Diabetic retinopathy(DR)is a common complication of diabetes.Sodium-glucose cotransporter 2(SGLT-2)inhibitors are widely used in diabetic patients as hypoglycemic drugs and also play a role in the prevention and treatment of DR.At present,there has been no systematic study on the clinical treatment of DR by SGLT-2 inhibitors.This paper re-views the research progress of SGLT-2 inhibitors in the treatment of DR,in order to provide more ideas for the clinical treatment of DR.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective We aimed to investigate the relationship between microscopic pattern of blood stasis and renal pathological grade and related physical and chemical indexes in children with Henoch-Sch?nlein purpura nephritis(HSPN).Methods We conducted a retrospective analysis of 800 HSPN children from the medical records of the First Affiliated Hospital of Henan University of Chinese Medicine.Laboratory indicators(blood routine test,urine routine test,coagulation test,liver function)and renal pathological indicators of them were collected.According to the severity of renal pathological microscopic lesions,the microscopic pattern of blood stasis was divided into three types,including choroidal discord,dead blood coagulation and intracarenal disease accumulation.The classification of renal microscopic pattern of blood stasis and the correlation between laboratory indexes and renal pathological index were analyzed by Spearman grade correlation and binary Logistic regression analysis.Results(ⅰ)There was no statistical difference of the distribution of the renal microscopic pattern of blood stasis in the different traditional Chinese medicine patterns.(ⅱ)There were significant differences in the contents or the grade of albumin and fibrinogen in the HSPN children with different microscopic pattern of blood stasis(all P＜0.05).(ⅲ)The maximum area under the receiver operating characteristic(ROC)curve between fibrinogen and intracarenal disease accumulation was 0.594(95％CI from 0.540 to 0.633,P＜0.001);sensitivity was 0.447,specificity was 0.725;the best threshold on the ROC curve of 0.172 was 3.755 g/L.(ⅳ)There were positive correlations between the content of fibrinogen,ISKDC grade and Bohle A grade respectively with the scores of intracarenal disease accumulation type(r=0.176,r=0.315,r=0.656;all P＜0.001).(ⅴ)There were positive correlations between the content of fibrinogen,ISKDC grade and Bohle A grade respectively with the renal microscopic pattern of blood stasis(r=0.157,r=0.377,r=0.429;all P＜0.001).Conclusion The microscopic renal pattern of blood stasis can not only reflect the severity of renal blood stasis,but also reflect the severity and long-term prognosis of renal diseases.Albumin and urinary protein grade can reflect the early stage of the microscopic renal pattern of the blood stasis(choroidal discord).The content of fibrinogen increases with the aggravation of renal microscopic pattern of blood stasis,reflecting the end-stage of HSPN,which has the correlation with the formation and severity of related indexes.Fibrinogen can be used as a laboratory indicator to assist in the diagnosis of irreversible lesionsin the renal pathology of HSPN children.

Objective To investigate the modeling of Henoch-Sch?nlein purpura nephritis based on data mining,and to provide a reference for the preparation of a standardized Henoch-Sch?nlein purpura nephritis animal model.Methods We searched the CNKI,Wanfang Data,VIP,China Biomedical Literature Database,and PubMed Chinese-English Database by computer to obtain studies of animal experiments relating to Henoch-Sch?nlein purpura nephritis in the past 20 years.The species,modeling method,dosage,dosing cycle,modeling standards,and detection indexes were screened manually,and a database was established by using Microsoft Excel 2021 software for statistical analysis.The association rules of high-frequency indicators were analyzed using SPSS Modeler 18.0,and Cytoscape 3.6.1 was used to visually upgrade the association network diagram.Results A total of 106 articles that met the inclusion criteria were summarized.SD rats and KM mice were the mostly commonly used animal models of Henoch-Sch?nlein purpura nephritis and most studies used drug-induced models.Bovine serum albumin(BSA)+lipopolysaccharide(LPS)+carbon tetrachloride(CCl4)+castor oil,ovalbumin(OVA)+Freund's complete adjuvant,gliadin+Indian ink,and BSA+staphylococcal enterotoxin B(SEB)were used to produce the animal models,generally with cycles of 5～14 weeks.The standard of modeling was skin purpura and increased numbers of urine red blood cells.Proteinuria,glomerular mesangial hyperplasia in kidney tissue,and immune complex mainly composed of immunoglobulin A(IgA)deposited in small blood vessels indicated successful modeling.There were 36 medical indexes,including 23 indexes related to the kidney and urine and nine indexes related to blood.Among these,10 indexes,such as 24 h urine protein quantification,interleukin,renal pathology,urine red blood cell count,IgA,circulating immune complex and creatinine were used in≥10%of cases.Cluster analysis of high-frequency indicators showed that the comprehensive evaluation model of 24 h urinary protein quantification+interleukin+renal pathology+urinary red blood cell count+IgA was mostly used.Conclusions Most existing animal models of Henoch-Sch?nlein purpura nephritis have used male SD rats or female Kunming mice,and most models were induced by drugs.Among these,the method of stasis-heat syndrome combined with IgA nephropathy(disease-syndrome combination method)has the advantages of good repeatability and a high modeling rate,and may thus provide a reference for the selection of animal experimental models of Henoch-Sch?nlein purpura nephritis.

Purpose To evaluate the added value of time of flight(TOF)and point spread dispersion(PSF)reconstruction in mediastinal lymph node metastasis of lung cancer in 18F-FDG PET/CT imaging.Materials and Methods Sixty-eight lung cancer patients with mediastinal lymph node metastasis who underwent PET/CT examination in the First People's Hospital of Foshan from March 9,2020 to July 23,2021 were analyzed retrospectively.The different methods,including ordered subsets estimation maximization(OSEM),OSEM+TOF,OSEM+PSF,OSEM+TOF+PSF,were used to reconstruct the images.The resolution of different reconstruction algorithms for mediastinal lymph node metastasis of lung cancer,as well as the differences of signal-to-noise ratio(SNR)and standard uptake value(SUV)were compared,respectively.Results The highest values of SUVmean,SUVmax and SNR were obtained via OSEM+TOF+PSF method,which increased by 21.99%,22.86%and 60.14%,compared with conventional OSEM method(t=28.321,19.11,11.059,all P<0.01).The difference percentage in smaller lesions that diameter≤22 mm was significantly higher than that in larger lesions that diameter>22 mm(24.1%vs.21.1%,25.3%vs.19.3%,70.6%vs.63.3%;Z=-3.658,-4.313,-2.154,all P<0.05),and the difference percentage in low contrast lesions that SNR≤15.31 was significantly higher than that in high contrast lesions that SNR>15.31(23.6%vs.21.4%,25.3%vs.21.1%,85.7%vs.46.0%;Z=-3.519,-2.336,-5.106,all P<0.05).Among the evaluation results of lesion detectability of different reconstruction algorithms,OSEM+TOF+PSF image showed the mediastinal lymph node metastasis most clearly(87.4%of the lesions were clearly existing),which was significantly higher than that of OSEM image(73.1%of lesions were clearly existing)(χ2=11.704,P=0.001),however,the proportion of lesions clearly existing in OSEM+PSF image did not significantly increase compared with OSEM image(73.1%vs.75.8%;χ2=0.361,P=0.548).Conclusion The combination of TOF and PSF can significantly improve the detection ability,SNR and SUV of mediastinal lymph node metastasis of lung cancer,especially in small and low contrast lesions.

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. In particular, increasing evidence has showed that astrocyte-mediated neuroinflammation is involved in the pathogenesis of PD. As a precious traditional Chinese medicine, bear bile powder (BBP) has a long history of use in clinical practice. It has numerous activities, such as clearing heat, calming the liver wind and anti-inflammation, and also exhibits good therapeutic effect on convulsive epilepsy. However, whether BBP can prevent the development of PD has not been elucidated. Hence, this study was designed to explore the effect and mechanism of BBP on suppressing astrocyte-mediated neuroinflammation in a mouse model of PD. PD-like behavior was induced in the mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg·kg^-1) for five days, followed by BBP (50, 100, and 200 mg·kg^-1) treatment daily for ten days. LPS stimulated rat C6 astrocytic cells were used as a cell model of neuroinflammation. THe results indicated that BBP treatment significantly ameliorated dyskinesia, increased the levels of tyrosine hydroxylase (TH) and inhibited astrocyte hyperactivation in the substantia nigra (SN) of PD mice. Furthermore, BBP decreased the protein levels of glial fibrillary acidic protein (GFAP), cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS), and up-regulated the protein levels of takeda G protein-coupled receptor 5 (TGR5) in the SN. Moreover, BBP significantly activated TGR5 in a dose-dependent manner, and decreased the protein levels of GFAP, iNOS and COX2, as well as the mRNA levels of GFAP, iNOS, COX2, interleukin (IL) -1β, IL-6 and tumor necrosis factor-α (TNF-α) in LPS-stimulated C6 cells. Notably, BBP suppressed the phosphorylation of protein kinase B (AKT), inhibitor of NF-κB (IκBα) and nuclear factor-κB (NF-κB) proteins in vivo and in vitro. We also observed that TGR5 inhibitor triamterene attenuated the anti-neuroinflammatory effect of BBP on LPS-stimulated C6 cells. Taken together, BBP alleviates the progression of PD mice by suppressing astrocyte-mediated inflammation via TGR5.
Humans ; Mice ; Rats ; Animals ; Aged ; Middle Aged ; Parkinson Disease/pathology* ; Astrocytes/pathology* ; Powders/therapeutic use* ; Ursidae/metabolism* ; NF-kappa B/metabolism* ; Neuroinflammatory Diseases ; Neurodegenerative Diseases/metabolism* ; Cyclooxygenase 2/metabolism* ; Lipopolysaccharides/pharmacology* ; Bile ; Mice, Inbred C57BL ; Microglia ; Disease Models, Animal

Vascular access devices are regarded as double-edged swords since being used as lifesaving accesses widely as well as causing vessel catheter associated infections and other complications.In severe cases, it may even endanger life. This paper expounded the importance and necessity of vessel catheter associated infections prevention and control from several aspects such as national policy promotion, medical insurance payment innovation and clinical management demand, analyzed the key links of vessel catheter associated infections prevention and control and the research status quo here and abroad based on the life cycle of the catheter, and pondered the future directions considering the current difficulties and blind spots.

Objective:To investigate the application value of ROX index in evaluating the effect of high-flow nasal cannula oxygen therapy (HFNC) on patients diagnosed with respiratory failure, and to find a simpler and more effective method to observe the efficacy of HFNC.Methods:A retrospective cohort study was conducted. Patients who were admitted to department of critical care medicine of the Tianjin Third Central Hospital from April 2020 to August 2022, diagnosed with type Ⅰ respiratory failure, and treated with HFNC after failure of conventional oxygen therapy were enrolled. Oxygenation index (PaO 2/FiO 2), fraction of inspired oxygen (FiO 2), gas flow rate at the initial time of admission, and pulse oxygen saturation (SpO 2), FiO 2 and respiratory rate (RR) at 2, 4, 6, 8, 10 and 12 hours of HFNC were collected, and ROX index was calculated. The patients with symptoms and PaO 2/FiO 2 improved after HFNC treatment and without higher respiratory support lately were defined as HFNC success, while other patients with symptoms worsening and needing follow-up non-invasive positive pressure ventilation (NIPPV) or invasive positive pressure ventilation (IPPV) were defined as HFNC failure. The tendency of changes in the ROX index at each time point was observed. Receiver operator characteristic curve (ROC curve) was plotted to obtain the optimum cut-off value of ROX index for predicting HFNC outcome and the optimal monitoring time point for HFNC. Results:A total of 142 patients were eventually enrolled, among whom 96 patients (67.61%) were in treated with HFNC successfully, while 46 patients (32.39%) were recorded as HFNC failure (39 patients and 7 patients received NIPPV or IPPV, respectively), with an overall intubation rate of 4.93% (7/142). Compared with the HFNC success group, the HFNC failure group had lower PaO 2/FiO 2 [mmHg (1 mmHg ≈ 0.133 kPa): 208.8±37.3 vs. 235.7±48.3, P < 0.01] and higher initial gas flow rate (L/min: 46.4±3.9 vs. 42.3±4.9, P < 0.01). However, there was no significant difference in gender, age, primary diagnosis, severity of disease, hemoglobin (Hb), C-reactive protein (CRP), and brain natriuretic peptide (BNP) between the two groups. In the HFNC failure group, there were 12 patients (26.09%) received progressive oxygen therapy within 12 hours of HFNC, of which 3 patients (6.52%) occurred within 6 hours, while the other 9 patients (19.57%) occurred after 6 hours. The initial ROX index was not statistically significant between the two groups. Both groups showed a continuous increasing ROX index with longer treatment duration of HFNC, and the ROX index at all of the time points of the HFNC failure group was significantly lower than that of the HFNC success group with statistically significant difference (2 hours: 9.39±2.85 vs. 10.91±3.51, 4 hours: 8.62±2.29 vs. 11.40±3.18, 6 hours: 7.62±1.65 vs. 11.85±3.45, 8 hours: 7.79±1.59 vs. 11.62±3.10, 10 hours: 7.97±1.62 vs. 12.44±2.75, 12 hours: 8.84±2.51 vs. 12.45±3.03, all P < 0.05). The ROC curve analysis showed that the areas under the ROC curve (AUC) of ROX index assessing the effect of HFNC at the time of treating 6, 8 and 10 hours were better than 2, 4 and 12 hours (0.890, 0.903, 0.930 vs. 0.585, 0.738 and 0.829), indicating that the ROX index could determine the efficacy at the early stage of HFNC (within 6 hours). When the optimum cut-off value of ROX index was 8.78, the sensitivity was 90.6%, and the specificity was 76.5%. Conclusion:The ROX index at 6 hours of HFNC has a certain predictive value for the efficacy of HFNC with an optimum cut-off value of 8.78, which can provide clinical health care personnel a method for observing the efficacy of HFNC, and guide the correct selection of oxygen therapy modality at an early stage and timely adjustment of oxygen therapy strategy.

OBJECTIVE: To investigate the clinical and prognostic characteristics of primary acute myeloid leukemia (AML) with 11q23/KMT2A rearrangements. METHODS: Clinical data of 90 patients with primary AML and 11q23/KMT2A rearrangements were analyzed retrospectively. RESULTS: By karyotyping analysis, 80 of the 90 patients had translocations involving 11q23/KMT2A, with t(9;11)(p22;q23), t(6;11)(q27;q23), t(10;11)(p12;q23) and t(11;19)(q23;p13) being the most common ones, while 10 cases were found to have non-translocation abnormalities. The overall complete remission (CR) rate was 75.6%, and patients with t(6;11) had lower CR rate compared with non-t(6;11) patients (47.1% vs. 82.2%, P = 0.005). After a median follow-up of 24.5 months, the patients receiving allo-hematopoietic stem cell transplantation (allo-HSCT) had significantly higher 3-year overall survival (OS) (80.3% vs. 16.6%, P < 0.001) and 3-year event-free survival (EFS) (73.5% vs. 16.3%, P < 0.001) compared with non-transplant patients. Patients with t(6;11) had the lowest 3-year OS (11.8% vs. 56.0%, P < 0.001) and 3-year EFS (5.9% vs. 53.8%, P < 0.001) compared with other type of abnormalities. No significant difference was noted in the survival between patients with t(9;11) and non-t(9;11) regardless whether they had received HSCT. CONCLUSION The clinical characteristics of primary AML with 11q23/KMT2A rearrangements are heterogeneous. Patients did not receive HSCT had poorer survival, particularly with the presence of t(6;11). Allo-HSCT could significantly improve the survival of such patients.
Humans ; Retrospective Studies ; Leukemia, Myeloid, Acute/therapy* ; Translocation, Genetic ; Gene Rearrangement ; Prognosis

ObjectiveTo investigate the regulatory effect of Mankuining Formula （MKNF） on the gut microbiota and the NOD-like receptor （NLR）P3/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway-mediated inflammation in dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） mice. MethodSixty SPF C57BL/6 mice were randomly divided into a blank group， a model group， a MKNF group （20 g·kg^-1）， and a mesalazine group （0.266 g·kg^-1）， with 15 mice in each group. The UC model was induced in mice by freely drinking a 3% DSS solution for 7 days. After 12 hours of modeling， the treatment groups received daily oral administration， while the other groups received an equal volume of normal saline by gavage. Daily body weight and disease activity index （DAI） were recorded. On the 8th day， mice were euthanized after anesthesia， and the colon and feces were collected. The colon length was measured， and histopathological changes were observed after hematoxylin-eosin （HE） staining. Tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） levels in the colon were detected by enzyme-linked immunosorbent assay （ELISA）. The differences in gut microbiota among the groups were analyzed using 16S rRNA sequencing technology. The protein content of NLRP3/Caspase-1/GSDMD in colon tissues was detected by Western blot. ResultCompared with the blank group， mice in the model group showed increased DAI （P<0.01）， shortened colon length （P<0.01）， severe colon mucosal damage， elevated levels of TNF-α， IL-1β， and IL-18 （P<0.01）， increased protein content of NLRP3/Caspase-1/GSDMD in colon tissues （P<0.01）， altered gut microbiota structure with decreased abundance of Actinobacteria， Bacteroidetes， and Proteobacteria， and increased abundance of Firmicutes at the phylum level. At the genus level， there was a decrease in Lactobacillus， Alloprevotella， and Yersinia， and an increase in Bacteroides， Bacillus， and Lachnospiraceae_NK4A136. Compared with the model group， the MKNF group and the mesalazine group showed a significant reduction in DAI after the 3^rd day （P<0.01）， a significant increase in colon length （P<0.01）， alleviated colon inflammation and mucosal structural damage， and decreased TNF-α， IL-1β， and IL-18 levels in the colon （P<0.01）， reduced protein content of NLRP3/caspase-1/GSDMD in colon tissue （P<0.05， P<0.01），an increase in the abundance of Proteobacteria and Bacteroidetes， and a decrease in Firmicutes at the phylum level. ConclusionMKNF can alleviate UC-induced colonic inflammation， reduce colon damage， and improve dysbiosis of the gut microbiota by inhibiting the classical pyroptosis pathway.