PURPOSE: The secondary damage of spinal cord injury (SCI) starts from the collapse of the blood spinal cord barrier (BSCB) to chronic and devastating neurological deficits. Thereby, the retention of the integrity and permeability of BSCB is well-recognized as one of the major therapies to promote functional recovery after SCI. Previous studies have demonstrated that activation of hypoxia inducible factor-1α (HIF-1α) provides anti-apoptosis and neuroprotection in SCI. Endogenous HIF-1α, rapidly degraded by prolylhydroxylase, is insufficient for promoting functional recovery. Dimethyloxalylglycine (DMOG), a highly selective inhibitor of prolylhydroxylase, has been reported to have a positive effect on axon regeneration. However, the roles and underlying mechanisms of DMOG in BSCB restoration remain unclear. Herein, we aim to investigate pathological changes of BSCB restoration in rats with SCI treated by DOMG and evaluate the therapeutic effects of DMOG. METHODS: The work was performed from 2022 to 2023. In this study, Allen's impact model and human umbilical vein endothelial cells were employed to explore the mechanism of DMOG. In the phenotypic validation experiment, the rats were randomly divided into 3 groups: sham group, SCI group, and SCI + DMOG group (10 rats for each). Histological analysis via Nissl staining, Basso-Beattie-Bresnahan scale, and footprint analysis was used to evaluate the functional recovery after SCI. Western blotting, TUNEL assay, and immunofluorescence staining were employed to exhibit levels of tight junction and adhesion junction of BSCB, HIF-1α, cell apoptosis, and endoplasmic reticulum (ER) stress. The one-way ANOVA test was used for statistical analysis. The difference was considered statistically significant at p < 0.05. RESULTS: In this study, we observed the expression of HIF-1α reduced in the SCI model. DMOG treatment remarkably augmented HIF-1α level, alleviated endothelial cells apoptosis and disruption of BSCB, and enhanced functional recovery post-SCI. Besides, the administration of DMOG offset the activation of ER stress induced by SCI, but this phenomenon was blocked by tunicamycin (an ER stress activator). Finally, we disclosed that DMOG maintained the integrity and permeability of BSCB by inhibiting ER stress, and inhibition of HIF-1α erased the protection from DMOG. CONCLUSIONS Our findings illustrate that the administration of DMOG alleviates the devastation of BSCB and HIF-1α-induced inhibition of ER stress.
Spinal Cord Injuries/pathology* ; Animals ; Apoptosis/drug effects* ; Amino Acids, Dicarboxylic/therapeutic use* ; Recovery of Function/drug effects* ; Rats ; Rats, Sprague-Dawley ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Male ; Spinal Cord/blood supply*

Objective To explore the correlation between lymphoscintigraphy stage of breast cancer-related lymphedema(BCRL)before treatments and the therapeutic effect of liposuction combined with lymphatic-venous anastomosis(LVA).Methods Data of 67 BCRL patients who received liposuction combined with LVA 3 months later were retrospectively analyzed.The patients were divided into partial(P-stage)and total obstruction(T-stage)groups according to lymphoscintigraphic findings of the affected upper limb lymphatic before treatments.Bilateral upper limb lymphedema index(UELi),the percentage of excess UELi(UPE)of the affected limb lymphedema,the ratio of before treatments UPE to post treatments UPE(rUPE)of the affected limb,as well as the lymphedema functioning,disability and health questionnaire for the affected upper limb lymphedema(Lymph-ICF-UL)score 3 and 6 months after treatments were recorded.The clinical parameters and improvements of the affected upper limb lymphedema were compared between groups.Results Lymphoscintigraphy before treatment showed 29 cases in P-stage group and 38 cases in T-stage group.Significant differences of the incidence of cellulitis before treatments and volume of fat particles extracted were found between groups(both P＜0.05).Three and 6 months after treatments,UELi and UPE of the affected limb and Lymph-ICF-UL scores of all 67 patients were lower than those before treatments(all P＜0.05).Conclusion Lymphoscintigraphy stage of BCRL before treatments was correlated with therapeutic effect of liposuction combined with LVA.

Objective To evaluate and compare the success rate and short-term clinical prognosis of transfemoral transcatheter aortic valve replacement(TF-TAVR)for patients with pure aortic regurgitation(PAR)of different annulus sizes.Methods This study is a single center retrospective study,selecting symptomatic PAR patients who received TF-TAVR treatment at Zhongshan Hospital Fudan University from September 2019 to September 2023.Based on preoperative CT results,all patients were divided into three groups:Group A(aortic annulus circumference＜80 mm),Group B(80 mm≤aortic annulus circumference＜85 mm),and Group C(aortic annulus circumference≥ 85 mm).The primary endpoint was success rate and 30d all-cause mortality,while the secondary endpoint was TAVR related complications.Results A total of 61 PAR patients were included in this study,including 27 in Group A,21 in Group B,and 13 in Group C.The overall success rate is 82.0％,and the 30 d all-cause mortality rate is 3.3％.The success rate of Group C patients was significantly lower(P=0.012),with higher rates of conversion to surgery and valve-in-valve implantation(P=0.022 and P=0.040).In terms of secondary endpoint events,there were no significant differences among the three groups in major bleeding events,major vascular complications,stroke,myocardial infarction,newly developed atrial fibrillation,implantation of new pacemakers,coronary artery occlusion,and postoperative moderate to severe perivalvular leakage(all P＞0.05).Conclusions The circumference of the aortic valve annulus is a key factor affecting the success rate of TF-TAVR in PAR,and PAR patients with an aortic valve annulus circumference less than 85mm may be more suitable for TF-TAVR.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Objective To explore the acupoint selection rules of acupuncture and moxibustion for the treatment of chronic pelvic pain in women through data mining techniques,and analyse the research hotspots and frontiers in this field with the help of visual analysis tools.Methods The clinical research literature of acupuncture and moxibustion for the treatment of chronic pelvic pain in women,which was included in China National Knowledge Infrustruction(CNKI),Wanfang Data Knowledge Service Platform(Wanfang),China Science and Technology Journal Database(VIP),and PubMed from the time of establishment of the database to September 2023 was searched.Noteexpess 3.9 was used for de-weighting,Excel 2016 was used to plot the volume of publications,IBM SPSS Modeler 18.0 was used for correlation analysis of acupoints,and Vosviewer 1.6.18 and Citespace 6.3.R1 were used to visual analysis authors and keywords.Results Data mining included 278 Chinese literature and 15 English literature,of which contains a total of 314 sets of acupoint prescriptions and 94 acupoints.The core acupoints included Guanyuan(RN4),Sanyinjiao(SP6),Zhongji(RN3),etc.The association analysis showed that Sanyinjiao-Zhongji and Guanyuan-Zhongji had the highest level of support;the high-frequency meridians included conception vessel(CV),spleen and stomach meridians,etc.;and the commonly used specific acupoints were rendezvous points.The top four authors in terms of publications were Wang Xin,Meng Zhen-Zhen,Liao Mu-Xi,and Duan Zhi-Fang;the keyword hotspots were mainly about therapies,such as acupuncture and moxibustion,acupuncture,and warming-needle moxibustion.Conclusion Acupuncture and moxibustion for the treatment of chronic pelvic pain in women has a certain rules of selecting and using acupoints,and the hotspots of research are mainly based on clinical treatment,and the research on the mechanism is weak,which is expected to become a hotspot in the future.

Bronchial asthma is a common chronic respiratory disease, which is involved in a variety of cells and cellular components. In 2019, the guidelines for the diagnosis and treatment of asthma issued by the Global Initiative for Asthma (GINA) Committee put forward the concept of type 2 inflammatory asthma for the first time. The updated evolution of GINA guidelines has promoted the development of biological agents and disease treatment, providing effective prevention and treatment for patients with severe asthma and improving disease outcome. This paper expounds the disease mechanism and management suggestions of type 2 inflammatory asthma in GINA guidelines, and analyzes the relevant clinical studies on targeted treatment of type 2 inflammatory asthma in recent years, in order to provide reference for in-depth understanding of level 3 prevention and management of patients with type 2 inflammatory asthma.
Humans ; Asthma/prevention & control*

Bronchial asthma is a common chronic respiratory disease, which is involved in a variety of cells and cellular components. In 2019, the guidelines for the diagnosis and treatment of asthma issued by the Global Initiative for Asthma (GINA) Committee put forward the concept of type 2 inflammatory asthma for the first time. The updated evolution of GINA guidelines has promoted the development of biological agents and disease treatment, providing effective prevention and treatment for patients with severe asthma and improving disease outcome. This paper expounds the disease mechanism and management suggestions of type 2 inflammatory asthma in GINA guidelines, and analyzes the relevant clinical studies on targeted treatment of type 2 inflammatory asthma in recent years, in order to provide reference for in-depth understanding of level 3 prevention and management of patients with type 2 inflammatory asthma.
Humans ; Asthma/prevention & control*

Insomnia is extremely common and is a risk factor for a variety of physical and psychological disorders in addition to contributing to the reduced quality of life of patients and the burden of healthcare costs. Although cognitive behavioral therapy is the first-line treatment for insomnia, its difficulty of access and high cost have hindered its application. Therefore, pharmacotherapy remains the common treatment choice for patients and clinicians. Existing chemical drugs including benzodiazepine receptor agonists, dual orexin receptor antagonists, melatonin and its receptor agonists, histamine antagonists, antidepressants, and antipsychotics are able to induce and/or maintain sleep and have good therapeutic effects on acute insomnia, but their efficacy on chronic insomnia is indefinite. Furthermore, they have several side effects and affect sleep structure and physiological function. Under the guiding principle of holistic view and treatment based on syndrome differentiation, traditional Chinese medicine(TCM) has shown a good effect in clinical practice, but with little high-grade clinical evidence. The mechanism, dose, half-life period, adjustment of sleep structure, and side effects of hypnotic drugs are key factors to be considered for clinical use. This paper analyzed and summarized the drugs for insomnia from the above aspects, and is expected to provide references for the application and development of sedative and hypnotic drugs.
Humans ; Sleep Initiation and Maintenance Disorders/chemically induced* ; Quality of Life ; Sleep ; Hypnotics and Sedatives/pharmacology* ; Antidepressive Agents/pharmacology*