OBJECTIVE To mine and analyze adverse event signals associated with inebilizumab， and to provide reference for safe and rational clinical use. METHODS Reports of adverse event related to inebilizumab were collected from the FDA adverse event reporting system （FAERS） database， from Q2 2020 to Q4 2024. Adverse events were standardized and categorized according to the preferred term （PT） and system organ class （SOC） of the Medical Dictionary for Regulatory Activities （MedDRA） version 26.0. Signals were mined using the reporting odds ratio （ROR） method and the Bayesian confidence propagation neural network （BCPNN） method. RESULTS A total of 783 adverse event reports with inebilizumab as the primary suspected drug were identified， involving 297 patients. Most reports originated from the United States and Japan， with physicians being the primary reporters. Female patients outnumbered males， and the most common age group was 45-64 years. Using the ROR method and BCPNN method， a total of 29 valid adverse event signals were detected， involving 12 SOCs and comprising 225 adverse event reports. The five most frequently reported PTs were headache， nausea， fatigue， infectious pneumonia and arthralgia. The five PTs with the strongest signal intensity were： B-cell recovery， decreased blood immunoglobulin G， spinal compression fracture， COVID-19 and acute respiratory distress syndrome. Among the 29 valid signals for adverse event， 19 were not documented in the drug package inserts， involving 10 SOCs and comprising 107 adverse event reports. These encompassed nervous system disorders， general disorders and administration site conditions， eye disorders， among others. CONCLUSIONS Inebilizumab treatment not only causes adverse events documented in the product information， such as infections， immunoglobulin reduction and infusion-related reactions but also leads to potential signals， including B-cell recovery， spinal compression fracture. When using this drug in clinical practice， the patient’s risk of infection and baseline immune status should be assessed， relevant indicators should be closely monitored， and targeted preventive measures should be considered when necessary.

OBJECTIVE: To observe the effect of acupuncture at Jiaji (EX-B2) points on upper limb motor dysfunction in patients after stroke. METHODS: A total of 62 patients with upper limb motor dysfunction after stroke were randomly assigned to an observation group (n=31, 3 cases dropped out) and a control group (n=31, 2 cases dropped out). Both groups received routine medical treatment and rehabilitation training. The control group was treated with conventional acupuncture at the affected side's Jianyu (LI15), Quchi (LI11), Shousanli (LI10), Huantiao (GB30), Yanglingquan (GB34), and Zusanli (ST36) etc. On this basis, the observation group received additional acupuncture at the affected side's Jiaji points from C₄ to T₅. Treatment was administered once daily, five times a week, for four weeks. Motor evoked potential (MEP) latency and amplitude of the abductor pollicis brevis and abductor digiti minimi, Fugl-Meyer assessment for upper extremity (FMA-UE), and Wolf motor function test (WMFT) scores were compared before and after treatment in the two groups. RESULTS: After treatment, both groups showed increased MEP amplitudes and decreased latencies of the abductor pollicis brevis and abductor digiti minimi (P<0.05), as well as increased FMA-UE and WMFT scores (P<0.05); the observation group had greater MEP amplitudes, shorter latencies, and higher FMA-UE and WMFT scores compared to the control group (P<0.05). CONCLUSION Acupuncture at Jiaji (EX-B2) points could enhance the excitability of upper limb motor neural pathways in upper limb motor dysfunction after stroke patients, thereby promoting motor function recovery of the upper limb.
Humans ; Acupuncture Therapy ; Male ; Female ; Middle Aged ; Acupuncture Points ; Stroke/complications* ; Upper Extremity/physiopathology* ; Aged ; Adult ; Stroke Rehabilitation ; Treatment Outcome

In current clinical practice, various dermal templates and skin substitutes are used to enhance wound healing. However, the role of wound commensal microbiome in regulating scaffold performance and the healing process remains unclear. In this study, we investigated the influence of both natural and synthetic scaffolds on the wound commensal microbiome and wound repair in three distinct models including diabetic wounds, burn injuries, and germ-free (GF) wounds. Remarkably, synthetic electrospun polycaprolactone (PCL) scaffolds were observed to positively promote microbiome diversity, leading to enhanced diabetic wound healing compared to the natural scaffolds Integra® (INT) and MatriDerm® (MAD). In contrast, both natural and synthetic scaffolds exhibited comparable effects on the diversity of the microbiome and the healing of burn injuries. In GF wounds with no detectable microorganisms, a reversed healing rate was noted showing natural scaffold (MAD) accelerated wound repair compared to the open or the synthetic scaffold (PCL) treatment. Furthermore, the response of the wound commensal microbiome to PCL scaffolds appears pivotal in promoting anti-inflammatory factors during diabetic wound healing. Our results emphasize that the wound commensal microbiome, mediated by different scaffolds plays an important role in the wound healing process.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Periodontal disease is a risk factor for many systemic diseases such as Alzheimer's disease and adverse pregnancy outcomes. Cleft palate (CP), the most common congenital craniofacial defect, has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection. A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring. However, the precise relationship remains unclear. In this study, the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P. gingivalis injected intravenously and orally into pregnant mice. We investigated an obvious increasing CP (12.5%) in sonicated P. gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium. Then glycolysis and H4K12 lactylation (H4K12la) were detected to elevate in both mouse embryonic palatal mesenchyme (MEPM) cells and macrophages under P. gingivalis exposure which further promoted the transcription of metallopeptidase domain17 (ADAM17), subsequently mediated the shedding of transforming growth factor-beta receptor 1 (TGFBR1) in MEPM cells and mer tyrosine kinase (MerTK) in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate, eventually caused abnormalities in palate fusion and ossification. The abnormal efferocytosis also led to a predominance of M1 macrophages, which indirectly inhibited palatal osteogenesis via extracellular vesicles. Furthermore, pharmacological ADAM17 inhibition could ameliorate the abnormality of P. gingivalis-induced abnormal palate development. Therefore, our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
Animals ; Female ; Porphyromonas gingivalis ; Pregnancy ; Mice ; Cleft Palate/etiology* ; Glycolysis

Objective:To investigate the efficacy and safety of obinutuzumab combined with short-course dexamethasone in patients with relapsed immune thrombocytopenia (ITP) who had previously been treated with rituximab.Methods:A retrospective case series study was conducted. A total of 8 patients with relapsed ITP after treatment with rituximab who received obinutuzumab combined with short-course dexamethasone between January 2023 and January 2024 in the First Affiliated Hospital of Harbin Medical University were collected. The clinical characteristics, changes in platelet counts, changes in peripheral blood B-lymphocyte counts, treatment outcome and treatment-related adverse events were analyzed.Results:There were 1 male and 7 females in 8 patients with relapsed ITP after treatment with rituximab. The median age [ M ( Q1, Q3)] of the 8 enrolled patients was 52.5 (40.5, 56.0) years. The median relapsed times was 2.0 (2.0, 2.5) times and the median course of disease was 16.0 (13.0, 18.5) months. The platelet count increased from 8.73 (5.79, 11.65)×10 9/L pre-treatment to 180.00 (83.40, 255.00)×10 9/L post-treatment, and the difference was statistically significant ( Z = -2.37, P = 0.018); conversely, peripheral blood B-lymphocyte count decreased from 322.59 (148.29, 403.07) × 10 9/L pre-treatment to 1.23 (0.57, 1.76) ×10 9/L post-treatment, and the difference was statistically significant ( Z = -2.52, P = 0.012). After obinutuzumab and short-course dexamethasone treatment, 6 patients achieved complete remission, 1 case showed response, and 1 case had no response. No severe adverse events were observed during treatment and follow-up in all patients. Conclusions:Obinutuzumab combined with short-course dexamethasone appears to be effective in treating relapsed ITP patients after treatment with rituximab, and its safety is good.

In recent years,the incidence rate of type 1 diabetes is on the rise.The causes of the disease are extremely complex,and the pathogenesis has not yet been fully clarified.Different types of studies have confirmed that the occurrence and evolution of type 1 diabetes is a typical process of polygene,multifactor,multi-stage and multi-channel,which is considered to be caused by the combined effect of genetic and environ-mental factors.At present,it is believed that environmental factors are related to the interaction of infection factors,diet factors,early exposure events,intestinal flora,immune factors,other factors and genetic factors.This article reviews the research on environmental factors of type 1 diabetes in recent years.

As a key member of the insulin-like growth factor family， insulin-like growth factor-‍Ⅰ （IGF-‍Ⅰ） is mainly synthesized in the liver and is widely distributed in the human body， and it is involved in the physiological processes such as cell proliferation， differentiation， metabolism， and apoptosis. Studies have shown that the level of IGF-‍Ⅰ is negatively correlated with the severity of liver cirrhosis， and IGF-‍Ⅰ mainly affects the progression of liver cirrhosis by inhibiting liver fibrosis， promoting DNA damage repair， and regulating lipid metabolism. Monitoring of IGF-‍Ⅰ level is expected to provide an evaluation indicator for improving the prognosis of patients with liver cirrhosis， and stimulating the action pathway of IGF-‍Ⅰ or regulating its expression level may become a new method for the treatment of liver cirrhosis. This article reviews the research advances in IGF-‍Ⅰ in liver cirrhosis， in order to provide new ideas for the diagnosis and treatment of liver cirrhosis.

Background/Aims: Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency. Methods: Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations. Results: For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association. Conclusions Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.