The ubiquitination modification of henipavirus (HNV) M protein is essential for its nuclear-cytoplasmic trafficking and viral budding, but the precise regulatory mechanism has remained unclear. A recent study published in Emerging Microbes & Infections demonstrated that the RAD6A-RAD18 ubiquitination complex plays a unique and pivotal role in the nuclear-cytoplasmic trafficking of the HNV M protein and the process of viral budding. Furthermore, this study revealed that treating cells with TZ9 (a RAD6 inhibitor) or RAD18 RING domain-binding peptides markedly impaired the ubiquitination level of HNV M protein, resulting in its nuclear retention and subsequent impairment of viral budding and replication. These findings lay a theoretical foundation for the development of novel antiviral drugs and specific antiviral therapies targeting HNV infections, and provide valuable references for investigating the biological functions of M protein’s ubiquitination as well as the replication and pathogenic mechanisms of other paramyxoviruses.

The ubiquitination modification of henipavirus (HNV) M protein is essential for its nuclear-cytoplasmic trafficking and viral budding, but the precise regulatory mechanism has remained unclear. A recent study published in Emerging Microbes & Infections demonstrated that the RAD6A-RAD18 ubiquitination complex plays a unique and pivotal role in the nuclear-cytoplasmic trafficking of the HNV M protein and the process of viral budding. Furthermore, this study revealed that treating cells with TZ9 (a RAD6 inhibitor) or RAD18 RING domain-binding peptides markedly impaired the ubiquitination level of HNV M protein, resulting in its nuclear retention and subsequent impairment of viral budding and replication. These findings lay a theoretical foundation for the development of novel antiviral drugs and specific antiviral therapies targeting HNV infections, and provide valuable references for investigating the biological functions of M protein’s ubiquitination as well as the replication and pathogenic mechanisms of other paramyxoviruses.

Objective To explore the cut-off values of mean corpuscular volume(MCV)and mean corpuscular hemoglobin(MCH)for thalassemia screening among pregnant women in Sichuan.Taking genetic testing as the golden standard,the efficacy of MCV or MCH,Hb electrophoresis alone,MCV or MCH combined with Hb electrophoresis in thalassemia screening of pregnant women was evaluated.Methods A total of 554 pregnant women with red blood cell parameters MCV ≤90fl or MCH≤29pg were catagorized in the study group.All 554 pregnant women were tested for Hb electrophoresis and thalassemia gene.At the same time,640 pregnant women who had been excluded thalassemia by genetic test were catagorized in the control group randomly.The Receiver Operating Characteristic(ROC)curves was drawn by software SPSS 23.0 to find out the cut-off values and efficacy of MCV or MCH in screening thalassemia of pregnant women.The efficacy of MCV or MCH,Hb electrophoresis alone,MCV or MCH combined with Hb electrophoresis in thalassemia screen-ing of pregnant women was analyzed.Results A totla of 159 pregnant women were diagnosed as thalassemia by genetic testing(28.7％,159/554).There are 108 cases of α-thalassemia(67.9％,108/159),47 cases of β-thalassemia(29.6％,47/159),and 4 cases ofα-combined β-thalassemia(2.5％,4/159).The most common gene types of α-thalassemia were-α3.7/αα(29.6％,47/159)and--SEA/αα(27.7％,44/159).The most common gene type of β-thalassemia was β-CD17(11.3 percent,18/159).The level of Hb,MCV and MCH of pregnant women with thalassemia was lower than that in the control group.The level of Hb,MCV and MCH of pregnant women with β thalassemia was lower than that with α thalassemia.The level of Hb,MCV and MCH of pregnant women with-SEA/αα thalassemia was lower than that with-α3 7/αα thalassemia.The differences were all statistically significant(P＜0.05).The cut-off value of MCV and MCH for screening thalassemia was 84.4 fl and 28.1pg,respectively.When using 84.4fl as the cut-off value of MCV to screen thalassemia,the sensitivity and specificity was 90％and 78％,respectively.When using 28.1pg as the cut-off value of MCH to screen thalassemia,the sensitivity and specificity was 92％and 81％,respectively.Taking genetic testing as the gold standard,comparing the cut-off value of MCV or MCH with MCV or MCH screening method,when screening the 554 pregnant women with Hb electrophoresis alone,the result showed lower sensitivity and higher rate of missed diagnoses.All differences were statistically sig-nificant(P＜0.05).When screening thalassemia in the study group by using MCV or MCH combined with Hb electrophoresis,the speci-ficity was much lower.All differences were statistically significant(P＜0.05).Conclusion The most common α-thalassemia gene types were-α3.7/αα and--SEA/αα in Sichuan.The most common β-thalassemia gene type was CD17.The appropriate cut-off value of MCV and MCH for screening thalassemia among pregnant women in Sichuan was 84.4 fl and 28.lpg,respectively,with high sen-sitivity and specificitym and low rate of missing diagnoses.Using Hb electrophoresis alone for screening thalassemia kept higher rate of missing diagnoses.While using Hb electrophoresis combined with MCV or MCH for screening thalassemia did not reduce the rate of missed diagnoses.

Aim To investigate the effect of hypobaric hypoxia on macrophage necroptosis and atherosclerotic plaque instability and explore the underlying mechanisms.Methods Mouse bone marrow-derived macrophages were i-solated and cultured,and divided into control group(21％oxygen concentration)and hypoxia group(3％oxygen concen-tration).After 48 hours,cell necroptosis was detected,and the expression of cell necroptosis related proteins was deter-mined by Western blot.Healthy male ApoE-/-mice were randomly divided into control group and hypobaric hypoxia group.After the intervention for 16 weeks,the plasma lipids and inflammatory cytokines were measured,the areas of ath-erosclerotic plaque and necrotic core were evaluated by HE staining.The content of plaque collagen was detected by Mas-son staining.The number of macrophages in the plaque and the expression of necrotic apoptosis related proteins were de-tected by immunohistochemical staining and Western blot.Results Hypoxia induced increased necrotic apoptosis of macrophages(P＜0.01),while necroptotic inhibitor necrostatin-1(Nec-1)reduced hypoxia induced cell death(P＜0.05);hypoxia leads to a decrease in the expression of adenosine deaminase acting on RNA 1(ADAR1)in macrophages(P＜0.01),and an increase in the expression of Z-DNA binding protein 1(ZBP1),phosphorylated receptor-interacting serine/threonine-protein kinase(p-RIPK3),and phosphorylated mixed lineage kinase domain-like protein(p-MLKL)(all P＜0.01).Compared with the control group,the plasma lipid levels of ApoE-/-mice in the hypobaric hypoxia group did not change significantly(P＞0.05),the plasma inflammatory cytokines(TNF-α,IL-1β,IL-6 and MCP-1)increased(all P＜0.05),the area of atherosclerotic plaque increased(P＜0.05),the area of plaque necrotic core increased,the content of plaque collagen decreased,the number of macrophages increased,the expression of ADAR1 decreased,and the expres-sion of ZBP1 and p-MLKL increased(all P＜0.01).Conclusion Hypobaric hypoxia causes the imbalance of A-DAR1/ZBP1 expression in macrophages,activates RIPK3/MLKL signaling pathway,promotes macrophage necroptosis,in-creases the area of plaque necrosis core,and leads to increase instability of atherosclerotic plaque.

Objective To investigate the clinical characteristics,diagnosis and treatment of ileal injury secondary to percutaneous nephrolithotomy percutaneous nephrolithotomy(PCNL).Methods The diagnosis and treatment of a patient were reviewed,and relevant literature were retrieved.Results The patient was a 41-year-old male,who underwent stage PCNL(initial percutaneous nephrostomy,followed by secondary PCNL)due to right ureteral calculi with severe hydronephrosis.On postoperative day 1,he developed abdominal distension and pain.Abdominal X-ray revealed subdiaphragmatic free gas,and CT showed pelvic and abdominal fluid and gas accumulation,suggesting peritonitis due to intestinal perforation.Emergency exploratory laparotomy identified a 3 mm×3 mm ileal perforation approximately 30 cm from the ileocecal valve,which was repaired surgically.The patient recovered well and was discharged after one week,with no discomfort reported during a 6-month follow-up.Conclusion The clinical features of ileal injury secondary to PCNL include early postoperative abdominal distension,pain and peritonitis.Diagnosis relies on clinical manifestations,abdominal X-ray and CT,with surgical exploration if necessary.Conservative management under vigilant observation can be cautiously adopted for localized injuries,while surgical repair is required for peritonitis or failed conservative therapy.

Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.

Objective To explore the cut-off values of mean corpuscular volume(MCV)and mean corpuscular hemoglobin(MCH)for thalassemia screening among pregnant women in Sichuan.Taking genetic testing as the golden standard,the efficacy of MCV or MCH,Hb electrophoresis alone,MCV or MCH combined with Hb electrophoresis in thalassemia screening of pregnant women was evaluated.Methods A total of 554 pregnant women with red blood cell parameters MCV ≤90fl or MCH≤29pg were catagorized in the study group.All 554 pregnant women were tested for Hb electrophoresis and thalassemia gene.At the same time,640 pregnant women who had been excluded thalassemia by genetic test were catagorized in the control group randomly.The Receiver Operating Characteristic(ROC)curves was drawn by software SPSS 23.0 to find out the cut-off values and efficacy of MCV or MCH in screening thalassemia of pregnant women.The efficacy of MCV or MCH,Hb electrophoresis alone,MCV or MCH combined with Hb electrophoresis in thalassemia screen-ing of pregnant women was analyzed.Results A totla of 159 pregnant women were diagnosed as thalassemia by genetic testing(28.7％,159/554).There are 108 cases of α-thalassemia(67.9％,108/159),47 cases of β-thalassemia(29.6％,47/159),and 4 cases ofα-combined β-thalassemia(2.5％,4/159).The most common gene types of α-thalassemia were-α3.7/αα(29.6％,47/159)and--SEA/αα(27.7％,44/159).The most common gene type of β-thalassemia was β-CD17(11.3 percent,18/159).The level of Hb,MCV and MCH of pregnant women with thalassemia was lower than that in the control group.The level of Hb,MCV and MCH of pregnant women with β thalassemia was lower than that with α thalassemia.The level of Hb,MCV and MCH of pregnant women with-SEA/αα thalassemia was lower than that with-α3 7/αα thalassemia.The differences were all statistically significant(P＜0.05).The cut-off value of MCV and MCH for screening thalassemia was 84.4 fl and 28.1pg,respectively.When using 84.4fl as the cut-off value of MCV to screen thalassemia,the sensitivity and specificity was 90％and 78％,respectively.When using 28.1pg as the cut-off value of MCH to screen thalassemia,the sensitivity and specificity was 92％and 81％,respectively.Taking genetic testing as the gold standard,comparing the cut-off value of MCV or MCH with MCV or MCH screening method,when screening the 554 pregnant women with Hb electrophoresis alone,the result showed lower sensitivity and higher rate of missed diagnoses.All differences were statistically sig-nificant(P＜0.05).When screening thalassemia in the study group by using MCV or MCH combined with Hb electrophoresis,the speci-ficity was much lower.All differences were statistically significant(P＜0.05).Conclusion The most common α-thalassemia gene types were-α3.7/αα and--SEA/αα in Sichuan.The most common β-thalassemia gene type was CD17.The appropriate cut-off value of MCV and MCH for screening thalassemia among pregnant women in Sichuan was 84.4 fl and 28.lpg,respectively,with high sen-sitivity and specificitym and low rate of missing diagnoses.Using Hb electrophoresis alone for screening thalassemia kept higher rate of missing diagnoses.While using Hb electrophoresis combined with MCV or MCH for screening thalassemia did not reduce the rate of missed diagnoses.

Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.

ObjectiveTo explore the effectiveness and potential mechanism of Shugan Jianpi Granules （疏肝健脾颗粒） combined with Chushi Zhiyang Ointment （除湿止痒软膏） in the treatment of atopic dermatitis with sleep disturbance of liver constraint and spleen deficiency syndrome. MethodsSixty-six patients with atopic dermatitis combined with sleep disturbance of liver constraint and spleen deficiency syndrome were randomly divided into 33 cases each in the treatment group and the control group. Both groups were treated with Chushi Zhiyang Ointment for external use. The treatment group additionally received Shugan Jianpi Granules orally， one dose per day； and the control group received cetirizine hydrochloride tablets orally， 10mg per day， taken before bedtime. Both groups were under the treatment for 4 weeks. Clinical effectiveness was evaluated after treatment， and the SCORing Atopic Dermatitis （SCORAD） index， pruritus visual analog scale （VAS） score， Insomnia Severity Index （ISI） score， and Pittsburgh Sleep Quality Index （PSQI） score were recorded before and after treatment， and serum levels of melatonin （MLT）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-13 （IL-13）， and tumor necrosis factor-α （TNF-α） were measured. The patients were also tested for blood routine， liver function and kidney function before and after treatment， and the occurrence of adverse events was also observed. ResultsThe total effective rate in the treatment group （90.63%， 29/32） was significantly higher than that in the control group （66.67%， 20/30， P＜0.05）. After the interventions， the scores for SCORAD， VAS， ISI， and PSQI， as well as the levels of IL-4， IL-6， IL-13， and TNF-α， were significantly reduced in both groups. In contrast， the MLT levels in treatment group significantly elevated compared to that before treatment （P＜0.05）. Comparing between the two groups after treatment， the scores of SCORAD， ISI， PSQI， and VAS， as well as the levels of serum IL-4 and IL-13 in the treatment group were significantly lower than those in the control group， while the MLT levels were markedly higher than that in the control group （P＜0.05 or P＜0.01）. There was no obvious abnormality in blood routine， liver function and kidney function in both groups when compared before and after treatment. The incidence rate of adverse reactions was 9.38% （3/32） in the treatment group and 13.33% （4/30） in the control group， and the difference between groups showed no statistical difference （P＞0.05）. ConclusionOn the basis of topical application of Chushi Zhiyang Ointment， the combined application of Shugan Jianpi Granules can significantly alleviate the degree of skin lesions and itching， and improve the quality of sleep in atopic dermatitis patients with sleep disturbance of liver constraint and spleen deficiency syndrome， and its mechanism may be related to regulating the immune balance， reducing the secretion of inflammatory factors， and elevating the level of MLT.

Stroke is the main cause of death and disability among adults in China and is characterized by high incidence， disability， mortality， and recurrence rates. The combination of traditional Chinese and Western medicine has great potential in treating stroke and its sequelae. The classic traditional Chinese medicine prescription Da Chengqitang （DCQT） has a long history and proven efficacy in treating stroke. Clinically， DCQT is often used to treat stroke and its sequelae. However， the number and quality of clinical trials of DCQT in treating stroke need to be improved. Because of the insufficient basic research， the active ingredients and multi-target mechanism of action of DCQT remain unclear. Our research group has previously confirmed that DCQT can effectively reverse neurological damage， reduce iron deposition， and downregulate the levels of pro-inflammatory cytokines in the rat model of hemorrhagic stroke. The treatment mechanism is related to the nuclear factor erythroid 2-related factor 2 （Nrf2）-mediated signaling pathway and p38 mitogen-activated protein kinase （MAPK） signaling-mediated microglia activation. To clarify the pharmacodynamic basis and anti-stroke mechanism of DCQT， this article reviews the research progress in the treatment of stroke with DCQT in terms of clinical trials， pharmacodynamic material basis， safety evaluation， and mechanisms of absorbed components. This article summarizes 45 major phytochemical components of DCQT， 11 of which are currently confirmed absorbed components. Among them， emodin， rhein， chrysophanol， aloe-emodin， synephrine， hesperidin， naringin， magnolol， and honokiol can be used as quality markers （Q-markers） of DCQT. The mechanism of DCQT in treating stroke is complex， involving regulation of inflammatory responses， neuronal damage， oxidative stress， blood-brain barrier， brain-derived neurotrophic factor， and anti-platelet aggregation. This article helps to deeply understand the pharmacodynamic basis and mechanism of DCQT in treating stroke and provides a theoretical basis for the clinical application of DCQT in treating stroke and the development of stroke drugs.