Objective To study the effect of formononetin on the cell damage of glucose/oxygen deprivation/reoxy-genation glyconeurons via the PARP1 signaling pathway,and to offer theoretical support for the use of Caragana isoflavones in the treatment of cerebral ischemia-reperfusion injury.Methods In mouse neurons(HT22),a model of Oxygen-glucose deprivation/reoxygenation(OGD/R)was created.Western blot was used to detect the expres-sion of PARP1 and PARG in HT22 neurons at various time points of glucose-oxygen deprivation/reoxygenation,and the optimal time point of pathway modification was chosen.After OGD/R,HT22 cells were treated with form-ononetin,PARP1 inhibitor(PJ34),and PARG inhibitor,and six groups were developed:control group,control group+formononetin group,OGD/R group,OGD/R+formononetin group,OGD/R+PJ34 group,OGD/R+PARG inhibitor group.HT22 cells were grown normally without OGD/R therapy in the control group.The expres-sion levels of apoptotic factors and associated proteins in each group were determined using immunofluorescence and Western blot.Results PARP1 pathway was activated most obviously in HT22 cells after 3 hours of glucose and ox-ygen deprivation/reoxygenation.Under the condition of OGD/R 3 h,treatment with formononetin,PJ34 or PARG inhibitor could increase E3 ubiquitin ligase(Iduna),inhibit the expression of PARP1 and PARG pathway proteins,reduce the expression of AIF and P53,and increase the phosphorylation level of AKT protein.Conclusion Form-ononetin can block the PARP1/AIF/Akt signaling pathway by raising the expression of Iduna protein in the pres-ence of OGD/R,hence decreasing the damage to HT22 mouse neurons.

Background and purpose:In 2016 the National Cancer Institute(NCI)decided stopping to use NCI-60 cell lines for drug screening,suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research.The reason for NCI-60 cells'retirement'was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials.Since the major cancer behaviors,such as proliferation and metastasis,are fundamentally altered with long-term culture,the tumor cell lines are not representative of the characteristics of cancer in patients.Currently,scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past.Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research.Methods:Breast cancer tissues were collected in the Department of Breast Surgery,Affiliated Hospital of Guizhou Medical University.The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University(approval number:2022 ethics No.313),and the collection and use of tumor tissues complied with the Declaration of Helsinki.The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium.After the cells proliferated,the media were replaced with DEME medium.Cell line STR genotyping was done to determine cell-specific genetic markers and identification.Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors.Results:We created 6 primary breast cancer cell lines.The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features,clinical diagnosis,therapeutic regimens,clinical effectiveness and prognostic outcomes.The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines.Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines.Conclusion:We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.

As a common clinical Chinese medicine, Prunellae Spica has the effects of clearing liver-fire, improving eyesight, resolving massesand detumescence, and has strong anti-tumor effects against thyroid cancer, breast cancer, liver cancer and other cancers. Extracts of Prunellae Spica and its active components can play an anti-tumor role in a variety of ways, including cell apoptosis, inhibiting cell invasion and metastasis, inhibiting cell proliferation, inducing autophagy, anti tumor angiogenesis, reversing tumor multidrug resistance and regulating immune function, by regulating miRNA and Wnt/β-catenin, PI3/AKT, AMPK/mTOR/ULK1, RANKL/RANK/OPG and other signal pathways . In this paper, the anti-tumor mechanism of Prunellae Spica extract was reviewed, in order to provide reference for further research and application.

Angelicae Sinensis Radix, drived from a medicinal and edible plant Angelica sinensis, with the reputation of "nine Angelica recipes out of ten". The volatile oils from Angelicae Sinensis Radix was the main medicinal component of Angelicae Sinensis Radix, mainly including benzene phthalides, terpenoids and alkanes, its chemical composition was complex. Such factors as growth environment, concoction process, extraction methods and other factors all can trigger changes in volatile oil constituents and content from Angelicae Sinensis Radix. Angelicae Sinensis Radix essential oil has diverse pharmacological activities such as anti-hypotension, protection of ischemia-reperfusion injury, asthma, anti-inflammatory and anti-cancer, etc., implying its high clinical application value. This paper reviewed the literature on the volatile oil of Angelicae Sinensis Radix in the past ten years, the chemical components of Angelicae Sinensis Radix were sorted out and the factors affecting the chemical components were summarized, focusing on its anti-hypotensive, ischemia-reperfusion injury protection, asthma and other active effects, in order to provide reference for the further development and utilization of the volatile oil of Angelicae Sinensis Radix.

Objective To investigate the neuroprotective effect and mechanism of salvia polyphenolic acid for injection (SAFI) on cerebral ischemia-reperfusion injury in rats. Methods A total of 100 SD rats were randomly divided into sham surgery group,model group,low-,medium-and high-dose (5,10,20 mg·kg-1) salvia polyphenolic acid groups,with 20 rats in each group. After being continuously administrated by intraperitoneal injection of SAFI once daily for three days,the rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established using the thread embolization method at 1 hour after the last administration. The neurological deficit of rats was evaluated by Zea Longa score. The cerebral infarction volume was detected by 2,3,5-triphenyltetrazolium chloride(TTC) staining. The levels of serum NADPH oxidase(NOX),4-hydroxynonanal(4-HNE),8-hydroxydeoxyguanosine (8-OHdG),monocyte chemoattractant protein-1 (MCP-1),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-18(IL-18),interleukin-6(IL-6),and intercellular adhesion molecule-1 (ICAM-1) were detected by ELISA kits. Hematoxylin-eosin (HE) staining and Nissl staining were used to observe the pathological changes of brain tissue and the morphology of neurons. The apoptosis of neuronal cells in brain tissue was detected by TUNEL. Immunofluorescence staining was used to detect the expression level of glial fibrillary acidic protein (GFAP) in brain tissue. Western Blot was used to detect the protein expression of NLRP3 and Caspase1 in brain tissue. Results Compared with the sham surgery group,neurological deficit scores in model group increased remarkably (P<0.01). The cerebral infarction volume increased significantly (P<0.01). Serious pathological damage of brain was observed,and neuronal density decreased significantly(P<0.01). The apoptosis rate of cortical cells increased obviously (P<0.01). The levels of serum NOX,4-HNE,8-OHdG,MCP-1,TNF-α,IL-1β,IL-18,IL-6 and ICAM-1 increased significantly (P<0.05,P<0.01). The protein expression of GFAP,NLRP3 and Caspase1 in brain significantly upregulated (P<0.01). Compared with the model group,neurological deficit scores in medium-and high-dose SAFI groups decreased remarkably (P<0.01). The cerebral infarction volume decreased significantly (P<0.01). Neuronal damage was ameliorated to varying degrees,and neuronal density increased significantly(P<0.05,P<0.01). The apoptosis rate of cortical cells decreased obviously (P<0.01). The levels of serum NOX,4-HNE,8-OHdG,MCP-1,TNF-α,IL-1β,IL-18,IL-6 and ICAM-1 decreased significantly (P<0.05,P<0.01). The protein expression of GFAP,NLRP3 and Caspase1 in brain significantly downregulated(P<0.01). Conclusion SAFI has a protective effect on MCAO/R rats,which can significantly reduce oxidative stress and inflammatory responses,thereby reducing pathological damage and apoptosis of brain tissue. Its mechanism may be related to the inhibition of NLRP3/Caspase-1 signaling pathway and astrocyte activation.

Successful aging is an important strategy to actively deal with aging as well as a crucial measure to maintain national security and social harmony and stability, and the assessment of successful aging is the prerequisite and basis for relevant measures. However, standardized assessment tools for successful aging have not yet been formed by far, which has had a certain impact on the in-depth research in successful aging. This article summarizes and analyzes the comprehensive assessment methods and tools for successful aging at home and abroad, and provides references for the research into comprehensive assessment tools for successful aging, with a view to promoting the formation of standardized and comprehensive assessment tools for successful aging and developing comprehensive assessment tools for successful aging for Chinese elderly based on China's conditions.

Anaplastic lymphoma kinase (ALK) fusion gene, as a tumor driver gene, was crucial for the occurrence and development of non-small cell lung cancer (NSCLC). Recently, targeted ALK fusion gene has become the main treatment method for ALK-positive NSCLC. The first and second generation ALK inhibitors (ALKi), such as crizotinib, ceritinib, alectinib and ensartinib have been approved in China. However, there was no guidance for the management of ALKi adverse reactions. Therefore, this "Recommendations from experts in the management of adverse reactions to ALK inhibitors (2021 version)" has been summarized, led by Lung Cancer Professional Committee of Sichuan Cancer Society and Sichuan Medical Quality Control Center for Tumor Diseases, to provide practical and feasible strategies for clinical ALKi management specification of adverse reactions.
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Carcinoma, Non-Small-Cell Lung ; Crizotinib ; Humans ; Lung Neoplasms/genetics* ; Protein Kinase Inhibitors/adverse effects* ; Receptor Protein-Tyrosine Kinases/antagonists & inhibitors*

Objective:To understand the current situation and influencing factors of successful aging in widowed elderly.Methods:From May to October 2019, 225 widowed elderly people were investigated by questionnaire in 7 communities and 5 villages in Shandong Province. The Successful Aging Scale of the Flood was used to assess their successful aging status. The general data sheet, Physical Activity Scale for the Elderly (PASE), Multidimensional Scale of Perceived Social Support(MSPSS), Connor-Davidson Resilience Scale (CD-RISC) and Mini Mental State Examination(MMSE) were used to measure its influencing factors.Results:The successful aging score of the widowed elderly was 46.22 ± 9.49. The results of multiple linear regression analysis showed that the influencing factors of the successful aging of the widowed elderly were: social activity participation, household registration, consciously successful aging status, psychological resilience, MMSE—attention and computing power, perceived social support—other people, leisure physical activity, which can explain a total of 70.7% of the regression equation.Conclusions:The successful aging status of widowed old people is at a low level, and its influencing factors have both common factors and specific characteristics compared with those with spouses. In particular, more attention should be paid to "participation in social activities", and the widowed old people should be actively encouraged to participate and improve their successful aging.

BACKGROUND: Anaplastic lymphoma kinase (ALK) rearrangement is a common driver gene of non-small cell lung cancer (NSCLC). Ceritinib is a second-generation ALK inhibitor, which can bring survival benefits to ALK-positive metastatic NSCLC. However, few studies focus on the safety and efficacy of ceritinib in China. Therefore, this study intends to investigate the safety and preliminary efficacy of ceritinib 450 mg with meals in Chinese patients with ALK-positive NSCLC through a real world study. METHODS: From October 2018 to December 2019, patients with ALK-positive NSCLC from 8 medical centers in Sichuan province were recruited in this study. All of these participants received ceritinib 450 mg/d with food. The basic characteristics, adverse effects (AEs) and responses were collected and analyzed in order to evaluate the safety and efficacy of ceritinib. RESULTS: A total of 109 patients were included in this study. Data cutoff was January 23, 2020. The median duration of treatment exposure was 5.87 mon (range: 0.4 mon-15.7 mon). Total AEs were reported in 98 (89.9%) of 109 patients and grade 3 or 4 AEs were reported in 22.9% of patients. Most common AEs (mainly grade 1 or 2) were diarrhea (60.6%), elevated alanine aminotransferase (ALT)(38.5%) and aspartate aminotransferase (AST)(37.6%). As of data cutoff, 45 patients discontinued ceritinib. The overall response rate (ORR) was 37.6% (95%CI: 28.5%-47.4%) and disease control rate (DCR) was 86.2% (95%CI: 78.3%-92.1%). CONCLUSIONS The treatment of ceritinib 450 mg with food for Chinese ALK-positive NSCLC patients had a good safety profile and favorable DCR in real-world setting. However, this conclusion needs to be further verified by large sample, prospective trials.

Objective: To study Duraphat fluoride varnish on the remineralization of demineralized permanent enamel by carbonated beverages. Methods: 30 permanent premolar teeth from 12 to 25 years old young people were collected from orthodontic extraction. Enamel blocks were prepared from each tooth and randomly divided into group A (Coco cola), B(deionized water), C(Coco cola + Duraphat), D(Coco cola + 2％ NaF) and E(Coco cola + artificial saliva) (n = 15), the specinens were respectively treated for 7 d. The enamel surface were observed by scanning electron microscope(SEM). The Ca2 + and P3 + content(weight percentage) were detected by energy spectrum analyzer. Results: The surface of permanent enamel of group A showed a characteristic honeycomb-like appearance, that of group B were smooth. Group C showed irregular large globule deposits on the surface, group D showed some globule structures on the surface, group E showed a little deposits on the surface. Ca2 + and P3 + content of group A was lower than that of group B, in group C was higher than in group E(P＜ 0. 05). Ca2 + content in group D was higher than that in group E(P＜ 0. 05). Conclusion: Duraphat fluoride varnish can promote the remineralization of demineralized permanent enamel by carbonated beverage.