Objective To discusses the role of suboccipital retrosigmoid approach in surgical treatment of cerebellopontine angle meningiomas.Methods The clinical data of 32 patients with cerebellopontine angle meningiomas,underwent microsurgery through suboccipital retrosigmoid approach in our hospital from January 1998 and December 2014,were analyzed retrospectively.The treatment efficacy was analyzed.Results In these 32 patients,all of them received tumor removal.After the operation and during the follow-up,the preoperative symptoms and signs disappeared in 22 patients,and relieved in 7.The cranial nerve deficit was unchanged in 3;new neurological deficit was presented in 5,and 8 months-3 years follow up showed that excepted for two patients with permanent damage,the other 3 patents got recovery within 3-6 months of follow up.No tumor recurrence was noted.Conclusion Suboccipital retrosigmoid approach offers excellent exposure to cerebellopontine angle region in surgical treatment of cerebellopontine angle meningiomas,enjoying tiny operational trauma,quick recovery and few complications.

Quantitative proteomics is a mass spectrometry-based toolkit used to analyze and quantify entire proteins contained in whole cells, tissues or organisms. It has become an increasingly important element in exploring the mechanism of various biological processes such as discovering novel biomarkers and unknown drug targets. Emerging advances in biological mass spectrometry instrumentation and data acquisition methodologies have provided a state-of-the-art platform for protein quantification, prompting the research of proteomics evolving from the simple qualitative to the accurate quantitative approach. This review aims to introduce the most recent advancements in mass spectrometry instrumentation and methodologies of data acquisition, focusing on their characteristics and applying fields. It also highlights several significant applications of biological mass spectrometry in pharmaceutical research such as quantifitation of drug transporters and metabolizing enzymes, and pharmacokinetic study of therapeutic peptides and proteins.

Background: The mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2) inhibitor trametinib has shown promising therapeutic effects on melanoma, but its efficacy on colorectal cancer (CRC) is limited. Synthetic lethality arises with a combination of two or more separate gene mutations that causes cell death, whereas individual mutations keep cells alive. This study aimed to identify the genes responsible for resistance to trametinib in CRC cells, using a synthetic lethal short hairpin RNA (shRNA) screening approach. Methods: We infected HT29 cells with a pooled lentiviral shRNA library and applied next-generation sequencing to identify shRNAs with reduced abundance after 8-day treatment of 20 nmol/L trametinib. HCT116 and HT29 cells were used in validation studies. Stable ring finger protein 183 (RNF183)-overexpressing cell lines were generated by pcDNA4-myc/his-RNF183 transfection. Stable RNF183-knockdown cell lines were generated by infection of lentivi-ruses that express RNF183 shRNA, and small interference RNA (siRNA) was used to knock down RNF183 transiently. Quantitative real-time PCR was used to determine the mRNA expression. Western blotting, immunohistochemical analysis, and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the protein abundance. MTT assay, colony formation assay, and subcutaneous xenograft tumor growth model were used to evaluate cell proliferation. Results: In the primary screening, we found that the abundance of RNF183 shRNA was markedly reduced after treatment with trametinib. Trametinib induced the expression of RNF183, which conferred resistance to drug-induced cell growth repression and apoptotic and non-apoptotic cell deaths. Moreover, interleukin-8 (IL-8) was a downstream gene of RNF183 and was required for the function of RNF183 in facilitating cell growth. Additionally, elevated RNF183 expression partly reduced the inhibitory effect of trametinib on IL-8 expression. Finally, xenograft tumor model showed the synergism of RNF183 knockdown and trametinib in repressing the growth of CRC cells in vivo. Conclusion: The RNF183-IL-8 axis is responsible for the resistance of CRC cells to the MEK1/2 inhibitor trametinib and may serve as a candidate target for combined therapy for CRC.

Objective To investigate the progression of breast cancer in mice induced by chronic binding stress and the regulatory mechanism of Xiaoyao SAN based on TGF-β1/CD147 signal pathway.Methods 40 BABL/c mice were randomly divided into tumor group,model group,Xiaoyaosan group and Mifepristone group,and then 4T1 cell line was inoculated into the armpits of each group of mice.After Tumor formation,mice in all groups except tumor group were subjected to chronic restraint stress for 21 days.Meanwhile,mice in Xiaoyaosan and Mifepristone groups were gavaged with the corresponding drugs,and mice in the other two groups were gavaged with normal saline.After the modeling,the mice were sacrificed after anaesthesia.The weight and volume of the tumors and visceral index of the mice were measured.The contents of serum tumor markers(CA199,CEA,VEGF),serum neurotransmitters(DA and CORT),and inflammatory mediators(TGF-β1 and IL-10)in tumor tissues were detected by Elisa.The expressions of iNOS and Arg-1,the polarization markers of macrophages,and the expressions of CD147 and its downstream signaling molecules MMP2,MMP9 and VEGF in tumor tissues were all detected by immunohistochemistry and Western blot.Results Compared with tumor group,in model group,tumor weight and volume,serum CA199,CEA,VEGF,CORT content,tumor TGF-β1 and IL-10 content were significantly increased;visceral index and serum DA content were significantly reduced;the expression of M2-type polarization marker Arg-1 in tumor macrophages was significantly increased,while the expression of M1-type polarization marker iNOS was significantly decreased;the expressions of CD147 and its downstream signaling molecules MMP2,MMP9 and VEGF were significantly increased.Both Xiaoyaosan and mifepristone could effectively reverse the above changes.Conclusion The mechanism of chronic restraint stress promoting breast cancer progression in mice is related to the increased release of TGF-β1 from M2-type polarization of tumor-associated macrophages,which activates CD147 and its downstream related signals.Xiaoyaosan could relieve the M2-type polarization of macrophages caused by increased corticosterone under stress conditions,reduce the production of TGF-β1,inhibit CD147 and its downstream signal,and thus inhibit the progression of breast cancer caused by chronic restraint stress in mice.

Pathological mood changes,mainly depression,occurring during the diagnosis and treatment of breast cancer are referred to as breast cancer-related depression(BCRD).Numerous epidemiological and clinical studies have confirmed that BCRD is a complex condition that is difficult to treat and has a poor prognosis.Most existing clinical treatments involve the use of postoperative chemotherapy for breast cancer,and antidepressant drugs,which treat breast cancer and depression as two independent diseases and have various disadvantages such as low efficiency and strong adverse reactions.Traditional Chinese Medicine(TCM)has a unique value in the prevention and treatment of BCRD via its ability to regulate multiple pathways and targets using multiple components at the same time.In this paper,we review the mechanism of BRCD and the therapeutic mechanisms of TCM from the aspects of neurological disorders,inflammatory immune response,and intestinal flora disorders,with a view to providing references for the clinical application and research of TCM in the treatment of BCRD.

【Objective】 To investigate the clinical efficacy and safety of low-dose rituximab combined with dexamethasone in the treatment of refractory ITP (RITP) in children. 【Methods】 A total of 31 RITP children, admitted to the Hematology Department of Kunming Children′s Hospital from January 2016 to December 2019 and agreed to receive low-dose rituximab (100 mg/ time, once a week, for 4 successive weeks) combined with dexamethasone (0.6 mg/kg, once a day, for 4 successive days) were enrolled and studied. Blood routine was monitored every other day during treatment, and adverse drug reactions were recorded. The influence of gender, disease course and age on prognosis was compared by χ² test. 【Results】 1) Among the 31 cases, 11 (35.5%) had platelets >100×10⁹/L after 4 weeks and had no recurrence in 6 months; 9 (29%) had platelets >30×10⁹/L but <100×10⁹/L and had no recurrence in 6 months; 11 (35.5%) showed no recovery of platelets, which were consistently lower than 30×10⁹/L. 2) Rituximab was used in 4 cases (12.9%), 1 case (3.2%) presented with severe drug-induced rashes; Headache, vomiting and elevated blood pressure occurred in 2 cases (6.4%). 1 case (3.2%) presented with laryngeal edema. 3) There was no difference in the total effective rate among different gender, age and disease course (P >0.05). 【Conclusion】 The total effective rate of low-dose rituximab combined with dexamethasone for children with refractory ITP in 6 months is 64.5%, and the adverse reactions are tolerable, so it can be used as a treatment option for children with refractory ITP.

Objective To study the core behavioral symptoms,biological indicators,and pathological changes of a mouse model of breast cancer complicated with depression induced using 4T1 breast cancer cell inoculation combined with chronic restraint stress(CRS).Methods BABL/c mice were randomly divided into Control,Stress,Tumor,and stress combined with tumor(S+T)groups.Mice in the tumor and S+T groups were inoculated under the front legs with breast cancer 4T1 cells.After tumor formation,mice in the stress and S+T groups were subjected to CRS for 21 days.The body weight and food intake of each group were monitored during modeling.After the experiment,the occurrence of depression-like behavior of mice in each group was evaluated by sucrose preference test,open field test,elevated plus-maze test,and forced swimming test.After the mice were decapitated,the weights and volumes of the tumors were measured.Concentrations of serum tumor markers,including carbohydrate antigen(CA199),carcinoembryonic antigen(CEA),and vascular endothelial growth factor(VEGF),and related neurotransmitters,including 5-hydroxytryptamine(5-HT),norepinephrine(NE),and corticosterone(CORT),were determined using ELISA.HE staining was used to observe histopathological changes to the hippocampus and tumor.Results In S+T group mice,body weight and food intake were significantly decreased,tumor weight and volume were significantly increased,serum tumor marker(CA199,CEA,VEGF)levels were significantly increased,enthusiasm and desire to explore a new environment were reduced,stress and despair behaviors were significantly increased,and levels of the serum neurotransmitters 5-HT and NE and levels of CORT were significantly increased.In addition,the cell arrangement in the tumor tissue was loose,the amount of intercellular substance decreased,the pathological nuclear classification phase was increased,the arrangement and morphology of neurons in the CA3 region of the hippocampus were disordered,and there were obvious nuclear vacuolation-like changes.Conclusions A mouse model of breast cancer complicated with depression induced by 4T1 breast cancer cell inoculation combined with CRS showed the typical dual symptoms and biological indicators of breast cancer and depression and can be used as a good reference model for experimental studies of breast cancer complicated with depression.