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Objective To analyse the analgesic effect and possible mechanism of panax notoginseng saponin (PNS) on mouse models of chronic inflammatory pain caused by complete Freund’s adjuvant (CFA). Methods A total of 48 male C57BL/ 6J mice were divided randomly into four groups: normal saline control group (Ctrl), CFA group (CFA), CFA + PNS group (CFA+PNS), CFA + dexamethasone (DEX) group (CFA+DEX). Von Frey filaments were used to detect mechanical pain in mice. Immunohistochemistry was used to detect the number and morphological changes of glial fibrillary acidic protein (GFAP) positive astrocytes. Western blotting was used to detect the expressions of GFAP, nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in mice’s spinal cord segments in each group. Results Compared with the Ctrl group, mice in the CFA group showed a significant decrease in mechanical pain thresholds at day 1, day 3, day 5, day 7, and day 14. Additionally, there was a significant decrease in NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of the mice. PNS intervention could relieve mechanical pain and down-regulate the expressions of NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of mice, with no significant difference compared with the CFA+DEX group. CFA group mice had significantly more GFAP positive cells in their posterior horns than Ctrl group mice, as measured by immunohistochemistry; PNS intervention decreased the number of GFAP positive cells in the posterior horn of the spinal cord in model mice;DEX had no effect on the number of GFAP positive cells in the dorsal horn of spinal cord. According to Western blotting results, GFAP expression in the spinal cord of the CFA group was significantly more than that of the Ctrl group; PNS intervention significantly reduced GFAP expression in the spinal cord of CFA group mice;DEX had no effect on the expression of GFAP in the posterior horn of spinal cord. Conclusion PNS has a good alleviating effect on inflammatory pain, and its mechanism may be related to inhibition of astrocyte activation and NLRP3 inflammasome activation.
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The occurrence and development of many eye diseases are closely related to genetic and environmental factors, among which epigenetic modification is an important bridge connecting genetic and environmental factors. It can affect the levels of related genes by influencing gene transcription or translation, thereby playing a role in the pathogenesis of ocular diseases. DNA methylation is an important part of epigenetic modification which is usually regulated by three processes: de novo methylation, maintenance methylation, and demethylation, and plays an essential role in regulating gene expression. At present, researchers have conducted that DNA methylation plays an important role in repair of damage to corneal endothelium, mitochondrial dynamics regulation and diabetic retinopathy, oxidative stress response and cataracts and other eye diseases, providing new ideas in the treatment of related ocular diseases. This study presented a brief review of the role of DNA methylation in the development of related ocular diseases and provided new perspectives and directions for the screening, diagnosis, and treatment of eye diseases.
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Objective:To construct and evaluate a screening and diagnostic system based on color fundus images and artificial intelligence (AI)-assisted screening for optic neuritis (ON) and non-arteritic anterior ischemic optic neuropathy (NAION).Methods:A diagnostic test study. From 2016 to 2020, 178 cases 267 eyes of NAION patients (NAION group) and 204 cases 346 eyes of ON patients (ON group) were examined and diagnosed in Zhongshan Ophthalmic Center of Sun Yat-sen University; 513 healthy individuals of 1 160 eyes (the normal control group) with normal fundus by visual acuity, intraocular pressure and optical coherence tomography examination were collected from 2018 to 2020. All 2 909 color fundus images were as the data set of the screening and diagnosis system, including 730, 805, and 1 374 images for the NAION group, ON group, and normal control group, respectively. The correctly labeled color fundus images were used as input data, and the EfficientNet-B0 algorithm was selected for model training and validation. Finally, three systems for screening abnormal optic discs, ON, and NAION were constructed. The subject operating characteristic (ROC) curve, area under the ROC (AUC), accuracy, sensitivity, specificity, and heat map were used as indicators of diagnostic efficacy.Results:In the test data set, the AUC for diagnosing the presence of an abnormal optic disc, the presence of ON, and the presence of NAION were 0.967 [95% confidence interval ( CI) 0.947-0.980], 0.964 (95% CI 0.938-0.979), and 0.979 (95% CI 0.958-0.989), respectively. The activation area of the systems were mainly located in the optic disc area in the decision-making process. Conclusion:Abnormal optic disc, ON and NAION, and screening diagnostic systems based on color fundus images have shown accurate and efficient diagnostic performance.
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Objective:To observe any effect of transcranial direct current stimulation (tDCS) on learning, memory ability and the morphology of neurons in the hippocampus and cortex of rats with cognitive impairment, and also to seek any correlation between the rats′ behavior and the thickness of the granular layer in the CA1 region of the hippocampus.Methods:Thirty Sprague-Dawley rats were randomly divided into an observation group, a model group and a control group, each of 10. Cognitive impairment was induced in the observation and model groups by intraperitoneal injection of scopolamine, while the control group was injected with saline solution over the same period of time. After successful modeling, the observation group was given tDCS, while the model and control groups were connected with electrodes but not given any electrical stimulation. After 16 consecutive days of treatment, behavioral changes of each group were quantified using a shuttle box and a Morris water maze. On the 30th day after the mode-ling, the brains were collected to observe any changes in the morphology of the hippocampal and cortical neurons. The thickness of the hippocampal granular layer was also measured.Results:In the observation group the average rate of electrical impulses after the intervention [(60.5±6.67)/min] was significantly less than in the model group [(145.8±19.31)/min], while the time to find a platform was significantly shorter. The rats of the observation group also crossed the D quadrant of the platform significantly more quickly than the model group, on average. Compared with the control group, the granular layer in the CA1 region of the hippocampus [(93.47±1.07)μm] was significantly thinner on average than in the model group but compared with the model group, the observation group had significantly thicker layers [95.17±1.49)μm] on average. The thickness was negatively correlated with the number of shocks and the time to find the platform, but positively correlated with the number of crossings of the platform in the D quadrant.Conclusions:The degree of impairment generated by intraperitoneal injection of scopolamine correlates with the thickness of the CA1 granular layer of the hippocampus, at least in rats. tDCS can improve the learning and memory of such rats. Its mechanism may be related to promoting structural recovery of hippocampal cortical neurons and increasing the thickness of the granular layer.
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Urosepsis caused by upper urinary tract stone obstruction is a common critically disease in urology.However, it rarely occurs in the patient who underwent a dialysis with uremia.We report a patient who underwent an implantation of ureteral stent to control the infection, and we saved the patient with perinephric hematoma following the surgery. We removed the stones in the left ureteral through a flexible ureteroscope two month later.The hematoma was completely absorbed 6 months after the implantation of ureteral stent.
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Objective:To explore the value of pre-ablation stimulated thyroglobulin (psTg) before 131I treatment combined with lymph node ratio (LNR) in predicting 131I treatment response in patients with papillary thyroid cancer (PTC). Methods:From January 2016 to December 2018, 178 PTC patients (47 males, 131 females; age (43.2±12.6) years) treated with 131I in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. According to 131I treatment response, patients were divided into excellent response (ER) group and non-ER group. The clinical data of the two groups were compared by χ2 test, independent-sample t test and Mann-Whitney U test. The cut-off values and AUCs of psTg and LNR to predict treatment response were calculated according to the ROC curve. Factors affecting 131I treatment response were analyzed by logistic multivariate regression analysis. Results:There were 118 patients (66.3%, 118/178) in ER group and 60 patients (33.7%, 60/178) in non-ER group, and there were significant differences in N stage ( χ2=11.15, P=0.004), 131I treatment dose ( χ2=12.65, P<0.001), American Thyroid Association (ATA) initial risk stratification ( χ2=15.25, P<0.001), number of metastatic lymph nodes ( χ2=22.63, P<0.001), LNR ( U=1 506.00, P<0.001) and psTg ( U=919.00, P<0.001) between the two groups. The cut-off values of psTg and LNR predicting ER were 3.97 μg/L and 0.29, with the AUC of 0.870 and 0.787 respectively. PsTg (odds ratio ( OR)=10.88, 95% CI: 4.67-25.36, P<0.001) and LNR ( OR=5.30, 95% CI: 1.85-15.23, P=0.002) were independent factors to predict 131I treatment response in PTC patients. When psTg≥3.97 μg/L, LNR ( OR=9.40, 95% CI: 2.06-42.92, P=0.004) was an independent factor affecting 131I treatment response in PTC patients. Conclusions:PsTg and LNR are independent factors affecting 131I treatment response in PTC patients. When psTg≥3.97 μg/L, LNR can be used as a supplementary factor to predict 131I treatment response. The combination of psTg and LNR can better predict 131I treatment response in PTC patients.
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Objective:To evaluate the effectiveness and feasibility of 3D ResSE-Unet-based intelligent delineation of clinical target volume (CTV) in postoperative adjuvant radiotherapy for breast cancer.Methods:A total of 974 cases of breast cancer treated in the Cancer Diagnosis and Treatment Center of the Fourth Affiliated Hospital of Guangxi Medical University from September 2018 to June 2022 were enrolled in this study, including 614 cases receiving total mastectomy and 360 cases treated with breast-conserving surgery. They were divided into a training set, a validation set, and a testing set. The training set consisted of 874 cases and was used to build a model of 3D ResSE-Unet-based intelligent CTV delineation. The validation set comprised 40 cases and was used to evaluate the feasibility and effectiveness of the clinical application of AI-based CTV design in the radiotherapy for breast cancer. The testing set was composed of 60 cases and was used to test the accuracy of intelligent CTV. The Wilcoxon rank test was used to compare the Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and average surface distance (ASD) obtained using the intelligent delineation model.Results:The intelligent delineation model showed high precision. The CTV of cases treated with total mastectomy (CTV cw) and the CTV of cases treated with breast-conserving surgery (CTV b) had DSCs greater than 0.80 and greater than 0.88, respectively. Therefore, compared with CTV cw, CTV b had a higher DSC (0.91 ± 0.03 vs.0.83 ± 0.05, t = 7.11, P < 0.05). Both CTV cw and CTV b had lower HD 95 [(7.56 ± 3.42) mm vs.(8.77 ± 5.89) mm] and ASD [(1.85 ± 0.71) mm vs.(1.86 ± 0.83)mm], without statistically significant difference ( P > 0.05). The left/right supraclavicular and infraclavicular CTV (CTV2) had DSCs greater than 0.8. CTV2 also had low average HD95 and ASD, without statistically significant difference ( P > 0.05). Conclusions:The 3D ResSE-Unet-based intelligent CTV delineation has better consistency and feasibility in postoperative adjuvant radiotherapy for breast cancer, especially the CTVs after breast-conserving surgery.
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Epilepsy is a disorder of the brain charac-terized by abnormal neuron excitability.However,the underlying molecular mechanism of neuron excitability modulation remains elusive.With the help of bioinformatic methods,we have identified receptor-type tyrosine-pro-tein phosphatase-like N(PTPRN)as a critical gene dur-ing epileptogenesis.PTPRN recruits NEDD4L ubiquitin E3 ligase to NaV1.2 sodium channels,facilitating NEDD4L-mediated ubiquitination and endocytosis.Knockout of PTPRN endows hippocampal granule cells with augmented depolarization currents and higher intrinsic excitability,which is reflected by increased seizure susceptibility of transgenic mice.On the contrary,reduced neuron excit-ability and decreased seizure susceptibility are observed after PTPRN overexpression.Meanwhile,we find that a 133 aa fragment recaptures modulation effect of PTPRN full-length,and this fragment shows therapeutic potential towards epilepsy caused by NaV1.2 gain of function vari-ants.In brief,our results demonstrate PTPRN playsa criti-calroleinregulatingneuronexcitability,providing a poten-tial therapeutic approach for epilepsy.
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Objective:To investigate and analyze the status quo of death cognition and hospice care attitude of clinical medical graduate students, to compare the differences between the two groups, and to explore the correlation between death cognition and hospice care attitude, so as to provide the reference for the reform and construction of death cognition and hospice care education in medical colleges and universities in China.Methods:A survey was carried out on 496 doctoral and postgraduate students majoring in clinical medicine by using the "Questionnaire of General Sociology Survey", the Chinese version of the "Death Attitude Profile Revised Scale", and the Chinese version of the "Frommelt Attitudes Toward Care of the Dying Scale Form B (FATCOD-B)" to investigate the death cognition and hospice care attitude of 496 doctoral and postgraduate students majoring in clinical medicine, and classified and compared the survey results of the two groups. The results of this study were statistically analyzed by t-test, Pearson correlation analysis and other statistical methods. Results:A total of 469 valid questionnaires were recovered after excluding 27 unqualified questionnaires. Statistical analysis showed that the scores of each dimension in the death attitude description scale of doctoral students were ranked as follows: approach acceptance (4.28±0.53), neutral acceptance (3.99±0.41), death avoidance (2.74±0.63), fear of death (2.65±0.57) and escape acceptance (2.47±0.69) the scores of postgraduates were ranked as neutral acceptance (3.96±0.52), approach acceptance (2.84±0.61), fear of death (2.78±0.65), death escape (2.62±0.73), escape acceptance (2.39±0.77). At the same time, the scores of hospice care attitude in the doctoral group were higher than those in the master group [(110.63±8.96) vs. (106.78±6.52)], and the difference was statistically significant ( P<0.001). In addition, the scores of "fear of death" and the scores of hospice care attitudes were negatively correlated with the scores of doctoral and master students ( r=-0.25, r=-0.21), while the scores of hospice care attitudes were positively correlated with the scores of "neutral acceptance" in death cognition ( r=0.50, r=0.32). However, the hospice care attitude scores of doctoral students were negatively correlated with the "death avoidance" scores in death cognition ( r=-0.27). Conclusion:Doctoral and postgraduate students have a certain awareness of hospice care, while their death cognition and hospice care attitude still need to be improved and strengthened from sociology, psychology, ethics and other perspectives. The above will promote the harmony between doctors and patients while meeting the needs of an aging society in China.
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Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.
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Objective:To assess the severity of hypoxic-ischemic brain damage (HIBD) in neonatal rats and predict the occurrence of subsequent neurobehavioral abnormalities after brain injury by scoring and magnetic resonance imaging (MRI).Methods:7-day-old of 60 Sprague-Dawley (SD) rats were randomly divided into control group (14 rats), sham operation group (14 rats) and HIBD model group (32 rats). HIBD model was established by right common carotid artery dissection with Rice-Vannucci method and hypoxia. Within 24 h after modeling, the rats in the model group were evaluated by general condition score and Longa score, and the surviving rats with moderate and severe HIBD were selected for the experiment. 24 h after modeling, 5 rats of the model group were randomly selected for 2,3,5-triphenyltetrazole chloride staining to verify cerebral infarction. 1 week after modeling, 6 rats from each group were randomly selected for hematoxylin-eosin staining to observe HIBD brain injury. 4 weeks after modeling, 4 rats were randomly selected from the control group and the sham operation group, and 8 rats from the remaining model group were used to evaluate the volume of brain damage by MRI. 5-6 weeks after modeling, the remaining 8 rats from each group were subjected to the Cylinder test, and at 13 weeks, they underwent the Morris water maze test to evaluate their neurobehavior.Results:In HIBD model group, 19 rats with moderate to severe HIBD were selected from 32 rats. 24 h after modeling, cerebral infarction was verified in all rats, indicating moderate to severe HIBD. Brain tissue pathology observed 1 week after modeling revealed predominantly gray matter brain damage. MRI showed that 7 out of 8 rats had moderate to severe HIBD. Compared to the control and sham operation groups, the model group exhibited a significant decrease in the usage rate of the left forelimb in the Cylinder test at 5-6 weeks after modeling ( P<0.05), and the latency period in Morris water maze test was significantly prolonged at 13 weeks after modeling ( P<0.05), and the times of crossing platform quadrant were significantly reduced ( P<0.05). There was no significant difference in the right brain injury volume between 24 h and 4 weeks model group ( P>0.05). The brain injury volume in model group was negatively correlated with the usage rate of left forelimb in cylinder test at 5-6 weeks and the times of crossing platform quadrant in Morris water maze test at 13 weeks ( P<0.05), and positively correlated with latency period in Morris water maze test at 13 weeks ( P<0.05). Conclusions:Within 24 h of HIBD modeling, the severity of brain injury can be preliminarily predicted by general condition score and Longa score. 4 weeks after modeling, in the chronic phase of brain injury, MRI was proved to be an excellent predictor for mid-term and long-term neurobehavioral abnormalities in HIBD rats.
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Objective:To develop the rehabilitation needs questionnaire for stroke patients, so as to provide a tool for medical staff to implement continuous rehabilitation services.Methods:Based on the conceptual framework of the International Classification of Function, Disability and Health, and on the basis of literature review and qualitative research, the questionnaire items were preliminatively established after two rounds of Delphi expert consultation, and 130 stroke patients admitted to the Department of Neurology and Rehabilitation of the First Hospital of Shanxi Medical University from April to December 2021 were selected to test the reliability and validity of the questionnaire. And 200 stroke patients were selected for confirmatory factor analysis to form a formal scale.Results:Exploratory factor analysis extracted a total of 4 common factors: physiological function rehabilitation needs, social rehabilitation environmental support needs, emotional/psychological support needs, rehabilitation knowledge/information needs. After project analysis and 3 exploratory factor analysis, a final questionnaire containing 16 items was formed.The Cronbach α of the questionnaire was 0.935, with a broken half reliability of 0.824. The fitting index of confirmatory factor analysis was within the standard range. The χ2/ df was 2.979, the incremental fitting index was 0.907, the comparative fitting index was 0.906, and the root mean square error of approximation was 0.100. Conclusions:The reliability and validity of the rehabilitation needs questionnaire for stroke patients are good, which can preliminarily assess the rehabilitation needs of stroke patients.
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Objective:To investigate the clinical efficacy of modified Guipi Decoction combined with omeprazole in the treatment of acute non-variceal upper gastrointestinal bleeding (ANVUGIB) with failure of the spleen to control blood vessels syndrome.Methods:Prospective cohort study. A total of 120 patients from January 2018 to December 2021 Taihe County Hospital of Traditional Chinese Medicine with ANVUGIB of failure of the spleen to control blood vessels syndrome were selected, and the patients were divided into observation group and control group according to the random number table method, with 60 cases in each group. The control group was treated with a large dosage of proton pump inhibitor (omeprazole injection was injected intravenously first, and then omeprazole enteric coated tablets were taken); the observation group took Guipi Decoction on the basis of the control group, and both groups were treated for 7 days. TCM syndrome score, Hemoglobin (Hb) and hematocrit (HCT) levels were measured by colorimetry before and after the treatment. BUN was detected by urease glutamate dehydrogenase method. Prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) levels were detected by immunoturbidimetry. The adverse reactions during treatment were recorded and the clinical efficacy was evaluated.Results:Two patients in the observation group and two patients in the control group dropped out of the study. After treatment, the scores of main symptoms, secondary symptoms and total scores in the observation group were lower than those in the control group ( t values were respectively 10.73, 4.45, 7.98, P<0.05). After treatment, the levels of HCT [(41.25 ± 5.03)% vs. (38.19 ± 5.26)%, t=2.95], Hb [(81.09 ± 5.23) g/L vs. (78.39 ± 5.37) g/L, t=2.74] in the observation group were higher than those in the control group ( P<0.01), and BUN [(4.38±0.96) mmol/L vs. (5.39 ± 1.13) mmol/L, t=5.19] was lower than that in the control group ( P<0.01); PT [(12.48 ± 0.67) s vs. (13.22 ± 0.73) s, t=5.69], APTT [(24.66 ± 2.29) s vs. (27.78 ± 2.04) s, t=7.75] were lower than those in the control group ( P<0.01), and FIB [(3.68 ± 0.62) g/L vs. (3.41 ± 0.74) g/L, t=2.13] level was higher than that in the control group ( P<0.05). The total effective rate of the observation group was 93.1% (54/58), and that of the control group was 79.3% (46/58), with statistical significance ( χ2=4.64, P=0.031). During the treatment, the incidence of adverse reactions in the control group was 3.4% (2/58), while that in the observation group was 1.7% (1/58), without statistical significance ( χ2=0.34, P=0.559). Conclusion:High-dosage omeprazole treatment with the addition of internal administration of Guipi Decoction can significantly improve coagulation function, correct the signs and symptoms associated with insufficient blood volume in the body circulation, improve hemostatic efficiency, and reduce the risk of bleeding in patients with ANVUGIB, without increasing the risk of patient safety with the drug.
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The development of chronic liver disease can be promoted by excessive fat accumulation, dysbiosis, viral infections and persistent inflammatory responses, which can lead to liver inflammation, fibrosis and carcinogenesis. An in-depth understanding of the etiology leading to chronic liver disease and the underlying mechanisms influencing its development can help identify potential therapeutic targets for targeted treatment. Orphan nuclear receptors (ONRs) are receptors that have no corresponding endogenous ligands to bind to them. The study of these ONRs and their biological properties has facilitated the development of synthetic ligands, which are important for investigating the effective targets for the treatment of a wide range of diseases. In recent years, it has been found that ONRs are essential for maintaining normal liver function and their dysfunction can affect a variety of liver diseases. ONRs can influence pathophysiological activities such as liver lipid metabolism, inflammatory response and cancer cell proliferation by regulating hormones/transcription factors and affecting the biological clock, oxidative stress, etc. This review focuses on the regulation of ONRs, mainly including retinoid related orphan nuclear receptors (RORs), pregnane X receptor (PXR), leukocyte cell derived chemotaxin 2 (LECT2), Nur77, and hepatocyte nuclear factor 4α (HNF4α), on the development of different types of chronic liver diseases in different ways, in order to provide useful references for the therapeutic strategies of chronic liver diseases based on the regulation of ONRs.
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Humans , Orphan Nuclear Receptors/metabolism , Receptors, Steroid/physiology , Ligands , Liver , Liver Diseases , Intercellular Signaling Peptides and ProteinsABSTRACT
BACKGROUND@#Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient's medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu's Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion.@*METHODS@#Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration <10 g/dL were randomly assigned to an individualized strategy, a restrictive strategy following China's guideline or a liberal strategy with a transfusion threshold of hemoglobin concentration <9.5 g/dL. We evaluated two primary outcomes: the proportion of patients who received red blood cells (superiority test) and a composite of in-hospital complications and all-cause mortality by day 30 (non-inferiority test).@*RESULTS@#We enrolled 1182 patients: 379, 419, and 384 received individualized, restrictive, and liberal strategies, respectively. Approximately 30.6% (116/379) of patients in the individualized strategy received a red-cell transfusion, less than 62.5% (262/419) in the restrictive strategy (absolute risk difference, 31.92%; 97.5% confidence interval [CI]: 24.42-39.42%; odds ratio, 3.78%; 97.5% CI: 2.70-5.30%; P <0.001), and 89.8% (345/384) in the liberal strategy (absolute risk difference, 59.24%; 97.5% CI: 52.91-65.57%; odds ratio, 20.06; 97.5% CI: 12.74-31.57; P <0.001). No statistically significant differences were found in the composite of in-hospital complications and mortality by day 30 among the three strategies.@*CONCLUSION@#The individualized red-cell transfusion strategy using the West-China-Liu's Score reduced red-cell transfusion without increasing in-hospital complications and mortality by day 30 when compared with restrictive and liberal strategies in elective non-cardiac surgeries.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT01597232.
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Humans , Adult , Postoperative Complications , Erythrocyte Transfusion/adverse effects , Blood Transfusion , Hospitals , Hemoglobins/analysisABSTRACT
Tumor brings great threat to human public health. In recent years, incidence rate and mortality of tumor were rapidly increased in the world. Anti-tumor therapies have undergone the development of cytotoxic therapy, targeted therapy, and immunotherapy. Among them, tumor immunotherapy is rapidly developed and becomes an important anti-tumor therapy in recent years, although it also brings some related side effects. Tumor microenvironment (TME) is composed of immune cells, vascular vessels, fibroblasts, the extracellular matrix, etc. TME significantly affects the efficacy of immunotherapy. Macrophages in the TME are named as tumor associated macrophages (TAMs). Recently, increasing studies have shown that TAMs play an important role in the regulation of tumor immunity, especially in tumor immune surveillance and immune escape. Currently, more and more anti-tumor immunotherapy strategies targeting TAMs are at the development stage. Based on the important role of TAMs in the TME and their potential as therapeutic targets in tumor immunotherapy, we first reviewed the subtypes and functions of TAMs, as well as the roles of TAMs in tumors. Furthermore, we summarized the research progress on anti-tumor strategies targeting TAMs and the current status of drug targeting TAMs. The current review will provide new ideas and novel insights for tumor immunotherapy.
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Objective To analyze the quality of blood smear examinations for malaria parasites in Chenzhou City, so as to provide insights into sustainable consolidation of malaria elimination achievements. Methods All positive blood smears from fever patients were irregularly sampled from each county (district) of Chenzhou City from 2018 to 2022 and reexamined, and no less than 3% negative blood smears were reexamined. The preparation, dyeing, cleanliness and microscopic examination results of blood smear were reexamined, and the quality of blood smear reexaminations was assessed using a descriptive statistical method. Results A total of 13 625 fever patients received blood smear examinations for malaria parasites in Chenzhou City from 2018 to 2022, of which 21 were positive and 13 604 were negative; 687 blood samples were reviewed, and the percentage of negative blood smear reexaminations was 4.90% (666/13 604), with a 63.51% rate of qualified negative blood smears preparation, a 67.87% rate of qualified dyeing and a 76.13% rate of qualified cleanliness, and no missing diagnosis found. There were 21 positive blood smears reexamined, and the proportions of qualified blood smears preparation, dyeing and cleanliness were all 85.71%, with 2 smears mistaking Plasmodium species (9.52%). The percentage of qualified negative blood smears preparation was 51.41% in 2022, which reduced by 31.61% in relative to that (75.17%) in 2019 (χ2 = 9.033, P < 0.05), and the percentage of qualified negative blood smears dyeing was 60.19% in 2022, which reduced by 28.82% in relative to that (84.56%) in 2019 (χ2 = 19.498, P < 0.05), while the percentage of qualified negative blood smears cleanliness was 62.96% in 2022, which reduced by 28.93% in relative to that (88.59%) in 2019 (χ2 = 23.826, P < 0.001). In addition, there were no significant differences in the proportion of qualified negative blood smears preparation (χ2 = 0.260, P > 0.05) or dyeing (χ2 = 1.094, P > 0.05) among the three years, while a significant difference was detected in the percentage of qualified negative blood smears cleanliness (χ2 = 12.175, P < 0.05). Conclusions No missing diagnosis was seen in blood smear examinations for malaria parasites among fever patients in Chenzhou City after malaria elimination; however, there were reductions in proportions of qualified blood smears preparation, dyeing and cleanliness. Quality control of blood smear examinations is recommended to be reinforced in key regions of Chenzhou City.
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[Abstract] Objective To explore the potential pathophysiological mechanism of depression by screening the expression profiles and competing endogenous RNA (ceRNA) regulatory network microRNA(miRNA), long non-coding RNA(lncRNA) and circular RNA (circRNA) in the hippocampus of chronic stress depression rat model. Methods Twelve SD rats were divided into blank group and model group. Chronic mild unpredictability stress (CUMS) was used to construct the rat model of depression. The whole transcriptome analysis was performed on the hippocampus of the rats, and the possible regulatory networks among lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA were explored by bioinformatics method. Results According to the | fold change | ≥1. 5 and P≤0. 05, 29 differentially expressed miRNAs (21 up-regulated and 8 down-regulated), 686 differentially expressed lncRNAs (163 up-regulated and 523 down-regulated) and 8 differentially expressed circRNAs (3 up-regulated and 5 down-regulated) were identified. Gene Ontology (GO) and Kytot Encyclopedia of Genes and Genomes(KEGG) pathway analysis showed that the target genes of miRNAs were mainly enriched in the Golgi apparatus and calcium ion binding process in the cell membrane, the functions of lncRNAs target genes involved nucleic acid binding regulation, cytokine and protein ubiquitination, etc, and the functions of host genes of circRNAs were associated with cellular stimulation response, metabolic process, catalytic activity and other processes. The ceRNA network of lncRNAs and circRNAs showed complex interactions between non-coding RNA (ncRNA) and mRNA related to synaptic plasticity, such as protein Wnt-sa(WNT5a) and collagentype III alpha1(COL8a1) related to axon orientation and laminin A2(LAMA2) related to neurodevelopment. Conclusion The ceRNA network of lncRNA and circRNA shows that the complex interaction betweens ncRNA and mRNA is highly associated with the neuroplasticity, which support the neuroplasticity hypothesis of depression.
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To investigate the regulation of N6- methyladenosine ( m6A ) modification on L-type calcium channels in atrial myocytes under high hydrostatic pressure, mediated by methyltransferase-like protein 3 ( METTL3 ). Methods C57BL/6J mice were randomly assigned to the control group and the hypertension group ( treated with continuous administration of angiotensin for four weeks ). Masson staining was used to observe the fibrosis of mouse atrial tissue, while dot blot assay and Western blot were used to detect the levels of m6A, METTL3, and Cavi1 2 in the atrial tissue. A high hydrostatic pressure model was constructed using the HL-1 cell line cultured in vitro, and METTL3 was intervened to observe changes in m6A expression levels, METTL3 and Cavi1 2 levels in cells,and action potential duration ( APD ) and L-type calcium current ( I
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Aim To observe whether the mechanosensitive ion channel Piezo1 was involved in the senescence of atrial fibroblasts by activating β-catenin based on our previous study which found marked increase of Piezo1 mRNA in senescent atrial fibroblasts. Methods Primary mouse atrial fibroblasts (MAFs) were isolated from male C57BL/6 mice (3-4 weeks) by enzyme digestion, and tert-butyl hydroperoxide (TBHP) was used to induce the senescence of cells. The ratio of senescent cells was detected by senescence-associated β-galactosidase (SA-β-Gal) staining. The protein levels of Piezo1, β-catenin/p-β-catenin, senescence-associated proteins p53 and p21 in the cells treated with TBHP (100 μmol · L