Frontier knowledge and future directions of programmed cell death in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common renal malignancies of the urinary system. Patient outcomes are relatively poor due to the lack of early diagnostic markers and resistance to existing treatment options. Programmed cell death, also known as apoptosis, is a highly regulated and orchestrated form of cell death that occurs ubiquitously throughout various physiological processes. It plays a crucial role in maintaining homeostasis and the balance of cellular activities. The combination of immune checkpoint inhibitors plus targeted therapies is the first-line therapy to advanced RCC. Immune checkpoint inhibitors(ICIs) targeted CTLA-4 and PD-1 have been demonstrated to prompt tumor cell death by immunogenic cell death. Literatures on the rationale of VEGFR inhibitors and mTOR inhibitors to suppress RCC also implicate autophagic, apoptosis and ferroptosis. Accordingly, investigations of cell death modes have important implications for the improvement of existing treatment modalities and the proposal of new therapies for RCC. At present, the novel modes of cell death in renal cancer include ferroptosis, immunogenic cell death, apoptosis, pyroptosis, necroptosis, parthanatos, netotic cell death, cuproptosis, lysosomal-dependent cell death, autophagy-dependent cell death and mpt-driven necrosis, all of which belong to programmed cell death. In this review, we briefly describe the classification of cell death, and discuss the interactions and development between ccRCC and these novel forms of cell death, with a focus on ferroptosis, immunogenic cell death, and apoptosis, in an effort to present the theoretical underpinnings and research possibilities for the diagnosis and targeted treatment of ccRCC.

Genome-wide identification, evolution and expression profiles analysis of bHLH gene family in Castanea mollissima.

The basic helix-loop-helix (bHLH) transcription factors (TFs) gene family is an important gene family in plants, and participates in regulation of plant apical meristem growth, metabolic regulation and stress resistance. However, its characteristics and potential functions have not been studied in chestnut (Castanea mollissima), an important nut with high ecological and economic value. In the present study, 94 CmbHLHs were identified in chestnut genome, of which 88 were unevenly distributed on chromosomes, and other six were located on five unanchored scaffolds. Almost all CmbHLH proteins were predicted in the nucleus, and subcellular localization demonstrated the correctness of the above predictions. Based on the phylogenetic analysis, all of the CmbHLH genes were divided into 19 subgroups with distinct features. Abundant cis-acting regulatory elements related to endosperm expression, meristem expression, and responses to gibberellin (GA) and auxin were identified in the upstream sequences of CmbHLH genes. This indicates that these genes may have potential functions in the morphogenesis of chestnut. Comparative genome analysis showed that dispersed duplication was the main driving force for the expansion of the CmbHLH gene family inferred to have evolved through purifying selection. Transcriptome analysis and qRT-PCR experiments showed that the expression patterns of CmbHLHs were different in different chestnut tissues, and revealed some members may have potential functions in chestnut buds, nuts, fertile/abortive ovules development. The results from this study will be helpful to understand the characteristics and potential functions of the bHLH gene family in chestnut.

Research Progress on the Role of Laminin Subunit Alpha 4 in Diseases / 中国医学科学院学报

Laminin subunit alpha 4 (LAMA4),a member of the laminin family,is present in the intercellular matrix of adult tissues as a major component of basement membrane.LAMA4 is involved in the adhesion of cells and can bind to corresponding integrins to activate relevant signaling pathways,playing an essential role in the growth,proliferation,and migration of cells.It has been demonstrated that LAMA4 is associated with the occurrence and development of a variety of diseases including tumors,and the expression of LAMA4 can be used as a biomarker of tumor diagnosis and prognosis.This paper summarizes the current research progress in LAMA4 with the focus on the relationship between LAMA4 and diseases,especially tumor,with a view to provide new directions for the future research.

Clinical application of a quantitative method of atlantoaxial reduction angle in basilar invagination / 中华外科杂志

Objectives: To investigate the clinical application effect of a quantitative method of atlantoaxial reduction angle in basilar invagination. Methods: A retrospective analysis of clinical and radiographic data was conducted of 38 patients with complicated atlantoaxial dislocation and basilar invagination admitted to the Department of Neurosurgery, First Affiliated Hospital of Chongqing Medical University from May 2020 to May 2022. There were 5 males and 33 females, aged (53.5±9.9) years (range: 38 to 80 years). All patients underwent C1-2 interarticular fusion cage implantation+occipital-cervical fixation by pressing rob with the cantilever technique. The atlantoaxial reduction model of previous studies by our team was used to calculate the reduction angles before surgery. Then titanium rods of prebending angle were prepared according to the calculation before the operation. After that quantitative reduction of angle was performed during the operation. The paired t-test was used to compare the difference between the theoretical and actual reset value. Results: The theoretical reduction angle of all patients was (10.62±1.78)° (range: 6.40° to 13.20°), the actual reduction angle was (10.53±1.63)° (range: 6.70° to 13.30°) and there was no statistical difference between them (t=1.688, P=0.100). The theoretical posterior occipitocervical angle after the operation of all patients was (117.37±5.88)° (range: 107.00° to 133.00°), the actual posterior occipitocervical angle after the operation was (118.25±6.77)° (range: 105.40° to 135.80°) and there was no statistical difference between them (t=-0.737, P=0.466). The postoperative follow-up time of the patients was more than 6 months and the symptoms of all patients were relieved. All patients had satisfactory fusion between small joints without incision infection, internal fixation fracture, displacement, atlantoaxial redislocation, and other long-term complications. Conclusion: The quantitative method of atlantoaxial reduction angle in basilar invagination can calculate the theoretical reduction angle of the clivus axis angle and guide the preparation of the pre-bending titanium rod before surgery, so as to realize the quantification of the atlantoaxial reduction angle.

Engineering and process management-based design of Comprehensive Biotechnology Experiment course / 生物工程学报

Based on the demand of enterprise talents and the characteristics of manufacturing process management in biotechnology, in order to make the students acquire the ability to solve complex engineering problems in the production process, we developed a "Comprehensive Biotechnology Experiment" course, where two-step enzymatic production of l-aspartate and l-alanine were the key processes. In this course, we drew lessons from the site management of the production enterprise, performed the experimental operation mode of four shifts and three operations. The content of this course includes principles, methods and experimental techniques of several core curricula and the site management mode of enterprises. As to the evaluation, the summary of the experimental staff's handover records and the content of teamwork were examined and scored. Through teaching practice and continuous improvement, we developed a complete experimental teaching process and assessment mechanism. Overall, the Comprehensive Biotechnology Experiment course achieved good teaching effect, which may serve as a reference to promote the development of experimental teaching of biotechnology.

Genome-wide identification, evolution and transcriptome analysis of GRAS gene family in Chinese chestnut (Castanea mollissima).

GRAS transcription factors play an important role in regulating various biological processes in plant growth and development. However, their characterization and potential function are still vague in Chinese chestnut (Castanea mollissima), an important nut with rich nutrition and high economic value. In this study, 48 CmGRAS genes were identified in Chinese chestnut genome and phylogenetic analysis divided CmGRAS genes into nine subfamilies, and each of them has distinct conserved structure domain and features. Genomic organization revealed that CmGRAS tend to have a representative GRAS domain and fewer introns. Tandem duplication had the greatest contribution for the CmGRAS expansion based on the comparative genome analysis, and CmGRAS genes experienced strong purifying selection pressure based on the Ka/Ks. Gene expression analysis revealed some CmGRAS members with potential functions in bud development and ovule fertility. CmGRAS genes with more homologous relationships with reference species had more cis-acting elements and higher expression levels. Notably, the lack of DELLA domain in members of the DELLA subfamily may cause de functionalization, and the differences between the three-dimensional structures of them were exhibited. This comprehensive study provides theoretical and practical basis for future research on the evolution and function of GRAS gene family.

Advances in diagnosis and treatment of hilar cholangiocarcinoma / 国际外科学杂志

Hilar cholangiocarcinoma is the most common extrahepatic malignant tumor in clinic, accounting for about 50%-60% of bile duct tumors. Currently, radical surgical resection is regarded as the best treatment for early hepatic hilar cholangiocarcinoma, but, it’s early lesions have no obvious clinical symptoms. Most patients are already in the advanced stage of the disease when they are admitted to hospital. The surgical resection rate is low, and the 5-year survival rate does not exceed 25%. Locally advanced hepatic hilar cholangiocarcinoma are treated with neoadjuvant chemoradiation therapy followed by surgery, it can prolong survival time of the patient. At the same time, the recurrence rate after surgery can reach 50%-70%, and the cancer easily invades microvessels, lymphatic vessels, peripheral nerves and liver, which is one of the most challenging problems in the field of biliary surgery. Therefore, early diagnosis, perioperative management, adequate and accurate preoperative staging assessment, intraoperative standardized resection, postoperative adjuvant therapy of hilar cholangiocarcinoma, it is of great significance to improve the rate of radical surgical resection and prolong the survival time of patients.

Analysis of anticipatory grief and its influencing factors among the main caregivers of maintenance hemodialysis patients / 中国实用护理杂志

Objective:To investigate the status of anticipatory grief among the main caregivers of maintenance hemodialysis patients, and to analyze its influencing factors.Methods:From April 2021 to July 2021, the main caregivers of 180 patients undergoing maintenance hemodialysis in Xiangdong Hospital Affiliated to Hunan Normal University and Liling Traditional Chinese Medicine Hospital in Hunan Province, were selected by convenience sampling method for the research object. The survey was carried out using the General Information Questionnaire, the Anticipatory Grief Scale and the Zarit Caregiver Burden Interview, multiple linear regression was used to analyze the influencing factors of anticipatory grief in the main caregivers of maintenance hemodialysis patients.Results:The total score of Anticipatory Grief Scale in the main caregivers of maintenance hemodialysis patients was 84.43±12.02, and the total score of Zarit Caregiver Burden Interview was 24.92 ± 7.98, which were positively correlated ( r = 0.557, P<0.01).In the multiple linear regression analysis, the caregiver ′s education level, age, gender, care burden and per capita monthly income and the patient ′s age were the influencing factors of anticipatory grief for the main caregivers of maintenance hemodialysis patients ( t values were -5.54-8.75, all P<0.05), which could explain 54.1% of the total variance. Conclusions:The anticipatory grief of the main caregivers of maintenance hemodialysis patients is at a relatively serious level. Medical care should pay more attention to the caregivers and their sadness in their communication, so as to detect problems in time, so as to take targeted measures to the current situation, which is effective to improve their level of grief and improve the quality of care.

Intervention effect of logotherapy on anxiety and depression in patients with chronic glomerulonephritis / 中国实用护理杂志

Objective:To observe and analyze the intervention effect of logotherapy on anxiety and depression in patients with chronic glomerulonephritis (CGN).Methods:Selected 102 CGN patients from March 2019 to May 2020 in Beijing Tiantan Hospital Affiliated to Capital Medical University as the research objects, the general information of the patients was collected, and the patients were randomly divided into the observation group and the control group with 51 cases in each group. The control group was given routine nursing intervention for CGN patients, and the observation group was given logotherapy therapy intervention based on the intervention of the control group. The differences in the scores of the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) between the two groups before and after 3 months of intervention.Results:There were no significant differences in SAS and SDS scores before and after intervention in the control group ( P>0.05). The SAS and SDS scores in the observation group after 3 months of intervention were (40.67 ± 4.17), (48.74 ± 5.01) points, which were significantly lower than (51.34 ± 5.04), (55.19 ± 5.49) points in the control group ( t=8.37, 3.32, both P<0.01). Conclusions:The positive psychological intervention of patients with logotherapy can effectively improve the anxiety and depression of patients with CGN.

Ablation therapy for large hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, and when a single tumor is larger than 5 cm in diameter, it is defined as large HCC. Large HCC has the characteristics of high degree of tumor malignancy and high risk of tumor metastasis and vascular invasion, which increases the difficulty of treatment. Surgical resection is the preferred treatment regimen for large HCC, but only 20%-30% of patients are candidates for surgical treatment. Transarterial chemoembolization (TACE) is recommended as the treatment regimen for unresectable large HCC in Chinese and international guidelines. It can control tumor progression and prolong the survival time of patients; however, repeated TACE has limited efficacy and may cause serious damage to liver function, and TACE alone can no longer meet clinical needs. With the development of tumor ablation techniques such as radiofrequency ablation, microwave ablation, and cryoablation, TACE combined with tumor ablation has become an important treatment method for large HCC. However, there are still controversies over the effect of ablation on large HCC, and therefore, how to choose the appropriate ablation time, reduce tumor residue and recurrence after ablation, and finally bring survival benefits to patients remains a difficult problem to be solved in clinical and scientific research. This article reviews the current status, predicaments, and future development trends of ablation therapy for large HCC.

Short-term efficacy of anti-IgE monoclonal antibody in patients with recurrent chronic rhinosinusitis with nasal polyps combined with asthma / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the short-term efficacy of anti-IgE monoclonal antibody (Omalizumab) in the treatment of recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) complicated with asthma. Methods: Patients with recurrent CRSwNP and comorbid asthma in Beijing TongRen Hospital from May to December of 2020 were continuously recruited and received a 4-month therapy of stable background treatment plus Omalizumab. Results of visual analog scales (VAS) of nasal symptoms, sino-nasal outcome test-22 (SNOT 22) and nasal polyp scores were collected at baseline and post-treatment (1, 2, 3 and 4 months after treatment). Blood routine tests, total nasal resistances (TNR), minimum cross-sectional areas (MCA), total nasal cavity volumes (NCV), forced expiratory volumes in one second (FEV1)/forced vital capacity (FVC) and adverse events were collected at baseline and 4 months after treatment. All results were evaluated for short-term efficacy of Omalizumab. GraphPad Prism 8.2.1 was used for statistic analysis. Results: Ten patients were collected, including 3 males and 7 females, aged (41.13±12.64) years old (x¯±s). Compared to results at baseline, the VAS scores of nasal obstruction, rhinorrhea, hyposmia and headache after 4 months treatment were significantly decreased (1.80±1.48 vs 6.70±2.83, 2.40±1.27 vs 6.40±3.44, 2.70±2.91 vs 8.20±2.25, 0.60±1.08 vs 3.60±2.72, t value was 5.045, 4.243, 5.312, 3.402, respectively, all P<0.01). The scores of SNOT-22 (25.6±20 vs 61.3±33.32, t=4.127, P=0.002 6), nasal polyp scores (2.20±0.92 vs 4.60±0.84, t=9.000, P<0.01) and the count and percentage of eosinophils in peripheral blood were significantly decreased ((94.10±97.78)×109/L vs (360.00±210.80)×109/L, (32.90±27.06)% vs (64.40±20.73)%, t value was 3.678, 2.957, respectively, all P<0.05). NCV (0-5 cm and 0-7 cm) of patients were improved from baseline ((12.62±2.84) cm3 vs (10.40±2.09) cm3, (27.50±14.15) cm3 vs (16.81±6.40) cm3, t value was 2.371, 2.445, respectively, all P<0.05). Conclusions: The 4-month treatment of Omalizumab can significantly improve the nasal symptoms and quality of life of patients with recurrent CRSwNP complicated with asthma, shrink nasal polyps size and reduce the number of peripheral blood eosinophils. Omalizumab can be used as an alternative therapy for refractory CRSwNP patients in the future.

The combination of YAP/TAZ predicts the clinical prognosis in patients with cholangiocarcinoma after radical resection / 中华内科杂志

Objective:Cholangiocarcinoma (CCA) is a malignant tumor derived from bile duct epithelial cells with extremely poor prognosis. The Hippo-Yes-associated protein (YAP)/transcription activator with PDZ binding motif (TAZ) signaling plays a critical role in cancer stem cell biology. Previous studies have shown that the positive expression of YAP/TAZ in CCA predicts larger tumor size and unfavorable clinical outcomes. We aim to evaluate the prognostic value of YAP/TAZ detection in CCA patients.Methods:CCA patients who underwent radical resection were retrospectively analyzed at our institution from January 2011 to June 2016. Postoperative pathological specimens were scored by YAP/TAZ immunohistochemical staining. The prognostic value of YAP/TAZ was analyzed by multivariate Cox-proportional hazards model.Results:A total of 91 CCA patients were enrolled. During a median follow-up time of 11.0 months, 69.2% patients relapsed and 45.1% died. The median OS and DFS were 10.7 months and 8.8 months respectively. The YAP/TAZ dual positive patients owned a worse TNM stage ( P=0.015), poorer tissue differentiation ( P=0.007), and a higher CA199 than those in negative patients. Multivariate Cox analysis identified that YAP/TAZ dual positivity as a significant factor predicted poorer OS ( P=0.010) and DFS ( P=0.028) in CCA patients after radical resection. In subgroup analysis, YAP/TAZ combination also significantly predicted OS ( P=0.044) and DFS ( P=0.043) in CCA patients with positive lymphatic metastasis and/or surgical margin who required adjuvant therapy. Conclusions:YAP/TAZ positivity is an independent predictive factor for survival in CCA patients after radical resectiony.

Endoscopic characteristics associated with malignancy in colorectal laterally spreading tumors / 中华消化内镜杂志

Objective:To investigate the independent predictors for malignancy in colorectal laterally spreading tumors (LSTs) by therapeutic endoscopy.Methods:Data of consecutive patients with colorectal LSTs who underwent endoscopic treatment in Beijing Friendship Hospital between June 2013 and March 2019 were collected for retrospective analysis. Patients′ gender, age, body mass index, smoking history, and endoscopic and histological results were reviewed. Univariate analysis was used to identify the associated factors for malignancy of colorectal LSTs. Factors with statistical significance in univariate analysis were used in multivariate logistic regression to determine the independent predictors.Results:A total of 323 patients with 341 colorectal LSTs were involved in the study. The rate of malignancy was highest in non-granular pseudo depressed (NG-PD) subtype [85.48% (53/62)], followed by granular nodular mixed (G-NM) subtype [76.97% (117/152)]. Both of the above rates were significantly higher than that of granular homogenous (G-H) subtype [29.51% (18/61), P<0.001] and non-granular flat elevated (NG-FE) subtype [24.24% (16/66), P<0.001]. Univariate analysis showed that NG-PD subtype ( P<0.001, OR=18.40, 95% CI: 7.46-45.42), G-NM subtype ( P<0.001, OR=10.45, 95% CI: 5.30-20.58), rectosigmoid location ( P<0.001, OR=2.33, 95% CI: 1.47-3.69) and size ≥2 cm ( P<0.001, OR=2.60, 95% CI: 1.60-4.00) associated with malignancy for colorectal LSTs. In multivariate logistic regression, NG-PD subtype ( P<0.001, OR=17.51, 95% CI: 7.06-43.43), G-NM subtype ( P<0.001, OR=8.25, 95% CI: 4.07-16.73) and size ≥2 cm ( P=0.032, OR=1.80, 95% CI: 1.05-3.08) remained to be independent predictors. Conclusion:LSTs of NG-PD subtype, G-NM subtype or size ≥2 cm are high risk factors of malignancy, in which cases, en bloc resection is required.

Diagnosis and treatment of intrahepatic cholangiocarcinoma / 国际外科学杂志

Intrahepatic cholangiocarcinoma (ICC) is a liver malignant tumor, and its incidence is second only to hepatocellular carcinoma, accounting for 5%-30% of patients with primary liver cancer. Usually it is characterized by insidious attack, high degree of malignancy, postoperative recurrence, and being asymptomatic at the early stage, most patients have developed into the advanced stage when the diagnosis is confirmed. Thus, early laboratory examinations and imaging judgments are particularly important, providing opportunities for early radical resection of patients. The purpose of this paper is to review and update the medical literature to provide new ideas for diagnosis and treatment of ICC.

Application of upper arm totally implantable venous access ports in 34 patients with tumor / 中华临床营养杂志

Objective To investigate the safety,feasibility and clinical application effect of upper arm totally implantable venous access port (TIVAP) inserted by the combination of oncologists and nurses in patients with tumor.Methods A total of 34 patients,who needed long-term transfusion treatment,were included in this study with upper arm TIVAP from March 2017 and December 2017.There were 20 males and 14 females.The median age was 63 (35 ～ 83) years.Upper arm TIVAP was implanted by both doctors and nurses into the patients with tumor,and the TIVAP related success rate,complications and patients satisfaction were recorded.Results 34 patients all succeeded in TIVAP implantation with the operation success rate of 100％.The average operation time was about 40 minutes (30 to 60 minutes) from the disinfecting cloth to the end of the suture.The operations of all patients were successful.After the operation two patients died of cancer progression,one patient had soft tissue infection around capsular bag,None of the patients had other complications such as blocked infusion,catheter shift,port reversal,and so on,and the incidence of complication was 2.94％ (1/34).Conclusions Upper arm TIVAP has the advantages of safe puncture,shorter operation time,few intra-operative and post-operative complications and higher feasibility for operation by both oncologist and nurse,which can supplement the limitations and deficiencies of the chest wall port and PICC in a certain extent,therefore is a good choice for clinical application.

Argon-helium cryoablation for the treatment of hepatic metastases from nasopharyngeal carcinoma:initial results in 16 patients / 介入放射学杂志

Objective To evaluate the efficacy and safety of CT-guided percutaneous argon-helium cryoablation in treating hepatic metastases from nasopharyngeal carcinoma. Methods The clinical data of 16 patients with hepatic metastases from nasopharyngeal carcinoma, who had received percutaneous argonhelium cryoablation therapy, were retrospectively analyzed. The quality of life before and after therapy, and the postoperative complications were recorded. After argon-helium cryoablation therapy, the progression-free survival (PFS), the overall survival (OS), and the one-month, 3-month, 6-month, 12-month postoperative tumor local control rates were calculated. Results In all 16 patients, no severe complications occurred and the quality of life was significantly improved after argon-helium cryoablation therapy. The one-month, 3-month, 6-month, 12-month postoperative tumor local control rates were 100％, 87.5％, 80.0％ and 58.3％respectively. The median PFS was 11 months (95％CI: 8.4-13.6 months), and the median survival time was19 months (95％CI: 9.2-28.8 months) . After argon-helium cryoablation therapy, the half-year, one-year and2-year survival rates were 93.8％, 75％ and 43.8％ respectively. Conclusion For the treatment of hepatic metastases from nasopharyngeal carcinoma, CT-guided percutaneous argon-helium cryoablation is minimally-invasive, safe and effective with reliable curative effect.

Upregulation of PLOD2 promotes invasion and metastasis of osteosarcoma cells / 中华肿瘤杂志

Objective@#To investigate the relationship of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) expression and the clinical characteristics of osteosarcoma, and explore the potential mechanism of tumour metastasis promoted by PLOD2.@*Methods@#The expression of PLOD2 in osteosarcoma tissues and paired adjacent tissues were detected by immunohistochemistry and qRT-PCR. Correlation of PLOD2 expression in osteosarcoma with the clinical pathologic features was analyzed by Chi square test and Kaplan-Meier analysis.Fibrillar collagen formation and collagen deposition in the tumor tissues were detected by picrosirius red staining. We transfected U-2OS cells with LV-vector, LV-over/PLOD2, sh-NC and sh-PLOD2. The expression of PLOD2 was detected by qRT-PCR. The impact of POLD2 on U-2OS cell invasion was determined by wound-healing assay and Transwell migration assay. The expressions of PLOD2/FAK/JAK2-STAT3 signal pathway related proteins were detected by western blotting.@*Results@#The high expression level of PLOD2 in osteosarcoma tissues was 72.5%, significantly higher than 0% in paired adjacent noncancerous tissues (P<0.01), the expression of PLOD2 was positively correlated with lymph node metastasis, pulmonary metastasis and poor outcome (P<0.01). The same results were also observed in qRT-PCR assay. The median survival time of patients with high expression of PLOD2 protein was 13 months, significantly shorter than 32 months of patients with low expression of PLOD2 (P<0.05). The result of picrosirius red staining showed that the percentage of collagen fiber deposition in the osteosarcoma tissue with high level of PLOD2 was (74.43+ 9.63)%, significantly higher than (9.67±1.28)% in tissue with low expression of PLOD2 (P<0.001). The result of wound-healing and Transwell migration assay showed that over-expression of PLOD2 markedly promoted the invasion, however, knockdown of PLOD2 suppressed the invasion of U-2OS cells (both P<0.01). The result of western blotting showed that over-expression of PLOD2 significantly increased the expression levels of p-FAK, p-JAK2, p-STAT3, but knockdown PLOD2 decreased the levels of p-FAK, p-JAK2, p-STAT3 in U-2OS cells.@*Conclusions@#Up-regulation of PLOD2 in osteosarcoma is correlated with lymphatic and distant metastasis. PLOD2 promotes invasion and metastasis of osteosarcoma might through FAK/JAK2-STAT3 signal pathway.

Mechanism of MALAT1 induced osimertinib resistance in HCC827 lung cancer cells / 中华肿瘤杂志

Objective@#To test the effect of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) and/or osimertinib on the proliferation and apoptosis of HCC827 cells, and explore the potential mechanism of MALAT1 induced resistance to osimertinib.@*Methods@#We transfected HCC827 cells with LV-vector or LV-over/MALAT1. Stable transfected cells (HCC827/Vector, HCC827/MALAT1) were selected by adding puromycin. HCC827/MALAT1 cells were further transfected with the shRNA-negative control (NC) or shRNA-human epidermal growth factor receptor 3 (ERBB3) plasmid. The effects of overexpression of MALAT1, knockdown of ERBB3 and/or osimertinib on the proliferation of HCC827 cells were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. Cell apoptosis induced by MALAT1 overexpression, knockdown of ERBB3 and/or osimertinib treatment were analyzed by flow cytometry analysis. The expressions of EGFR and ERBB3 signal pathway related proteins in HCC827 cells treated with overexpression of MALAT1, knockdown of ERBB3 and/or osimertinib treatment were detected by western blot.@*Results@#The MTT assay showed that sensitivity to osimertinib of HCC827/MALAT1 cells were significantly repressed. The 50% inhibitive concentration (IC50) of osimertinib >4 000 nmol/L in HCC827/MALAT1 cells. However, knockdown of ERBB3 facilitated the anti-proliferation effect of osimertinib, and the IC50 of osimertinib in shRNA-ERBB3 cells was (17.27±3.21) nmol/L. The results of flow cytometry analysis showed that the apoptotic rate of HCC827/MALAT1 cells induced by 10 nmol/L osimertinib was (8.38±0.92)%, significantly lower than (27.17±5.83)% of knockdown of ERBB3 (P<0.01). Western blotting showed that the expression of p-ERBB3, p-AKT and p-extracellular regulated protein kinases (ERK) in HCC827/MALAT1 cells was markedly up-regulated, while the expression of p-epithelial growth factor receptor (EGFR) was inhibited. The expressions of p-ERBB3, p-AKT and p-ERK were marginally affected by osimertinb. However, osimertinib downregulated the expressions of p-EGFR, p-ERBB3, p-AKT and p-ERK in ERBB3 deleted cells.@*Conclusions@#MALAT1 confers resistance to osimertinb in HCC827 cells by activating of the ERBB3/PI3K/AKT and ERBB3/MAPK/ERK signaling pathways.

Role of the system of orexin/receptors in neurological diseases / 生理学报

The neuropeptide orexin is widely distributed in the nervous system. Previous studies showed that orexin is involved in the feeding behavior regulation by binding to its receptor 1 (OX1R) and receptor 2 (OX2R) to activate the downstream signaling pathway. Recent studies have demonstrated that the system of orexin and its receptors are also involved in important physiological processes such as sleep-wake, learning and memory, and pathological processes of various neurological diseases. In this review, we summarized the research progress on the function of the orexin and its receptor system in physiological and pathological processes, and revealed the correlation between orexin and nervous system diseases, in order to provide the theoretical guidance for the diagnosis and treatment of the related diseases in the future.

Identification of a novel STK11 gene mutation in a family affected with hereditary Peutz-Jeghers syndrome / 中华医学遗传学杂志

OBJECTIVE To explore the genetic basis for a family affected with Peutz-Jeghers syndrome (PJS). METHODS Genomic DNA was extracted from peripheral blood and oral swab samples from the patient and her relatives. Next-generation sequencing (NGS) was used to analyze 106 target genes by capturing the exons and adjacent intronic regions. Suspected pathogenic mutation was verified by NGS. RESULTS A missense STK11 mutation was detected in the proband, which was not reported previously. The mutation has caused substitution of Leucine by Proline. NGS has detected the same mutation in the mother but not among other relatives. CONCLUSION This hereditary case of PJS may be attributed to the missense mutation of the STK11 gene.