ABSTRACT
Objective:To investigate the clinical significance of tumor budding as an indicator of postoperative distant organ metastasis after radical gastrectomy in elderly patients diagnosed with gastric cancer.Methods:The clinical and pathological data of 124 elderly patients who experienced metastasis after undergoing radical gastrectomy were retrospectively analyzed.The analysis was conducted from March 2015 to June 2022, focusing on the clinicopathological factors that influenced the occurrence of postoperative distant metastasis in these patients.Tumor budding in gastric cancer tissues was assessed using hematoxylin-eosin staining, and its clinical significance was analyzed.Results:The tumor budding grade of gastric cancer tissues showed a significant correlation with vascular invasion( χ2=6.731, P=0.009), the number of lymph node metastases( rs=0.481, P<0.001), and the time of distant metastasis( rs=-0.450, P<0.001).In the univariate analysis, factors such as tumor budding grade, tumor size, vascular invasion, postoperative chemotherapy, cancerous nodule, preoperative serum carbohydrate antigen 125, and the number of lymph node metastases were found to influence distant metastasis-free survival after radical gastrectomy in elderly patients(all P<0.05).The multifactorial analysis also indicated that tumour outgrowth grade was an important independent prognostic factor for postoperative distant metastasis in elderly gastric cancer patients( HR=3.731, P<0.001). Conclusions:The findings of this study indicate that tumor budding may serve as a potential marker for predicting distant organ metastasis in elderly patients who have undergone radical gastrectomy.This discovery holds significant clinical implications.
ABSTRACT
The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.
Subject(s)
Mice , Animals , Alzheimer Disease/pathology , Receptor, Nerve Growth Factor , Amyloid beta-Peptides , Autoantibodies , Mice, TransgenicABSTRACT
ObjectiveTo investigate whether there exists gender differences in mechanical pain hypersensitivity induced by the subcutaneous injection of macrophage colony-stimulating factor (M-CSF) in normal mice and to explore the preliminary mechanism. MethodsThirty 10-week-old C57BL/6J mice were randomly divided into three groups, (n = 10 mice/group, half male and half female). The albumin control group (BSA, 0.3 μg), low dose M-CSF group (L M-CSF, 0.075 μg) and high dose M-CSF group (H M-CSF, 0.3 μg) received 50 μL BSA or M-CSF injected subcutaneously into the left medial thigh once daily for 3 consecutive days. Before and after drug administration, von-Frey mechanical sensitivity test was used to detect the mechanical paw withdrawal threshold (PWT) in each group. Immunofluorescence was performed to examine the expression changes of Ionized calcium-binding adaptor molecule 1 (Iba1) in skin, calcitonin gene-related peptide (CGRP) and phosphorylated ERK1/2 (p-ERK) in L5-L6 DRG and lumbar spinal dorsal horn. ResultsIn female mice, only high dose of M-CSF caused mechanical allodynia, whereas in male mice both doses produced marked allodynia. Mechanically, high-dose M-CSF induced massive aggregation of subcutaneous macrophages (marked by Iba1) in male and female mice, but more dramatic dependence in female mice. Similar gender differences were also found in the increase of p-ERK and CGRP expression in dorsal root ganglion (DRGs). Notably, CGRP expression was especially elevated in the fibers of DRG in male mice. Correspondingly, the expressions of p-ERK and CGRP+ terminals in the superficial spinal dorsal horn of male mice were significantly higher than those of female mice after M-CSF treatment. ConclusionSubcutaneous injection of M-CSF triggers sexual dimorphism in mechanical pain hypersensitivity, which is related with differential changes in peripheral macrophage expansion and sensitization of the nociceptive pathway.
ABSTRACT
ObjectiveTo investigate the analgesic action and mechanism of intrathecal 2R, 6R-hydroxynorketamine (2R, 6R-HNK) on spared nerve injury (SNI)-induced chronic neuropathic pain (CNP) in female mice. MethodsSNI was used to establish acute and chronic CNP models in female mice. The mice were randomly divided into different groups with administration of vehicle, 2R, 6R-HNK or S-ketamine (10 mg/kg intraperitoneal injection/i.p. or 7, 21 μmol/L intrathecal injection/i.t.) at 3 weeks after or 30 min/1 d before operation (n = 3 - 7 mice/group). The curative or preventive effect of 2R, 6R-HNK was evaluated by mechanical paw withdrawal threshold (PWT) and the analgesic efficiency. Finally, immunofluorescence and RT-PCR of dorsal root ganglion (DRG) and spinal dorsal horn (SDH) were used to explore the possible mechanisms. ResultsCompared with vehicle, intrathecal injection of 2R, 6R-HNK largely reversed SNI-induced bilateral mechanical allodynia in a delayed-and-dose-dependent way. Among them, 21 μmol/L 2R, 6R-HNK reached its maximum analgesic efficiency (75.32±7.69) % at 2 d. Pre-intrathecal delivery of 2R, 6R-HNK also delayed the development of bilateral mechanical hypersensitivity 2 - 3 d induced by SNI. Mechanically, 2R, 6R-HNK reversed not only the abnormal excitability of neurons in bilateral DRG and superficial SDH, but also the upregulation of calcitonin gene-related peptide (CGRP) and brain-derived nerve growth factor (BDNF) in DRG. ConclusionIntrathecal administration of 2R, 6R-HNK exerts an analgesic effect against CNP, probably via suppressing abnormal neuronal excitability in ascending pain pathway as well as down-regulating CGRP and BDNF expression in DRG neurons.
ABSTRACT
This study aims to investigate the expression, prognosis, and clinical significance of C5orf46 in gastric cancer and to study the interaction between the active components of C5orf46 and tarditional Chinese medicine. The ggplot2 package was utilized for differential expression analysis of C5orf46 in gastric cancer tissues and normal tissues. The survival package was used for survival analysis, univariate regression analysis, and multivariate regression analysis. Nomogram analysis was used to assess the connection between C5orf46 expression in gastric cancer and overall survival. The abundance of tumor-infiltrating lymphocytes was calculated by GSVA package. Coremine database, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and PubChem database were used to search the potential components corresponding to C5orf46 gene and tarditional Chinese medicine. Molecular docking was performed to explore the binding affinity of potential components to C5orf46. Cell experiments were performed to explore the expression of C5orf46 gene in cells of the blank group, model group, and drug administration groups. As compared with normal tissues, C5orf46 expression was higher in gastric cancer tissues, which had more significant predictive effects in the early stages(T2, N0, and M0). The more advanced the tumor node metastasis(TNM) stage, the higher the C5orf46 expression and the lower the probability of survival of patients with gastric cancer. The expression of C5orf46 positively correlated with the helper T cells1 in gastric cancer and the macrophage infiltration level in gastric cancer, and negatively correlated with B cells, central memory T cells, helper T cells 17, and follicular helper T cells. Seven potential components of C5orf46 were obtained, and three active components were obtained after the screening, which matched five tarditional Chinese medicines, namely, Sojae Semen Nigrum, Jujubae Fructus, Trichosanthis Fructus, Silybi Fructus, and Bambusae Concretio Silicea. Molecular docking revealed that sialic acid and adeno-sine monophosphate(AMP) had a good binding ability to C5orf46. The results of real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot showed that, as compared with the model group, the mRNA and protein expression levels of C5orf46 were significantly lower in the drug administration groups. The lowest expression level was found at the concentration of 40 μmol·L~(-1). The results of this study provide ideas for the clinical development of traditional Chinese medicine compounds for the treatment of gastric cancer as well as other cancers.
Subject(s)
Humans , Stomach Neoplasms/metabolism , Medicine, Chinese Traditional , Molecular Docking Simulation , Prognosis , Computational BiologyABSTRACT
OBJECTIVE@#To explore whether the protein Deglycase protein 1 (DJ1) can ameliorate Alzheimer's disease (AD)-like pathology in Amyloid Precursor Protein/Presenilin 1 (APP/PS1) double transgenic mice and its possible mechanism to provide a theoretical basis for exploring the pathogenesis of AD.@*METHODS@#Adeno-associated viral vectors (AAV) of DJ1-overexpression or DJ1-knockdown were injected into the hippocampus of 7-month-old APP/PS1 mice to construct models of overexpression or knockdown. Mice were divided into the AD model control group (MC), AAV vector control group (NC), DJ1-overexpression group (DJ1 +), and DJ1-knockdown group (DJ1 -). After 21 days, the Morris water maze test, immunohistochemistry, immunofluorescence, and western blotting were used to evaluate the effects of DJ1 on mice.@*RESULTS@#DJ1 + overexpression decreased the latency and increased the number of platform traversals in the water maze test. DJ1 - cells were cured and atrophied, and the intercellular structure was relaxed; the number of age spots and the expression of AD-related proteins were significantly increased. DJ1 + increased the protein expression of Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), light chain 3 (LC3), phosphorylated AMPK (p-AMPK), and B cell lymphoma-2 (BCL-2), as well as the antioxidant levels of total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and Glutathione peroxidase (GSH-PX), while decreasing the levels of Kelch-like hydrates-associated protein 1 (Keap1), mammalian target of rapamycin (mTOR), p62/sequestosome1 (p62/SQSTM1), Caspase3, and malondialdehyde (MDA).@*CONCLUSION@#DJ1-overexpression can ameliorate learning, memory, and AD-like pathology in APP/PS1 mice, which may be related to the activation of the NRF2/HO-1 and AMPK/mTOR pathways by DJ1.
Subject(s)
Animals , Mice , Alzheimer Disease/therapy , AMP-Activated Protein Kinases/metabolism , Amyloid beta-Protein Precursor/metabolism , Antioxidants/metabolism , Disease Models, Animal , Hippocampus/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Mammals/metabolism , Mice, Inbred C57BL , Mice, Transgenic , NF-E2-Related Factor 2/metabolism , Presenilin-1/metabolism , TOR Serine-Threonine Kinases/metabolismABSTRACT
This study aimed to investigate the mechanism and target sites of Shenfu Injection in the intervention of chronic heart fai-lure based on the PI3K/Akt/mTOR autophagy signaling pathway. The chronic heart failure model was induced in rats by subcutaneous injection of isoproterenol. The model rats were randomly divided into model group, Shenfu Injection group, and 3-methyladenine autophagy inhibitor(3-MA) group. A normal group was also set up. After 15 days of administration, cardiac function indexes of the rats were detected by echocardiography. The serum N-terminal pro-B-type natriuretic peptide(NT-proBNP) levels were measured using the ELISA. HE and Masson staining was performed to observe the morphological changes in myocardial tissues, and electron microscopy was used to observe the autophagosomes in myocardial tissues. Western blot was conducted to measure the changes in autophagy-related proteins(LC3 Ⅱ/Ⅰ and p62), PI3K, Akt, mTOR, and phosphorylation levels. The results showed that compared with normal group, model group in rats led to reduced cardiac function, significant activation of cardiac autophagy, increased fibrotic lesions in myocardial tissues, structural disorder of the myocardium, increased autophagosomes, and cytoplasmic vacuolization. Compared with model group, Shenfu Injection group in rats led to cardiac function significantly improved, myocardial fibrosis decreased, and the number of autophagosomes and cytoplasmic vacuolization decreased. The phosphorylation levels of PI3K, Akt, and mTOR were significantly increased(P<0.01). In the 3-MA group, autophagy was inhibited through the activation of the PI3K/Akt/mTOR signaling pathway, resulting in improved cardiac function, reduced myocardial fibrosis, and no significant cytoplasmic vacuolization. The findings suggest that Shenfu Injection can activate the PI3K/Akt/mTOR signaling pathway and inhibit autophagy, thereby improving cardiac function.
Subject(s)
Rats , Animals , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Rats, Sprague-Dawley , TOR Serine-Threonine Kinases/metabolism , Heart Failure/drug therapy , Autophagy , FibrosisABSTRACT
This study investigated the mechanisms and targets of Shenfu Injection in the intervention in chronic heart failure(CHF) through the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/caspase-1 signaling pathway. A CHF model was induced in rats by subcutaneous injection of isoproterenol. Model rats were randomly divided into a model group, a Shenfu Injection group, and a MCC950(NLRP3 inhibitor) group, and a blank group was also set up as a control. After 15 days of treatment, echocardiography was performed to measure cardiac function parameters [left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS)]. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of N-terminal pro-brain natriuretic peptide(NT-proBNP), interleukin(IL)-1β, and IL-18. Hematoxylin-eosin(HE) and Masson staining were used to observe morphological changes in myocardial tissues, and Western blot was used to measure the expression levels of NLRP3/caspase-1 pathway-related proteins [NLRP3, caspase-1, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), IL-1β, and IL-18]. The study found that isoproterenol-induced CHF in rats resulted in decreased cardiac function, worsened myocardial fibrosis, increased expression levels of NLRP3, ASC, caspase-1, GSDMD-N, IL-1β, and IL-18 in myocardial tissues, elevated serum inflammatory factors, and induced myocardial cell pyroptosis. Following Shenfu Injection intervention, the Shenfu Injection group showed significantly improved LVEF and LVFS, a significant decrease in NT-proBNP, a marked downregulation of NLRP3, ASC, caspase-1, GSDMD-N, IL-1β, and IL-18 protein expression levels, reduced serum inflammatory factors IL-1β and IL-18 expression in CHF rats, and a decrease in the rate of TUNEL-positive cells. Shenfu Injection can significantly improve cardiac function in CHF, inhibit myocardial fibrosis, and alleviate the progression of myocardial cell pyroptosis through the inhibition of the NLRP3/caspase-1 pathway.
Subject(s)
Rats , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis , Interleukin-18/metabolism , Caspase 1/metabolism , Stroke Volume , Isoproterenol , Ventricular Function, Left , Heart Failure/drug therapy , Fibrosis , Drugs, Chinese HerbalABSTRACT
Based on mass spectrometry(MS)-guided separation strategy, compound 1 was obtained from the roots of Rhus chinensis. By comprehensive analysis of high resolution-electrospray ionization-mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) data, and quantum chemical calculation of NMR(qcc-NMR) parameters, compound 1 was elucidated as rhuslactone, a 17-epi-dammarane triterpenoid with a rare 17α-side chain. An HPLC-ELSD method for its quantification in R. chinensis was established and adopted for the quantification of rhuslactone in different batches of R. chinensis. Rhuslactone displayed a good linear relationship within the range of 0.021 3-1.07 μmol·mL~(-1 )(r=0.997 6), and the average recovery was 99.34% [relative standard deviation(RSD) 2.9%). Moreover, the results of the evaluation test of the preventive effects of rhusalctone on coronary heart disease(CHD) and thrombosis showed that rhuslactone(0.11 nmol·mL~(-1)) significantly alleviated heart enlargement and venous congestion and increased cardiac output(CO), blood flow velocity(BFV), and heart rate, thereby reducing thrombus formation in zebrafish with CHD. The effects of rhuslactone on CO and BFV were superior to that of digoxin(1.02 nmol·mL~(-1)), and its effect on improving heart rate was comparable to that of digoxin. This study provides experimental references for the isolation, identification, quality control, and application of rhuslactone from R. chinensis against CHD. It is worth mentioning that this study has discussed some omissions in the determination of the stereochemistry of C-17 in dammarane triterpenoids in the present coursebook Chemistry of Chinese Medicine and some research papers, that is, the compound may be 17-epi-dammarane triterpenoid. This paper has also proposed steps for the establishment of C-17 stereochemistry.
Subject(s)
Animals , Zebrafish , Rhus/chemistry , Triterpenes/analysis , Coronary Disease , ThrombosisABSTRACT
BackgroundPatients with schizophrenia are at high risk of suffering from metabolic syndrome. Most previous studies on the influencing factors of metabolic syndrome focused on the inpatients and limited ones on patients dwelling in community. ObjectiveTo explore the influencing factors at different risk levels of metabolic syndrome in community-dwelling patients with schizophrenia in Guangzhou, so as to provide references for future interventions on metabolic syndrome in this patient population. MethodsIn November 2021, 3 339 patients with schizophrenia who were registered in and administered by Guangzhou Mental Health Information System were included. All these patients had finished the physical examination in 2020, and whether they had metabolic syndrome was assessed basing on Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition). Patients were divided into high-risk group (n=423), critical group (n=1 524) and metabolic syndrome group (n=1 392) according to the Chinese expert consensus on the management of metabolic syndrome in patients with schizophrenia. Multiple logistic regression analysis were performed on the risk factors of metabolic syndrome in community-dwelling patients with schizophrenia. ResultsThe prevalence rate of metabolic syndrome in community-dwelling patients with schizophrenia was 41.69%. Univariate analysis showed that the results in gender (χ2=44.610), age (χ2=55.992), marriage status (χ2=30.755), illness course (χ2=25.913) and body mass index (χ2=829.265) were significantly different among the three groups (P<0.01). Kruskal-Wallis H test showed that the levels of waist circumference (H=920.331), systolic blood pressure (H=436.673), diastolic blood pressure (H=393.337), fasting blood glucose (H=807.304), triglyceride (H=1 134.125) and high-density lipoprotein cholesterol (H=593.615) among the three groups were significantly different (P<0.01). Logistic regression analysis showed that age ≥50 (OR=1.761, 95% CI: 1.087~2.853), overweight (OR=2.418, 95% CI: 1.862~3.140) and obesity (OR=57.903, 95% CI: 14.340~233.802) were risk factors contributing to high-risk patients becoming critical population (P<0.05 or 0.01). Female gender (OR=1.295, 95% CI: 1.034~1.622), aged 40~49 (OR=2.597, 95% CI: 1.582~4.263), age ≥50 (OR=4.392, 95% CI: 2.609~7.395), overweight (OR=7.844, 95% CI: 6.018~10.223) and obesity (OR=426.785, 95% CI: 105.724~1 722.839) were risk factors for high-risk patients developing into metabolic syndrome population (P<0.05 or 0.01). ConclusionThe prevalence rate of metabolic syndrome is higher in community-dwelling patients with schizophrenia. Female gender, older age, overweight and obesity would increase the risk of metabolic syndrome in schizophrenic patients. [Funded by Health Science and Technology Project in Guangzhou (number, 20221A010028)]
ABSTRACT
Objective: To investigate the natural history and risk factors for continued allergy in infants with IgE-mediated cow's milk protein allergy (CMPA). Methods: This was a prospective cohort study that included 72 infants under 24 months of age diagnosed with IgE-mediated CMPA in the allergy clinic of the Children's Hospital, Capital Institute of Pediatrics from October 2019 to November 2020. General information, clinical manifestations, serum total IgE, cow's milk specific IgE, and cow's milk protein component specific IgE were collected. Follow-ups were conducted at 24 and 36 months of age, and the patients were divided into the persistent allergy group and the tolerance group based on whether they developed cow's milk tolerance at 36 months of age. Mann-Whitney U test, chi-square test, and binary Logistic regression were used for intergroup comparison and multivariate analysis. Results: Among the 72 CMPA children, there were 42 boys and 30 girls, with an age of 10 (7, 15) months at enrollment. Cow's milk protein tolerance was observed in 32 cases (44%) and 46 cases (64%) at 24 and 36 months of age, respectively. There were 26 cases in the persistent allergy group and 46 cases in the tolerance group. The proportion of respiratory symptoms, history of wheezing, positive specific IgE for α-lactalbumin and the total IgE level in the persistent allergy group were higher than that in the tolerance group (7 cases (27%) vs. 0, 6 cases (23%) vs. 2 cases (4%), 67% (14/21) vs. 26% (10/39), 225 (151, 616) vs. 48 (21, 185) kU/L, χ2=10.82, 4.16, 9.57, Z=4.07, all P<0.05). Multivariate Logistic regression analysis showed that anaphylaxis (OR=21.14, 95%CI 2.55-175.14, P=0.005), a history of allergic rhinitis (OR=5.94, 95%CI 1.54-22.86, P=0.005), elevated milk specific IgE (OR=1.04, 95%CI 1.01-1.08, P=0.024), and positive casein specific IgE (OR=6.64, 95%CI 1.39-31.69, P=0.018) were risk factors for continuous CMPA. Conclusions: Most infants with IgE-mediated CMPA can achieve tolerance within 3 years. Anaphylaxis, a history of allergic rhinitis, elevated milk specific IgE levels, and casein sensitization are risk factors for continuous allergy.
Subject(s)
Male , Animals , Female , Cattle , Infant , Humans , Child , Milk Hypersensitivity/diagnosis , Caseins , Prospective Studies , Anaphylaxis , Risk Factors , Rhinitis, Allergic , Immunoglobulin E , Milk Proteins/adverse effectsABSTRACT
Microglia, the main immune macrophages in the central nervous system, can be highly involved in the occurrence and development of Alzheimer's disease(AD)through microglia polarization and receptor protein expression. Traditional Chinese Medicine has been demonstrated to have regulatory effects on MG. Many active components in Traditional Chinese herbs play important roles in decreasing β-amyloid peptide(Aβ)accumulation, inhibiting neuro-inflammation and regulating microglia polarization etc. In this study the role of microglia in the pathogenesis of AD and the mechanism by which Traditional Chinese Medicine regulating microglia are reviewed to provide a reference for the treatment of AD.
ABSTRACT
Tripartite motif containing protein 7 (TRIM7), as a member of the E3 ubiquitin ligase TRIM family, plays an important regulatory role in immune regulation, metabolism and other physiological processes. The aberrant expression of TRIM7 is closely related to the development and progression of hepatocellular carcinoma (HCC) and it shows a complex regulatory role. However, the regulatory mechanism for the expression of TRIM7 in HCC remains unknown. In this study, multiple online databases were used to analyze the expression of TRIM7 in HCC and data indicated that TRIM7 expression was upregulated in HCC and correlated to poor prognosis. Subsequently, the transcription factor binding sites in the TRIM7 promoter region were analyzed using UCSC and JASPAR databases, and the results showed that TRIM7 promoter contains four SP1 binding sites. In this work, we demonstrated that SP1 could directly bind to its binding sites in TRIM7 promoter and positively regulate the transcriptional activity driven by the TRIM7 promoter using dual luciferase reporter experiments and the ChIP-PCR method. Moreover, our results also showed SP1 overexpression upregulated the expression of TRIM7 at both mRNA and protein levels (P<0. 01),and SP1 inhibitor, mithramycin A, could reverse the activated effect of SP1 on TRIM7 expression (P<0. 01). In conclusion, this study preliminarily reveals the regulatory mechanism of TRIM7 upregulation in HCC, which provides an important theoretical basis for further study of the gene function, early diagnosis and targeted therapy.
ABSTRACT
Objective:To explore the safety and early prognosis of robot assisted living donor kidney transplantation(KT)and plot the learning curve of mastering the operation.Methods:From July 2020 to March 2021, 30 cases of living robot assisted KT were completed.The follow-up period was 3 months.Cumulative sum analysis was performed for plotting the learning curve.According to the learning curve, they were divided into two groups of practice period(the first 17 cases)and proficiency period(the last 13 cases). Time of each operative stage and early prognosis were compared.Kidney function and perioperative complications of two groups were compared for evaluating the safety and effectiveness of robot assisted KT.Results:The average operative duration was (221.4±36.1)min.No intestinal obstruction, delayed graft function, urinary leakage and incision infection occurred during perioperative period.The average anal exhaust time was(1.9±0.2)days.During follow-ups, both pulmonary infection(2 cases)and acute rejection(1 case)improved after treatment.According to the learning curve, venous anastomosis(10 cases), arterial anastomosis(12 cases), warm ischemic time(12 cases)and ureteral anastomosis(17 cases)should be performed for reaching a proficiency level.An average of 15 operations was required for achieving proficiency throughout operations.Significant inter-group differences existed in operative duration [(235.5±31.6)vs(203.0±34.3)min, P=0.012] and warm ischemic time [(63.7±24.9)vs(47.0±11.3)min, P=0.033]. At some postoperative timepoints, creatinine of proficiency group was lower than that of practice group, such as Day 7 post-operation [(192.7±135.2)vs(107.8±27.9)μmol/L, P=0.022] and Day 30 post-operation [(147.8±46.3)vs(112.3±28.0)μmol/L, P=0.021]. However, no significant difference existed in estimated glomerular filtration rate at Day 7 post-operation [(56.1±34.1)ml/(min·1.73m 2)vs(72.0±18.5)ml/(min·1.73m 2), P=0.14] and Day 30 post-operation [(56.2±18.9)ml/(min·1.73m 2)vs(68.7±15.3)ml/(min·1.73m 2), P=0.14]. Conclusions:Robot assisted KT is both safe and feasible.And the learning curve requires 17 cases for reaching a proficiency level.
ABSTRACT
Objective: To analyze the clinical features of IgE-mediated cow's milk protein allergy (CMPA) in children aged 0-5 years. Methods: This cross-sectional study collected the data on children diagnosed with CMPA in the Department of Allergy at the Children's Hospital of the Capital Institute of Pediatrics from October 2019 to November 2020 and improved peripheral blood routine,total IgE defection, milk specific IgE (sIgE) defection,SPT and milk component defection,diagnosis of severe anaphylaxis based on clinical manifestations. Rank-sum test and chi-square test are used for statistical analysis of clinical characteristics between groups. Results: A total of 106 children (67 boys and 39 girls) were enrolled with the age of 15 (8, 34) months, including 42 cases (≤ 1 year of age), 39 cases (>1-<3 years of age) and 25 cases(≥3 years of age), the onset age of 6 (5, 8) months. Among them, 95 cases (89.6%) were reacted after consuming milk or its products, 42 cases (39.6%) had reaction due to skin contact and 11 cases (10.4%) reacted after exclusive breastfeeding. The onset time of milk product consumption was 45 (1, 120) min, skin contact pathway was 10 (5, 30) min and symptoms in breastfeeding pathway was 121 (61, 180) min. There was statistical difference among the time of symptoms (χ2=77.01, P<0.001).The cutaneous reaction was most common (100 cases, 94.3%), followed by digestive (20 cases, 18.9%) and respiratory (16 cases, 15.1%), and the nervous symptoms (1 case, 0.9%) were uncommon and 24 cases (22.6%) had at least one episode of anaphylaxis. There were 87 cases (82.1%) also diagnosed with other food allergies, 94 cases (88.7%) with previous eczema, 57 cases (53.8%) with history of rhinitis, and 23 cases (21.7%) with history of wheezing. The total IgE level was 191.01 (64.71, 506.80) kU/L, and the cow's milk sIgE level was 3.03 (1.11, 15.24) kU/L. The maximum diameter of the wheal in SPT was 8.2 (4.0, 12.0) mm. Component resolved diagnosis showed that 77 cases (81.9%) were sensitized to at least one out of 4 main components, including casein, α lactalbumin, β lactoglobulin and bovine serum albumin.The possibility of anaphylaxis in children with milk sIgE grade Ⅳ-Ⅵ was higher than that in children with grade 0-Ⅲ (57.7% (15/26) vs. 12.5% (10/80), OR=9.545, 95%CI 3.435-26.523). Children with milk SPT ≥+++ had a higher probability of anaphylaxis than those with milk SPT ≤++ (34.4% (11/32) vs. 11.5% (3/26), OR=4.016, 95%CI 0.983-16.400). Anaphylaxis were more common in α lactalbumin positive children than in negative children (34.3% (13/38) vs. 14.2% (8/56), χ2=1.23,P=0.042). Conclusions: CMPA in children has early onset and diversified clinical manifestations, which are mainly cutaneous symptoms. Most children are sensitized to at least one allergen component. Serum sIgE level, SPT reaction and allergen components play important roles in the diagnosis and evaluation of CMPA, and higher milk sIgE level may predict a higher risk of anaphylaxis.
Subject(s)
Animals , Cattle , Child , Female , Humans , Male , Allergens , Anaphylaxis/etiology , Cross-Sectional Studies , Immunoglobulin E , Lactalbumin , Milk Hypersensitivity/diagnosis , Skin TestsABSTRACT
OBJECTIVE@#To investigate the changes in bacterial flora in fecal samples, at the tumor loci and in adjacent mucosa in patients with colorectal cancer (CRC).@*METHODS@#We collected fecal samples from 13 patients with CRC and 20 healthy individuals and tumor and adjacent mucosa samples from 6 CRC patients. The differences in bacterial composition between the fecal and mucosa samples were analyzed with 16S rDNA sequencing and bioinformatics methods. We also detected the total number of bacteria in the feces using flow cytometry, isolated and identified the microorganisms in the fecal and mucosa samples using common bacterial culture media. We further tested the effects of 7 isolated bacterial strains on apoptosis of 3 CRC cell lines using lactate dehydrogenase detection kit.@*RESULTS@#The bacterial α-diversity in the feces of healthy individuals and in adjacent mucosa of CRC patients was significantly higher than that in the feces and tumor mucosa in CRC patients (P < 0.05). Lactobacillaceae is a specific bacteria in the feces, while Escherichia, Enterococcus, and Fusobacterium are specific bacteria in tumor mucosa of CRC patients as compared with healthy individuals. Cell experiment with3 CRC cell lines showed that Bacteroides fragilis isolated from the tumor mucosa of CRC patients produced significant inhibitory effects on cell proliferation (P < 0.0001), while the isolated strain Fusobacterium nucleatum obviously promoted the proliferation of the cell lines (P < 0.001).@*CONCLUSION@#The bacterial flora in the feces, tumor mucosa and adjacent mucosa of CRC patients is significantly different from that in the feces of healthy individuals, and the fecal flora of CRC patients can not represent the specific flora of the tumor mucosa. Inhibition of F. nucleatum colonization in the tumor mucosa and promoting B. fragilis colonization may prove beneficial for CRC treatment.
Subject(s)
Humans , Bacteria , Colorectal Neoplasms/pathology , Feces/microbiology , Gastrointestinal Microbiome , Intestinal MucosaABSTRACT
ObjectiveTo study the effect of Huazhuo Jiedu Huoxue Tongluo (HJHT) prescription on the intestinal flora in rats with cerebral ischemia-reperfusion injury, and to explore the mechanism of Chinese medicinal prescription regulating intestinal flora to restore the balance of brain-gut axis. MethodFifty male SPF SD rats were randomly assigned into sham group, model group, high-dose HJHT group (25.0 g·kg-1), medium-dose HJHT group (12.5 g·kg-1), and low-dose HJHT group (6.25 g·kg-1), with 10 rats in each group. The rat model of permanent middle cerebral artery infarction was established according to Longa method and previous research experience, and reperfusion was performed 2 h after ischemia. The recovery of neurological function deficit and the percentage of cerebral infarction area were detected 72 h after administration. Real-time PCR was performed to detect the mRNA levels of Occludin and zonula occludens-1 (ZO-1) in rat colon. Hematoxylin-eosin (HE) staining was conducted to reveal the intestinal damage. The feces of 6 rats in each group were collected for 16S rRNA sequencing. The expression of Treg and Th17 in intestinal tissue, peripheral blood, and brain tissue were detected. ResultCompared with the sham group, the model group showed obvious neurological deficit (P<0.05) and large cerebral infarction area (P<0.05). High-dose and medium-doses HJHT alleviated the symptoms of neurological impairment (P<0.05) and reduce the cerebral infarction area (P<0.05) compared with the model group. Compared with the sham group, the model group showed destroyed structure of colonic mucosa and incomplete epithelial cells and goblet cells, while high-dose and medium-doses HJHT alleviated such changes. The mRNA levels of Occludin and ZO-1 in the model group were lower than those in the sham group (P<0.05),and the high-dose HJHT groups were higher than the model group (P<0.05). The intestinal flora structure was significantly different between the model group and the sham group while similar between the high-dose HJHT group and sham group. Compared with the sham group, the model group showed down-regulated expression of Treg and up-regulated expression of Th17 in the intestinal tissue, peripheral blood, and brain tissue, and high-dose and medium-dose HJHT alleviated the changes in the expression of Treg and Th17 in the model group (P<0.05). ConclusionHuazhuo Jiedu Huoxue Tongluo prescription may improve the permeability of intestinal wall by adjusting the abundance and diversity of intestinal microorganisms to reduce the migration of intestinal Th17 cells toward the ischemic lateral brain tissue, mitigate the inflammatory response, and thus alleviate the cerebral ischemia-reperfusion injury in rats.
ABSTRACT
Hyperthyroidism is a systemic disease characterized by clinical signs and symptoms of hypermetabolism and sympathetic nervous excitement. Based on the clinical diagnostic criteria of traditional Chinese and western medicine for hyperthyroidism,the present study summarized and evaluated animal models of hyperthyroidism. In model evaluation,the models with high coincidence degree in western medicine included the exogenous drug delivery model, the model immune to adenovirus expressing thyrotropin receptor (TSHR),the model immune to nucleic acid, and the model of yin deficiency and effulgent fire syndrome in the disease-syndrome combination. The models with high coincidence degrees in traditional Chinese medicine included the exogenous drug delivery model, the model immune to adenovirus expressing TSHR,and the model of liver-yang ascendant hyperactivity syndrome and the model of yin deficiency and effulgent fire syndrome in the disease-syndrome combination. In light of the coincidence degree, and advantages and disadvantages of traditional Chinese and western medicine,the ideal hyperthyroidism animal models are the exogenous drug delivery model, and the model immune to adenovirus expressing TSHR. In addition to the evaluation of the coincidence degree of animal models of hyperthyroidism in traditional Chinese and western medicine,this study also analyzed the advantages,disadvantages, and problems of the animal models of hyperthyroidism. Most of the animal models of hyperthyroidism were not consistent with the complexity of hyperthyroidism in clinical practice, and standardized and unified syndrome differentiation standards and four-examination information collection standards have not yet been formed. Besides, there have been few studies on the hyperthyroidism model in disease-syndrome combination in traditional Chinese medicine. To make the animal models of hyperthyroidism suitable for clinical practice,the present study proposed the improvement directions of animal models of hyperthyroidism and the necessity of promoting the evaluation system to provide a theoretical basis for the evaluation of the curative effect of Chinese medicine on hyperthyroidism, and exploration of its pharmacological action, as well as the follow-up research on the pathogenesis,prevention, and treatment of hyperthyroidism,which is expected to establish a perfect disease-syndrome model of hyperthyroidism in line with clinical characteristics of traditional Chinese and western medicine.
ABSTRACT
To evaluate the efficacy and safety of Chinese patent medicines in the treatment of ankylosing spondylitis(AS) by frequency network Meta-analysis. Randomized controlled trials(RCTs)of Chinese patent medicines for AS were retrieved from CNKI, Wanfang, VIP, CBM, PubMed, EMbase and Cochrane Library databases from the time of database establishment to January 2021. The quality of the included RCTs was evaluated according to the Cochrane bias risk standard, and the data was analyzed by RevMan 5.3 and Stata/MP 15.1. A total of 12 kinds of Chinese patent medicines in 55 RCTs were included. According to Meta-analysis, in term of the effectiveness, the top three optimal medication regimens were Biqi Capsules, Yishen Juanbi Pills and Yaobitong Capsules combined with western medicine. The top three interventions to reduce the erythrocyte sedimentation rate(ESR)were Yishen Juanbi Pills, Xianling Gubao Capsules and Fufang Xuanju Capsules combined with western medicine. The top three interventions to reduce the C-reactive protein(CRP)were Biqi Capsules, Xianling Gubao Capsules and Fufang Xuanju Capsules combined with western medicine. In terms of the safety, top three optimal medication regimens were Total Glucosides of Paeony Capsules, Yishen Juanbi Pills, and Wangbi Tablets combined with western medicine. This network Meta-analysis suggests that Chinese patent medicines combined with conventional western medicine can effectively improve the joint pain symptoms of AS patients and reduce the acute inflammatory indicators, with high safety. However, the literature included in this study is generally of low methodological quality, and the conclusion needs to be verified by high-quality research.
Subject(s)
Humans , Capsules , China , Drugs, Chinese Herbal/adverse effects , Network Meta-Analysis , Nonprescription Drugs/therapeutic use , Spondylitis, Ankylosing/drug therapyABSTRACT
Deficits in the clearance of amyloid β protein (Aβ) by the peripheral system play a critical role in the pathogenesis of sporadic Alzheimer's disease (AD). Impaired uptake of Aβ by dysfunctional monocytes is deemed to be one of the major mechanisms underlying deficient peripheral Aβ clearance in AD. In the current study, flow cytometry and biochemical and behavioral techniques were applied to investigate the effects of polysaccharide krestin (PSK) on AD-related pathology in vitro and in vivo. We found that PSK, widely used in therapy for various cancers, has the potential to enhance Aβ uptake and intracellular processing by human monocytes in vitro. After administration of PSK by intraperitoneal injection, APP/PS1 mice performed better in behavioral tests, along with reduced Aβ deposition, neuroinflammation, neuronal loss, and tau hyperphosphorylation. These results suggest that PSK holds promise as a preventive agent for AD by strengthening the Aβ clearance by blood monocytes and alleviating AD-like pathology.