Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

BACKGROUND: Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China. METHODS: We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model. RESULTS: From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%). CONCLUSIONS CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Humans ; Heart Defects, Congenital/mortality* ; Male ; Female ; China/epidemiology* ; Infant ; Child, Preschool ; Adult ; Child ; Adolescent ; Infant, Newborn ; Middle Aged ; Young Adult ; Aged ; Rural Population

OBJECTIVE: To investigate the midterm clinical efficacy of medial patellofemoral complex (MPFC) reconstruction for recurrent patellar dislocation with high-grade trochlear dysplasia. METHODS: A retrospective analysis was carried out among adult patients who underwent arthroscopically assisted MPFC reconstruction between January 2014 and December 2020. Dejour classification was evaluated to grade trochlear dysplasia; tibial tubercle-trochlear groove (TT-TG) distance and Insall-Salvati index were measured. Preoperative and postoperative patient-reported outcome measures (PROMs) were compared, including International Knee Documentation Committee (IKDC) score, Kujala score, Lysholm score and Tegner score. Information regarding returning-to-sport rate, re-instability events and complications was collected. Patellar tilt (PT), lateral patellar displacement (LPD) and bisect offset (BSO) ratio were measured based on axial computed tomography before and after surgery to assess the patellofemoral congruence. RESULTS: A total of 46 MPFC reconstructions in 43 patients were enrolled, including 16 male and 27 female. Mean age at surgery was (22.2±7.6) years (range: 14-44 years). Mean follow-up was (49.9±22.6) months (range: 18-102 months). The percentages of Dejour B, C and D dysplasia were 37.0% (17/46), 43.5% (20/46), and 19.6% (9/46), respectively. Mean Insall-Salvati index was 1.2±0.2 (range: 0.85-1.44), and mean TT-TG distance was (19.6±3.5) mm (range: 10.6-28.7 mm). At latest follow-up, there were significant improvements in all PROMs (P < 0.001): IKDC score, from 56.3±15.1 to 86.2±8.1; Kujala score, from 58.9±15.6 to 92.6±5.4; Lysholm score, from 63.7±15.0 to 94.0±5.7; Tegner score, from 3.1±1.4 to 4.7±1.4, and there were no significant differences in the improvements of the scores between the patients with Dejour B, C and D dysplasia. Overall, ninety percent of the patients returned to their preoperative sports level. One patient reported a postoperative subluxation, while no cases of infection, limited range of motion or patella fracture were observed. PT, LPD and BSO ratio were all significant altered (P < 0.001) after MPFC reconstruction. CONCLUSION Arthroscopically assisted MPFC reconstruction yielded satisfactory midterm clinical results for recurrent patellar dislocation with high-grade trochlear dysplasia. No significant differences of improvements in knee function were observed among the three types of high-grade trochlear dysplasia.
Humans ; Patellar Dislocation/surgery* ; Male ; Female ; Adult ; Arthroscopy/methods* ; Retrospective Studies ; Adolescent ; Young Adult ; Patellofemoral Joint/surgery* ; Recurrence ; Plastic Surgery Procedures/methods* ; Patella/surgery* ; Treatment Outcome

Objective:Proteins are closely associated with the development, progression, and immunotherapy of head and neck squamous cell carcinoma（HNSCC）. However, few clinical models utilize proteomics to predict prognosis and immunotherapy efficacy. In this study, we developed a protein prognostic model（PPM） to stratify survival outcomes and differential immunotherapy responses in HNSCC patients. Methods:Based on proteomic profiling, we constructed a PPM comprising 11 protein markers. Patients were classified into high-and low-risk groups according to PPM scores. The prognostic value of risk scores was evaluated using Cox regression analysis, and predictive accuracy was assessed via time-dependent receiver operating characteristic（ROC） curves. Additionally, we analyzed treatment responses to PD1/CTLA4 immunotherapy in PD1-or CTLA4-positive patients across risk groups. Results:Cox regression confirmed the risk score as an independent prognostic factor（HR=1.161, 95%CI 1.112-1.213, P<0.001）, with high-risk patients exhibiting significantly poorer survival than low-risk counterparts. The model demonstrated robust predictive accuracy, with 1-year and 3-year time-dependent ROC areas under the curve（AUC） of 0.713 and 0.707, respectively. In PD1/CTLA4-positive subgroups, low-risk patients showed superior immunotherapy responses compared to high-risk patients. Conclusion:The PPM can provide reliable prognostic stratification and preliminary guidance for immunotherapy in HNSCC. However, further clinical studies and basic experiments are needed for further verification.
Humans ; Immunotherapy ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Prognosis ; Head and Neck Neoplasms/genetics* ; Proteome ; Proteomics ; Gene Expression Profiling ; Transcriptome ; CTLA-4 Antigen ; Programmed Cell Death 1 Receptor ; Male ; Female ; Middle Aged

Objective To evaluate the clinical value of non-invasive ultrasound hemodynamic monito-ring in critically ill neonates in plateau area(altitude＞2 500 m).Methods A total of 205 critically ill neo-nates admitted to the NICU of Qamdo People's Hospital from September 2023 to December 2024 were ran-domly divided into the control group(n=105)and the observation group(n=100)using a random number table.There was no statistically significant difference in the baseline data between the two groups(P＞0.05).The observation group underwent noninvasive ultrasonic hemodynamic monitoring within 12 hours of admis-sion,measuring corrected flow time(FTC),stroke volume(SV),cardiac index,systemic vascular resistance index(SVRI),and myocardial contractility index(SMII).The control group received conventional monito-ring.The treatment was adjusted based on the results.The above parameters were remeasured 4-8 hours af-ter treatment adjustment.Hospital stay and 28 d survival rate were compared between the two groups.Multi-ple linear regression and binary logistic regression were used to analyze the factors influencing hospital stay and 28 d survival rate,respectively.Results Compared to pre-treatment levels,the observation group showed significant post-treatment decreases in FTC[(364.03±47.70)ms vs.(414.09±52.20)ms]and SVRI[(1 521.00±186.93)dyn·s·(cm5)-1·(m2)-1 vs.(1 720.00±347.31)dyn·s·(cm5)-1·(m2)-1].Con-versely,significant increases were observed in SV[(5.23±0.66)mL vs.(5.09±0.88)mL],cardiac index[(3.35±1.17)L·min-1·(m2)-1 vs.(3.19±0.99)L·min-1·(m2)-1],and SMII[(0.56±0.10)W/m2 vs.(0.51±0.14)W/m2](P＜0.05).The observation group had a significantly shorter hospital stay than the control group[(11.53±3.61)d vs.(13.83±2.56)d,P＜0.05].The 28 d survival rate was higher in the ob-servation group(100.0％vs.98.1％),although the difference was not statistically significant(P＞0.05).Multiple linear regression analysis revealed that both gestational age and cardiac index were negatively correla-ted with the duration of hospital stay.Binary logistic regression analysis indicated that birth weight was a sig-nificant factor influencing the 28 d survival rate(OR=4.600,95％CI:2.465-10.654,P=0.001).Conclusion Non-invasive ultrasonic hemodynamic monitoring can facilitate early identification of hemodynamic alterations in critically ill neonates in platean area,which could guide treatment and potentially reducing hospital stay.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.