AIM: To investigate the distribution characteristics of pathogens in patients with post-traumatic infectious endophthalmitis(PTIE)and their relationship with serum levels of macrophage inflammatory protein 1α(MIP-1α), heat shock protein 70(HSP70), and soluble triggering receptor expressed on myeloid cells 1(sTREM-1).METHODS:A total of 157 patients with PTIE from the Handan City Eye Hospital(The Third Hospital of Handan)from May 2023 to May 2025 were selected as the study group. They were divided into a good prognosis group and a poor prognosis group based on their uncorrected visual acuity at discharge. Meanwhile, 157 patients with ocular trauma but without endophthalmitis during the same period were selected as control group 1, and 157 healthy volunteers who underwent physical examinations during the same period were selected as control group 2. Aqueous humor and vitreous fluid samples were collected from the study group to detect the distribution of pathogens. The levels of serum MIP-1α, HSP70, and sTREM-1 were measured using the enzyme-linked immunosorbent assay. Multivariate Logistic regression analysis was performed to identify risk factors for poor prognosis. The predictive value of serum MIP-1α, HSP70, and sTREM-1 levels for poor prognosis was evaluated using receiver operating characteristic(ROC)and decision curve analysis(DCA).RESULTS: The general data of the participants in the three groups was comparable. A total of 173 pathogens were detected in the 157 patients with PTIE, with Gram-positive bacteria being the predominant type. The levels of serum MIP-1α and sTREM-1 in the study group were higher than those in control groups 1 and 2, while the level of HSP70 was lower than those in control groups 1 and 2(all P<0.05). There were no significant differences in the levels of serum MIP-1α, HSP70, and sTREM-1 between control groups 1 and 2(all P>0.05). In the poor prognosis group, the time of wound suture was ≥24 h, the wound location was in zones II/III, the type of trauma was rupture, the proportion of rupture injuries, and the levels of serum C-reactive protein, MIP-1α, and sTREM-1 were higher than those in the good prognosis group, while the level of HSP70 was decreased(all P<0.001). Multivariate Logistic regression analysis showed that the time of wound suture, wound location, type of trauma, C-reactive protein, MIP-1α, HSP70, and sTREM-1 were risk factors for poor visual prognosis in patients with PTIE(all P<0.05). The ROC curve results showed that the combined prediction of serum MIP-1α, HSP70, and sTREM-1 for poor visual prognosis in PTIE patients had an AUC value of 0.965, which was significantly higher than that of individual predictions(ZMIP-1α, ZHSP70, ZsTREM-1=3.628, 4.705, 3.930, all P<0.05). Additionally, the DCA curve showed that the combined prediction had a higher net benefit rate than individual predictions in the high-risk threshold range of 0.03-0.97.CONCLUSION:Gram-positive bacteria are the predominant type of pathogenic bacteria in patients with PTIE, with elevated levels of serum MIP-1α and sTREM-1 and decreased levels of HSP70. The combined detection of these three factors has a high predictive efficacy for visual prognosis in patients.

OBJECTIVE: To analyze the factors related to spontaneous re-eruption after intruded injury in permanent anterior teeth in children and adolescents. METHODS: Clinical data from 5- to 17-year-old patients who sustained intrusive luxation of permanent anterior teeth and treated in the Department of Pedia-tric Dentistry of Peking University School and Hospital of Stomatology from June 2015 to August 2024 were reviewed. Information of age, gender, degree of intrusion, direction of intrusion, tooth development, concomitant injuries, luxation and post-osteoclastic eruption of the adjacent teeth were recorded. The patients were divided into two groups based on whether they showed spontaneous re-eruption during advised observation after intrusion. Univariate and multifactor analysis were performed using Logistic regression. RESULTS: Data from 170 teeth in 139 patients whose age ranging from 5.3-16.3 years [mean age (9.0± 2.1) years] were examined. A gender disparity was observed among the patients, with 84 being male and 55 being female. Among the 170 teeth, 112 were categorized as successfully spontaneous re-eruption during advised observation after intrusion, while 58 were not. In terms of the degree of intrusion, 45 teeth (26.47%) had intrusion less than 3 mm, 102 teeth (60.00%) experienced intrusion between 3-7 mm, and 23 teeth (13.53%) were faced with intrusion exceeding 7 mm. As for the direction of intrusion, 117 teeth (68.82%) were straight intrusion while mesial-distal and buccal-lingual intrusion respectively accounting for 17 (10.00%) and 23 (13.53%). Multivariate Logistic regression analysis showed that mesial-distal intrusion (OR=0.167, 95%CI: 0.031-0.9048, P=0.038), intrusion of >7 mm (OR=0.065, 95%CI: 0.014-0.299, P < 0.001) and luxation of adjacent teeth (OR=0.369, 95%CI: 0.144-0.944, P=0.037) were independent risk factors for spontaneous re-eruption of traumatically intruded permanent anterior teeth in children and adolescents during advised observation after intrusion, while intrusion of < 3 mm (OR=9.860, 95%CI: 2.430-40.009, P=0.001) and post-osteoclastic eruption of adjacent teeth (OR=4.712, 95%CI: 1.528-14.531, P=0.007) were independent protective factors. The possibility of spontaneous re-eruption in permanent anterior teeth during advised observation after intrusion was decreased by 61.1% with the increase of root development using Cvek' s classification (OR=0.611, 95%CI: 0.408-0.914, P=0.017). Age (OR=1.077, 95%CI: 0.763-1.521, P=0.673) and laceration of gingival (OR=0.865, 95%CI: 0.290-2.578, P=0.794) didn't significantly affect the spontaneous re-eruption during advised observation after intrusion. CONCLUSION In this study, mesial-distal intrusion, intrusion of >7 mm and luxation of adjacent teeth were independent risk factors for spontaneous re-eruption of traumatically intruded permanent anterior teeth in children and adolescents during advised observation, while intrusion of < 3 mm and post-osteoclastic eruption of adjacent teeth were served as independent protective factors.
Humans ; Adolescent ; Child ; Female ; Male ; Tooth Eruption/physiology* ; Child, Preschool ; Tooth Avulsion/therapy* ; Dentition, Permanent ; Incisor/injuries* ; Remission, Spontaneous

OBJECTIVES: Intracranial aneurysm (IA) has an insidious onset, and once ruptured, it carries high rates of mortality and disability. Cardiometabolic factors may be associated with the formation and rupture of IA. This study aims to summarize the application of Mendelian randomization (MR) methods in research on cardiometabolic factors and IA, providing insights for further elucidation of IA etiology and pathogenesis. METHODS: Literature about MR-based IA studies published up to February 21, 2024, was retrieved from PubMed, Embase, Web of Science, CNKI, and Wanfang. Two researchers independently performed literature screening, data extraction, and quality assessment. A narrative synthesis approach was used to conduct a qualitative systematic review of the included studies. RESULTS: A total of 11 MR-based studies on IA published between 2017 to 2024 were included, of which 4 were rated as high quality. These studies investigated the associations between blood pressure, blood lipids, blood glucose, obesity-related indicators, and inflammatory cytokines with IA and its subtypes, though issues of duplication were noted. Four MR studies based on the same European population but using different instrumental variable selection criteria, as well as another MR study in a different European cohort, consistently identified blood pressure as a risk factor for IA and its subtypes. Findings for blood lipids, blood glucose, obesity-related indicators, and inflammatory cytokines were inconsistent across MR studies. CONCLUSIONS Blood pressure appears to increase the risk of IA and its subtypes. Associations between other cardiometabolic factors and IA/subtypes require further in-depth investigation. Given the inherent limitations of MR studies, causal inferences should be made cautiously in combination with other lines of evidence.
Humans ; Mendelian Randomization Analysis ; Intracranial Aneurysm/etiology* ; Risk Factors ; Blood Pressure ; Blood Glucose ; Obesity/complications* ; Cardiometabolic Risk Factors ; Lipids/blood*

[This corrects the article DOI: 10.1016/j.apsb.2021.07.004.].

Objective To explore the effects of Tepp-46, a pyruvate kinase M2 (PKM2) agonist, on the skin fibrosis of patients with systemic scleroderma (SSc) and its therapeutic effect on the SSc mouse models. Methods Full-thickness skin tissues of SSc patients and healthy controls were taken, and the expression levels of PKM2 and α-smooth muscle actin (α-SMA) were detected using immunohistochemical staining. The skin primary fibroblasts were isolated from the tissues, and the PKM2 protein expression was detected using Western blotting. SSc fibroblasts were stimulated with Tepp-46 of different concentrations, and Western blotting was used to measure the expression of PKM2, collagen type Ⅰα1 (ColⅠα1) and α-SMA protein after the stimulation. The C57BL/6 mice were randomly divided into three groups: control group, bleomycin (BLM) group and Tepp-46 group. BLM was injected subcutaneously to establish the SSc mouse model, at the same time, Tepp-46 treatment initiated in the Tepp-46 group. At 21 d after modeling, the mice were executed and their skins were taken. HE staining and Masson staining were used to analyze morphological changes of the skin. The immunohistochemical staining was used to examine the expression of PKM2 and α-SMA protein in the mouse skin. Western blotting was used to analyze the expression of ColⅠα1 and PKM2 in the mouse skin. Results Compared with the healthy controls, α-SMA protein expression in the dermis of SSc patients was higher, and PKM2 protein expression in the epidermis and dermis of SSc patients increased (P＜0.000 1). PKM2 protein expression in primary fibroblasts of SSc skin was higher than that of healthy controls (P＜0.01); after Tepp-46 stimulation, the levels of ColⅠα1 and α-SMA in SSc fibroblasts decreased (P＜0.01), but PKM2 protein was not affected. In the mice, HE and Masson stainings showed that compared with BLM group, the pathological changes of skin were alleviated in the Tepp-46 group. The immunohistochemical staining results showed the levels of PKM2 and α-SMA in the skin of Tepp-46 group were lower than those of the BLM group (P＜0.000 1). Western blotting results showed the level of ColⅠα1 in the Tepp-46 group was lower than that in the BLM group (P＜0.001). Conclusions The expression of PKM2 protein in SSc skin tissue and primary fibroblasts is up-regulated, and PKM2 agonist Tepp-46 can inhibit SSc skin fibrosis.

ObjectiveTo evaluate the clinical efficacy and safety of Tongluo Mingmu capsules in the treatment of diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome. MethodA randomized， double-blind， positive-control， and multi-center clinical trial design method was used. 416 patients with diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome in four test centers were included （the ratio of the treatment group to the control group was 3∶1）. On the basis of standardized hypoglycemic treatment， the treatment group was given both four Tongluo Mingmu capsules and two Calcium Dobesilate capsule agents three times a day， while the control group were given both two Calcium Dobesilate capsules and four Tongluo Mingmu capsule agents three times a day. The course of treatment was 12 weeks. The curative effect of Tongluo Mingmu capsules was evaluated by comparing the comprehensive curative effect of diabetic retinopathy， traditional Chinese medicine（TCM） syndrome score， corrected visual acuity， fundus changes， fundus fluorescence angiography， and other curative effect indexes before and after treatment in the two groups. At the same time， general examination， laboratory examination， and adverse events were performed to evaluate the safety of the drug. ResultThe baseline demographic data and disease characteristics of the treatment group and the control group were balanced and comparable， with the difference not statistically significant. After 12 weeks of treatment， the total effective rate of the comprehensive curative effect of diabetic retinopathy in the treatment group （61.0%， 189/310） was better than that in the control group （44.1%， 45/102）， and the difference was statistically significant （χ²=8.880， P<0.01）. The total effective rate of TCM syndromes in the treatment group （88.4%， 259/293） was better than that in the control group （69.9%， 65/93）， and the difference was statistically significant （χ²=17.927， P<0.01）. The disappearance rate of dry eyes （χ²=8.305）， dull complexion （χ²=4.053）， lassitude （χ²=10.267）， shortness of breath （χ²=8.494）， and dry stool （χ²=8.657） in the treatment group was higher than that in the control group， and the difference between the groups was statistically significant （P<0.05， P<0.01）. In terms of improving corrected visual acuity （χ²=8.382）， fundus changes （χ²=6.026） ， the treatment group was significantly better than the control group （P<0.05）. During the trial， the incidence of adverse events in the treatment group and the control group was 1.3% and 2.9%， respectively. There was no significant difference between the two groups. In addition， there were no serious adverse events and adverse events leading to withdrawal in both groups. ConclusionTongluo Mingmu capsules can improve the comprehensive curative effect of diabetic retinopathy and enhance the efficacy of TCM syndromes， visual acuity， fundus changes， and fundus fluorescein angiography， with great safety. Therefore， it can provide a new alternative therapeutic drug for patients with diabetic retinopathy.

[摘 要] 目的：探讨多结节非小细胞肺癌（NSCLC）组织中的驱动基因突变情况与临床病理特征的关系，为多结节NSCLC患者治疗提供分子诊断依据。方法：本研究共纳入2018年1月至2023年10月间云南省肿瘤医院分子诊断中心检测的121例多结节NSCLC患者的253个肺结节肿瘤组织标本，以第二代测序（NGS）技术或扩增阻滞突变系统PCR（ARMS-PCR）技术检测多结节NSCLC 组织中驱动基因突变情况，分析其与患者临床病理特征的关系，比较不同结节间肺癌驱动基因的突变异质性。结果：与非“宣威”NSCLC相比，“宣威”多结节NSCLC患者驱动基因突变具有显著的地域特点，表现在“宣威”患者具有较低（20%）的EGFR敏感突变（L858R、19-del）及较高（27.26%）的EGFR少见突变（主要为G719/S768I、G719）；“宣威”多结节NSCLC患者的KRAS突变率（27.27%）亦显著高于非“宣威”患者突变率（12.59%）（P<0.05）。此外，“宣威”多结节NSCLC患者驱动基因突变不一致率高达69.23%，远高于非“宣威”患者驱动基因突变不一致率（55.07%）（P<0.05）。结论：“宣威”多结节NSCLC患者具有较高的EGFR少见突变及KRAS突变率，同一患者不同病灶之间存在更高的驱动基因突变异质性，本研究将为“宣威”多结节NSCLC的诊疗策略提供更多的选择。

ObjectiveThe lung mesenchymal stem cells （LMSCs） induced by D-galactose （D-gal） were intervened by Wenfei Huaxian decoction-containing serum to explore the mechanism of Wenfei Huaxian decoction in delaying the senescence of LMSCs through the nicotinamide phosphoribosyltransferase/silent information regulator 1 （NAMPT/SIRT1） signaling pathway. MethodWenfei Huaxian decoction-containing serum was prepared. LMSCs were isolated by gradient density centrifugation， and they were cultured and identified in vitro. The senescence model in vitro was established by stimulating cells via D-gal for 24 h. LMSCs cells were modeled after being treated with different volume fractions （5%， 10%， 20%， 40%， and 80%） of Wenfei Huaxian decoction-containing serum for 24 h， and the cell proliferation level was detected by methyl thiazolyl tetrazolium （MTT） method. The cells were randomly divided into blank serum group， model group， and high， medium， and low dose groups of Wenfei Huaxian decoction-containing serum. Senescence-associated β-galactosidase （SA-β-gal） staining was used to detect the senescence of LMSCs in each group. The content of NAD + was detected by colorimetry. The levels of senescence-associated factors （p16 and p53）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in cell culture supernatant were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the relative expression of senescence-associated proteins and NAMPT/SIRT1 signaling pathway-related proteins. ResultCompared with the blank serum group， the proliferation of LMSCs was significantly inhibited after D-gal stimulation for 24 h （P<0.01）. Compared with the model group， the proliferation of LMSCs could be promoted after intervention with the corresponding Wenfei Huaxian decoction-containing serum （P<0.05， P<0.01）. Compared with the blank serum group， the SA-β-gal staining of LMSCs in the model group after D-gal stimulation was enhanced， and the content of NAD⁺ was increased （P<0.01）. The expression levels of senescence factors p16 and p53， as well as SASP pro-inflammatory factors IL-6 and TNF-α in the cell culture supernatant， were significantly increased （P<0.01）. The expression of senescence-associated proteins p16， p21， and p53 increased （P<0.01）， and the protein expression of NAMPT， SIRT1， peroxisome proliferator-activated receptor γ coactivator 1α （PGC-1α）， and forkhead box family transcription factor O1 （FoxO1） decreased （P<0.01）. Compared with the model group， the SA-β-gal staining of LMSCs in each group of Wenfei Huaxian decoction-containing serum was significantly reduced， and the content of NAD⁺ was decreased （P<0.01）. The senescence factors （p16 and p53） and inflammatory factors （IL-6 and TNF-α） in the cell culture supernatant were significantly decreased （P<0.01）. The expression of senescence-associated proteins （P16， P21， and P53） decreased （P<0.05， P<0.01）. The protein expressions of NAMPT， SIRT1， PGC-1α， and FoxO1 were significantly up-regulated （P<0.05， P<0.01）. ConclusionWenfei Huaxian decoction can alleviate senescence and inflammatory response damage of D-gal-induced LMSCs， and its mechanism may be related to the regulation of the NAMPT/SIRT1 signaling pathway.

Objective To analyze the influencing factors of unplanned extubation(UE)occurrence of peripherally inserted central catheter(PICC)in the patients with hematological diseases.Methods A retro-spective cohort study method was adopted.The data of 7 298 patients with hematological diseases implanted with PICC catheter and followed up to its removal from January 1,2016 to December 31,2020 in the Hematol-ogy Hospital of Chinese Academy of Medical Sciences were collected,including the demographic information,catheterization records,maintenance and extubation records.According to whether UE occurring,they were divided into the UE group(n=262)and normal extubation group(n=7 036).The general data were com-pared between the two groups.The COX regression was used to analyze the influencing factors of UE in pa-tients with hematological diseases.The dose-effect relationship between age and PICC UE occurrence risk was studied by the restrictive cubic spline method.Results The incidence rate of UE was 3.6％(262/7 298).The COX regression analysis results showed that the gender,disease diagnosis,fibrinogen,prothrombin time,PLT,catheter material,number of punctures during catheterization,positioning method of catheter tip,num-ber of catheter-related complications occurrence were related to PICC UE occurrence in the patients with he-matological diseases(P＜0.05).The results of restricted cubic spline showed that there was a"U"-type non-linear relationship between age and UE risk(X2=17.710,P＜0.05),and the risk of UE was the lowest when the age was 30 years old.Conclusion In PICC,the emphasis should be paid to the male patients with hemato-logical malignancies who have repeated punctures during catheterization,no intracardiac electrocardiographic positioning during catheterization,bleeding tendency,indwelling polyurethane catheters and repeated catheter-related complications in order to decrease the UC occurrence probability.