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.

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.

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.

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

BackgroundPatients with depressive disorder often exhibit impaired decision-making functions. However， the relationship between decision-making abilities and depressive and anxiety symptoms in these patients remains unclear. ObjectiveTo explore the characteristics of decision-making behavior in patients with depressive disorder， and to analyze its relationship with clinical symptoms. MethodsA total of 48 patients diagnosed with depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were recruited from the Department of Psychosomatic Medicine of the Affiliated Hospital of Southwest Medical University from October 2020 to May 2023. Concurrently， 52 healthy individuals matched for age and gender were recruited from Luzhou as the control group. Beck Depression Inventory （BDI） and Beck Anxiety Inventory （BAI） were used for assessment， and decision-making behavior was evaluated using Probabilistic Reversal Learning （PRL） task. Indicators assessed included the number of trials to criterion， perseverative errors， win-stay rate and lose-shift rate. Spearman correlation analysis was used to assess the correlation between BDI and BAI scores and PRL task indicators. ResultsThe depression group showed a significantly higher lose-shift rate compared with the control group （t=3.684， P<0.01）. There were no statistically significant differences between two groups in trials to criterion， perseverative errors and win-stay rate （t=0.329， 0.132， 0.609， P>0.05）. In depression group， BDI and BAI scores were positively correlated with the win-stay rate（r=0.450， 0.398， P<0.01）. ConclusionPatients with depressive disorder are more likely to change their decision-making strategies following negative outcomes. Furthermore， the severity of depressive and anxiety symptoms is associated with a greater propensity to maintain existing decisions after receiving positive feedback. ［Funded by 2019 Joint Project of Luzhou Science and Technology Bureau-Southwest Medical University （number， 2019LZXNYDJ39］

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.

Objective To study the role of photobiomodulation(PBM)in promoting the repair of spinal cord injury(SCI)by regulating microglial cells.Methods Forty-five C57BL/6J mice were randomly divided into the sham operation(Sham)group,surgery(SCI)group and the treatment(SCI+PBM)group,with 15 mice in each.After laminectomy of the T10 vertebral body in the three groups of mice,the SCI group and the SCI+PBM group were used to construct the model of spinal cord hemisection.The SCI+PBM group received immediate PBM treatment after spinal cord injury,while the other two groups did not.On the 1st,3rd,7th,14th,21st and 28th days(D1,D3,D7,D14,D21,D28)after the operation,the Basso Mouse Scale(BMS)was used to assess the recovery of the hind limb motor function of the mice.On the 28th day post operatively,immunofluorescence was used to detect the changes of neurons in the areas of injury in the three groups of mice.Quantitative real-time PCR and Western blotting experiments were used to detect the phenotypic changes of BV2 cells under the interventions of PBM with inflammatory stimulation.Western blotting experiments were conducted to detect the effects of PBM on the nuclear factor kappa-B(NF-κB)pathway.Results On the 28th day after the operation,the results of the mouse motor assessment showed that the BMS scores and related behaviors of the mice in the SCI+PBM group were better than those of the mice in the SCI group(P＜0.05),and the neurons in the SCI+PBM group far outnumbered those in the SCI group(P＜0.05).The results of quantitative real-time PCR and Western blotting experiments showed that on the 14th day after the operation,PBM promoted the activation of M2-type microglial cells in vivo but inhibited the activation of M1-type microglial cells.In vitro experiments confirmed that PBM could promote the polarization of BV2 cells towards M2-type microglial cells.In addition,PBM inhibited the activation of the NF-κB pathway in injured spinal cords and in activated BV2 cells.Conclusion PBM can promote the repair of spinal cord injury in SCI mice by promoting microglial cells through inhibiting the NF-κB pathway.

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.