OBJECTIVE To construct an insulin-resistant(IR)small intestinal organoid model of mice and study the protective effect of flavanomarein(FM)on the intestinal mucosal barrier in the model.METHODS ①Small intestinal organoid models of C57BL/6J and db/db of mice were constructed.The expressions of Ki-67,E-cadherin(E-cad),lysozyme(Lyz)and mucin-2(Muc-2)in small intestinal organ-oids were detected by 3D immunofluorescence.RT-qPCR was used to detect the expressions of fibro-nectin(Fn),glucagon-like peptide-1(GLP-1)and peotide YY(PYY)mRNA while Western blotting was used to detect the expressions of Fn,GLP-1 and PYY protein.The Lyz secretion level was detected by ELISA.② Small intestinal organoids were divided into five groups:C57BL/6J mice 'small intestinal organ-oids as the normal control group,db/db mice' intestinal organoids as the IR model group,db/db mice small intestinal organoids with flavanomarein 25,50 and 100 μmol·L-1 intervention for 48 h as IR model+ FM groups.RT-qPCR was used to detect the expression of Lyz mRNA while Western blotting was used to detect the expression of Lyz protein.RESULTS ① On the 6th day of small intestinal organoid culture,a ring structure with a clear luminal structure was formed and an IR mouse small intestinal organoid model was established.3D Immunofluorescence detection showed that the established small intestinal organoids all expressed Ki-67,E-cad,Lyz and MUC-2.Compared with the normal control group,the expres-sion of Fn mRNA in the IR model group was significantly increased(P<0.05)while the expressions of GLP-1 and PYY mRNA were significantly decreased(P<0.05).Compared with the normal control group,the expression of Fn protein in the IR model group was significantly decreased(P<0.05)while the expressions of GLP-1 and PYY protein were significantly increased(P<0.05).ELISA results showed that compared with the normal control group,the secretion levels of Lyz in the IR model group were signifi-cantly decreased(P<0.01).② RT-qPCR results showed that compared with the normal control group,the expression of Lyz mRNA in the IR model group was significantly decreased(P<0.01).Compared with the IR model group,the expression of Lyz mRNA in the IR model+FM 50 and 100 μmol·L-1 groups was significantly increased(P<0.05,P<0.01).Western blotting results showed that compared with the normal control group,the expression of Lyz protein in the IR model group was significantly decreased(P<0.01).Compared with the IR model group,the expression of Lyz protein in the IR model+FM 50 and 100 μmol·L-1 groups was significantly increased(P<0.05,P<0.01).CONCLUSION The constructed IR mouse small intestinal organoid model provides a more complete in vitro research model for exploring the pathophysiological mechanism by which drug interventions help repair the intestinal mucosal barrier.FM may maintain the intestinal mucosal barrier by reversing the decrease in Lyz expression levels in IR mice,thereby improving IR.

Objective To investigate the influencing factors for slowly progressive brainstem infarction and rapidly progressive brainstem infarction in patients with severe stenosis or occlusion of basilar artery.Methods A retrospective analysis was performed for 501 patients who attended Zhengzhou University People's Hospital from January 2013 to Decem-ber 2022 and were diagnosed with first-episode brainstem infarction after severe stenosis or occlusion of basilar artery by HR-MRI.The core volume of brainstem infarction was manually calculated,and the distribution of brainstem infarct vol-ume was analyzed.According to brainstem infarct volume and the time from stroke attack to imaging,the patients were di-vided into slowly progressive brainstem infarction group(0-<1 ml,6-24 hours)and rapidly progressive brainstem infarc-tion group(>5 ml,0-<6 hours),and the two groups were compared in terms of risk factors and collateral circula-tion.Results The 501 patients with severe stenosis or occlusion of basilar artery had a mean age of 66.14±10.37 years,among whom 39.13%were male patients.According to predefined thresholds,29 patients(16.29%)with severe stenosis or occlusion of basilar artery in the time window of 0-<6 hours were diagnosed with rapidly progressive brainstem infarc-tion,and 56 patients(17.34%)in the time window of 6-24 hours were diagnosed with slowly progressive brainstem infarc-tion.There were no significant differences between the two groups in the risk factors such as age,sex,NIHSS score,hy-pertension,diabetes,hyperlipidemia,and history of atrial fibrillation,coronary artery disease,and smoking.The Pear-son correlation analysis showed that collateral circulation in patients with severe stenosis or occlusion of the basilar artery was negatively correlated with rapidly progressive brainstem infarction(r=-0.619,P<0.001).Conclusions After se-vere stenosis or occlusion of the basilar artery,patients with good collateral circulation often have slowly progressive brain-stem infarction,while patients with poor collateral circulation often have rapidly progressive brainstem infarction.

Objective To determine the role of cathepsin D(CTSD)in cardiovascular events after acute ST-segment elevation myocar-dial infarction(STEMI).Methods A total of 96 patients with STEMI admitted to the Department of Cardiovascular Medicine of Second Hospital Affiliated to Shenyang Medical College from November 2022 to July 2023 were selected as the STEMI group.In addition,20 patients with normal coronary angiography hospitalized during the same period were selected as the control group.Coronary blood was collected from both groups,and the relative expression levels of CTSD in the arterial blood were detected and compared using real-time quantitative polymerase chain reaction.The STEMI group was divided into low,medium,and high CTSD groups based on CTSD expression,and major adverse cardiovascular events(MACE)that occurred within 6 months following percutaneous coronary interven-tion(PCI)were monitored.Results Arterial blood CTSD expression(1.31[1.03-1.75])in the STEMI group was higher than that in the control group(1.02[0.67-1.48])(P＜0.05).Statistically significant differences in platelet count as well as troponin T,N-terminal pro-B natriuretic peptide,and high-density lipoprotein cholesterol levels were observed among the three groups(P＜0.05).The incidence of MACE was significantly higher in the low CTSD group(65％)than in the high CTSD group(10％,P＜0.05).Receiver operating cha-racteristic(ROC)curve analysis showed that the area under the ROC curve for predicting MACE within 6 months after PCI in patients with STEMI was 0.765(95％CI:0.658-0.872,P＜0.001).Conclusion Whole blood CTSD expression level is abnormal in STEMI patient.CTSD may be an indicator for predicting the prognosis of STEMI and,therefore,a drug target for preventing and treating STEMI.

Objective To analyze the clinical and imaging features of hemichorea associated with non-ketotic hyperglycemia(HC-NH)and to explore the perfusion of cerebral blood flow in the patients.Methods A retrospective study was conducted on 23 HC-NH patients diagnosed in Henan Provincial People's Hospital from January 2018 to December 2023.The clinical manifesta-tions,imaging features and prognosis were collected and analyzed,and the correlation with cere-bral blood flow hypoperfusion was investigated.Results The symptoms were all lateral involun-tary movements,of which 4 cases presented only single upper limb(1 case was left upper limb,the other 3 cases were right upper limb),and 19 cases had both upper and lower limbs involved(10 cases were left limb,and 9 cases were right limb).After the onset of the symptoms,the blood glucose level was 19.72±4.72 mmol/L,glycated hemoglobin level was(13.60±3.68)％,but all of patients were negative to urine ketone bodies.Hyperdense lesions in the contralateral basal ganglia region on CT images were observed in 6 cases.Strip or patchy hyperintensity was seen on T1-weighted MR images.All patients had ipsilateral stenosis of the vessels and regional hypoperfu-sion of cerebral blood flow as shown by MR perfusion-weighted imaging.All symptoms were re-lieved after actively controlling blood glucose,improving blood circulation,and symptomatic man-agement.Conclusion HC-NH is quite rare in clinical practice,and its occurrence may be related to cerebral blood flow hypoperfusion triggered by basal nucleus degeneration.

Objective:To establish a set of artificial intelligence (AI) verification rules for blood routine analysis.Methods:Blood routine analysis data of 18 474 hospitalized patients from the First Hospital of Jilin University during August 1st to 31st, 2019, were collected as training group for establishment of the AI verification rules,and the corresponding patient age, microscopic examination results, and clinical diagnosis information were collected. 92 laboratory parameters, including blood analysis report parameters, research parameters and alarm information, were used as candidate conditions for AI audit rules; manual verification combining microscopy was considered as standard, marked whether it was passed or blocked. Using decision tree algorithm, AI audit rules are initially established through high-intensity, multi-round and five-fold cross-validation and AI verification rules were optimized by setting important mandatory cases. The performance of AI verification rules was evaluated by comparing the false negative rate, precision rate, recall rate, F1 score, and pass rate with that of the current autoverification rules using Chi-square test. Another cohort of blood routine analysis data of 12 475 hospitalized patients in the First Hospital of Jilin University during November 1sr to 31st, 2023, were collected as validation group for validation of AI verification rules, which underwent simulated verification via the preliminary AI rules, thus performance of AI rules were analyzed by the above indicators. Results:AI verification rules consist of 15 rules and 17 parameters and do distinguish numeric and morphological abnormalities. Compared with auto-verification rules, the true positive rate, the false positive rate, the true negative rate, the false negative rate, the pass rate, the accuracy, the precision rate, the recall rate and F1 score of AI rules in training group were 22.7%, 1.6%, 74.5%, 1.3%, 75.7%, 97.2%, 93.5%, 94.7%, 94.1, respectively.All of them were better than auto-verification rules, and the difference was statistically significant ( P<0.001), and with no important case missed. In validation group, the true positive rate, the false positive rate, the true negative rate, the false negative rate, the pass rate, the accuracy, the precision rate, the recall rate and F1 score were 19.2%, 8.2%, 70.1%, 2.5%, 72.6%, 89.2%, 70.0%, 88.3%, 78.1, respectively, Compared with the auto-verification rules, The false negative rate was lower, the false positive rate and the recall rate were slightly higher, and the difference was statistically significant ( P<0.001). Conclusion:A set of the AI verification rules are established and verified by using decision tree algorithm of machine learning, which can identify, intercept and prompt abnormal results stably, and is moresimple, highly efficient and more accurate in the report of blood analysis test results compared with auto-vefication.

In recent years, with the change of natural and social factors, such as climate warming, urbanization, land reclamation, human population growth, change of life customs, and convenient transportation, the human infectious diseases transmitted by insect vectors, well known as insect-borne infectious diseases, has increased significantly, causing a serious threat to public health. This paper focuses on the epidemiology, clinical characteristics, especially laboratory diagnosis of insect-borne infectious diseases, and emphasizes that medical institutions should pay attention to the rapid and accurate laboratory diagnosis of insect-borne infectious diseases. Metagenomic next generation sequencing has potential value in the diagnosis of insect-borne infectious diseases with unknown causes.

Immune checkpoint inhibitors (ICIs) show unique advantages in the treatment of lung cancer, making the treatment of lung cancer enter the era of immunotherapy, but ICIs will also have adverse reactions, and the incidence of immune-induced hematological toxicity is not very high. Immunotherapy-induced thrombocytopenia is a rare adverse event.We report one case of thrombocytopenia induced by ICIs and review the literature on thrombocytopenia associated with ICIs and discuss the clinical features, possible mechanisms, and optimal treatment. 
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Humans ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; Lung Neoplasms/drug therapy* ; Thrombocytopenia/chemically induced* ; Antibodies, Monoclonal, Humanized/adverse effects*

Objective:To investigate the effectiveness of probe-based near-infrared autofluorescence imaging (NIRAF) of the parathyroid gland.Methods:A total of 71 patients with thyroid cancer eligible for admission from May 4, 2023 to May 26, 2023 were selected, including 42 patients with thyroid cancer enrolled in the Department of Thyroid (hernia), Department of General Surgery, PLA General Hospital, including 29 females and 13 males, with a median age of 41 years, ranging from 21 to 76 years. A total of 29 patients with thyroid cancer were enrolled in the Department of Thyroid Surgery of Guangzhou First People’s Hospital, including 22 females and 7 males. The median age was 42.5 years, ranging from 24 to 72 years. The follow-up period was 1 month.Results:Among them, 196 suspicious parathyroid tissues were identified by the naked eye, and 207 suspicious parathyroid tissues were identified by probe NIRAF technology. Naked eye identification sensitivity, specificity and accuracy were 84.86%, 56% and 81.89%. The sensitivity, specificity and accuracy of parathyroid tissue identification by probe NIRAF were 92.66%, 80.00% and 90.53%, which were better than that of naked eye identification, and had a good coincidence rate with the results of immunocolloidal gold test or intraoperative freezing pathology (Kappa=0.61, P<0.001) . Conclusion:The probe-based NIRAF technique has a good ability to identify parathyroid tissue.

Objective:To investigate the clinical and imaging characteristics of central pontine myelinolysis (CPM) without hyponatremia and explore its pathogenesis.Methods:A retrospective analysis was performed. Six CPM patients without hyponatremia, admitted to Department of Neurology, He'nan Provincial People's Hospital from March 2021 to March 2023 were chosen. Demographic information, causes, medical history, clinical presentations, and MRI features at onset, and 1 and 3 months after onset were analyzed. The prognoses were evaluated by modified Rankin Scale (mRS) scores 3 months after onset: mRS scores≤2 was classified as good prognosis, and mRS scores>2 as poor prognosis.Results:In these 6 CPM patients without hyponatremia, 4 were males and 2 females; 4 patients had dizziness, 3 headache, 4 limb weakness, 2 cognitive decline, and 2 slow reaction. Four CPM patients had a history of hypertension, 5 had a history of diabetes, and 1 had a history of alcoholic cirrhosis. Hormone therapy, nutritional support and symptomatic treatment were given; 5 patients had obvious improvement, and 1 had poor prognosis 3 months after onset. MRI showed asymmetrical abnormal signal in the basal pons and bilateral brachium pontis, with T1WI hypointensity, T2WI hyperintensity, T2-FLAIR hyperintensity, DWI hyperintensity and clear boundary, and without obvious mass effect or enhancement. DWI sequence enjoyed good diagnostic sensitivity in early stage of CPM: high signal changes could occur within 24 h of clinical symptoms, and isointensity 3 months after onset.Conclusion:Causes of CPM without hyponatremia are mostly hypokalemia, diabetes, malnutrition, and chronic alcoholism; its characteristic MRI manifestations are "pig nose sign", "bat wing sign" and "trident sign".

Multiple myeloma (MM) is a common malignant hematological tumor in adults, which is characterized by clonal malignant proliferation of plasma cells in the bone marrow and secretion of a large number of abnormal monoclonal immunoglobulins (M protein), leading to bone destruction, hypercalcemia, anemia, and renal insufficiency (Alexandrakis et al., 2015; Yang et al., 2018). Since a large number of new drugs, represented by proteasome inhibitors and immunomodulators, have been successfully used to treat MM, treatment efficacy and survival of patients have been significantly improved. However, due to the high heterogeneity of this disease, patients have responded differently to treatments with these new drugs (Palumbo and Anderson, 2011; Wang et al., 2016; Huang et al., 2020). Growth and survival of MM cells depend on the bone marrow microenvironment, especially numerous inflammatory cytokines secreted by myeloma cells and bone marrow stromal cells, such as vascular endothelial growth factor (VEGF), interleukin (IL)‍-6, transforming growth factor-‍β (TGF‍‍-‍‍β), and IL-10. These cytokines can promote the growth of myeloma cells, induce angiogenesis, and inhibit antitumor immunity, and are often linked to patient prognosis (Kumar et al., 2017). In this era of new drugs, the prognostic values of the serum levels of these cytokines in MM need further evaluation.
Adult ; Humans ; Cytokines ; Disease Progression ; Interleukin-10 ; Interleukin-6/metabolism* ; Multiple Myeloma/drug therapy* ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A