Objective To genetically investigate the protective effects of statins on breast cancer. Methods Instrumental variables for the statin target gene HMGCR and five other cholesterol-regulated genes (LDLR, PCSK9, ABCG8, APOB, and NPC1L1) were obtained from previous expression quantitative trait locus (eQTL) studies. Cholesterol-regulated genes predicted by these instrumental variables served as the exposure factors. Mendelian randomization based on pooled data (SMR) was conducted to explore the genetic effects of exposure factors on the incidence risk of all breast cancers, ER+ breast cancer, and ER-breast cancer. Instrumental variables for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) were derived from a previous human genome-wide association study and restricted to be chromosomally located within 100 kb of the above cholesterol regulatory genes; the instrumental variables could predict TC, LDL-C, or non-HDL-C levels under the regulation of the abovementioned cholesterol-associated genes which were used as exposure factors. Two-sample Mendelian randomization (IVW, MR-PRESSO, and MR-Egger) was used to explore the genetic effects of exposure factors on the risk of all breast cancers, ER+ breast cancer, and ER− breast cancer. Results SMR analysis reported that elevated HMGCR expression was significantly associated with the increased incidence risk of all breast cancers and ER+ breast cancer (P=0.044 and P=0.039, respectively) but not with the change in incidence risk of ER− breast cancer (P=0.190); the other five regulatory genes were not significantly correlated with the change in incidence risk of all breast cancers, ER+ breast cancer, and ER− breast cancer (all P>0.05). IVW analysis reported that under the regulation of HMGCR, elevated levels of peripheral TC, LDL-C, and non-HDL-C significantly increased the incidence risk of all breast cancers (P=1.160e-05, P=1.248e-05, and P=1.869e-05) and the incidence risk of ER+ breast cancer (P=3.181e-04, P=2.231e-04, and P=3.520e-04), but they were not associated with a change in the incidence risk of ER− breast cancer (P=0.062, P=0.133, and P=0.055). The results of MR-PRESSO and MR-Egger analyses supported the IVW results. Conclusion Statins could reduce the incidence risk of ER+ breast cancer at the genetic level, but there is no such protective effects on ER− breast cancer.

Objective:To establish the common carotid artery aneurysm models of Wallstent double stent overlapping implantation in miniature pigs, and evaluate the safety and effectiveness of this procedure by observing the imaging and pathological changes.Methods:Sidewall aneurysm and fusiform aneurysm models in Bama miniature pigs were established surgically and 2 Wallstent stents were overlapped and implanted in situ. Aneurysm healing immediately after surgery and during 8 weeks of follow-up were evaluated according to 2D-DSA by O'Kelly-Marotta (OKM) grading scale and Kamran scale; degrees of stent adhesion immediately after surgery and status of stent endothelialization and aneurysm healing at 2, 4, and 8 weeks after surgery were observed by high resolution C-arm CT(HR-CBCT) and optical coherence tomography (OCT); and the changes of stent endothelialization were evaluated by comparing the HR-CBCT and OCT results with histopathology at 8 weeks after surgery. Perioperative adverse events were recorded.Results:After successful establishment of common carotid artery aneurysm models (including 4 sidewall aneurysms and 4 fusiform aneurysms with average diameter of [11.0±2.8] mm) in 8 miniature pigs, a total of 16 Wallstent stents (2 in each aneurysm) were implanted across the aneurysmal neck, with a technical success rate of 100%. No serious complications such as acute stent thrombosis, or aneurysm rupture and bleeding were observed in the perioperative period. The 2D-DSA immediately after surgery showed obvious intracranial contrast agent retention in 6 patients (1 patient in grading 1, 3 in grading 2, and 2 in grading 3) and aneurysm occlusion in 2 patients (grading 4). Eight weeks after follow-up, all 8 aneurysms had complete occlusions (grading 4); and 2 experimental pigs had in-stent restenosis, with stenosis rates of 52% and 67%, respectively. HR-CBCT and OCT immediately after surgery and during follow-up indicated that the stent metal braid was gradually covered by proliferating intima, with disappeared aneurysm. The cause of in-stent restenosis in 2 experimental pigs was local intima hyperplasia resulted from poor stent adhesion, and pathological findings indicated that the intima hyperplasia was mainly composed of smooth muscle cells and fibrous connective tissues.Conclusion:In animal models, Wallstent stent overlapping implantation is safe and effective in common carotid aneurysms, but intraoperative adverse adhesion of overlapping stent should be avoided.

Objective:To evaluate the feasibility, safety, treatment outcome, and the individualized surgical procedure selection of the interventional treatments of chylous leakage.Methods:From July 2019 to January 2022, the clinical data of 60 consecutive patients with chylous leakage underwent interventional treatment were respectively analyzed. The cases included chylothorax ( n=37), chylous ascites ( n=10), chyluria ( n=4), chylothorax combined with chylous ascites ( n=5), chylothorax combined with chylopericardium ( n=2), and pelvic chylous effusion ( n=2). Conservative treatment was considered to have failed for all patients. The lymphangiography was firstly performed to detect chylous leakage, then an individualized procedure was selected according to the lymphangiography results. The treatment outcomes and complications were recorded, and follow-up was performed. Results:Lymphangiography was technically successful in 55 of 60 patients (91.7%), and no cisterna chyli and thoracic duct opacification was observed in 5 patients. The procedures for the patients included lymphangiography alone ( n=23), thoracic duct embolization ( n=23), thoracic duct disruption ( n=5), lymphatic embolization for pelvic chylous effusion ( n=4), and balloon plasty for thoracic duct ( n=5). Clinical success was achieved in 53 of 60 cases (88.3%). The complication rate was 8.3% (5/60), and all complications were minor. The median follow-up time was 11 months (range 0.5-30 months) for 56 patients, and 4 patients were lost to follow-up. There was one patient presenting the reoccurrence of symptom, and 8 patients died. Conclusions:The interventional treatment of chylous leakage is safe with good outcomes and low complication rate. Individualized treatment procedures based on the lymphangiography findings is feasible and with good curative effect.

Pesticides' overuse and misuse have been reported to induce ingredient variations in herbal medicine, which is now gaining attention in the medicinal field as a form of alternative medicine. To date, available studies on pesticide-induced ingredient variations of herbal medicine are limited only on a few compounds and remain most others unexamined. In this study, a plant metabolomics-based strategy was performed to systematically explore the effects of two frequently used insecticides on the comprehensive constituents of Lonicerae Japonicae Flos (LJF), the flower buds of Lonicera japonica Thunb. Field trials were designed on a cultivating plot of L. japonica with controls and treatments of imidacloprid (IMI) and compound flonicamid and acetamiprid (CFA). Unbiased metabolite profiling was conducted by ultra-high performance liquid chromatography/quadrupole-Orbitrap mass spectrometer. After data pretreatment by automatic extraction and screening, a data matrix of metabolite features was submitted for statistical analyses. Consequently, 29 metabolic markers, including chlorogenic acids, iridoids and organic acid-glucosides were obtained and characterized. The relative quantitative assay was subsequently performed to monitor their variations across flowering developments. This is the first study that systematically explored the insecticide-induced metabolite variations of LJF while taking into account the inherent variability of flowering development. The results were beneficial for holistic quality assessment of LJF and significant for guiding scientific use of pesticides in the large-scale cultivation.

Objective: To observe the clinical efficacy of kidney tonifying and essence strengthening method in delaying physiological vascular aging. Method: Sixty-two subjects who completed the study were randomly divided into experimental group (31 cases) and control group (31 cases) with the matching research method. The experimental group was treated with kidney tonifying and essence strengthening recipe orally for 24 weeks, while the control group was not interfered with traditional Chinese medicine (TCM). Score of TCM syndrome in kidney deficiency syndrome, pulse wave velocity, intima-media thickness, plasma homocysteine level and serum superoxide dismutase level were evaluated before and after treatment. Result: Compared with before treatment period, the score of TCM syndrome in kidney deficiency syndrome, pulse wave velocity and plasma homocystenine level decreased, while the serum superoxide dismutase level increased in the experimental group after treatment (P<0.01). The score of TCM syndrome in kidney deficiency syndrome, pulse wave velocity, intima-media thickness and plasma homocysteine level increased, while the serum superoxide dismutase level decreased in control group after treatment (P<0.05, P<0.01). After treatment, the score of TCM syndrome in kidney deficiency syndrome in experimental group was lower than that in control group (P<0.01), and the serum superoxide dismutase level in experimental group was higher than that in control group (P<0.01). Conclusion: The kidney tonifying and essence strengthening method may delay the aging of physiological blood vessels caused by aging.

OBJECTIVE: To investigate the effect of bevacizumab in the treatment of children with optic pathway glioma (OPG). METHODS: A retrospective analysis was performed for the clinical data of 30 children with OPG who underwent chemotherapy. According to whether bevacizumab was used, they were divided into conventional chemotherapy (carboplatin, vincristine and etoposide) group with 12 children and combined chemotherapy (bevacizumab, carboplatin, vincristine and etoposide) group with 18 children. The children were followed up to 6 months after chemotherapy, and the two groups were compared in terms of visual acuity and tumor size before and after chemotherapy and adverse reactions during chemotherapy. RESULTS: The combined chemotherapy group had a significantly higher proportion of children achieving tumor regression than the conventional chemotherapy group (P<0.05), while there were no significant differences between the two groups in the proportion of children with improved visual acuity or adverse reactions (P>0.05). No chemotherapy-related death was observed in either group. CONCLUSIONS Bevacizumab combined with conventional chemotherapy can effectively reduce tumor size. Compared with conventional chemotherapy, such combination does not increase adverse reactions and can thus become a new direction for the treatment of OPG in children.
Antineoplastic Combined Chemotherapy Protocols ; Bevacizumab ; Carboplatin ; Child ; Humans ; Optic Nerve Glioma ; Retrospective Studies ; Vincristine

OBJECTIVE: To investigate the risk factors for recurrence of medulloblastoma (MB) within 2 years and their influence on progression-free survival (PFS). METHODS: A retrospective analysis was performed for the clinical data of 123 children with MB who were admitted from January to December, 2017. According to the presence or absence of recurrence, they were divided into recurrence group with 30 children and non-recurrence group with 93 children. The risk factors for recurrence within 2 years were analyzed, and PFS was compared between the children with different risk factors. RESULTS: Large-cell/anaplastic type and M stage were risk factors for MB recurrence within 2 years. The risk of recurrence in the children with M+ MB was 3.525 times that in those with M0 MB, and the risk of recurrence in the children with large-cell/anaplastic MB was 3.358 times that in those with classic MB (P<0.05). The survival analysis showed that the median PFS time was 20 months in the children with M+ MB, and the 20-month PFS rate was 50% ± 11% in the children with M+ MB and 81% ± 5% in those with M0 MB (P<0.05). The 20-month PFS rate was 80% ± 5% in the children with classic MB, 65% ± 10% in those with desmoplastic/nodular MB, 86% ± 13% in those with MB with extensible nodularity, and 36% ± 20% in those with large-cell/anaplastic MB (P<0.05). CONCLUSIONS Recurrence is an important influencing factor for the prognosis of MB, and M+ stage and large-cell/anaplastic MB are risk factors for recurrence. Children with such risk factors tend to have a low PFS rate.
Cerebellar Neoplasms ; Child ; Humans ; Medulloblastoma ; Neoplasm Recurrence, Local ; Prognosis ; Recurrence ; Retrospective Studies ; Risk Factors

Objective: To investigate the clinicopathologic features and differential diagnosis of breast lymphoma in core needle biopsy. Methods: Seventy-two cases of breast lymphoma in core needle biopsy between 2011 and 2016 were extracted from the pathology database of Fudan University Shanghai Cancer Center. The clinicopathologic features were analyzed. The histological diagnosis of the tumors was based on the WHO classifications of tumors of hematopoietic and lymphoid tissues. Immunohistochemistry and molecular methods were performed to detect related antigens and genes. Results: Seventy-one patients were female and one was male. The median age was 54 years. The tumors were located in the right breast in 32 (44.4%) patients and in the left breast in 40 (55.6%) patients. Seven patients had a previous history of lymphoma. Most of the cases presented as a single and painless breast mass. Sixty-three patients received systemic treatment, and nine patients received systemic therapy after excision. The common morphological feature was that single tumor cells infiltrated the stroma, without cohesiveness between tumor cells, and lacking glandular or nested epithelioid structures. The normal ductal and lobular structures of the mammary gland were typically preserved. The tumor cells in some cases were distributed in single rows, and should be differentiated from invasive carcinoma. All cases were positive for LCA, negative for CK. Sixty-eight cases were classified as B-cell lymphoma, including 63 cases (87.5%) of diffuse large B-cell lymphoma (DLBCL; including 3 cases of EBV-positive DLBCL and 60 cases of DLBCL, NOS), two cases of Burkitt lymphoma, one case of mantle cell lymphoma, one case of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue and one case of precursor B lymphoblastic leukemia/lymphoma. The remaining cases included two peripheral T-cell lymphoma (NOS), one extranodal NK/T cell lymphoma, nasal type and one myeloid sarcoma. In 63 cases of DLBCL, 22 cases (34.9%) expressed germinal center B-cell-like (GCB) phenotype and 41 cases (65.1%) showed non-germinal center B-cell-like (non-GCB) phenotype. Conclusions Core needle biopsy could be the preferred method for diagnosis of breast lymphoma. Diffuse large B-cell lymphoma is the most common histologic type of breast lymphoma, and non-GCB subtype is more frequent than GCB subtype.

PURPOSE: The characteristic expression of DNA damage response proteins in familial breast cancers with BRCA1, BRCA2, or non-BRCA1/2 mutations has not been analyzed in Chinese patients. Our study aimed to assess the differential expression of microcephalin 1 (BRIT1), ATM serine/threonine kinase (ATM), checkpoint kinase 2 (CHEK2), BRCA1, RAD51 recombinase (RAD51), and poly (ADP-ribose) polymerase 1 (PARP-1) and establish the profile of Chinese familial breast cancers with different mutation status. METHODS: We constructed five tissue microarrays from 183 familial breast cancer patients (31 with BRCA1 mutations; 14 with BRCA2 mutations, and 138 with non-BRCA1/2 mutations). The DNA response and repair markers used for immunohistochemistry analysis included BRIT1, ATM, CHEK2, BRCA1, RAD51, and PARP-1. The expressions of these proteins were analyzed in BRCA1/2 mutated tumors. The association between pathologic characteristics with BRCA1/2 mutation status was also analyzed. RESULTS: In familial breast cancer patients, BRCA1 mutated tumors were more frequent with high nuclear grade, estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 negative, low Ki-67, and positive CK5/6. BRCA1 mutated tumors had lower CHEK2 and higher cytoplasmic BRIT1 expression than BRCA2 and non-BRCA1/2 mutation tumors. BRCA2-associated tumors showed higher CHEK2 and cytoplasmic RAD51 expression than those in other groups. Nuclear PARP-1 expression in BRCA1/2-associated tumors was significantly higher than in non-BRCA1/2 mutation tumors. Moreover, we found quite a few of negative PARP-1 expression cases in BRCA1/2 mutated groups. CONCLUSION: The clinicopathologic findings of BRCA1-associated Chinese familial breast cancers were similar to the results of other studies. Chinese familial breast cancer patients with BRCA1/2 mutations might have distinctive expression of different DNA damage response proteins. The reduced expression of PARP-1 in Chinese BRCA1/2 mutated breast cancer patients could influence the therapeutic outcome of PARP-1 inhibitors.
Asian Continental Ancestry Group* ; Breast Neoplasms* ; Breast* ; Checkpoint Kinase 2 ; Cytoplasm ; DNA Damage* ; DNA Repair ; DNA* ; Estrogens ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Immunohistochemistry ; Phosphotransferases ; Rad51 Recombinase ; Receptor, Epidermal Growth Factor

Objective To research the role of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in the pathogenesis of alcoholic liver injury in mice.Methods Healthy and mature male mice were reared normally.They were divided at random into 5 groups,namely the normal group (n =10),the experimental-1 group (n =10),the experimental-2 group (n =10),the experimental-3 group(n =10),the experimental-4 group(n =10).The normal group was not treated.The mouse in experimental-1 group,experimental-2 group,experimental-3 group,experimental-4 group were given uninterruptedly 56 degree Beijing Red Star Erguotou by intragastric administration(14 mL · kg-1) for preparation of alcohol liver injury in mice.At the first week,the second week,the third week and the fourth week,respectively,the blood of mice was taken directly by eyeball enucleation.The serum levels of aspartate aminotransferase(AST) was measured with a aspartate aminotransferase assay kit.The expression levels of p-STAT3 in liver of mice was measured by Western blot.Results The serum levels of AST in normal group,experimental-1 group,experimental-2 group,experimental-3 group,experimental-4 group were (112 ±22),(126 ±24),(967 ±30),(1010 ±35),(206 ±23) U · L-1;comparison between experimental-1 group,experimental-4 group and normal group,the difference were without significantly (all P ＞ 0.05);comparison between experimemal-2 group,experimental-3 group and normal group,the difference had significantly (all P ＜ 0.01).The expression levels of p-STAT3 in the 5 groups were (0.52 ± 0.11),(3.21 ±0.33),(1.12 ± 0.21),(1.51 ± 0.23),(2.13 ± 0.26) AU;comparison between experimental-1 group,experimental-4 group and normal group,the difference had significantly (all P ＜ 0.01);comparison between experi mental-2 group,experimental-3 group and normal group,the difference had significantly(all P ＜0.05).ConclusionP-STAT3 may be involved in the acute phase response in the early stage of liver injury in mice,and participate in and promote hepatocyte injury.In the later stage,it may be beneficial to the regeneration,repair and inhibition of hepatocyte apoptosis.