Search

Objectives: Non-small cell lung cancer (NSCLC) patients with exon 20 insertion mutations (ex20ins) of the epidermal growth factor receptor (EGFR) were resistant to monotherapy of immune checkpoint inhibitor (ICI). However, recent reports have shown that the combination of ICI and chemotherapy (ICI-combined regimen) exhibited certain efficacy for NSCLC with EGFR ex20ins. The mechanisms behind this phenomenon have not been thoroughly clarified. Hence, we conducted this study tofind correlations between the tumor immune microenvironment of EGFR ex20ins and the efficacy of ICI-combined regimen., Methods: We performed single-cell transcriptome sequencing and multiplex immunofluorescence staining (mIF) to investigate the immune microenvironment of NSCLC patients with EGFR ex20ins, L858R, and EGFR wild-type. We analyzed 15 treatment-naïve NSCLC samples utilizing single-cell RNA sequencing (scRNA-seq). Another 30 cases of EGFR L858R and 4 cases of wild-type were recruited to compare the immune microenvironment with that of EGFR ex20ins (28 cases) by mIF., Results: We observed that cell components, function and interactions varied between EGFR ex20ins, L858R, and wild-type NSCLC.We discovered similar T cell and CD8+ T cell distributions among groups but found noninferior or even better T cell activation in ex20ins patients. Infiltrating CD8+ FOXP3- T cells were significantly lower in the tumor region of EGFR ex20ins compared to wild-type. T cells from the ex20ins group had a greater tendency to promote cancer cell inflammation and epithelial-mesenchymal transition (EMT) compared to wild-type group. For macrophages, there were more M2-like macrophages in ex20ins patients. M1-like macrophages in ex20ins group produced fewer antitumor cytokines than in other groups., Conclusions: The immune microenvironment of EGFR ex20ins is more suppressive than that of L858R and wild-type, suggesting that ICI monotherapy may not be sufficient for these patients. ICI-combined regimen might be a treatment option for EGFR ex20ins due to tumor-promoting inflammation and noninferior T cell functions in the immune microenvironment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

To analyze the infection and drug-resistant gene 23S rRNA mutations of mycoplasma pneumoniae (Mp) in hospitalized children aged 0-17 in Ningbo City from 2019 to 2023. Throat swabs were collected from hospitalized children with respiratory tract infections in Ningbo University Affiliated Women and Children's Hospital from 2019 to 2023. They were subjected to real-time fluorescence quantitative polymerase chain reaction detection to analyze Mp infection and drug-resistant gene (23S rRNA) mutations. Intergroup comparisons were made by the Chi-square test or Fisher's exact probability method. A total of 18 968 hospitalized children were included, with a total positive rate of 30.37% (5 760/18 968). The total positive rate of drug-resistant gene mutations was 82.45% (4 749/5 760). The positive rate of Mp in male children was 29.26%, which was lower than that in female children (31.67%, χ 2 =12.948, P <0.001). The positive rate of Mp drug-resistant gene mutations in male children was 82.52%, which was higher than that in female children(82.37%, χ 2 =0.021, P =0.885). The positive rates of Mp increased with age ( χ 2 =1 722.21, P <0.001). The positive rates of Mp drug-resistant gene mutations also increased with age ( χ 2 =13.152, P <0.001). In the four seasons, the total positive rate of Mp in summer and autumn was significantly higher than that in winter and spring ( χ 2 =1 085.149, P <0.001). Among them, the Mp positive rates in the summer and autumn of 2019 were as high as 38.26% and 34.49%, while in the summer and autumn of 2020, the Mp positive rates were 2.55% and 1.65%, respectively, which were the lowest in previous years. In the summer and autumn of 2023, the Mp positive rates increased to 47.22% and 51.06%. There was no statistically significant difference in the detection rate of Mp drug-resistant gene mutations among the four seasons. In Conclusion, Mp infection was more prevalent in the summer and autumn in Ningbo city and females and children aged 7-17 were more susceptible. The epidemic of Mp infection in Ningbo occurred in the summer of 2019. After the COVID-19 pandemic in 2020, the positive rate of Mp rapidly decreased and later remained in a low incidence state. After the lifting of restrictive prevention and control measures in 2023, the Mp positive rate returned to an epidemic state. The positive rate of Mp drug-resistant gene (23S rRNA) mutations was relatively high.

The effect of steaming treatment on salmon quality was explored by different multi-omics and electronic sensory system in this study. A comparison between conventional steaming (CS) and anaerobic steaming (AS) was conducted in organoleptic quality of salmon. Twelve key volatile compounds were identified, which contributed to the flavor difference. The concentrations of hexanal, (E)-2-octen-1-al, and decanal in AS salmon were significantly lower than in CS salmon, which account for 68.9-80.5 % of the latter. During steaming, the fatty acids and diacylglycerols decreased significantly by 37.4 % and 57.9 %, respectively. Anaerobic steaming limited the degradation of some oxidized lipids, further reduced some volatile secondary oxidation products. Nucleotides and derivatives, succinic acid, glutamic acid, hydroxyproline and betaine contributed to the saltness, umami, richness of steamed salmon. Metabolomics data revealed that the higher creatinine, Ala-Ala and Ala-Leu provided more umami and less bitterness to AS salmon., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Inhibition of immunocyte infiltration and activation has been suggested to effectively ameliorate nonalcoholic steatohepatitis (NASH). Paired immunoglobulin-like receptor B (PirB) and its human ortholog receptor, leukocyte immunoglobulin-like receptor B (LILRB2), are immune-inhibitory receptors. However, their role in NASH pathogenesis is still unclear. Here, we demonstrate that PirB/LILRB2 regulates the migration of macrophages during NASH by binding with its ligand angiopoietin-like protein 8 (ANGPTL8). Hepatocyte-specific ANGPTL8 knockout reduces MDM infiltration and resolves lipid accumulation and fibrosis progression in the livers of NASH mice. In addition, PirB -/- bone marrow (BM) chimeras abrogate ANGPTL8-induced MDM migration to the liver. And yet, PirB ectodomain protein could ameliorate NASH by sequestering ANGPTL8. Furthermore, LILRB2-ANGPTL8 binding-promoted MDM migration and inflammatory activation are also observed in human peripheral blood monocytes. Taken together, our findings reveal the role of PirB/LILRB2 in NASH pathogenesis and identify PirB/LILRB2-ANGPTL8 signaling as a potential target for the management or treatment of NASH., (© 2023. The Author(s).)

Esophageal squamous cell carcinoma (ESCC) has limited effective treatment strategies. DNA damage response (DDR) genes are of therapeutic interest in multiple cancer types. This study aimed to depict the landscape of DDR mutations in ESCC and evaluate the association between DDR mutations and known immunotherapy biomarkers. We recruited 250 Chinese patients with ESCC and performed next-generation sequencing. A total of 107 patients underwent a PD-L1 examination. Among the 250 patients, 73 (29.2%) harbored at least one DDR gene mutation and were defined as DDR-mut. Among the six functional DDR pathways, homologous recombination (HR) accounted for 12.4% (31/250). DDR-mut patients were significantly associated with higher tumor mutational burden than those in the DDR-wt group (p=7.4e-07). Patients with PDL1-H accounted for 21.2% (36/107) of the patients. PDL1-H was more prevalent in DDR-mut than DDR-wt, although the p-value did not reach a significant level (40.5% vs. 30%, p=0.29). Further analysis revealed that BRCA1, one of the most frequently mutated genes in the HR pathway, was significantly associated with PDL1-H (p=0.01). Our data revealed a subset of patients with ESCC harbored DDR gene mutations. Patients with these DDR gene mutations are significantly associated with immune biomarkers, implying the potential feasibility of combining DDR agents with immunotherapy in patients with DDR deficiency.

Objective: To evaluate the related factors of postoperative recurrence intrigeminal neuralgia (TN) patients treated with fully neuroendoscopic microvascular decompression (MVD). Methods: The clinical baseline data and preoperative MRI imaging data of 112 patients with TN treated by neuroendoscopic MVD from December 2008 to December 2020 in the Department of Neurosurgery, Beijing Shijitan Hospital Affiliated to Capital Medical University were retrospectively analyzed, including: area ratio of cerebellopontine area (CPA)(healthy side/affected side), trigeminal nerve(TGN)length ratio(healthy side/affected side), TGN angle ratio(healthy side/affected side), and criminal vessel type. Multivariate Cox proportional hazards model was used to analyze the factors affecting postoperative recurrence. Results: Among the 112 patients in this group, there were 49 males and 63 females. The age ranged from 20 to 82 (59±9) years, and the course of disease was 0.05 to 30.00 (5.60±5.15) years. Pain was located on the left side in 43 cases (38.39%) and on the right side in 69 cases (61.61%), respectively. All patients were followed up for more than 1 year, with an average follow-up time of 21.5 months, and 11 cases recurred. Multivariate Cox regression analysis revealed that disease duration≥3 years( HR =9.34, 95% CI :1.12-39.07), CPA area ratio(healthy side/affected side)>1 ( HR =27.47, 95% CI :1.69-44.20), criminal vessel type with vein( HR =35.39, 95% CI :1.26-18.60) and criminal vessel type with arteriovenous ( HR =46.07, 95% CI : 2.74-27.75) were the main factors influencing recurrence of MVD surgery (all P <0.05). Conclusion: The disease duration≥3 years, CPA area ratio(healthy side/affected side)>1, and criminal vessel type with vein/arteriovenous are the relevant factors that affect the recurrence rate after the fully neuroendoscopic MVD treatment for trigeminal neuralgia.

Background: Pharmacological research results showed that total flavonoids of Chuju (TFCJ) could be used to treat acute myocardial ischemia and myocardial ischemia-reperfusion injury. In this study, we explored the protective effect of TFCJ on ischemic stroke (IS) in the IS rat model. We hypothesized that TFCJ might exert its neuroprotective effects by suppressing apoptosis and oxidative stress that are closely related to PI3K/Akt/mTOR signaling pathway. Method: TFCJ (10, 20, and 40 mg/kg) was administered for 7 days. Rats (260 ± 20 g) were subjected to middle cerebral artery occlusion (MCAO) for 2 h and reperfusion for 24 h. The neuroprotective effect of TFCJ was substantiated in terms of neurological deficits, oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde), pathomorphological changes (HE staining and TUNEL staining), and neurobehavioral functions in the rats. Then, we employed network pharmacology to reveal the potential mechanism of TFCJ against IS. Western blot was used to determine the levels of PI3K/AKT/mTOR pathway proteins. The expression of BCL-2, BAX, and cleaved-Caspase-3 was also measured by Western blots and RT-PCR. Results: The histopathological assessment showed that TFCJ reduced MCAO-induced brain damage. Besides, TFCJ exerted a protective role in MCAO rats by alleviating cell apoptosis and oxidative stress. Network pharmacology showed that TFCJ might be used against IS through the PI3K/AKT signaling pathway. TFCJ reduced cell apoptosis and oxidative stress by increasing the level of p-AKT and p-mTOR in MCAO rats, while the effect of TFCJ was significantly reversed when applying LY294002 (PI3k inhibitor). Conclusion: These results indicated that TFCJ might decrease oxidative stress and apoptosis that are closely related to PI3K/Akt/mTOR pathway in IS. TFCJ is a promising authentic traditional Chinese medicine for the management of IS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Chen, Jiang, Mao and Yu.)

Background: Panax notoginseng saponins (PNS) have been deemed effective herb compounds for treating ischaemic stroke (IS) and improving the quality of life of IS patients. This study aimed to investigate the underlying mechanisms of PNS in the treatment of IS based on network pharmacology., Methods: PNS were identified from the Traditional Chinese Medicine System Pharmacology (TCMSP) database, and their possible targets were predicted using the PharmMapper database. IS-related targets were identified from the GeneCards database, OMIM database, and DisGeNET database. A herb-compound-target-disease network was constructed using Cytoscape, and protein-protein interaction (PPI) networks were established with STRING. GO enrichment and KEGG pathway analysis were performed using DAVID. The binding of the compounds and key targets was validated by molecular docking studies using AutoDock Vina. The neuroprotective effect of TFCJ was substantiated in terms of oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde) and the levels of IGF1/PI3K/Akt pathway proteins., Results: A total of 375 PNS targets and 5111 IS-related targets were identified. Among these targets, 241 were common to PNS, and IS network analysis showed that MAPK1, AKT1, PIK3R1, SRC, MAPK8, EGFR, IGF1, HRAS, RHOA, and HSP90AA1 are key targets of PNS against IS. Furthermore, GO and KEGG enrichment analysis indicated that PNS probably exert therapeutic effects against IS by regulating many pathways, such as the Ras, oestrogen, FoxO, prolactin, Rap1, PI3K-Akt, insulin, PPAR, and thyroid hormone signalling pathways. Molecular docking studies further corroborated the experimental results.The network pharmacology results were further verified by molecular docking and in vivo experiments., Conclusions: The ameliorative effects of PNS against IS were predicted to be associated with the regulation of the IGF1-PI3K-Akt signalling pathway. Ginsenoside Re and ginsenoside Rb1 may play an important role in the treatment of IS., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Cong Wang et al.)

Objective: To explore the efficacy and technical features of fully endoscopic microvascular decompression(MVD) in primary trigeminal neuralgia(PTN) via keyhole approach. Methods: The clinical data of 97 patients with PTN underwent fully endoscopic MVD via keyhole approach in the Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University from December 2014 to February 2019 was collected. During fully endoscopic MVD in PTN via keyhole approach, performer use natural clearance without grinding except developed rock bone crest or excessive retraction of the brain tissue, visually and panoramically observe and evaluate the CPA area, accurately identify the responsible vessels, to avoid the omission of responsible vessels or insufficient decompression. And the use of preplaced technology, bridging technology and submersible technology, ensure the efficacy of surgery and reduce the surgical side injuries.Barrow Neurological Institute (BNI) pain score was used to evaluate the efficacy and identify the recurrence. The surgical efficacy was analyzed. Results: The offending vessels were identified under endoscope in 96 cases. Among them, arterial compression was found in 77 cases, venous compression in 6 cases, and both arterial and venous compression in 13 cases. About the pain outcomes, 87 cases had immediate and complete relief of pain, 5 cases had almost relief of pain, 4 cases had partial relief of pain, and still needed medication control, but the dose was lower than that before operation, and 1 case had no obvious relief of pain. About complications, there were 4 cases of temporary facial numbness, 1 case of temporary hearing loss, both of them recovered after symptomatic treatment. There was no cerebral infarction or hemorrhage, intracranial or incision infection. All cases were followed up for 3.0-38.0 months with a median period of(22.4±2.2) months. During the follow-up periods, postoperative recurrence occurred in 3 cases. Conclusion: Fully endoscopic MVD for PTN through keyhole approach, provides panoramic view to avoid omission of offending vessels and reduce complications, seemed to be a safe and effective surgical method.

Cerebral ventricular infection (CVI) is one of the most dangerous complications in neurosurgery because of its high mortality and disability rates. Few studies have examined the application of neuroendoscopic surgical techniques (NESTs) to assess and treat CVI. This multicenter, retrospective study was conducted using clinical data of 32 patients with CVI who were assessed and treated by NESTs in China. The patients included 20 men and 12 women with a mean age of 42.97 years. NESTs were used to obliterate intraventricular debris and pus, fenestrate or incise the intraventricular compartment and reconstruct cerebrospinal fluid circulation, and remove artificial material. Intraventricular irrigation with antibiotic saline was applied after neuroendoscopic surgery (NES). Secondary hydrocephalus was treated by endoscopic third ventriculostomy or a ventriculoperitoneal shunt. Neuroendoscopic findings of CVI were used to classify patients into Grade I (n = 3), Grade II (n = 13), Grade III (n = 10), and Grade IV (n = 6) CVI. The three patients with grade I CVI underwent one NES, the 23 patients with grade II/III CVI underwent two NESs, and patients with grade IV CVI underwent two (n = 3) or three (n = 3) NESs. The imaging features and grades of neuroendoscopy results were positively related to the number of neurosurgical endoscopic procedures. Two patients died of multiple organ failure and the other 30 patients fully recovered. Among the 26 patients with secondary hydrocephalus, 18 received ventriculoperitoneal shunt and 8 underwent endoscopic third ventriculostomy. There were no recurrences of CVI during the 6- to 76-month follow-up after NES. Application of NESTs is an innovative method to assess and treat CVI, and its neuroendoscopic classification provides an objective, comprehensive assessment of CVI. The study trial was approved by the Institutional Review Board of Beijing Shijitan Hospital, Capital Medical University, China., Competing Interests: None

Background: Glioma is the most common primary malignant tumor in the central nervous system. Because of the resistance of glioma to chemoradiotherapy and its aggressive growth, the survival rate of patients with glioma has not improved. This study aimed to disclose the effect of retinol dehydrogenase 10 (RDH10) on the migration and invasion of glioma cells, and to explore the potential mechanism., Methods: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression levels of RDH10 in healthy glial cells and glioma cells. Human glioma cell strains, U87 and U251, were infected with negative control or RDH10-interfering lentiviruses. RT-PCR and Western blotting were performed to determine the knockdown efficiency. Scratch and transwell assays were used to assess cell migration and invasion after RDH10 knockdown. Finally, changes in transforming growth factor-β (TGF-β)/SMAD signaling pathway-related expression were examined by Western blotting. Differences between groups were analyzed by one-way analysis of variance., Results: RDH10 was highly expressed in glioma cells. Compared with the control group, RDH10 knockdown significantly reduced RDH10 messenger RNA and protein expression levels in U87 and U251 glioma cells (U87: 1.00 ± 0.08 vs. 0.22 ± 0.02, t = 16.55, P < 0.001; U251: 1.00 ± 0.17 vs. 0.39 ± 0.01, t = 6.30, P < 0.001). The scratch assay indicated that compared with the control group, RDH10 knockdown significantly inhibited the migration of glioma cells (U87: 1.00% ± 0.04% vs. 2.00% ± 0.25%, t = 6.08, P < 0.01; U251: 1.00% ± 0.11% vs. 2.48% ± 0.31%, t = 5.79, P < 0.01). Furthermore, RDH10 knockdown significantly inhibited the invasive capacity of glioma cells (U87: 97.30 ± 7.01 vs. 13.70 ± 0.58, t = 20.36, P < 0.001; U251: 96.20 ± 7.10 vs. 18.30 ± 2.08, t = 18.51, P < 0.001). Finally, Western blotting demonstrated that compared with the control group, downregulation of RDH10 significantly inhibited TGF-β expression, phosphorylated SMAD2, and phosphorylated SMAD3 (TGF-β: 1.00 ± 0.10 vs. 0.53 ± 0.06, t = 7.05, P < 0.01; phosphorylated SMAD2: 1.00 ± 0.20 vs. 0.42 ± 0.17, t = 4.01, P < 0.01; phosphorylated SMAD3: 1.00 ± 0.18 vs. 0.41 ± 0.12, t = 4.12, P < 0.01)., Conclusion: RDH10 knockdown might inhibit metastasis of glioma cells via the TGF-β/SMAD signaling pathway.

Objective: To study the operative method, special technique and curative effect of complete neuroendoscopic microvascular decompression(MVD) related to vertebrobasilar artery compression. Methods: Thirteen patients with functional cranial nerve disease caused by vertebrobasilar artery as direct or indirect responsible vessel accepted complete endoscopic MVD, including 11 patients with hemifacial spasm and 2 patients with trigeminal neuralgia. The procedure and curative effect of endoscopic surgery were analyzed retrospectively. Results: All procedures of complete neuroendoscopic MVD were successfully completed.Intraoperative observation by endoscope showed that 6 cases were oppressed directly by vertebral artery, 2 cases were oppressed directly by basilar artery, 5 cases were combined oppressed by displaced basilar artery and other vessels (1 case was superior cerebellar artery and 4 cases were anterior inferior cerebellar artery). During the operation, Teflon sheets was placed directly into the compression point in 2 cases, the "Pre-placed" technique was used to place Teflon sheets in 7 cases, and the "Set up bridge" technique was used to place Teflon sheets in 4 cases. Follow-up for 8-38 months,the symptoms disappeared completely in 12 cases and improved in 1 case. No deaths and severe complications occurred, such as postoperative bleeding, cerebellar infarction and intracranial infection. Conclusion: MVD related to vertebrobasilar artery compression can be performed by complete neuroendoscopic technique, which can achieve sufficient decompression effect and curative effect.Flexible use of the special technology of placing Teflon sheets by single-hand under endoscope, such as the "Pre-placed" and "Set up bridge" technique, is an important technical guarantee for the successful completion of endoscopic MVD.

Krüppel-like factors (KLFs) are zinc-finger transcriptional factors that regulate target gene expression. Recent studies have shown that KLFs play essential roles in cancer development, whereas the function of KLF7 in glioma remains unclear. In this study, we showed that KLF7 was up-regulated in glioma tissues and its expression was inversely correlated with the patients' survival. Functional experiments demonstrated that KLF7 promoted the proliferation, migration and tumorigenesis of glioma cells. Mechanistically, KLF7 transcriptionally activated argininosuccinate lyase (ASL), which was observed highly expressed in glioma tissues. The biosynthesis of polyamine, a urea cycle metabolite, was enhanced by KLF7 in glioma cells. In addition, ASL contributed to the growth of glioma cells triggered by KLF7. Our findings demonstrate KLF7 as an oncogene and link KLF7 to ASL-mediated polyamine metabolism in glioma., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To investigate the efficacy of soft neuroendoscopic techniques in the treatment of chronic subdural hematoma (CSDH). Methods: A retrospective analysis of 201 cases of CSDH diagnosed and treated at Beijing Shijitan Hospital (CMU) from January 2006 to December 2017 was conducted. From January 2006 to December 2010, 126 cases of CSDH were treated with skull drilling and drainage (non-endoscopic group). From January 2011 to December 2017, 75 cases of CSDH were treated with soft neuroendoscopy (endoscopic group). The operation time of the non-endoscopic and endoscopic groups, the hematoma clearance rate on the first day after surgery, the time of the drainage tube, the length of hospital stay, the incidence of complications, mortality and recurrence rate were compared. Results: There were no deaths in both groups. The average operation time of the non-endoscopic group was 43 min, compared with the average operation time of the endoscopy group of 50 min, there was no significant difference ( P> 0.05). The average hematoma clearance rate on the first day after surgery in the endoscopy group (98.2%) was significantly higher than that in non-endoscopic group (87.3%) ( P< 0.01). The average time of drainage tube in the endoscopy group (23 h) was significantly shorter than that in the non-endoscopic group (50 h) ( P< 0.01). On the first postoperative day, the proportion of patients with mRS≤3 in the endoscopic group was significantly higher than that in the non-endoscopic group ( P< 0.01). At the time of discharge, the proportion of patients with mRS≤3 in the endoscopy group was also significantly higher than that in the non-endoscopic group, P< 0.05. There was no significant difference in the average hospital stay between endoscopy group (7 d) and non-endoscopic group (8 d) ( P> 0.05). The postoperative complication rate in the endoscopy group was significantly lower than that in the non-endoscopic group ( P< 0.01). During 0.5-8 years of follow-up, the recurrence rate of CSDH in the endoscopic group (5.33%) was significantly lower than that in the non-endoscopic group (15.07%) ( P< 0.01). Conclusion: The application of visualization features of soft neuroendoscopy in the treatment of CSDH can significantly improve hematoma clearance, shorten the time of drainage tube, reduce postoperative complications and recurrence rate, and improve surgical outcomes.

Objective: To investigate the efficacy of endoscopic neurosurgery combined with intraventricular lavage for pyogenic ventriculitis. Methods: A retrospective analysis of 45 patients with pyogenic ventriculitis in six hospitals which included Beijing Shijitan Hospital and Peking Union Medical College Hospital from 2001 to 2017. Twenty-four patients (non-endoscopic group) were treated with external ventricular drainage combined with intraventricular antibiotics administration from 2001 to 2009. Twenty-one patients (endoscopic group) was treated by endoscopic neurosurgery combined with intraventricular antibiotics lavage from 2010 to 2017. The drainage time, mortality, and modified Rankin score (mRS) after 6 months of follow-up were compared between the two groups. Results: Drainage time: (20±6) days in the endoscopic group, and (42±10) days in the non-endoscopic group. There was a significant difference between the two groups ( P <0.001). Days in hospital: (29±7) days in the endoscopic group, and (51±11) days in the non-endoscopic group. There were significant differences between the two groups ( P <0.001). Mortality: 8 patients (33.3%) died in the non-endoscopy group, and 1 patient (4.76%) died in the endoscopy group. There was a significant difference between the two groups ( P =0.017). After 6 months of follow-up, patients of mRS≤3 were 14 cases (66.67%) in the endoscopy group, and 7 cases (29.17%) in the non-endoscopic group. There was a significant difference between the two groups ( P =0.001). Conclusion: Endoscopic neurosurgery combined with intraventricular antibiotics saline lavage for pyogenic ventriculitis is an effective assessment and treatment method, and it is worth further promotion and application.

Objective: miRNAs have been confirmed to be related to cell proliferation and apoptosis. In this study, we detected the potential effect of miR-448 on glioma cell proliferation and apoptosis., Materials and Methods: miR-448 and CTTN expression levels were detected in glioma cell lines with quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Cells were transfected with miR-448 mimics and inhibitor by using lipofectamine 2000 respectively. The proliferative ability of transfected cells was detected via methyl thiazolyl tetrazolium (MTT) and cell counting kit-8 (CCK8) assays. Cell apoptosis and cell-cycle were tested using flow cytometry. The regulatory correlation between miR-448 and CTTN was explored by bioinformatics analysis and luciferase reporter assay., Results: Lower expression of miR-448 and higher level of CTTN were detected in glioma cells. MiR-448 could regulate cell proliferation, cell apoptosis, and cell cycle. CTTN was negatively regulated by miR-448., Conclusions: miR-448 downregulates CTTN to inhibit cell proliferation and promote apoptosis in glioma, which indicates a potential therapeutic target of glioma.

We investigate the adiabatic magnetization process of the one-dimensional J - Q 2 model with XXZ anisotropy g in an external magnetic field h by using density matrix renormalization group (DMRG) method. According to the characteristic of the magnetization curves, we draw a magnetization phase diagram consisting of four phases. For a fixed nonzero pair coupling Q, (i) when g < -1, the ground state is always ferromagnetic in spite of h; (ii) when g > -1 but still small, the whole magnetization curve is continuous and smooth; (iii) if further increasing g, there is a macroscopic magnetization jump from partially- to fully-polarized state; (iv) for a sufficiently large g, the magnetization jump is from non- to fully-polarized state. By examining the energy per magnon and the correlation function, we find that the origin of the magnetization jump is the condensation of magnons and the formation of magnetic domains. We also demonstrate that while the experienced states are Heisenberg-like without long-range order, all the jumped-over states have antiferromagnetic or Néel long-range orders, or their mixing.

Objective: To establish a high phase liquid chromatography method of the content in quercetin,luteolin,apigenin,acacetin,and to compare the difference of content from four different varieties of Dendranthema morifolium in simultaneously., Methods: The UPLC methods were adopted,and the chromatographic column was Waters ACQUITYUPLC; the column was BEH C18（ 50 mm ×2. 1 mm,1. 7 μm）,the mobile phase was 0. 1% phosphoric acid solution-methanol in gradient elution,the flow rate was 0. 2 m L/min;and the detection wavelength was set at 320 nm; the column temperature 25 ℃; and the sample quantity was 1 μL., Results: In the range of 0. 0027 0. 0135 mg/m L（ r1= 0. 9962） concentration within quercetin in a good linear relationship between peak area. In the range of0. 0032 0. 0160 mg/m L（ r2= 0. 9963） concentration within luteolin in a good linear relationship between peak area. In the range of0. 0029 0. 0145 mg/m L（ r3= 0. 9964） of apigenin in the mass concentration and the peak area. In the range of 0. 0029 0. 0145 mg/m L（ r4= 0. 9963） concentration within acacetin in a good linear relationship between peak area., Conclusion: This method can be determined daisy quercetin,luteolin,apigenin,acacetin content in Dendranthema morifolium.

Background: Osteosarcoma is the most common bone malignancy in children and adolescents, and 20%-30% of the patients suffer from poor prognosis because of individual chemoresistance. The Hippo/yes-associated protein (YAP) signaling pathway has been shown to play a role in tumor chemoresistance, but no previous report has focused on its involvement in osteosarcoma chemoresistance. This study aimed to investigate the role of the Hippo/YAP signaling pathway in osteosarcoma chemoresistance and to determine potential treatment targets., Methods: Using the Cell Titer-Glo Luminescent cell viability assay and flow cytometry analysis, we determined the proliferation and chemosensitivity of YAP-overexpressing and YAP-knockdown osteosarcoma cells. In addition, using western blotting and the real-time polymerase chain reaction technique, we investigated the alteration of the Hippo/YAP signaling pathway in osteosarcoma cells treated with chemotherapeutic agents., Results: Mammalian sterile 20-like kinase 1 (MST1) degradation was increased, and large tumor suppressor kinase 1/2 (LATS1/2) total protein levels were decreased by methotrexate and doxorubicin, which increased activation and nuclear translocation of YAP. Moreover, YAP increased the proliferation and chemoresistance of MG63 cells., Conclusions: The Hippo/YAP signaling pathway plays a role in osteosarcoma chemoresistance, and YAP is a potential target for reducing chemoresistance.

A series of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at the C2-position were synthesized and evaluated for their antiproliferative activities against A549, MCF-7, HeLa, HT29 and HCT-116 cell lines. Most of the synthesized compounds exhibited broad spectrum antitproliferative activity against five cell lines, of which 5c was the most potent against HT29 cell line with an IC50 value of 5.53 μM, inducing a G2/M phase arrest in HT29 cells. Treatment of HT29 cells with 5c resulted in BubR1 phosphorylation and an increase of mitotic index in a time-dependent manner. Furthermore, 5c promoted tubulin polymerization in vitro. These results demonstrate that quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at C2-position may be potentially novel antitumor agents targeting tubulin to activate the spindle assembly checkpoint., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Promyelocytic leukemia protein (PML) has been implicated as a participant in multiple cellular processes including senescence, apoptosis, proliferation, and differentiation. Studies of PML function in hematopoietic differentiation previously focused principally on its myeloid activities and also indicated that PML is involved in erythroid colony formation. However, the exact role that PML plays in erythropoiesis is essentially unknown. In this report, we found that PML4, a specific PML isoform expressed in erythroid cells, promotes endogenous erythroid genes expression in K562 and primary human erythroid cells. We show that the PML4 effect is GATA binding protein 1 (GATA-1) dependent using GATA-1 knockout/rescued G1E/G1E-ER4 cells. PML4, but not other detected PML isoforms, directly interacts with GATA-1 and can recruit it into PML nuclear bodies. Furthermore, PML4 facilitates GATA-1 trans-activation activity in an interaction-dependent manner. Finally, we present evidence that PML4 enhances GATA-1 occupancy within the globin gene cluster and stimulates cooperation between GATA-1 and its coactivator p300. These results demonstrate that PML4 is an important regulator of GATA-1 and participates in erythroid differention by enhancing GATA-1 trans-activation activity.

Nkx2.5 plays protective roles in cardiac homeostasis and survival in the postnatal hearts. However, the underlying molecular mechanisms that mediate the protective functions of Nkx2.5 remain unknown. Here, we showed that Nkx2.5 was downregulated in response to various stresses and was required for protection against the stress-induced apoptosis of cardiomyocytes. SIRT1, a member of the sirtuin family of proteins, was found to be a direct transcriptional target of Nkx2.5 and was required for the Nkx2.5-mediated protection of cardiomyocytes from doxorubicin (DOX)-induced apoptosis. Moreover, using chromatin immunoprecipitation assays, we found that Nkx2.5 was able to bind to the SIRT1 promoter and that this binding was significantly decreased in DOX-treated mouse hearts. Furthermore, the cardiac-specific overexpression of SIRT1 decreased the DOX-induced apoptosis of cardiomyocytes in SIRT1 transgenic mouse hearts compared with the hearts of their wild-type littermates. These findings demonstrate that SIRT1 acts as a direct transcriptional target of Nkx2.5 that maintains cardiomyocyte homeostasis and survival.

A novel series of 4-substituted-piperazine-1-carbodithioate derivatives of 2,4-diaminoquinazoline were synthesized and tested for their antiproliferative activities against five human cancer cell lines including A549 (lung cancer), MCF-7 (breast adenocarcinoma), HeLa (cervical carcinoma), HT29 and HCT-116 (colorectal cancer). Most of the synthesized compounds showed broad spectrum antiproliferative activity (IC50 1.47-11.83 μM), of which 8f, 8m and 8q were the most active members with IC50 values in the range of 1.58-2.27, 1.84-3.27 and 1.47-4.68 μM against five cancer cell lines examined, respectively. Further investigations revealed that compounds 8f, 8m and 8q exhibited weak inhibition against dihydrofolate reductase and no activity against thymidylate synthase, while induced DNA damage and activated the G2/M checkpoint in HCT-116 cells., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Objective: To explore the operative techniques and efficacy of trans-sylvian-insular approach endoscopic surgery for hypertensive basal ganglia hemorrhage., Methods: A retrospective analysis was conducted in 54 patients with hypertensive basal ganglia hemorrhage from December 2009 to December 2011. All of them underwent neuroendoscopic surgery via a trans-sylvian-insular approach. The hematoma volume was 30 - 40 ml (n = 8), 40 - 50 ml (n = 42) and > 50 ml (n = 4). And the Glasgow Coma Scale (GCS) was 8 - 12 (n = 48) and 13 - 15 (n = 6)., Results: The clearance rate of hematoma was > 90% (n = 44) and 80% - 90% (n = 10). None suffered re-hemorrhage or death., Conclusion: As a mini-invasive and efficacious approach for hypertensive basal ganglia hemorrhage, trans-sylvian-insular approach endoscopic surgery has a high clearance rate of hematoma is high and causes minimal damage to normal brain tissue. It is worth of clinical promotion.

The higher order chromatin structure has recently been revealed as a critical new layer of gene transcriptional control. Changes in higher order chromatin structures were shown to correlate with the availability of transcriptional factors and/or MAR (matrix attachment region) binding proteins, which tether genomic DNA to the nuclear matrix. How posttranslational modification to these protein organizers may affect higher order chromatin structure still pending experimental investigation. The type III histone deacetylase silent mating type information regulator 2, S. cerevisiae, homolog 1 (SIRT1) participates in many physiological processes through targeting both histone and transcriptional factors. We show that MAR binding protein SATB1, which mediates chromatin looping in cytokine, MHC-I and β-globin gene loci, as a new type of SIRT1 substrate. SIRT1 expression increased accompanying erythroid differentiation and the strengthening of β-globin cluster higher order chromatin structure, while knockdown of SIRT1 in erythroid k562 cells weakened the long-range interaction between two SATB1 binding sites in the β-globin locus, MAR(HS2) and MAR(ε). We also show that SIRT1 activity significantly affects ε-globin gene expression in a SATB1-dependent manner and that knockdown of SIRT1 largely blocks ε-globin gene activation during erythroid differentiation. Our work proposes that SIRT1 orchestrates changes in higher order chromatin structure during erythropoiesis, and reveals the dynamic higher order chromatin structure regulation at posttranslational modification level.

Objective: To explore the therapeutic efficacies of endoscope for fourth ventricular outlet obstruction (FVOO)., Methods: Endoscopic third ventriculostomy (ETV) was performed for 30 cases. The circumstances of third ventricular floor and basal cistern were observed and recorded intra-operatively. Meanwhile the fourth ventricular exploration and fistulation were performed across enlarged aqueduct. And the velocity and flow rate of aqueduct, fourth ventricular outlet and stoma were evaluated post-operatively with Cine-MR (magnetic resonance)., Results: Standard ETV was performed successfully in 28 patients. Fourth ventricular exploration (n = 6) and outlet membrane fistulation (n = 2) were carried out. The mean follow-up period was 2.3 years (range: 0.5 - 4.0). The overall success rate was 78.6%., Conclusion: ETV is a viable therapeutic option for FVOO patients. The therapeutic effects of outlet membrane fistulation require further observations.

Tumor-induced osteomalacia (TIO), or oncogenic osteomalacia (OOM), is a rare acquired paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia. Recent evidence shows that tumor-overexpressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia. The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT). Surgical removal of the responsible tumors is clinically essential for the treatment of TIO. However, identifying the responsible tumors is often difficult. Here, we report a case of a TIO patient with elevated serum FGF23 levels suffering from bone pain and hypophosphatemia for more than three years. A tumor was finally located in first metacarpal bone by octreotide scintigraphy and she was cured by surgery. After complete excision of the tumor, serum FGF23 levels rapidly decreased, dropping to 54.7% of the preoperative level one hour after surgery and eventually to a little below normal. The patient's serum phosphate level rapidly improved and returned to normal level in four days. Accordingly, her clinical symptoms were greatly improved within one month after surgery. There was no sign of tumor recurrence during an 18-month period of follow-up. According to pathology, the tumor was originally diagnosed as "lomangioma" based upon a biopsy sample, "proliferative giant cell tumor of tendon sheath" based upon sections of tumor, and finally diagnosed as PMTMCT by consultation one year after surgery. In conclusion, although an extremely rare disease, clinicians and pathologists should be aware of the existence of TIO and PMTMCT, respectively.

Objective: To explore the feasibility, operating technique and precautions of endoscopic microvascular decompression for trigeminal neuralgia., Methods: A retrospective analysis was conducted for 21 patients with primary trigeminal neuralgia. All underwent neuroendoscopic microvascular decompression for trigeminal nerves., Results: The pains disappeared upon awaking post-anesthesia in 19 patients. In 2 patients, pains became significantly alleviated and disappeared after taking carbamazepine for 1 - 3 months. No patient suffered the injuries of trigeminal nerve and other cranial nerves. None had cerebellum edema or death. During the follow-up period, there was no recurrence of pains., Conclusion: Neuroendoscopic surgery may accomplish microvascular decompression for trigeminal nerve independently. As a minimally invasive and effective technique, it offers a clearer vision of local anatomy and decreases the probability of damaging nerves and vessels. There is no need for pulling cerebellum. It brings minimal damage to normal brain tissue compared with microsurgery. Further popularization is warranted.

Objective: To evaluate the method, strategy and efficacy of treating different types of quadrigeminal cistern arachnoid cysts (QCAC) with neuroendoscope., Methods: A retrospective analysis was conducted for 12 QCAC patients with obstructive hydrocephalus. They were classified into 3 types and underwent neuroendoscopic operation at our hospital between November 2005 and November 2009. Their surgical approaches, complications and efficacy were analyzed. The mean age of first diagnosis was 3.7 years old. There were 7 type II cases and 5 type III cases with a varying level of symptoms. The follow-up period was 6 - 24 months. Cine-MRI (magnetic resonance imaging) examination was performed both preoperatively and post-operatively., Results: Among them, 12 patients recovered well without any occurrence of hemorrhage, paralysis, lower cranial nerve injury, cerebrospinal fluid leakage, infection or death. Subdural effusion occurred in 3 cases, but disappeared within 6 months. Seven feverish cases recovered after a symptomatic treatment. The shapes of cysts and ventricles almost returned to a normal level in 8 cases. Three cases of arachnoid cyst had a slight change., Conclusion: In accordance with the QCAC patient types, different neuroendoscopic approaches can fully reconstruct the cerebrospinal fluid circulation. And the use of frameless navigation makes it more precise and safe.

The name of Wuzhuyu (Medicinal Evodia Fruit) comes from the place of "Wu", and the shape of its fruit, which is like a 'Zhuyu'. In addition, it is also called "Yi, Sha, Jiao, Dang, Yuejiao and Qiu" for different reasons; for example, "Yi" because of its processing and sacrificial function; and "Sha" because of the bug-killing function of its root and cortex. In Xin Xiu Ben Cao (Newly Revised Materia Medica) of the Tang Dynasty, its names were unified as Wuzhuyu. Because it can be eaten, it was also called "Shizhuyu". In the Song Dynasty, with the discontinued vogue of eating Zhuyu, people had difference attitudes to the "Wuzhuyu" and "Shizhuyu". Nowadays, "Wuzhuyu" is the established name of these kinds of materia medica.

A DH population containing 81 DH lines from an indica-japonica cross of rice and an RFLP linkage map consisting of 232 markers were used to map quantitative trait loci(QTLs) for harvest index, biomass, grain yield, sink capacity and plant height by a computer program QTLMapper1.0 based on mixed linear models. A total of 21 significant main-effect QTLs and 9 pairs of epistatic loci were detected. Of these, three detected QTLs for grain yield collectively accounted for 42% of the phenotypic variation with a LOD of 7.10. These three grain yield QTLs were corresponded either to QTLs for harvest index or QTLs for biomass in both locations and directions of additive effects, which sheds light on the genetic basis of the formula 'grain yield = biomass x harvest index'. Four detected QTLs for harvest index collectively explained 46% of the total phenotypic variation and four QTLs for biomass jointly accounted for 64% of the trait variation. No coincidence of harvest index QTLs with any biomass QTLs was found, therefore indicating the possibility of pyramiding favorable alleles for both traits through gene recombination so as to obtain a genotype possessing both high harvest index and heavy plant biomass. Five QTLs for plant height were detected that cumulatively explained 64% of the phenotypic variation with a LOD of 11.62. Among these, three with smaller effects respectively co-located with some of the QTLs for biomass, sink capacity and/or grain yield, but not with any of harvest index QTLs, thus suggesting that plant height was to some extent directly associated with 'source' and 'sink' but not with 'transportation' of the 'source-transportation-sink' concept, at least in this genetic background and environment. In view of a somewhat low resolution of the genetic map used in the study and the fact that when plant height QTLs co-located with those for yield and/or yield related traits, these co-located QTLs were all in the same directions of additive effects, it is more likely that these QTLs co-located in a same chromosomal region might be a single QTL which have effects on multiple traits. If this is true, the above observation have led us to assume that QTLs which have pleotropic effects on yield and/or yield related traits and plant height are very different from those which had relatively large effects only on plant height. The former contribute strongly to yield and/or yield related traits but weakly to plant height while the later contribute mainly to plant height. Obviously, due to that an increase of plant height is always coupled with an increase in lodging susceptibility, discriminating between above two types of QTLs is critical in breaking the traits' undesired association in breeding for improved yield potential of rice. In addition, based on the co-location analysis of main-effect QTLs for the studied traits, five genomic regions were found to be highly associated with harvest index, biomass, sink capacity and grain yield.