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.

The brain-gut interaction theory is a multidimensional integrative concept based on the brain-gut axis， involving neural， endocrine， and immune regulatory networks as well as the gut microbiota. Zang-fu organs （脏腑） theory in traditional Chinese medicine （TCM） shows a high degree of consistency with the brain-gut interaction theory， and the core functions such as the spleen and stomach governing the ascending of the clear and descending of the turbid， the liver governing the free flow of qi， and the heart governing mental and emotional activities are closely associated with the multi-level regulatory mechanisms of the brain-gut axis. TCM therapy can modulate brain-gut interactions through multiple pathways in the treatment of spleen and stomach diseases， including the regulation of gastrointestinal hormone secretion， neurotransmitter levels， the hypothalamic-pituitary-adrenal （HPA） axis， immune homeostasis and inflammatory responses， as well as the gut microecology. However， current basic research on the brain-gut interaction theory in TCM for spleen and stomach diseases still faces several challenges， such as difficulties in integrating TCM spleen-stomach theory with modern pathophysiology， lack of innovation in research concepts， and limitations in research methodologies. It is therefore proposed that multidisciplinary collaboration， multi-omics technologies， and targeted research approaches should be adopted to provide more comprehensive methods for basic research on TCM spleen and stomach diseases， thereby promoting the in-depth development of brain-gut interaction theory.

Jasmonic acid (JA) is a common plant hormone with regulatory effects on plant growth and development. The jasmonate ZIM-domain (JAZ) proteins (JAZs), as key regulators in the JA signaling pathway, are involved in multiple biological processes such as anthocyanin accumulation, flowering time modulation, and secondary metabolite synthesis in plants. JAZs are essential components of many regulatory signaling networks. The JAZ genes, members of the plant-specific TIFY family, have been identified in the genomes of a variety of horticultural plants. Here, we summarized the research progress in the roles of JAZs in horticultural plants, aiming to give insights into the further study of the biological functions and regulatory networks of JAZ genes in plants.
Horticulture ; Repressor Proteins/metabolism* ; Plant Proteins/metabolism* ; Cyclopentanes/metabolism* ; Oxylipins/metabolism* ; Plants/metabolism* ; Plant Development

Objective:To explore the clinical significance of trisomy 7 signaled by non-invasive prenatal testing (NIPT).Methods:Pregnant women with high risk for trisomy 7 by NIPT from January 2017 to December 2023 were selected as the study subjects, and the results of prenatal diagnosis and follow-up were analyzed. Literature related to pregnant women with a high risk for trisomy 7 by NIPT from January 2016 to July 2024 was retrieved from China Biomedical Literature Database, Wanfang Database, China National Knowledge Infrastructure and PubMed database. Relevant information such as the incidence of trisomy 7 by NIPT, positive predictive value (PPV), and pregnancy outcomes were collected. This study has been approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No. JS2022010).Results:A total of 51 women with a high risk for trisomy 7 by NIPT were identified. Thirty-two of them had chosen chromosomal microarray analysis (CMA) of amniotic fluid cells, and 1 case of mosaic trisomy 7 was detected, which had yielded a PPV of 3.13%. Four women had opted termination of pregnancy, 1 had miscarriage, 4 had pre-term and/or low weight birth, whilst the remaining 42(82.4%) had full-term delivery. In total 19 literature were retrieved, which had involved 278 cases of trisomy 7 signaled by NIPT, among which 5 fetuses with mosaic trisomy 7 (3.14%) were confirmed. Among the 211 women with follow-up outcomes, 2 (0.95%) had intrauterine growth restriction, 3 (1.42%) had abnormal fetal structure detected by ultrasound, 2 (0.95%) had miscarriage, 9 (4.27%) underwent pregnancy termination, 28 (13.27%) had preterm and/or low weight birth, whilst 167 (79.14%) had normal delivery. In 18 cases, chromosomal analysis of placental tissue was carried out, and 17 were confirmed to have mosaicism trisomy 7.Conclusion:The PPV for trisomy 7 signaled by NIPT is extremely low. Although most of such women had a full term delivery, adverse pregnancy outcomes may still occur in a minority of cases. Clinicians should provide adequate genetic counseling for such women and recommend appropriate prenatal diagnosis strategies and optimal perinatal management plans.

Objective:To compare the active respiratory circulation technique (ACBT) with the oscillatory positive pressure expiration technique (OPEP) in terms of their ability to improve pulmonary function and minimize complications after cardiac surgery, seeking to define an airway management strategy for such patients.Methods:A total of 101 patients who had undergone cardiac surgery were randomly divided into an ACBT group ( n=50) and an OPEP group ( n=51). On the 1st day after the operation, in addition to conventional medical treatment and early rehabilitation, the subjects were additionally provided with daily 20-minute sessions of ACBT or OPEP training for seven consecutive days. Before the operation, and on the 3rd and 7th day afterward, lung function was assessed using a pulmonary edema imaging assessment system (RALE), computed tomography and pulmonary function indexes. Any complications were also noted. Six-minute walking distance and the Barthel index quantified exercise endurance and ability in the activities of daily living, respectively. Turbidimetry was used to determine the levels of C-reactive protein in the blood. The duration of mechanical ventilation required, ICU stay time, length of postoperative and total hospital stays were also recorded. Results:On day seven after the operation, the average RALE scores of the ACBT and OPEP groups were (12.40±4.37) and (10.20±4.66), respectively—a significant difference. At the same time point, the incidence of atelectasis in the OPEP group was significantly lower than in the ACBT group. The OPEP group′s average maximum inspiratory pressure was a greater percentage of the predicted value, and its average 6-minute walk and BI score were also better. On the 3rd day after the operation, the incidence of lung consolidation in the ACBT group was significantly lower than that in the OPEP group, on average.Conclusions:The curative effect of ACBT is better than that of OPEP in the first few days after such an operation, but after a week OPEP more effectively restores respiratory muscle strength and relieves pulmonary complications. It is recommended to apply these two techniques in stages to optimize postoperative airway management. RALE scoring is an ideal tool for dynamic monitoring of pulmonary complications after cardiac surgery.

Activity cliffs(ACs)are generally defined as pairs of similar compounds that only differ by a minor structural modification but exhibit a large difference in their binding affinity for a given target.ACs offer crucial insights that aid medicinal chemists in optimizing molecular structures.Nonetheless,they also form a major source of prediction error in structure-activity relationship(SAR)models.To date,several studies have demonstrated that deep neural networks based on molecular images or graphs might need to be improved further in predicting the potency of ACs.In this paper,we integrated the triplet loss in face recognition with pre-training strategy to develop a prediction model ACtriplet,tailored for ACs.Through extensive comparison with multiple baseline models on 30 benchmark datasets,the results showed that ACtriplet was significantly better than those deep learning(DL)models without pre-training.In addition,we explored the effect of pre-training on data representation.Finally,the case study demonstrated that our model's interpretability module could explain the prediction results reasonably.In the dilemma that the amount of data could not be increased rapidly,this innovative framework would better make use of the existing data,which would propel the potential of DL in the early stage of drug discovery and optimization.

OBJECTIVE: To explore the clinical significance of trisomy 7 signaled by non-invasive prenatal testing (NIPT). METHODS: Pregnant women with high risk for trisomy 7 by NIPT from January 2017 to December 2023 were selected as the study subjects, and the results of prenatal diagnosis and follow-up were analyzed. Literature related to pregnant women with a high risk for trisomy 7 by NIPT from January 2016 to July 2024 was retrieved from China Biomedical Literature Database, Wanfang Database, China National Knowledge Infrastructure and PubMed database. Relevant information such as the incidence of trisomy 7 by NIPT, positive predictive value (PPV), and pregnancy outcomes were collected. This study has been approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No. JS2022010). RESULTS: A total of 51 women with a high risk for trisomy 7 by NIPT were identified. Thirty-two of them had chosen chromosomal microarray analysis (CMA) of amniotic fluid cells, and 1 case of mosaic trisomy 7 was detected, which had yielded a PPV of 3.13%. Four women had opted termination of pregnancy, 1 had miscarriage, 4 had pre-term and/or low weight birth, whilst the remaining 42 (82.4%) had full-term delivery. In total 19 literature were retrieved, which had involved 278 cases of trisomy 7 signaled by NIPT, among which 5 fetuses with mosaic trisomy 7 (3.14%) were confirmed. Among the 211 women with follow-up outcomes, 2 (0.95%) had intrauterine growth restriction, 3 (1.42%) had abnormal fetal structure detected by ultrasound, 2 (0.95%) had miscarriage, 9 (4.27%) underwent pregnancy termination, 28 (13.27%) had preterm and/or low weight birth, whilst 167 (79.14%) had normal delivery. In 18 cases, chromosomal analysis of placental tissue was carried out, and 17 were confirmed to have mosaicism trisomy 7. CONCLUSION The PPV for trisomy 7 signaled by NIPT is extremely low. Although most of such women had a full term delivery, adverse pregnancy outcomes may still occur in a minority of cases. Clinicians should provide adequate genetic counseling for such women and recommend appropriate prenatal diagnosis strategies and optimal perinatal management plans.
Humans ; Female ; Pregnancy ; Trisomy/diagnosis* ; Chromosomes, Human, Pair 7/genetics* ; Adult ; Prenatal Diagnosis/methods* ; Noninvasive Prenatal Testing/methods* ; Pregnancy Outcome ; Clinical Relevance

Activity cliffs (ACs) are generally defined as pairs of similar compounds that only differ by a minor structural modification but exhibit a large difference in their binding affinity for a given target. ACs offer crucial insights that aid medicinal chemists in optimizing molecular structures. Nonetheless, they also form a major source of prediction error in structure-activity relationship (SAR) models. To date, several studies have demonstrated that deep neural networks based on molecular images or graphs might need to be improved further in predicting the potency of ACs. In this paper, we integrated the triplet loss in face recognition with pre-training strategy to develop a prediction model ACtriplet, tailored for ACs. Through extensive comparison with multiple baseline models on 30 benchmark datasets, the results showed that ACtriplet was significantly better than those deep learning (DL) models without pre-training. In addition, we explored the effect of pre-training on data representation. Finally, the case study demonstrated that our model's interpretability module could explain the prediction results reasonably. In the dilemma that the amount of data could not be increased rapidly, this innovative framework would better make use of the existing data, which would propel the potential of DL in the early stage of drug discovery and optimization.

Objective:To investigate the characteristics, influencing factors, consequences, coping strategies, and preventive measures of workplace violence in medical consortiums.Methods:Medical professionals from a specialized hospital in South China and its consortium members (2 primary-level, 1 secondary-level, and 1 tertiary-level hospitals) were surveyed in December 2022 and July 2023. Quantitative research included 1013 participants, while qualitative research involved 35 participants. Workplace violence was assessed using the "National Case Study Tool for Workplace Violence in Healthcare Institutions-Survey Questionnaire", with qualitative analysis conducted through semi-structured interviews. Inter-group comparisons employed chi-square tests or Fisher's exact probability test, with logistic regression models for bivariate analysis.Results:The overall incidence rates of violence, psychological violence, and physical violence in this medical consortium were 31.7% (321/1, 013) , 30.6% (310/1, 013) , and 3.3% (33/1, 013) , respectively. Specifically, the overall violence rates in Level 1, Level 2, and Level 3 hospitals were 22.7% (41/181) , 27.4% (43/157) , and 35.1% (237/675) . The physical violence rates were 1.1% (2/181) , 10.2% (16/157) , and 2.2% (15/675) , respectively. The psychological violence rates stood at 22.7% (41/181) , 24.8% (39/157) , and 34.1% (230/675) . The total violence in tertiary hospitals was significantly higher than that in tertiary hospitals ( F=10.10, P=0.002) , and the incidence of psychological violence in tertiary hospitals was significantly higher than that in tertiary hospitals ( Flevel 1 vs level 3=8.61, P=0.003; Flevel 2 vs level 3=4.96, P=0.026) , incidence of verbal insults ( Flevel 1 vs level 3=8.25, P=0.004; Flevel 2 vs level 3=6.36, P= 0.012) was significantly higher than that of level 1 and level 2 hospitals. The incidence of physical violence in secondary hospitals was significantly higher than that of other two-level hospitals ( P<0.001) . Compared with other types of violence, the incidence of verbal insults is highest in hospitals at all levels. Higher anxiety about violence was a risk factor for psychological violence in hospitals at all levels ( Flevel1 hospital=15.44, P=0.004; Flevel2 hospital=22.87, P<0.001; Flevel3 hospital=84.12, P<0.001) . Health workers in all three levels of hospitals has a high level of approval of existing workplace violence interventions. The main causes of workplace violence were poor communication between doctors and patients (13.2%) , service attitude problems (12.5%) and patient illness (16.9%) . Conclusion:Workplace violence remains prevalent within this medical consortium. Targeted measures should be implemented based on hospital size, functions, and patient demographics.

Objective:To investigate the characteristics, influencing factors, consequences, coping strategies, and preventive measures of workplace violence in medical consortiums.Methods:Medical professionals from a specialized hospital in South China and its consortium members (2 primary-level, 1 secondary-level, and 1 tertiary-level hospitals) were surveyed in December 2022 and July 2023. Quantitative research included 1013 participants, while qualitative research involved 35 participants. Workplace violence was assessed using the "National Case Study Tool for Workplace Violence in Healthcare Institutions-Survey Questionnaire", with qualitative analysis conducted through semi-structured interviews. Inter-group comparisons employed chi-square tests or Fisher's exact probability test, with logistic regression models for bivariate analysis.Results:The overall incidence rates of violence, psychological violence, and physical violence in this medical consortium were 31.7% (321/1, 013) , 30.6% (310/1, 013) , and 3.3% (33/1, 013) , respectively. Specifically, the overall violence rates in Level 1, Level 2, and Level 3 hospitals were 22.7% (41/181) , 27.4% (43/157) , and 35.1% (237/675) . The physical violence rates were 1.1% (2/181) , 10.2% (16/157) , and 2.2% (15/675) , respectively. The psychological violence rates stood at 22.7% (41/181) , 24.8% (39/157) , and 34.1% (230/675) . The total violence in tertiary hospitals was significantly higher than that in tertiary hospitals ( F=10.10, P=0.002) , and the incidence of psychological violence in tertiary hospitals was significantly higher than that in tertiary hospitals ( Flevel 1 vs level 3=8.61, P=0.003; Flevel 2 vs level 3=4.96, P=0.026) , incidence of verbal insults ( Flevel 1 vs level 3=8.25, P=0.004; Flevel 2 vs level 3=6.36, P= 0.012) was significantly higher than that of level 1 and level 2 hospitals. The incidence of physical violence in secondary hospitals was significantly higher than that of other two-level hospitals ( P<0.001) . Compared with other types of violence, the incidence of verbal insults is highest in hospitals at all levels. Higher anxiety about violence was a risk factor for psychological violence in hospitals at all levels ( Flevel1 hospital=15.44, P=0.004; Flevel2 hospital=22.87, P<0.001; Flevel3 hospital=84.12, P<0.001) . Health workers in all three levels of hospitals has a high level of approval of existing workplace violence interventions. The main causes of workplace violence were poor communication between doctors and patients (13.2%) , service attitude problems (12.5%) and patient illness (16.9%) . Conclusion:Workplace violence remains prevalent within this medical consortium. Targeted measures should be implemented based on hospital size, functions, and patient demographics.