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.

Background Long-term exposure to ambient fine particulate matter (PM_2.5) may increase the risk of diabetes, and a healthy diet can effectively control fasting blood glucose levels. However, it is unclear whether dietary factors have a moderating effect on the risk of diabetes associated with atmospheric PM_2.5 exposure. Objective To investigate the association between long-term exposure to PM_2.5 and diabetes in rural areas of Ningxia, and potential interaction of long-term exposure to atmospheric PM_2.5 and diet on diabetes. Methods The study subjects were selected from the baseline survey data of the China Northwest Cohort-Ningxia (CNC-NX) , a natural population cohort. A total of 13917 subjects were included, excluding participants with missing covariate information. We utilized the annual average ambient PM_2.5 concentration from 2014 to 2018 as the long-term exposure level. Logistic regression and multiple linear regression were employed to analyze the associations of long-term atmospheric PM_2.5 exposure with diabetes and fasting blood glucose levels. Stratification by frequency of vegetable consumption, frequency of fruit consumption, and salty taste was used to examine moderating effects on the diabetes risk associated with atmospheric PM_2.5 exposure. Results The mean age of the 13917 subjects was (56.8±10.0) years, and the prevalence of diabetes was 9.8%. Between 2014 and 2018, the average annual concentration of PM_2.5 was (38.10±4.67) μg·m⁻³. The risk (OR) of diabetes was 1.018 (95%CI: 1.005, 1.032) and the fasting blood glucose was increased by 0.011 (95%CI: 0.004, 0.017) mmol·L⁻¹ for each 1 μg·m⁻³ increase in PM_2.5 concentration. Compared to those who consumed vegetables < 1 time per week, individuals who consume vegetables 1-3 times per week and ≥4 times per week had a reduced risk of developing diabetes by 27.1% (OR=0.729, 95%CI: 0.594, 0.893) and 16.8% (OR=0.832, 95%CI: 0.715, 0.971) respectively. Similarly, when compared to those who consumed fruits <1 time per week, individuals who consumed fruits 1-3 times per week and ≥4 times per week exhibited a reduced risk of diabetes by 16.4% (OR=0.836, 95%CI: 0.702, 0.998) and 18.2% (OR=0.818, 95%CI: 0.700, 0.959) respectively. Fasting blood glucose decreased by 0.202 (95%CI: -0.304, -0.101) mmol·L⁻¹ in participants who ate vegetables 1-3 times per week. The effect of salty taste on diabetes and fasting blood glucose was not significant. The results of stratified analysis by dietary factors and PM_2.5 concentration showed that the risks of diabetes were increased in the low PM_2.5 pollution-low vegetable intake frequency group and the high PM_2.5 pollution-low vegetable intake frequency group compared with the low PM_2.5 pollution-high vegetable intake frequency group, with OR values of 3.987 (95%CI: 2.943, 5.371) and 1.433 (95%CI: 1.143, 1.796) respectively. The risk of diabetes was 50.1% higher in participants with high PM_2.5 pollution and low fruit intake frequency than in participants with low PM_2.5 pollution and high fruit intake frequency (OR=1.501, 95%CI: 1.171, 1.926). No interaction was found between salty taste and PM_2.5 on diabetes. Conclusion Long-term exposure to ambient PM_2.5 is associated with an increased fasting blood glucose and an elevated risk of diabetes in rural Ningxia population. Increasing the frequency of weekly consumption of vegetables or fruits may have a certain protective effect against diabetes occurrence, as well as a moderating effect on diabetes and fasting blood glucose levels associated with long-term exposure to atmospheric PM_2.5.

Objective Scutellaria baicalensis stems and leaves glucuronic hydrolase(sbsl GUS)was used to enzymatically hydrolyze scutellarin in Erigeron breviscapus(Vant.)Hand.Mazz.to prepare scutellarein,and the high-purity scutellarein was obtained through separation and purification.Methods Orthogonal experiments were used to optimize the process parameters for the extraction of Erigeron breviscapus(Vant.)Hand.Mazz..Using the rate of enzymatic hydrolysis conversion of scutellarin as the index,the amount of enzyme,pH,temperature,time and antioxidant were investigated,and the preparation process parameters of scutellarein were optimized.Ethanol extraction,activated carbon decolorization,and fractional crystallization were used to purify the crude extract.Results The extraction process was determined to be:segments of Erigeron breviscapus were decocted twice with 10 times water for 1 hour each time.The preparation process of scutellarein was as follows:the amount of sbsl GUS extract and Erigeron breviscapus decoction was 1∶10 based on crude drugs,0.5%sodium metabisulfite was added,pH value was about 6.0,the temperature was about 45℃,and the time was 20 hours.The crude extract of scutellarein with the content more than 60%was obtained.The crude extract was purified by fractional crystallization,refluxed with 80%ethanol,decolorized with activated carbon,concentrated and crystallized,and the scutellarein extract with content more than 85%was obtained.Conclusion sbsl GUS enzymatic hydrolysis technology,which was used to prepare scutellarein,is simple and feasible.This study provides a new way for the manufacture of scutellarein.

ObjectiveTo explore the potential mechanism of Zuogui Jiangtang Jieyu Formula （左归降糖解郁方， ZJJF） for diabetic rats with depression. MethodsSixty rats were randomly divided into normal group， model group， wingless MMTV integration site family member 5a （Wnt5a） agonist group， ZJJF group， and ZJJF plus Wnt5a inhibitor group， with 12 rats in each group. Except for the normal group， the rats were fed with high-fat chow， streptozotocin injection， and chronic mild unpredictable stress combination， to establish model of diabetes mellitus complicated with depression. After successful modelling， rats in the Wnt5a agonist group were given bilateral hippocampal stereotactic injections of Wnt5a agonist Foxy-5 with 5 μl each for 7 consecutive days； rats in ZJJF group were given 20.52 g/（kg·d） of ZJJF by gavage； rats in ZJJF plus Wnt5a inhibitor group were given the drug by gavage， and bilateral hippocampal stereotactic injections of Wnt5a inhibitors Box5， with the same dosage and injection method as above. The normal group and model group were given 10 ml/（kg·d） of normal saline by gavage. All groups were gavaged for 4 consecutive weeks. At the end of the intervention， the depression-like behaviour of rats was evaluated using the forced swimming experiment （immobility time） and the absent field experiment （number of activities）； the blood glucose and insulin levels of rats were measured and the insulin resistance index was calculated； the dendritic morphology of dentate gyrus neurons in the hippocampus was observed using Golgi staining； the level of dentate gyrus neuron proliferation was measured using 5-bromodeoxyuracil nucleoside （Brdu） injection and immunofluorescence； RT-qPCR and Western blot were used to detect the mRNA and protein expression of Wnt5a， Ras homologue genomic member A （RhoA） and Rho homologue-associated coiled-coil protein kinase 1 （ROCK1） in the dentate gyrus. ResultsCompared with the normal group， rats in the model group had significantly higher blood glucose， insulin and insulin resistance indices， longer immobility time， fewer activities， lower Brdu integral optical density values and Wnt5a， RhoA， ROCK1 protein and mRNA expression in the dentate gyrus of the hippocampus （P＜0.05 or P＜ 0.01）； the dendritic branches of rat hippocampal dentate gyrus neurons could be seen to be significantly reduced or broken， and their length shortened. Compared with the model group， the blood glucose， insulin and insulin resistance indices of rats in ZJJF group and the ZJJF plus Wnt5a inhibitor group significantly reduced （P＜0.05 or P＜0.01）； the immobility time of rats in the Wnt5a agonist group and ZJJF group was significantly shortened， the number of activities increased， the Brdu integral optical density values elevated， and the Wnt5a， RhoA， ROCK1 protein and mRNA expression elevated （P＜0.05 or P＜0.01）， and the number of dendritic branches of hippocampal dentate gyrus neurons significantly increased， the length lengthened， and the complexity of dendrites increased. Compared with the Wnt5a agonist group， rats in the ZJJF group showed significant decrease in blood glucose， insulin and insulin resistance indices， prolongation of immobilisation time， reduction in the number of activities， and reduction in the Brdu integral optical density value； except for the Wnt5a mRNA in ZJJF group， Wnt5a， RhoA， ROCK1 protein and mRNA expression reduced in both ZJJF group and ZJJF plus Wnt5a inhibitor group （P＜0.05 or P＜0.01）. Compared with ZJJF group， Wnt5a， RhoA， ROCK1 protein and mRNA expression were reduced in ZJJF plus Wnt5a inhibitor group （P＜0.05 or P＜0.01）. ConclusionZJJF can improve hyperglycemia and depressive-like behaviours in rat models of diabetes with depression， and its antidepressant effects may be related to the activation of hippocampal Wnt5a/RhoA signaling and promotion of dentate gyrus neuron dendritic growth.

Objective:To systematically evaluate the recurrence risk prediction model of diabetic foot ulcers (DFU) .Methods:Research on DFU recurrence risk prediction models was electronically searched in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and China Biomedical Service System. The search period was from database establishment to July 20, 2023. Two researchers independently screened literature and conducted data extraction and quality evaluation using the prediction model research data extraction table and the Prediction Model Risk of Bias Assessment Tool (PROBAST) .Results:A total of 8 articles were included, including 14 models. The area under the receiver operating characteristic (ROC) curve included in the model ranged from 0.660 to 0.940. The most common five predictors in the model were ulcers location, glycosylated hemoglobin, smoking, combined peripheral neuropathy and diabetes course. All 8 articles had a high risk of bias, mainly due to insufficient sample size, improper handling and reporting of missing data, and a lack of internal validation, which might lead to overfitting of the model. Only one article was subjected to external validation.Conclusions:The research on DFU recurrence risk prediction models is still in the development stage, and the predictive performance of various studies is still acceptable, but there is a high risk of bias. Future research still needs to use rigorous statistical analysis methods to construct new risk prediction models and improve internal and external validation.

Objective To analyze the relationship between dietary and lifestyle inflammatory scores and metabolic syndrome, diabetes mellitus, cardiovascular disease, non-alcoholic fatty liver disease, tumor and other common metabolic diseases, and to explore the impact of dietary and lifestyle inflammatory potential on metabolic diseases, so as to provide new ideas for the diagnosis, treatment and prevention of metabolic diseases. Methods Databases such as CNKI, Wanfang , and PubMed were searched, and literatures related to the dietary and lifestyle inflammatory scores (DLIS) and metabolic diseases were reviewed . Results Seven articles showed that dietary and lifestyle inflammation scores had a positive correlation with metabolic diseases, and two articles showed that only lifestyle inflammatory scores had a positive correlation with metabolic diseases. Conclusion Dietary and lifestyle inflammatory scores may be positively correlated with metabolic diseases, but some results are still controversial. Further studies are needed to prove the correlation between DLIS and metabolic diseases.

Objective To establish a reference intervals(RIs)of serum squamous cell carcinoma antigen(SCC-Ag)in healthy population in Nanning region and provide clinical evidence to support diagnosis and prognosis of squamous cell carcinoma.Methods A total of 10 197 reference individuals who joined a routine physical examina-tion in the Health Management Center of Guangxi International Zhuang Medical Hospital from March 2019 to De-cember 2021 were collected.The level of serum SCC-Ag was detected by chemiluminescence microparticle immuno-assay.The Mann-Whitney U test was applied to compare the differences in serum SCC level between genders or ad-jacent age groups.The unilateral 95th percentile determined the upper limit of the RIs by the nonparametric method.Another 1 035 healthy subjects with the same conditions as the reference population were selected for refer-ence validation.Results The serum SCC-Ag level showed a skewed distribution(Z＝0.08,P＜0.05).The ser-um SCC-Ag level of males was considerably higher than that of females.There was significant difference in serum SCC-Ag level between males aged 18－30 and 31－40,51－60 and 61－90(P＜0.05).There was significant difference in serum SCC-Ag level between females aged 18－30 and 31－40,31－40 and 41－50,51－60 and 61－ 90(P＜0.05).The reference intervals of serum SCC-Ag was as follows:0－1.64 ng/mL for males and females aged 18－30 years;0－1.57 ng/mL and 0－1.70 ng/mL for males aged 31－60 years and 61－90 years,respec-tively;0－1.50 ng/mL,0－1.52 ng/mL and 0－1.42 ng/mL for females aged 31－40 years,41－60 years and 61－90 years,respectively.Conclusions The RIs of serum SCC-Ag in healthy population in the Nanning region are successfully established according to different genders and ages.

Background The contribution of long-term ambient PM_2.5 exposure to hypertension should not be ignored. However, the conclusions of whether dietary factors play a role in regulating PM_2.5-related hypertension are still inconsistent. Objective To explore the correlation between long-term exposure to ambient PM_2.5 and blood pressure indicators (systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure) in adults in Ningxia and a potential moderating effect of dietary factors. Methods A set of cross-sectional survey data from March, 2013 to May, 2018 was retrieved from the China Northwest Cohort-Ningxia, and the average ambient PM_2.5 concentration in the previous three years was also collected to estimate the long-term exposure of the participants. Binary logistic regression model was used to validate the correlation between long-term exposure to ambient PM_2.5 and hypertension in Ningxia, and linear model was used to study the correlation between long-term exposure to ambient PM_2.5 and blood pressure indicators (systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure), and to explore the influence of dietary factors on ambient PM_2.5-related hypertension. Results A total of 11470 participants were included in the study, 42.2% male and 57.8% female. The three-year average ambient PM_2.5 concentration before the baseline survey was 37.0 μg·m⁻³. Each 1 μg·m⁻³ increase in ambient PM_2.5 was associated with an increased risk of hypertension (OR=1.111, 95%CI: 1.097, 1.125), and increased systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure by 0.886 (95%CI: 0.783, 0.990), 0.570 (95%CI: 0.500, 0.641), 0.676 (95%CI: 0.600, 0.751), and 0.316 (95%CI: 0.243, 0.389) mmHg, respectively. The stratified analysis showed that the OR and 95%CI of hypertension were 1.171 (1.097, 1.254), 1.117 (1.064, 1.174), and 1.160 (1.116, 1.207) respectively for each 1 μg·m⁻³ increased in PM_2.5 with low frequency of vegetable and fruit consumption and salty taste respectively. The OR and 95%CI of hypertension were decreased when the moderate and high frequency of vegetable and fruit intake and moderate and light taste applied, the values were 1.091 (1.062, 1.121) and 1.114 (1.097, 1.131), 1.105 (1.082, 1.129) and 1.111 (1.092, 1.13), 1.115 (1.090, 1.140) and 1.102 (1.083, 1.121) respectively. Compared with low frequency of vegetable and fruit intake and salty taste, the increase degree of ambient PM_2.5 related systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure also decreased in middle and high frequency of vegetable and fruit intake and moderate and light taste. Conclusion Long-term exposure to ambient PM_2.5 is significantly associated with increased risks of hypertension and blood pressure in Ningxia area. Increasing the frequency of vegetable and fruit intake and decreasing salty taste may reduce the effect of ambient PM_2.5 on hypertension and blood pressure.

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.
Humans ; Male ; Female ; Adult ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Middle Aged ; Retrospective Studies ; Hematologic Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Leukemia, Myeloid, Acute/therapy* ; Recurrence ; Graft vs Host Disease/etiology* ; Chronic Disease