ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

Objective:To investigate the efficacy and safety of endovascular therapy (EVT) for early neurological deterioration (END) in patients with minor stroke due to acute anterior circulation large vessel occlusion.Methods:Consecutive patients with mild stroke due to acute anterior circulation large vessel occlusion admitted to Mianyang Central Hospital from October 2015 to October 2023 were included retrospectively. Minor stroke was defined as a baseline National Institutes of Health Stroke Scale (NIHSS) score <6. END was defined as an increase of ≥4 in NIHSS score compared to baseline within 12 hours of onset. According to whether EVT was performed or not, they were divided into EVT group and standard medical treatment (SMT) group. At 90 days after onset, the modified Rankin Scale was used to evaluate the outcome. 0-1 was defined as excellent outcome (primary outcome measure) and 0-2 was defined as good outcome (secondary outcome measure). The safety endpoints included symptomatic intracranial hemorrhage (sICH) within 72 hours after EVT and all-cause mortality within 90 days. Multivariate logistic regression analysis was used to determine the correlation between EVT and clinical outcome. Results:A total of 164 patients with minor stroke due to acute anterior circulation large vessel occlusion were included. Eighty-four patients (51.2%) developed END, of which 52 (61.9%) underwent EVT and 32 (38.1%) received SMT; 60 patients (71.4%) had excellent outcome, and 64 (76.2%) had good outcome. There was no significant difference in demographic and baseline clinical data between the EVT group and the SMT group. The excellent outcome rate of the EVT group at 90 days after onset showed a trend higher than that of SMT group (78.8% vs. 59.4%; χ2=3.680, P=0.055), but there was no significant difference in the good outcome rate and safety endpoints between the two groups. Multivariate logistic regression analysis showed that after adjusting for confounding factors, EVT was significantly and independently associated with excellent outcome at 90 days (odds ratio 4.955, 95% confidence interval 1.331-22.284; P=0.024). Conclusion:For patients with minor stroke due to anterior circulation large vessel occlusion who experience END, EVT may improve their functional outcome without increasing the risk of sICH and mortality.

Objective To investigate the impact of Qizhi Jiangtang Capsule (QZJT) on renal damage in diabetic nephropathy (DN) mice via NOD like receptors family pyrin domain containing 3/caspase-1/ Gasdermin D (NLRP3/caspase-1/GSDMD) signaling pathway. Methods Mice were randomly allocated into six experimental groups: a normal control group (NC), a diabetic nephropathy model group (DN), a low-dose QZJT treatment group (L-QZJT), a high-dose QZJT treatment group (H-QZJT), a positive control group administered Shenqi Jiangtang Granules (SQJT), and an ML385 group (treated with an inhibitor of nuclear factor erythroid 2-related factor 2, Nrf2). Upon successful model induction, therapeutic interventions were commenced. Renal function impairment in the mice was evaluated through quantification of fasting blood glucose (FBG), 24-hour urinary albumin (UAlb), serum creatinine (SCr), blood urea nitrogen (BUN), and the kidney-to-body mass ratio (K/B). Renal tissue pathology was evaluated using HE and PAS staining. Serum levels of inflammatory cytokines IL-1β and IL-18 were quantified by ELISA. Levels of podocyte markers and proteins involved in relevant pathways were assessed using Western blot analysis. Results Compared with the NC group, FBG, 24 h UAlb, SCr, and BUN were increased in the DN group, and the K/B mass ratio was also increased. In contrast, compared with the DN group, FBG, 24 h UAlb, SCr, and BUN in both the low-dose (L-QZJT) and high-dose Quanzhou Jintang (H-QZJT) groups were decreased, and the K/B mass ratio was decreased as well. The therapeutic efficacy of H-QZJT was comparable to that of Shenqi Jiangtang Granules. QZJT ameliorated renal histopathological injury in DN mouse, increased the protein levels of Nephrin (a podocyte marker), and decreased the protein levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), pro-caspase-1, and GSDMD-N. After ML385 treatment, renal cells exhibited swelling and morphological changes, the inflammatory infiltrate area was enlarged, the protein levels of NLRP3, ASC, pro-caspase-1, and GSDMD-N were up-regulated, and the levels of IL-1β and IL-18 were increased. Conclusion QZJT may inhibit podocyte pyroptosis by acting on the Nrf2 to regulate the NLRP3/caspase-1/GSDMD pathway, thus improving renal damage in DN mouse.
Animals ; Diabetic Nephropathies/pathology* ; Podocytes/pathology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Pyroptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 1/genetics* ; Signal Transduction/drug effects* ; Mice ; Phosphate-Binding Proteins/genetics* ; Male ; Intracellular Signaling Peptides and Proteins/metabolism* ; Mice, Inbred C57BL ; Kidney/pathology* ; Gasdermins

ObjectiveTo observe the effect of gene mutation on the effectiveness of arsenic-containing Chinese herbal compound formulas in the treatment of myelodysplastic syndromes （MDS） of different traditional Chinese medicine （TCM） patterns， so as to provide the basis for the clinical application. MethodsClinical data of 442 MDS patients who were treated with arsenic-containing herbal compound formulas were retrospectively collected， including the baseline demographic and clinical characteristics of the patients. Based on the TCM four examinations， the patients were divided into the spleen-kidney deficiency group as well as the qi-yin deficiency group， and according to the results of the next-generation sequencing （NGS） test， they were divided into the group with and without gene mutation respectively. The influence of gene mutation on the clinical effectiveness of patients with different TCM patterns was analyzed， the baseline demographic and clinical characteristics of the patients with different outcomes of the two TCM patterns were compared， and multivariate Logistic regression analysis was conducted on the influencing factors of the effective rate of MDS patients with gene mutation. ResultsA total of 190 cases were included in the spleen-kidney deficiency group （119 cases with gene mutation） and 43 cases in the qi-yin deficiency group （23 cases with gene mutation）. No statistically significant differences were noted in effectiveness assessment， total effective rate， and total response rate between the spleen-kidney deficiency group and the qi-yin deficiency group （P＞0.05）. In the spleen-kidney deficiency group， the total effective rate of MDS with gene mutation was 65.55% （78/119）， which was lower than 80.28% （57/71） of MDS without gene mutation， with statistical significance （P = 0.033）， while no statistical differences in effectiveness assessment and total response rate were noted （P＞0.05）. In the qi-yin deficiency group， no statistical differences were observed in effectiveness assessment， total effective rate， and total response rate of the patients in with or without gene mutation （P＞0.05）. In the spleen-kidney deficiency group with gene mutation， the rate of complex karyotype （P = 0.031） and the mutation rate of CBL gene （P = 0.032） in the ineffective population were higher than those in the effective population， while the mutation rate of DDX41 gene in the effective population was higher than that in the ineffective population （P = 0.033）. No statistically significant differences were found in other gene mutations， age， gender distribution， number of gene mutations， bone marrow hyperplasia degree， blast cell range， reticular fiber tissue proliferation or not， and prognosis of chromosomal abnormalities between the effective and ineffective populations （P＞0.05）. In the qi-yin deficiency group with gene mutation， no statistically significant differences were found in various items between populations with different outcomes （P＞0.05）. Multivariate Logistic regression analysis showed that complex karyotype， CBL mutation， and DDX41 mutation were independently associated with the effective rate of MDS with spleen-kidney deficiency and gene mutation （P＜0.05）. DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group （OR＞1）， while complex karyotype and CBL mutation were independent risk factors （OR＜1）. ConclusionThe arsenic-containing TCM compound formulas exhibited better effectiveness in MDS with spleen-kidney deficiency pattern without mutation； and in MDS with spleen-kidney deficiency pattern without complex karyotypes， CBL mutation， and with DDX41 mutations. Furthermore， DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group， while complex karyotype and CBL mutation were independent risk factors. In MDS with qi-yin deficiency pattern， gene mutation-related factors showed no significant impact on the effectiveness of arsenic-containing TCM compound formulas.

Objective To investigate the regulatory role of the programmed cell death protein 1 (PD-1) and its ligand programmed cell death protein ligand 1 (PD-L1) signaling on the subtypes and functions of natural killer (NK) cells at the maternal-fetal interface during the second trimester in mice following Toxoplasma gondii infection during the first trimester. Methods Twelve 6- to 8-week-old female mice of the C57BL/6J strain were divided into a control group and an infection group, of 6 mice in each group. On the 6.5th day of pregnancy (Gd6.5), each pregnant mouse in the infection group was intraperitoneally injected with 150 tachyzoites of the Toxoplasma gondii PRU strain, while mice in the control group were injected with an equal volume of physiological saline. On the 12.5th day of pregnancy (Gd12.5), uterus and placenta tissues were sampled from pregnant mice for pathological observations, and the mRNA expression levels of PD-1, PD-L1, and tumor necrosis factor-α (TNF-α) were quantified in uterus and placenta tissues. The PD-1 and DX5 expression was measured on NK cells at the maternal-fetal interface using flow cytometry. In addition, the in vitro JEG-3 trophoblast cells and NK-92MI cells co-culture system was established as the control group, and the addition of T. gondii tachyzoites in the co-culture system served as the infection group. The PD-1, PD-L1, and DX5 mRNA expression was quantified in cells using real-time fluorescence quantitative reverse transcription PCR (RT-qPCR) assay, and the TNF-α concentration was measured in the cell culture supernatant using enzyme-linked immunosorbent assay (ELISA). Results On Gd12.5, clear and intact cellular structures of placental decidual tissues were seen in pregnant mice in the control group, with no remarkable abnormal changes found in the uterine columnar epithelial cells, and inflammatory cell infiltration and blood stasis at varying degrees were found in uterine and placental tissues from pregnant mice in the infection group. The relative PD-1, PD-L1, and TNF-α mRNA expression was (1.004 ± 0.004), (1.001 ± 0.001), and (1.001 ± 0.001) in uterine tissues from pregnant mice in the control group and (2.480 ± 0.720), (3.355 ± 0.920), and (2.391 ± 0.073) in the infection group, respectively. The relative PD-1, PD-L1, and TNF-α mRNA expression was (1.007 ± 0.010), (1.006 ± 0.006), and (1.001 ± 0.001) in the uterine tissues in the control group and (6.948 ± 1.918), (3.225 ± 1.034), and (1.536 ± 0.150) in the infection group, respectively. The relative PD-1, PD-L1, and TNF-α mRNA expression was higher in both the uterine (t = 3.55, 4.43 and 33.02, all P values < 0.05) and placental tissues (t = 5.36, 3.72 and 6.18, all P values < 0.05) in the infection group than in the control group. Flow cytometry showed that the proportions of PD-1⁺ NK cells, PD-1⁺ DX5⁺ NK cells, and DX5⁺ NK cells were (12.200 ± 1.082)%, (9.373 ± 7.728)%, and (44.000 ± 4.095)% in uterine tissues from pregnant mice in the control group, and (21.733 ± 1.630)%, (18.767 ± 1.242)%, and (73.367 ± 0.611)% in the infection group, respectively. The proportions of PD-1⁺ NK cells, PD-1⁺ DX5⁺ NK cells, and DX5⁺ NK cells were (1.100 ± 0.510)%, (2.277 ± 1.337)%, and (96.167 ± 2.831)% in placental tissues from mice in the control group, and (26.867 ± 9.722)%, (23.433 ± 6.983)%, and (82.467 ± 2.248)% in the infection group, respectively. The proportions of PD-1⁺ NK cells (t = 8.45, P < 0.05) and DX5⁺ NK cells (t = 12.29, P < 0.05) were higher in uterine tissues from pregnant mice in the infection group than in the control group, and no significant difference was seen in the proportion of PD-1⁺ DX5⁺ NK cells (Z = -1.09, P > 0.05). The proportions of PD-1⁺ NK cells (t = 4.58, P < 0.05) and PD-1⁺ DX5⁺ NK cells (t = 5.15, P < 0.05) were higher in placental tissues from pregnant mice in the infection group than in the control group, while the proportion of DX5⁺ NK cells was lower in the infection group than in the control group (t = -6.56, P < 0.05). RT-qPCR assay revealed that the relative PD-1, PD-L1, and DX5 mRNA expression was (1.010 ± 0.005), (1.002 ± 0.003), and (1.001 ± 0.001) in the JEG-3 cells and NK92MI cells co-culture system and (3.638 ± 1.258), (0.397 ± 0.158), and (4.267 ± 1.750) in the control group, and ELISA measured that the TNF-α concentration was higher in the cell culture supernatant in the infection group [(22.056 ± 3.205) pg/mL] than in the control group [(12.441 ± 0.001) pg/mL] (t = 5.20, P < 0.05). The PD-1(t = 3.62, P < 0.05) and DX5 mRNA expression (t = 3.23, P < 0.05) was higher in the infection group than in the control group, and the PD-L1 mRNA expression was lower in the infection group than in the control group (t = -6.63, P < 0.05). Conclusions Following T. gondii infection, both PD-L1 expression and PD-1 expression on DX5⁺ NK cells at the maternal-fetal interface are upregulated in mice during the second trimester; however, the proportion of DX5⁺ NK cells decreases. These findings suggest that PD-1/PD-L1 signaling may suppress NK cell functions by modulating DX5⁺ NK cell subsets.

Stroke is a critical health issue in China, and carotid artery stenosis and plaque play key roles in its prevalence. Despite the acknowledged significance of this condition, detailed information regarding the prevalence of carotid artery stenosis and plaque across the Chinese population has been scarce. This study analyzed data from the China Stroke High-risk Population Screening and Intervention Program for 2020-2021, focusing on 194 878 Chinese adults aged 40 years and above. It assessed the prevalence of carotid artery stenosis and plaque and identified their associated risk factors. Results revealed a standardized prevalence of 0.40% for carotid artery stenosis and 36.27% for carotid plaque. Notably, the highest rates of stenosis were observed in north and south China at 0.61%, while southwestern China exhibited the highest plaque prevalence at 43.17%. Key risk factors included older age, male gender, hypertension, diabetes, stroke, smoking, and atrial fibrillation. This study highlights significant geographical and demographic disparities in the prevalence of these conditions, underlining the urgent need for targeted interventions and policy reforms. These measures are essential for reducing the incidence of stroke and improving patient outcomes, addressing this significant health challenge in China.
Humans ; China/epidemiology* ; Male ; Female ; Prevalence ; Middle Aged ; Carotid Stenosis/epidemiology* ; Risk Factors ; Aged ; Adult ; Plaque, Atherosclerotic/epidemiology* ; Stroke/epidemiology* ; Aged, 80 and over

BACKGROUND:Circular RNAs(circRNAs)play important roles in a variety of diseases or tumors,and recent findings have revealed that circRNAs are abnormally expressed in knee osteoarthritis and are involved in disease progression through microRNA/mRNA regulation. OBJECTIVE:To investigate the effect of circRNA WD repeat containing protein 1(circ-BRWD1)/miR-488-3p/DNA methyltransferase 3A(DNMT3A)on the proliferation and apoptosis of chondrocytes in knee osteoarthritis. METHODS:Real-time fluorescence quantitative PCR was performed to detect the expression of circ-BRWD1,miR-488-3p,DNMT3A in knee osteoarthritis chondrocytes.Cells were divided into si-NC group,si-circ-BRWD1 group,vector group,circ-BRWD1 group,si-circ-BRWD1+anti-miR-NC group,si-circ-BRWD1+anti-miR-488-3p group,miR-NC group,miR-488-3p group,anti-miR-NC group,anti-miR-488-3p group,miR-488-3p+vector group,miR 488-3p+DNMT3A group.Real-time fluorescence quantitative PCR was used to detect circ-BRWD1,miR-488-3p,DNMT3A expression,MTT and flow cytometry assay were used to detect cell proliferation and apoptosis.Western blot assay was used to detect DNMT3A and proliferation/apoptosis-related protein expression.Dual luciferase reporter assay was used to Dual luciferase reporter assay to detect the targeting relationship of circ-BRWD1 with miR-488-3p and miR-488-3p with DNMT3A. RESULTS AND CONCLUSION:circ-BRWD1 and DNMT3A were highly expressed and miR-488-3p was lowly expressed in knee osteoarthritis chondrocytes compared with normal chondrocytes.Knockdown of circ-BRWD1 or overexpression of miR-488-3p inhibited proliferation and induced apoptosis in knee osteoarthritis chondrocytes.circ-BRWD1 targeted negative regulation of miR-488-3p and inhibition of miR-488-3p reversed the effect of circ-BRWD1 knockdown on chondrocyte proliferation and apoptosis in knee osteoarthritis.miR-488-3p targeted negative regulation of DNMT3A and upregulation of DNMT3A reversed the effect of miR-488-3p overexpression on chondrocyte proliferation and apoptosis in knee osteoarthritis.circ-BRWD1 could regulate the expression of DNMT3A by regulating miR-488-3p.To conclude,knockdown of circ-BRWD1 inhibits chondrocyte proliferation and induces apoptosis in knee osteoarthritis,and the mechanism of action may be related to the regulation of miR-488-3p/DNMT3A axis.

Objective:To explore the risk factors for duodenal papillary adenocarcinoma by comparing the differences in clinical and endoscopic features between patients with duodenal papillary adenomas and adenocarcinomas.Methods:This study retrospectively included patients diagnosed as having duodenal papillary adenocarcinoma and adenoma from January 1st 2018 to June 1st 2023 at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School. Demographic, clinical manifestations, laboratory tests, imaging, endoscopic and pathological characteristics of patients with adenomas and adenocarcinomas were collected and compared. Multivariable logistic regression analysis was employed to identify high-risk factors for duodenal papillary adenocarcinoma.Results:A total of 119 cases of adenocarcinoma and 171 cases of adenoma were included. There were statistically significant differences between the two groups in terms of patient age, body mass index (BMI), clinical symptoms, family history of malignant tumors, bile duct dilation, pancreatic duct dilation, lesion size, adenoma site classification, stage assessed by EUS, and involvement of the bile and pancreatic ducts ( P<0.05). Univariate logistic regression analysis revealed that non-ampullary lesions, involvement not limited to the major duodenal papilla assessed by EUS, involvement of the bile and pancreatic ducts assessed by EUS, age ≥60 years, lesion size ≥1.5 cm, clinical symptoms, family history of malignant tumors, bile duct dilation, and pancreatic duct dilation were risk factors for duodenal papillary adenocarcinoma. Multivariate logistic regression analysis showed that non-ampullary lesions ( OR=7.00, 95% CI:1.44-34.15, P=0.016), involvement not limited to the major duodenal papilla assessed by EUS ( OR=13.77, 95% CI: 4.69-40.45, P<0.001), age ≥60 years ( OR=2.52, 95% CI: 1.23-5.18, P=0.011), bile duct dilation ( OR=2.58, 95% CI: 1.12-5.94, P=0.026), and lesion size ≥1.5 cm ( OR=2.76, 95% CI:1.36-5.59, P=0.005) were independent risk factors for duodenal papillary adenocarcinoma. Conclusion:This study shows the independent risk factors for duodenal papillary adenocarcinoma, which include non-ampullary lesions, involvement not limited to the major duodenal papilla assessed by EUS, age ≥60 years, bile duct dilation, and lesion size ≥1.5 cm.

Objective To investigate the safety and efficacy of sodium fluorescein-guided microsurgery in children with medulloblastoma,and to analyze the surgical efficacy and prognosis.Among them,12 cases underwent unilateral telovelar approach,2 cases underwent bilateral telovelar approach,and 6 cases underwent telovelar approach combined with transvermian approach.The intraoperative dose of sodium fluorescein was 2 mg/kg.Methods The clinical data of 20 patients with medulloblastoma treated with fluorescein sodium assisted microsurgery from January 2018 to August 2023 in Xinjiang Autonomous Region People's Hospital were retrospectively analyzed.Results Of the 20 patients,12 were male and 8 were female.The mean age of onset was(7.9±3.7)years.In all cases,there was clear tumor fluorescence,none of the cases had adverse reaction associated with the use of sodium fluorescein.There were 16 cases of gross-total resection,3 cases of near-total resection,1 case of partial resection,1 case of intracranial infection,2 case of subcutaneous effusion,2 cases of cerebellar mutism.The follow-up time was from 3 to 72 months.5 cases did not receive sufficient radiotherapy and chemotherapy,and 9 cases died due to tumor progression or recurrence.In all cases,the longest overall survival was 72 months,the mean survival time was 39.2 months,and the median survival time was 41.2 months.Conclusion Fluorescein sodium assisted microsurgery is safe and effective in pediatric medulloblastoma surgery.

In this paper,a case of toxic epidermal necrolysis(TEN)after application of tigecycline in an elderly patient was analyzed,and was analyzed and discussed combined with domestic and foreign literature.According to the criteria for assessing the association of adverse drug reactions,the TEN present in this patient is likely to be related to tigecycline.It is suggested that clinicians and pharmacists should be vigilant and pay attention to TEN that may be caused by tigecycline in clinical work.