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*

In recent years， the potential anti-tumor effects of metformin have attracted widespread attention in the field of cancer treatment. This article summarizes the research progress of metformin in the treatment of malignant tumors，finding its potential application in the treatment of malignant tumors in the digestive system （biliary tract cancer，gastric cancer，esophagus cancer，colorectal cancer，pancreatic cancer，liver cancer） and reproductive system （prostate cancer，ovarian cancer，breast cancer， cervical cancer），non-small cell lung cancer，renal cell carcinoma，and melanoma. Metformin can inhibit the proliferation of tumor cells and extend the overall survival of patients. Its mechanisms of action include，but are not limited to，inhibiting the activity of mitochondrial complex Ⅰ，activating adenosine monophosphate-activated protein kinase/p53 signaling pathway，and blocking the cell cycle. Additionally，the combined use of metformin with chemotherapy drugs has shown potential for reducing toxicity and enhancing efficacy. It can enhance the sensitivity of biliary tract cancer，ovarian cancer，and melanoma cells to chemotherapy drugs， improve the drug resistance of gastric and colorectal cancer cells to chemotherapy，and reduce the toxic reactions of breast cancer patients during chemotherapy. Metformin is also used as an immunomodulator，applied in the immunotherapy of patients with esophagus cancer，colorectal cancer，cervical cancer，non-small cell lung cancer，and melanoma.

BACKGROUND:Confirming the reliability and validity of the My jump 2 application for measuring lower limb vertical stiffness may offer the possibility of it as an alternative to the Kistler three-dimensional force platform for measuring lower limb stiffness. OBJECTIVE:To verify the reliability and validity of the My Jump 2 application in measuring lower limb vertical stiffness of college students. METHODS:The drop jump data of the participants were collected through the Kistler three-dimensional force platform and the My Jump 2 application,and the vertical stiffness of the participants'lower limb vertical stiffness was calculated.The intraclass correlation coefficient was used to analyze the data measured by the My Jump 2 application and the Kistler three-dimensional force platform,attempting to verify the reliability of the My Jump 2 application.The bias and average between the two devices were drawn into a Bland-Altman diagram to verify the consistency between the two test methods.Finally,the test-retest reliability of the My Jump 2 applications at 30 cm and 40 cm was analyzed using the Cronbach's alpha(α)and coefficient of variation.Pearson product-moment correlation was used to analyze the correlation of My Jump 2 applications. RESULTS AND CONCLUSION:My Jump 2 application has high reliability and validity when measuring the vertical stiffness of the lower limb.At the same time,due to its advantages of low cost,convenient portability and field testing for large samples,it can be used as an alternative to the Kistler three-dimensional force platform to test the vertical stiffness of the lower limb in college students and similar populations.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Purpose/Significance Disease description texts are analyzed to reach a deeper understanding of the current status of on-line consultations for sleep disorders and the thematic characteristics of users with sleep disorders.Method/Process Data about sleep dis-orders from"haodf.com"website is collected by using a web crawler.Furthermore,the main themes about patients'description are i-dentified by the latent Dirichlet allocation(LDA)model.Result/Conclusion The departments of sleep disorders are more dispersed,and the main treatment is drug therapy.Online consultations could improve 83.2％of patients'condition.The themes of patients's disease descriptions include medication and consultation,external environment,description of symptoms,surrogate questions and causes.It is suggested that the platform and doctors should pay attention to the prognosis of patients'medication and mental health status,and pay at-tention to the popularization of comorbidities.

OBJECTIVE: To explore the clinical application value of mineralized collagen (MC) bone scaffolds in repairing various types of skull defects, and to assess the suitability and repair effectiveness of porous MC (pMC) scaffolds, compact MC (cMC) scaffolds, and biphasic MC composite (bMC) scaffolds. METHODS: A retrospective analysis was conducted on the clinical data of 105 patients who underwent skull defect repair with pMC, cMC, or bMC between October 2014 and April 2022. The cohort included 63 males and 42 females, ranging in age from 3 months to 55 years, with a median age of 22.7 years. Causes of defects included craniectomy after traumatic surgery in 37 cases, craniotomy in 58 cases, tumor recurrence or intracranial hemorrhage surgery in 10 cases. Appropriate MC scaffolds were selected based on the patient's skull defect size and age: 58 patients with defects <3 cm² underwent skull repair with pMC (pMC group), 45 patients with defects ≥3 cm² and aged ≥5 years underwent skull repair with cMC (cMC group), and 2 patients with defects ≥3 cm² and aged <5 years underwent skull repair with bMC (bMC group). Postoperative clinical follow-up and imaging examinations were conducted to evaluate bone regeneration, the biocompatibility of the repair materials, and the occurrence of complications. RESULTS: All 105 patients were followed up 3-24 months, with an average of 13 months. No material-related complication occurred in any patient, including skin and subcutaneous tissue infection, excessive ossification, and rejection. CT scans at 6 months postoperatively showed bone growth in all patients, and CT scans at 12 months postoperatively showed complete or near-complete resolution of bone defects in all patients, with 58 cases repaired in the pMC group. The CT values of the defect site and the contralateral normal skull bone in the pMC group at 12 months postoperatively were (1 123.74±93.64) HU and (1 128.14±92.57) HU, respectively, with no significant difference ( t=0.261, P=0.795). CONCLUSION MC exhibits good biocompatibility and osteogenic induction ability in skull defect repair. pMC is suitable for repairing small defects, cMC is suitable for repairing large defects, and bMC is suitable for repairing pediatric skull defects.
Humans ; Tissue Scaffolds ; Male ; Female ; Collagen ; Retrospective Studies ; Adult ; Child ; Adolescent ; Middle Aged ; Child, Preschool ; Skull/surgery* ; Young Adult ; Infant ; Plastic Surgery Procedures/methods* ; Tissue Engineering/methods* ; Craniotomy/methods* ; Bone Regeneration ; Treatment Outcome ; Porosity ; Biocompatible Materials

Zhishi Xiebai Guizhitang is a classical prescription for the treatment of chest impediment with the method of warming Yang. It is included in the Catalogue of Ancient Classical Prescriptions issued by the National Administration of Traditional Chinese Medicine （First Batch）， with the effect of activating Yang， dissipating mass， moving Qi and resolving phlegm. Its main symptoms include chest fullness and pain， or even chest pain radiating to the back， wheezing， coughing， shortness of breath， and Qi reversal from the hypochondrium. In modern traditional Chinese medicine， Zhishi Xiebai Guizhitang is clinically used in the treatment of cardiovascular system， digestive system， respiratory system and other diseases， among which coronary heart disease， unstable angina pectoris， myocardial infarction， sinus bradycardia and other cardiovascular diseases have particularly significant effects. This paper reviewed the pharmacological studies of Zhishi Xiebai Guizhitang in the past 10 years. The results showed that each single medicine and the whole prescription alleviated the above cardiovascular diseases to a certain extent， with the pharmacological effects of improving intravascular environment， myocardial ischemia， myocardial ischemia-reperfusion injury， and myocardial hypoxia， anti-inflammation， plaque stabilisation， etc.， and the pharmacological mechanism involved the regulation of relevant active substances in vivo as well as related signaling pathways and ion channels， mainly including thromboxane B₂ （TXB₂）， prostacyclin I₂（PGI₂） and phosphatidylinositol 3-kinases/protein kinase B/endothelial nitric oxide synthase （PI3K/Akt/eNOS） signaling pathways， and ATP-sensitive potassium channels. In addition， the relationship between the pharmacological effects of some single medicines and transient receptor potential ankyrin 1 （TRPA1） has been reported that TRPA1 is a key to understanding the mechanism of Zhishi Xiebai Guizhitang in treating cardiovascular diseases， which is worth of further study.

Objective:To explore the risk assessment and prevention management of hospital-associated venous thromboembolism (HA-VTE) in plateau area.Methods:This was a prospective observational study. A total of 200 patients hospitalized for acute medical diseases or surgery in the People′s Hospital of Tibet Autonomous Region from May to June 2022 were consecutively enrolled. Padua score or Caprini risk assessment model was used for dynamic risk assessment and stratification of VTE in all patients. At the same time, bleeding risk was assessed according to age, complications, trauma history, drug therapy, invasive procedures and other factors. The implementation of mechanical and/or drug prophylaxis was dynamically recorded during hospitalization. The change of VTE risk and prevention during hospitalization were the primary outcome, and the occurrence of HA-VTE events and bleeding events during hospitalization or within 90 days after enrollment were the secondary outcome.Results:A total of 196 patients were enrolled in the study, including 130 (66.3%) in internal medicine and 66 (33.7%) in surgery. There were 64 (49.2 %) and 27 (40.9%) patients with high risk of VTE within 1 day after admission among medical and surgical patients, respectively. During hospitalization, 58 (44.6%) and 49 (74.2%) patients with high risk of VTE were re-evaluated among medical and surgical patients, respectively. There were 39 (30.0%) medical patients and 54 (81.8%) surgical patients who had an increased risk of VTE due to changes in their conditions. In terms of VTE prevention, 32 patients (16.3%) received VTE prophylaxis, only 17 medical patients (8.7%) with high risk of VTE received drug prophylaxis, and 2 patients (1.0%) with high risk of VTE developed HA-VTE events after drug prophylaxis. A total of 8 (4.1%) surgical patients received drug prophylaxis, of which 1 (0.5%) received mechanical prophylaxis at the same time, and no surgical patients experienced HA-VTE events after prophylaxis. HA-VTE events occurred in 11 patients (5.6%) during hospitalization or within 90 days after enrollment.Conclusion:Considering the complex and changeable risk factors of VTE, insufficient VTE prevention and high incidence of HA-VTE in hospitalized patients in plateau areas, Padua score and Caprini risk assessment model are recommended for early, dynamic and full VTE risk assessment of patients, so as to standardize the VTE prevention and improve the quality of health management of hospitalized patients in plateau areas.

BACKGROUND: Cholecystectomy is a standard surgery for patients suffering from gallbladder diseases, while the causal effects of cholecystectomy on colorectal cancer (CRC) and other complications are still unknown. METHODS: We obtained genetic variants associated with cholecystectomy at a genome-wide significant level ( P value <5 × 10 -8 ) as instrumental variables (IVs) and performed Mendelian randomization (MR) to identify the complications of cholecystectomy. Furthermore, the cholelithiasis was also treated as the exposure to compare its causal effects to those of cholecystectomy, and multivariable MR analysis was carried out to judge whether the effect of cholecystectomy was independent of cholelithiasis. The study was reported based on Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines. RESULTS: The selected IVs explained 1.76% variance of cholecystectomy. Our MR analysis suggested that cholecystectomy cannot elevate the risk of CRC (odds ratio [OR] =1.543, 95% confidence interval [CI]: 0.607-3.924). Also, it was not significant in either colon or rectum cancer. Intriguingly, cholecystectomy might decrease the risk of Crohn's disease (OR = 0.078, 95% CI: 0.016-0.368) and coronary heart disease (OR = 0.352, 95% CI: 0.164-0.756). However, it might increase the risk of irritable bowel syndrome (IBS) (OR = 7.573, 95% CI: 1.096-52.318). Cholelithiasis could increase the risk of CRC in the largest population (OR = 1.041, 95% CI: 1.010-1.073). The multivariable MR analysis suggested that genetic liability to cholelithiasis could increase the risk of CRC in the largest population (OR = 1.061, 95% CI: 1.002-1.125) after adjustment of cholecystectomy. CONCLUSIONS The study indicated that cholecystectomy might not increase the risk of CRC, but such a conclusion needs further proving by clinical equivalence. Additionally, it might increase the risk of IBS, which should be paid attention to in clinical practice.
Humans ; Mendelian Randomization Analysis ; Irritable Bowel Syndrome ; Colorectal Neoplasms/genetics* ; Cholelithiasis/complications* ; Cholecystectomy/adverse effects* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

Objective To construct oligomeric hyaluronic acid(5 KDa)-modified ellagic acid-loaded liposomes(EA-HA-L)to improve the aqueous solubility,in vitro transdermal effect and whitening activity of ellagic acid.Methods Oligomeric hyaluronic acid-modified cholesterol(HA-Chol)was prepared by esterification reaction and structurally characterized by FTIR and 1H NMR;Oligomeric hyaluronic acid-modified ellagic acid-loaded liposomes were prepared by film dispersion-ultrasound method,and the prescribing process was optimized by Box-Behnken design-response surface method,and the particle sizes,the polydispersity index(PDI),zeta potential and encapsulation rate of liposomes under the optimal prescribing process were determined;the difference in solubility between EA-HA-L and free EA was evaluated;in vitro transdermal effect of liposomes were investigated using rat abdominal skin;inhibitory effect on tyrosinase and intracellular tyrosinase in mouse melanoma cells(B16-F10)was surveyed via dopa oxidation method.Results HA-Chol was synthesized and characterized;the optimized prescription process was mass ratio of 10:1 for soy phospholipids to HA-Chol,lipid-drug ratio of 40:1,hydration temperature of 30℃,hydration time of 60 min,ultrasound intensity of 35％,ultrasound time of 21 min,and the particle size of EA-HA-L produced under the optimized prescription process was(140.30±1.30)nm,PDI was(0.29±0.01),the encapsulation rate of ellagic acid was 91.16％±3.06％,and the zeta potential was(-5.67±0.09)mV;after EA was encapsulated by liposomes,the solubility of EA in water increased by about 40-fold;the cumulative transdermal amount of EA-HA-L was 46.98±2.17 μg·cm-2 in 24 h,and the intradermal retention was 66.15±0.61 μg·cm-2,which was 1.72 times higher than that of free EA(P<0.0001)and 1.23 times higher than plain liposome(EA-L)(P<0.01);and the tyrosinase inhibitory activity of EA-HA-L was higher than that of both free EA and EA-L in the EA concentration range of 50-400 μg·mL-1.Conclusion Oligomeric hyaluronic acid-modified ellagic acid-loaded liposomes with small particle size and high encapsulation rate were successfully prepared.EA-HA-L significantly improved the water solubility of EA and possessed better transdermal effect and stronger whitening activity than free EA and EA-L.