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:To discuss the effects of bone marrow-derived mesenchymal stem cells(BMSCs)transplantation on mitophagy in the vascular dementia(VaD)rats through reactive oxygen species(ROS)/nuclear factor erythroid 2-related factor 2(Nrf2)signaling,and to clarify its mechanism.Methods:Forty-five male adult SD rats were randomly divided into sham operation group,model group,unloaded group,BMSCs group,and MSCs+ML385(Nrf2 inhibitor)group(combination group),and there were 9 rats in each group.After intraperitoneal anesthesia,the VaD models were established in all groups except sham operation group.Morris water maze test was used to detect the learning and memory abilities of the rats in various groups;HE staining was used to observe the histopathological morphology of brain tissue of the rats in various groups;Nissl staining was used to observe the changes of Nissl bodies in hippocampus region of brain tissue of the rats in various groups;transmission electron microscope was used to observe the ultrastructure of hippocampus region of the rats in various groups;fluorescence probe method was used to detect the ROS levels in hippocampus neurons in various groups;Western blotting method was used to detect the expression levels of Nrf2,heme oxygenase-1(HO-1),PTEN-induced putative kinase 1(PINK1),parkin RBR E3 ubiquitin protein ligase(Parkin),Beclin-1,ubiquitin-binding protein p62(P62),and microtubule-associated protein 1A/1B-light chain 3(LC3-Ⅱ/LC3-Ⅰ)ratio in brain tissue of the rats in various groups.Results:The Morris water maze results showed that compared with sham operation group,the escape latency of the rats in model group was significantly increased(P<0.01),while the number of crossing time and residence time were significantly decreased(P<0.01).Compared with model group,the escape latency of the rats in BMSCs group was significantly decreased(P<0.01),while the number of crossing time and residence time were significantly increased(P<0.01).Compared with BMSCs group,the escape latency of the rats in combination group was significantly increased(P<0.01),while the number of crossing time and residence time were significantly decreased(P<0.01).The HE staining results showed that hippocampus neurons of the rats in sham operation group were normal in quantity and morphology,with uniform staining and clear structure.Compared with sham operation group,the hippocampus tissue of the rats in model group showed sparse arrangement,disordered structure,reduced neuronal quantity,varied morphology,uneven staining,nuclear pyknosis,and partial neuronal necrosis.Compared with model group,the neuronal damage of the rats in hippocampus regio in BMSCs group was alleviated,with restored morphology and improved neuronal loss.Compared with BMSCs group,the neurons of the rats in hippocampus region in combination group showed irregular morphology,disordered structure,unclear cell boundaries,uneven staining,and nuclear pyknosis.The Nissl staining results showed that the hippocampal neurons in sham operation group were tightly arranged with intact morphology,obvious nucleoli,and abundant darkly stained Nissl bodies.Compared with sham operation group,the neurons in hippocampus region of the rats in model group showed pyknosis,vacuolization,and sparse Nissl bodies.Compared with model group,the BMSCs group showed reduced neuronal pyknosis,relatively intact morphology,and increased Nissl bodies.Compared with BMSCs group,the combination group showed neuronal pyknosis,loss of morphological integrity,and fragmented Nissl bodies.The transmission electron microscope results showed that mitochondria in sham operation group exhibited oval shape with intact double-membrane structure and cristae.Compared with sham operation group,the mitochondria in model group showed swelling,disrupted membranes,broken cristae,and numerous autophagosomes.Compared with model group,the BMSCs group showed improved mitochondrial structure and reduced autophagosomes.Compared with BMSCs group,the combination group showed swollen mitochondria,disrupted membranes,broken cristae,and visible autophagosomes.The fluorescence probe results showed that compared with sham operation group,the ROS levels in the hippocampus neurons in brain tissue of the rats in model group were significantly increased(P<0.01);compared with model group,the ROS levels in hippocampus neurons in brain tissue of the rats in BMSCs group were significantly decreased(P<0.01);compared with BMSCs group,the ROS levels in hippocampus neurons in brain tissue of the rats in combination group were significantly increased(P<0.01).The Western blotting results showed that compared with sham operation group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in model group were significantly decreased(P<0.01);compared with model group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in BMSCs group were significantly increased(P<0.01);compared with BMSCs group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in combination group were significantly decreased(P<0.01);compared with sham operation group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,and LC3-Ⅱ/LC3-Ⅰ ratio of the rats in model group were significantly increased(P<0.01),while the expression level of P62 protein was significantly decreased(P<0.01);compared with model group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,as well as the LC3-Ⅱ/LC3-Ⅰ ratio,of the rats in BMSCs group were significantly decreased(P<0.01),while the expression level of P62 protein was significantly increased(P<0.01);compared with BMSCs group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,as well as the LC3-Ⅱ/LC3-Ⅰ ratio,of the rats in combination group were significantly increased(P<0.01),while the expression level of P62 protein was significantly decreased(P<0.01).Conclusion:BMSCs can alleviate the hippocampal neuronal pathological changes and improve cognitive function in the VaD rats,and its mechanism may be related to the regulation of ROS/Nrf2 signaling pathway to inhibit mitophagy.

Objective To investigate the expression and clinical significance of lncRNA insulin growth factor 2 anti-sense IGF2-AS in colorectal cancer;To verify the biological function of IGF2-AS in cells and to screen protein mole-cules regulated by IGF2-AS.Methods Using bioinformatics to predict the expression and clinical significance of IGF2-AS in colorectal cancer;Using RT-qPCR to detect the expression of IGF2-AS mRNA;Using small interfering RNA to knockdown IGF2-AS;Using CCK8,Transwell assay and flow cytometry to detect proliferation,migration,and apoptosis,respectively;Using label free quantitative proteomics to screen for factors regulated by IGF2-AS;Using databases such as GenCards,OMIM,TTD,and proteomics results screening for core targets regulated by IGF2-AS in colorectal cancer.Results Bioinformatics analysis showed that IGF2-AS was significantly upregulated in colorectal cancer(P＜0.001),its expression might be related to TNM stage(P＜0.01)and the presence of lymph node metastasis(P＜0.001);RT-qPCR results showed that as compared to the control group,the expression level of IGF2-AS mRNA was significantly up-regulated in colorectal cancer tissues(P＜0.01)and most colon cancer cells(P＜0.000 1);Clinical pathological data indicated that the expression of IGF2-AS was potentially asso-ciated with the lymph node metastasis(P＜0.05);The proliferation rate and migration rate of colorectal cancer cells transfected with IGF2-AS siRNA were significantly reduced(P＜0.000 1),and the apoptosis rate was signifi-cantly increased(P＜0.05);There were 13 proteins including KRAS,TCF7L2 and CASP3,that were potentially core targets regulated by IGF2-AS.Conclusions IGF2-AS is significantly up-regulated in colorectal cancer and may play a cancer promoting role in colorectal cancer development.

Objective To analyze the current status,hot spots and trends of Chinese and English researches in the field of aspiration after dysphasia in the past twenty years. Methods The articles about aspiration after dysphasia were retrieved from CNKI and Web of Science(WOS)core collec-tion database,from January,2003 to June,2023,and were analyzed with CiteSpace 6.1.R6. Results A total of 3 231 articles were included.The annual articles were published more and more year by year.The most English literatures came from the United States.Hot spots mainly focused on the assessment of dysphasia,prevention of complication,nutrition and rehabilitation therapy.It would concentrate on the application of the volume-viscosity swallow test and assessment scales,rehabilitation,penetration aspiration,outcome and effect validation,quality of life,feeding and nutrition condition,and evidence-based nursing,etc.,in the future. Conclusion The researches in the field of aspiration after dysphasia have been increasing in recent years,and the themes and contents of researches have been deepening.

Objective:To investigate the clinical application value of the new tracer mitoxantrone hydrochloride in imaging of cervical lymph nodes and identifying of parathyroid, recurrent laryngeal nerve during thyroid cancer radical surgery.Methods:A prospective controlled study was conducted between January 2022 and April 2024 at Tianjin First Central Hospital, recruiting 180 patients with thyroid cancer, including 54 males and 126 females, aged from 26 to 69 years. The patients were randomly divided into three groups: the mitoxantrone hydrochloride lymph node tracing group (MHI group), the nanocarbon lymph node tracing group (nanocarbon group), and the control group without lymph node tracers, with 60 cases in each group. All patients underwent total thyroid resection and regional lymph node dissection. The number of detected lymph nodes and positive metastatic lymph nodes and surgical field clarity scores and the identification rate of parathyroid glands and the instances of inadvertent excision were compared between the groups. Serum calcium and parathyroid hormone (PTH) levels at different perioperative time points and treatment-related complications were analyzed. One-way ANOVA, chi-square test and two independent sample non-parametric tests, were employed for statistical analyses.Results:The mean operation time, neck drainage volume and hospital stay in the MHI group and the nanocarbon group were respectively significantly lower than those in the control group ( P<0.05). The mean staining intensity score, tracer success rate and surgical field clarity score in MHI group were respectively significantly higher than those in nanocarbon group ( P<0.05). The mean numbers of dissected lymph nodes positive metastatic nodes and identification rates of parathyroid glands in MHI group were respectively significantly higher than those in both the nanocarbon and control groups ( P<0.05). The rates of inadvertent parathyroid excision in both MHI group and nanocarbon group were significantly lower than those in control group ( P<0.05). On postoperative day 1 and day 5, mean serum calcium and PTH levels in MHI group were respectively significantly higher than those in nanocarbon group and control groups. However, on postoperative day 1, there was no difference in mean serum calcium levels between the nanocarbon group and the control group ( P>0.05), though PTH level in the nanocarbon group was higher than that in the control group. By postoperative day 5, both serum calcium and PTH levels were higher in the nanocarbon group compared to the control group ( P<0.05). On postoperative days 30, there were no differences in serum calcium and PTH levels between the MHI group and the nanocarbon group ( P>0.05). The risks of facial numbness, hand and foot tetany and choking during drinking were lower in both the MHI and nanocarbon groups compared to the control group ( P<0.05). Conclusion:MHI demonstrates advantages in rapid targeted delivery and clear staining of the surgical field during regional lymph node dissection in radical thyroidectomy for thyroid cancer, effectively reducing the risk of collateral damage to the recurrent laryngeal nerve and parathyroid glands.

Objective:To explore the genetic characteristics of a child with 18q terminal deletion syndrome.Methods:Clinical data of a child presented at the Lianyungang Maternal and Child Health Care Hospital on July 20, 2023 was collected. Peripheral blood sample from the child was subjected to G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA). Relevant literature was searched from CNKI, WanFang and PubMed databases over the past decade (from November 1, 2013 to November 1, 2023) using keywords including "18q-syndrome", "18q deletion syndrome" and "18q terminal deletion". This study was approved by Medical Ethics Committee of the Lianyungang Maternal and Child Health Care Hospital (Ethics No. LYG-MER2021017).Results:The child, a 4-year-and-6-month-old female, had manifested short stature, intellectual disability, distinctive facial features, aortic regurgitation, auditory canal atresia, and white matter lesions. She was found to have a karyotype of 46, XX, del(18)(q21), whilst the result of CMA was arr[GRCh37]18q21.33q23(60065821_77317445)×1. Both of her parents were found to have a normal karyotype. Literature review has retrieved 7 reports which involved 11 cases with a terminal 18q23 deletion. The phenotypes of cardiac abnormalities have been diverse, with pulmonary stenosis, atrial septal defect and ventricular septal defect being most common.Conclusion:The 18q terminal deletion probably underlay the multiple congenital anomalies and mental retardation in this child.

Objective To observe the effects of Ditan Yizhi Decoction on learning and memory ability,structure of hippocampal tissue,neuronal morphology of hippocampus,and the expression of endoplasmic reticulum autophagy-related protein FAM134B in hippocampal tissue;To explore the mechanism of its therapeutic effect on vascular dementia.Methods Totally 32 SD rats were randomly divided into sham-operation group,model group,donepezil group and Ditan Yizhi Decoction group,with 8 rats in each group.The model group,donepezil group and Ditan Yizhi Decoction group were prepared with a modified permanent ligation method of bilateral common carotid arteries to create a rat model of vascular dementia,the common carotid artery was separated in the sham-operation group,but not ligated.After modeling,the donepezil group was given donepezil hydrochloride,Ditan Yizhi Decoction group was given Ditan Yizhi Decoction,and the sham-operation group and model group were given equal volume of distilled water for gavage for 4 consecutive weeks.Morris water maze experiment was used to evaluate the learning and memory ability,HE staining and Nissl staining were used to observe the morphological changes of hippocampus,ultrastructure of hippocampal neurons was observed using transmission electron microscopy,Western blot was used to detect the protein expression of FAM134B and p-FAM134B in hippocampal tissue.Results Compared with the sham-operation group,the escape latency period was prolonged of the rats in model group,and the number of crossing the original platform and the duration of stay in the target quadrant was reduced(P<0.01),the gap between neurons in CA1 region of the hippocampus increased,the cell morphology was irregular,the boundaries were blurred,the neurons shrinked,the Nissl bodies dissolved and broke,the number decreased,the endoplasmic reticulum arrangement was scattered,mitochondria swelled and deformed,and the expressions of FAM134B and p-FAM134B protein in hippocampal tissue increased(P<0.01).Compared with the model group,the escape latency period of rats in donepezil group and Ditan Yizhi Decoction group were significantly shortened,and the number of crossing the original platform and the duration of stay in the target quadrant were increased(P<0.01),the morphology and quantity of neurons in CA1 region of the hippocampus were more regular,with a decrease in neuronal pyknosis,an increase in the number of Nissl bodies,and a reduction in dissolution and fragmentation,the swelling and deformation of the endoplasmic reticulum were restored,and the expression of FAM134B and p-FAM134B protein in hippocampal tissue increased(P<0.01).Moreover,the effects of Ditan Yizhi Decoction group were better than those of the donepezil group(P<0.01).Conclusion Ditan Yizhi Decoction can improve the learning and memory ability and the morphology of neurons in vascular dementia rats.The mechanism may related to increasing the expression and phosphorylation of FAM134B protein,thereby promoting endoplasmic reticulum autophagy.

Objective To explore the status quo and potential profile of self-management in elderly patients with venous leg ulcers,analyse the differences and influencing factors in different profiles,and provide references for clinical nursing.Methods Convenient sampling method was used to select patients who were followed up in the department of vascular surgery and vascular department of 3 tertiary A hospitals in Shanghai from October 2022 to May 2023 as the study subjects.General data questionnaire,Chronic Wound Patient Self-management Behavior Questionnaire,Health Literacy Management Scale,Brief Illness Perception Questionnaire,Social Support Rating Scale,Chronic Disease Self-Efficacy Scale and Geriatric Depression Scale-15 were used for investigation.Mplus 8.3 was used for potential profile analysis,and SPSS 25.0 was used for univariate analysis and multiple Logistic regression analysis.Results A total of 316 valid questionnaires were collected,and the patients were divided into 3 potential profiles according to their self-management level:low management-inefficient wound response,middle management-highly effective compliance and high management-efficient wound response,accounting for 25.63％,46.84％and 27.53％respectively.Multiple Logistic regression analysis showed that duration of illness,depression,health literacy,self-efficacy and illness perception were factors influencing the potential profile of self-management in elderly patients with venous leg ulcers.Conclusion The self-management level of elderly patients with venous leg ulcers is at a medium level and has obvious classification characteristics.Clinical nurses can take targeted nursing measures according to different characteristics of patients to improve their self-management ability.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

OBJECTIVE: To investigate the effectiveness of "hybrid" suture with en masse combined with double-layer repair under arthroscopy in repair of delaminated rotator cuff tear by comparison with en masse suture. METHODS: Fifty-six patients with delaminated rotator cuff tears met selection criteria between June 2020 and January 2022 were included in the study. Patients were divided into two groups ( n=28) using a random number method. The patients in trial group underwent arthroscopic "hybrid" suture with the combination en masse and double-layer suture. The patients in control group underwent en masse suture under arthroscopy. There was no significant difference between the two groups ( P>0.05) in terms of gender, age, rotator cuff tear side, tear size, cause of injury, disease duration, and preoperative American Association of Shoulder and Elbow Surgeons (ASES) score, the University of California at Los Angeles (UCLA) shoulder scoring, visual analogue scale (VAS) score, and shoulder range of motion (forward flexion and lateral external rotation). The operation time, the difference of ASES score, UCLA score, VAS score, and shoulder range of motion (forward flexion and lateral external rotation) between pre- and post-operation were recorded and compared between the two groups ( P>0.05). The rotator cuff healing was examined by MRI and evaluated based on the classification criteria of rotator cuff healing proposed by Sugaya et al. RESULTS: Three cases (1 case in the trial group and 2 cases in the control group) were excluded from the study due to loss of follow-up. Twenty-seven cases in the trial group and 26 cases in the control group were included in the final study analysis. All operations of the two groups were completed successfully. There was no significant difference in the operation time between groups ( P>0.05). The follow-up time was 10-12 months (mean, 10.9 months) in the trial group and 10-13 months (mean, 11.4 months) in the control group. All incisions healed by first intention. No surgery-related complications occurred. The UCLA score, ASES score, VAS score, and shoulder range of motion (forward flexion and lateral external rotation) of both groups at 9 months after operation were significantly superior to those before operation ( P<0.05). The difference of UCLA score, ASES score, and VAS score between before and after operation in the trial group were significantly better than those in the control group ( P<0.05). There was no significant differences between the two groups in the difference of shoulder range of motion (forward flexion and lateral lateral rotation) ( P>0.05). At 9 months after operation, according to the classification criteria of rotator cuff healing proposed by Sugaya et al, MRI showed that the rotator cuff healing of the trial group was significantly better than that of the control group ( P<0.05). CONCLUSION Compared with en masse suture, arthroscopic "hybrid" suture for the repair of delaminated rotator cuff tear has advantages in relieving pain and improving shoulder joint function, and the rotator cuff healing is better.
Humans ; Rotator Cuff Injuries/surgery* ; Prospective Studies ; Shoulder Joint/surgery* ; Treatment Outcome ; Arthroscopy/methods* ; Sutures ; Range of Motion, Articular ; Magnetic Resonance Imaging