Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To investigate the predictive value of preoperative aspartate aminotransferase to alanine aminotransferase ratio (AAR) for early recurrence after radical resection of single small hepatocellular carcinoma.Methods:A retrospective cohort study was conducted to analyze the clinical data of 137 patients who underwent radical resection of liver cancer at the General Hospital of Ningxia Medical University from January 2017 to July 2021. These patients were categorized into a recurrence group ( n = 72) and a non-recurrence group ( n = 65) based on early postoperative recurrence. Univariate and multivariate logistic regression analyses were conducted in the training cohort to identify independent risk factors for early recurrence of small hepatocellular carcinomas. Subsequently, the AARs were grouped, and patients with similar propensity scores estimated by the logistic model were matched 1:1 using the Propensity Score Match method with a caliper value of 0.02 to eliminate confounders. Logistic regression analysis was then repeated to assess the predictive value of the matched AAR for postoperative recurrence in patients with single small hepatocellular carcinoma. Results:Univariate analysis revealed that age ( χ2 = 4.22, P = 0.040), the ratio of fibrinogen to albumin ( χ2 = 8.26, P = 0.004), and the AAR ( χ2 = 5.83, P = 0.016) were significantly associated with early recurrence of small liver cancer after radical resection. Multivariate logistic regression analysis further identified age ( P = 0.042), the ratio of fibrinogen to albumin ( P = 0.024), and the AAR ( P = 0.018) as independent risk factors for early recurrence of single small hepatocellular carcinoma following radical surgery. After excluding confounding factors using the Propensity Score Match method, 25 patient pairs were successfully matched. Post-matching logistic regression analysis revealed that an AAR > 0.74 ( P = 0.005) and age > 60 years ( P = 0.024) were independent risk factors for early recurrence in patients with single small hepatocellular carcinoma following radical resection. Conclusion:Preoperative AAR is an independent risk factor for early recurrence in patients with single small hepatocellular carcinoma following surgery, demonstrating excellent predictive value.

Idiopathic pulmonary fibrosis(IPF)is a chronic,progressive interstitial lung disease.IPF incidence is increasing yearly with high mortality and poor prognoses.At present,IPF pathogenesis remains unclear,and its treatments are limited.The experimental model is important to further study IPF pathogenesis and explore effective preventive and therapeutic measures.In recent years,its modeling method have been continuously developed and optimized.This study summarizes the establishment method and research progress of IPF experimental models in recent years to provide ideas and references for preclinical research to select appropriate experimental models.

OBJECTIVE To investigate the efficacy and safety of clobazam in the additional treatment of refractory epilepsy in children， and provide reference for clinically safe and rational drug use. METHODS The literatures about additional clobazam treatment for refractory epilepsy in children were searched from PubMed， The Cochrane Library， Embase， CNKI， VIP and Wanfang database during the inception to November 2023. After literature screening and data extraction， the quality of included literature was evaluated according to quality evaluation tool for methodological evaluation indicators of non-randomized controlled trial， and then meta-analysis of single-group rate and sensitivity analysis were performed by using RevMan 5.3 software. RESULTS Finally， 18 one-arm studies were included， with a total of 1 424 children. The results showed that compared with before additional treatment， the proportion of patients with seizures-free （proportion of patients with seizure reduction of 100%） was 24%[95%CI （0.18，0.32）， P＜0.000 01] after conversion； the proportion of patients with seizure reduction ≥75% was 32%[95%CI（0.25，0.40）， P＜0.000 1] after conversion； the proportion of patients with seizure reduction ≥50% was 53%[95%CI（0.44，0.61），P＜0.000 01]； the proportion of patients with seizure reduction ＜50% or no change was 35%[95%CI（0.24，0.49），P＝0.04] after conversion； the proportion of patients with seizure increase was 9%[95%CI（0.05，0.18），P＜0.000 01] after conversion. The proportion of patients with adverse reactions was 31%[95%CI（0.23，0.40），P＜0.000 1] after conversion； the proportion of patients with discontinuation due to adverse reactions was 10%[95%CI（0.07， 0.15）， P＜0.000 01] after conversion. The common adverse drug reactions were drowsiness， fatigue and behavior change， etc. The results of the sensitivity analysis showed that the study was robust. CONCLUSIONS Clobazam is an effective additional therapy for refractory epilepsy in children， but its adverse effects should be vigilant.

Objective To understand the epidemiological characteristics of Chlamydia trachomatis infection in Hubei province, and to provide scientific basis for prevention and control. Methods The data of Chlamydia trachomatis infection cases reported through the China Information System for Disease Control and Prevention from 2008 to 2022 were collected for epidemiological statistical analysis. Results The incidence of Chlamydia trachomatis infection in Hubei Province showed an increasing trend from 2008 to 2022, with an average annual reported incidence of 2.26/100 000. The top three reported incidence areas were Shiyan (6.04/100 000), Yichang (5.62/100 000) and Shennongjia (3.47/ 100 000). The reported incidence in southeast area was significantly higher than that in other areas (χ²=2869.603 , P < 0.001). The high incidence age group was 20-39 years old, accounting for more than 70%. The reported incidence in females was higher than that in males (χ²=1429.27 , P < 0.001). Housework and unemployment were the most common professions (43.54%). The case reporting institutions were mainly comprehensive hospitals (87.29%). Conclusion To effectively control the infection and transmission of Chlamydia trachomatis, it is necessary to strengthen the health popularization of STD knowledge, intervention and early active screening of high-risk groups.

Objective To investigate the changes and features of firing activities of interneurons in dorsal hippocampus during the acquisition and consolidation of associative memory.Methods Trace eyeblink conditioning(tEBC)was utilized as a behavioral model of associative memory.A total of 18 wild-type C57BL/6 mice(male,10～12 weeks old,weighing 22～25 g)were randomly divided into a paired group(n=9)and an unpaired group(n=9).Paired presentations of conditioned stimulus(CS)and unconditioned stimulus(US)were utilized to train these mice.The mice from the paired group were given US training in 250 ms after CS training,and those from the unpaired group received similar doses of CS and US training,but with no paired relationship in time.After 4 consecutive days'training,the mice of the paired group acquired tEBC,manifesting conditioned eyeblink responses(CR).Tetrode arrays were applied to record neuronal activity in dorsal hippocampus during both tEBC training epoch and the 1.5 h epoch after training.The putative interneurons(n=105)were identified according to their firing rate and spike width from trough to peak.Specific changes in hippocampal interneurons activity during tEBC training and post-training slow wave sleep were analyzed respectively.Results ①At the early stage of CR acquisition(the 1st and 2nd days),CS could evoke significantly greater activity of dorsal hippocampal interneurons in the paired group(P＜0.05).During sharp wave ripples(SWR)in the post-training slow wave sleep,the firing rate of dorsal hippocampal interneurons was significantly lower in the paired group than the unpaired group(P＜0.05).②At the late stage of CR acquisition(the 3rd and 4th days),no significant differences in CS evoked activity of dorsal hippocampal interneurons were observed between the paired group and unpaired group,neither in the firing rate of dorsal hippocampal interneurons during SWR in the post-training slow wave sleep between the 2 groups.Conclusion The dorsal hippocampal interneurons show opposite changes in firing activity during the acquisition and consolidation of associative memory.

Schwann cells (SCs), a type of glial cell in the peripheral nervous system, can serve as a source of mesenchymal stem cells (MSCs) to repair injured pulp. This study aimed to investigate the role of SCs in tooth germ development and repair of pulp injury. We performed RNA-seq and immunofluorescent staining on tooth germs at different developmental stages. The effect of L-type calcium channel (LTCC) blocker nimodipine on SCs odontogenic differentiation was analyzed by real-time polymerase chain reaction and Alizarin Red S staining. We used the PLP1-CreERT2/ Rosa26-GFP tracing mice model to examine the role of SCs and Cav 1.2 in self-repair after pulp injury. SC-specific markers expressed in rat tooth germs at different developmental stages. Nimodipine treatment enhanced mRNA levels of osteogenic markers (DSPP, DMP1, and Runx2) but decreased calcium nodule formation. SCs-derived cells increased following pulp injury and Ca v 1.2 showed a similar response pattern as SCs. The different SCs phenotypes are coordinated in the whole process to ensure tooth development. Blocking the LTCC with nimodipine promoted SCs odontogenic differentiation. Moreover, SCs participate in the process of injured dental pulp repair as a source of MSCs, and Cav 1.2 may regulate this process.

Palliative care not only embodies modern life perspectives, but also encompasses significant traditional Chinese cultural elements.The primary objective of palliative care is to alleviate patient suffering, preserve their dignity, and facilitate a peaceful passing.Traditional Chinese medicine, known for its simplicity, accessibility, affordability, and efficacy in disease prevention and treatment, adopts a holistic approach to address systemic pain through personalized treatment based on symptom differentiation.This approach aims to enhance the quality of life for terminally ill patients.To equip palliative care providers with essential clinical skills in traditional Chinese medicine, the National Center of Gerontology and Beijing Palliative Care Guidance Center collaborated with experts and scholars to develop guidelines focusing on common end-of-life symptoms.Through extensive deliberation, expert evaluation, and revisions, this guidance document was crafted as a valuable resource for palliative care practitioners, traditional Chinese medicine clinicians, and researchers in the field.

Schwann cells (SCs), a type of glial cell in the peripheral nervous system, can serve as a source of mesenchymal stem cells (MSCs) to repair injured pulp. This study aimed to investigate the role of SCs in tooth germ development and repair of pulp injury. We performed RNA-seq and immunofluorescent staining on tooth germs at different developmental stages. The effect of L-type calcium channel (LTCC) blocker nimodipine on SCs odontogenic differentiation was analyzed by real-time polymerase chain reaction and Alizarin Red S staining. We used the PLP1-CreERT2/ Rosa26-GFP tracing mice model to examine the role of SCs and Cav 1.2 in self-repair after pulp injury. SC-specific markers expressed in rat tooth germs at different developmental stages. Nimodipine treatment enhanced mRNA levels of osteogenic markers (DSPP, DMP1, and Runx2) but decreased calcium nodule formation. SCs-derived cells increased following pulp injury and Ca v 1.2 showed a similar response pattern as SCs. The different SCs phenotypes are coordinated in the whole process to ensure tooth development. Blocking the LTCC with nimodipine promoted SCs odontogenic differentiation. Moreover, SCs participate in the process of injured dental pulp repair as a source of MSCs, and Cav 1.2 may regulate this process.