BACKGROUND: Inflammation plays a critical role in severe cerebral venous thrombosis (CVT) pathogenesis, but the benefits of anti-inflammatory therapies remain unclear. This study aimed to investigate the association between steroid therapy combined with anticoagulation and the prognosis of acute/subacute severe CVT patients. METHODS: A prospective cohort study enrolled patients with acute/subacute severe CVT at Xuanwu Hospital (July 2020-January 2024). Patients were allocated into steroid and non-steroid groups based on the treatment they received. Functional outcomes (modified Rankin scale [mRS]) were evaluated at admission, discharge, and 6 months after discharge. Serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), cerebrospinal fluid (CSF) IL-6, and intracranial pressure were measured at admission and discharge in the steroid group. Fundoscopic Frisén grades were assessed at admission and 6 months after discharge. Univariate and multivariate logistic regression were used to evaluat associations between steroid use and favorable outcomes (mRS ≤2) at the 6-month follow-up. Paired tests assessed changes in hs-CRP and other variables before and after treatment, and Spearman's correlations were used to analyze relationships between these changes and functional improvements. RESULTS: A total of 107 and 58 patients in the steroid and non-steroid groups, respectively, were included in the analysis. Compared with the non-steroid group, the steroid group had a higher likelihood of achieving an mRS score of 0-2 (93.5% vs . 82.5%, odds ratio [OR] = 2.98, P  = 0.037) at the 6-month follow-up. After adjusting for confounding factors, the result remained consistent. Pulsed steroid therapy did not increase mortality during hospitalization or follow-up, nor did it lead to severe steroid-related complications (all P  >0.05). Patients in the steroid group showed a significant reduction in serum hs-CRP, IL-6, CSF IL-6, and intracranial pressure at discharge compared to at admission, as well as a significant reduction in the fundoscopic Frisén grade at the 6-month follow-up compare to at admission (all P  <0.001). A reduction in serum inflammatory marker levels during hospitalization positively correlated with improvements in functional outcomes ( P  <0.05). CONCLUSION: Short-term steroid use may be an effective and safe adjuvant therapy for acute/subacute severe CVT when used alongside standard anticoagulant treatments, which are likely due to suppression of the inflammatory response. However, these findings require further validation in randomized controlled trials. TRAIL REGISTRATION ClinicalTrials.gov , NCT05990894.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Anticoagulants/therapeutic use* ; C-Reactive Protein/metabolism* ; Interleukin-6/metabolism* ; Intracranial Thrombosis/drug therapy* ; Prospective Studies ; Steroids/therapeutic use* ; Venous Thrombosis/drug therapy*

Clopidogrel effectively inhibits platelet aggregation in response to ADP by irreversibly binding to the platelet P2Y₁₂ receptor through its active metabolite. However, the observed discrepancies between the pharmacokinetics (PK) and pharmacodynamics (PD) of clopidogrel present substantial challenges in individualizing of antiplatelet therapy. To address these challenges, a robust liquid chromatography-tandem mass spectrometry method has been developed to facilitate the real-time assessment of platelet P2Y₁₂ receptor occupancy. This method has been validated in animal models, providing a reliable link between individual PK profiles and PD effects. Target receptor occupancy offers a comprehensive overview of interindividual variations in clopidogrel metabolism, regulation of P2Y₁₂ receptor expression, and platelet turnover. Moreover, it directly correlates with the inhibitory effect on platelet aggregation. The levels of platelet P2Y₁₂ occupancy accurately reflect the extent of clinical factors influencing the PD of clopidogrel, including dosage, drug-drug interactions (DDI), and type 2 diabetes mellitus (T2DM). As a normalized metric, platelet P2Y₁₂ occupancy not only serves potential as a diagnostic tool for personalized clopidogrel therapy but also aids in elucidating the role of the P2Y₁₂ signaling pathway in cases of abnormal on-treatment platelet reactivity.

The clinical and imaging manifestations of the dural arteriovenous fistula(DAVF)located in the great cerebral vein area with progressive bilateral thalamic edema lack specificity and are easily confused with a variety of diseases.The authors reported a case presented with psychiatric and behavioral abnormalities,followed by bilateral thalamic lesions.Initially,the diagnosis was considered as a glioma of the thalamus,encephalitis and straight sinus thrombosis,but the clinical and imaging findings progressively worsened.Through multi-modal imaging examinations,a DAVF in the great cerebral vein territory was finally diagnosed.By reporting the case and reviewing the literature,this paper aimed to explore the clinical manifestations and imaging features of the disease to reduce the incidence of misdiagnosis.

Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16α-carbonitrile (PCN) induced the hepatic and circulating levels of FABP4 and exacerbated ASH in a PXR-dependent manner. Our mechanism study established FABP4 as a transcriptional target of PXR. Treatment with andrographolide, a natural compound and dual inhibitor of PXR and FABP4, alleviated mice from ASH. In summary, our results showed that the PXR-FABP4 gene regulatory axis plays an important role in the progression of ASH, which may have accounted for the contraindication of rifampicin in patients of alcoholic liver disease. Pharmacological inhibition of PXR and/or FABP4 may have its promise in the clinical management of ASH.

d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS, also known as vitamin E-TPGS) is a biodegradable amphiphilic polymer prepared by esterification of vitamin E with polyethylene glycol (PEG) 1000. It is approved by the US Food and Drug Administration (FDA) and has found wide application in nanocarrier drug delivery systems (NDDS). Fully characterizing the in vivo fate and pharmacokinetic behavior of TPGS is important to promote the further development of TPGS-based NDDS. However, to date, a bioassay for the simultaneous quantitation of TPGS and its metabolite, PEG1000, has not been reported. In the present study, we developed such an innovative bioassay and used it to investigate the pharmacokinetics, tissue distribution and excretion of TPGS and PEG1000 in rat after oral and intravenous dosing. In addition, we evaluated the interaction of TPGS with cytochromes P450 (CYP450s) in human liver microsomes. The results show that TPGS is poorly absorbed after oral administration with very low bioavailability and that, after intravenous administration, TPGS and PEG1000 are mainly distributed to the spleen, liver, lung and kidney before both being slowly eliminated in urine and feces as PEG1000. In vitro studies show the inhibition of human CYP450 enzymes by TPGS is limited to a weak inhibition of CYP3A4. Overall, our results provide a clear picture of the in vivo fate of TPGS which will be useful in evaluating the safety of TPGS-based NDDS in clinical use and in promoting their further development.

Objective:To investigate the long-term outcomes of laparoscopic ventral rectopexy (LVR) for obstructive defecation with overt pelvic structural abnormalities.Methods:The retrospective cohort study was conducted. The clinical data of 31 obstructive defecation patients with overt pelvic structural abnormalities who were admitted to the Renji Hospital of Shanghai Jiaotong University School of Medicine from June 2014 to August 2020 were collected. There were 6 males and 25 females, aged 59(range, 32?81)years. All 31 patients underwent LVR through transabdominal approach. Observation indicators: (1) the Cleveland clinic constipation score (CCCS); (2) severity of obstructive defecation; (3) patients assessment of constipation quality of life (PAC-QoL). Follow-up was conducted using telephone interview and outpatient examination up to October 2021. One professional researcher assessed the constipation symptoms and quality of life of patients through outpatient interview or mobile software platform of Questionnaire Star. Measurement data with skewed distribution were represented as M(range), and comparison before and after operation was conducted using the Wilcoxon sign rank test. Results:(1) The CCCS. All 31 patients underwent LVR for the first time and were followed up for 61.8(range, 11.0?87.0)months. The constipation symptoms of the 22 patients were improved. The CCCS of the 31 patients before surgery and at the last follow-up time were 15.8(range, 8.0?26.0) and 10.7(range, 2.0?20.0), respectively, showing a significant difference ( Z=?3.98, P<0.05). (2) Severity of obstructive defecation. The severity scores of frequency of bowel movements, difficult of bowel movements, sensation of incomplete defecation, abdominal distension or pain, time of each bowel movements, daily unsuccessful times of defecation, artificial assisted defecation for the 31 patients were 2.9(range, 1.0?4.0), 3.0(range, 1.0?4.0), 1.9(range, 0?3.0), 0.5(range, 0?3.0), 2.6(range, 2.0?4.0), 2.0(range, 0?4.0), 0.9 (range, 0?2.0) before surgery, versus 1.7(range, 0?4.0), 1.6(range, 0?4.0), 1.2(range, 0?4.0), 0.3(range, 0?3.0), 1.7(range, 0?3.0), 1.4(range, 0?3.0), 0.7(range, 0?2.0) after surgery, respectively. There were significant differences in the frequency of bowel movements, difficult of bowel movements, sensation of in-complete defecation, abdominal distension or pain, time of each bowel movements, daily unsuccessful times of defecation for the 31 patients before and after surgery ( Z=?3.38, ?3.80, ?2.54, ?2.31, ?3.64, ?2.75, P<0.05) and there was no significant difference in the artificial assisted defecation for the 31 patients before and after surgery ( Z=?1.31, P>0.05). (3) PAC-QoL. The score of physical discomfort, satisfaction, worries and concerns, psychological discomfort for the 31 patients were 2.3(range, 1.0?4.0), 3.2(range, 1.0?4.8), 2.2(range, 0.6?4.0), 1.8(range, 0.4?3.9) before surgery, versus 1.6(range, 0?4.0), 2.3(range, 0?4.0), 1.7(range, 0?4.0), 1.3(range, 0?4.0)after surgery, respectively, showing significant differences before and after surgery ( Z=?3.49, ?2.17, ?2.50, ?3.05, P<0.05). Conclusions:The long-term outcomes of LVR for obstructive defecation with overt pelvic structural abnorma-lities are satisfactory. Symptoms as frequency of bowel movements, difficult of bowel movements, sensation of incomplete defecation, abdominal distension or pain, time of each bowel movements and daily unsuccessful times of defecation will be significantly improved after LVR and the constipation quality of life of patients will be improved.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the mechanism of SLE is yet to be fully elucidated. The aim of this study was to explore the role of two-pore segment channel 2 (TPCN2) in SLE pathogenesis. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of TPCN2 in SLE. We performed a loss-of-function assay by lentiviral construct in Jurkat and THP-1 cell. Knockdown of TPCN2 were confirmed at the RNA level by qRT-PCR and protein level by Western blotting. Cell Count Kit-8 and flow cytometry were used to analyze the cell proliferation, apoptosis, and cell cycle of TPCN2-deficient cells. In addition, gene expression profile of TPCN2-deficient cells was analyzed by RNA sequencing (RNA-seq). RESULTS: TPCN2 knockdown with short hairpin RNA (shRNA)-mediated lentiviruses inhibited cell proliferation, and induced apoptosis and cell-cycle arrest of G2/M phase in both Jurkat and THP-1 cells. We analyzed the transcriptome of knockdown-TPCN2-Jurkat cells, and screened the differential genes, which were enriched for the G2/M checkpoint, complement, and interleukin-6-Janus kinase-signal transducer and activator of transcription pathways, as well as changes in levels of forkhead box O, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin, and T cell receptor pathways; moreover, TPCN2 significantly influenced cellular processes and biological regulation. CONCLUSION TPCN2 might be a potential protective factor against SLE.
Apoptosis/genetics* ; Cell Division ; Humans ; Jurkat Cells ; Lupus Erythematosus, Systemic/genetics* ; RNA, Small Interfering/genetics*

As an important part of the construction of national emergency management system, emergency material support is the material basis and important guarantee for the smooth implementation of emergency work. In the face of the outbreak and spread of COVID-19, China′s public health emergency management system and emergency management system have achieved certain results in epidemic prevention and control, but also exposed some shortcomings. The authors summarized the management experience and existing problems of China′s emergency medical materials in storage, production, transportation and deployment during the COVID-19 epidemic, and discussed the management path and method of emergency medical materials in peacetime and wartime, which should be jointly built by the government, society, enterprises and the public. The following suggestions are put forward: multi agent participation in expanding the scope and scale of emergency medical supplies reserve, refining and adjusting the inventory and structure of emergency medical supplies reserve; establishing a supply chain list of emergency medical supplies to ensure the " wartime" production capacity; establishing a comprehensive management information platform for medical materials with " peacetime and wartime integration" ; and improving the awareness and ability of community and family′s " peacetime" medical material reserve.

Objective: To establish a method for the determination ofsamarium oxide and lanthanum oxide by inductively coupled plasmamass spectrometryin the air of workplace. Methods: Samarium, lanthanum and their compounds in the air of workplace were collected through microporous filter. The samples were digested by nitricacid and perhydrol (V/V=4∶1) and detected by inductively coupled plasmamass spectrometry. Results: The linear range ofsamarium oxide and lanthanum oxide was 0-50.00 μg/L, Sm₂O₃: y=0.0119x, r=0.9999; La₂O₃: y=0.0617x, r=0.9998. The detection limits were less than 0.1 μg/L, and the minimum detection concentration were less than 1.52×10^-5 mg/m³. The sampling efficiency were 100%, the recovery rates were 95.70%-102.01%, and the precision were 0.78%-1.58%. Conclusion The indicators established in this study are conformed with the requirements of Chinese Occupational Standars of GBZ/T 210.4-2008, "The Guidelines for the Development of Occupational Hygiene StandarsMehods Part 4: Determination of Chemical Substances in the Air of Workplace".

Long non-coding RNAs (lncRNAs) can promote or inhibit the occurrence and development of pancreatic cancer,lung cancer,gastric cancer and breast cancer by regulating the expression of protein,signal pathway and cell cycle in different ways.Further studies of mechanisms of different lncRNAs in tumors may provide new methods for the diagnosis and treatment of cancers.