Kounis syndrome is an acute coronary syndrome triggered by an allergic reaction, which is clinically rare and frequently subject to misdiagnosis or missed diagnosis. This article presents a case report of a 70-year-old male patient who developed a rash, pruritus, and chest pain following colon polyp resection. Coronary angiography revealed occlusion of the left anterior descending artery, and blood flow was restored after stent implantation. However, the patient experienced recurrent symptoms accompanied by loss of consciousness. Drug skin tests confirmed positive reactions to chlorhexidine and fondaparinux sodium, leading to a diagnosis of type Ⅱ Kounis syndrome. By avoiding allergenic drugs and combining antihistamines with symptomatic treatment to correct myocardial ischemia, the patient′s clinical symptoms significantly improved, and he eventually recovered and was discharged from the hospital. This case underscores the importance of maintaining vigilance for this syndrome in patients with allergies accompanied by chest pain and promptly identifying and avoiding allergens.

Objective:To systematically evaluate the clinical efficacy of melatonin for neonatal hypoxic-ischemic encephalopathy (HIE).Methods:From the inception of the databases to December 1, 2022, randomized controlled trials (RCTs) and cohort studies on the use of melatonin for HIE were searched in the following databases: PubMed, Web of Science, Cochrane library, Embase, Chinese Medical Journal Full-text Database, CNKI, Wanfang Database and VIP Database. Meta-analysis, literature risk assessment and sensitivity analysis were conducted using R4.2.2 software and RevMan5.4 software.Results:A total of 4 eligible RCTs were found, including 155 patients. Meta-analysis showed that melatonin could reduce the mortality rate ( RR=0.336, 95% CI0.157-0.718, P=0.005) and white blood cell count in HIE infants ( MD=-1.74, 95% CI -3.404--0.079, P=0.040). Sensitivity analysis showed that the Meta-analysis results were generally stable after excluding the studies one by one. Conclusions:Current evidence shows that melatonin can reduce mortality in HIE infants. However, the included studies have high risk of bias and small sample sizes. More high-quality studies are still needed.

ObjectiveTo explore the molecular mechanism implicated in the treatment of primary myelofibrosis （PMF） using Chinese medicinal herbs （CMH） by bioinformatics and molecular dynamics. MethodsData mining was performed to find the high-frequency CMH in treating PMF between the year of 1985 and 2024 by searching CNKI， Chinese Science and Technology Journal Database （CCD）， and China Academic Journal Database （CSPD）. TCMSP， SwissTargetPrediction and related reports were used to collect the main active ingredients of high-frequency CMH and their targets. The PMF datasets GSE44426 and GSE124281 were downloaded from GEO database， and R software was used for data normalization and differentially expressed genes （DEGs） screening. Key module hub genes were obtained by weighted gene co-expression network analysis （WGCNA） analysis. The common intersection genes of active ingredient targets， DEGs and key module hub genes of CMH were selected， and the target network was generated using Cytoscape 3.9.2 software. The core target network was generated by topological analysis， while key pathways were selected by GO and KEGG pathway enrichment analysis， and protein interaction relationships were obtained from the String database， so as to construct drug-ingredient-target network and protein interaction network （PPI） relationship diagrams. Discovery Studio 2020 software was used to perform molecular docking， and the GROMACS program was used to perform molecular dynamics simulation. ResultsA total of 21 prescriptions were collected involving 121 herbs. There were 9 herbs with a frequency ≥10 times， which were Danshen （Radix et Rhizoma Salviae Miltiorrhizae）， Huangqi （Radix Astragali）， Baizhu （Rhizoma Atractylodis Macrocephalae）， Danggui （Radix Angelicae Sinensis）， Dangshen （Radix Codonopsis）， Gancao （Radix et Rhizoma Glycyrrhizae）， Baishao （Radix Paeoniae Alba）， Fuling （Poria） and Shudihuang （Radix Rehmanniae Praeparata） from high- to low-frequency. A total of 98 active ingredients and 1125 potential targets were obtained from 9 high-frequency CMH. GSE44426 and GSE124281 data sets screened out 24 gene samples， including 14 of the healthy control group and 10 of the PMF group， and identified 319 DEGs between the two groups， including 122 up-regulated genes and 197 down-regulated genes. WGCNA screened out 24 co-expression module genes and found that the five modules closely related to the onset of PMF were MEpink， MEdarkred， MEblack， MEgrey， and MEturquoise， involving 7112 key module hub genes. The GO and KEGG enrichment analyses indicated that lipids and the atherosclerosis pathways were mainly involved in the mechanism of above high-frequency CMH in treating PMF， which included six hub protein targets： HSP90AA1， HSP90AB1， SRC， MAPK1， IL1B and IL10. From the drug-ingredient-target network， seven active ingredients of CMH targeting at these six hub targets were found， including verbascoside， verbascos isoflavone， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The molecular docking and molecular dynamics analyses showed that the key CMH were Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and among the seven active ingredients， calycosin had the highest binding affinity with HSP90AB1. ConclusionThe main CMH for the treatment of PMF may be Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and the active ingredients include verbascoside， verbascos isoflavones， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The relevant targets are HSP90AA1， HSP90AB1， SRC， MAPK1， IL-10， and IL-1β， and the most critical pathways are lipid and atherosclerosis pathways.

The education concepts of four famous traditional Chinese medicine（TCM） doctors（XIAO Longyou， SHI Jinmo， KONG Bohua and WANG Fengchun） in Beijing during the Republic of China were compared， the commonalities in their education concepts of TCM were sorted out， and the root system of the cultivation and growth of talents in TCM， as well as the direction and way of further development were searched， so as to improve the quality of the inheritance and development of TCM. Based on the systematic review of text and opinion method（SrTO） developed by the centre for evidence-based health care at the Joanna Briggs Institute（JBI） in Australia， this study was conducted to collate and analyze the relevant information， including 14 books， 115 journal papers and 7 documents. Related theory construction and practice of early tutor and academic education have been summarized from college， continuing and tutor education， academic research， examination， and so on. And then the connections and commonalities between the different forms of education in the period were summarized to form a SrTO-based narrative， opinion， text assessment and review instrument（NOTARI） summary table. The findings revealed that these four esteemed TCM doctors and educators， through their substantial influence on TCM education in Beijing， emphasized the importance of classics in teaching and clinical practice， underscored the cultivation of virtue， preserved the traditional teaching model， and championed the establishment of TCM schools. They also put forward novel requisites for the compilation of curricula， teaching materials， and books. Moreover， they advocated for a unified perspective on TCM and western medicine， fostering talent capable of bridging the gap between the two. They encouraged the standardization of TCM teaching examination system， and actively participated in scientific research and book writing. The four TCM doctors transcended the traditional boundaries of TCM practice， fostering a new TCM model of education-clinical-research， and profoundly influencing the contemporary TCM colleges and teacher education.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

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 investigate the regulatory effects of acupuncture and moxibustion on chromatin remodeling complex core catalytic subunit of Brahma-related gene 1(Brg1),histone deacetylase(HDAC)3,HDAC9,and males absent on the first(MOF)in the colon tissue of rats with Crohn disease(CD). Methods:Using the random number table method,60 male Sprague-Dawley rats were divided into 5 groups,including a normal group,a model group,an acupuncture group,a medicinal cake-insulated moxibustion group,and an acupuncture-moxibustion group,with 12 rats in each group.CD rat models were prepared using 2,4,6-trinitrobenzene sulfonic acid(TNBS)in all groups except the normal group.The normal and model groups received no interventions.In the acupuncture group,rats were intervened with acupuncture at bilateral Zusanli(ST36)and Shangjuxu(ST37),20 min/session,once a day.The medicinal cake-insulated moxibustion group received medicinal cake-insulated moxibustion at Qihai(CV6)and bilateral Tianshu(ST25)with 2 cones per point per session,once a day.The acupuncture-moxibustion group received both acupuncture and moxibustion interventions simultaneously.Each intervention was performed for 10 consecutive days.Observations included general condition,disease activity,macroscopic damage,and pathological changes in the rat's colon tissue.Real-time fluorescence quantitative polymerase chain reaction was used to measure the mRNA expression of chromatin remodeling-related enzymes Brg1,HDAC3,and HDAC9,while Western blotting detected the protein expression of Brg1,HDAC3,HDAC9,and MOF in rat's colon tissue. Results:The model group showed significantly increased diarrhea score,occult blood score,macroscopic damage score of colon tissue,and colon macroscopic damage index(CMDI)score,as well as elevated mRNA expression levels of HDAC3 and HDAC9,protein expression levels of HDAC3,HDAC9,and MOF,and decreased mRNA and protein expression levels of Brg1 compared to the normal group(P<0.01).In contrast,compared to the model group,the diarrhea score,occult blood score,macroscopic damage score,CMDI score,mRNA expression levels of HDAC3 and HDAC9,and protein expression levels of HDAC3,HDAC9,and MOF were significantly reduced(P<0.05 or P<0.01),while the mRNA and protein expression levels of Brg1 were significantly increased(P<0.01)in the acupuncture group,the medicinal cake-insulated moxibustion group,and the acupuncture-moxibustion group. Conclusion:Both medicinal cake-insulated moxibustion and acupuncture,either used alone or in combination,can regulate the abnormal expression of chromatin remodeling-related enzymes Brg1,HDAC3,HDAC9,and MOF in the colon tissue,thus reducing colon inflammation in CD rats.

Objective:To investigate the value of ultrasound and Ki-67 for early predicting pathological complete response (pCR) of triple negative breast cancer(TNBC) after neoadjuvant chemotherapy (NAC).Methods:Retrospective analysis was performed in 190 patients with TNBC who underwent surgery after NAC treatment at the Cancer Hospital of Fudan University from January 2019 to December 2022. All patients underwent ultrasound examination before and after 2 and 4 cycles of NAC treatment. According to the operation pathological results after NAC, the patients were divided into pCR group and non-pCR group. The differences in ultrasound and Ki-67 parameters were compared between the pCR and non-pCR groups, and binary Logistic regression analysis was performed to determine the independent predictors for pCR. The ROC curve was plotted to evaluate the diagnostic efficacy.Results:Tumor maximum diameter, relative change rates of tumor maximum diameter after 2-cycle and 4-cycle NAC (ΔD2, ΔD4), relative change rate of lymph node short diameter after 2-cycle NAC (ΔS2), T-stage, N-stage and Ki-67 showed statistically significant differences between the pCR group and the non-pCR group (all P<0.05). Logistic regression analysis showed that ΔD4, T-stage, N-stage and Ki-67 were independent predictors for pCR ( OR=1.029, P=0.011; OR=0.300, P=0.009; OR=0.653, P=0.048; OR=1.028, P=0.001). The area under the curve (AUC) of pCR was 0.804 (95% CI=0.742-0.866), the sensitivity and specificity were 67.5% and 83.2% respectively. Conclusions:The combination parameters of ΔD4, T-stage, N-stage and Ki-67 have certain clinical value for predicting pCR of TNBC.

The experience of famous and veteran physicians in traditional Chinese medicine （TCM） is a supplement to the cognition of industry groups and a high-quality learning resource. Digital inheritance of the experience of famous and veteran TCM physicians refers to the use of digital technology to record， organize， protect， spread， share and innovate the knowledge， skills and experiences of famous and veteran TCM physicians， which helps to overcome the inefficiency of traditional experience inheritance and realize the inheritance and development of TCM culture. Digital inheritance has certain advantages in accessibility， loss resistance， accuracy， innovation ability and effectiveness， which can assist the digital preservation， analysis and excavation of the experience of famous and veteran TCM physicians， and is an important supplement to the traditional way of learning from teachers. Digital inheritance is usually divided into the following steps： building a database of TCM knowledge， building a database of experienced medical records of famous and veteran TCM physicians， discovering laws by data mining， and assisting clinical decision-making with machine learning. The digital inheritance of famous and veteran TCM physicians is not only the use of experience information， but also the process of innovation and productization based on experience， which may become a new service model of TCM diagnosis and treatment.

Objective:To evaluate the effect of dexmedetomidine on the thioredoxin-interacting protein (TXNIP)/apoptosis signal-regulated kinase 1 (ASK1) signaling pathway in a mouse model of intestinal ischemia-reperfusion (I/R).Methods:Thirty-two SPF healthy adult male C57BL/6J mice, aged 8-10 weeks, weighing 18-22 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group), TXNIP inhibitor resveratrol group (Res group) and dexmedetomidine group (Dex group). The mouse model of intestinal I/R injury was developed by clamping the superior mesenteric artery for 45 min followed by 120-min reperfusion in anesthetized animals. Resveratrol 30 mg/kg was intraperitoneally injected before developing the model in Res group, and dexmedetomidine 25 μg/kg was intraperitoneally injected at 30 min before ischemia in Dex group. Blood samples were collected by cardiac puncture at the end of 120-min reperfusion, then the mice were sacrificed, and the small intestine tissues were removed for microscopic examination and for determination of the serum diamine oxidase (DAO) concentration (by enzyme-linked immunosorbent assay) and expression of TXNIP, ASK1 and cleaved-caspase-3 in small intestinal tissues (by Western blot). The apoptosis rate of intestinal epithelial cells was calculated. The intestinal damage was assessed and scored according to Chiu. Results:Compared with group Sham, the Chiu′s score, serum DAO concentrations and apoptosis rate of intestinal epithelial cells were significantly increased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was up-regulated in group I/R ( P<0.05). Compared with group I/R, the Chiu′s score, serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was down-regulated in group Res ( P<0.05). Compared with I/R group, the Chiu′s score, serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was down-regulated in Dex group ( P<0.05). Conclusions:The mechanism by which dexmedetomidine alleviates intestinal I/R injury may be related to inhibition of the TXNIP/ASK1 signaling pathway and reduction of cell apoptosis in mice.