ObjectiveTo investigate the improvement effect of Qibai Pingfei capsules on pulmonary vascular remodeling in rats at different stages of chronic obstructive pulmonary disease （COPD） and to analyze its possible mechanism of action. MethodsMale Sprague-Dawley （SD） rats were randomly divided into a normal group， an early COPD model group， an advanced COPD model group， an early-intervention high-dose group， a late-intervention high-dose group， an early-intervention low-dose group， a late-intervention low-dose group， an early-intervention pyrrolidine dithiocarbamate （PDTC） group， and a late-intervention PDTC group， with 15 rats in each group. A rat model of early COPD was constructed by using cigarette smoke combined with airway infusion using lipopolysaccharide（LPS）， and a rat model of advanced COPD was constructed by using airway infusion with LPS， cigarette smoke， and hypoxia. All groups except the normal group were given LPS airway drops on days 1 and 14 of the experiment， smoked for 1 h per day， and administered the drug once a day for 40 weeks from day 15 onward. In the high- and low-dose groups， rats were given 1 g·kg^-1 and 250 mg·kg^-1 Qibai Pingfei capsules， respectively by gavage， and in PDTC groups， rats were given 100 mg·kg^-1 of PDTC by intraperitoneal injection. The advanced COPD model group underwent 6 h of hypoxia per day in weeks 5-6. Lung function and mean pulmonary artery pressure were tested in rats. Morphologic changes in lung tissues were detected by hematoxylin-eosin（HE）staining. Collagen deposition in lung tissues was examined by Masson staining， and the levels of inflammatory factors including interleukin-1β（IL-1β）， interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α）in lung tissues were detected by enzyme-linked immunosorbent assay （ELISA）. The number of inflammatory cells in the alveolar lavage fluid of rats in each group was detected by Giemsa staining， and the protein expression of Toll-like receptor 4（TLR4）， myeloid differentiation factor 88（MyD88）， nuclear factor-κB（NF-κB）， TNF-α， vascular endothelial-cadherin（VE-cadherin）， α-smooth muscle actin（α-SMA）， and platelet endothelial cell adhesion molecule-1（CD31） was detected by Western blot in the lung tissues of rats. ResultsCompared with the normal group， the model group showed significantly decreased forced expiratory volume in 0.3 s （FEV_0.3）， forced vital capacity （FVC）， and FEV_0.3/FVC ratio related to lung function （P<0.05）， thickening of pulmonary vasculature， increased collagen deposition in the lungs， and enhanced mean pulmonary arterial pressure and expression levels of IL-6， IL-1β， and TNF-α （P<0.05）. Additionally， the model group also exhibited increased numbers of macrophages， lymphocytes， and neutrophils （P<0.05）， significantly higher protein expression of TLR4， MyD88， NF-κB， TNF-α， and α-SMA （P<0.05）， and significantly lower protein expression of VE-cadherin and CD31 （P<0.05）. Lung function was significantly improved in the Qibai Pingfei capsules groups compared with the model group （P<0.05）， with mean pulmonary arterial pressure reduced and pulmonary vascular thickening and collagen deposition in the lungs ameliorated. The Qibai Pingfei capsules groups also showed reduced expression levels of IL-6， IL-1β， and TNF-α （P<0.05） and decreased numbers of macrophages， lymphocytes， and neutrophils （P<0.05）， as well as reduced protein expression of TLR4， MyD88， NF-κB， TNF-α， and α-SMA （P<0.05） and elevated protein expression of VE-cadherin and CD31 （P<0.05） in rat lung tissues. ConclusionQibai Pingfei capsules inhibits inflammatory response and endothelial-to-mesenchymal transition probably by regulating the TLR4/NF-κB signaling pathway， thus improving pulmonary vascular remodeling in COPD model rats and showing therapeutic effects in the early stage of COPD.

As the brain's resident immune cells, microglia perform crucial functions such as phagocytosis, neuronal network maintenance, and injury restoration by adopting various phenotypes. Dynamic imaging of these phenotypes is essential for accessing brain diseases and therapeutic responses. Although numerous probes are available for imaging pro-inflammatory microglia, no PET tracers have been developed specifically to visualize anti-inflammatory microglia. In this study, we present an ¹⁸F-labeled PET tracer (QTFT) that targets the P2Y₁₂, a receptor highly expressed on anti-inflammatory microglia. [¹⁸F]QTFT exhibited high binding affinity to the P2Y₁₂ (14.43 nmol/L) and superior blood-brain barrier permeability compared to other candidates. Micro-PET imaging in IL-4-induced neuroinflammation models showed higher [¹⁸F]QTFT uptake in lesions compared to the contralateral normal brain tissues. Importantly, this specific uptake could be blocked by QTFT or a P2Y₁₂ antagonist. Furthermore, [¹⁸F]QTFT visualized brain lesions in mouse models of epilepsy, glioma, and aging by targeting the aberrantly expressed P2Y₁₂ in anti-inflammatory microglia. In a pilot clinical study, [¹⁸F]QTFT successfully located epileptic foci, showing enhanced radioactive signals in a patient with epilepsy. Collectively, these studies suggest that [¹⁸F]QTFT could serve as a valuable diagnostic tool for imaging various brain disorders by targeting P2Y₁₂ overexpressed in anti-inflammatory microglia.

Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To evaluate the effect of combining contralateral high-frequency transcranial magnetic stimulation (rTMS) with biofeedback-controlled empty swallowing training on dysphagia among stroke survivors.Methods:Eighty dysphagic stroke survivors were divided at random into a control group, a biofeedback group, an rTMS group and a combined treatment group, each of 20. In addition to routine dysphagia rehabilitation, the biofeedback group and the rTMS group received empty swallowing training based on biofeedback or high-frequency rTMS applied to the healthy motor cortex as appropriate. The combined treatment group was given both. The treatment was administered once daily, 5 days a week for 3 consecutive weeks. Before and after the treatment, all of the subjects′ swallowing was evaluated using the penetration aspiration scale (PAS), functional oral intake scale (FOIS) and a standardized swallowing assessment (SSA). The latency and amplitude of the mylohyoid muscle′s motor evoked potentials (MEPs) were also recorded before and after the treatment.Results:After the treatment, significant improvement was observed in the average PAS, FOIS and SSA scores as well as in the latency and amplitude of the MEPs in the four groups. The average results in the combined treatment group were significantly better than in the other 3 groups. The latency of the mylohyoid muscle′s MEP was significantly shorter in the combined group than in the control and biofeedback groups on average, while the amplitude was significantly greater than in the control group.Conclusion:Combining contralateral high frequency rTMS with empty swallowing training based on biofeedback can better improve the swallowing of dysphagic stroke survivors.

Objective:To explore the clinical features and genetic etiology of a patient with adult-onset globoid cell leukodystrophy/Krabbe disease (KD).Methods:A patient who was admitted to the Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology on February 15, 2022 due to exacerbation of right leg weakness for over 4 years was selected as the study subject. Clinical data and results of medical imaging and genetic analysis were analyzed. Candidate variants were verified by family analysis.Results:The patient, a 36-year-old woman, had spasmodic gait as the primary presentation. Cranial magnetic resonance imaging (MRI) revealed symmetrical abnormalities in the bilateral corticospinal tracts, and the activity of β-galactocerebrosidase (GALC) in her white blood cells was significantly decreased. The patient was found to harbor compound heterozygous variants of the GALC gene, namely c.461C>A (p.Pro154His) and c. 1901T>C (p.Leu634Ser). Her mother, sister and nephew were heterozygous carriers of the c. 461C>A (p.Pro154His) variant, whilst her father was heterozygous for the c.1901T>C (p.Leu634Ser) variant. Conclusion:The patient was ultimately diagnosed with adult-onset KD, for which the compound heterozygous variants of the GALC gene may be accountable.

Objective:To analyze the correlation between serum antibody titers of anti-contactin associated protein-like 2 (CASPR2) antibody and clinical features and prognosis in encephalitis.Methods:A retrospective analysis was conducted on the clinical data of 31 patients diagnosed with anti-CASPR2 antibody encephalitis at the First Affiliated Hospital of Zhengzhou University from January 2018 to April 2024. Patients were divided into low titer group (≤1∶32) and high titer group (>1∶32) based on serum anti-CASPR2 antibody titers, and their clinical characteristics, auxiliary examination results, and prognosis were compared between the two groups.Results:Among the 31 patients with anti CASPR2 antibody encephalitis (male∶female=1∶1.4), there were 16 cases in the low titer group and 15 cases in the high titer group; The age of patients in the high titer group was (33.9±17.9)years, which was lower than that of patients in the low titer group [(52.9±17.9)years], and the difference was statistically significant ( P=0.006). The proportion of patients with prodromal infection in the high titer group (6/15) was higher than that in the low titer group (1/16, P=0.037). There was no statistically significant difference in the cerebrospinal fluid related test results, imaging examination of intracranial abnormal lesions, abnormal electroencephalogram, serum abnormal tumor markers, and serum abnormal rheumatic immune indicators between the two groups of patients (all P>0.05). During hospitalization, one patient in the high titer group died; During the follow-up period, one patient died and three patients relapsed, all of whom were in the high titer group. During follow-up, the mRS scores of 6 patients ranged from 3 to 5 points (indicating functional impairment), with 4 cases in the high titer group and 2 cases in the low titer group. The proportion of patients with poor prognosis in the high titer group (9/15) was higher than that in the low titer group (2/16), and the difference was statistically significant ( P=0.021). Conclusions:Patients with high serum anti-CASPR2 antibody titers and encephalitis have a lower age of onset and are prone to pre infection triggers. High antibody titers may be associated with a higher risk of disease recurrence and poor prognosis for patients.

Objective To observe the clinical efficacy of dynamic joint mobilization combined with core stability training in the treatment of nonspecific low back pain.Methods 60 patients with nonspecific low back pain were randomly assigned into either the treatment group or control group.Each group had 30 patients.The treatment group received a therapeutic regimen combining dynamic joint mobilization and core stability training,while the control group only received core stability training.Both groups were evaluated for therapeutic effectiveness using the Visual Analogue Scale(VAS)for pain,the Oswestry Disability Index(ODI),and the range of motion(ROM)of the lumbar spine before treatment,and at the 1st,3rd,and 6th weeks after treatment.At the conclusion of the treatment,a thorough assessment of the overall therapeutic efficacy was performed.Results At the 1st,3rd,and 6th weeks post-treatment,both groups showed statistically significant differences in VAS scores,ODI scores,and ROM scores over time(P＜0.05).The improvements in these indices were significantly greater in the treatment group compared to the control group(P＜0.05).The treatment group had considerably higher therapeutic effective-ness compared to the control group(P＜0.05).Conclusions Dynamic joint mobilization combined with core stabil-ity training is effective in treating nonspecific low back pain.It can help with pain relief,lumbar and back function restoration,and lumbar and back mobility improvement.This approach is worthy of clinical application and promotion.