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.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/ mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.

Objective: To explore the relationship between 24 hour movement behavior and physical fitness in college students, so as to provide a reference for physical fitness interventions for college students. Methods: A survey was conducted from September 23 to November 12, 2022, involving 342 college students selected from one comprehensive college among Shanghai City, Hubei Province and Zhejiang Province. Accelerometers were used to measure 24 hour movement behavior, and programs specified in the National Physical Fitness Standards for Students (2014 revision) were used to evaluate physical fitness. Compositional linear regression was used to analyze the association between 24 hour movement behavior and physical fitness. The effects of compositional isotemporal substitution of 24 hour movement behavior on physical fitness were also examined. Results: The geometric means for sleep, sedentary behavior, light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were 515.89, 678.88 , 196.30, 48.92 min/d, respectively, and the comprehensive physical fitness score was (73.09±8.55). The proportion of participants who passed the fitness test was 72.51%. Overall, 20.76% had excellent or good scores, whereas 6.73% failed. Compositional linear regression indicated that physical fitness was significantly positively associated with MVPA ( β =2.55) and LPA ( β = 5.88 )( P <0.05), but no significantly associated with sleep ( β =-5.18) and sedentary behavior ( β =-3.24)( P >0.05). Isotemporal substitution indicated that reallocation of 15 minutes from sleep and sedentary behavior to MVPA resulted in a 0.71 and 0.64 point increase in physical fitness, respectively. Similarly, reallocating the same duration to LPA led to a 0.50 and 0.43 point increase in physical fitness, respectively. Dose response analysis revealed that the mutual substitution of LPA with sedentary behavior and sleep had symmetry, whereas the mutual substitution of MVPA with sedentary behavior and sleep had asymmetry. The effectiveness of replacing sleep or sedentary behavior with MVPA in improving physical fitness decreased with increasing allocation time, whereas the adverse effects of replacing MVPA with sleep or sedentary behavior increased with increasing allocation time. Conclusion In the context of 24 hour movement behavior, increasing the time spent on LPA and MVPA is beneficial for physical fitness among college students. It should be recommend that college students actively transition from sedentary behavior to engaging in physical activity, with a particular emphasis on incorporating MVPA.

Osteoclasts are the only cells responsible for bone resorption in the body, and osteoblasts are the main cells responsible for bone regeneration in the body. Under physiological conditions, these cells maintain a dynamic balance to maintain bone homeostasis. It was widely believed that the imbalance of bone metabolism is mainly affected by the expression of related inflammatory factors. However, with the gradual expansion of related studies in recent years, autophagy has been shown to be closely related to the differentiation, apoptosis and functions of osteoclasts and osteoblasts. AMP-activated protein kinase (AMPK) is an important regulator of energy metabolism in vivo and is involved in the regulation of autophagy and bone homeostasis in bone metabolism-related cells. Periodontitis is a chronic infectious disease, and its typical symptoms are alveolar bone resorption. At present, controlling the level of periodontal inflammation and alveolar bone resorption more effectively in clinical practice remains a challenge. The detection of AMPK and autophagy levels in bone metabolism-related cells shows certain prospects for the clinical prevention and treatment of periodontitis in the future. Therefore, this article reviews the regulation of periodontal inflammation levels and bone homeostasis through cell autophagy related to AMPK-mediated bone metabolism.

Objective:To investigate the regulatory role of defferentially expressed LOC107987438 in the pathogenesis of depressive disorder and provide a theoretical basis for its clinical application in depressive disorder.Methods:Differential expression of LOC107987438 was verified by quantitative real-time polymerase chain reaction(qRT-PCR)in peripheral blood monocular cells(PBMCs)of 60 patients with depressive disorder and 60 health controls. In addition, its diagnostic value was assessed by receiver operating characteristic(ROC)curves. Based on the ceRNA mechanism of lncRNA, the miRDB database was applied to predict the target miRNAs of LOC107987438, and the miRNAs with target score ≥ 80 among them were screened out.The screened miRNAs were then used to predict their potential target mRNAs through four databases which were TargetScan 8.0, miRTarBase, mirDIP and miRPathDB. Moreover, the predicted target mRNAs were annotated for gene ontology(GO)function annotation and tokoyo encyclopedia of genes and genomes(KEGG) pathway enrichment analysis via ClusterProfiler 4.0.5 package of R 4.1.1. Finally, a protein-protein interaction network was constructed using the STRING 11.5 platform to retrieve the interacting genes.Results:The qRT-PCR results showed that normalized expression of LOC107987438 in PBMCs of patients with depressive disorder was higher than that in health controls(depressive disorder: 2.084±1.357, health controls: 1.000±0.660, P<0.001). The ROC curve results showed that the area under curves(AUC)of LOC107987438 was 0.759(95% CI: 0.675-0.842, P<0.05), indicating its high potential diagnostic value. Bioinformatics analysis showed that hsa-miR-4670-3p, hsa-miR-619-3p, hsa-miR-6721-5p and hsa-miR-297 were the miRNAs with high bindings to LOC107987438. The results of KEGG signaling pathway enrichment revealed that hypoxia-inducible factor 1(HIF-1)signaling pathway, phosphatidylinositol 3-kinase-AKT(PI3K-Akt) signaling pathway and erythroblastic oncogene B(ErbB) signaling pathway were closely associated with depressive disorder. Among the top ten key genes screened by the protein-protein interaction network, kirsten rats arcomaviral oncogene homolog(KRAS), androgen receptor(AR), cyclic-AMP response binding protein1(CREB1), insulin-like growth factor 1(IGF1), cyclin-dependent kinase inhibitor 1B(CDKN1B) and calcium/calmodulin-dependent protein kinase type Ⅱ alpha(CAMK2A)were strongly associated with depressive disorder. Conclusion:The establishment of ceRNA regulatory network of LOC107987438 provides a theoretical basis for exploring the pathophysiology of depressive disorders.

Objective:To investigate the efficacy of radiofrequency ablation combined with ozone therapy under CT guidance in the treatment of lumbar disc herniation.Methods:A total of 93 patients with lumbar disc herniation who were admitted to The First Hospital of Jiaxing from January 2019 to May 2022 were included in this study. They were randomly divided into an observation group ( n = 47) and a control group ( n = 46). The control group was treated with radiofrequency ablation and the observation group was treated with radiofrequency ablation combined with ozone therapy. Efficacy was compared between the two groups at 3 months after surgery. The pain was compared between the two groups before and 7 days and 3 months after surgery. Inflammatory factors were compared between the two groups before and 7 days after surgery. The lumbar spine function was compared between the two groups before and 3 months after surgery. Results:At 3 months after surgery, the excellent and good rate in the observation group was significantly higher than that in the control group [89.36% (42/47) vs. 71.74% (33/47), χ2 = 4.63, P < 0.05). At 7 days and 3 months after surgery, Visual Analogue Scale scores in the observation group were (2.91 ± 0.54) points and (1.32 ± 0.31) points, respectively, which were significantly lower than (3.76 ± 0.62) points and (2.08 ± 0.47) points in the control group ( t = 7.06, 9.22, both P < 0.001). At 7 days after surgery, serum interleukin-1β, interleukin-6, and tumor necrosis factor-α in the observation group were (0.24 ± 0.05) μg/L, (18.49 ± 3.47) ng/L, and (97.94 ± 17.43) ng/L, respectively, which were significantly lower than (0.37 ± 0.09) μg/L, (24.31 ± 4.12) ng/L, and (148.87 ± 20.13) ng/L, respectively in the control group ( t = 8.63, 7.37, 13.05, all P < 0.05). At 3 months after surgery, the Japanese Orthopedic Association score in the observation group was significantly higher than that in the control group [(25.68 ± 2.28) points vs. (21.17 ± 3.24) points, t = -7.78, P < 0.001], and the Oswestry Disability Index in the observation group was significantly lower than that in the control group [(9.84 ± 1.43) points vs. (13.46 ± 2.18) points, t = 9.49, P < 0.001]. Conclusion:Radiofrequency ablation combined with ozone therapy under CT guidance is highly effective on lumbar disc herniation. The combined therapy can reduce pain and inflammatory reactions in patients and improve lumbar function.

Objective Explore the feasibility and accuracy of using deep learning techniques for gender inference in panoramic dental radiography images of Chinese Han population.Methods A total of 10,600 OPG images from Han individuals aged 18 to 70(5,300 males and 5,300 females)were collected and randomly divided into training set,validation set,and test set in an 8:1:1 ratio.MobileNetV2,Swin Transformer Small,and Swin Transformer Tiny models were trained,and the classification performance of the models was evaluated and visually displayed using accuracy,F1 score,and Grad-CAM algorithm.Results The accuracy of MobileNetV2,Swin Transformer Small,and Swin Transformer Tiny models was 97.57%,95.13%,and 96.28%respectively,with MobileNetV2 model showing the best overall performance.The Grad-CAM algorithm revealed that male OPG images mainly focused on the left and right mandibular branches and alveolar bone,while female OPG images mainly focused on the maxillary sinus,left mandibular branch,and posterior alveolar bone.Conclusion This study demonstrates that the gender inference model based on deep learning techniques for OPG images of Chinese Han population has high accuracy and generalization ability,providing a new approach for forensic gender determination in forensic medicine.

Objective:To evaluate the influence of manual digitorum sensory stimulation (MDSS) of hemiplegic fingers in median nerve F-wave in stroke patients.Methods:Thirty patients with hemiplegia after stroke, admitted to Department of Rehabilitation Medicine, Second Affiliated Hospital of Anhui Medical University from June 2019 to October 2022 were selected; all patients had thumb flexor modified Ashworth scale (MAS) grading≥1. Hemiplegic MDSS was given; bilateral median nerve F-wave before MDSS and median nerve F-wave at the hemiplegic side immediately after MDSS were recorded.Results:Compared with that at the healthy side before MDSS, amplitude of median nerve F-wave at the hemiplegic side was significantly increased ( P<0.05). Compared with that before MDSS, amplitude of F-wave at the hemiplegic side after MDSS in patients with thumb flexor MAS grading≤2 were significantly decreased ( P<0.05), while that in patients with thumb flexor MAS grading≥3 was significantly increased ( P<0.05). Conclusion:Amplitudes of median nerve F-wave at the hemiplegic side in patients with different thumb flexor MAS grading show that MDSS can not only inhibit the excitability of tonic motor unit related to muscle spasm, but also enhance the excitability of kinetic-motor unit mainly related to explosive power in severe muscle spasm.

Objective:To investigate the effects of excessive fluoride exposure on astrocytes and the expression of glial fibrillary acidic protein (GFAP), in vitro and in vivo. Methods:(1) In vivo experiment: 24 SPF SD rats, half male and half female, were randomly divided into control and fluoride exposed groups according to sex and body weight, 12 rats in each group. Rats were fed with < 1 mg/L and 50 mg/L sodium fluoride solution prepared by tap water for 6 months, respectively. The expression levels of GFAP protein in rat brain tissue were measured by immunofluorescence, immunohistochemistry and Western blotting. (2) In vitro experiment: adult (6-month-old) rat cortical astrocytes were extracted and cultured in primary culture (4 mmol/L sodium fluoride solution for 24 h), and the astrocytes were identified by immunofluorescence, and GFAP mRNA and protein expression levels were detected by real-time fluorescence quantitative PCR and Western blotting, respectively, and astrocytes apoptosis and calcium ion content were detected by flow cytometry. Results:(1) In vivo experiment: the results of immunofluorescence, immunohistochemistry and Western blotting showed that the GFAP protein expression level in brain tissue of rats exposed to fluoride was higher than that of control group (0.440 ± 0.200 vs 0.250 ± 0.120, t =-5.93, P = 0.027; 0.270 ± 0.020 vs 0.240 ± 0.050, t =-4.87, P = 0.040; 1.017 ± 0.001 vs 0.486 ± 0.006, t =-52.48, P = 0.001). (2) In vitro experiment: GFAP positive cells were identified as astrocytes by immunofluorescence; GFAP mRNA expression level was higher in fluoride exposed group than that of control group by real-time fluorescence quantitative PCR (2.780 ± 0.120 vs 0.134 ± 0.005, t =-37.84, P = 0.001). The Western blotting results showed that the GFAP protein expression level was higher in fluoride exposed group than that of control group (2.76 ± 0.10 vs 1.38 ± 0.05, t =-20.44, P = 0.002). Flow cytometry results showed that the apoptosis rate of astrocytes was higher in fluoride exposed group than that of control group (%: 55.0 ± 1.0 vs 3.5 ± 0.6, t =-10.28, P = 0.009) and the calcium ion content was lower than that of control group (%: 54 ± 9 vs 72 ± 13, t = 4.64, P = 0.043). Conclusion:Excessive fluoride exposure causes increased GFAP expression in astrocytes in vitro and in vivo, promotes apoptosis, and affects calcium signaling pathways.

Objective:To compare the safety and efficacy of laparoscopic and open hepatectomy for hepatolithiasis.Methods:Between January 2014 and May 2020, the clinicopathological data of 254 patients with hepatolithiasis who underwent laparoscopic or open hepatectomy at the First Department of Hepatobiliary Surgery,Affiliated Hospital of North Sichuan Medical College were collected retrospectively. There were 74 males and 180 females with age of (56±8) years (range: 38 to 77 years). Of the 254 patients, 162 underwent laparoscopic surgery (laparoscopic group) and 92 underwent open surgery (open group). Propensity score matching(PSM) was performed to match baseline characteristics of the two groups,and then the perioperative results and follow-up efficacy were compared between the two groups. The t-test, Mann-Whitney U test, χ 2 test or Fisher′s exact probability method was used to compare the perioperative data and follow-up results of the two groups after matching, respectively. Results:Each group had 63 patients after PSM with well-balanced baseline characteristics. There was no statistic difference in the type of hepatectomy,combined common bile duct exploration rate,T tube drainage placement rate,operation time,intraoperative transfusion rate,intraoperative accidental injury rate,initial and final stone clearance rate,and stone recurrence rate between the two groups. However,compared with the open hepatectomy group, the laparoscopic group had significantly lower intraoperative blood loss ( M(IQR))(300(175)ml vs. 350(145)ml, Z=3.227, P=0.001),shorter postoperative hospital stay((10.6±4.1)days vs. (14.0±4.0)days, t=4.634, P<0.01),shorter time to postoperative oral intake ((1.8±1.1)days vs. (2.9±1.6)days, t=4.556, P<0.01), and lower postoperative complication rate (25.4%(16/63) vs. 49.2%(31/63), χ2=7.635, P=0.006). Conclusion:Laparoscopic hepatectomy is safe and effective for hepatolithiasis with the advantages of less intraoperative blood loss,lower postoperative complications and faster postoperative recovery.