摘要:ObjectiveTo observe the changes in the expression and distribution of G protein-gated inwardly rectifying potassium channel subunit 2 (GIRK2) in the dorsal root ganglion (DRG) and spinal cord dorsal horn of rats with remifentanil-induced hyperalgesia.MethodsHyperalgesia was induced by intravenous infusion of remifentanil 4 μg/kg/min for 2 h in adult male SD rats. At 6th hour and on days 1, 3 and 5 following remifentanil treatment, we used immunofluorescence to examine the changes in the GIRK2 distribution and expression. Immunoblotting was used to detect GIRK2 expression of the total protein and membrane protein in DRG and spinal dorsal horn of rats. Behavioral testing was applied to evaluate the effect of intrathecal injection of GIRK2-specific agonist ML297 on thermal nociceptive threshold on day 1 after remifentanil infusion.Resultsmmunofluorescence results showed that GIRK2 was mainly co-localized with IB4-positive small neurons in DRG and nerve fibers in spinal dorsal horn. GIRK2 expression was significantly downregulated following remifentanil treatment. Immunoblotting results revealed that on day 1 following intravenous infusion of remifentanil, compared with those in the control group, GIRK2 expression levels of the total protein and membrane protein in DRG (0.47 ± 0.10 vs. 1.01 ± 0.17, P < 0.001; 0.47 ± 0.11 vs. 1.06 ± 0.12, P < 0.001) and spinal dorsal horn (0.52 ± 0.09 vs. 1.10 ± 0.08, P < 0.001; 0.54 ± 0.10 vs. 1.01 ± 0.13, P < 0.001) were all significantly decreased. The behavioral results showed that intrathecal ML297 effect on thermal withdrawal latency was significantly reduced following remifentanil treatment (P < 0.001).ConclusionsRemifentanil might induce hyperalgesia via down-regulating GIRK2 expression in rat DRG and spinal cord dorsal horn.
摘要:ObjectiveTo compare the therapeutical effect of exosomes derived from fibroblasts and mesenchymal stem cells on acute wound healing.MethodsPrimary human dermal fibroblasts (hDF) were isolated, cultured and identified. Human bone marrow mesenchymal stem cell exosomes (hMSC-EXO) and hDF exosomes (hDF-EXO) were extracted by ultracentrifuga tion. After 24 h of coincubation with hDF-EXO or hMSC-EXO, hDFs proliferation and migratory capacity were evaluated by cell counting kit-8 (CCK8) assay and scratch test. Full-thickness cutaneous wounds were created on 8-week-old female C57BL/6 mice, and topically applied with PBS (control), hDF-EXO or hMSC-EXO. Wounds were measured at day 0, 2, 4, 7, and the uptake of exosomes in wound was observed at day 1. Quantitative PCR (qPCR) analysis was performed to detect the mRNA expression levels of TNF-α, IL-6, IL-1β, IL-10 in wound at day 1. HE staining was conducted to analyze the histological structure of wounds at day 7, while immunofluorescence staining was used to examine expression of PDGFR-α、α-SMA、Ki67.ResultshDF exhibited certain fibrolast-like characteristics with respect to expression of cell surface markers and specific proteins. hDF-EXO and hMSC-EXO presented exosomal morphology, size, and markers, and both concentrations were not statistically different (P>0.05); CCK8 assay showed that both exosomes promoted hDF cell viability, compared with the negative control (P<0.01), and hDF-EXO group had greater cell viability than hMSC-EXO group (P<0.01). Scratch test indicated that hDF-EXO induced a significant increase in scratch healing rate versus the negative control (P<0.01), hMSC-EXO (P<0.05). In vivo experiments showed wound tissues took up exosomes at day 1. qPCR detected TNF-α, IL-6, IL-1β expression levels in wound at day 1 were lower in exosomes group than in the control group, and were the lowest in hMSC-EXO group (all P<0.01). Wound areas were measured smaller at day 7 in exosomes group than in the control group (all P<0.01) and hDF-EXO group had better closure than hMSC-EXO group (P<0.05). HE staining revealed that compared with control group, scar, incomplete epidermis and few collagen deposition remained in the hMSC-EXO group, whereas hDF-EXO group showed re-epithelialization, continuous neo-epidermis and regenerated dermis. Immunofluorescence staining suggested that the number of fibroblasts, myofibroblasts, proliferating cells was higher in both exosomes group than that in the control group, especially the highest in hDF-EXO group.ConclusionOur study shows both exosomes accelerate wound healing, whereas hDF-EXO is more effective in promoting fibroblasts proliferation, migration, transition to myofibroblasts, and hMSC-EXO may play a role in inhibiting inflammatory reaction during early stage of wound healing.
摘要:ObjectiveTo investigate the mechanism of Akkermansia muciniphila (A. muciniphila) regulating the visceral hypersensitivity in irritable bowel syndrome (IBS) rats induced by neonatal maternal separation (MS) and water avoidance stress (WAS).MethodsNeonatal male Sprague-Dawley rats were randomly divided into sham WAS group (blank group), MS+WAS group (IBS model group) and A. muciniphila group. IBS model was established by MS combined with WAS in both IBS model group and A. muciniphila group. Meanwhile, the rats in the A. muciniphila group were given 1 mL 1×109 CFU/mL A. muciniphila by gavage daily for 10 days. Visceral pain responses were detected by behavioral observations and abdominal withdrawal reflex scores.ResultsCompared with IBS model group, A. muciniphila group exhibited significant increase of body weight and visceral pain threshold, significantly decreased numbers of fecal particles and proportions of unformed stools, significantly higher expression levels of cannabinoid receptor type 2 (CB2R) mRNA in colon tissues.ConclusionA. muciniphila may alleviate the visceral hypersensitivity in IBS rats by regulating the expression of CB2R mRNA in colonic tissues.
摘要:ObjectiveTo analyze the criminal behavior characteristics of alcohol-related crime offenders and explore the relationship between criminal behavior characteristics and criminal responsibility capacity.MethodsBasic information, alcohol use information, psychiatric symptoms before and after the crime, criminological behavioral characteristics and conclusion of judicial evaluation were collected.ResultsThe drinking history of the chronic alcoholism group 25.0 (13.3~30.0) years was significantly longer than that of the acute alcoholism group 1.2 (0~14.3) years. In the chronic alcoholism group, 85.0% drank alcohol at least once a day, 52.5% had morning or bedtime drinking habits, and 92.5% drank mainly alone. Violent crimes accounted for 57.6%. Delirium existed in 52.5% of the chronic alcoholics' mental state at the time of the crime, and 84.6% of the acute alcoholics' mental state was hazy. In the chronic alcoholism group, 42.5% committed the crime with pathological motive, and in the acute alcoholism group, 69.2% committed the crime with realistic motive. Acute alcoholism group 96.2% were assessed as complete criminal responsibility capacity, and chronic alcoholism group 50.0% were assessed as complete criminal responsibility capacity.ConclusionCompared with acute alcoholism offenders, chronic alcoholics had a longer drinking duration, more frequency drinking, and obvious morning drinking or bedtime drinking habits. The nature of alcoholism crime cases was mostly violent. Compared with the chronic alcoholism group, the acute alcoholism group had highly selective motives for committing crimes and were mostly rated as complete criminally responsibility.
摘要: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.
摘要:ObjectiveTo analyze the induction effect of Fusobacterium nucleatum (Fn) on endoplasmic reticulum stress-related proteins Glucose-regulating protein 78(GRP78) and X-box binding protein 1(XBP1) in esophageal squamous cell carcinoma (ESCC), and to explore its potential mechanism and clinical significance.MethodsESCC cells KYSE150 and KYSE140 were infected with Fn for 12 h, 24 h and 48 h. The oxidative stress indexes (ROS, MDA and SOD) and the expression of GRP78 and XBP1 in each group were detected by oxidative stress index kit and Western blot. The experiment was divided into Fn groups, Fn+siNC1 groups, Fn+siGRP78 groups, Fn+siNC2 groups and Fn+siXBP1 groups; the oxidative stress indexes, paclitaxel (PTX) response efficacy, abilities of proliferation, invasion and metastasis in each group were compared. The infection of Fn and the expression of GRP78 and XBP1 in 234 ESCC and paracancerous tissues were detected by RNA scope and immunohistochemistry. The correlation between each factor and clinicopathological characteristics of patients was analyzed by Chi-square test. The influence of each factor on the survival of patients was compared by Kaplan-meier survival estimate.ResultsCompared with Fn uninfected KYSE150 and KYSE140 cells, the content of ROS and MDA was gradually increased, the activity of SOD was gradually decreased, and the expression of GRP78 and XBP1 was gradually increased in Fn infected groups (12 h, 24 h and 48 h) (P < 0.05). Compared with Fn groups, Fn+siNC1 groups, and Fn+siNC2 groups, ROS and MDA contents were decreased, SOD activity was increased, PTX response efficacy was enhanced, and abilities of proliferation, invasion and metastasis were decreased in Fn+siGRP78 and Fn+siXBP1 groups (P < 0.05). The rates of Fn, GRP78 and XBP1 in ESCC tissues were 43.16%, 69.66% and 60.68%, respectively. And the three indexes were significantly consistent (P < 0.05). The patients with positive Fn infection and high expression of GRP78 and XBP1 were mostly males with a history of smoking and drinking, and the tumor differentiation degree was low, the invasion degree was deep, the lymph node metastasis rate was high, and the clinical stage was mostly stage Ⅲ/Ⅳ. The 5-year survival time of patients with above positive indexes was shortened (P < 0.05).ConclusionsFn could induce endoplasmic reticulum stress by inducing the high expression of GRP78 and XBP1, and promote the malignant evolution of ESCC.
摘要:ObjectiveTo construct 131Ⅰ-labeled hepatoma nucleic acid nanotrain and to explore its feasibility as a new nuclide carrier targeting hepatoma.MethodsThree short nucleic acid chains self-assembled to a long nucleic acid chain after being annealed, and 131Ⅰ-NT was obtained by radioiodine labeling using chloramine T method. The labeling efficiency and radiochemical purity of the nanoparticles were measured by paper chromatography. The stability of the labeled products in vitro at different temperatures and different storage solvents was detected. The specific uptake of nanoparticles by hepatocellular carcinoma cells was observed by laser confocal microscopy, and the radioactive uptake ratio of 131Ⅰ-NT combined with human hepatocellular carcinoma cell HepG2 and normal hepatocyte L02 was measured. The biodistribution of 131Ⅰ-NT was obtained through injecting 131Ⅰ-NT into HepG2 tumor-bearing mice via tail vein.ResultsThe labeling rate of 131Ⅰ-NT was (93.05±0.74) %, and the radiochemical purity post purification was (98.35±0.32) %. Its radiochemical purity in PBS and pure serum at 4℃ for 24 h was (92.77±0.04) % and (89.43±0.2) %, respectively. The radioactivity uptake rate of HepG2 cells was higher than that of L02 cells after 131Ⅰ-NT was incubated with two kinds of cells for 2 h significantly. After injection of 131Ⅰ-NT through tail vein, the radioactive uptake per gram of tumor tissue were (4.9±0.55)%ID/g, (10.12±0.32)%ID/g and (4.25±0.31)%ID/g at 30 min, 1 h and 2 h, respectively. The T/M ratio was 7.33±2.04, 36.54±12.72 and 44.93±7.90 respectively.ConclusionsThe 131Ⅰ-labeled long chain nucleic acid nanotrain was constructed successfully, which possesses relatively high stability in vitro , and high targeting ability to HepG2 cells in vitro and HepG2 tumor-bearing mouse model. Our study demonstrated that 131Ⅰ-NT may be a potential radionuclide carrier targeting human liver cancer, which provides a new idea for the targeted radionuclide diagnosis and treatment of hepatocellular carcinoma.
摘要:ObjectiveTo investigate the effect and mechanism of Scutellaria Baicalensis polysaccharides on intestinal immunity in mice with ulcerative colitis (UC).MethodsC57BL/6 mice were randomly assigned to blank group, model group, mesalazine group and Scutellaria Baicalensis polysaccharides low-dose, medium-dose and high-dose groups (n=10 mice/group). The daily status of mice was observed and the disease activity index (DAI) score was recorded. The expression of cytokines including IL-6, IL-17 and IL-23 in serum was detected by ELISA. After the mice were sacrificed, HE was used to observe the intestinal mucosal damage in mice, and the colonic tissue damage index (TDI) score was recorded. Western blot and immunohistochemistry were used to detect the expression levels of Janus kinase 2 (JAK2), signal transducer and activator of transcription (STAT3), p-JAK2 and p-STAT3 proteins.ResultsCompared with the blank group, the DAI score of the model group was significantly increased, the contents of IL-6, IL-17 and IL-23 in serum were significantly increased, the ratio of p-JAK2/JAK2 and p-STAT3/STAT3 in colon tissue was significantly increased, and the expression levels of p-JAK2 and p-STAT3 were significantly increased. Compared with the model group, the DAI score of mice in each administration group was significantly decreased. The contents of IL-6, IL-17 and IL-23 in serum were decreased, the TDI score was decreased, the ratio of p-JAK2/JAK2 and p-STAT3/STAT3 in colon tissue was decreased, and the expression of p-JAK2 and p-STAT3 was decreased.ConclusionScutellaria Baicalensis polysaccharides may improve the inflammatory effect of UC mice through JAK2/STAT3 pathway and IL-23/IL-17 inflammatory axis.
摘要:ObjectiveArtificial intelligence (AI) full smear automated diatom detection technology can perform forensic pathology drowning diatom detection more quickly and efficiently than human experts.However, this technique was only used in conjunction with the strong acid digestion method, which has a low extraction rate of diatoms. In this study, we propose to use the more efficient proteinase K tissue digestion method (hereinafter referred to as enzyme digestion method) as a diatom extraction method to investigate the generalization ability and feasibility of this technique in other diatom extraction methods.MethodsLung tissues from 6 drowned cadavers were collected for proteinase K ablation and made into smears, and the smears were digitized using the digital image matrix cutting method and a diatom and background database was established accordingly.The data set was divided into training set, validation set and test set in the ratio of 3:1:1, and the convolutional neural network (CNN) models were trained, internally validated, and externally tested on the basis of ImageNet pre-training.ResultsThe results showed that the accuracy rate of the external test of the best model was 97.65 %, and the area where the model features were extracted was the area where the diatoms were located. The best CNN model in practice had a precision of more than 80 % for diatom detection of drowned corpses.ConclusionIt is shown that the AI automated diatom detection technique based on CNN model and enzymatic digestion method in combination can efficiently identify diatoms and can be used as an auxiliary method for diatom detection in drowning identification.
摘要:ObjectiveTo examine the current status of preschoolers' eating behaviors and investigate its correlation with family cohesion and adaptability.MethodsA cross-sectional study was conducted involving 21,954 preschoolers and their families from Pingshan District, Shenzhen, between September 2021 and December 2021. A general demographic questionnaire, the Chinese version of Family Adaptability and Cohesion Evaluation Scale Ⅱ (FACESⅡ-CV) and Chinese Preschoolers’ Eating Behavior Questionnaire (CPEBQ) were used to collect the relevant information. Multiple linear regression was used to analyze the association of family cohesion and adaptability with eating behaviors of preschoolers.ResultsTypes of family cohesion and adaptability were significantly correlated with all the 7 dimensions of preschoolers' eating behaviors, including food fussiness (R2=0.252, F=114.457, P<0.001), food responsiveness (R2 = 0.111, F =24.973, P<0.001), eating habit (R2= 0.304, F =139.658, P<0.001), satiety responsiveness (R2 = 0.259, F =105.332, P<0.001), external eating (R2 = 0.182, F =50.150, P<0.001), emotional eating (R2 = 0.234, F =91.084, P<0.001) and initiative eating (R2 = 0.349, F =168.608, P<0.001). After adjusting for confounding factors, our study showed that types of family cohesion and adaptability were independent predictors of preschoolers' eating behaviors (P<0.05).ConclusionsTypes of family cohesion and adaptability have a significant predictive effect on the 7 dimensions of preschoolers' eating behaviors. Higher scores of family cohesion and adaptability imply stronger initiative eating ability and less poor dietary behaviors in preschoolers.
摘要:ObjectiveTo explore the co-expression of PTBP1 and p-AXL in osteosarcoma and its clinicopathological significance for prognosis evaluation.MethodsThe expression of PTBP1 and AXL and their prognostic value in osteosarcoma were analyzed by GEO and Target data. Paraffin biopsy specimens and clinical information from 76 cases of osteosarcoma and 37 cases of non-malignant bone tissue (callus, osteofibrous dysplasia and osteoid ostema) were obtained from the First Affiliated Hospital of Sun Yat-sen University from March 2016 to October 2020. The expressions of PTBP1 and p-AXL proteins in osteosarcoma were detected by immunohistochemistry.ResultsGEO database showed that the expression levels of PTBP and AXL in osteosarcoma tumor group were higher than those in normal tissues, but did not reach statistical significance. Target database showed that the high expression of PTBP1 had shorter Overall survival(OS) and Progression-free survival(PFS) than low PTBP1 expression, but did not reach statistical significance (P=0.064; P=0.134). Immunohistochemical staining included 76 cases of osteosarcoma and 37 cases of non-malignant bone tissue. The expression rate of PTBP1 and p-AXL protein in osteosarcoma tissues was higher than that in non-malignant bone tissue. The expression of p-AXL is correlated with lung metastasis (P=0.025). Kaplan-Meier analysis showed that lung metastasis, recurrence, PTBP1 expression, co-expression of PTBP1/p-AXL influence the prognosis of patients in OS. Multivariate Cox regression analysis showed that lung metastasis (P<0.000 1) and positive expression of PTBP1 (P=0.041) were independent risk factors for osteosarcoma patients in OS. Co-expression of PTBP1 and p-AXL had shorter OS (P=0.017) and PFS (P=0.043) than non-coexpression osteosarcoma patients.ConclusionsPTBP1 and p-AXL were highly expressed in osteosarcoma tissues. The co-expression of PTBP1 and p-AXL was associated with poor prognosis of patients, and PTBP1 could be used as an independent prognostic indicator of patients with osteosarcoma.
摘要:ObjectiveThe glymphatic system regulates cerebral spinal fluid and interstitial fluid transport which might be one of the pathways of central nervous system (CNS) leukemia at the early stage. This study aimed to investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space (DTI-ALPS) in pediatric acute lymphoblastic leukemia (ALL) without clinically diagnosed CNS infiltration.MethodsTwenty-five ALL and typically developing (TD) children were prospectively recruited, and all subjects underwent DTI. Group differences in brain water diffusivities and ALPS-index were evaluated using the analysis of covariance. The Spearman correlation analysis was used to evaluate the relationship between biological characteristics and significant parameters in pediatric ALL.ResultsCompared with TDs, decreased Dxassoc value (PFDR-corrected = 0.048) and increased Dzassoc value (PFDR-corrected = 0.033) were found in pediatric ALL. Hence, lower ALPS-index was found in children with ALL (PFDR-corrected < 0.001). ALPS-index was negatively associated with the risk classification (rs = -0.47, P = 0.018) as well as immunophenotype (rs = -0.40, P = 0.046) in pediatric ALL.ConclusionsOur results show dysfunction of the glymphatic system is presented in pediatric ALL without clinically diagnosed CNS infiltration, which suggests that the glymphatic system might be one of pathway in the early-stage of ALL CNS infiltration. The DTI-ALPS method can be used to evaluate the change of glymphatic system, providing a new method for exploring the underlying mechanisms and early detection of pediatric ALL CNS infiltration.
关键词:acute lymphoblastic leukemia;children;central nervous system;MRI;the glymphatic system
摘要:ObjectiveTo investigate the mRNA expression levels of various aquaporins (AQPs) in luteinized granulosa cells from follicles of different diameters.MethodsFrom March 25, 2022 to September 23, 2022 in our reproductive medicine center, 48 women undergoing in-vitro fertilization (IVF) were enrolled and divided into the antagonist group and the agonist group according to the ovarian stimulation protocol. Follicular fluid samples were collected on the day of oocyte pick-up and granulosa cells were extracted from follicles of different diameters: small (<13 mm), medium (13~18 mm) and large (≥18 mm). After RNA quantification, 22 cases (66 samples) were included for analysis and mRNA expression levels of AQPs were compared among the three follicle groups.ResultsThe mRNA expression of aquaporin 2 (AQP2) in luteinized granulosa cells increased with the increase of follicle diameter (linear trend P = 0.004) and the difference was statistically significant between two groups of large and small follicles (P = 0.017). Statistical difference was found in the antagonist group (P = 0.049 6), but not in the agonist group (P = 0.108).ConclusionThe mRNA level of AQP2 in luteinized granulosa cells increases with the increase of follicle diameter and its expression is related to the ovarian stimulation protocol, suggesting that AQP2 may play a role in follicle growth and follicular fluid formation, and its mRNA expression level may be regulated by follicle stimulating hormone (FSH) and luteinizing hormone (LH).
摘要:ObjectiveTo summarize and analyze the clinical characteristics, diagnosis process, treatment process, and obstetric outcomes of pregnant women with Cushing's syndrome, helping to optimize pregnancy management.MethodsA retrospective study was conducted on 8 pregnant women with Cushing’s syndrome who were hospitalized in the First Affiliated Hospital, Sun Yat-sen University between January 2006 and August 2022. The clinical characteristics, management and obstetric outcomes were recorded.ResultsPreeclampsia was detected in 4 cases,pre-gestational diabetes mellitus in 2 cases, gestational diabetes mellitus in 5 cases, and hypokalemia in all 8 cases. Elevated serum cortisol, disappearance of day-night rhythm of cortisol, increased 24-hour urine cortisol and decrease in serum ACTH were found in 8 cases by laboratory examination. Furthermore, adrenal adenoma was detected in all 8 cases by ultrasonography or Magnetic Resonance Imaging. Three cases underwent laparoscopic adrenalectomy in the second trimester and 4 cases received surgery after delivery. The diagnosis of adrenal cortical adenoma was confirmed by pathological report. Six cases had preterm birth, while one patient delivered after 37 weeks of gestation and one patient suffered from spontaneous abortion. Among 7 cases of live birth, 6 patients underwent cesarean section and 1 patient had vaginal delivery. Of all newborns, 3 had low birth weight. One case had a birth defect. Four infants were transferred to the neonatal intensive care unit, and two infants died. One child was diagnosed with nephrotic syndrome at 2 years of age.ConclusionsCushing's syndrome is rare and high risk during pregnancy. It requires multidisciplinary diagnosis, treatment, and long-term follow-up. Drug therapy carries a risk of progression and requires intensive care during pregnancy, postpartum follow-up, and specialist treatment.
摘要:ObjectiveTo investigate the diagnosis and treatment of familial hypokalemic periodic paralysis with acidosis.MethodsThe proband's medical history, clinical manifestations, laboratory examinations and imaging characteristics were retrospectively analyzed, and prevalence situation of family members was investigated in detail. Next generation sequencing technology was used to detect the pathogenic gene loci related to periodic paralysis, and the relevant literatures were summarized.ResultsThe proband was definitely diagnosed as familial hypokalemic periodic paralysis. There was a heterozygous mutation in the SCN4A gene of the proband, which was c.2006G>A, resulting in amino acid changes R669H.The proband's grandfather, father and uncle shared the same variation.ConclusionsFamilial hypokalemic periodic paralysis with paroxysmal acidosis is rare, which is easily misdiagnosed as renal tubular acidosis. c 2006G>A mutation in SCN4A gene is the molecular basis of the disease in this family. The clinical phenotypes of different gene mutations are different, and gene screening is helpful for diagnosis and treatment.
关键词:hypokalemic periodic paralysis;SCNA4;mutation;family study
摘要:ObjectiveTo explore the clinical diagnosis and treatment of rare primary lumbar intervertebral space infection with Klebsiella pneumoniae and Enterobacter cloacae, and provide clinical experience for the diagnosis and treatment of this rare spinal infection.MethodsAn elderly male patient with low back pain and numbness in the left lower extremity for more than 7 months, which aggravated for more than 1 week, was diagnosed with lumbar disc herniation after laboratory and imaging examinations. After admission, the symptoms became acutely aggravated, and re-examination of lumbar enhanced MRI showed local enhancement at the posterior edge of the L3/4 intervertebral space. The VAS score was 9 points, and the lumbar JOA score was 6 points. A posterior lumbar interbody fusion of L3-L5 was performed, and L3/4 intervertebral disc specimens were collected during the operation for bacterial culture.ResultsBacterial culture results showed Klebsiella pneumoniae and Enterobacter cloacae infection. The patient was treated with sensitive antibiotics for 6 weeks after the operation, and the patient was cured during the follow-up of half a year after the operation.ConclusionFor middle-aged and elderly patients with clinical manifestations of acute severe low back pain or lower extremity pain, the possibility of spinal infection should be considered when routine laboratory and imaging examinations suggest lumbar degenerative diseases.
关键词:infection of lumbar intervertebral space;Klebsiella pneumoniae;enterobacter cloacae;differential diagnosis
摘要:ObjectiveTo reveal the molecular pathogenesis of Hunter syndrome in three families in southern China and to clarify the correlation between phenotype and genotype, so as to lay a foundation for future prenatal or preimplantation genetic diagnosis.MethodsOn the basis of initial clinical diagnosis and pedigree analysis, qualitative detection of glycosaminoglycans in urine was performed first, and then anticoagulant blood samples were collected from the children and their relatives. DNA was extracted and the IDS gene sequence was analyzed by PCR and Sanger sequencing. Various methods such as RT-PCR and bioinformatics analysis were used to identify the pathogenicity of the new variants.ResultsThe urine test results of the patients in the three families were all strongly positive(++). Probands were all male, with hemizygous mutations in IDS gene from their mothers, and the mutation sites were c.615_622delCATACAGT, c.847_848delGT and IVS7 ds+1 G>A, respectively. The cross-species conservation analysis showed that the amino acid of IDS gene mutation site was highly conserved during species evolution. Compared with the normal protein, mutant proteins exhibited significant differences in the predicted results of advanced structure. The variants identified in the three families were classified as pathogenic by ACMG criteria.ConclusionsThe three probands were diagnosed with Hunter syndrome. The c.615_622del(p.Il206Valfs*18), c.847_848del(p.Val283Alafs*57) and IVS7 ds+1 G>A (p.G336Dfs*12) of IDS gene are all novel pathogenic mutations, which are the underlying causes of morbidity in children. This study has further enriched the mutation spectrum of IDS gene.
摘要:ObjectivesTo assess the correlation between blastocyst morphology score, serum human chorionic gonadotropin β subunit (β-hCG) levels on day 12 after transfer and live birth outcomes among cycles tested HCG-positive after thawed single blastocyst transfer; to analyze the predictive value of serum β-hCG levels on live birth.MethodsWe reviewed the data of 519 frozen-thawed single blastocyst transfer cycles (FET) that had been tested HCG-positive from January 2016 to May 2020 at our IVF center. These FET cycles were firstly divided into 4 groups (AA, AB, BA, and BB) according to Gardner's grading system of inner cell mass (ICM) and trophectoderm cell (TE), and then 4 groups (stages 3, 4, 5 and 6) according to the degree of blastocyst expansion. Serum β-hCG concentrations on day 12 after transfer and live birth rates were compared among groups transferred with different blastocysts grading and expansion stage. The relationship between Gardner’s grading or expansion stage of blastocysts and serum β-hCG levels was determined by correlation test, and ROC curves were plotted to determine the threshold values of serum β-hCG for predicting live birth.Results(1) The serum β-hCG concentration in the AA group and AB group on the 12th day after the transfer was significantly higher than that in the BB group (P <0.001, P <0.001). However, there was no significant difference in the live birth rate when different ICM/TE-graded blastocysts were transferred (P = 0.120). There were no significant differences in serum β-hCG concentration on day 12 after transfer and live birth rate among blastocysts with different expansion stages (P = 0.091, P = 0.557). (2) There was a significant weak correlation between blastocyst ICM/TE grading and serum β-hCG concentration on day 12 (rs = -0.221, P <0.001), and even after controlling for confounding factors ( rs = -0.228, P <0.001);There was no significant correlation between blastocyst’s expansion stage and serum β-hCG concentration on day 12 after the transfer (rs = -0.052, P = 0.240), and the association remained insignificant after controlling for confounding factors (rs = -0.029, P = 0.508). (3) ROC curve analysis showed that the cut-off value for predicting live birth by serum β-hCG on day 12 was 657.5 mU/mL (P < 0.001).ConclusionsNeither the ICM/TE grade nor the expansion stage of blastocysts affect the live birth rate,there is significant difference in the level of β-hCG produced by blastocyst with different ICM/TE grade;Our results suggest that early serum β-hCG level can predict live birth.
摘要:Colorectal cancer is one of the most common cancer types with the highest morbidity and mortality. It is necessary to harvest sufficient lymph nodes to perform an accurate postoperative pathologic assessment. Carbon nanoparticles have been widely used as a new kind of tracer in colorectal cancer due to its lymphotropic property, safety and long effectiveness. Carbon nanoparticles were reported to be able to help locate the primary tumor, trace regional lymph nodes, determine the extent of lymph node excision, reduce surgical difficulty, preserve more intestines, increase the number of postoperative lymph node detection, and reduce the operation time and hospital stay. In this article, the mechanism of carbon nanoparticles will be introduced. The effect in colorectal surgery and further research direction will be reviewed.
摘要:Natural Killer (NK) cells are another type of anti-tumor immune cells with promising clinical application in addition to T cells. NK cell activity is mainly regulated by its surface receptors and immune microenvironment. The strong immunosuppressive microenvironment of glioma results in low efficiency of NK cell immunotherapy. This article reviews NK cells in the immunotherapy for glioma from the interaction of glioma-NK cell, and the latest research progress of targeted NK cells compounds, monoclonal antibody, and cytokine therapy, focusing on the genetic modification of NK cells in the present situation and trend of glioma immunotherapy, and molecular mechanism of glioma cells related to immune escape. We hope this article will provide theoretical basis and new ideas for NK cell-based immunotherapy of glioma.
摘要:Esophageal squamous cell carcinoma is a common malignancy in the Asia-Pacific region, especially in China, where the morbidity remains high in spite of the improved overall survival due to advances in medical technology. Immunotherapy becomes a hot spot in recent tumor research when it has provided significant survival benefits in patients with advanced malignant tumors, such as lung cancer, breast cancer, colon cancer, etc. In esophageal squamous cell carcinoma, immunotherapy promotes survival benefit as well. However, because of the complex and changeable biological functions and gene expression regulation of malignant tumors, the conclusions based on a single-omics analysis are often incomprehensive. Currently, most of the immune-related studies on esophageal squamous cell carcinoma are still confined to a single-omics study like genomics, with limitations and one-sidedness. Since multi-omics analysis helps us better understand tumors from a wider and deeper perspective, this review explores and summarizes immune-related features of esophageal squamous cell carcinoma from a multi-omics perspective.
摘要:Primary insomnia is one of the common sleep disorders. It is a type of insomnia with unknown causes, which is often accompanied by a variety of daytime dysfunction and sleep-wake disorders. Neuroimaging and neuroelectrophysiology studies suggest that there may be default mode network dysfunction in patients with primary insomnia, which is closely related to daytime dysfunction and sleep-wake disorder. This article summarizes the characteristics of default mode network dysfunction of primary insomnia and introduces related research in neural structural imaging, functional imaging and neuroelectrophysiology, as well as the role and the mechanism of default mode network impairment leading to daytime dysfunction and sleep-wake disorder of primary insomnia.
摘要:Diabetic kidney disease (DKD) is one of the most common microvascular complications in patients with diabetes. DKD is also the main cause of end-stage renal failure, with very complex pathogenesis. A large number of experiments have confirmed that epigenetic mechanisms, including histone chemical modifications and lipid metabolites 12/15-lipoxygenase (12/15-LO), are involved in regulating the characteristic pathophysiological process of DKD, based on which, this review further explores the pathogenesis of DKD and provides the new research direction for DKD treatment.
关键词:diabetic kidney disease (DKD);12/15-lipoxygenase (12/15-LO);histone chemical modifications;metabolic memory;TGF-β