Revealing the oncogenic role of elevated GNL3L expression in esophageal squamous cell carcinoma: insights into the STAT3 pathway.

Background: Esophageal squamous cell carcinoma (ESCC) patients carries a poor prognosis, with limited effective therapeutic targets. This study aimed to clarify the clinical significance of guanine nucleotide-binding protein like 3-like (GNL3L) protein expression in ESCC and its role in malignant progression. Methods: GNL3L expression and associated cancer-promoting pathways in ESCC were interrogated via bioinformatics analysis through use of The Cancer Genome Atlas (TCGA) database. Subsequent verification of GNL3L protein expression in ESCC, coupled with clinical data, was conducted through immunohistochemistry and followed by a comprehensive prognostic analysis. We further investigated potential signaling pathways facilitating ESCC progression, employing a combination of bioinformatics analysis and immunohistochemical (IHC) experiments. Results: Bioinformatics analysis unveiled a significant elevation in GNL3L expression, particularly in gastrointestinal tumors and ESCC. Immunohistochemistry confirmed elevated GNL3L expression in ESCC tissues. Regression analysis established a correlation between elevated GNL3L expression and advanced tumor node metastasis (TNM) stage, with high expression associated with poor prognosis in patients with ESCC. Our integrated approach of bioinformatics and IHC analysis indicated a potential role of the signal transducers and activators of transcription 3 (STAT3) signaling pathway in ESCC progression. Conclusions: High GNL3L expression significantly contributes to the malignant progression of ESCC. This study further elucidates the mechanisms driving ESCC progression and offers possible insights for more effective diagnosis and treatment strategies.

Effect of follicle-stimulating hormone and luteinizing hormone on apoptosis, autophagy, and the release and reception of some steroid hormones in yak granulosa cells through miR-23a/ASK1 axis.

Follicle-stimulating hormone (FSH), luteinizing hormone (LH), miR-23a, apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase (JNK), autophagy and apoptosis play crucial roles in follicular development. However, their role in yak granulosa cells (GCs) remains unknown. Therefore, we examined the effect of miR-23a, ASK1, FSH, and LH on apoptosis, autophagy, and the release and reception of some steroid hormones in these cells. Our results showed that miR-23a overexpression significantly increased the abundance of Beclin1, the LC3II/I ratio, and the number of Ad-mRFP-GFP-LC3-labeled autophagosomes, and decreased p62 abundance. Additionally, Bax abundance and the number of terminal deoxynucleotidyl transferase deoxynucleotide triphosphate nick end labeling-positive cells were reduced, while Bcl2 expression was increased. Overexpression of miR-23a also significantly increased the abundance of estradiol receptor α (ER-α) and ß (ER-ß) and the concentrations of estradiol (E2), progesterone (P4) in yak GCs. Here, treating yak GCs with miR-23a decreased ASK1 expression, which regulates ASK1/JNK-mediated apoptosis, autophagy, E2 and P4 levels, and ER-α/ß abundance. In contrast, treatment of yak GCs with FSH (10 µg/mL) and LH (100 µg/mL) increased miR-23a abundance, regulating the subsequent effect on ASK1/JNK-mediated apoptosis, autophagy, ER-α/ß abundance, and E2 and P4 concentrations. In conclusion, miR-23a enhances autophagy in yak GCs, attenuates apoptosis, and increases ER-α/ß abundance and E2 and P4 concentrations by downregulating ASK1. Additionally, FSH and LH can regulate these effects of miR-23a by altering its expression. These results provide important insights that can inform the development of strategies to reduce abnormal follicular atresia and improve the reproductive rate of yaks.

Probiotics intervention in colorectal cancer: From traditional approaches to novel strategies / 中华医学杂志(英文版)

The intestine harbors a large population of microorganisms that interact with epithelial cells to maintain host healthy physiological status. These intestinal microbiota engage in the fermentation of non-digestible nutrients and produce beneficial metabolites to regulate host homeostasis, metabolism, and immune response. The disruption of microbiota, known as dysbiosis, has been implicated in many intestinal diseases, including colorectal cancer (CRC). As the third most common cancer and the second leading cause of cancer-related death worldwide, CRC poses a significant health burden. There is an urgent need for novel interventions to reduce CRC incidence and improve clinical outcomes. Modulating the intestinal microbiota has emerged as a promising approach for CRC prevention and treatment. Current research efforts in CRC probiotics primarily focus on reducing the incidence of CRC, alleviating treatment-related side effects, and potentiating the efficacy of anticancer therapy, which is the key to successful translation to clinical practice. This paper aims to review the traditional probiotics and new interventions, such as next-generation probiotics and postbiotics, in the context of CRC. The underlying mechanisms of probiotic anti-cancer effects are also discussed, including the restoration of microbial composition, reinforcement of gut barrier integrity, induction of cancer cell apoptosis, inactivation of carcinogens, and modulation of host immune response. This paper further evaluates the novel strategy of probiotics as an adjuvant therapy in boosting the efficacy of chemotherapy and immunotherapy. Despite all the promising findings presented in studies, the evaluation of potential risks, optimization of delivery methods, and consideration of intra-patient variability of gut microbial baseline must be thoroughly interpreted before bench-to-bedside translation.

Self-assembled and Zn(II)-coordinated dipeptide nanoparticles with membrane-rupturing action on bacteria.

Metal ion-coordinated self-assembled short-chain amino acid peptide molecules with multi-photon excitation wavelengths and their photoluminescence properties are advantageous for fluorescence-based diagnostics and treatments of biological diseases based on their extra features of antibacterial agents. We have designed a novel strategy based on tryptophan molecule coordinated with Zn(II) ions in the form of biocompatible spherical nanoparticles of diameter 30-80 nm which have been used for antibacterial treatments against different kinds of pathogenic bacteria (Escherichia coli, Salmonella typhimurium, and Pseudomonas). Preferably, we have used tryptophan-phenylalanine (Trp-Phe), a dipeptide molecule having tryptophan as principal material against E. coli strains as antimicrobial agents for surface rupturing and killing purposes. Furthermore, based on single amino acid, tryptophan, self-assembled and Zn(II)-coordinated dipeptide nanoparticles (Zn-DPNPs) were studied against three types of multi-drug-resistant bacteria as an active antimicrobial agent. These antibacterial efficient nanoparticles may have best alternative of antibiotic drugs for clinical applications. The capability of self-assembled fluorescence behavior of Zn-coordinated dipeptide molecules and higher hydrophobicity against bacterial cell wall will perform as antimicrobial fluorescent agents. KEY POINTS: • Zn(II) and Cu(II) better coordinated into self-assembled NPs. • Fluorescence signals showed interaction of NPs with gram -ve cell wall. • Significant surface-damaging effects were observed in the case of Cu-DPNPs and Zn-DPNPs.

MTDH-stabilized DDX17 promotes tumor initiation and progression through interacting with YB1 to induce EGFR transcription in Hepatocellular Carcinoma.

Metadherin (MTDH) is a well-established oncogene in various cancers including Hepatocellular Carcinoma (HCC). However, the precise mechanism through which MTDH promotes cancer-related signaling pathways in HCC remains unknown. In this study, we identified DDX17 as a novel binding partner of MTDH. Furthermore, MTDH increased the protein level of DDX17 by inhibiting its ubiquitination. We confirmed that DDX17 was a novel oncogene, with dramatically upregulated expression in HCC tissues. The increased expression of DDX17 was closely associated with vascular invasion, TNM stage, BCLC stage, and poor prognosis. In vitro and in vivo tests demonstrated that DDX17, a downstream target of MTDH, played a crucial role in tumor initiation and progression. Mechanistically, DDX17 acted as a transcriptional regulator that interacted with Y-box binding protein 1 (YB1) in the nucleus, which in turn drove the binding of YB1 to its target epidermal growth factor receptor (EGFR) gene promoter to increase its transcription. This in turn increased expression of EGFR and the activation of the downstream MEK/pERK signaling pathway. Our results identify DDX17, stabilized by MTDH, as a powerful oncogene in HCC and suggest that the DDX17/YB1/EGFR axis contributes to tumorigenesis and metastasis of HCC.

Effect of mirror therapy with augmented reality on attention of stroke patients / 中国康复理论与实践

ObjectiveTo investigate the effect of mirror therapy with augmented reality on attention of stroke patients. MethodsFrom January, 2020 to December, 2022, 60 stroke patients in the First People's Hospital of Changzhou were randomly divided into control group (n = 30) and observation group (n = 30). Both groups received routine occupational therapy, and the observation group received mirror therapy with augmented reality additionally, for four weeks. They were assessed with Digit Span Test (DST), Digit Cancellation Test (D-CAT3 and D-CAT3P), Symbol Digit Modalities Test (SDMT) and Paced Auditory Serial Addition Test (PASAT) before and after treatment. ResultsBefore treatment, there was no significant difference in the scores of the DST, D-CAT3, D-CAT3P, SDMT and PASAT between two groups (P > 0.05). After treatment, all the indexes improved in the observation group (|t| > 3.663, P < 0.01), and improved more in the observation group than in the control group (|t| > 2.037, P < 0.05). ConclusionThe mirror therapy with augmented reality could effectively improve attention of stroke patients in the short term.

Clinical distribution and drug resistance characteristics of carbapenem-resistant Klebsiella pneumoniae / 中华预防医学杂志

To explore the clinical distribution and drug resistance characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP), in order to provide reference for the prevention and treatment of CRKP infection. Retrospective analysis was performed on 510 clinical isolates of CRKP from January 2017 to December 2021, and strain identification and drug sensitivity tests were conducted by MALDI-TOF mass spectrometer and VITEK-2 Compact microbial drug sensitivity analyzer. The carbapenemase phenotype of CRKP strain was detected by carbapenemase inhibitor enhancement test. The CRKP strain was further categorized by immunochromogenic method and polymerase chain reaction (PCR) was used for gene detection. The results showed that 302 strains (59.2%) were derived from sputum, 127 strains (24.9%) from urine and 47 strains (9.2%) from blood. 231 (45.3%) were mainly distributed in intensive care, followed by 108 (21.2%) in respiratory medicine and 79 (15.5%) in neurosurgery. Drug susceptibility test result shows that the resistant rate of tigecycline increased from 1.0% in 2017 to 10.1% in 2021, the difference was statistically significant (χ2=14.444,P<0.05). The results of carbapenemase inhibitor enhancement test showed that 461 carbapenemase strains (90.4%) of 510 CRKP strains, including 450 serinase strains (88.2%), 9 metalloenzyme strains (1.8%), and 2 strains (0.4%) produced both serine and metalloenzyme. 49 strains (9.6%) did not produce enzymes. Further typing by immunochromogenic assay showed that 461 CRKP strains were KPC 450 (97.6%) and IMP 2 (0.4%). 7 NDM (1.5%); 2 strains of KPC+NDM (0.4%); PCR results were as follows: 450 strains of blaKPC (97.6%), 2 strains of blaIMP (0.4%), 7 strains of blaNDM (1.5%), and 2 strains of blaKPC+NDM (0.4%). In conclusion, CRKP strains mainly originated from sputum specimens and distributed in intensive care department, and the drug resistance characteristics were mainly KPC type in carbapenemase production. Clinical microbiology laboratory should strengthen the monitoring of CRKP strains, so as to provide reference for preventing CRKP infection and reducing the production of bacterial drug resistance.

Principles of extramural health care for chronic wounds in China / 中华创伤杂志(英文版)

Development of extramural health care for chronic wounds is still in its infancy in China, and thus it is urgent and vital to establish a correct concept and practicable principles. The authors reviewed recent domestic and international literature and summarized the following treatment procedures and principles for extramural health care of chronic wounds. (1) The patient needs to do self-assessment of the wound by using available simple methods; (2) The patient consults with professional physicians or nurses on wound care to define the severity and etiology of the non-healing wound; (3) Professionals evaluate the existing treatment strategies; (4) Etiological treatments are given by professionals; (5) Patients buy needed dressings via the more convenient ways from pharmacies, e-commerce platform or others; (6) Professionals provide a standardized and reasonable therapeutic plan based on the patient's wound conditions; (7) Both professionals and the patient pay attention to complications to prevent adverse outcomes; (8) Professionals strengthen the public education on wound care and integrated rehabilitation. This review expected to provide new perspectives on the therapeutic strategies for chronic wounds in an extramural setting.

Research progress on occupational exposure to carbon nanotubes and carbon nanotubes-induced pulmonary fibrosis / 中国职业医学

Carbon nanotube (CNT), as a new nanomaterial, is widely used in commercial and industrial production. The occupational exposure of workers involved in CNT production and manufacturing is gradually increasing. CNT mainly enters the human body through the respiratory system, and mainly exerts toxic effects on the respiratory system, including decreased lung function, lung inflammation, and pulmonary fibrosis. Pulmonary fibrosis, as one of the important diseases caused by CNT exposure, has attracted attention and been studied. The process of pulmonary fibrosis induced by CNT has four stages: acute pulmonary inflammatory response, structural destruction and parenchymal injury of lung tissue, impaired lung tissue repair and pulmonary fibrosis. The molecular mechanisms of CNT induced pulmonary fibrosis may be related to cell proliferation, epithelial-mesenchymal transition, fibroblast-myofibroblast differentiation, pulmonary inflammation, immune response and oxidative stress. In the future, it is needed to explore the pathogenesis of pulmonary fibrosis caused by CNT through animal experiments, and carry out large sample and multi-center epidemiological studies for verification.

Tidal breathing nasal nitric oxide in preschool children aged 3 to 5 years / 中华实用儿科临床杂志

Objective:To explore the threshold of tidal breathing nasal nitric oxide (TB-nNO) in diagnosing primary ciliary dyskinesia (PCD) in children aged 3 to 5 years.Methods:Retrospective study.The TB-nNO values were examined of 165 healthy children aged 3-5 in a kindergarten in Xicheng District, Beijing, from March 27 to March 29, 2018, which were also measured in children aged 3-5 years who were diagnosed as PCD, cystic fibrosis, bronchiolitis obliterans, bronchiectasis caused by other diseases and asthma in the Second Department of Pediatric Pneumology, Beijing Children′s Hospital, Capital Medical University from January 2018 to December 2021.Relevant factors associated with TB-nNO in normal children were screened by a multiple linear regression model.The cut-off value of TB-nNO in diagnosing PCD in preschool children aged 3-5 years was determined by calculating the maximum area under the receiver operating characteristic (ROC) curve.Results:TB-nNO value in healthy children aged 3, 4 and 5 years were (94.8±36.4) nL/min, (103.3±50.7) nL/min and (106.9±61.5) nL/min, respectively.The mean TB-nNO value in 9 children with PCD was (18.9±10.8) nL/min.TB-nNO values in 49 children with asthma, 19 children with bronchiolitis obliterans, 17 children with bronchiectasis and 6 children with cystic fibrosis were (97.7±51.1) nL/min, (93.2±49.2) nL/min, (93.7±75.3) nL/min and (45.4±18.2) nL/min, respectively.Using 30 nL/min of TB-nNO as the cut-off point, the sensitivity and specificity of TB-nNO in diagnosing PCD were 88.9% (8/9) and 96.9%, respectively.The area under the ROC curve was 98.3% (95% CI: 95.3%-100.0%). Conclusions:TB-nNO value of 30 nL/min can be used as the cut-off point in the diagnosis screening of PCD in children aged 3-5 years.Its diagnostic value in this age group should be further evaluated.

Research progress of multiple MRI-based radiomics in glioma / 国际生物医学工程杂志

Imaging histology plays a key role in the diagnosis of tumors, prognostic assessment, and evaluation of tumor response to therapy. Multimodal magnetic resonance imaging (MRI) imaging histology can link the imaging histological presentation of a tumor to its molecular phenotype, offering greater advantages in the grading of gliomas and in the prediction and prognosis of treatment response. It utilizes conventional and advanced techniques to differentiate brain tumors from non-neoplastic lesions and can be used for the diagnosis of gliomas and the differentiation of gliomas from brain metastases. Semi-automated and automated tumor segmentation techniques have also been developed for the assessment of the recurrence of gliomas. In this review paper, the research progress in multimodal MRI imaging histology was reviewed, including the prediction of important molecular biological markers of glioma, graded diagnosis of glioma, differential diagnosis with brain metastases, and assessment of postoperative recurrence.

Study on the correlation between retinal microvascular density and damage to visual field in patients with sellar region tumor / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the changes of retinal microvascular density in patients with sellar region tumor, and its correlation with the damage to visual field, and to explore its application value in evaluating optic nerve injury of those patients.METHODS: Cross-sectional study. A total of 157 patients(292 eyes)with sellar region tumor, including 82 cases(152 eyes)of pituitary adenoma and 75 cases(140 eyes)of craniopharyngioma, were selected from neurosurgery department and ophthalmology department of Beijing Tiantan Hospital, Capital Medical University between October 2018 and May 2022. A total of 90 people(180 eyes)during the same period, including the family members of patients, students and staff in Beijing Tiantan Hospital, Capital Medical University were collected as control group. All participants underwent optical coherence tomography angiography(OCTA)examination. The changes of retinal microvascular density and its correlation with visual field parameters were compared between the two groups.RESULTS: In patients with sellar region tumor, the radial peripapillary capillary(RPC)and superficial retinal capillary plexus(SRCP)density were significantly lower than that in the control group [50.81%(46.49%, 53.49%)vs. 52.78%(50.73%, 54.51%)and 50.57%(48.13%, 52.73%)vs. 51.63%(49.78%, 53.02%), all P<0.05]. The RPC density in the craniopharyngioma group was lower than that in the pituitary adenoma group [49.71%(44.33%, 53.14%)vs. 51.37%(47.42%, 53.95%), P<0.05]. The MD, PSD and VFI of the sellar region tumor group were -4.33(-12.22, -1.85)dB, 3.37(1.91, 8.82)dB and 92%(65%, 97%)respectively. RPC density of patients with sellar region tumor was positively correlated with MD and VFI, and was negatively correlated with PSD. The SRCP density of each quadrant was positively correlated with MD, and was positively correlated with VFI except Para-T and it was negatively correlated with PSD(all P<0.05).CONCLUSION: Retinal microvascular changes were present in patients with sellar region tumor. Lower vessel density indicates more severe damage to visual field. In the clinic, visual field examinations combined with OCTA were helpful to find the optic nerve injury of patients.

Application and prospect of gene therapy for fundus vascular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Fundus vascular diseases, including neovascular age-related macular degeneration(nAMD)and diabetic retinopathy(DR), are the leading causes of visual impairment worldwide. With the accelerated aging and increased incidence of diabetes, the prevalence of these two fundus diseases will continue to rise. Currently, intraocular injection of anti-vascular endothelial growth factor(anti-VEGF)remains the first-line treatment for fundus vascular diseases, but disadvantages exist, such as frequent intraocular injections, high cost and poor compliance, thus more durable and effective therapeutic strategies need to be explored. The successful application of gene therapy in inherited retinal diseases(IRDs)provides a new idea for the treatment of fundus vascular diseases. With the ongoing of several clinical trials, gene therapy for fundus vascular diseases is expected to be employed in the clinical setting. But there still remain some concerns, including the optimal therapeutic targets selection, administration route and safety issues. This review focuses on the application and prospect of gene augmentation and gene editing-mediated anti-VEGF therapy for the treatment of nAMD and DR.

Characterization of a D-mannitol oxidase from Paenibacillus sp. and its application in the preparation of D-mannose / 生物工程学报

D-mannose has many functional activities and is widely used in food, medicine, agriculture and other industries. D-mannitol oxidase that can efficiently convert D-mannitol into D-mannose has potential application in the enzymatic preparation of D-mannose. A D-mannitol oxidase (PsOX) was found from Paenibacillus sp. HGF5. The similarity between PsOX and the D-mannitol oxidase (AldO) from Streptomyces coelicolor was 50.94%. The molecular weight of PsOX was about 47.4 kDa. A recombinant expression plasmid pET-28a-PsOX was constructed and expressed in Escherichia coli BL21(DE3). The Km and kcat/Km values of PsOX for D-mannitol were 5.6 mmol/L and 0.68 L/(s·mmol). Further characterization of PsOX showed its optimal pH and temperature were 7.0 and 35 ℃, respectively, while its enzyme activity could be stably remained below 60 ℃. The molar conversion rate of 400 mmol/L D-mannitol by PsOX was 95.2%. The whole cells of PsOX and AldO were used to catalyze 73 g/L D-mannitol respectively. The reaction catalyzed by PsOX completed in 9 h and 70 g/L D-mannose was produced. PsOX showed a higher catalytic efficiency compared to that of AldO. PsOX may facilitate the enzymatic preparation of D-mannose as a novel D-mannose oxidase.

Estimation of the population, death, and quality of life in Shaanxi Province, western China: a cross-sectional study / 中华医学杂志(英文版)

BACKGROUND@#Measuring the health of the population is of great significance to the development of a region. We aimed to estimate the population, probability of death, and quality of life in western China.@*METHODS@#We calculated the age-specific mortality rate and prevalence rate of diseases and injuries using the Full Population Database and the Home Page of Inpatient Medical Record. We used multiple interpolation methods to insert missing information from the death data and the model of Kannisto to adjust the mortality rate for elderly individuals. The age-specific prevalence rate of diseases and injuries was adjusted according to the standard ratio of age and methods of equal proportional allocation. Life expectancy was calculated by a life table, and the quality of life was estimated using the Sullivan method.@*RESULTS@#The total population continued to increase in 2015 to 2019 in the Shaanxi Province, China. The mortality rate of children under five has improved, and the mortality rate of people over 65 is decreasing year by year. Life expectancy increased from 74.66 years in 2015 to 77.19 years in 2019. Even with the total risk of disease and injury, the health-adjusted life expectancy increased by 1.90 years within 5 years, and the number of unhealthy years significantly improved. Health-adjusted life expectancy increased by 1.75 years when only considered the ten major disease systems (tumors; endocrinology, nutrition and metabolism; mental and behavioral disorders; nervous system; sensory diseases; circulatory system; respiratory system; digestive system; genitourinary system; musculoskeletal system and connective tissue), and the number of unhealthy years increased slightly.@*CONCLUSIONS@#In the past five years, Shaanxi Province has made progress in improving life expectancy and controlling the development of chronic diseases. It is necessary to take specific preventive measures and improve the quality of basic public health services.

Effects of total flavone of oldenlandia diffusa on the proliferation and apoptosis of hepatocellular carcinoma stem cell / 西安交通大学学报(医学版)

【Objective】 To investigate the effects of total flavone of oldenlandia diffusa (FOD) on the proliferation and apoptosis of hepatocellular carcinoma (HCC) stem cells sorted from Huh7. 【Methods】 Human HCC cell lines Huh7 was cultured in vitro; CD133 positive (CD133+) stem cells in Huh7 cell line were sorted by flow cytometry, and stem cell markers such as Nanog, Oct4 and Sox2 were tested by Western blotting. CD133+-Huh7 was stimulated by different concentrations (0 μg/mL, 50 μg/mL, 100 μg/mL and 400 μg/mL) of FOD for different time (24 h, 48 h, 72 h and 96 h). CCK8 and plate cell cloning assay were used to detect the effect of FOD on CD133+-Huh7 proliferation while Annexin V-PE/7-AAD was used to detect the effect of FOD on CD133+-Huh7 apoptosis. Western blotting was used to detect the protein expressions of protein 53 (P53), factor associated suicide-Fas-associating protein with a novel death domain (Fas-FADD), B-cell lymphoma-2 (Bcl-2), Cleaved-Caspase3, and Bcl-2 associated X protein (Bax). 【Results】 More than 95% of stem cells were purified for further experiments. Cell proliferation of CD133+-Huh7 was significantly inhibited by FOD, with the significant suppression at the concentration of 100 μg/mL for 72 h compared with negative control group (P<0.05). The apoptosis rate was significantly upregulated than that in the negative control group (P<0.05). The protein expression of Bcl2 decreased while Bax and Cleaved-Caspae3 increased via FAS/FADDD and P53 axis. 【Conclusion】 FOD can significantly inhibit the proliferation and promote the apoptosis of CD133+-Huh7.

An overview of disease treatment strategies targeting the alternative splicing of pre-mRNA / 药学学报

Alternative splicing of pre-messenger RNA (pre-mRNA) is a crucial mechanism for the diversity of the human transcriptome and proteome. Alternative splicing is a complex gene regulation process. Whole-transcriptome analysis shows that 95% of human exonic genes are alternatively spliced, involving various cis-acting elements and trans-acting factors. Any changes in any component or step may cause erroneous splicing events and lead to the occurrence of various related diseases. In addition to gene replacement therapy that directly changes the splicing results, RNA splicing modification is expected to become a new therapeutic strategy to alleviate or treat diseases by targeting and correcting abnormal pre-mRNA splicing. Splicing modification tools currently developed including RNA trans-splicing, antisense oligonucleotides, small interfering RNA, and small molecule drugs can correct abnormal splicing through different ways. This article reviews the resent progress of epigenetic regulation of pre-mRNA alternative splicing in recent years, and discusses the occurrence and regulation of alternative splicing, the types of diseases caused by related splicing defects, and the current-used tools for targeting and altering splicing. The importance of splicing modification strategies in the future treatment of human diseases is envisioned.

A TCA-based Ideological and Political Teaching Model for the Biochemistry Course: Its Construction and Application / 中国生物化学与分子生物学报

Driven by initiatives of constructing the Four New Disciplines (new engineering, new medical sciences, new agriculture and new liberal arts) for higher education, Biochemistry teaching with ideological and political concerns is critical to the education achievements. Over the past 6 years, FMMU has carried out trials and practices on TCA model in Biochemistry teaching which can serve as a shared formula. TCA is originally an abbreviation for “tricarboxylic acid” cycle, and herein it stands for thinking and teamwork (T), critique (C) and appreciation (A), which hopefully could provide students with moral norms for cognition, science and life. Accordingly, a strategy is proposed to help systematically implement this “TCA” model, which highlights the notion of “3-integration for teaching”, “3-thinking for learning” and 3-step for setting”. Such “TCA”-based ideological and political model is adaptable to various universities in designing advanced teaching activities. In the case of FMMU, we created a “TCA pigeon” ideological and political pattern, with “pigeon” signifying medicine, the Air Force and peace, showing the distinctive features of a military medical university. Meanwhile, we have designed three advanced teaching activities. Specifically, “the magic biochemical-circle”, a shared learning platform that develops thinking abilities with a focus on autonomous learning and personal demonstration; “inter-guidance by basic and clinical teachers”, a heuristic large class that elicits critical thinking on basis of feedback, discussion and iteration; a task-driven “virtual reality (VR) program” enables students to deal with complicated situation and to undertake troubleshooting. The above “TCA pigeon” pattern has shown a generally favorable result among students in developing their skills such as holistic thinking, deep learning, introspecting and self-improvement. Yet, a few problems still occurred in practice and remained to be resolved.