Lung cancer is one of the most common cancers worldwide and is the leading cause of cancer deaths. Lung adenocarcinoma is the most common type of lung cancer. Due to the lack of effective biomarkers and therapeutic targets in the proliferation and metastasis of lung adenocarcinoma, the overall treatment of lung adenocarcinoma is not optimistic. Therefore, there is a need to find new ideas and methods for lung adenocarcinoma treatment. The 26S proteasome is a multiprotein complex responsible for degrading misfolded proteins and maintaining intracellular protein homeostasis. During the development of non-small cell lung cancer (NSCLC), the regulatory granule subunit of the 26S proteasome promotes the malignant progression of tumours by regulating tumour-associated proteins, immune cells, and related signalling pathways. The proteasome core particle is a key subunit for degrading proteins, and its inhibitors have shown promising anti-tumour effects when combined with conventional chemotherapeutic agents. However, limited by toxic side effects and tumour heterogeneity, targeted inhibitors against the 26S proteasome are still not widely used in NSCLC treatment. This article reviews the mechanism of action and related therapeutic research of 26S proteasome regulatory particle subunits and core particle subunits in NSCLC, and explores the potential of these inhibitors in clinical application.
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Humans ; Proteasome Endopeptidase Complex/chemistry* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Animals ; Proteasome Inhibitors/therapeutic use* ; Antineoplastic Agents/therapeutic use*

A Clinical pharmacist was fully involved in the anticoagulation drug treatment management process of a 104-year-old patient with a large area of cerebral infarction combined with chronic kidney disease stage Ⅴ and secondary deep vein thrombosis.After the patient was diagnosed with deep vein thrombosis,the clinical pharmacist comprehensively analyzed the patient's super-advanced age,history of atrial fibrillation,large area of cerebral infarction,extremely poor kidney function,deep vein thrombosis,and high bleeding risk indicated by the HAS-BLED score.They worked with the clinical doctor to develop an individualized anticoagulation treatment strategy for the patient.At the beginning of the treatment,warfarin was given to the patient at a daily dose of 1.25 mg,and the patient's coagulation indicators and kidney function were dynamically rechecked.The patient's blood creatinine level did not show significant changes throughout the anticoagulation treatment process.On the 8th day of medication,the patient's INR was 2.47,and the clinical pharmacist suggested adjusting the Warfarin to an alternate-day dose of 1.25 mg and 0.625 mg.Subsequently,the patient's INR was 2.41,and the condition improved,leading to discharge.Throughout the anticoagulation drug management process,the clinical pharmacist participated in the clinical decision-making for anticoagulant drug selection,provided professional medication guidance,and pharmacological monitoring to ensure the safe clinical use of drugs for special populations.

Objective:To compare the efficacy and safety between WangShiBaoChiWan and mosapride in the treatment of functional dyspepsia (FD).Methods:From September 2019 to September 2020, patients with postprandial fullness and early satiation who met the Rome Ⅳ criteria for FD diagnosis were enrolled from 15 hospitals, including the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), Beijing Traditional Chinese Medicine Hospital Affiliated to Capital Medical College. The subjects were randomly divided into WangShiBaoChiWan (experimental) group and mosapride (control) group in the ratio of 1∶1. The treatment regimens were WangShiBaoChiWan+ mosapride simulator, WangShiBaoChiWan simulator+ mosapride, respectively with a treatment period of 2 weeks. The primary efficacy outcome was the improvement rates of main symptoms before and after treatment, the secondary efficacy primary efficacy outcome was the total clinical effective rate and the change of the single symptom score. And the safety indicator included adverse events. Independent sample t-test, paired t-test and chi-square test were used for statistical analysis. Results:A total of 251 FD patients were enrolled in the full analysis set, including 124 in the experimental group and 127 in the control group; 241 FD patients were in the per-protocol analysis set, including 117 in the experimental group and 124 in the control group. The analysis of per-protocol analysis set showed that the improvement rates of the main symptoms of the experimental group and the control group were (66±29)% and (60±30)%, respectively, and the difference was not statistically significant ( P>0.05). The improvement rate of the main symptoms of the experimental group reached 117% of that of the control group, which exceeded the expected non-inferiority standard of 80%. The total clinical effective rates of the experimental group and the control group were 76.07% (89/117) and 75.81% (94/124), respectively, and the difference was not statistically significant ( P>0.05). The results of full analysis set showed that the incidence of adverse events of the experimental group and the control group was 1.62% (2/124) and 1.57% (2/127), respectively, and the difference was not statistically significant ( P>0.05). There were no serious adverse events in the two groups. Conclusion:The improvement rate of the main symptoms of WangShiBaoChiWan is not inferior to that of mosapride in the treatment of FD, and it has good safety.

Objective:To evaluate the effect of synthetic CpG oligodeoxynucleotide (CpG-ODN) as adjuvant on immune response induced by inactivated human adenovirus (HAdV)-55 antigen in BALB/c mice.Methods:HAdV-55 virus QS prototype strain was purified by plaque to construct a seed bank of vaccine candidate strain. The amplified product of vaccine candidate strain was inactivated by 0.05%β-propiolactone, and purified to prepare perfect virus particle antigen. The purified HAdV-55 antigen was mixed with the same volume CPG-ODN and aluminum hydroxide adjuvant in low-dose group (0.2 mg/ml) and high-dose group (1 mg/ml), respectively, and inoculated BALB/c mice after emulsification. Meanwhile, the control group was set with PBS, and the immunization was enhanced once every 21 days. Respectively on primary immune 21 and 35 days after collecting venous blood in mice and separation of serum, serum was collected at the end of the time of separating spleen lymphocytes in mice. The levels of HAdV-55 specific IgG antibody and neutralization antibody in serum of immunized mice were observed by ELISA and micro-neutralization test, and the levels of lymphocytes secreting IL-4 and IFN-γ cytokines were detected by ELISpot.Results:No matter with or without adjuvant, along with the increase of the number of immunization and vaccination dose of inactivated HAdV-55 antigen induced BALB/c mice virus specific IgG antibody was also significantly increased. However, neutralizing antibody can reach detectable level only after enhanced immunity, and the geometric mean titer (GMT) of neutralizing antibody is between 1: 11 and 1: 23. Different adjuvants have significant effects on the immune response of mice. Low dose antigen combined with CPG-ODN and aluminum hydroxide mixed adjuvant can induce higher humoral and cellular immune responses in mice, and the levels of specific IgG antibody and neutralizing antibody are 2.2 and 1.8 times higher than those in the aluminum hydroxide adjuvant group, respectively. The number of lymphocytes secreting IFN-γ was 2.3 times that of the group immunized with aluminum hydroxide adjuvant.Conclusions:The novel CPG-ODN adjuvant significantly increased the immunogenicity of the inactivated HAdV-55 whole virus antigen in BALB/c mice and directed the cellular immune response toward Th1 type.

The thioredoxin system is composed of thioredoxin (Trx), thioredoxin reductase (TR) and reduced nicotinamide adenine dinucleotide phosphate. Trx is an important antioxidant molecule that can resist cell death caused by various stresses and plays a prominent role in redox reactions. TR is a protein containing selenium (selenocysteine), mainly in three forms, i.e. TR1, TR2 and TR3. TR1 mainly distributed in the cytoplasm, TR2 mainly distributed in the mitochondria, and TR3 mainly distributed in the testes. TR can regulate cell growth and apoptosis. After the cell becomes cancerous, the expression of TR increases to promote cell growth and metastasis. Trx system is closely related to neurodegenerative diseases, parasitic infections, acquired immunodeficiency syndrome, rheumatoid arthritis, hypertension, myocarditis and so on. The Trx system can remove the reactive oxygen species (ROS) in the body, keep the inside and outside of the cell in a balanced state, and it interacts with the thioredoxin interacting protein (TXNIP), which plays an important role in the regulation of glucose metabolism and tumor treatment. The Trx system is an important target for drug treatment of many diseases. In this paper, the research progress of the thioredoxin system was reviewed.

Background:There is no specific therapy for inflammatory bowel disease(IBD),and the pathogenesis of IBD is not fully clear. Aims:To explore the expression and clinical significance of IL-17BR in colon mucosa and peripheral blood mononuclear cell(PBMC)of patients with IBD. Methods:Colon mucosal biopsy specimens of 40 Crohn's disease(CD) patients,32 ulcerative colitis(UC)patients and 25 healthy controls and PBMC of 30 CD patients,27 UC patients and 25 healthy controls were collected. The expressions of IL-17BR in colon mucosa and PBMC were determined by immunohistochemistry and flow cytometry,respectively,and correlations between IL-17BR expression and levels of CRP, ESR,CDAI score and Mayo score were analyzed. Serum levels of TNF-α before and after infliximab(IFX)treatment were determined by ELISA,and correlations with IL-17BR were analyzed. Results:Compared with healthy controls,IL-17BR expressions in colon mucosa of CD and UC patients were significantly increased(P<0.05). IL-17BR expressions were significantly higher in active CD and UC patients than in remission CD and UC patients(P <0.05). No significant differences in IL-17BR expression in PBMC were found among CD,UC patients and healthy controls(P>0.05). The expression of IL-17BR in colon mucosa was positively correlated with CRP,ESR,CDAI score or Mayo score in CD,UC patients(P <0.05). After treatment with IFX,expression of IL-17BR in colon mucosa and serum TNF-α level were significantly decreased in CD patients(P<0.01). Expression of IL-17BR was positively correlated with serum TNF-α level in CD patients(P<0.05). Conclusions:The increasing of IL-17BR expression in IBD patients is closely correlated with activity of inflammation and TNF-α level. IL-17BR may play a vital role in immune response of intestinal mucosa,and can be used as a new marker for reflecting the activity of IBD.

Objective To analyze the experience of scientific research management in a Traditional Chinese medicine (TCM) hospitals.Methods We systematically summarized the experience of existing practices and established a TCM scientific research delicacy management model including project process management,funds management,personnel evaluation,institutional construction and output transfer.Results The scientific research management model was suitable for the hospital development,in accordance with daily medical and teaching practice.Conclusions Scientific research ability had gradually become an important indicator of TCM hospital evaluation.This management model could provide reference for related issues.

Objective To explore the problems in traditional Chinese medicine (TCM) scientific research project management and provide possible countermeasures.Methods Through cluster sampling,all the scientific research administrators and staff in a hospital were selected.A questionnaire about TCM hospital scientific research management was designed and used in our study.Results The majority of participants were basically satisfied with current scientific research management in TCM.Problems were analyzed including complex project application,singular evaluating standard,inflexible fund management,and backward professional concept.Conclusions The management of scientific research projects in TCM should combine professional characteristics,innovatively and comprehensively improve management concept,system,team and method.

Objective To make a meta-analysis of the effectiveness of hyperthermic perfusion chemotherapy (HPC) combined with bevacizumab for malignant ascites or malignant pleural effusion,and to provide the references for further practice and studies.Methods VIP,Wanfang data,PubMed and CNKI were searched from inception to January 2018.HPC combined with bevacizumab or HPC alone for malignant ascites or pleural effusion were collected for controlled clinical trial (CCT).According to inclusion and exclusion criteria,two reviewers checked studies,extracted data and assessed quality of the included studies.RevMan 5.3 software was used to make a meta-analysis.Results A total of 4 CCT involved 226 patients.Meta-analysis showed that compared with the HPC alone,HPC combined with bevacizumab had a higher rate in clinical efficiency (OR =4.82,95 ％ CI 2.45-9.49,P ＜ 0.000 01),malignant ascites or pleural effusion control rate (OR =4.06,95 ％ CI 1.09-15.11,P ＜ 0.05),quality of life improvement rate (OR =6.79,95 ％ CI 3.53-13.08,P ＜ 0.000 01),and the difference was statistically significant.Conclusion HPC combined with bevacizumab can improve the clinical effective rate,effusion control rate and quality of life improvement rate of the patients with malignant ascites or pleural effusion.

Objective To detect the expression of tumor necrosis factor-α-induced protein-8 like-3 (TIPE3) in colonic mucosa of patients with colon cancer,and to analyze the correlation between its abnormal expression and clinicopathological features of patients with colon cancer.Methods The expression of TIPE3 mRNA in 58 cases of colon cancer and tumor adjacent tissues was detected by realtime polymerase chain reaction (RT-PCR).The expression of TIPE3 at protein level in 83 cases of colon cancer and tumor-adjacent tissues was determined by SP immunohistochemistry.Nonparametric rank-sum test and chi-square test were performed for statistical analysis.Results The relative expression of TIPE3 mRNA in the colon cancer tissues was 0.719 (0.104 to 0.887),which was lower than that of tumor-adjacent tissues (4.770,1.732 to 6.800),and the difference was statistically significant (Z=-6.345,P＜0.05).There was no statistically significant difference in the expression of TIPE3 mRNA in colon cancer tissues between different gender,age and TNM stage (all P＞0.05).The expression of TIPE3 mRNA in group of patients with lymph node metastasis (0.113,0.061 to 0.375) was lower than group of patients without lymph node metastasis (0.489,0.327 to 0.956;Z=3.815,P＜0.01).The expression of TIPE3 mRNA of patients survived less than five years after operation (0.104,0.049 to 0.220) was lower than that of patients survived over five years (0.482,0.266 to 0.908;Z=-3.653,P＜0.01).The expression of TIPE3 mRNA of patients with recurrence after operation (0.188,0.091 to 0.493) was lower than that of patients without recurrence (0.409,0.233 to 1.010;Z=-2.431,P=0.015).The recurrence rate of TIPE3 mRNA high expression group in five years after operation was lower than that of TIPE3 mRNA low expression group (23.1％,6/26 vs 56.2％,18/32);and the difference was statistically significant (x2 =6.508,P＜0.05).The expression of TIPE3 at protein level of colon cancer tissues (44.6 ％,37/83) was lower than that of tumor-adjacent tissues (68.7 ％,57/83;x2 =8.004,P＜0.05).The expression of TIPE3 at protein level was not correlated with age and gender (both P＞0.05).The positive expression rate of patients at stage Ⅱ was higher than that of patients at stage Ⅲ (60.5％,23/38 vs 29.7％,1/37);and the difference was statistically significant (x2 =7.174,P＜ 0.05).The positive expression rate of TIPE3 in group of patients with lymph node metastasis was lower than that of groups of patients without lymph node metastasis (28.2％,11/39 vs 59.1％,26/44),and the difference was statistically significant (x2=7.983,P =0.005).Conclusions The expression of TIPE3 in colon cancer tissues is lower than that in tumor-adjacent tissues.Furthermore,it is correlated with lymph node metastasis,recurrence rate and survival rate.TIPE3 may be involved in the genesis,development,invasion and metastasis of colon cancer.