Anti-tumor drug research and development in non-small cell lung cancer (NSCLC) is rapidly developing, and the clinical application of high-throughput sequencing technology is also becoming widespread. Accordingly, researchers are focusing on human epidermal growth factor receptor-2 (HER-2) gene as a rare target of NSCLC, and a series of exploratory studies has been performed. Traditional chemotherapy and immunotherapy are unsatisfactory in the HER-2 mutant population, whereas the survival improvement of anti-HER-2 monoclonal antibodies and pan-HER inhibitors is limited. The development of antibody drug conjugate (ADC) ushers in a turning point for HER-2-mutated NSCLC, and new ADC drugs represented by trastuzumab deruxtecan are making a breakthrough. It opens up a new era of precision therapy for advanced HER-2-mutated NSCLC. Additionally, novel HER-2 inhibitors show very encouraging initial efficacy and safety, and clinical trials are ongoing. This review focuses on the latest progress of research on HER-2-mutated NSCLC.

In the era of evidence-based medicine, it is necessary to explore the unique advantages of traditional Chinese medicine (TCM) based on standardized technical methods and operating procedures in order to achieve the modernization and internationalization of TCM and benefit all humanity. The proposal of a three-pronged evidence system combining TCM theory, human experience and experimental evidence marks an important progress in the thinking method of the TCM evaluation system. The multi-evidence body integrated through appropriate methods provides a strong support for the clinical guideline recommendations and evidence-based health decision-making in TCM. Based on the current methodological progress of international evidence synthesis and grading, this paper proposes a novel approach for integrating multi-evidence in TCM: the MERGE framework. The aim is to establish a solid foundation for the development of this methodology and provide guidance for the advancement of evidence-based medicine framework in TCM.

Rosuvastatin(RVS)is an excellent drug with anti-inflammatory and lipid-lowering properties in the aca-demic and medical fields.However,this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia(HHcy),including high oral dosage,poor targeting,and long-term toxic side effects.In this study,we applied nanotechnology to construct a biomimetic nano-delivery system,macrophage membrane(M?m)-coated RVS-loaded Prussian blue(PB)nanoparticles(MPR NPs),for improving the bioavailability and targeting capacity of RVS,specifically to the plaque lesions associated with HHcy-induced atherosclerosis.In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4(TLR4)/hypoxia-inducible factor-1α(HIF-1α)/nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathways,reducing pyroptosis and inflammatory response in macrophages.Additionally,MPR NPs reversed the abnormal distribution of adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)/ATP binding cassette transporter G1(ABCA1)/ATP binding cassette transporter G1(ABCG1)caused by HIF-1α,promoting cholesterol efflux and reducing lipid deposition.In vivo studies using apolipoprotein E knockout(ApoE-/-)mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable bio-security,and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes.These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.

Objective:To investigate the clinical features of patients with epilepsy in Neurosurgery Outpatient and influencing factors for their seizure control.Methods:Six hundred and seventy-three epilepsy patients admitted to Neurosurgery Outpatient of 6 hospitals including Fifth Affiliated Hospital of Zhengzhou University from September 2017 to December 2022 were chosen. Clinical data (including general demographic data, education level, onset age, onset cycle and duration, course of onset, family annual income and seizure control) were collected using a questionnaire prepared by He'nan Epilepsy Systematic Diagnosis and Treatment Center to summarize the clinical features. Univariate and multivariate Logistic regressions were used to analyze the influencing factors for their seizure control.Results:(1) In these 673 epilepsy patients, 50 (7.4%), 78 (11.6%), 192 (28.5%), 100 (14.9%), 68 (10.1%), 72 (10.7%) and 113 (16.8%), respectively, were <1 year old (infant stage), 1-2 years old (children stage), 3-5 years old (preschool stage), 6-16 years old (juvenile stage), 17-39 years old (young stage), 40-64 years old (middle-aged stage) and ≥65 years old (elderly stage). In the past medical treatment history, 23.0% (155/673) patients did not receive intervention, 72.4% (487/673) received medication, and 4.6% (31/673) received surgical treatment; 55.9% (376/673) had good seizure control and 44.1% (297/673) had poor seizure control. (2) Secondary education ( OR=2.199, 95% CI: 1.037-15.221, P=0.033), primary education or below ( OR=3.544, 95% CI: 2.101-21.343, P=0.012), daily seizures ( OR=4.788, 95% CI: 1.369-33.103, P=0.011), each seizure lasted ≥3 min ( OR=4.179, 95% CI: 3.338-18.550, P=0.003), course of disease≥3 years ( OR=0.199, 95% CI: 0.077-0.602, P=0.001), course of disease for 1-3 years ( OR=0.379, 95% CI: 0.108-0.882, P=0.031), and currently taken antiepileptic drugs for 3 or more ( OR=6.237, 95% CI: 2.195-17.837, P=0.001) were independent risk factors for poor seizure control in epilepsy patients. Conclusion:In Neurosurgery Outpatient, children with diseases before childhood enjoy the largest proportion; drug therapy remains the main treatment; low education level, short seizure cycle, long duration of attack, long course of disease, and multiple drugs used in these patients imply poor anti-epileptic effecacy.

Cohesion between sister chromatids occurs during DNA replication, is regulated by cohesin, and depends on acetylation of cell division cycle associated 5 (CDCA5) and cohesin. WAPL can promote dissociation of cohesin from DNA, and CDCA5 can antagonize the effect of WAPL and stabilize sister chromatids cohesion by stabilizing the binding of cohesin to DNA. CDCA5 mRNA has a high transcription level in a variety of tumor cell lines, suggesting that CDCA5 may be related to the higher malignant proliferation activity of tumor cells, and has been confirmed in various tumors such as liver cancer and lung cancer, and CDCA5 may be a potential targeted molecule for the treatment of malignant tumors.

Objective To investigate the effect of acidic tumor microenvironment on invasion and migration and its mechanism in glioma cells. Methods (1) The pH value of the medium was adjusted by acid-base titration. Human glioma cells U87 and U251 were cultured in the acid group and the normal group with pH values of 6.4 and 7.4, respectively; and 3 d after cultivation, the expressions of hypoxia-inducible factor-2α (HIF-2α) and CD44 were detected by Western blotting; Transwell assay was used to examine the invasion and migration of U87 and U251 cells; immunofluorescence was employed to examine the CD44 expression. (2) The U87 and U251 cells were divided into small interfering RNA (siRNA) -nonsense sequence group and siRNA-CD44-1 group, and the siRNA nonsense sequences and siRNA-CD44-1 interfering fragments were transfected by lipofectin-3000, respectively; three d after transfection, the migration and invasion abilities of cells from the two groups were detected by Transwell assay. (3) U87 and U251 cells were divided into acid group (cultured with a pH value of 6.4), blank control group, siRNA nonsense sequence group, siRNA-CD44-1 group, and siRNA-CD44-2 group; and cells from the later four groups were cultured with a pH value of 7.4; after culture for 4 d, the siRNA-nonsense sequence group, siRNA-CD44-1 group and siRNA-CD44-2 group were transfected with siRNA-nonsense sequences, siRNA-cd44-1 interfering fragments and siRNA-CD44-2 interfering fragments, respectively; three d after transfection, the expressions of CD44, N-Ca, Vimentin, and matrix metalloproteinase (MMP)-2 proteins in these 5 groups were detected by Western blotting. Results (1) As compared with the normal group, the expression levels of HIF-2α and CD44 in U87 and U251 cells of the acid group were significantly increased; both Transwell and invasion experiments showed that the number of transmembrane cells in the acid group was significantly larger than that in the normal group (P<0.05); immunofluorescence staining showed that the CD44 expression in acid group was significantly higher than that in normal group (P<0.05). (2) Both Transwell and invasion experiments showed that the number of transmembrane cells in the siRNA-CD44-1 group was significantly smaller than that in the siRNA nonsense sequence group (P<0.05). (3) Western blotting showed that the expression levels of CD44, N-Ca, Vimentin and MMP-2 in U87 and U251 cells of the blank control group, siRNA nonsense sequence group, siRNA-CD44-1 group, and siRNA-CD44-2 group were obviously decreased as compared with those in the acid group; the expression levels of CD44, N-Ca, Vimentin and MMP-2 in U87 and U251 cells of the siRNA-CD44-1 group and siRNA-CD44-2 group were obviously lower than those in the siRNA nonsense sequence group. Conclusion Acidic tumor microenvironment enhances the capabilities of invasion and migration of glioma cells through increasing CD44 expression.

Objective To study the influence of micro (miR)-325 in progression of glioma and its molecular mechanism by regulating transferrin receptor (TFRC) gene expression in glioma cells. Methods (1) Thirty-five glioma tissues and paired adjacent normal tissues were collected during surgical excision performed in our hospital from January 2015 to January 2018. The miR-325 and TFRC mRNA expression levels in the glioma tissues and paired adjacent normal tissues were detected by inverse transcription-quantitative PCR (RT-qPCR); the expression of miR-325 in glioma tissues of patients with different clinical characteristics and the survival curves of patients with low or high miR-325 expressions were compared. (2) RT-qPCR was used to examine the miR-325 expression in HA, U251, and U87 cell lines in vitro; the regulatory relations between miR-325 and its potential target gene TFRC in U251, and U87 cell lines were measured by luciferase report assay; miR-325 mimic and its negative control were transfected into U251 and U87 cell lines for 48 h, and then, the mRNA and protein expressions of TFRC were detected by RT-qPCR and Western blotting, respectively; control small interfering RNA (siRNA)+nonsense inhibitor, TFRC siRNA+nonsense inhibitor, and siTFRC+miR-325 inhibitor were transfected into U251 and U87 cell lines for 48 h, respectively, Western blotting was employed to detect the TFRC protein expression, cell proliferation was detected by CCK-8 assay, and cell invasion was detected by Transwell assay; pcDNA3.1 empty vector+nonsense sequence, TFRC pcDNA3. 1+nonsense sequence, TFRC pcDNA3.1+miR-325 mimic were transfected into U251 and U87 cell lines for 48 h, respectively, TFRC protein expression was detected by Western blotting, cell proliferation was detected by CCK-8 assay, and cell invasion was detected by Transwell assay. Results (1) As compared with those in the adjacent tissues, the miR-325 expression was significantly decreased and the TFRC mRNA expression was statistically increased in glioma tissues (P<0.05); the TFRC mRNA expression and miR-325 expression were negatively correlated in glioma tissues (P<0.05); as compared with patients with Karnofsky functional status scores≥80, patients with scores<80 had significantly decreased miR-325 expression; as compared with glioma tissues of WHO grading I-II, glioma tissues of grading III-IV had significantly decreased miR-325 expression (P<0.05); the survival rate of patients with low miR-325 expression was statistically lower than that of patients with high miR-325 expression (P< 0.05). (2) As compared with that in HA cells, the miR-325 expression was statistically down-regulated in U87 and U251 cells (P<0.05); in TFRC wild-type (TFRC WT) transfected cells, the miR-325 mimic group had significantly lower luciferase activity than the nonsense sequence group, while the miR-325 inhibitor group had significantly higher luciferase activity than the nonsense inhibitor group (P<0.05); as compared with those in the nonsense sequence group, the TFRC mRNA and protein expressions were statistically decreased in U87 and U251 cells of miR-325 mimic group; as compared with those in the control siRNA+nonsense inhibitor group, the TFRC protein expression and absorbance value were significantly decreased, and number of invasive cells was significantly smaller in the siTFRC+nonsense inhibitor group; and as compared with those in the siTFRC+nonsense inhibitor group, the TFRC protein expression and absorbance value were significantly increased, and number of invasive cells was significantly larger in the siTFRC+miR-325 inhibitor group (P<0.05); as compared with the pcDNA3.1 empty vector+nonsense sequence group, the TFRC protein expression and absorbance value were significantly increased, and number of invasive cells was significantly larger in the TFRC pcDNA3.1 +nonsense sequence group, and as compared with the TFRC pcDNA3.1+nonsense sequence group, the TFRC protein expression and absorbance value were significantly decreased, and number of invasive cells was significantly smaller in the TFRC pcDNA3.1+miR-325 mimic group (P<0.05). Conclusion The miR-325 expression is decreased in glioma cells and has a tumor suppressor effect; patients with low miR-325 expression have poor prognosis; miR-325 inhibits cancer cell progression by inhibiting the expression of the target gene TFRC.

Objective To explore the application value and clinical effect of the bi-directional quality control module for Surgical Package in artificial femoral head replacement. Methods A total of 360 patients undergoing artificial femoral head replacement in our hospital from June 2015 to June 2017 were selected and divided into observation group and control group, 180 cases in each group. The observation group,used bi-directional quality control module of surgical bag, while the control group used conventional management model of surgical bag . The operation time, the incidence of surgical bag, postoperative complications and postoperative satisfaction were compared. Results The average operation time in the observation group was (69.2 ± 11.6)min, the average operation time in the control group was (76.8 ± 14.5)min, P<0.01. The total defect rate in the observation group was 2.2% . The total defect rate in the control group was 22.2%, P<0.01; the observation group had less severe pain, incision split, fever, postoperative bleeding, incision infection than the control group, P<0.05. Patient satisfaction score was (89.38±7.83) points in the observation group, (79.18±5.55) points in the control group, P<0.01. Conclusions The bi-directional quality control module of surgical package can shorten the operation time, reduce the defect surgical packages, reduce the incidence of postoperative complications , improve the quality of operation, and improve patient satisfaction in the application of artificial femoral head replacement. It is worthy of clinical application.

Objective To investigate the regulating mechanism of Notch1 signaling pathway on the invasion and migration ofglioma initiating cells (GICs).Methods (1) Box-plotting was conducted to analyze the mRNA expression of Notch1 in normal brain tissue and glioblastoma tissue using Bredel Brain,Sun Brain and TCGA databases;Kaplan-Meier survival analysis was conducted to analyze the association between the prognosis of glioma patients with the expression of Hes1 in TCGA database;Heatmap was conducted to analyze the expression of Notch1 and CXCR4 in GICs and common cell line in GEO database.(2) Magnetic activated cell sorting was adopted to establish cell lines of U87 GICs and U251 GICs;immunofluorescence staining was used to detect expression of CXCR4 and Notch1.After the cell lines of U87 GICs and U251 GICs were divided into DMSO,shNC,MK0752 and shNotchl groups,the shNotch1 and shNC groups were transfected respectively with recombinant lentivirus of Notch1-shRNA and its control sequence while the MK0752 and DMSO groups were added respectively with MK-0752 of 80 nmol/mL and the same amount of DMSO.The protein expression of Notch1,CXCR4 and p-mTOR was detected by Westem blotting in the 4 groups.The capabilities of invasion and migration of the GICs were detected by Transwell assay in the shNotch1 and shNC groups.Results (1) The box-plotting showed the mRNA expression of Notch 1 in the glioblastoma tissue was significantly higher than in the normal brain tissue (P＜0.05).The Kaplan-Meier survival analysis showed that the life span ofglioma patients with high expression of Hes1 was significantly shorter than that of those with low expression of Hes1 (P＜0.05).Heatmaps showed that the expression levels of Notch1 and CXCR4 in GICs were higher than in the common cell line.(2) The immunofluorescence staining showed that Notch1 and CXCR4 were highly expressed and colocalized in cell lines of U87 GICs and U251 GICs.The Western blotting showed that the protein expression of Notch1,CXCR4 and p-mTOR in the cell lines of U87GICs and U251 GICs in the MK0752 and shNotch1 groups was lower than that in the DMSO and shNC groups.Transwell assay showed that the penetrating-membrane cells per visual field in the shNotch1group were significantly fewer than those in the shNC group (P＜0.05).Conclusion Notch1 signaling pathway can promote invasion and migration of GICs through regulating CXCR4 expression.

Objective Few studies are reported on the clinical characteristics of glioma-related epilepsy (GRE).Postoperative recurrence of epilepsy in some patients seriously affects their recovery.We aimed to explore the duration, frequency and type of the epileptic seizure as well as possible factors for postoperative recurrence of epilepsy.Methods We recorded the frequency and duration of epileptic seizures, analyzed the recurrence-related factors using the Cox regression model, and investigated the risk factors of recurrent epilepsy.Results The postoperative recurrence of epilepsy was found in 24 (26.97%) of the 89 cases, which, compared with the 65 non-recurrence cases, had a significantly longer seizure duration (7[3-10] vs 5[2-9] min, P<0.05) and higher onset frequency (6.5[4-9] vs 5[3-9] times/mo, P<0.05) preoperatively.After surgery, the 24 recurrence cases showed a remarkably reduced seizure duration (1[0.5-2.0] min, P<0.05) and onset frequency (1.5[1-3] times/mo, P<0.05).The main risk factors for epileptic recurrence included the level of the glioma-involved site (HR=6.728, 95% CI: 2.994-15.116), peritumoral edema (>2 cm) (HR=2.867, 95% CI: 1.210-6.795), brain wave type (HR=2.501, 95% CI: 1.058-5.914), and preoperative frequency of epileptic seizure (>6 times/mo) (HR=5.100, 95% CI: 2.437-10.677).Conclusion Postoperative recurrence of epilepsy is associated with the clinical pathological parameters, and the changes of the frequency and duration of epileptic seizures before and after surgery may provide some new theoretical reference for the treatment and prognosis of the disease.