Objective To investigate the activation of microglia and astrocytes, the secretion of pro-inflammatory factors, and the survival of neurons in the hippocampus of mice with acute seizures induced by pentylenetetrazol (PTZ) 24 hours after the onset of seizures. Methods Adult male C57BL/6 mice were randomly assigned to the control group and the PTZ-induced acute epileptic seizure group using random numbers, with 28 mice in each group. The activation status of microglia and astrocytes in the CA1 region of the hippocampus was evaluated by immunofluorescence 24 hours after the onset of seizures. RNA was extracted from the hippocampal tissue to detect the expression level of inflammatory factor mRNA, and HE staining was used to assess the survival of neurons in the hippocampus. Results Twenty-four hours after PTZ-induced acute seizures in mice, the numbers of activated Iba1⁺ microglia (55.72±4.29 vs 35.71±9.66, P＜0.001) and GFAP⁺ astrocytes (51.61±8.21 vs 37.64±5.27, P＜0.01) in the CA1 region were significantly increased compared with the control group; the proportion of M1 microglia was significantly increased (0.58±0.02 vs 0.35±0.08, P＜0.0001), while the proportion of M2 microglia was significantly decreased (0.25±0.08 vs 0.44±0.09，P＜0.01); the mRNA level of pro-inflammatory factor IL-1β in the hippocampus was significantly higher than that in the control group (2.49±1.61 vs 1.02±0.68, P＜0.05); the numbers of neurons in the CA1 (284.91±73.32 vs 498.88±176.79, P＜0.05) and CA3 (247.42±50.20 vs 457.78±150.08, P＜0.05) regions during the acute phase was significantly reduced compared with the control group. Conclusions Twenty-four hours after PTZ-induced acute epileptic seizures in mice, microglia and astrocytes in the CA1 region of the hippocampus are activated, with microglia mainly presenting the M1 phenotype to exert pro-inflammatory effects, secretions of pro-inflammatory factors increasing, and surviving hippocampal neurons decreasing.

Objective:To explore the role of conducting a"thematic morning report"based on post-competency in the standardized residents training in hospital in the Intensive Care Unit(ICU).Methods:A total of 60 resident training physicians who participated in the standardized residents training in hospital in the ICU of this hospital from January 2020 to December 2022 were included,and randomly divided into an observation group and a control group,with 30 in each group.The observation group adopted an interactive teaching method of themed morning report based on post-competency,while the control group adopted the traditional teaching method.The assessment results of clinical theoretical knowledge and operational skills of the two groups of resident training physicians under different teaching methods were compared.The 360°assessment method was used to record the multi-directional evaluation of patients or their families,nurses,colleagues,and teaching teachers on the post-competence of resident training physicians(self-learning ability,team collaboration ability,effective communication ability,and learning interest).Results:The assessment scores of clinical theoretical knowledge and practical skills in the observation group after teaching were higher than those in the control group,with statistically significant differences(theoretical assessment:t=2.101,P＜0.05;practical assessment:t=9.647,P＜0.05).The post-competence scores of nurses,colleagues,and teaching teachers on resident training physicians in the observation group were higher than those in the control group after one-month regular training,and the differences were statistically significant(nurses'evaluation of self-learning ability:t=3.182,P=0.002,team collaboration ability:t=3.978,P＜0.05,effective communication ability:t=2.180,P=0.0335,learning interest:t=3.884,P＜0.05;colleagues'evaluation of self-learning ability:t=2.888,P=0.005,team cooperation ability:t=6.816,P＜0.05,effective communication ability:t=3.833,P＜0.05,learning interest:t=4.086,P＜ 0.05;teaching teacher's evaluation of self-learning ability:t=3.429,P=0.001,team cooperation ability:t=3.086,P=0.003,effective communication ability:t=3.493,P=0.001,learning interest:t=3.126,P=0.003).There was a statistically significant difference in the satisfaction scores of patients or their familymembers towards the two groups of resident training physicians(t=3.126,P=0.003).Conclusion:The use of the interactive teaching method of thematic morning report based on post-competency in the standardized residents training in hospital in the ICU can not only improve the theoretical practice and case analysis test scores of resident training physicians,but also improve the post-competence and the satisfaction of patients and their families.

Due to the complexity of traditional Chinese medicine （TCM） interventions and the diversity of herbal components， single-omics technologies such as genomics， transcriptomics， proteomics， and metabolomics often cannot comprehensively elucidate the scientific connotations of TCM. Multi-omics technologies driven by system biology can analyze the theoretical connotations and application mechanisms of TCM from different levels such as genes， gene expression， proteins， and metabolites， in line with the holistic view of TCM， which helps to promote the modernization of TCM. By reviewing the literature on the application of omics technologies in the field of TCM， it is found that multi-omics technologies have been widely used in TCM for syndrome differentiation， evaluation of herbal quality， elucidation of pharmacological mechanisms， and drug toxicity assessment， providing comprehensive explanations of the mechanisms of action of TCM and overcoming the limitations of single-omics technologies， and having obtained significant achievements. However， multi-omics technologies also face challenges such as high cost， difficulties in data analysis due to large data volumes， and insufficient translation of research results. In the future， it is expected that through strengthening interdisciplinary cooperation， conducting long-term and dynamic clinical research， standardizing and normalizing data analysis processes， adopting appropriate and reasonable multi-omics integration patterns， establishing multi-omics databases for TCM， revealing the individualized characteristics， therapeutic mechanisms， and disease regulatory networks of TCM， the modernization of TCM will be promoted.

Objective To construct a Type 1 diabetes model in miniature pigs and explore postoperative care strategies for effectively prolonging the survival time of the model pigs.Methods Seven Banna miniature pigs were selected for pancreatectomy.Glucose,vitamins,and antibiotics were administered for 3-5 days after surgery to aid recovery.Blood glucose and urine glucose levels were measured twice a day in the morning and evening to adjust insulin supplementation accordingly.The model pigs were observed daily and records were kept,including orexis,psychosis,weakness,skin ulcer,and feces and urine.Body weight was measured weekly until the death of the model animals.Based on the model pigs'condition,glucose injection and Ringer's lactate solution were administered to supplement nutrition and correct electrolyte imbalances.Results All seven Banna miniature pigs showed typical symptoms of diabetes:random blood glucose levels higher than 11.1 mmol/L after pancreatectomy,far exceeding the average blood glucose level of 6.0 mmol/L in normal pigs;positive urine glucose;and progressive weight loss.These features indicated the successful construction of Type 1 diabetes model.Additionally,Type 1 diabetic pigs that survived more than 8 weeks showed progressive hair loss and skin ulceration.Euthanasia was performed on model pigs when they were unable to stand or even eat independently,and pathological examination and HE staining were conducted on tissues collected from affected organs such as the liver,kidneys,and skin.Pathological sections revealed liver congestion,massive glycogen accumulation,ballooning degeneration of hepatocytes,and progressive liver fibrosis,along with glomerular congestion,vacuolar degeneration in renal tubular epithelial cells,proteinuria,dermal congestion,thinning of vascular walls,and varying degrees of parakeratosis and dyskeratosis in the liver,kidneys,and skin tissues due to prolonged hyperglycemia.The average survival time of the constructed Banna miniature pig diabetes model was 44 d,with a maximum survival time of 121 d.Conclusion Type 1 diabetes model can be constructed successfully in Banna miniature pigs through pancreatectomy.With meticulous postoperative care,a long-term Type 1 diabetes model with significant complications can be achieved,providing a stable large-animal model for Type 1 diabetes treatment strategies.

Background: and Purpose CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeatprimed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. Conclusions Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

Background: and Purpose CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeatprimed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. Conclusions Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

Background: and Purpose CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeatprimed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. Conclusions Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

We here investigated the effect of MS4A6D(the membrane spanning 4-domain subfamily A(MS4A)superfamily protein 6D),one of the tetraspanins which specifically expresses on the membrane of macrophages,on carrageenan(CGN)-induced mouse foot pad swelling and its possible mechanism.Male C57BL/6 wild-type(WT)and various gene knockout(including Ms4a6d-/-,Nlrp3-/-,Casp-1-/-and IlR1-/-)mice were recruited and injected with 100 μl 1%CGN(w/v)and 20 μl CaCl2(50 mmol/L)to establish the foot pad swelling model,and then the severity of foot pad swelling in WT and gene knockout mice were compared.H&E staining was performed to investigate the pathological changes,and immunofluorescence was used to detect the infiltration of F4/80+ macrophages in the foot pad tissue.Finally,Western blot was used to determine the protein expression of NLRP3,IL-1 β,TNF-α and IL-6.Data showed that the combined injection of 100 μl 1%CGN(w/v)and 20 μl CaCl2(50 mmol/L)significantly promoted the swelling of foot pads,while the degree of foot pad swelling in Ms4a6d-/-mice was significantly lower than that in WT littermates(P<0.05);Significant tissue damage and inflammatory infiltration as well as necrotic lesions were observed in the WT foot pads,whereas,the degrees from Ms4a6d-/-foot pads showed significantly reduced;The protein levels of Caspase-1 and IL-1β in the foot pad tissue of the WT model were significantly higher than those of the Ms4a6d-/-groups;Compared with WT controls,the degree of foot pad swelling in Nlrp3-/-,Casp-1-/-,and IlR1-/-mice induced by 1%CGN(w/v)and CaCl2(50 mmol/L)were also significantly reduced(P<0.05).Taken together,MS4A6D promotes the activation of NLRP3 inflammasome in macrophages and induces IL-1β secretion,by thus deteriorates CGN-mediated swelling of mouse foot pads.

Objective:To explore the efficacy of ixazomib combination treatment therapies for multiple myeloma (MM), and the influencing factors of prognosis.Methods:The clinical data of 80 MM patients admitted to Yancheng Third People's Hospital from January 2020 to January 2022 were retrospectively analyzed. All patients received 3 courses of ixazomib combination treatment therapies (28 d was 1 course). All combination treatment therapies included ID group (ixazomib + dexamethasone, 11 cases) and ID + immunomodulator group (ixazomib + dexamethasone + lenalidomide/thalidomide, 50 cases), ID + other chemotherapy drugs group (ixazzomib + dexamethasone + doxorubicin liposome/cyclophosphamide/bendamustine, 19 cases). The clinical efficacy of patients in different treatment regimens was compared, and the prognosis was followed up and recorded. The clinical characteristics between the survival and the dead patients were compared. Cox proportional risk model was used to make multivariate analysis of the overall survival of MM patients receiving ixazomib combination therapies.Results:The treatment was effective in 9 cases (81.82%) of the ID group, 32 cases (64.00%) of the ID + immunomodulator group, and 9 cases (47.37%) of the ID + other chemotherapy drugs group. There was no statistically significant difference in the effectiveness rate of 3 ixazomib combination regimens ( χ2 = 0.62, P = 0.432). All patients were followed up for 5 to 20 months, with an average follow-up time of (15±4) months. There were statistically significant differences in immunoglobulin type, Durie-Salmon stage, early treatment line and therapeutic efficacy between the survival group (49 cases) and the death group (31 cases) (all P < 0.05). Multivariate Cox regression analysis showed that the clinical effectiveness (effectiveness vs. ineffectiveness: OR = 0.242, 95% CI 0.103-0.567, P = 0.001) and the previous first-line treatment (the first-line vs. the other lines: OR = 0.577, 95% CI 0.452-0.736, P < 0.001) were independent protective factors for the overall survival of MM. Conclusions:The 3 ixazomib combination therapies have a certain efficacy in the treatment of MM; ID regimen has the best clinical efficacy and survival. The clinical effectiveness and the previous first-line treatment are independent protective factors for the survival of MM.

Background: and Purpose The association of dyslipidemia with stroke has been inconsistent, which may be due to differing associations within etiological stroke subtypes. We sought to determine the association of lipoproteins and apolipoproteins within stroke subtypes. Methods: Standardized incident case-control STROKE study in 32 countries. Cases were patients with acute hospitalized first stroke, and matched by age, sex and site to controls. Concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), and apoB were measured. Non-HDL-C was calculated. We estimated multivariable odds ratio (OR) and population attributable risk percentage (PAR%). Outcome measures were all stroke, ischemic stroke (and subtypes), and intracerebral hemorrhage (ICH). Results: Our analysis included 11,898 matched case-control pairs; 77.3% with ischemic stroke and 22.7% with ICH. Increasing apoB (OR, 1.10; 95% confidence interval [CI], 1.06 to 1.14 per standard deviation [SD]) and LDL-C (OR, 1.06; 95% CI, 1.02 to 1.10 per SD) were associated with an increase in risk of ischemic stroke, but a reduced risk of ICH. Increased apoB was significantly associated with large vessel stroke (PAR 13.4%; 95% CI, 5.6 to 28.4) and stroke of undetermined cause. Higher HDL-C (OR, 0.75; 95% CI, 0.72 to 0.78 per SD) and apoA1 (OR, 0.63; 95% CI, 0.61 to 0.66 per SD) were associated with ischemic stroke (and subtypes). While increasing HDL-C was associated with an increased risk of ICH (OR, 1.20; 95% CI, 1.14 to 1.27 per SD), apoA1 was associated with a reduced risk (OR, 0.80; 95% CI, 0.75 to 0.85 per SD). ApoB/A1 (OR, 1.38; 95% CI, 1.32 to 1.44 per SD) had a stronger magnitude of association than the ratio of LDL-C/HDL-C (OR, 1.26; 95% CI, 1.21 to 1.31 per SD) with ischemic stroke (P<0.0001). Conclusions The pattern and magnitude of association of lipoproteins and apolipoproteins with stroke varies by etiological stroke subtype. While the directions of association for LDL, HDL, and apoB were opposing for ischemic stroke and ICH, apoA1 was associated with a reduction in both ischemic stroke and ICH. The ratio of apoB/A1 was the best lipid predictor of ischemic stroke risk.