ObjectiveTo explore the vascular endothelial injury in male mice caused by exposure to polystyrene microplastics （PS-MPs） and the intervention effect of luteolin on vascular remodeling. Additionally， to investigate the mechanism through the oxidative system and metabolomics. MethodsThirty-two C57BL/6 mice （6-8 weeks old） were randomly divided into the saline group （saline group）， the 0.1 mg/kg PS-MPs exposure group （0.1PS-MPs group）， the 1 mg/kg PS-MPs exposure group （1PS-MPs group）， and the 1 mg/kg PS-MPs + luteolin treatment group （1PS-MPs + Lut group）， with 8 mice in each group. After 8 weeks of intervention， the body weight， blood pressure， aortic organ coefficient， and aortic histopathological changes of mice in each group were detected； the total cholesterol （TC）， triglyceride （TG）， and high-density lipoprotein cholesterol （HDL-C） lipid metabolism-related indicators in the aorta of mice were detected； the reactive oxygen species （ROS）， glutathione （GSH）， and malondialdehyde （MDA） oxidative stress-related indicators were detected； the endothelin （ET-1）， nitric oxide （NO）， vascular endothelial growth factor A （VEGF-A）， vascular cell adhesion molecule-1 （VCAM-1/CD106）， and intercellular adhesion molecule-1 （ICAM-1/CD54） endothelial function-related indicators and serum metabolomics were detected. ResultsCompared to the saline group， exposure to PS-MPs resulted in pathological thickening of the mouse aorta， increased aortic organ coefficient， and elevated blood pressure. Lipid metabolism-related indicators， including TC and TG， were elevated， while HDL-C was reduced， indicating lipid metabolism disorder in mice. Oxidative stress markers such as ROS and MDA increased， whereas GSH decreased， demonstrating oxidative damage. Vascular endothelial inflammation and injury markers， including ET-1， VEGF-A， VCAM-1， and ICAM-1， were upregulated， while the vasodilatory substance NO was downregulated， confirming endothelial injury. Furthermore， serum metabolomics results revealed that PS-MPs exposure induced endothelial damage by disrupting metabolic pathways such as the citrate cycle. Compared to the PS-MPs group， luteolin significantly reversed these effects， attenuating oxidative stress and lipid metabolism disorders， and effectively repairing endothelial injury. ConclusionPS-MPs induce vascular toxicity through oxidative stress and lipid metabolism. Luteolin effectively alleviates endothelial damage and vascular remodeling.

Objective To investigate the cardiac protective effect of Taohong Tongluo granules on coronary microvascular dysfunction(CMD)rats.Methods SD rats were randomly assigned to sham-operated group,CMD group,nicorandil group(5 mg/kg),or Taohong Tongluo granule group(50 mg/kg).Animals were administered corresponding drugs for 7 d according to the grouping,and the CMD model was prepared 2 h after the last administration.The rat CMD model was induced by injecting embolization microspheres(diameter 40-120 μm,approximately 1 000 microspheres)into the left ventricular cavity.Twenty-four hours after modeling,echocardiography was performed to measure the left ventricular ejection fraction(EF),fractional shortening(FS),and end-diastolic volume(EDV).The damaged myocardial area was assessed by 2,3,5-triphenyltetrazolium chloride(TTC)staining.Myocardial morphological changes were observed by hematoxylin-eosin(H-E)staining.The protein expression levels of NOD-like receptor family pyrin domain containing protein 3(NLRP3),apoptosis-associated speck-like protein(ASC),and cysteine aspartic acid specific protease(caspase)-1 in rat myocardial tissue were detected by immunohistochemical staining and Western blotting.Results Echocardiography showed that the EF and FS values in the Taohong Tongluo granule group,CMD group,and nicorandil group were significantly lower than those in the sham-operated group(all P＜0.001).The EF and FS values in the Taohong Tongluo granule group and nicorandil group were significantly higher than those in the CMD group(all P＜0.01).However,there were no significant differences in EDV among the groups(all P＞0.05).H-E staining showed no abnormalities in the myocardium in the sham-operated group.The CMD group exhibited microsphere embolism in the myocardium,myocardial cell dissolution and rupture,and inflammatory infiltration.The lesions in the nicorandil group and the Taohong Tongluo granule group were relatively milder,and the number of thrombi in both groups was lower than that in the CMD group(both P＜0.01).The results of TTC staining indicated that the areas of damaged myocardial regions in both the nicorandil group and the Taohong Tongluo granule group were smaller than that in the CMD group(P＜0.05 or P＜0.01).Moreover,the area in the Taohong Tongluo granule group was smaller than that in the nicorandil group(P＜0.05).The results of immunohistochemical staining showed that in the CMD model,the expression of ASC and caspase-1 proteins,as well as the number of positive cells for these proteins,was increased and was distributed in myocardial and interstitial cells.The numbers of ASC and caspase-1 positive cells in the Taohong Tongluo granule group were lower than that in the CMD group(both P＜0.01).The Western blotting showed that the expression levels of NLRP3,ASC,and caspase-1 proteins in the Taohong Tongluo granule group were all lower than those in the CMD group(all P＜0.05).Conclusion Taohong Tongluo granules can improve cardiac function,ameliorate hemodynamic parameters,and reduce myocardial infarction area in rats with CMD induced by microsphere embolism.The mechanism is related to the inhibition of myocardial inflammasome activation,thereby attenuating the myocardial injuries.

Objective To investigate the effect of polystyrene microplastics(PS-MPs)on myocardial injury in mice and its molecular mechanism.Methods A total of 60 male C57BL/6 mice were randomly divided into normal sa-line group,0.1,1,10 mg/kg PS-MPs exposed group,and doxorubicin[5 mg/(kg·w)]group treated for 8 weeks.After treatment,we measured blood pressure,cardiac organ coefficient,cardiac histopathological changes,oxidative stress markers reactive oxygen species(ROS),malondialdehyde(MDA),glutathione(GSH),4-hydroxynonenal(4-HNE)and nuclear factor E2-related factor 2(Nrf2),serum centroid injury markers creatine kinase MB(CK-MB)and troponin(cTnT),ferroptosis marker recombinant glutathione peroxidase 4(GPX4),Recombinant solute carrier family 7(SLC7 A11)as well as ferrous ions(Fe2+).Results Compared with the neg-ative control group,vacuolation,inflammatory infiltration and collagen fiber deposition were evident in the hearts of mice after PS exposure.The levels of myocardial injury markers CK-MB and cTnT significantly increased.Cardiac organ coefficient decreased,blood pressure increased,oxidative stress markers and ferroptosis markers increased.Conclusion PS-MPs exposure can induce oxidative stress and activate ferroptosis pathway,resulting in myocardial injury in mice.

Background::Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.Methods::We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (each from three CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. Results::Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. Conclusions::Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

ObjectiveTo analyze the distribution of traditional Chinese medicine （TCM） patterns as well as factors related to acute exacerbation in group E of chronic obstructive pulmonary disease （COPD）. MethodsThe general data of 161 COPD patients， including gender， age， body mass index （BMI）， disease course， smoking history， and past history， were collected. In terms of the four examinations of TCM， the differentiated patterns included phlegm-heat obstructing the lung， turbid phlegm obstructing the lung， phlegm stasis obstructing the lung， lung-spleen qi deficiency， and lung-kidney deficiency. The modified British Medical Research Council （mMRC） scale and COPD assessment test （CAT）， the pulmonary function indicators including forced expiratory volume in the first second （FEV1） and ratio of forced expiratory volume to forced vital capacity at second 1 （FEV1/FVC）， GOLD grade， and the patient's acute exacerbations in the previous year were recorded. Multivariate regression analysis was performed using logistic regression model to determine the relevant factors of patients in COPD group E. The distribution of acute exacerbations in different TCM symptom patients in group E was analyzed. ResultsThere were 80 patients （49.69%） in group E and 81 patients （50.31%） in non-group E. In group E， 23 （28.75%） patients had a history of two acute exacerbations， while 35 （43.75%） had three acute exacerbations， and 22 （27.5%） had more than three acute exacerbations. There were 13 （16.25%） cases of phlegm-heat obstructing the lung pattern， 6 （7.5%） cases of turbid phlegm obstructing the lung pattern， 8 （10%） cases of phlegm stasis obstructing the lung pattern， 22 cases （27.5%） of lung-spleen qi deficiency pattern， and 31 （38.75%） cases of lung-kidney deficiency pattern. There were significant differences in smoking history， disease course， TCM pattern， TCM syndrome score， mMRC score， and CAT score between groups （P＜0.05）. A total of 107 of the 161 patients completed pulmonary function tests， and the differences in FEV1， FEV1/FVC and GOLD grades between groups were statistically significant （P＜0.05）. Multivariate regression analysis showed that TCM pattern， TCM syndrome score and CAT score were statistically significant factors for COPD patients in group E （P＜0.05）. There were statistically significant differences in the number of acute exacerbations in different TCM patterns in group E （P＜0.05）. The patients with two acute exacerbations in the past year were mainly phlegm-heat obstructing the lung and lung-spleen qi deficiency patterns， while the three acute exacerbations were mainly seen in lung-spleen qi deficiency and lung-kidney deficiency patterns， and more than three exacerbations were more common with lung -kidney deficiency pattern. ConclusionsPatients in COPD group E were mainly the lung-spleen qi deficiency and lung-kidney deficiency patterns. Deficiency of healthy qi is the main reason for the increase in the number of acute exacerbations， and TCM patterns and CAT score were the main related factors.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Purpose: Drug resistance is one of the main causes of chemotherapy failure in patients with small cell lung cancer (SCLC), and extensive biological studies into chemotherapy drug resistance are required. Materials and Methods: In this study, we performed lncRNA microarray, in vitro functional assays, in vivo models and cDNA microarray to evaluate the impact of lncRNA in SCLC chemoresistance. Results: The results showed that KCNQ1OT1 expression was upregulated in SCLC tissues and was a poor prognostic factor for patients with SCLC. Knockdown of KCNQ1OT1 inhibited cell proliferation, migration, chemoresistance and promoted apoptosis of SCLC cells. Mechanistic investigation showed that KCNQ1OT1 can activate transforming growth factor-β1 mediated epithelial-to-mesenchymal transition in SCLC cells. Conclusion Taken together, our study revealed the role of KCNQ1OT1 in the progression and chemoresistance of SCLC, and suggested KCNQ1OT1 as a potential diagnostic and prognostic biomarker in SCLC clinical management.

Objective:To investigate the diagnosis, treatment and prognosis of ureteral endometriosis with hydronephrosis.Methods:A retrospective study was performed of 92 cases diagnosed as ureteral endometriosis with surgery confirmed in Peking University First Hospital from January 2000 to January 2021.Results:The incidence of ureteral endometriosis was 0.9% (92/10 222), with an average age of (40.0±6.0) years. Among 92 cases, urological symptoms and pelvic pain including dysmenorrheal, periodic abdominal pain were the main forms of clinical characteristics, while 11 patients (12%, 11/92) were asymptomatic. All patients with ureteral endometriosis had hydronephrosis and hydroureter before surgery, hydronephrosis were left sided in 48 (52%, 48/92) patients, right sided in 39 (42%, 39/92) patients, both sided in 5 (5%,5/92) patients. The distal and middle sections of ureteral obstructions existed in 73 (79%, 73/92) patients and 19 (21%, 19/92) patients, respectively. Out of the 92 ureteral lesions 71 (77%, 71/92) patients were extrinsic lesions, 21 (23%, 21/92) patients presented intrinsic lesions. Of the 38 cases who took preoperative radionuclide renal dynamic imaging examination, there were 6 (16%, 6/38) cases of mildly damaged, 7 (18%, 7/38) cases of moderately dameged, 14 (37%, 14/38) cases of severely damaged, and 11 (29%, 11/38) cases of normal renal function. Laparotomy was decided in 25 (27%, 25/92) patients, and laparoscopic surgery in 67 (73%, 67/92) patients. In cases of ureteral surgery, ureterolysis, partial ureteral resection and ureterocystoneostomy, partial ureteral resection and end-to-end ureteral anastomosis and nephroureterectomy were undertaken in 52 (57%, 52/92), 20 (22%, 20/92), 12 (13%, 12/92) and 8 (9%, 8/92) patients separately. The median follow up was 108 months (range: 6 to 240 months). During the follow-up period, 68 (87%, 68/78) patients took urinary ultrasound after surgery, and 60 (88%, 60/68) cases of hydronephrosis disappeared, and 8 (12%, 8/68) cases were better than before.Conclusion:Most of the patients with ureteral endometriosis are impaired with renal function, and early surgical treatment could effectively relieve urinary obstruction and promote the recovery of renal function.

Objective:To analyze the clinical characteristics and prognostic factors of severe fever with thrombocytopenia syndrome patients with high novel Bunya viral load.Methods:The clinical data of 141 patients with severe fever with thrombocytopenia syndrome whose viral load higher than 1×10 4 copies/mL were retrospectively collected from May 20, 2013 to October 30, 2019 in Weihai Central Hospital. All patients were diagnosed by laboratory tests. According to the prognosis, the cases were divided into survival group and death group. The clinical manifestations, laboratory test results and the influence of viral load on the conditions and the risk factors of prognosis were compared and analyzed. Chi-square test, rank sum test and logistic regression analysis were used for statistical analysis. Results:There were 76 patients in survival group, with a median age of 64 years. There were 65 patients in death group, with a median age of 71 years. There were significant differences in neurological injury, coma, hemorrhage, atrial fibrillation with rapid ventricular rate, and renal injury between the survival group and the death group ( χ2=16.45, 64.06, 11.25, 6.98 and 33.80, respectively, all P<0.01). There were significant differences in activated partial thromboplastin time (APTT), aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase isoenzymes (CK-MB), lactic acid dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), creatinine, and platelet count between the survival group and the death group ( Z=6.33, 4.51, 2.93, 4.65, 5.00, 4.93, 5.36 and -4.34, respectively, all P<0.01). The RNA quantification of viral load in 138 cases ranged from 1.06×10 4 to 6.53×10 7 copies/mL, and the remaining three cases were higher than 1.00×10 8 copies/mL. The viral load of the two groups were 4.63(4.32, 5.22) and 5.29(4.92, 6.17) lg copies/mL, respectively ( Z=4.91, P<0.01). The mortalities of patients with viral loads of 1.00×10 4-<1.00×10 5 copies/mL, 1.00×10 5-<1.00×10 6 copies/mL and 1.00×10 6-<1.00×10 7 copies/mL were 29.33%(22/75), 51.28%(20/39), 80.95% (17/21), respectively. Six cases with viral loads higher than 1.00×10 7 copies/mL were dead. Logistic regression analysis showed that when age ≥60 years old, viral load >1.00×10 6 copies/mL, platelet count <30.00×10 9/L, LDH ≥5 000.00 U/L, APTT ≥84.00 s, the risk of death increased significantly. Conclusions:The occurrences of coma, hemorrhage, atrial fibrillation with rapid ventricular rate, renal injury suggest that the patients′ conditions are more serious and the risk of death is higher. Age, viral load, platelet count, LDH and APTT can be used as indicators to assess the risk of death.

Objective:To measure the coagulation function of patients with adenomyosis so as to explore its relationship with increased menstrual amount and its clinical significance.Methods:From January 2014 to May 2019, clinical data of patients with hysterectomy in which 111 pathologically diagnosed adenomyosis (case group) and 115 with uterine myoma (control group) in Peking University First Hospital were retrospectively analyzed. The changes in coagulation function of the two groups were compared, and the correlation between coagulation and uterine volume in the adenomyosis group was analyzed.Results:(1) The activated partial thromboplastin time (APTT) was longer in the adenomyosis group than that in the uterine myoma group [(30.4±3.1), (29.6±2.5) s, respectively; P<0.05], while the thrombin time (TT) was shorter than that in the control group [(14.2±1.2), (14.6±1.0) s, respectively; P<0.05]. (2) According to the results of the Pearson correlation test, there was a positive correlation between prothrombin time (PT; r=0.135, P=0.042) and fibrinogen (FIB-C; r=0.139, P=0.036). (3) Platelet counts were higher in the anemia group of adenomyosis than that in the non-anemia group [(323±79)×10 9/L, (274±56)×10 9/L, respectively; P<0.05]. (4) FIB-C in non-anemia group of adenomyosis was lower than non-anemia group of uterine myoma [(2.8±0.5), (3.0±0.6) g/L, respectively; P<0.05], the anemia group of adenomyosis shortened TT compared with the anemia group of uterine myoma [(14.4±1.2), (15.2±0.9) s, respectively; P<0.05]. Conclusion:Patients with adenomyosis have abnormal coagulation function, which may be related to the increase amount of menstruation, and anemia may also be involved in coagulation disorders.