Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

Sexual dimorphism in the brain underlies behavioral differences between sexes. The bed nucleus of the stria terminalis (BNST) is a complex nucleus that differs between males and females, but the sexual dimorphism in cytoarchitecture and the connectome of its oval subdivision (ovBNST) remains largely unexplored. By combining snRNA-seq and transgenic labeling, we found a higher density of ovBNST proenkephalin (ovBNST^PENK) neurons in male than female mice. Anatomically, we virally mapped the efferents and afferents of ovBNST^PENK neurons, finding reciprocally dimorphic connections with the hypothalamus and striatum. Gene enrichment analysis suggests that ovBNST^PENK neurons are modulated by the upstream dopamine pathway. Functionally, by applying caspase-3-mediated depletion of ovBNST^PENK neurons, we found that loss of these neurons enhanced locomotor activity in male but not female mice, without altering the anxiety-like phenotypes in either sex. Our study may pave the way for a better understanding of the anatomical and functional profiles of ovBNST^PENK neurons from a sexually dimorphic perspective.
Animals ; Male ; Female ; Septal Nuclei/physiology* ; Sex Characteristics ; Neurons/physiology* ; Enkephalins/metabolism* ; Mice ; Mice, Transgenic ; Protein Precursors/metabolism* ; Mice, Inbred C57BL ; Neural Pathways/physiology*

Objective To analyze the characteristics and related influencing factors of transfusion reactions in pediatric patients,so as to provide evidence for clinical treatment and prevention of transfusion reactions.Methods A retrospective study was conducted on children who received blood transfusions at our hospital from 2019 to 2023 in terms of the incidence,types,time of occurrence,and related influencing factors of transfusion reactions.Results A total of 69 926 transfusions were performed from 2019 to 2023,with 711 cases of transfusion reactions,resulting in an incidence of 1.02%.The inci-dence of transfusion reactions decreased annually from 2019(1.89%)to 2022(0.50%).The incidence of transfusion reac-tions to apheresis platelets,frozen plasma,suspended leukocyte-depleted red blood cells and cryoprecipitate coagulation fac-tor were 2.16%(551/25 565),0.50%(92/18 277),0.25%(65/25 679)and 0.74%(3/405),respectively,with a-pheresis platelet transfusion of a significantly higher incidence compared to other blood components(P<0.05).As of trans-fusion reaction types,allergic reactions accounted for 86.22%(613/711),febrile non-hemolytic transfusion reactions(FNHTR)accounted for 13.08%(93/711),and acute hemolytic transfusion reactions accounted for 0.70%(5/711).Multivariate logistic regression analysis showed that apheresis platelet transfusion was an independent risk factor for allergic reactions(P<0.05),while suspended leukocyte-depleted red blood cells transfusion was an independent risk factor for FNHTR(P<0.05).In terms of the occurrence time of transfusion reactions,compared to apheresis platelets and frozen plas-ma,transfusion reactions caused by suspended leukocyte-depleted red blood cells transfusion occurred later(apheresis platelets P<0.05,frozen plasma P<0.05).Conclusion The results suggest that blood components transfused are significant influencing factors for the characteristics of transfusion reactions in pediatric patients,affecting the incidence,types,and oc-currence time of transfusion reactions,which provides reference for clinical treatment and prevention of transfusion reactions.

Objective:To investigate value of contrast-enhanced ultrasound(CEUS)in predicting ischemic-type biliary lesions(ITBLs)in patients with thickened hilar bile duct wall at early stage after liver transplantation.Methods:A total of 45 patients,who underwent liver transplantation at the Liver Transplantation Center of Beijing Friendship Hospital Affiliated to Capital Medical University from June 25,2020 to December 28,2022,and occurred hilar bile duct wall thickening at early stage after surgery,were prospectively included.CEUS was performed on biliary tract when the thickened hilar bile duct wall was first detected by routine ultrasound,and the enhanced mode of duct wall at each phase was recorded.Subsequently,according to the results of cholangiography,these patients were divided into ITBLs group(15 cases)and non-ITBLS group(30 cases).The enhanced degree of each phase of CEUS of two groups was qualitatively analyzed and compared,and the diagnostic efficacy of CEUS for ITBLs after liver transplantation was evaluated.Results:There were no significant differences in source of liver donor,biliary anastomosis,autoimmune liver disease,hepatic artery occlusion(HAO),rejection,cytomegalovirus infection and cholangitis between the two groups(P>0.05).The compared results of the enhanced mode of CEUS at arterial phase between the two groups indicated that 25 patients(83.3%)were hyper-enhancement,and 5 patients(16.7%)were iso-enhancement,and 0 patient was hypo-enhancement or non-enhancement in non-ITBLS group.The compared results also indicated that 3 patients(20.0%)were hyper-enhancement,and 4 patients(26.7%)were iso-enhancement,and 8 patients(53.3%)were hypo-enhancement or non-enhancement in ITBLs group.The difference of above results between the two groups was statistically significant(x2=22.946,P<0.000).There was no significant difference between the two groups in the enhanced mode at the late phase(P>0.05).The accuracy,sensitivity,specificity,positively predictive value and negatively predictive value of the prompted hypo-enhancement or non-enhancement at arterial phase of CEUS on biliary tract were respectively 84.4%,53.3%,100%,100%and 84.4%in diagnosing ITBLs.For 8 patients who were diagnosed as ITBLs by CEUS,the diagnostic time of CEUS for ITBLs was 1 to 6 months[3.0(1-5)months]ahead of that of cholangiography.Conclusion:CEUS can more accurately predict ITBLs before the biliary tract occurs significant morphological change,which can significantly advance the diagnostic time for ITBLs.

Objective To develop and evaluate the equivalence of the Mandarin test material for tracking of noise tolerance(TNT)test.Methods Six different speech materials were developed(themes including daily life,entertainment,family,festivals,outdoors,and school).Four-minute TNT tests were measured in 21 normal hear-ing subjects using six different test materials.For each session,the tolerable noise level(TNL)and TNT scores were acquired and calculated for 3 time windows(31～240 s,31～120 s,151～240 s).Results Statistic analysis showed significant differences in the TNL(F=43.611,P＜0.05)among the normal hearing listeners.There were statistically significant differences in standardize z-scored TNT scores of the six different materials in the three time windows(P＜0.05).Post-hoc comparisons revealed that all significant differences involved the family and daily life themes.Conclusion Entertainment,festival,outdoors and school themed test materials can serve as the materials of Mandarin tracking of noise tolerance test and can be appied in research and clinical testing.

Objective:To investigate the application value of Pelvic Inflammation No.1 formula of transdermal meridian point-targeted drug delivery therapy in the treatment of patients with chronic pelvic inflammatory disease(damp-heat stasis type).Methods:All patients with chronic pelvic inflammatory disease(damp-heat stasis type)visited Danzhou Hospital of Traditional Chinese Medi-cine from August 2017 to March 2021 and were randomly grouped,57 patients in the control group were treated with simple Western medicine,and 57 patients in the observation group were combined with Pelvic Inflammation No.1 formula transdermal meridian target-ed transdermal medication,and the therapeutic efficacies were compared after 3 months of treatment.Results:After treatment,serum matrix metalloproteinase-9(MMP-9),D dimer(D-D),IL-6 and other indexes in the observation group were lower than those in the control group,and IL-10 was higher than that in the control group,the difference was statistically significant(P<0.05).After treat-ment,the carbohydrate antigen CA125 in the observation group was lower than that in the control group,and the CD4+/CD8+and CD4+cells in the observation group were higher than those in the control group(P<0.05).After treatment,the score of summary of health status surveys(SF-36)in the observation group was higher than that in the control group,and the total score of TCM symptoms was lower than that in the control group(P<0.05).The total effective rate in the observation group was 96.49%(55/57),which was higher than 82.46%(46/57)in the control group(P<0.05).Conclusion:For patients with chronic pelvic inflammatory disease(damp-heat stagnation type),combined with Pelvic Inflammation No.1 formula transdermal via acupoints targeted drug therapy can help to regu-late inflammatory factors,regulate immune function,and improve clinical efficacy.

Respiratory syncytial virus (RSV) is an enveloped, negative-sense, single-stranded RNA virus of the Orthopneumovirus  genus of the Pneumoviridae family in the order Mononegavirales. RSV can cause acute upper and lower respiratory tract infections, sometimes with extrapulmonary complications. The disease burden of RSV infection is enormous, mainly affecting infants and older adults aged 75 years or above. Currently, treatment options for RSV are largely supportive. Prevention strategies remain a critical focus, with efforts centered on vaccine development and the use of prophylactic monoclonal antibodies. To date, three RSV vaccines have been approved for active immunization among individuals aged 60 years and above. For children who are not eligible for these vaccines, passive immunization is recommended. A newly approved prophylactic monoclonal antibody, Nirsevimab, which offers enhanced neutralizing activity and an extended half-life, provides exceptional protection for high-risk infants and young children. This review provides a comprehensive and detailed exploration of RSV's virology, immunology, pathogenesis, epidemiology, clinical manifestations, treatment options, and prevention strategies.
Humans ; Respiratory Syncytial Virus Infections/prevention & control* ; Respiratory Syncytial Viruses/pathogenicity* ; Respiratory Syncytial Virus, Human/pathogenicity* ; Antiviral Agents/therapeutic use*

Objective:To analyze clinical efficacy and safety of dermabrasion for the treatment of familial benign chronic pemphigus.Methods:Clinical data were retrospectively collected from 6 patients with familial benign chronic pemphigus, who underwent dermabrasion in the Department of Dermatology, the First Affiliated Hospital of Dalian Medical University from February 2019 to July 2020. There were 3 males and 3 females, they were aged from 39 to 65 years, and their disease duration ranged from 10 to 40 years. All the patients were postoperatively followed up for 14 - 34 months. Response rates were calculated, and adverse reactions and recurrence were observed.Results:Dermabrasion was performed on the 6 patients in 55 body areas. After operation, complete recovery was observed in 36 areas (65.5%), marked improvement was noted in 13 areas (23.6%), and moderate improvement was observed in 6 areas (10.9%) ; there were no areas with no response, resulting in an overall response rate of 89.1%. Postoperatively, the patients experienced no obvious discomfort, and only slight hypopigmentation and mild scars remained. During the follow-up of 14 to 34 months, no recurrence was observed in the treated areas.Conclusion:Dermabrasion was safe and effective for the treatment of familial benign chronic pemphigus.

Objective:To analyze the gene mutation type and clinical phenotype of patients with PRRT2 mutation, and explore their relations with prognosis. Methods:A total of 18 patients with PRRT2 gene mutation (1 patient with novel mutation in PRRT2 gene, and 17 probands in 17 families with PRRT2 gene mutation) were enrolled in Department of Neurology, First Affiliated Hospital of Air Force Medical University from January 2018 to July 2023. Serum of the patients was collected for whole exon sequencing, and mutation sites and types of PRRT2 gene were analyzed. SWISS-MODEL website was used to predict the changes in protein structure caused by PRRT2 gene mutation. The relations of gene mutation type and clinical phenotype with prognosis of these patients were analyzed. Results:(1) All 18 patients with PRRT2 gene mutation were heterozygous mutation, including 12 frameshift mutations, 5 missense mutations, and 1 integer mutation. The clinical phenotype included benign familial infantile epilepsy (BFIE) in 5 patients, epilepsy in 6 patients, exercise-induced paroxysmal kinesigenic dyskinesia (PKD) in 5 patients, and infantile convulsion and choreoathetosis (ICCA) in 2 patients. A total of 8 mutation sites were found in 18 patients with PRRT2 gene mutation, of which 3 mutation sites have been reported, and 5 mutation sites have not been reported, including c.647(exon2)C>A, c.647(exon2)C>G, c.170(exon2)delC, c.981(exon3)C>G, and lossl(EXON: 2)(all). (2) Eighteen patients mainly accepted oxcarbazepine, levetiracetam, and sodium valproate in combination or monotherapy. Among them, 5 BFIE patients, 2 ICCA patients and 3 epilepsy patients were seizure-free after treatment. PKD patients did not respond well to oxcarbazepine. (3) Three frameshift mutations (mutation sites: c.649 [exon2]_c.650 [exon2] insC, c.640 [exon2]_c.641 [exon2] insC, and c.170 [exon2] delC) led to premature termination of protein translation, resulting in significant changes in protein structure. Four missense mutations (mutation sites: c.640[exo2]G>C, c.647[exon2]C>A, c.647[exon2]C>G, and c.981[exon3]C>G) had little effect on protein structure changes. No relation was found between changes of protein structure caused by different mutation types and prognosis. Conclusion:PRRT2 gene mutation patients with clinical phenotypes of BFIE and ICCA have good prognosis, but the mutation type is not related with the prognosis of patients.

Objective:To evaluate the efficacy and safety of a China original liquid pulsation system for the treatment of meibomian gland dysfunction (MGD).Methods:A non-randomized controlled clinical trial was conducted.Twenty-two patients (44 eyes) diagnosed with MGD in Eye and ENT Hospital of Fudan University from February to August 2022 were enrolled.The patients were assigned into two groups according to their willingness.Of the 22 patients (44 eyes), 10 patients (20 eyes) in single liquid pulsation system group were treated with single liquid pulsation system for 12 minutes, and 12 patients (24 eyes) in intense pulsed light (IPL) group were treated with a course (4 times) of IPL, warm compresses and meibomian gland massage at three-week intervals.There was no difference in age and other baseline clinical indexes between the two groups (all at P<0.05). The meibum grading, quality grading of tear film lipid layer, Symptom Assessment Questionnaire in Dry Eye (SANDE) questionnaire score, first and average tear breakup time (BUT), corneal fluorescein sodium staining (CFS) score, tear meniscus height (TMH), and the area of meibomian gland loss were determined at baseline, 1 and 3 months after treatment.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Eye and ENT Hospital of Fudan University (No.2021069). Written informed consent was obtained from each patient before any medical examination. Results:Statistically significant group effects and time effects were found in the quality of tear film lipid layer ( Hgroup=4.39, P=0.036, Htime=6.30, P=0.043) and average BUT ( Fgroup=4.41, P=0.038; Ftime=4.08, P=0.049) in the two groups.The meibum grading, first BUT and TMH 1 and 3 months after treatment were significantly better than before treatment in single liquid pulsation system group (all at P<0.05). Compared with before treatment, there was no significant improvement in the meibum grading, distribution of tear film lipid, first BUT and TMH at 1 and 3 months after treatment in IPL group (all at P>0.05). In both groups, the SANDE and CFS scores 1 and 3 months after treatment were better than those before treatment, showing statistically significance (all at P<0.05). In terms of safety, neither instrument-related adverse events nor extra complaints of discomfort were reported in the single liquid pulsation system group.In both groups, the number of patients with positive CFS staining significantly decreased, and no new cases with positive CFS appeared after treatment. Conclusions:This China original liquid pulsation system is a safe and effective physical therapy in improving tear film dysfunction and ocular surface symptoms of MGD patients within 3 months after treatment.