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 observe the effect of quercetin on mechanical allodynia,astrocyte activation,and upregulation of pain-related transient receptor potential vanilloid 1(TRPV1)and P2X purinoceptor 3(P2X3)in mice with paclitaxel-induced peripheral neuropathy.Methods Twenty-four C57BL/6 mice were divided randomly into control,model,and model+quercetin groups(n=8 mice per group).Paclitaxel(total dose 8 mg/kg)was injected intraperitoneally into mice in the model and model+quercetin groups to establish the model.Mice in the control group were injected intraperitoneally with the same volume of vehicle.On day 8 after the first injection,mice in the model+quercetin group were injected with 60 mg/kg quercetin solution orally and mice in the other groups were injected with the same volume of vehicle.Mechanical pain was measured by the von Frey test.Activation of astrocytes in the spinal dorsal horn was detected by immunofluorescence.Expression levels of TRPV1 and P2X3 in dorsal root ganglia were detected by immunofluorescence and Western Blot.Results(1)Compared with model group,the mechanical pain of mice in model+quercetin group were relieved.(2)Compared with model group,the activation of astrocytes and the expressions of TRPV1 and P2X3 in mice of model+quercetin group were alleviated(P＜0.05).Conclusions Quercetin can significantly reduce mechanical pain in mice with paclitaxel-induced peripheral neuropathy.This mechanism maybe related to alleviating the activation of astrocytes in the spinal dorsal horn and reducing expression of TRPV1 and P2X3 in the dorsal root ganglia.

Objective: To investigate the epidemiological characteristics of overseas imported dengue fever and malaria cases in Yunnan Province from 2015 to 2021, so as to provide insights into the prevention and control of overseas imported arthropod-borne infectious diseases. Methods: The data pertaining to imported dengue fever and malaria cases in Yunnan Province from 2015 to 2021 were collected from the Chinese Disease Prevention and Control Information System, and the temporal distribution, regional distribution, population distribution, sources, diagnosis and treatment of imported dengue fever and malaria cases were descriptively analyzed. Results: Totally 4 332 overseas imported dengue fever cases and 2 011 overseas imported malaria cases were reported in Yunnan Province form 2015 to 2021, which accounted for 30.09% of all reported dengue fever cases and 98.53% of all reported malaria cases. The number of overseas imported dengue fever and malaria cases peaked from August to November (83.13% of all imported dengue fever cases) and from April to July (59.08% of all imported malaria cases), and the cases were predominantly reported in Dehong Prefecture (50.99% and 58.88%), with farmers as the predominant occupation (40.21% and 67.93%). The dengue fever and malaria cases were mainly imported from Southeast Asia (99.04% and 88.21%), and the proportions of definitive diagnosis of dengue fever and malaria were 88.33% and 97.80% at township hospitals, respectively. Conclusions The number of overseas imported dengue fever and malaria cases peaked from August to November and from April to July in Yunnan Province from 2015 to 2021, and the cases were predominantly reported in Dehong Prefecture and imported from Southeast Asia, with farmers as the predominant occupation.

Objective:To investigate the antibacterial and osteogenic properties of biomimetic mineralized iodine-loaded coating with micro-nano topography on the surface of bone implants.Methods:After the fiber network structure of sodium hydrogen titanate was constructed by alkali thermal reaction on the surface of Ti6Al4V (noted as AT), it was biomimetically mineralized in the modified simulated body fluid to form a micro-nano topology with high specific surface area (noted as AT-CaP), and finally loaded with PVPI to construct a novel antibacterial osseointegration coating (noted as AT-CaP-PVPI). The study was conducted in AT, AT-CaP, and AT-CaP-PVPI groups, in each of which 3 parallel experiments were performed. The morphology and colony counting of Staphylococcus aureus on the coating surface were observed to detect the in vitro antibacterial performance of the coating. Fifteen male SD rats were randomly divided into 3 groups ( n=5): AT, AT-CaP, and AT-CaP-PVPI. After intramedullary injection of Staphylococcus aureus into the lower end of the femur in the SD rats, titanium rods coated with AT, AT-CaP, and AT-CaP-PVPI were inserted into the marrow cavity. The osteogenesis, volume ratio of new bone mass and number of trabeculae on the surface of the femoral implants were compared between the 3 groups 4 weeks after operation. Results:In AT and AT-CaP groups, a large number of bacteria grew in their inherent elliptical or spherical shape on the implant surface and a large number of colonies were seen on the plate; in AT-CaP-PVPI group, the bacteria on the coating surface exhibited membrane deformation and depression, some of them were completely broken and dissolved, and a large number died. There was almost no new bone formation around the implants in AT group; new bone scattered around the implants with discontinuous distribution in AT-CaP group; a great amount of new bone was seen around the implants with even distribution but no signs of infection in AT-CaP-PVPI group. The volume ratio of new bone mass and the number of trabeculae on the implant surface in AT-CaP-PVPI group were 0.453±0.206 and 6.055±0.536, respectively, significantly higher than those in AT group (0.046±0.028 and 1.667±1.249) and AT-CaP group (0.188±0.052 and 3.804±0.889) ( P<0.05). Conclusion:Biomimetic mineralized iodine-loaded coating with micro-nano topography on the surface of bone implants shows good antibacterial and osteogenic properties.

Using machine learning algorithms to construct an early prediction model of brucellosis to improve the diagnosis efficiency of Brucellosis. This study was a case-control study. 2 381 brucellosis patients from Beijing Ditan Hospital affiliated to Capital Medical University were retrospectively collected as case group, and healthy people from Beijing Chaoyang Hospital affiliated to Capital Medical University were collected as control group from May 9, 2011 to November 29, 2021. The relevant clinical information and full blood count results of 13 257 data were collected and five algorithms of machine learning were used to construct an early predication model of brucellosis by using machine learning: random forest, Naive Bayes, decision tree, logistic regression and support vector machine;14 074 data (2 143 cases incase group and 11 931 cases in control group) were used to establish the early predication model of brucellosis, and 1 564 (238 cases in case group and 1 326 cases in control group) data were used to test the predication efficiency of the brucellosis model. The results showed that the support vector machine algorithm has the best predication performance by comparing the five machine learning models. The area under receiver curve (AUC) of receiver operating characteristic (ROC) was 0.991, and the accuracy, precision, specificity and Recall were 95.6%, 95.5%, 95.4% and 95.9%, respectively. Based on the SHAP plot, platelet distribution width (PDW) and basophil relative value (BASO%) results were low, and men with high coefficient of variation (R-CV), erythrocyte hemoglobin concentration (MCHC), and platelet volume (MPV) were predicted to be at high risk of brucellosis. Platelet distribution width (PDW) contributed the most to the prediction model, followed by red blood cell distribution width coefficient of variation (R-CV). In conclusion, the establishment of a high-precision early predication method of brucellosis based on machine learning may be of great significance for the early detection and treatment of brucellosis patients.
Male ; Humans ; Retrospective Studies ; Case-Control Studies ; Bayes Theorem ; Algorithms ; Machine Learning

Using machine learning algorithms to construct an early prediction model of brucellosis to improve the diagnosis efficiency of Brucellosis. This study was a case-control study. 2 381 brucellosis patients from Beijing Ditan Hospital affiliated to Capital Medical University were retrospectively collected as case group, and healthy people from Beijing Chaoyang Hospital affiliated to Capital Medical University were collected as control group from May 9, 2011 to November 29, 2021. The relevant clinical information and full blood count results of 13 257 data were collected and five algorithms of machine learning were used to construct an early predication model of brucellosis by using machine learning: random forest, Naive Bayes, decision tree, logistic regression and support vector machine;14 074 data (2 143 cases incase group and 11 931 cases in control group) were used to establish the early predication model of brucellosis, and 1 564 (238 cases in case group and 1 326 cases in control group) data were used to test the predication efficiency of the brucellosis model. The results showed that the support vector machine algorithm has the best predication performance by comparing the five machine learning models. The area under receiver curve (AUC) of receiver operating characteristic (ROC) was 0.991, and the accuracy, precision, specificity and Recall were 95.6%, 95.5%, 95.4% and 95.9%, respectively. Based on the SHAP plot, platelet distribution width (PDW) and basophil relative value (BASO%) results were low, and men with high coefficient of variation (R-CV), erythrocyte hemoglobin concentration (MCHC), and platelet volume (MPV) were predicted to be at high risk of brucellosis. Platelet distribution width (PDW) contributed the most to the prediction model, followed by red blood cell distribution width coefficient of variation (R-CV). In conclusion, the establishment of a high-precision early predication method of brucellosis based on machine learning may be of great significance for the early detection and treatment of brucellosis patients.
Male ; Humans ; Retrospective Studies ; Case-Control Studies ; Bayes Theorem ; Algorithms ; Machine Learning

Glioblastoma is carcinogenesis of glial cells in central nervous system and has the highest incidence among primary brain tumors. Brain metastasis, such as breast cancer and lung cancer, also leads to high mortality. The available medicines are limited due to blood-brain barrier. Abnormal activation of phosphatidylinositol 3-kinases (PI3K) signaling pathway is prevalent in glioblastoma and metastatic tumors. Here, we characterized a 2-amino-4-methylquinazoline derivative XH30 as a potent PI3K inhibitor with excellent anti-tumor activity against human glioblastoma. XH30 significantly repressed the proliferation of various brain cancer cells and decreased the phosphorylation of key proteins of PI3K signaling pathway, induced cell cycle arrest in G1 phase as well. Additionally, XH30 inhibited the migration of glioma cells and blocked the activation of PI3K pathway by interleukin-17A (IL-17A), which increased the migration of U87MG. Oral administration of XH30 significantly suppressed the tumor growth in both subcutaneous and orthotopic tumor models. XH30 also repressed tumor growth in brain metastasis models of lung cancers. Moreover, XH30 reduced IL-17A and its receptor IL-17RA in vivo. These results indicate that XH30 might be a potential therapeutic drug candidate for glioblastoma migration and brain metastasis.

Objective:To investigate the clinical and mycological characteristics, treatment and prognosis of invasive candidiasis(IC)in the elderly.Methods:This retrospective study included aged patients(≥65 years)admitted to the Peking University First Hospital between January, 2010 and December, 2019, who were diagnosed with IC based on positive culture results.The infecting strains were re-identified and their antifungal drug resistance was tested.The clinical and mycological characteristics, treatment and prognosis information of the elderly patients were collected and compared with those of non-elderly adults.Results:A total of 99 aged patients were included, with a median age of 78(70-83)years and a male-to-female ratio of 2.1∶1.0.The elderly accounted for 62.7%(99/158)of the adult IC patients.Compared with their younger counterparts, elderly patients were more likely to need medium-to long-term hospitalization and intensive care unit(ICU)stay, and to show concurrent heart failure, respiratory failure or renal failure, to require mechanical ventilation, and to show deep-seated bacterial infections and multifocal Candida colonization, especially for those with previous fluconazole exposure( P<0.05). Bloodstream was the most common Candida transmission route(71/99, 71.7%)and Candida albicans was the most prevalent species(47/99, 47.5%). Antifungal resistance was highest for fluconazole(17/117, 14.5%)and voriconazole(15/117, 12.8%). No significant difference was found between elderly patients and non-elderly patients in terms of infected sites, Candida species, and antifungal resistance( P>0.05). A total of 86 patients(86.9%)received systemic antifungal treatment and fluconazole was the most commonly used drug(35/86, 40.7%). The thirty-day all-cause mortality in aged IC patients was 32.6%(29/89), significantly higher than in younger patients( P=0.022). Logistic regression analysis revealed that advanced age( OR=1.12, 95% CI: 1.06-1.20, P<0.001), renal failure( OR=4.81; 95% CI: 1.65-14.03; P=0.004), and a high Candida score( OR=1.81, 95% CI: 1.06-3.11, P=0.031)significantly increased the risk of death. Conclusions:Elderly patients were the main affected population of IC, and the mortality of IC steadily increases with age.Treatment for aged IC patients should be proactive and cautious.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknown etiology and limited therapeutic options. Activation of fibroblasts is a prominent feature of pulmonary fibrosis. Here we report that lncRNA DACH1 (dachshund homolog 1) is downregulated in the lungs of IPF patients and in an experimental mouse model of lung fibrosis. LncDACH1 knockout mice develop spontaneous pulmonary fibrosis, whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation, collagen deposition and differentiation of mouse lung fibroblasts. Similarly, forced expression of LncDACH1 not only prevented bleomycin (BLM)-induced lung fibrosis, but also reversed established lung fibrosis in a BLM model. Mechanistically, LncDACH1 binding to the serine/arginine-rich splicing factor 1 (SRSF1) protein decreases its activity and inhibits the accumulation of Ctnnb1. Enhanced expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung fibroblasts. Furthermore, loss of LncDACH1 promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in mouse lung fibroblasts, whereas such effects were abolished by silencing of Ctnnb1. In addition, a conserved fragment of LncDACH1 alleviated hyperproliferation, ECM deposition and differentiation of MRC-5 cells driven by TGF-β1. Collectively, LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation, suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis.

Objective:To analyze the causes of death of elderly inpatients,so as to provide direction for the precaution of geriatrics.Methods:The first page data of hospitalized medical records of elderly inpatients in medical department in the Second Hospital of Dalian Medical University from 2102 to 2019 were extracted, and the causes of death were analyzed. The statistical analysis was performed by Excel and SPSS 21.0 statistical software.Results:The number of deaths of elderly inpatients in medical department from 2012 to 2019 was 5 249. The proportion of deaths in ICU was 34.43%(1 807/5 249), in oncology department was19.03%(999/5 249), and in cardiovascular department was12.08%(634/5 249). The average age was (78.52 ± 7.82) years. Besides, the age of men was younger than women: (78.18 ± 8.00) years vs. (79.02 ± 7.52) years, and the differences was statistically significant ( P<0.01). Men(59.1%, 3 099/5 249) were more than women (40.96%, 2 150/5 249). The largest number of deaths was in the age of 75-84 years (42.56%, 2 234/5 249). The number of cases with combined above five diseases was 4 552(86.72%, 4 552/5 249). The top three causes of deaths of elderly inpatients in medical department from 2012 to 2019 were cardiocerebrovascular diseases (27.21%, 1 428/5 249), malignant tumor (25.74%, 1351/5 249) and respiratory system diseases (22.10%, 1160/5 249). From 2012 to 2015, the top three causes of deaths were malignant tumor, cardiocerebrovascular diseases and respiratorysystem diseases. From 2016 to 2019,the top three causes of deaths were cardiocerebrovascular diseases, malignant tumor, and respiratory system diseases. The most common cause in cardiocerebrovascular diseases of death was coronary heart disease (51.47%,735/1 428), cerebrovascular disease (43.70%,624/1 428),and hypertension(4.34%, 62/1 428). Among the patients with malignant tumor death, first cause of death waslung malignant tumor (37.53%, 507/1 351), the others in turn were gastric carcinoma (11.10%,150/1 351) and intestinal cancer (11.10%,150/1 351). Among the patients with respiratory system diseases, first cause of death was pulmonary infection (69.66%,808/1 160), the others in turn were chronic obstructive pulmonary disease (15.43%, 179/1 160) and interstitial lung disease (5.09%, 59/1 160). Conclusions:The average age of elderly inpatients in medical department is (78.52 ± 7.82) years. The death age of male is less than that of female, and the number is slightly more than that of female. The top three causes of deaths of elderly inpatients in medical department are cardiocerebrovascular diseases, malignant tumor, respiratorysystem diseases. From 2012 to 2015 the first cause of deaths is malignant tumor. From 2016 to 2019, the cardiocerebrovascular diseases rise to the first.