Chemotherapeutic drugs generally lack specificity, and so the development of a carrier that can actively target delivery of chemotherapy drugs without immunogenicity to organisms has attracted increasing attention. In this work, a multivalent aptamer (Multi-Apt) was constructed by hybridizing a long single-stranded DNA (ssDNA) with tandem repeated sequences synthesized by rolling circle amplification (RCA) with several ssDNA encoding aptamer AS1411 sequences. The double-helix structure was used to load the anti-tumor drug doxorubicin (Dox) for targeted treatment of B16 cells. The binding ratio of RCA product to ssDNA was optimized by agarose gel electrophoresis, and the loading and release of Dox were explored using a microplate reader. The targeting and growth inhibition of Multi-Apt-Dox on B16 cells were investigated by fluorescence microscopy, flow cytometry, microplate reader, CCK-8 assay and wound healing assay. The results showed that the optimal molar ratio of RCA product to ssDNA was 1:50. Fluorescence microscopic pictures, flow cytometry analysis and microplate reader experimental results showed that each Multi-Apt could load approximately 200 Dox molecules, and the affinity of Multi-Apt for B16 cells was 46-fold higher than that of free AS1411. Cell experimental results demonstrated that Multi-Apt induced selective cytotoxicity after intracellular degradation and drug release, thereby greatly reducing the adverse reactions of Dox to normal cells and providing a new strategy for targeted drug delivery in tumor treatment.

In recent years, China has been facing the dual challenges of declining fertility rates and births, with male reproductive health issues, especially the decline in semen quality, identified as a pivotal contributor to this phenomenon. Meanwhile, accumulating evidence indicates that air pollutants, an increasingly severe environmental problem, can damage semen quality not only directly through their biological toxicity but also indirectly by disrupting the composition of microbial communities in the gut and semen, thereby dysregulating immune function, endocrine homeostasis, and oxidative stress responses. The gut microbiota and semen microbiota, as important components of the human microecosystem, play crucial roles in maintaining reproductive health. This article comprehensively reviewed the research progress on the potential effects of air pollutants (particulate matter and gaseous pollutants), gut microbiota, and semen microbiota on semen quality. Specifically, it elucidated the mechanisms of interaction between these factors and explored how they affect male fertility.

Objective To evaluate the caries excavation efficacy and minimally invasive potential of three dentine caries excavation methods including traditional excavation,chemomechanical excavation,and fluorescence-aided caries excavation using micro-computerized tomography(micro-CT).Methods This study was approved by the Biomedical Research Ethics Committee,and all patients provided informed consent.Thirty molars and premolars with dentin caries were collected and randomly divided into three groups.The samples were obtained by traditional excavation(traditional excavation group),chemomechanical excavation(chemomechanical excavation group),and fluorescence-aided caries ex-cavation(fluorescence-aided caries excavation group),and the operation time for each sample was recorded.Micro-CT was used to scan and record the caries volume and healthy tooth volume of each tooth before and after caries excavation.The caries excavation efficacy and minimally invasive potential of the three caries excavation methods were evaluated based on the caries volume and the healthy tooth volume before and after caries excavation.Results In terms of caries excavation operation time,the chemomechanical excavation group(501.7 s±143.6 s)had a longer operation time than the traditional excavation group(263.9 s±121.2 s)and the fluorescence-aided caries excavation group(284.2 s±135.6 s),with a statistically significant difference(P＜0.01);there was no significant difference between the traditional excava-tion group and the fluorescence-aided caries excavation group.In terms of caries excavation efficacy,the ratio of residu-al caries volume to initial caries volume was determined in the traditional excavation group(0.087±0.04),followed by the fluorescence-aided caries excavation group(0.36±0.10),and the chemomechanical excavation group was the high-est(0.51±0.10);the observed disparity between the groups exhibited statistical significance(P＜0.01).In terms of min-imally invasive potential,the ratio of the traditional excavation group(0.87±0.05)was lower than the chemomechanical excavation group(0.99±0.01)and fluorescence-aided caries excavation group(0.98±0.01),with statistically signifi-cant differences(P＜0.01);the difference between the ratio of the chemomechanical excavation group and the fluores-cence-aided caries excavation group was not statistically significant.Conclusion The traditional excavation group had the shortest operation time,but the traditional excavation removed too much healthy dentin and demineralized dentin.The chemomechanical excavation group retained demineralized dentin and healthy dentin and had the best minimally in-vasive potential,but the caries excavation efficacy was poor and the operation time was long.The fluorescence-aided car-ies excavation preserved part of the demineralized dentin and healthy dentin,had certain minimally invasive potential,and the clinical operation time was moderate.

Purpose: This study aims to evaluate the efficacy and safety of trastuzumab biosimilar (HLX02) in combination with pertuzumab and chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) after progression of trastuzumab. Materials and Methods: In this prospective, single-arm, phase II study, patients with HER2-positive MBC after progression of trastuzumab received pertuzuamb, HLX02, and chemotherapy in Beijing Cancer Hospital from March 2020 to December 2022. The primary endpoint was progression-free survival (PFS), and secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov (NCT05188495). Results: A total of 45 patients were included in this study. Twelve patients (26.7%) were treated in second-line and 33 patients (73.3%) were in third-line and later setting. Eighty percent and 15.5% patients had previously received pyrotinib/lapatinib and T-DM1, respectively. With a median follow-up of 24.4 months (range, 1.2 to 43.9 months), the median PFS was 7.6 months (95% confidence interval, 4.3 to 10.9), OS was not reached, the ORR was 31.1%, and DCR was 91.1%. The treatment was well tolerated. Conclusion The combination of trastuzumab biosimilar HLX02, pertuzumab, and chemotherapy exhibited promising efficacy and a favorable safety profile as second- and beyond-line treatment in HER2-positive MBC.

Objective:To explore the clinical application value of limb remote ischemic postconditioning (LRIPC) in patients with acute cerebral infarction after recanalization.Methods:A total of 78 patients with acute cerebral infarction admitted to the First Affiliated Hospital of Shantou University Medical College from June 2017 to March 2019 were selected. According to the random number table method, they were divided into the observation group with 39 cases (LRIPC + conventional medical treatment) and the control group with 39 cases (conventional medical treatment). The National Institutes of Health Stroke Scale (NIHSS) and Montreal Cognitive Assessment scale (MoCA) scores, the changes of cerebral blood perfusion, cerebral infarction volume and the levels of nerve function indexes before and after the treatment were compared and analyzed.Results:After the treatment, the NIHSS scores in the observation group were lower than thosein the control group, and the MoCA scores were higher than those in the control group, the differences were statistically significant ( P<0.05). After the treatment, the mean transit time of cerebral blood flow in the observation group was shorter than that in the control group, while the regional cerebral blood flow and regional cerebral blood volume were higher than those in the control group, the differences were statistically significant ( P<0.05). After the treatment, the volume of cerebral infarction in the observation group was lower than that in the control group ( P<0.05). After the treatment, the levels of matrix metalloproteinase 9 and S-100B protein in the observation group were lower than those in the control group: (142.45 ± 36.23) mg/L vs. (176.89 ± 42.63) mg/L, (2.52 ± 0.46) μg/L vs. (3.61 ± 0.75) μg/L; and the level of nerve growth factor was higher than that in the control group: (143.49 ± 10.58) μg/L vs. (124.96 ± 13.62) μg/L, the differences were statistically significant ( P<0.05). Conclusions:LRIPC can improve the nerve functions, cognitive functions andreduce the volume of cerebral infarction by improving cerebral blood flow. It also has a good effect on alleviating the neurological functional impairment after vascular recanalization.

Myostatin (Mstn) is known as growth/differentiation factor-8 (GDF-8). Knockout or knockdown of Mstn gene promotes muscle development and reduces fat content. Here we prepared Mstn knockdown mice by RNA interference, then the morphology of the skeletal muscle, the content of triglyceride (TG), the content and composition of fatty acids in the skeletal muscle were detected. The expression of Mstn reduced in muscle of Mstn knockdown mice compared to the controls. The cross sectional areas of the skeletal muscle myofibers were significantly larger while the content of TG was less than that of the controls, and the ratios of n-3/n-6 and unsat/sat in the knockdown mice increased significantly. Subsequently, we detected the expression of genes associated with fatty acid metabolism. The expression of the genes associated with lipolysis and fatty acid transportation were up-regulated, while the genes associated with fatty acid synthesis were down-regulated. Of these genes, the up-regulation of a gene associated with β oxidation, Cpt1b, was up-regulated remarkably. We further detected the enzyme activity of CPT1 in skeletal muscle and obtained the same results with gene expression. Moreover, chromatin immunoprecipitation assay was performed and we found that SMAD3, a transcription factor downstream of Mstn, directly binds to the promoter of Cpt1b gene. These results showed that knockdown of Mstn up-regulated the expression of Cpt1b through the binding of SMAD3 to the promoter of Cpt1b, then promoted the β oxidation metabolism of intramuscular fatty acids.
Animals ; Carnitine O-Palmitoyltransferase/metabolism* ; Fatty Acids ; Lipid Metabolism ; Mice ; Mice, Knockout ; Muscle, Skeletal/metabolism* ; Myostatin/metabolism* ; Oxidation-Reduction ; Up-Regulation

Objective: To analyze the clinical pathological characteristics and prognosis of breast cancer patients with uncommon metastases. Methods: Clinical data of 68 cases of breast cancer with uncommon metastases from 2012 to 2015 was retrospectively analyzed. The definition of uncommon sites of metastases is the metastatic sites except for lymph node, chest wall, breast, bone, liver, lung, brain and peritoneal and pleural metastases. Results: Among the 68 patients, the uncommon metastatic sites included adrenal gland, ovary, pancreas, eyes, uterus, spleen, rectum, bladder, kidney, thyroid gland and parotid gland. The top three common metastatic sites were adrenal gland (44.1%, 30/68), ovary (41.2%, 28/68) and pancreas (11.8%, 8/68); 75.0% (51/68) of the patients had other common metastases. The median survival time after uncommon metastases was 23.5 months (range: 1.4-116.0 months). The univariate analysis showed that the patients without metastases outside the special sites had a better survival than those with common metastases (median survival time were 36.0 and 18.0 months, respectively; P = 0.007). Conclusion: Breast cancer metastasis is widespread, in addition to the common sites, the cancer can be transferred to many other sites. Patients with uncommon metastases from breast cancer may have a favorable prognosis if they do not accompany with other common metastases, and local treatment may improve the survival of some selected patients. Many ovarian metastases are found after the operation, and the possibility of ovarian metastasis should be considered in the selection of the method of ovarian ablation.

Aim Using chronic pre-pregnancy stress to establish a postpartum depression animal model, given a single YG,and acute ketamine was served as control, to explore the pathology of PPD and the anti-depressive mechanism of the YG on the PPD model on AKT/mTOR signaling pathway. Methods Thirty-two fe-male Balb / c were randomly assigned to two groups, the control group ( Control, Con) and the pre-pregnancy stressed group(Model,Mod) , which was subjected to 3 weeks chronic restraint stress. After the last stressor, the pre-pregnancy stressed group was housed with a male. After about 4 weeks later, the mice gave birth to pups. Then at 3 weeks postpartum, we tested the ma-ternal tail suspension test ( TST). Both YG and Ket-amine was single administered 24 hours before behavior test, with single saline for control group and PPD mod-el group. After TST,the mouse hippocampus were ex-tracted to detect the expression of AKT and mTOR. Results After 3 weeks postpartum, the model mice showed depression-like behaviors. Immobility in TST was significantly increased in vehicle groups(P <0. 01). Acute YG improved performance in the TST (P< 0. 01), which was similar to ketamine. And the PPD model mice group showed decreased phosphorylation of AKT and mTOR (P < 0. 01,P < 0. 01), compared to control group. A single dose of YG or ketamine normal-ized AKT/ mTOR signaling in the PPD model mice(P< 0. 01,P < 0. 01),( P < 0. 01,P < 0. 01). Conclu-sions Chronic pre-pregnancy stress can induce dams into postpartum depression and its mechanism maybe associated with down-regulating AKT/ mTOR signa-ling. Acute YG exerts fast antidepressant effect on this PPD model similar to ketamine, and its mechanism may be related to up-regulating AKT/ mTOR signaling in the hippocampus.

Humans ; Pneumoconiosis ; diagnosis

Objective To explore the incidence and risk factors of depression in coronary heart disease patients who underwent revascularization therapy. Methods A total of 493 patients who were admitted in Tianjin chest hospital from April 2012 to February 2013 were enrolled, among whom 258 patients acceptted coronary artery bypass grafting (CABG) and the rest 235 patients underwent percutaneous coronary intervention (PCI). Self-rating depression scale (SDS) was employed to assess the state of patients at both1 day before and 7 days after the operations. According to the postopera?tive scores, CABG group was divided into the depression group (n=90) and non-depression group (n=168) while PCI group was also divided into depression group (n=54) and non-depression group (n=181). Basic clinical datum of patients were col?lected and analyzed and independent risk factors of depression was analyzed though logistic multi-variant regression. Results The incidence of postoperative depression among CABG patients was significantly higher than that in PCI patients (P<0.05).(1)In the CABG group, age, ratio of female gender, alcohol intake, rate of past depression, length of anaesthesia, length of staying in ICU and incidence of postoperative cognitive dysfunction(POCD)were all higher in depression subgroup than those in non-depression subgroup. Female and preoperative depression were both independent risk factors for postoper?ative depression in patients underwent CABG.(2)In PCI group, ratio of female gender, blood pressure, incidence of Diabe?tes Mellitus, the rate of past Myocardiac infaction (MI), length of intervention therapy and the number of planted stents were all higher in depression subgroup than non-depression subgroup. Female, past MI and length of intervention therapy are all independent factors of post-operative depression in patients underwent PCI. Conclusion Incidence of depression in pa?tients underwent revascularization is high. Female is the dependent risk factor in both CABG group and PCI group. Com?pared with PCI, CABG had greater influence on development of depression in postoperative patients.