The c-Jun N-terminal kinase （JNK） signaling pathway， a key member of the mitogen-activated protein kinase （MAPK） family， plays a central role in the pathogenesis and progression of central nervous system （CNS） diseases by regulating core biological processes such as apoptosis， inflammatory responses， synaptic plasticity， and autophagy. This article sorts out and analyzes relevant literature published domestically and internationally in recent years， summarizing the mechanisms of action of the JNK signaling pathway in common CNS diseases and the research progress in traditional Chinese medicine （TCM） interventions in CNS diseases through the regulation of the JNK signaling pathway. Studies have shown that active components of TCM， such as berberine， paeoniflorin， and astragaloside Ⅳ， as well as compound formulations like Heixiaoyao san， Ditan tang， and Buyang huanwu tang， can exert neuroprotective effects in various CNS disorders， including Alzheimer’s disease， Parkinson’s disease， cerebral ischemia-reperfusion injury， and epilepsy， by inhibiting the aberrant activation of the JNK signaling pathway， thereby alleviating neuroinflammation， oxidative stress， and neuronal apoptosis， while improving synaptic function and cognitive behavioral deficits， regulating autophagy， and maintaining blood-brain barrier integrity.

In today's society， depression is a kind of highly prevalent chronic mental illness. It leads to a high disability rate and a heavy economic burden. Depression is defined by fundamental symptoms of low mood and diminished pleasure. Its causes and mechanisms remain unclear， and it presents a broad spectrum of symptoms and a persistent nature that significantly impacts both physical and mental well-being. Treatment in Western medicine primarily focuses on alleviating symptoms， yet it entails numerous adverse effects and contraindications. Traditional Chinese medicine （TCM） treatment is based on resolving depression， which is often accompanied by soothing liver， and the key medicine is Bupleuri Radix. Bupleuri Radix associated prescriptions refer to a class of prescriptions using Bupleuri Radix as the sovereign medicinal or having a high dose of Bupleuri Radix， which are widely used in the field of anti-depression. Previous studies from animal experiments， clinical research， and modern pharmacological research have confirmed that Bupleuri Radix associated prescriptions have precise anti-depression efficacy in multiple ways and at multiple levels， but lack a comprehensive and systematic summarization. This paper summarized and analyzed the literature related to the clinical application and mechanism of action of Bupleuri Radix associated prescriptions in anti-depression treatment. The results showed that the anti-depression mechanism of the Bupleuri Radix associated prescriptions （such as Xiaochaihu Tang， Xiaoyao San， Sini San， Chaihu Shugan San， and Chaihu jia Longgu Muli San） was associated with the effects of regulating monoamine neurotransmitters， the brain-derived neurotrophic factor （BDNF）， intestinal flora， and the hypothalamic-pituitary-adrenal （HPA） axis， inhibiting inflammatory responses， and modulating related signaling pathways. Applying them in clinical practice can effectively alleviate patient symptoms， lower the TCM syndrome score and the severity of depression， and also reduce adverse reactions. This underscores advantages of TCM in depression treatment， which offers patients a secure， effective， and more individualized alternative treatment regimen. On this basis， the shortcomings of current studies and the future trend were analyzed. This study aimed to provide an evidence-based medicine basis for the research and development of novel antidepressant medications.

OBJECTIVES: To investigate the association of HOTAIR gene rs920778 single nucleotide polymorphism (SNP) with breast cancer susceptibility and response to HER2-targeted therapy in a Chinese population. METHODS: TaqMan probe-based real-time quantitative PCR was used for genotyping of the rs920778 locus (chr12:54,376,218) in peripheral blood genomic DNA from 287 breast cancer patients and 260 healthy individuals from northern Anhui Province. The genotype (GG, GT and TT) and allele (G/T) distribution frequencies were compared between the two groups to evaluate their association with breast cancer risk. Multivariate logistic regression analysis was conducted to assess the relationship between SNP at this locus and aggressive clinicopathological features (including tumor size, lymph node metastasis, ER/PR/HER2 status, and molecular subtypes) of breast cancer. For the HER2-positive subgroup, the association between rs920778 genotype and responses to dual-targeted therapy (trastuzumab [6 mg/kg q3w]+pertuzumab [420 mg q3w] + docetaxel [75 mg/m²]) was analyzed. The primary endpoints included pathological complete response rate (pCR), objective response rate (ORR), and progression-free survival (PFS). RESULTS: The TT genotype of rs920778 was associated with a significantly increased breast cancer susceptibility (OR=1.54, 95% CI: 1.09-2.19; P=0.017), an advanced tumor stage (P<0.001), lymph node metastasis (P<0.001), and the triple-negative subtype (P<0.001). In HER2-positive patients, TT genotype carriers had a markedly reduced objective response rate to dual HER2-targeted therapy (33.3% vs 89.3%, P=0.001) and a lower pathological complete response rate after neoadjuvant therapy (P=0.018). CONCLUSIONS The TT genotype of HOTAIR rs920778 serves as an independent risk factor for breast cancer susceptibility and aggressive progression in Chinese population and may predict the resistance to HER2-targeted therapies, suggesting its potential as a prognostic biomarker for precision oncology.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/drug therapy* ; Case-Control Studies ; China ; Drug Resistance, Neoplasm/genetics* ; Genetic Predisposition to Disease ; Genotype ; Polymorphism, Single Nucleotide ; Receptor, ErbB-2 ; RNA, Long Noncoding/genetics* ; East Asian People/genetics*

Postdural puncture headache(PDPH)is a common complication of neuraxial anesthesia.It can occur after accidental dural puncture during epidural anesthesia,intentional dural puncture for spinal anesthesia,or other diagnostic or therapeutic procedures involving dural puncture.Clini-cally,PDPH presents as postural dull or pulsating headaches,often accompanied by auditory and(or)vis-ual symptoms.It can also be associated with potential complications such as chronic headaches,back pain,cranial nerve dysfunction,subdural hematoma,and cerebral venous sinus thrombosis.This article reviews current researches on the pathophysiology,risk factors,prevention,and treatment of PDPH,aiming to pro-vide a reference for clinical practice.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To explore the improving effect and mechanism of saikosaponin A on insomnia rats based on cAMP/PKA/CREB pathway.Methods Seventy-five SD rats were randomly divided into blank group,model group,low-dose saikosaponin A group(0.625 mg·kg-1),high-dose saikosaponin A group(2.500 mg·kg-1)and Estazolam group(0.1 mg·kg-1),with 15 rats in each group.Insomnia rat model was established by intraperitoneal injection of Phenylalanine(PCPA,0.1 mg·kg-1).The general condition and circadian rhythm of rats were observed;the sleep latency and sleep duration of rats were measured by pentobarbital sodium righting experiment.The sleep phase of rats was observed,and the duration of slow wave sleep phase 1(SWS1),slow wave sleep phase 2(SWS2),rapid eye movement sleep phase(REMS)and total sleep time(TST)were recorded.The mRNA expression levels of hypothalamic circadian genes Clock,Bmal1 and clock-controlled genes Rev-erbα and Rorα were determined by qRT-PCR.The expression level of NeuN in hippocampus was determined by immunofluorescence.The level of cAMP in brain tissue was determined by ELISA.The expression levels of Clock,Bmal1,Rev-erbα,Rorα and cAMP/PKA/CREB pathway-related proteins in brain tissue were determined by Western Blot.Results Compared with the blank group,the rats in the model group had disordered circadian rhythms,extreme excitement,irritability,and reduced sleep;the sleep latency was significantly prolonged(P＜0.05),and the sleep duration and SWS1,SWS2,REMS and TST were significantly shortened(P＜0.05).The arrangement of neurons was disordered,and the IOD value of NeuN positive neurons was significantly decreased(P＜0.05).The mRNA and protein expression levels of Clock,Bmal1,Rev-erbα and Rorα in brain tissue were significantly decreased(P＜0.05).The expression levels of cAMP,p-PKA/PKA and p-CREB/CREB in brain tissue were significantly decreased(P＜0.05).Compared with the model group,the aggressiveness of the rats in the administration group was significantly weakened,the circadian rhythm was rhythmic,the activity was reduced,and the sleep was increased.The sleep latency was significantly shortened(P＜0.05),and the sleep duration and SWS1,SWS2,REMS and TST were significantly prolonged(P＜0.05).The disorder of neuronal arrangement was restored,and the IOD value of NeuN positive neurons was significantly increased(P＜0.05).The mRNA and protein expression levels of Clock,Bmal1,Rev-erbα and Rorα in brain tissue were significantly increased(P＜0.05).The protein expression levels of cAMP,p-PKA/PKA and p-CREB/CREB in brain tissue were significantly increased(P＜0.05).Conclusion Saikosaponin A may improve the circadian rhythm of insomnia rats by activating cAMP/PKA/CREB pathway.

The glucose metabolism is crucial for sustained brain activity as it provides energy and is a carbon source for multiple biomacromolecules; glucose metabolism decreases dramatically in Alzheimer’s disease (AD) and may be a fundamental cause for its development. Recent studies reveal that the alternative splicing events of certain genes effectively regulate several processes in glucose metabolism including insulin receptor, insulin-degrading enzyme, pyruvate kinase M, receptor for advanced glycation endproducts, and others, thereby, influencing glucose uptake, glycolysis, and advanced glycation end-products-mediated signaling pathways. Indeed, the discovery of aberrant alternative splicing that changes the proteomic diversity and protein activity in glucose metabolism has been pivotal in our understanding of AD development. In this review, we summarize the alternative splicing events of the glucose metabolism-related genes in AD pathology and highlight the crucial regulatory roles of splicing factors in the alternative splicing process. We also discuss the emerging therapeutic approaches for targeting splicing factors for AD treatment.

The cochlear auditory epithelium contains two types of sound receptors, inner hair cells (IHCs) and outer hair cells (OHCs). Mouse models for labelling juvenile and adult IHCs or OHCs exist; however, labelling for embryonic and perinatal IHCs or OHCs are lacking. Here, we generated a new knock-in Fgf8^P2A-3×GFP/+ (Fgf8^GFP/+) strain, in which the expression of a series of three GFP fragments is controlled by endogenous Fgf8 cis-regulatory elements. After confirming that GFP expression accurately reflects the expression of Fgf8, we successfully obtained both embryonic and neonatal IHCs with high purity, highlighting the power of Fgf8^GFP/+. Furthermore, our fate-mapping analysis revealed, unexpectedly, that IHCs are also derived from inner ear progenitors expressing Insm1, which is currently regarded as an OHC marker. Thus, besides serving as a highly favorable tool for sorting early IHCs, Fgf8^GFP/+ will facilitate the isolation of pure early OHCs by excluding IHCs from the entire hair cell pool.
Animals ; Mice ; Hair Cells, Auditory, Inner ; Cochlea/metabolism* ; Hair Cells, Auditory, Outer/metabolism* ; Disease Models, Animal ; Fibroblast Growth Factor 8/metabolism*

Objective:To investigate epidemiological characteristics of arsenic poisoning-related skin lesions in an arsenic tailing area in Hunan Province.Methods:A cross-sectional study was conducted. From October 2016 to January 2017, all residents aged over 18 years (except pregnant women) were enrolled from 3 villages in Baiyun Town, Shimen County, Hunan Province by using a cluster-sampling method. Demographic information was collected through a face-to-face questionnaire interview. All residents received skin examination performed by professional dermatologists, and blood, urine, and hair samples were collected for the measurement of arsenic levels. Non-conditional logistic regression analysis was performed to analyze factors associated with arsenic poisoning-related skin lesions.Results:A total of 1 092 eligible residents in the arsenic tailing area were recruited in this study, and 756 (69.2%, 95% CI: 66.5%, 72.0%) presented with arsenic poisoning-related skin lesions, including hyperkeratosis, hypo- or hyper-pigmentation. The median ( Q1, Q3) arsenic levels were 0.31 (0.14, 0.74) μg/g in hair samples ( n = 1 079), 0.84 (0.67, 1.10) μg/L in blood samples ( n =1 091), and 60.31 (41.71, 91.52) μg/L in urine samples ( n =1 092). Multivariable analysis showed that the occurrence of arsenic poisoning-related skin lesions was associated with age, residential location, and occupational arsenic exposure history, but was not associated with gender, ethnicity, education levels, migration history, arsenic levels in hair, blood, or urine. Compared with the group aged 18 - 39 years, the group aged 40 - 59 years and the group aged over 60 years showed significantly higher risks of arsenic poisoning-related skin lesions (adjusted OR = 11.34, 95% CI: 5.98, 21.50, P < 0.001; adjusted OR = 71.82, 95% CI: 35.81, 144.05, P < 0.001, respectively). Compared with the residents in the Wangyangqiao village, residents in the Heshan village and Huangchang village showed significantly higher risks of arsenic poisoning-related skin lesions (adjusted OR = 2.89, 95% CI: 2.05, 4.08, P < 0.001; adjusted OR = 4.13, 95% CI: 1.94, 8.78, P < 0.001, respectively). The risk of arsenic poisoning-related skin lesions was significantly higher in residents with occupational exposure history than in those without (adjusted OR = 1.99, 95% CI: 1.04, 3.83, P = 0.039) . Conclusion:Nearly 70% of the residents presented with arsenic poisoning-related skin lesions in an arsenic tailing area in Hunan Province, and the duration and previous degree of arsenic exposure were associated with the risk of arsenic poisoning-related skin lesions.

Purpose To evaluate the application of mismatch repair (MMR) genes proteins expression and methylationspecific to screen for Lynch syndrome patients.Methods 126 endometrial carcinoma patients were tested the protein expression of hMSH2,hMSH6h,hMLH1,hPMS2 by immunohistochemically of SP,and the methylation status of hMLH1 genes by the methylation-specific PCR.Results The result of MMR immunocytochemistry showed that 22％ (28/126) cases lacked MMR protein expression,including hMLH1-/hPMS2-in 12 cases,4 hMSH2-/hMSH6-,6 hPMS2-,3 hMLH6-and 3 hMLH1-.Meanwhile,the methylation-specific PCR test showed that 9 cases was methylation status of hMLH1 genes in 15 cases hMLH1-,and suggested the patients might be sporadic endometrial carcinoma.Conclusion Immunohistochemical of SP staining for MMR proteins in endometrial carcinoma patients,accompanied by testing for the methylation status of hMLH1 genes,may be an effective approach to screen for Lynch syndrome.