cox regression analyses were conducted to explore the prognostic value of IL-23+ cells. We found that IL-23A expression correlated with disease progression, while IL-23+ cells were clearly stained within prostate cancer tissue. Patients with higher Gleason scores and multiple metastatic lesions tended to have more IL-23+ cell infiltration. Further analyses showed that patients with higher levels of IL-23+ cells had significantly worse overall survival (hazard ratio [HR] = 2.996, 95% confidence interval [95% CI]: 1.812-4.955; P = 0.001) and a higher risk of developing castration resistance (HR = 2.725, 95% CI: 1.865-3.981; P = 0.001). Moreover, subgroup analyses showed that when patients progressed to a castration-resistant status, the prognostic value of IL-23+ cells was observed only in patients treated with abiraterone instead of docetaxel. Therefore, we showed that high IL-23+ cell infiltration is an independent prognosticator in patients with metastatic prostate cancer. IL-23+ cell infiltration may correlate with abiraterone effectiveness in castration-resistant prostate cancer patients.
Subject(s)
Humans , Male , Abiraterone Acetate/therapeutic use , Androstenes , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease-Free Survival , Interleukin-23/metabolism , Prostatic Neoplasms, Castration-Resistant/pathology , Retrospective Studies , Treatment OutcomeABSTRACT
The purpose of our study is to investigate the prognostic value of phosphatase and tensin homolog on chromosome 10 (PTEN) expression in patients with de novo metastatic castration naïve prostate cancer (mCNPC). A total of 205 patients with mCNPC at Fudan University Shanghai Cancer Center (Shanghai, China) were retrospectively examined. Immunohistochemical staining of PTEN was performed on prostate biopsy samples of these patients. Associations among clinicopathological features, patient survival and PTEN protein expression were analyzed. PTEN loss occurred in 58 of 205 (28.3%) patients. Loss of PTEN was significantly correlated with high metastatic volume (P = 0.017). No association between PTEN expression and Gleason score was observed. Patients with PTEN loss had significantly shorter progression-free survival (PFS, P < 0.001) and overall survival (OS, P < 0.001) compared with patients with intact PTEN expression. Multivariate analysis showed that elevated alkaline phosphatase, high metastatic volume and PTEN loss were independent poor prognostic factors for PFS. The Eastern Cooperative Oncology Group performance status (ECOG PS)#8805; 2 and PTEN loss were independent poor prognostic factors for OS. The adjusted hazard ratio of PTEN loss for PFS and OS was 1.67 (95% confidence interval [CI]: 1.14-2.43, P = 0.008) and 1.95 (95% CI: 1.23-3.10, P = 0.005), respectively. PTEN loss was also significantly associated with shorter PFS (P = 0.025) and OS (P < 0.001) in patients with low-volume metastatic disease. Our data showed that PTEN loss is an independent predictor for shorter PFS and OS in patients with de novo mCNPC.
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Humans , Male , China/epidemiology , PTEN Phosphohydrolase/genetics , Prognosis , Prostatic Neoplasms , Retrospective StudiesABSTRACT
Objective:To investigate the effect of lappaconitine (LA) on neuropathic pain (NPP) mediated by retrograde transport of purinergic P2X3 receptor (P2X3R) in dorsal root ganglion (DRG) neurons of rats with chronic constriction injury (CCI) of the sciatic nerve.Methods:Seventy-two male healthy SD rats were selected to construct the NPP model following CCI of the sciatic nerve by ligating the right sciatic nerve. according to the random number table method. The rats were divided into CCI group, CCI+LA group and normal control group according to the random number table method, with 24 rats in each group. In normal control group, the right sciatic nerve was exposed without ligation. In CCI+LA group, the rats were given 2 g/L LA (ie, 4 mg/kg intravenously for once a day for one day only) after the same treatment as CCI group. Other two groups were injected with the identical amount of normal saline in the same way. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were evaluated before injury and at 2, 6, 12 and 24 hours after injury to evaluate the symptoms of neuralgia caused by nerve injury. The proximal and distal nerve fragments were collected in the three groups at 2, 6, 12 and 24 hours after injury. Western blotting was applied to analyze the expression of P2X3R at 2, 6, 12 and 24 hours after injury and the expression of neurotrophic factor (NGF) and tyrosine kinase receptor A (TrkA) at 24 hours after injury to evaluate the effect of LA on P2X3R, NGF and TrkA.Results:There were insignificant differences in MWT and TWL among all groups before injury (all P>0.05). Compared with normal control group, MWT and TWL were significantly decreased in CCI group and CCI+LA group at 2, 6, 12 and 24 hours after injury (all P<0.05 or 0.01). There were insignificant differences in MWT and TWL between CCI group and CCI+LA group at 2 and 6 hours after injury (all P>0.05), while MWT and TWL were significantly higher in CCI+LA group than those in CCI group at 12 and 24 hours after injury (all P<0.05 or 0.01). In the proximal sciatic nerve segment, Western blotting showed similar levels of P2X3R among all groups at 2, 6, 12 and 24 hours after injury (all P>0.05). In the distal sciatic nerve segment, Western blotting showed higher expression of P2X3R in CCI group than that in normal control group at 2, 6, 12, 24 hours after injury (all P<0.01), higher expression of P2X3R in CCI+LA group than that in normal control group at 2, 6 and 12 hours after injury (all P<0.05), similar expression of P2X3R expression between CCI+LA group and normal control group at 24 hours after injury ( P>0.05), similar expression of P2X3R between CCI group and CCI+LA group at 2 and 6 hours after injury (all P>0.05), and lower expression of P2X3R in CCI+LA group than that in CCI group at 12 and 24 hours after injury ( P<0.05 or 0.01). In the proximal and distal nerve fragments, the expression of NGF was lower in normal control group than that in CCI group and CCI+LA group ( P<0.05 or 0.01), but was similar between CCI group and CCI+LA group at 24 hours after injury ( P>0.05). In the proximal and distal nerve fragments, there were insignificant differences in the expression of TrkA among all groups at 24 hours after injury (all P>0.05). Conclusion:Early LA treatment after injury can alleviate mechanical and thermal hyperalgesia in NPP rats, which may be related to the reduction of P2X3R retrograde transport in DRG neuron axonal.
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Purpose@#The purpose of this study was to investigate the prevalence and risk factors of overactive bladder (OAB) in young adults and to explore the influence of OAB on mental health. @*Methods@#Between October 2019 and January 2020, 14,010 anonymous questionnaires were distributed to freshmen at 2 universities in Henan, China. The students came from all over the country. The questionnaire included general items and information necessary to calculate the overactive bladder symptom score, the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) score, Self-Esteem Scale (SES) score, and Self-Rating Depression Scale (SDS) score. The relationships between the prevalence of OAB and its risk factors were evaluated. @*Results@#The overall prevalence of OAB was 6.0%, with 4.3% of participants characterized as having dry OAB and 1.7% as having wet OAB. The prevalence of mild OAB was 5.5%, and that of moderate OAB was 0.5%; no severe OAB was observed. Higher prevalence rates of OAB were found among women, respondents with constipation, and respondents with primary nocturnal enuresis (PNE) (P <0.05). Compared to healthy controls, the OAB group exhibited a higher mean SDS score (52.12±8.986 vs. 47.71±9.399, P<0.001) and mean PSQI score (5.28±2.486 vs. 4.27±2.431, P<0.001), but a lower mean SES score (27.78±3.599 vs. 29.57±4.109, P<0.001). @*Conclusions@#OAB significantly affects the mental health of young adults. Female sex, constipation, and PNE are risk factors for OAB.
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Objective: To evaluate the safety and feasibility of laparoscopic surgery after neoadjuvant chemotherapy for pancreatic cancer. Methods: Clinical data of 8 patients underwent laparoscopic surgery after neoadjuvant chemotherapy for pancreatic cancer at Fudan University Shanghai Cancer Center from September 2019 to June 2020 were reviewed retrospectively. There were 5 males and 3 females,aged from 47 to 72 years old. All patients underwent abdominal enhanced CT and PET-CT before operation to accurately evaluate the tumor stage and exclude distant metastasis. Results: Neoadjuvant chemotherapy with AG regimen(gemcitabine 1 000 mg/m2 and albumin bound paclitaxel 125 mg/m2) was received for 2 to 6 cycles before surgery. All 8 patients successfully completed the operation,including 5 cases of pancreaticoduodenectomy,2 cases of radical antegrade modular pancreatosplenectomy(RAMPS),and 1 case of total pancreatectomy. No conversion to laparotomy or laparoscopic assisted surgery. The operation time was 240 to 450 minutes,the blood loss was 100 to 500 ml,the postoperative length of stay was 10 to 16 days. During the follow-up period up to December 31, 2020, there was 1 case suffered grade B pancreatic leakage and abdominal infection. The numbers of resected lymph nodes were 9 to 31. All patients received R0 resection. The follow-up times were 4.5 to 9.5 months. One patient underwent RAMPS was diagnosed as liver metastasis after 2 months of the operation,and the other 7 patients still survived without tumor recurrence. Conclusion: Minimally invasive surgery of pancreatic cancer after neoadjuvant chemotherapy is safe and feasible in experienced pancreatic minimally invasive centers.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , China , Laparoscopy , Neoadjuvant Therapy , Neoplasm Recurrence, Local , Pancreatectomy , Pancreatic Neoplasms/surgery , Positron Emission Tomography Computed Tomography , Retrospective StudiesABSTRACT
Objective: To explore the protective effects of anthrahydroquinone-2,6-disulfonate (AH 2 QDS) on the kidneys of paraquat (PQ) poisoned rats via the apelin-APJ pathway. Methods: Male Sprague Dawley rats were divided into four experimental groups: control, PQ, PQ+sivelestat, and PQ+AH 2 QDS. The PQ+sivelestat group served as the positive control group. The model of poisoning was established via intragastric treatment with a 20% PQ pesticide solution at 200 mg/kg. Two hours after poisoning, the PQ+sivelestat group was treated with sivelestat, while the PQ+AH 2 QDS group was given AH 2 QDS. Six rats were selected from each group on the first, third, and seventh days after poisoning and dissected after anesthesia. The PQ content of the kidneys was measured using the sodium disulfite method. Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes. Apelin expression in the renal tissues was detected using immunofluorescence. Western blotting was used to detect the expression levels of the following proteins in the kidney tissues: IL-6, TNF-α, apelin-APJ (the apelin-Angiotensin receptor), NF-κB p65, caspase-1, caspase-8, glucose-regulated protein 78 (GRP78), and the C/EBP homologous protein (CHOP). In in vitro study, a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ. Twenty-four hours after poisoning, sivelestat and AH 2 QDS were administered. The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe. Results: The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH 2 QDS group. Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group. Vacuolar degeneration of the renal tubule epithelial cells, deposition of crescent-like red staining material in renal follicles, infiltration by a few inflammatory cells, and a small number of cast formation were also observed. However, these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH 2 QDS group (P<0.05). On the third day after poisoning, immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH 2 QDS group than in the PQ group. Western blotting analysis results showed that IL-6, TNF-α, NF-κB p65, caspase-1, caspase-8, GRP78, and CHOP protein levels in the PQ group were higher than in the PQ+AH 2 QDS group (P<0.05). The expression of apelin-APJ proteins in the PQ+AH 2 QDS group was higher than in the PQ+sivelestat and PQ groups (P<0.05); this difference was significant on Day 3 and Day 7. The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH 2 QDS group and the PQ+sivelestat group was significantly lower than in the PQ group (P<0.05). Conclusions: This study confirms that AH 2 QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat. The mechanism of the protective effects of AH 2 QDS may be linked to reduction in cellular oxidative stress, PQ content of renal tissue, inflammatory injury, endoplasmic reticulum stress, and apoptosis. AH 2 QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.
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Objective: To explore the protective effects of anthrahydroquinone-2,6-disulfonate (AH 2 QDS) on the kidneys of paraquat (PQ) poisoned rats via the apelin-APJ pathway. Methods: Male Sprague Dawley rats were divided into four experimental groups: control, PQ, PQ+sivelestat, and PQ+AH 2 QDS. The PQ+sivelestat group served as the positive control group. The model of poisoning was established via intragastric treatment with a 20% PQ pesticide solution at 200 mg/kg. Two hours after poisoning, the PQ+sivelestat group was treated with sivelestat, while the PQ+AH 2 QDS group was given AH 2 QDS. Six rats were selected from each group on the first, third, and seventh days after poisoning and dissected after anesthesia. The PQ content of the kidneys was measured using the sodium disulfite method. Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes. Apelin expression in the renal tissues was detected using immunofluorescence. Western blotting was used to detect the expression levels of the following proteins in the kidney tissues: IL-6, TNF-α, apelin-APJ (the apelin-Angiotensin receptor), NF-κB p65, caspase-1, caspase-8, glucose-regulated protein 78 (GRP78), and the C/EBP homologous protein (CHOP). In in vitro study, a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ. Twenty-four hours after poisoning, sivelestat and AH 2 QDS were administered. The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe. Results: The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH 2 QDS group. Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group. Vacuolar degeneration of the renal tubule epithelial cells, deposition of crescent-like red staining material in renal follicles, infiltration by a few inflammatory cells, and a small number of cast formation were also observed. However, these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH 2 QDS group (P<0.05). On the third day after poisoning, immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH 2 QDS group than in the PQ group. Western blotting analysis results showed that IL-6, TNF-α, NF-κB p65, caspase-1, caspase-8, GRP78, and CHOP protein levels in the PQ group were higher than in the PQ+AH 2 QDS group (P<0.05). The expression of apelin-APJ proteins in the PQ+AH 2 QDS group was higher than in the PQ+sivelestat and PQ groups (P<0.05); this difference was significant on Day 3 and Day 7. The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH 2 QDS group and the PQ+sivelestat group was significantly lower than in the PQ group (P<0.05). Conclusions: This study confirms that AH 2 QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat. The mechanism of the protective effects of AH 2 QDS may be linked to reduction in cellular oxidative stress, PQ content of renal tissue, inflammatory injury, endoplasmic reticulum stress, and apoptosis. AH 2 QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.
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In this study, the molecular mechanism of Cinnamomi Cortex-Rehmanniae Radix (CR) in the prevention and treatment of osteoporosis (OP) was investigated by integrating compatibility analysis of compound, bioinformatics and metabolomics. The rat OP models were established, and the Micro-CT indexes and pathological sections were comprehensively evaluated. The results showed that compared with the model group, the indexes such as bone mineral density (BMD) and bone volume/tissue volume (BV/TV) were significantly increased after CR treatment (P < 0.05), and the bone trabeculae were arranged into mesh. The results of UHPLC-Q-TOF/MS mainly involved amino acid metabolism, lipid metabolism and estrogen metabolism pathways. Integrating bioinformatics and metabolomics analysis, it was finally found that: ① cinnamic acid and ethylcinnamate inhibit inflammatory factors such as TNF, IL-1β, and IL-13, thereby preventing and treating OP; ② multiple active ingredients of CR target ESR2, PPARG, and CYP19A1, GABRA1 and other targets, regulate cAMP synthesis, AMPK signaling pathway and lipid metabolism, thereby regulating estrogen levels to prevent and treat OP; ③ oleic acid, arachic acid, etc. act on AR, VDR and other targets, and regulate HIF-1 signaling pathway and AGE-RAGE signaling pathway, thereby regulating osteoblasts and osteoclasts, and affecting calcium and phosphorus absorption to maintain bone homeostasis. This study clarified the molecular mechanism of CR in preventing and treating OP from the perspective of multi-directional regulation of inflammatory factors, estrogen and bone homeostasis, and provided theoretical basis for the clinical application of CR and the development of compound. This experiment complied with the ethical standards of animal experiments and was approved by the Animal Ethics Committee of Shaanxi University of Chinese Medicine (No. SUCMDL20210309002).
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Objective@#To determine the association between physical health fitness with Chinese reading ability of schoolaged children, so as to provide evidence for improving children s reading ability.@*Methods@#A questionnaire survey was conducted among 1 923 school aged children in grades 2-6 in a primary school in Wuhan, Hubei Province, China. The questionnaire included basic demographic information and Dyslexia Checklist for Chinese Children and the Pupil Rating Scale Revised Screening. At the same time, participants underwent physical fitness tests which included an assessment of height, weight, and lung capacity, as well as a 50 meter run, sit forward bend, one minute skipping rope task, sit ups, and a 50 × 8 round trip.@*Results@#A total of 59 children were identified with dyslexia. Normal children achieved higher scores than children with dyslexia in the total physical health score, as well as the one minute skipping rope score, one minute sit up score, and sitting forward score ( P <0.05). Multiple linear regression analyses showed that the reading ability of girls was higher than that of boys ( β =-3.04, P <0.01), and the children who regularly participated in more intense physical activity and who had higher fitness scores had a higher reading ability ( β =-1.68, -0.08, P <0.01). Children s reading ability increased significantly with parental educational level( P <0.05).@*Conclusion@#Gender, parents education level, physical exercise intensity, and children s physical fitness were identified as influencing factors of school age children s reading ability. A positive correlation was found between children s physical health level and reading ability.
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Objective@#To investigate the progression of depressive and anxiety symptoms of children, especially whose parents were frontline workers in the combat of the coronavirus disease 2019 (COVID-19), and to provide evidence for children s mental health promotion.@*Methods@#In June and December 2020, two surveys were conducted among the children in a primary school in Qiaokou District, Wuhan. The questionnaire included demographic information, student learning conditions, and depressive/anxiety symptoms.@*Results@#A total of 963 children completed both surveys. The detection rate of depressive and anxiety symptoms at follow up was significantly higher than that at the baseline survey (depressive symptoms: OR=1.45, 95%CI =1.16-1.83; anxiety symptoms: OR=1.79, 95%CI =1.41-2.28, P <0.01). There was no statistically significant change in depressive/anxiety symptoms among children whose parents were frontline workers compared with those whose parents were not( P >0.05). Girls, lower learning efficiency, and less interaction with teachers in class were risk factors for depressive or anxiety symptoms of children( P < 0.05 ).@*Conclusion@#Mental health status of children requires continuous attention. Moreover, timely psychological protection should be given to prevent the occurrence of psychological problems and the further deterioration of psychological problems.
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Although anti-thrombotic therapy has been successful for prevention of deaths from acute myocardial infarction (MI), by far, there are few preventive and therapeutic options for ischemic heart failure (IHF) after MI. Qi-Tai-Suan (QTS) is an oleanolic acid (OA) derivative which once underwent a clinical trial for treating hepatitis. In this study, we investigated the potential cardioprotective effect of QTS on IHF. IHF mouse model was constructed by coronary artery ligation in male C57BL/6J mice, and the protective effects of QTS on IHF were examined by echocardiography measurement, histological and TUNEL analysis, etc. We found that QTS exhibited promising cardioprotective effect on IHF. QTS treatment significantly improved cardiac function of IHF mice and the symptoms of heart failure. Notably, QTS had much better oral bioavailability (F = 41.91%) in mice than its parent drug OA, and took effects mainly as its original form. Mechanistically, QTS ameliorated ischemic heart failure likely through suppression of cardiac apoptosis, inflammation and fibrosis. Taken together, QTS holds great promise as a preventive and therapeutic agent for ischemic heart failure and related diseases.
Subject(s)
Animals , Male , Mice , Apoptosis , Fibrosis , Heart Failure/drug therapy , Inflammation/drug therapy , Mice, Inbred C57BL , Myocardial Ischemia/pathology , Oleanolic Acid/pharmacologyABSTRACT
For healthy term or preterm neonates who do not require resuscitation after birth, delayed cord clamping (DCC) for 1-3 min has been shown to have a beneficial effect on neonatal and infant health. DCC is recommended as a standard procedure by the World Health Organization. Umbilical cord milking (UCM) can be considered as an alternative when DCC is unfeasible. However, the safety of UCM in preterm infants less than 28 weeks still needs more evidence.
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Objective:To investigate the incidence of hypothyroxinemia in very low birth weight infant (VLBWI) and its effect on early postnatal feeding and weight gain.Methods:This retrospective study analyzed 164 cases of VLBWIs admitted to the Neonatal Intensive Care Unit of Peking University First Hospital from January 2017 to December 2018. According to the gestational age, these VLBWIs were divided into <30 weeks group ( n=85) or ≥30 weeks group ( n=79), and the basic data and thyroid function were compared. According to the levels of serum tetraiodothyronine and free tetraiodothyronine at the first thyroid function test, the subjects were further assigned into normal thyroxine group and hypothyroxinemia group. The risk factors of hypothyroxinemia identified at the first detection were analyzed by single and multiple-facter analysis. The results of the second detection of thyroxine were also analyzed. On the basis of the first detection and receiving treatment or not, the <30 weeks and ≥30 weeks groups were divided into normal thyroxine, hypothyroxinemia treated and hypothyroxinemia untreated subgroups, and differences in the tolerance of early feeding and weight gain were compared between different groups. Two independent samples/paired t-test, rank sum test, Chi-square test and logistic regression were used for statistical analysis. Results:Out of the 164 VLBWIs with the gestational age of (29.7±2.0) weeks and birth weight of (1 210±210) g, 27 cases (16.5%) were extremely low birth weight infants. The age at their first detection was (10.7±3.1) d and the incidence of hypothyroxinemia was 45.1% (74/164), including 71 mild and three severe cases, with a higher incidence in the ≥30 weeks group comparing to the <30 weeks group [55.7%(44/79) vs 35.5%(30/85), χ 2= 6.883, P=0.009]. All the three severe cases were in the ≥30 weeks group. The gestational age ( OR=1.413, 95% CI:1.044-1.912, P=0.025) and male infant ( OR=2.082, 95% CI: 1.047-4.143, P=0.037) were the risk factors of hypothyroxinemia. At the second detection, the incidence of hypothyroxinemia in VLBWIs with normal thyroid function at their first test was 47.6% (39/82), which is higher in the ≥30 weeks group than in the <30 weeks group [64.5%(20/31) vs 37.3%(19/51), χ 2= 5.745, P=0.017]. Among the infants with hypothyroxinemia at the first detection, those untreated had a significantly higher incidence of hypothyroxinemia at the second detection than those treated [81.3%(26/32) vs 38.7%(12/31), χ 2= 11.905, P=0.001]. The incidence of abdominal distension within 21 days, feeding volume on day 7, 14, and 21, and neonatal weight gain within 7, 14, and 21 days were similar between normal thyroxine, hypothyroxinemia treated and hypothyroxinemia untreated subgroups within the ≥30 weeks or the <30 weeks groups (all P>0.05). Conclusions:VLBWI is at high risk of hypothyroxinemia. Two times of postnatal thyroid function tests can help to detect the delayed hypothyroxinemia. Thyroxine level and receiving treatment or not may have no significant effect on the early postnatal feeding and weight gain.