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.

To analyze the distribution of serotypes and antimicrobial resistance of clinical Salmonella isolates from multiple centers across China.

This study explored the mechanism of Xiangsha Liujunzi Decoction(XSLJZD) in the treatment of functional dyspepsia(FD) based on inositol-requiring enzyme 1(IRE1)/apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase(JNK) pathway-mediated autophagy in interstitial cells of Cajal(ICC). Forty-eight SPF-grade male SD suckling rats were randomly divided into a blank group and a modeling group, and the integrated modeling method(iodoacetamide gavage + disturbance of hunger and satiety + swimming exhaustion) was used to replicate the FD rat model. After the model replications were successfully completed, the rats were divided into a model group, high-dose, medium-dose, and low-dose groups of XSLJZD(12, 6, and 3 g·kg~(-1)·d~(-1)), and a positive drug group(mosapride of 1.35 mg·kg~(-1)·d~(-1)), and the intervention lasted for 14 days. The gastric emptying rate and intestinal propulsion rate of rats in each group were measured. The histopathological changes in the gastric sinus tissue of rats in each group were observed by hematoxylin-eosin(HE) staining. The ultrastructure of ICC was observed by transmission electron microscopy. The immunofluorescence double staining technique was used to detect the protein expression of phospho-IRE1(p-IRE1), TNF receptor associated factors 2(TRAF2), phospho-ASK1(p-ASK1), phospho-JNK(p-JNK), p62, and Beclin1 in ICC of gastric sinus tissue of rats in each group. Western blot was used to detect the related protein expression of gastric sinus tissue of rats in each group. Compared with those in the blank group, the rats in the model group showed decreased body weight, gastric emptying rate, and intestinal propulsion rate, and transmission electron microscopy revealed damage to the endoplasmic reticulum structure and increased autophagosomes in ICC. Immunofluorescence staining revealed that the ICC of gastric sinus tissue showed a significant elevation of p-IRE1, TRAF2, p-ASK1, p-JNK, and Beclin1 proteins and a significant reduction of p62 protein. Western blot revealed that the expression levels of relevant proteins in gastric sinus tissue were consistent with those of proteins in ICC. Compared with the model group, the body weight of rats in the high-dose and medium-dose groups of XSLJZD was increased, and the gastric emptying rate and intestinal propulsion rate were increased. Transmission electron microscopy observed amelioration of structural damage to the endoplasmic reticulum of ICC and reduction of autophagosomes, and the p-IRE1, TRAF2, p-ASK1, p-JNK, and Beclin1 proteins in the ICC of gastric sinus tissue were significantly decreased. The p62 protein was significantly increased. Western blot revealed that the expression levels of relevant proteins in gastric sinus tissue were consistent with those of proteins in ICC. XSLJZD can effectively treat FD, and its specific mechanism may be related to the inhibition of the expression of molecules related to the endoplasmic reticulum stress IRE1/ASK1/JNK pathway in ICC and the improvement of autophagy to promote gastric motility in ICC.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Autophagy/drug effects* ; Rats ; Rats, Sprague-Dawley ; Interstitial Cells of Cajal/metabolism* ; Dyspepsia/physiopathology* ; Protein Serine-Threonine Kinases/genetics* ; MAP Kinase Kinase Kinase 5/genetics* ; MAP Kinase Signaling System/drug effects* ; Humans ; Endoribonucleases/genetics* ; Multienzyme Complexes

OBJECTIVE: To investigate effectiveness of the modified edge resection technique for composite labia minora and clitoral hood reduction with preserved microstructures. METHODS: A retrospective analysis was conducted on 36 female patients, who were diagnosed with composite hypertrophy of the labia minora and clitoral hood and admitted between September 2022 and December 2024. The patients' ages ranged from 18 to 45 years (mean, 27.4 years). The primary surgical motivations included poor appearance alone (8 cases), functional impairment alone (14 cases), both poor appearance and functional impairment (12 cases), and psychological factors (2 cases). All patients were treated with the modified edge resection technique for composite labiaminora and clitoral hood reduction with preserved microstructures. The surgical technique emphasized precise adjustments to the clitoral-labial junction and optimization of the anterior labial structure to ensure a natural postoperative appearance and functional integrity. Postoperative follow-up assessed improvements in appearance and function of clitoral hood and labia minora, complications, and overall patient satisfaction. RESULTS: One patient exhibited suboptimal wound healing, while the remaining patients experienced no complications such as postoperative bleeding, hematoma, wound dehiscence, suture cutting, or labial edema and enlargement. Thirty patients were followed up with a duration of 1-6 months (mean, 2.4 months). In the early postoperative period, 2 patients perceived asymmetry of the bilateral labia minora; 1 underwent labial revision surgery, while the other achieved near-symmetry without intervention. At last follow-up, 25 patients experienced varying degrees of relief from preoperative functional impairments, while the remaining patients showed no improvement; 27 patients reported varying degrees of improvement in appearance, 2 reported no change, and 1 reported a worse appearance compared to preoperatively. Sixteen patients were very satisfied with the surgical results, 8 were satisfied, 5 were moderate satisfied, and 1 was dissatisfied, with a satisfaction rate of 80% (24/30). CONCLUSION The modified edge resection technique for composite labia minora and clitoral hood reduction with preserved microstructures which preserves and optimizes fine anatomical structures through precise adjustments at the clitoral-labial junction, achieves high patient satisfaction with both aesthetic and functional outcomes while minimizing postoperative complications.
Humans ; Female ; Adult ; Retrospective Studies ; Vulva/pathology* ; Clitoris/pathology* ; Middle Aged ; Plastic Surgery Procedures/methods* ; Adolescent ; Patient Satisfaction ; Young Adult ; Treatment Outcome ; Hypertrophy/surgery*

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.

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.

Radiomics provides quantitative support for the diagnosis,treatment strategy and prognosis evaluation of brain arteriovenous malformation(bAVM)through high-throughput analysis of imaging data,and it also shows significant advantages in clinical symptom prediction,personalized treatment and clinical outcome prediction.Emerging imaging techniques,such as blood oxygen level-dependent cerebrovascular reactivity imaging and ultrasound technology,provide a new perspective for evaluating the hemodynamic changes and epilepsy susceptibility associated with bAVM.In addition,advances in deep learning algorithms in automatic segmentation of bAVM lesions have greatly improved the accuracy and efficiency of segmentation.With the continuous progress of imaging technology,data analysis algorithms and software,radiomics is expected to play a greater role in precision medicine and individualized treatment,bringing better diagnosis and treatment services and better treatment effects for bAVM patients.

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.

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.