Objective To investigate the effects of ischemia time and storage periods on RNA quality in fresh-frozen breast cancer(BC)and esophageal cancer(EC)tissue samples in order to establish evidence-based protocols for biobank sample management.Methods The tumor(T)and paired normal(N)tissue samples from 6 cases of BC and 6 cases of EC were collected and cryopreserved in Biobank,Shantou Central Hospital.Mirror paraffin-embedded tissues were simultaneously prepared into sections for morphological analysis.The samples were divided into two groups of<15 min and 15-30 min according to ischemia time,and RNA quality was analyzed at 4 storage periods of 8-10 months(T1),14-16 months(T2),26-28 months(T3)and 38-40 months(T4).Results In 96 analyzed samples,93.8%(90/96)exhibited high quality(RIN≥6),with 89.6%(43/48)in BC and 97.9%(47/48)in EC.Significant differences in RIN were observed between BC group and EC group(8.050 vs.8.600,P=0.009).In EC group,RIN value was significantly negatively correlated with RNA yield(P<0.001).Moreover,RIN values of tumor-normal pairs exhibited markedly significant differences(7.550 vs.9.000,P<0.001).In contrast,no significant difference was detected in BC group(8.200 vs.7.700,P=0.348).Statistical analysis showed that RIN value was positively correlated with 28S/18S(P<0.001),but had no correlation with tumor content(P=0.676)and necrotic content(P=0.055).Neither ischemia time(<15 min vs.15-30 min:8.200 vs.8.300,P=0.932)nor storage periods(T1-T4:8.400,7.700,8.450,8.600,P=0.163)compromised RNA quality.Conclusion Organ origin and tissue type could influence RNA quality of fresh-frozen tissue samples.However,limited ischemia time(≤30 min)and long-term storage period(38-40 months)do not adversely affect RNA quality in fresh-frozen breast cancer and esophageal cancer tissue samples.

Objective:To systematically evaluate the molecular characteristics and prognostic value of ammonia death-related genes in hepatocellular carcinoma(HCC).Methods:Consensus unsupervised clustering was used to identify ammonia death-related molecular subtypes in HCC samples.Weighted gene co-expression network analysis(WGCNA)was applied to identify gene modules associated with ammonia death.Support vector machine(SVM)and LASSO algorithms were used to screen four hub genes,and a risk score system was constructed based on a LASSO-Cox regression model.The association between the risk model and patient survival,tumor microenvironment,and re-sponse to immunotherapy was further analyzed.Results:Consensus clustering identified two distinct ammonia death-related molecular subtypes(P<0.05).The constructed risk score model showed good predictive performance for overall survival in HCC patients and was closely associated with immune infiltration characteristics of the tumor microenviron-ment and immunotherapy responsiveness(P<0.05).Conclusion:The ammonia death-related risk score model may serve as a novel prognostic biomarker for HCC and provide potential guidance for immunotherapy strategies.

Objective:To systematically evaluate the molecular characteristics and prognostic value of ammonia death-related genes in hepatocellular carcinoma(HCC).Methods:Consensus unsupervised clustering was used to identify ammonia death-related molecular subtypes in HCC samples.Weighted gene co-expression network analysis(WGCNA)was applied to identify gene modules associated with ammonia death.Support vector machine(SVM)and LASSO algorithms were used to screen four hub genes,and a risk score system was constructed based on a LASSO-Cox regression model.The association between the risk model and patient survival,tumor microenvironment,and re-sponse to immunotherapy was further analyzed.Results:Consensus clustering identified two distinct ammonia death-related molecular subtypes(P<0.05).The constructed risk score model showed good predictive performance for overall survival in HCC patients and was closely associated with immune infiltration characteristics of the tumor microenviron-ment and immunotherapy responsiveness(P<0.05).Conclusion:The ammonia death-related risk score model may serve as a novel prognostic biomarker for HCC and provide potential guidance for immunotherapy strategies.

Objective To investigate the effects of ischemia time and storage periods on RNA quality in fresh-frozen breast cancer(BC)and esophageal cancer(EC)tissue samples in order to establish evidence-based protocols for biobank sample management.Methods The tumor(T)and paired normal(N)tissue samples from 6 cases of BC and 6 cases of EC were collected and cryopreserved in Biobank,Shantou Central Hospital.Mirror paraffin-embedded tissues were simultaneously prepared into sections for morphological analysis.The samples were divided into two groups of<15 min and 15-30 min according to ischemia time,and RNA quality was analyzed at 4 storage periods of 8-10 months(T1),14-16 months(T2),26-28 months(T3)and 38-40 months(T4).Results In 96 analyzed samples,93.8%(90/96)exhibited high quality(RIN≥6),with 89.6%(43/48)in BC and 97.9%(47/48)in EC.Significant differences in RIN were observed between BC group and EC group(8.050 vs.8.600,P=0.009).In EC group,RIN value was significantly negatively correlated with RNA yield(P<0.001).Moreover,RIN values of tumor-normal pairs exhibited markedly significant differences(7.550 vs.9.000,P<0.001).In contrast,no significant difference was detected in BC group(8.200 vs.7.700,P=0.348).Statistical analysis showed that RIN value was positively correlated with 28S/18S(P<0.001),but had no correlation with tumor content(P=0.676)and necrotic content(P=0.055).Neither ischemia time(<15 min vs.15-30 min:8.200 vs.8.300,P=0.932)nor storage periods(T1-T4:8.400,7.700,8.450,8.600,P=0.163)compromised RNA quality.Conclusion Organ origin and tissue type could influence RNA quality of fresh-frozen tissue samples.However,limited ischemia time(≤30 min)and long-term storage period(38-40 months)do not adversely affect RNA quality in fresh-frozen breast cancer and esophageal cancer tissue samples.

As a major global public health problem, pulmonary diseases threaten human life and health while causing a huge economic burden. The messenger RNA (mRNA)-based inhalation preparation, which effectively targets pulmonary cells can overcome the problems of traditional therapy, such as high side effects, low pulmonary bioavailability, and difficulty in synthesizing target proteins in vitro, thus providing new ideas for the treatment of pulmonary diseases. However, as the lung structure is complex and mRNA has trouble entering cells, researchers have been attempting to develop a suitable nano delivery system for higher delivery efficiency. This review introduces the barriers to pulmonary delivery, discusses the recent research development of the mRNA pulmonary delivery systems, including lipid nanoparticles, polymeric nanoparticles, polypeptides and exosomes, summarizes their limitations and looks forward to the application of mRNA inhalation preparations.

Aim To explore the effects of putative receptor protein related to ATI (APJ) homodimer on the behaviors-the proliferation, migration and tube formation of human umbilical vein endothelial cells (HU-VECs). Methods HUVECs at logarithmic growth stage were randomly divided into PBS, Apelin-13 + TM1 (APJ monomer group) and Apelin-13 + PBS group (APJ homodimer group). Western blot and Matrix-Assisted Laser Desorption/Ionization Time of Fligh Mass Spectrometry (MALDI-TOF MS) were used to detect the expression of APJ and APJ homodimer in HUVECs, respectively. Real-Time Cell Analyzers (RT-CA) was used to detect the concentration of the maximum effect of Apelin-13. Cell viability was detected by CCK-8. The cell migration ability was detected by scratch test, and the number of tubes formed on matri-gel that made artificial basement membrane was counted. Results Western blot and MALDI-TOF MS showed that APJ and APJ homodimer were expressed in HUVECs. The EC50 of Apelin-13 was 2.26 x 10

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.
Humans ; Middle Aged ; Aged ; Multiple Myeloma/drug therapy* ; Bendamustine Hydrochloride/therapeutic use* ; Prospective Studies ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Humans ; Child ; Glioma/pathology* ; Brain Neoplasms/pathology* ; Central Nervous System/pathology* ; World Health Organization ; Central Nervous System Neoplasms/pathology* ; Mutation

Objective: To examine the clinical characteristics and prognostic factors of elderly patients with mantle cell lymphoma (MCL) and the impact of nutrition and underlying diseases on the prognosis of elderly patients with MCL. Methods: retrospectively analyzed 255 elderly patients with MCL from 11 medical centers, including Peking University Third Hospital between January 2000 and February 2021. We analyzed clinical data, such as age, gender, Mantle Cell Lymphoma International Prognostic Index score, and treatment options, and performed univariate and multivariate prognostic analysis. We performed a comprehensive geriatric assessment on elderly MCL patients with medical records that included retraceable underlying disease and albumin levels, and we investigated the impact of basic nutrition and underlying disorders on MCL prognosis in the elderly. Results: There were 255 senior individuals among the 795 MCL patients. Elderly MCL was more common in males (78.4%), with a median age of 69 yr (ages 65-88), and the majority (88.6%) were identified at a late stage. The 3-yr overall survival (OS) rate was 42.0%, with a 21.2% progression-free survival (PFS) rate. The overall response rate (ORR) was 77.3%, with a 33.3% total remission rate. Elderly patients were more likely than younger patients to have persistent underlying illnesses, such as hypertension. Multivariate analysis revealed that variables related with poor PFS included age of ≥80 (P=0.021), Ann Arbor stage Ⅲ-Ⅳ (P=0.003), high LDH level (P=0.003), involvement of bone marrow (P=0.014). Age of ≥80 (P=0.001) and a high LDH level (P=0.003) were risk factors for OS. The complete geriatric assessment revealed that renal deficiency was associated with poorer OS (P=0.047) . Conclusions: Elderly MCL patients had greater comorbidities. Age, LDH, renal function, bone marrow involvement, and Ann Arbor stage are all independent risk factors for MCL in the elderly.
Male ; Adult ; Humans ; Aged ; Lymphoma, Mantle-Cell/drug therapy* ; Prognosis ; Retrospective Studies ; Bone Marrow/pathology* ; Risk Factors

OBJECTIVES: To study the clinical and bronchoscopic characteristics of tracheobronchial tuberculosis (TBTB) in children and to identify factors influencing residual airway obstruction or stenosis. METHODS: The clinical data of children with TBTB were retrospectively collected. The children were divided into two groups based on the last bronchoscopic result within one year of follow-up: a group with residual airway obstruction or stenosis (n=34) and a group without residual airway obstruction or stenosis (n=58). A multivariate logistic regression analysis was used to identify the factors influencing residual airway obstruction or stenosis in children with TBTB. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of the factors influencing residual airway obstruction or stenosis in children with TBTB. RESULTS: A total of 92 children with TBTB were included, and the main symptoms were cough (90%) and fever (68%). In children under 1 year old, the incidence rates of dyspnea and wheezing were significantly higher than in other age groups (P<0.008). Chest CT findings included mediastinal or hilar lymph node enlargement (90%) and tracheobronchial stenosis or obstruction (61%). The lymphatic fistula type was the main type of TBTB observed bronchoscopically (77%). All children received interventional treatment, and the effective rate was 84%. During one year of follow-up, 34 children had residual airway obstruction or stenosis. The TBTB diagnostic time and the initiation of interventional treatment were significantly delayed in the group with residual airway obstruction or stenosis compared with the group without residual airway obstruction or stenosis (P<0.05). The multivariate logistic regression analysis showed that the TBTB diagnostic time was closely related to residual airway obstruction or stenosis in children (P<0.05). ROC curve analysis showed that at the cut-off value of 92 days of TBTB diagnostic time, the area under the curve for predicting residual airway obstruction or stenosis in children with TBTB was 0.707, with a sensitivity of 58.8% and a specificity of 75.9%. CONCLUSIONS The clinical manifestations of TBTB are nonspecific, and symptoms are more severe in children under 1 year old. TBTB should be suspected in children with tuberculosis and chest imaging indicating airway involvement. Delayed diagnosis of TBTB is associated with the development of residual airway obstruction or stenosis.
Infant ; Child ; Humans ; Bronchoscopy/methods* ; Constriction, Pathologic/complications* ; Bronchial Diseases/therapy* ; Retrospective Studies ; Tuberculosis/diagnosis* ; Airway Obstruction/therapy*