Alternative splicing (AS), a critical mechanism in gene expression regulation, is essential for cellular physiological processes such as proliferation, metabolism, and apoptosis via generating diverse mRNA isoforms and expanding protein diversity. In the field of oncology, AS has been significantly implicated in the regulation of various biological processes involved in tumorigenesis and cancer progression. Specific mutations or expression changes in splicing factors, such as SF3B1, SRSF2, and U2AF1, play key roles in multiple types of cancer. This review summarizes novel therapeutic strategies for cancer targeting alternative splicing, including inhibiting spliceosome components, antisense oligonucleotide (ASO) therapy, and approaches to overcome drug resistance and immune evasion in cancer. These strategies, which modulate the activity of splicing factors and RNA-modifying enzymes, show promise in addressing chemoresistance and enhancing the efficacy of immunotherapy. This review provides a comprehensive exploration of alternative splicing mechanisms, their role in cancer, and their potential as a therapeutic target, highlighting the importance of alternative splicing in cancer research and therapy.

Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-G_q complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.

Objective To explore the imaging manifestations of Rosai-Dorfman disease(RDD)in children.Methods A total of 12 children with RDD confirmed by pathology were retrospectively enrolled,including 8 cases underwent non-contrast CT(NCCT)+contrast enhanced CT(CECT),2 cases underwent NCCT+CECT+non-contrast MR(NCMR)+contrast enhanced MR(CEMR),1 case underwent NCCT+NCMR and CEMR,while 1 case underwent NCCT and X-ray examinations.Imaging manifestations of RDD in children were observed.Results Among 12 cases,intranodal type RDD was found in 7 case,extranodal type RDD in 3 cases,and mixed type(with both lymph nodes and extranodal sites affected)RDD were noticed in 2 cases.In 7 cases of intranodal type RDD,NCCT and CECT showed multiple lymph node enlargements in both sides of the neck,with uniform isodensity on NCCT and mild-moderate progressive enhancement in 5 cases,while with low-density necrotic area and ring-shaped enhancement in 2 cases.Among 3 cases of extranodal RDD,the lesion in 1 case involved nasal cavity and posterior group of ethmoid sinuses on CT and MRI,which developed circular soft tissue mass centered on nasal septum with moderate heterogeneous enhancement,also compressed the adjacent bone with destruction.In another case of extranodal RDD,CT showed that the lesion involved left ilium and bilateral parietal bones,with bone destruction accompanied by obvious periosteal reaction and soft tissue mass,which was mildly enhanced.In the rest 1 case of extranodal RDD,CT and X-ray film showed that the lesion involved the upper segment of right femur and left parietal bone,with osteolytic destruction accompanied by layered periosteal reaction.The lesions in both 2 cases of mixed type RDD involved brain(1 case involved left parieto-occipital lobe,1 case involved bilateral temporal lobes,left frontal lobe and bilateral occipital lobes),presented as isodensity on CT and equal or slightly low signal intensity on T 1WI,equal-high mixed signal intensity on T2WI,some shaped like brain gyral with mild edema of surrounding tissue,and nodular or mass-like significant enhancement.RDD involvements of bilateral lung,mediastinum and hilar lymph nodes were also observed in the above 2 cases,chest CT showed multiple nodular or small patchy uniform high-density shadows in bilateral lungs,as well as enlarged mediastinum and hilar lymph nodes.Conclusion Imaging manifestations of pediatric RDD had certain specificity,being helpful to diagnosis.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Objective To investigate the correlation between skeletal muscle fat content and diabetic peripheral neuropathy(DPN)in patients with type 2 diabetes mellitus(T2DM).Methods 290 patients with T2DM admitted to our hospital were enrolled in this study from January 2023 to February 2024 and divided into two groups according to whether they were complicated with DPN:simple T2DM group(T2DM,n=98)and T2DM with DPN group(DPN,n=192).The general data,biochemical indexes and fat distribution indexes measured based on quantitative CT were compared between the two groups.Spearman correlation was used to analyze the relationship between fat distribution indexes and DPN,logistic regression analysis of influencing factors of T2DM complicated with DPN.Results Age,DM duration,WHR,FIns,insulin resistance index(HOMA-IR)and FF were higher in DPN group than in T2DM group(P<0.05).Ca,subcutaneous abdominal fat area(SFA)and liver fat content were lower in DPN group than in T2DM group(P<0.05).Spearman correlation analysis showed that DPN was negatively correlated with SFA and liver fat content(r=-0.127,-0.123,P<0.05),and positively correlated with FF(r=0.117,P<0.05).Logistic regression analysis showed that without adjusting for confounding factors and adjusting for DM duration,WHR,HOMA-IR,Ca,SFA and liver fat content,FF was an influential factor for DPN in T2DM patients.Conclusions Skeletal muscle FF was associated with DPN in patients with T2DM.

Objective To investigate the karyotypes and the correlation of chromosomal abnormalities in the fetuses with increased nu-chal translucency(NT),so as to provide a basis for prenatal genetic counseling.Methods The clinical data of 386 singleton pregnant women with NT≥2.5mm who underwent invasive prenatal diagnosis at the First Affiliated Hospital of Nanjing Medical University from January 2018 to April 2022 were retrospectively analyzed.The fetuses were grouped according to NT thickness(2.5-3.4,3.5-3.9,4.0-4.9,5.0-5.9,and ≥6.0 mm),fetal ultrasound abnormalities(isolated increased NT,non-isolated increased NT),and maternal age(advanced age ≥35 years,non-advanced age＜35 years).The chi-square test was used to compare the differences of the incidence of fetal chromosomal abnormalities among various groups.Results Among the 386 fetuses with increased NT,chromosomal abnormalities were detected in 87 cases with an overall detection rate of 22.5％(87/386),including chromosomal numerical abnormalities accounted for 82.8％(72/87)and copy number variations(CNVs)accounted for 17.2％(15/87).The detection rates of chromosomal abnormal-ities and numerical abnormalities increased with NT thickness(P＜0.05),while no statistically significant difference of CNV abnormali-ty rates was found(P=0.41).The detection rates of chromosomal abnormalities(36.5％)and CNV abnormalities(14.1％)in the non-isolated increased NT group were significantly higher than those in the isolated increased NT group(18.6％and 1.0％,respective-ly,both P＜0.05).The detection rates of chromosomal abnormalities(34.7％)and numerical abnormalities(31.6％)in the fetuses of advanced maternal age mothers with increased NT were significantly higher than those in the non-advanced age group(18.4％and 14.2％,respectively,both P＜0.05).However,the difference of CNV abnormality rates between the two groups was not statistically sig-nificant(P=0.62).Conclusion The detection rate of fetal chromosomal abnormalities elevated with increased NT thickness.Ad-vanced maternal age and the presence of other ultrasound abnormalities were the high-risk factors for fetal chromosomal abnormalities.The risks of CNV abnormalities may not be significantly correlated with NT thickness or maternal age but associated with the presence of other ultrasound abnormalities.

Large inter-individual and intra-individual differences in the expression and activity of drug-metabolizing enzymes(DMEs)contribute to unpredictable drug response and toxicity,which is a challenge facing precision medicine.Nuclear receptor-mediated transcriptional regulation and epigenetic mechanisms including histone modifications,non-coding RNAs,and DNA methylation can help to explain the individual variability in DME expressions.However,several questions remain unanswered.Recently,epitranscriptomics,an emerging field,provides new insights into the regulation of gene expression.As the most abundant RNA modification in eukaryotes,N6-methyladenosine(m6A)modifi-cation plays key roles in various physiological and pathological processes.This review summarizes the recent progress in m6A modification-mediated individual variability in DME expression in terms of the role of m6A modification in regulating basal expression of DMEs,crosstalk between m6A modification and nuclear receptors during the ontogeny of DMEs,and the contribution of m6A modification to xenobi-otic exposure-mediated changes in DME expression.This review aims to provide data for the elucida-tion of individual variations in drug metabolism in clinic.

ObjectiveTo investigate the protective effects and mechanisms of Bushen Zhuyun prescription （BSZY） on abortion rats with kidney deficiency-corpus luteum inhibition syndrome. MethodsAn abortion rat model with kidney deficiency-corpus luteum inhibition syndrome was constructed. Pregnant mice aged 8-10 weeks were randomly divided into a control group （Control）， a model group （Model）， low-dose BSZY （BSZY-L）， medium-dose BSZY （BSZY-M）， and high-dose BSZY （BSZY-H） groups （2.57， 5.14， 10.28 g·kg^-¹）， and a Zishen Yutai Pill （ZSYT） group （1.575 g·kg^-¹）. Hematoxylin-eosin （HE） staining was used to evaluate histopathological changes in ovarian and decidual tissue of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of estrogen （E₂）， progesterone （P）， luteinizing hormone （LH）， prolactin （PRL）， and follicle-stimulating hormone （FSH） in serum. The candidate targets of BSZY were obtained from the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0 databases， while disease targets for recurrent spontaneous abortion （RSA） were retrieved from GeneCards， DrugBank， Online Mendelian Inheritance in Man （OMIM）， and Therapeutic Target Database （TTD）. The intersection targets were identified by the Venny 2.1.0 platform. Pathway enrichment analysis was conducted based on the Metascape database to predict the potential mechanisms of BSZY. Additionally. Western blot was used to verify the effects of BSZY on the expression of estrogen receptor （ERα）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） and explore its protective mechanism on RSA rats. ResultsCompared with the control group， the model group exhibited significantly decreased uterine， ovarian， and embryonic wet weights （P<0.05， P<0.01）， with an abortion rate of 57.18%. The ovarian tissue showed varying degrees of reduction in primordial follicles， primary follicles， mature follicles， and corpora lutea， along with a large number of atretic follicles. The endometrium was thinner， and decidual tissue exhibited cellular edema and disorganized arrangement. In contrast， compared with the model group， the BSZY groups at all doses and the ZSYT group demonstrated increased uterine， ovarian， and embryonic wet weights， along with a reduced abortion rate. The number of primordial follicles， primary follicles， mature follicles， and corpora lutea increased， while atretic follicles decreased. The endometrium thickened， and decidual tissue displayed normal cellular structure with tight arrangement. Additionally， the model group showed significantly decreased levels of E₂， P， PRL， and FSH in serum （P<0.05， P<0.01）， along with a decreasing trend in LH level. In contrast， the BSZY groups at all doses exhibited significantly elevated levels of E₂， P， LH， PRL， and FSH in serum （P<0.05， P<0.01）. Network pharmacology predictions suggested that BSZY may exert protective effects against abortion in rats by activating the ERα/PI3K/Akt signaling pathway. Western blot results confirmed that BSZY significantly upregulated the expression of ERα， PI3K， and p-Akt proteins （P<0.05， P<0.01）. ConclusionBSZY has a protective effect on the abortion rats with kidney deficiency-corpus luteum inhibition syndrome， possibly by activating the ERα/PI3K/Akt signaling pathway to reduce ovarian apoptosis and regulate endocrine function， thereby lowering the abortion rate.

Based on the analysis of the relevant records of the contralateral bloodletting technique, it is believed that this needling technique has 3 key characteristics, including "contralateral selection of points", "points on the four extremities dominated" and "collaterals selected rather than meridian points". Through the studies on philology and the annotation by the doctors in the past dynasties, a part of point prescriptions for the contralateral bloodletting is investigated, and those not belonged to the category of this needling technique in Suwen: Miuci Lun (On Contralateral Bloodletting) are distinguished. It is concluded that the failure of consensus-making in classifying point prescriptions is due to the lack of understanding on the characteristics of contralateral bloodletting and the misunderstanding on the errors of sentences and words. It is suggested that the study on theoretic concepts should lay on the problems relevant with the generalization and alienation of concepts. The mode of "combination of the detail with the whole" should be adopted. It starts from grasping the overall by systematic review, and followed by deliberating in details, so as to correctly identify the original concept and connotation.
Humans ; Bloodletting/methods* ; Acupuncture Points ; History, Ancient ; Meridians ; China

Petroleum hydrocarbon pollution has become one of the global environmental problems, posing a serious threat to the environment and human health. Microbial remediation plays an important role in the remediation of petroleum hydrocarbon-contaminated environment. Nevertheless, the stress factors present in the environment polluted by petroleum hydrocarbons limit the effectiveness of microbial remediation. This paper reviews the common stress factors in petroleum hydrocarbon-polluted environment and the response mechanisms of microorganisms to these factors. Furthermore, we introduce the methods to improve microbial tolerance, such as irrational modification, rational modification based on systems biology tools or tolerance mechanisms, and the construction of microbial consortia. The application of these methods is expected to improve the viability and remediation efficiency of microorganisms in petroleum hydrocarbon-contaminated environment and provide new perspectives and technical support for environmental remediation.
Biodegradation, Environmental ; Petroleum/metabolism* ; Hydrocarbons/isolation & purification* ; Bacteria/genetics* ; Environmental Pollutants/isolation & purification* ; Petroleum Pollution