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.

Acute ischemic stroke （AIS） is a common disease that threatens human life and health， and it has high disability and mortality rates. Ischemia-reperfusion injury （IRI） is a significant factor causing secondary injury of ischemic brain tissue during AIS treatment. In recent years， studies on the pathophysiological mechanism of ischemic stroke believe that IRI is the result of the combined action of multiple injury mechanisms， and the secretion of inflammatory factors and the infiltration of inflammatory cells play an extremely important role in the process of such injury. A large number of inflammatory cell infiltration and inflammatory factor secretion can induce neuronal apoptosis or necrosis and lead to microvascular dysfunction， secondary cerebral hemorrhage or cerebral edema， thereby causing irreversible damage to the brain. The functional polymorphism of inflammatory genes may be an important factor affecting the incidence rate and outcome of ischemic stroke. Studies have shown that by regulating neuroinflammation and other mechanisms， remote ischemic preconditioning （RIPC） can effectively reduce IRI in cerebral tissue after ischemia in AIS patients， exert a cerebral protection effect， and improve the prognosis of patients. This article reviews the role and mechanism of the regulation of inflammatory response by RIPC in AIS， so as to provide a reference for clinical prevention and treatment strategies for ischemic stroke and the research on related mechanisms.

Objective:To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and compliance.Method:Use a retrospective real-world study, clinical data from 156 children aged 5-16 years who received subcutaneous immunotherapy (SCIT) with double mite allergen preparation in the pediatrics department of the Third Affiliated Hospital of Sun Yat sen University from June 2019 to September 2020 were selected for allergic rhinitis (AR) and/or allergic asthma (bronchial asthma, BA), including gender, age, total VAS(visual analogue scale) score and CSMS(combined symptom and medication scores) score at different time points (before treatment, 4-6 months, 1 year, and 2 years after initiation of desensitization), peripheral blood eosinophil counts (EOS), serum total IgE (tIgE), specific IgE (tIgE), and serum IgE (tIgE), specific IgE (sIgE), tIgG4, and incidence of local and systemic adverse reactions. All patients had a consistent regimen during the initial treatment phase (dose-escalation phase), which was performed as directed. Among them, 81 cases (observation group) continued to continue subcutaneous injection of 1 ml of vial No. 3 every 4-6 weeks during the dose maintenance phase, while 75 cases (control group) followed the old traditional regimen during the maintenance phase (i.e., change to a new vial to halve the amount of vial No. 3 by 0.5 ml, and then 0.75 ml after 1-2 weeks, and 1 ml in a further interval of 1-2 weeks). The clinical efficacy, safety and adherence to the treatment were compared between the two groups.Results:A total of 81 cases of 156 children were included in the observation group, of which 58 children with AR, 15 children with BA, and 8 children with AR combined with BA; 75 cases were included in the conventional control group, of which 52 children with AR, 16 children with BA, and 7 children with AR combined with BA. In terms of safety, the difference in the incidence of local and systemic adverse reactions between the two groups was not statistically significant ( χ2=1.541 for local adverse reactions in the control group, χ2=0.718 for the observation group; χ2=0.483 for systemic adverse reactions in the control group, χ2=0.179 for the observation group, P value >0.05 for all of these), and there were no grade Ⅱ or higher systemic adverse reactions in any of them. In the control group, there were 15 cases of dropout at 2 years of follow-up, with a dropout rate of 20.0%; in the observation group, there were 7 cases of dropout at 2 years of follow-up, with a dropout rate of 8.6%, and there was a statistically significant difference in the dropout rates of the patients in the two groups ( χ2=4.147, P<0.05). Comparison of serological indexes and efficacy (compared with baseline at 3 different time points after treatment, i.e., 4-6 months, 1 year and 2 years after treatment), CSMS scores of the observation group and the conventional control group at 4-6 months, 1 year and 2 years after treatment were significantly decreased compared with the baseline status ( t-values of the conventional group were 13.783, 20.086 and 20.384, respectively, all P-values <0.001, and t-values of the observation group were 15.480, 27.087, 28.938, all P-values <0.001), and VAS scores also decreased significantly from baseline status in both groups at 4-6 months, 1 year, and 2 years of treatment ( t-values of 14.008, 17.963, and 27.512 in the conventional control group, respectively, with all P-values <0.001, and t-values of 9.436, 13.184, and 22.377 in the observation group, respectively; all P-values <0.001). Intergroup comparisons showed no statistically significant differences in CSMS at baseline status, 4-6 months, 1 year and 2 years ( t-values 0.621, 0.473, 1.825, and 0.342, respectively, and P-values 0.536, 0.637, 0.070, and 0.733, respectively), and VAS was no statistically significant difference in comparison between groups at different time points ( t-values of 1.663, 0.095, 0.305, 0.951, P-values of 0.099, 0.925, 0.761, 0.343, respectively); suggesting that the treatment regimens of the observation group and the conventional control group were clinically effective, and that the two regimens were comparable in terms of efficacy. The peripheral blood eosinophil counts of the observation group and the conventional control group decreased significantly from the baseline status at 4-6 months, 1 year and 2 years of treatment ( t-values of the conventional group were 3.453, 5.469, 6.273, P-values <0.05, and the t-values of the observation group were 2.900, 4.575, 5.988, P-values <0.05, respectively). 4-6 months, 1 year and 2 years compared with the baseline status tIgE showed a trend of increasing and then decreasing ( t-value in the conventional group was -5.328, -4.254, -0.690, P-value was 0.000, 0.000, 0.492, respectively, and t-value in the observation group was -6.087, -5.087, -0.324, P-value was 0.000, 0.000, 0.745, respectively). However, the results of intergroup comparisons showed no statistically significant differences in serological indices and efficacy between the two groups in terms of peripheral blood eosinophil counts at baseline status, 4-6 months, 1 year and 2 years ( t-values of 0.723, 1.553, 0.766, and 0.234, respectively; P-values of 0.471, 0.122, 0.445, and 0.815, respectively), tIgE ( t-values of 0.170, -0.166, -0.449, 0.839, P-values 0.865, 0.868, 0.654, 0.403, respectively), tIgG4 ( t-values 1.507, 1.467, -0.337, 0.804, P-values 0.134, 0.145, 0.737, 0.422, respectively). Conclusion:Both immunotherapy regimens for airway allergic diseases with double mite allergen subcutaneous immunotherapy have significant clinical efficacy, low incidence of adverse reactions, and the observation group has better patient compliance than the control group.

Objective To form the expert consensus on the limb management of patients with transvenous temporary cardiac pacing,standardize the limb management of patients with transvenous temporary cardiac pacing,and reduce complications related to the limb.Methods Using evidence-based methods,the evidence in this field was searched,evaluated and summarized,and relevant recommendations and research conclusions were extracted and classified by the level of evidence quality,and then the first draft of the consensus was formed.From December 2023 to January 2024,through 2 rounds of expert consultation and 4 rounds of expert meetings,the content was adjusted and the consensus was reached.Results Totally 16 experts participated in the consultation.The positive coefficient is 100%;the authoritative coefficient is 0.847 and 0.836;the average value of each index is more than＞3.8;the coefficient of variation is less than 0.21.The Kendall's harmony coefficient of the 2 rounds of expert consultation is 0.372 and 0.314,respectively,which were statistically significant.The consensus covers the preoperative,intraoperative and postoperative on limb management of patients with transvenous temporary cardiac pacing.Totally 11 themes were involved,including the preoperative preparation,position and catheter fixation in operation,position and catheter fixation in postoperative,activity,turn and transfer,duty shift on limb,nursing care after withdrawal of the catheter,prevention of deep vein thrombosis of the operative limb and prevent infection.Conclusion The consensus is highly scientific,and it is helpful to standardize the limb management of patients with transvenous temporary cardiac pacing.

Objective:To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and compliance.Method:Use a retrospective real-world study, clinical data from 156 children aged 5-16 years who received subcutaneous immunotherapy (SCIT) with double mite allergen preparation in the pediatrics department of the Third Affiliated Hospital of Sun Yat sen University from June 2019 to September 2020 were selected for allergic rhinitis (AR) and/or allergic asthma (bronchial asthma, BA), including gender, age, total VAS(visual analogue scale) score and CSMS(combined symptom and medication scores) score at different time points (before treatment, 4-6 months, 1 year, and 2 years after initiation of desensitization), peripheral blood eosinophil counts (EOS), serum total IgE (tIgE), specific IgE (tIgE), and serum IgE (tIgE), specific IgE (sIgE), tIgG4, and incidence of local and systemic adverse reactions. All patients had a consistent regimen during the initial treatment phase (dose-escalation phase), which was performed as directed. Among them, 81 cases (observation group) continued to continue subcutaneous injection of 1 ml of vial No. 3 every 4-6 weeks during the dose maintenance phase, while 75 cases (control group) followed the old traditional regimen during the maintenance phase (i.e., change to a new vial to halve the amount of vial No. 3 by 0.5 ml, and then 0.75 ml after 1-2 weeks, and 1 ml in a further interval of 1-2 weeks). The clinical efficacy, safety and adherence to the treatment were compared between the two groups.Results:A total of 81 cases of 156 children were included in the observation group, of which 58 children with AR, 15 children with BA, and 8 children with AR combined with BA; 75 cases were included in the conventional control group, of which 52 children with AR, 16 children with BA, and 7 children with AR combined with BA. In terms of safety, the difference in the incidence of local and systemic adverse reactions between the two groups was not statistically significant ( χ2=1.541 for local adverse reactions in the control group, χ2=0.718 for the observation group; χ2=0.483 for systemic adverse reactions in the control group, χ2=0.179 for the observation group, P value >0.05 for all of these), and there were no grade Ⅱ or higher systemic adverse reactions in any of them. In the control group, there were 15 cases of dropout at 2 years of follow-up, with a dropout rate of 20.0%; in the observation group, there were 7 cases of dropout at 2 years of follow-up, with a dropout rate of 8.6%, and there was a statistically significant difference in the dropout rates of the patients in the two groups ( χ2=4.147, P<0.05). Comparison of serological indexes and efficacy (compared with baseline at 3 different time points after treatment, i.e., 4-6 months, 1 year and 2 years after treatment), CSMS scores of the observation group and the conventional control group at 4-6 months, 1 year and 2 years after treatment were significantly decreased compared with the baseline status ( t-values of the conventional group were 13.783, 20.086 and 20.384, respectively, all P-values <0.001, and t-values of the observation group were 15.480, 27.087, 28.938, all P-values <0.001), and VAS scores also decreased significantly from baseline status in both groups at 4-6 months, 1 year, and 2 years of treatment ( t-values of 14.008, 17.963, and 27.512 in the conventional control group, respectively, with all P-values <0.001, and t-values of 9.436, 13.184, and 22.377 in the observation group, respectively; all P-values <0.001). Intergroup comparisons showed no statistically significant differences in CSMS at baseline status, 4-6 months, 1 year and 2 years ( t-values 0.621, 0.473, 1.825, and 0.342, respectively, and P-values 0.536, 0.637, 0.070, and 0.733, respectively), and VAS was no statistically significant difference in comparison between groups at different time points ( t-values of 1.663, 0.095, 0.305, 0.951, P-values of 0.099, 0.925, 0.761, 0.343, respectively); suggesting that the treatment regimens of the observation group and the conventional control group were clinically effective, and that the two regimens were comparable in terms of efficacy. The peripheral blood eosinophil counts of the observation group and the conventional control group decreased significantly from the baseline status at 4-6 months, 1 year and 2 years of treatment ( t-values of the conventional group were 3.453, 5.469, 6.273, P-values <0.05, and the t-values of the observation group were 2.900, 4.575, 5.988, P-values <0.05, respectively). 4-6 months, 1 year and 2 years compared with the baseline status tIgE showed a trend of increasing and then decreasing ( t-value in the conventional group was -5.328, -4.254, -0.690, P-value was 0.000, 0.000, 0.492, respectively, and t-value in the observation group was -6.087, -5.087, -0.324, P-value was 0.000, 0.000, 0.745, respectively). However, the results of intergroup comparisons showed no statistically significant differences in serological indices and efficacy between the two groups in terms of peripheral blood eosinophil counts at baseline status, 4-6 months, 1 year and 2 years ( t-values of 0.723, 1.553, 0.766, and 0.234, respectively; P-values of 0.471, 0.122, 0.445, and 0.815, respectively), tIgE ( t-values of 0.170, -0.166, -0.449, 0.839, P-values 0.865, 0.868, 0.654, 0.403, respectively), tIgG4 ( t-values 1.507, 1.467, -0.337, 0.804, P-values 0.134, 0.145, 0.737, 0.422, respectively). Conclusion:Both immunotherapy regimens for airway allergic diseases with double mite allergen subcutaneous immunotherapy have significant clinical efficacy, low incidence of adverse reactions, and the observation group has better patient compliance than the control group.

Objective:To explore the possible mechanism of Bupiwei Xieyinhuo Shengyang Prescription on gastroesophageal reflux disease (GERD) based on network pharmacology and molecular docking technology.Methods:The main active components and target information of Bupiwei Xieyinhuo Shengyang Prescription were screened by TCMSP database, and targets were identified by GeneCards, OMIM, TTD and PharmGKB databases. The intersection of active ingredient components and disease targets was selected to construct PPI network by STRING. Cytoscape CytoNCA plug-in was used to extract core targets for analysis. GO function enrichment and KEGG pathway enrichment analysis were performed using Metascape. Cytoscape 3.7.2 was used to construct the "component-target-signal pathway" network, and Autodock was used to complete molecular docking verification. Animal experiments were further used for verification. SPF SD male rats were selected and GERD model was established by esophageal stent implantation. After 14 days of intervention, serum TNF-α and COX-2 levels of rats in each group were detected for verification.Results:A total of 215 effective compounds were screened from Bupiwei Xieyinhuo Shengyang Prescription. The main targets of GERD were TNF, IL6, CASP3, TP53 and PTGS2, which mainly focused on cancer pathway, AGE-RAGE signaling pathway, calcium signaling pathway and NF-κB signaling pathway. The results of molecular docking showed that the binding potential and activity of the key active components of Bupiwei Xieyinhuo Shengyang Prescription and the core target were better. Compared with the model group, Bupiwei Xieyinhuo Shengyang Prescription could reduce the serum expression levels of TNF-α and COX-2 ( P<0.01). Conclusions:By regulating TNF, IL6, CASP3, TP53, PTGS2 and other core targets, Bupiwei Xieyinhuo Shengyang Prescription can regulate NF-κB signaling pathway, calcium signaling pathway and other signaling pathways to play a role in the treatment of GERD.

Objective:To investigate the efficacy and characteristics of levonorgestrel intrauterine system in in vitro fertilization (IVF) assisted pregnancy for infertility patients with atypical endometrial hyperplasia and adenomyosis. Methods:The clinical characteristics of 3 infertility patients with atypical endometrial hyperplasia and adenomyosis admitted to the Reproductive Medicine Center, the Fifth Clinical Medical College of Shanxi Medical University from 2019 to 2021 were retrospectively analyzed. All patients underwent IVF as soon as possible after the successful treatment of levonorgestrel intrauterine system. Using progestin-primed ovarian stimulation protocol and gonadotropin-releasing hormone antagonist protocol, the ring was removed before frozen-thawed transfer.Results:Two cases of atypical endometrial hyperplasia were completely relieved, one case received healthy singleton fetus, and one case received biochemical pregnancy. One case had complete remission of adenomyosis and received healthy singleton fetus.Conclusion:Levonorgestrel intrauterine system in the treatment of infertility caused by atypical endometrial hyperplasia and adenomyosis can not only achieve better therapeutic effect but also effectively improve endometrial receptivity.

Objective:To investigate the efficacy and characteristics of levonorgestrel intrauterine system in in vitro fertilization (IVF) assisted pregnancy for infertility patients with atypical endometrial hyperplasia and adenomyosis. Methods:The clinical characteristics of 3 infertility patients with atypical endometrial hyperplasia and adenomyosis admitted to the Reproductive Medicine Center, the Fifth Clinical Medical College of Shanxi Medical University from 2019 to 2021 were retrospectively analyzed. All patients underwent IVF as soon as possible after the successful treatment of levonorgestrel intrauterine system. Using progestin-primed ovarian stimulation protocol and gonadotropin-releasing hormone antagonist protocol, the ring was removed before frozen-thawed transfer.Results:Two cases of atypical endometrial hyperplasia were completely relieved, one case received healthy singleton fetus, and one case received biochemical pregnancy. One case had complete remission of adenomyosis and received healthy singleton fetus.Conclusion:Levonorgestrel intrauterine system in the treatment of infertility caused by atypical endometrial hyperplasia and adenomyosis can not only achieve better therapeutic effect but also effectively improve endometrial receptivity.

To explore the correlation of mid-term oral glucose tolerance test (OGTT) and maternal weight gain with adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM). A total of 2611 pregnant women with GDM who were examined and delivered in Women's Hospital, Zhejiang University School of Medicine from July 1st 2017 to 30th June 2018 were enrolled in this study. According to the number of abnormal items of mid-term OGTT results or maternal gestational weight gain (GWG), patients were classified. The incidence of adverse perinatal outcomes in each group and its relation with OGTT results and GWG were analyzed. The incidence of gestational hypertension, premature delivery, macrosomia and large for gestational age infant (LGA) in three abnormal items GDM patients were significantly higher than those in one or two abnormal items GDM patients (all <0.017). The incidence of gestational hypertension and premature delivery in two abnormal items GDM patients were higher than those in one abnormal item GDM patients (all <0.017). The incidence of gestational hypertension and macrosomia in excessive GWG patients were significantly higher than those in inadequate and appropriate GWG patients (all <0.017), and the incidence of LGA were higher than that in inadequate GWG patients (all <0.017). The incidence of premature delivery and low birth weight infants in appropriate GWG patients were significantly lower than those in inadequate and excessive GWG patients, and the incidence of small for gestational age infant (SGA) were significantly lower than that in inadequate GWG patients (all <0.017). In one abnormal item GDM patients, inadequate GWG was a risk factor for premature delivery and SGA (=1.66, 95%: 1.10-2.52; =2.20, 95%: 1.07-4.53), and protective factor for LGA (=0.40, 95%: 0.27-0.59). And excessive GWG was a risk factor for gestational hypertension, premature delivery and low birth weight infants (=2.15, 95%: 1.35-3.41; =1.80, 95%: 1.20-2.72; =2.18, 95%: 1.10-4.30).In two abnormal items GDM patients, inadequate GWG was a protective factor for macrosomia and LGA (=0.24, 95%: 0.09-0.67; =0.54, 95%: 0.34-0.86), while excessive GWG was risk factor for premature delivery (=1.98, 95%: 1.23-3.18).In three abnormal items GDM patients, there was no significant relationship between GWG and adverse pregnancy outcomes. For GDM women with one or two items of elevated blood glucose in OGTT, reasonable weight management during pregnancy can reduce the occurrence of adverse pregnancy outcomes. For those with three items of elevated blood glucose in OGTT, more strict blood glucose monitoring and active intervention measures should be taken in addition to weight management during pregnancy.
Blood Glucose ; Blood Glucose Self-Monitoring ; Body Mass Index ; Diabetes, Gestational/epidemiology* ; Female ; Gestational Weight Gain ; Glucose Tolerance Test ; Humans ; Pregnancy ; Pregnancy Outcome

Objective To observe the changes of blood flow density in the macular area of normal eyes,and to analyze its correlation with age.Methods A cross-sectional study.Two hundred and fifty normal healthy subjects (125 males and 125 females,aged 44.76± 14.77) in routine ophthalmologic examination at the Department of Ophtalmology of Guangdong Provincial People's Hospital during June 2017 to June 2018 were enrolled.Among them,20 to 29,30 to 39,40 to 49,50 to 59,and ≥ 60 years old were 50 subjects (50 eyes) in each.BCVA,slit lamp microscope,indirect ophthalmoscope,OCT angiography (OCTA) examinations were conducted for all eyes.The subjects were examined by both eyes,and the data of 1 eye was selected by EXCEL to generate random numbers,including 126 right eyes and 124 left eyes.The range of 6 mm × 6 mm in the macular area was scanned using a frequency domain OCTA instrument.The software automatically divides it into three concentric circles centered on the macular fovea,which were foveal area with a diameter of 1 mm,parafoveal area of 1 to 3 mm,and foveal peripheral area of 3 to 6 mm.The blood flow density of superficial capillary vessel,deep capillary vessel and foveal avascular area (FAZ) within a 300 μm width (FD-300),FAZ area,perimeter (PERIM),non-circularity index,center retinal thickness (CRT) were measured.The relationship between the blood flow density in macula,CRT,FAZ and age was analyzed by Pearson correlation analysis.Results The mean blood flow density of superficial capillary vessel and deep capillary vessel were (51.61 ± 2.54)％ and (54.04± 5.46)％,respectively.The average FD-300,CRT,PERIM and non-circularity index were (285.55 ± 12.13) μm,(2.150 ± 0.367) mm,1.10 ± 0.04,respectively.The relevance of the results showed that the age was negatively correlated with the blood flow density of whole area (r=-0.335,-0.279;P＜0.01),parafoveal area (r=-0.255,-0.368;P＜0.01),foveal peripheral area (r=-0.330,-0.269;P＜0.01) in superficial capillary vessel and deep capillary vessel as well as FD-300 (r=-0.311,P＜0.01),but not correlated with the blood flow density of foveal area (r=-0.071,-0.118;P=0.264,0.064).There was no relationship between the age and the FAZ area,PERIM,non-circularity index (r=-0.070,-0.055,0.074;P=-0.267,0.385,0.142).The age was negatively correlated with the average CRT (r=-0.217,P＜0.01),but not correlated with the CRT in foveal area (r=0.115,P=0.068).The CRT was positively correlated with the blood flow density of superficial capillary vessel and deep capillary vessel in foveal area (r=0.715,0.653;P＜0.01),but negatively correlated with the FAZ area (r=-0.669,P＜0.01).Conclusion The capillary blood flow density ofmacular area in the normal eyes decreases with age.