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*

Among tumor microenvironment (TME), the entire metabolic characteristics of tumor-resident cells are reprogrammed to benefit the expansion of tumor cells, which count on glutamine in large part to fuel the tricarboxylic acid cycle for energy generation and anabolic metabolism support. Endothelial cells that are abducted by tumor cells to form a pathological tumor vascular network for constructing the hypoxic immunosuppressive TME, also rely on glutaminolysis as the "engine" of angiogenesis. Additionally, the glutamine metabolic preference benefits the polarization of TAMs towards pro-tumoral M2 phenotype as well. Herein, we developed a type of siRNA micelleplexes (MH@siGLS1) to reverse immunosuppressive TME by targeting glutaminolysis within tumor-resident cells for tumor vasculature normalization- and TAMs repolarization-enhanced photo-immunotherapy. Tumor cell starvation and antioxidant system destruction achieved by MH@siGLS1-mediated glutaminolysis inhibition could promote photodynamic therapy efficacy, which was available to trigger immunogenic cell death for adaptive antitumor immune responses. Meanwhile, glutaminolysis inhibition of tumor endothelial cells and TAMs could realize tumor vascular normalization and TAMs repolarization for antitumor immunity amplification. This study provides a unique perspective on cancer treatments by focusing on the interrelations of metabolic characteristics and the biofunctions of various cell types within TME.

Gastrointestinal tumors(GT)are characterized by both high malignancy and high mortality and have become the major diseases for prevention in the elderly.GT often present detectable changes, including bleeding and abnormal mucosal morphology.However, many technical difficulties remain in accurately monitoring the tumor itself and related abnormal lesions mentioned above, which are the key factors affecting the early detection rate of gastrointestinal tumors.In recent years, with progresses in artificial intelligence(AI)applications for digestive endoscopy image analysis, biosensors, new biomarkers and other areas, AI holds promise for the detection of bleeding, morphological and structural abnormalities of the mucosa, tumors and other major disorders.Here we review the progress of AI applications in geriatric digestive diseases affecting digestive organs and the mucosa in light of morphology and function, to provide a reference for reducing the incidence of both geriatric emergencies and GT.

One case of de novo donor specific antibody(dnDSA)mediated rejection after pediatric kidney transplantation(KT)was analyzed retrospectively.The risk factors and prevention procedures associated with dnDSA induction, and the clinical features and protocols for late post-transplant antibody-mediated rejection(AMR)in pediatric patients were presented.

Objective : To investigate the status of occupational stress and analyze its influencing factors among frontline employees working in a chemical fiber manufacturing enterprise, so as to provide insights into the development of occupational stress interventions. Methods : The frontline employees working in a chemical fiber manufacturing enterprise were selected as the study subjects using a cluster sampling method in October 2018. The status of occupational stress was investigated using the Chinese version of the effort-reward imbalance ( ERI ) questionnaire. The influencing factors for occupational stress were identified using a multivariable logistic regression model. Results : A total of 1 780 questionnaires were sent out, and 1 115 valid ones ( 62.64% ) were recovered. Among the 1 115 respondents, there were 427 men ( 38.30% ) and 688 women ( 61.70% ), and 71.22% were at ages of 21 to 39 years. There were 561 respondents with < 1 year of service ( 50.31% ), and the longest length of service was 11 years. In addition, there were 1 069 respondents ( 95.87% ) exposed to high noise, and 346 respondents ( 31.03% ) were diagnosed at a high occupational-stress state and 769 ( 68.97% ) at a low state. Multivariable logistic regression analysis identified 5 years or longer of service ( OR=1.540, 95%CI: 1.057-2.245 ) and exposure to high noise ( OR=1.917, 95%CI: 1.004-3.659 ) as risk factors for occupational stress among frontline employees in the chemical fiber manufacturing enterprise. Conclusions There are 31.03% of frontline employees at a high occupational-stress state in the chemical fiber manufacturing enterprise, and a high occupational-stress state is associated with exposure to high noise and 5 years or longer of service.

Objective:To analyze the clinical efficacy of inter-spinal distraction fusion and fixation and Posterior lumbar interbody fusion in the treatment of lumbar disc herniation with stenosis, and to evaluate the health economics of the two surgical methods.Methods:Retrospectivly analyzed the clinical data of 400 patients with lumbar disc herniation with stenosis, who were enrolled in Beijing Friendship Hospital, Capital Medical University from Jan. 2015 to Jan. 2019, including 190 male cases and 210 female cases, aged from 50 to 87 years old, with the average age of 67.97. All patients were divided into two groups according to different surgical methods. Among them, 200 patients used interspinous process fusion and distraction fixation (ISDFF group), the other 200 cases used posterior lumbar decompression and pedicle internal fixation (PLIF group). All patients completed the follow-up time of more than 1 year after operation. The basic information of patients′ age, gender, total number of days in hospital, intraoperative bleeding, operation time, surgical incision length and other basic information were observed. The Oswestry dysfunction index (ODI), the Japanese Orthopaedic Association Score (JOA) and the visual analog scale (VAS) were used to evaluate the relief of symptoms before and after the two groups of patients. Total medical expenses, anesthesia expenses, surgical expenses and other expenses were analysed. The software of SPSS 20.0 were conducted to analyze data.Results:The patients in the ISDFF group were (70.84±8.93) years old, and the PLIF group was (65.10±10.23) years old ( t=5.98, P=0.008). The operation time in the ISDFF group was (59.21±16.22) min, and the operation time in the PLIF group was (81.31±17.24) min( t=13.20, P<0.001). The bleeding volume of the ISDFF group was (33.24±11.31) mL, and the bleeding volume of the PLIF group was (67.30±17.61) mL ( t=23.02, P<0.001). The length of the surgical incision in the ISDFF group was (8.27±2.53) cm, and the length of the surgical incision in the PLIF group was (11.15±1.91) cm ( t=11.848, P<0.001). The total hospitalization time in the ISDFF group was (15.15±0.54) days, and the total hospitalization time in the PLIF group was (19.86±0.97) days( t=4.26, P<0.001). There was no significant difference in preoperative ODI, JOA and VAS between the two groups ( P>0.05). Symptoms of postoperative patients were significantly improved compared with preoperative. There were statistical differences in ODI, JOA and VAS between the two groups before and after operation ( P<0.05). However, ODI, JOA and VAS were no statistical difference between the two groups after operation. Complications occurred in 5 cases of the two groups of patients, including two cases of superficial infection in the PLIF group, two cases of dural tear in the PLIF group, one case of spinous process fracture in the ISDFF group. The total hospitalization fee for ISDFF was (57 450±8 670) (yuan), and the total hospitalization fee for PLIF was (75 770±1 640) (yuan), with statistical differences ( t=9.92, P<0.001). The cost of ISDFF operation was 1864±38.19 (yuan), and the cost of PLIF operation was 2352±41.39 (yuan) ( t=8.65, P<0.001). ISDFF antibacterial drug usage fee was 635.5±64.69 (yuan), PLIF antibacterial drug usage fee was 1449±307.1 (yuan) ( t=2.59, P<0.001). The one-time medical material cost during the ISDFF operation was (38 990±300) (yuan), and the one-time medical material cost during the PLIF operation was (52 110±150) (yuan) ( t=5.88, P<0.001). The excellent and good rate of ISDFF group was 92%, and that of PLIF group was 86%. In this study, the total cost of hospitalization was used as an indicator to measure the cost, and further cost-effectiveness evaluation was made. For every good patient, the cost of the ISDFF group was 62 450 yuan, and the cost of the PLIF group was 88, 100 yuan. Conclusions:ISDFF is beneficial to reduce the cost of medical insurance in China, which is in line with the direction of national reform to reduce medical expenditure. It is a surgical method worthy of wide promotion and has a good application prospect.

Objective:To analyze the effect of inter-spinal distraction fusion and fixation (ISDFF) combined with limited decompression on the treatment of lumbar spinal stenosis in elderly patients.Methods:A total of 32 elderly patients with lumbar spinal stenosis, aged from 80 to 87 years old (mean age: 82.0±2.0 years) including 10 males and 22 females, in the Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University from January 2016 to January 2020 were enrolled in this retrospective study. Clinical evaluation and imaging measurement were performed before operation, after operation, 6 months and 24 months after operation. SPSS software was used for statistical analysis. Measured data of normal distribution were expressed as means±standard deviation. One way analysis of variance was used for comparison between groups. Paired t-test was used to compare between preoperative and postoperative as well as between preoperative and 24 months′ follow-up. Results:All of the 32 patients had one or more common accompanying diseases, such as hypertension, diabetes, coronary heart disease, and so on. All patients were successfully completed the operation with a total of 32 segments. VAS score was decreased from (6.22±0.91) before operation to (1.94±0.76) at 24 months( t=16.52, P<0.001). ODI score was also demonstrated the similar trend, from (54.17±10.65) preoperatively to (19.91±4.20) at 24 months follow-up( t=15.89, P<0.001). JOA score was significantly increased from (11.69±3.36) before surgery to (23.44±1.66) at the last follow-up ( t=-19.90, P<0.001). In the change of imaging, the intervertebral angle was decreased from preoperation (9.12±4.65) to (6.77±2.70) at 24 months( t=3.53, P=0.001). The posterior disk height was increased from (0.68±0.19) cm to (0.76±0.19) cm at the last follow-up( t=-2.45, P=0.020). Conclusions:As a new type of minimally invasive internal fixator, the ISDFF combined with limited decompression can relieve the pain of elderly patients with lumbar spinal stenosis and improve the quality of life. It is suitable for the treatment of elderly patients with lumbar spinal stenosis.

Objective:To explore the safety and feasibility of optimized pathological evaluation system of donor's kidney and modified surgery during adult dual kidney transplantation(DKT)and evaluate its effectiveness to provide more alternative protocols for kidney transplantation from extended criteria donors.Methods:DKT was performed in 10 recipients using the same protocol from June 2019 to May 2021.And retrospective reviewing was performed for clinical data, including characteristics of donors and recipients, optimized pathological evaluation system, modified surgery, treatment regimens, complications and follow-ups.Results:There were 8 male and 2 female donors with an age of(57.9±12.8)years and BMI(24.1±4.1)kg/m 2.The percentage of DCD was 70% and DBD 30%.The serum creatinine before procurement was 107.6(93.3-163.5)μmol/l.Zero-point puncture biopsy was performed for both kidneys and optimized pathological evaluation system was implemented(Banff criteria & Remuzzi score). The pathological results indicated that glomerular sclerosis for left and right kidneys were 2.0(1.5-2.0)and 1.5(1.0-2.0). And Remuzzi score for left and right kidneys were(4.4±1.2)and(3.6±1.5)points respectively.All recipients were male with an age of(43.1±9.0)years and BMI(22.2±1.9)kg/m 2.All PRAs were negative pre-operation.Modified surgery was performed in all recipients(two kidneys were implanted outside iliac vessels without patch and artery of superior kidney was anastomosed to internal iliac artery). Operative duration was(195±54.3)min and serum creatinine before discharge 125.0(102.0-199.0)μmol/L.Renal dynamic scintigraphy indicated that glomerular filtration rate was(30.0±8.2)ml/min for left kidney and(29.2±13.9)ml/min for right kidney.MRA results indicated that morphologies of renal arteries and veins were regular.The time between operation and discharge was(22.4±4.7)days.Compared with SKT, serum creatinine before discharge of DKT was lower and DGF incidence of DKT was higher without statistical significance.The time between operation and discharge was longer for DKT than that for SKT( P<0.05). The complications consisted of 20% donor derived infection(DDI)and 50% DGF.And there was no surgical complication associated with vessels and ureter.Renal function remained stable during 6-month follow-ups. Conclusions:Optimized pathological evaluation system of donor's kidney and modified surgery during adult dual kidney transplantation are both safe and feasible.The postoperative function of transplanted dual kidney is successfully restored.However, long-term follow-ups are required for evaluating its effectiveness.

Objective:To investigate the predictive value of cerebroplacental ratio (CPR) for adverse perinatal outcomes of induction of labor in prolonged pregnancy.Methods:This retrospective study recruited 315 singleton pregnant women who had induced labor due to prolonged pregnancy (≥41 gestational weeks) in the First Affiliated Hospital of Chongqing Medical University from January 1, 2019 to April 30, 2020. Based on the occurrence of adverse perinatal outcomes (emergency delivery due to persistent abnormal fetal heart rate monitoring, umbilical artery blood pH at birth <7.2, 5 min Apgar scores<7, transferring to neonatal intensive care unit after birth, chorioamnionitis and vaginal delivery converted to cesarean section), they were divided into two groups: case group ( n=76) and normal group ( n=239). Clinical features and umbilical artery blood flow, middle cerebral artery (MCA) flow and CPR measured in the last ultrasound scan before induction were compared between the two groups using student's t-test, Mann-Whitney U test and Chi-square test. Receiver operating characteristic (ROC) curve was used to analyze the predictive values of umbilical artery blood flow, MCA flow and CPR for the adverse perinatal outcomes. Multivariate logistic regression analysis was used to screen the meaningful predictors. Results:Compared with the normal group, the umbilical artery pulsatility index (PI) (0.9±0.1 vs 0.8±0.1, t=-5.458, P<0.001) and the percentage of abnormal CPR (<1.0) increased significantly [21.1%(16/76) vs 6.3%(15/239), χ2=14.190, P<0.001] in the case group, while the MCA-PI and CPR decreased significantly (1.1±0.2 vs 1.3±0.3, t=5.658, P<0.001; 1.2±0.3 vs 1.6±0.5, t=8.940, P<0.001). The areas under the ROC curves of umbilical artery PI, MCA-PI and CPR for predicting adverse perinatal outcomes were 0.71, 0.71 and 0.77, respectively. CPR had the highest sensitivity (0.74) compared with umbilical artery PI (0.68) and MCA-PI (0.71), but the specificity of them were similar (0.67, 0.66 and 0.66). Multivariate logistic regression analysis showed that only CPR was the independent risk factor for adverse perinatal outcomes ( OR=0.028, 95% CI: 0.010-0.080, P<0.001). Conclusions:As an indicator for early prediction of adverse perinatal outcomes of induction of labor in prolonged pregnancy, CPR was more sensitive but less specific.

Objective: To analyze the influencing factors for hospitalization of pneumoconiosis patients, so as to provide reference for improving the timeliness of treatment and quality of life in these patients. Methods: The pneumoconiosis patients in Changshan, Wenling and Changxing ( having mining industry ) of Zhejiang Province were selected by stratified and typical sampling methods. Their demographic features, prevalence of pneumoconiosis and hospitalization status were collected by a questionnaire survey. Logistic regression analysis was conducted to analyze the influencing factors for hospitalization. Results: Among 166 pneumoconiosis patients, 122 ( 73.49% ) chose to be hospitalized. The multivariate logistic regression analysis revealed that the patients who scored higher in ED-5Q ( OR=65.821, 95%CI: 3.831-1130.781 )and who would communicate with other pneumoconiosis patients ( OR=3.744, 95%CI: 1.261-11.115 ) were more likely to be hospitalized; the patients who were under the medical insurance for urban employees were more likely to be hospitalized than those who were under the new rural cooperative medical care system ( OR=0.033, 95%CI: 0.007-0.154 ) and others ( OR=0.038, 95%CI: 0.002-0.960 ) . Conclusion The quality of life, communication with other pneumoconiosis patients and type of medical insurance were the influencing factors for hospitalization of pneumoconiosis patients.