Background and aims Hepatocellular carcinoma (HCC) cells are metabolically reprogrammed for excessive uptake and metabolism of many nutrients. The tumor suppressive microRNA-148a-3p (miR-148a-3p) is downregulated in HCC, whereas its function in regulating HCC cell metabolism remains obscure. Herein we aimed to delineate the role of miR-148a-3p in HCC cell metabolism by using novel bioengineered miR-148a-3p (BioRNALeu/miR-148a-3p) agent produced in vivo. Methods BioRNALeu/miR-148a-3p was designed by using human leucyl transfer RNA fused hsa-pre-miR-34a carrier, overexpressed in Escherichia coli (E. coli), and purified to high homogeneity. After transfection into HCC cells, the released miR-148a-3p levels were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was determined by CellTiter-Glo assays. Targets were validated by dual-luciferase reporter assays, immunoblotting, and immunofluorescence confocal imaging. Glycolysis capacity was evaluated by Seahorse XF assays, and glucose, lactate, and amino acid levels were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Results BioRNALeu/miR-148a-3p was efficiently processed into target miR-148a-3p in HCC cells to effectively inhibit cell proliferation in a dose- and time-dependent manner. Mechanistically, miR-148a-3p suppressed the protein levels of glucose transporter GLUT1/SLC2A1 and L-type amino acid transporter LAT1/SLC7A5 via acting on their 3′-untranslated regions, as well as amino acid transporter ASCT2/SLC1A5. These, in turn, led to a reduction of glucose uptake, lactate production, and glycolytic flux in HCC cells, and alteration of intracellular amino acid metabolome including glutamine, leucine, phenylalanine, tyrosine, and methionine. Conclusions Reintroduction of miR-148a-3p into HCC cells modulates glucose and amino acid metabolism via regulating multiple SLC transporters, thereby suppressing HCC cell viability. These findings highlight the role of miR-148a-3p in HCC cell metabolism and potential of bioengineered miRNA molecules for functional studies and therapeutic development.

Objective To analyze the prevalence status of cardiometabolic risk factor (CMRF) and its aggregation among workers engaged in new forms of employment. Methods A total of 5 429 new employment workers (including couriers, online food delivery workers, and ride hailing drivers) who underwent health medical examinations at a tertiary hospital in Beijing City were selected as the research subjects using the judgment sampling method. Data on waist circumference, blood pressure, blood glucose, and blood lipid levels were collected to analyze their CMRF [central obesity, elevated blood pressure, elevated blood glucose, elevated triglycerides, and reduced high-density lipoprotein cholesterol (HDL-C)] and their aggregation (with ≥ 2 of the above 5 risk factors) status. Results The detection rates of central obesity, elevated blood pressure, elevated blood glucose, elevated triglycerides, and reduced HDL-C were 61.2%, 38.2%, 29.5%, 40.9% and 22.6%, respectively. The detection rates of CMRF aggregation was 57.8%. The result of multivariable logistic regression analysis showed that male, age ≥45 years, smoking, overweight, and obesity were risk factors for CMRF aggregation (all P<0.05). Conclusion The detection rate of CMRF and its aggregation among workers with new forms of employment in Beijing City is relatively high. Targeted prevention and control efforts should be strengthened for high-risk populations, especially males, workers aged ≥45 years, smokers, and those who are overweight or obese.

Objective To analyze the spatiotemporal evolution patterns of mortality and disease burden of smoking-related prostate cancer(PCa)from 1990 to 2021 and to predict the future trends,so as to provide evidence-based insights for optimizing regional PCa prevention policies and smoking cessation interventions.Methods Based on data from the Global Burden of Disease Study(GBD)2021,annual mortality,disability-adjusted life years(DALYs),years of life lost(YLLs),years lived with disability(YLDs),and age-standardized rates(ASRs)for PCa across 204 countries and 21 regions from 1990 to 2021 were obtained.Estimated annual percentage change(EAPC)was used to assess the disease burden and mortality of smoking-related PCa across global,regional,socio-demographic index(SDI),and age groups.An autoregressive integrated moving average(ARIMA)model was employed to predict trends in these indicators up to 2050.Results In 2021,smoking-related PCa caused 12 992 global deaths,a 30.74％increase compared to 1990.However,from 1990 to 2021,the global age-standardized mortality rate(ASMR),age-standardized DALYs rate(ASDR),age-standardized YLDs rate(ASYR),and age-standardized YLLs rate(ASLR)for smoking-related PCa declined,with EAPCs being-1.43(95％CI:-1.77--1.12),-1.39(95％CI:-1.66--1.12),-0.41(95％CI:-0.67--0.15)and-1.51(95％CI:-1.78--1.23).In 2021,the region with the highest number of deaths from PCa was Asia(4663 deaths),followed by Europe(4647 deaths),and Oceania had the lowest number of deaths(9 deaths).From 1990 to 2021,the mortality rate of PCa in most regions generally showed a downward trend.High SDI regions showed the most significant declines in ASMR,ASDR,and ASLR[EAPCs:-3.17(95％CI:-3.31--3.02),-2.91(95％CI:-3.02--2.83),and-3.22(95％CI:-3.35--3.09)].For ASYR,only high-SDI regions exhibited a decline,whereas low-middle-SDI regions saw the largest increase[EAPC:1.26(95％CI:1.19-1.33)].In 2021,the number of PCa deaths was more concentrated in the age groups of 70-74 and 75-79,with 2312 and 2278 deaths,respectively.From 1990 to 2021,ASMR,ASDR,and ASLR showed an overall downward trend,EAPC were-2.84(95％CI:-3.21--1.83),-2.77(95％CI:-3.13--1.75),and-2.84(95％CI:-3.14--1.71),with the most significant decline observed in individuals aged 35-39.Projections to 2050 indicated continuing declines in all burden metrics,which would stabilize in later years.Conclusion Despite a global decline in smoking-related PCa burden over the past three decades,significant regional disparities persist,with low-and middle-income countries facing ongoing challenges.Implementing stricter tobacco control policies is critical to mitigating smoking-related health risks.

Central venous pressure(CVP)is a commonly used hemodynamic index in clinical practice,and the accuracy of its measurement results is influenced by the measurement technical specifications.Based on research evidence and clinical practice,this article interprets the main content of the group standard of CVP measurement technology,and proposes suggestions for its use.It aims to guide clinical nursing staff to correctly understand the principles and methods of CVP measurement,and promote the standardization of nursing practice and the accuracy of measurement results.

OBJECTIVE: To explore the application effect of self-developed anatomical main nail insertion guide in proximal femoral nail antirotation (PFNA) internal fixation for the treatment of intertrochanteric fractures (IFF) in elderly patients. METHODS: A retrospective analysis was performed on 62 patients with AO31-A2 intertrochanteric fractures who underwent PFNA surgery and met the inclusion criteria from January 2022 to December 2024. They were divided into the conventional PFNA insertion group (conventional operation group) and the anatomical main nail insertion guide-assisted PFNA insertion group(guide group). The conventional operation group (PFNA) included 31 patients, 14 males and 17 females, the age ranged from 64 to 90 with an average of (75.2±11.6) years old;the guide group (PFNA) included 31 patients, 10 males and 21 females, the age ranged fron 67 to 97 with an average of (78.6±13.4) years old. The incision length of the main nail entry, the number of fluoroscopies from satisfactory reduction to before main nail insertion, operation time, intraoperative blood loss, 3-day postoperative VAS score, postoperative hip function Harris score, complications, etc. were observed and compared between the two groups. RESULTS: All patients were followed up for a period ranging from 4 to 12 months, with an average follow-up duration of (6.8±1.6) months. Compared with the guide group, the conventional operation group showed significant differences in the following parameters:the entrance length of the main screw was (6.74±3.77) cm vs. (5.13±1.31) cm, the number of fluoroscopies before the insertion of the main screw was (10.32±3.08) times vs. (7.71±2.41) times, the operation time was (150.45±53.47) minutes vs. (127.48±30.37) minutes, and the intraoperative blood loss was (196.77±121.06) ml vs. (140.97±86.00) ml, with P<0.05 indicating statistical significance.There was no statistically significant difference in 3-day postoperative VAS between the two groups (P>0.05). There was a statistically significant difference in the Harris scores between the conventional operation group and the guided operation group one month post-surgery (60.61±6.60) vs. (65.48±5.19) points (P<0.05). and there was no statistically significant difference in hip Harris scores between the two groups at 3 months after operation (P>0.05). During the 3-month follow-up after operation, neither group had incision infection, screw loosening, cutting, pressure sores, deep vein thrombosis, etc., and there was no statistically significant difference in the complication rate between the two groups. CONCLUSION It is quickly and accurately to implant PFNA assisted by the anatomical major nail implant guide in treatment of osteoporotic intertrochanteric fracture in the elderly.Compared with the traditional operation, it can shorten the operation time and reduce the surgical and X-ray trauma, and beneficial to the rapid rehabilitation of patients.
Humans ; Male ; Female ; Aged ; Hip Fractures/surgery* ; Bone Nails ; Retrospective Studies ; Aged, 80 and over ; Middle Aged ; Fracture Fixation, Intramedullary/instrumentation* ; Fracture Fixation, Internal/instrumentation*

PURPOSE: Although there are significant differences between China and the United States (US) in trauma medical services, there has been no direct comparative research on the epidemiological data of trauma centers between the 2 countries. This study aims to fill this research gap by directly comparing trauma centers in China and the US, providing valuable data and insights for the development of trauma centers in both countries, promoting academic exchange and cooperation internationally, and enhancing the level of global trauma medical care. METHODS: This is a multicenter retrospective descriptive study. Data were collected for trauma patients with an injury severity score ≥16 treated from September 2013 to September 2019 at 2 hospital trauma centers in these 2 countries. Detailed clinical data (including injury mechanism, age, injury site, injury severity score, pre-hospital transport time, whether blood transfusion was performed, whether resuscitative thoracotomy was conducted, hospital and intensive care unit stay duration, the number of organ donor patients, mortality rates, and costs) were meticulously compiled and retrospectively analyzed to identify differences between the 2 trauma centers. The comparison was conducted using SPSS 23 software. Continuous variables are reported as median (Q₁, Q₃), and Mann Whitney U test is used to compare the median of continuous variables. Use clinically relevant critical points to classify continuous variables, with categorical variables represented as n (%), and comparisons were made between the 2 groups using the χ² test or Fisher's exact test. Statistical significance was defined as a 2-sided p < 0.05. RESULTS: These results point to significant differences in trauma center capacity, pre-hospital transport times, treatment procedures, hospital stay duration, mortality rates, and costs between the 2 centers. The volume of patients in trauma centers is less in China (2465 vs. 5288). Pre-hospital transport time was notably longer in China (180 min vs. 14 min), and the rate of emergency blood transfusions was lower in China (18.4% vs. 50.6%), Emergency thoracotomy was not performed in China but was conducted in 9.8% of cases in the US. Hospitalization costs were significantly lower in China than in the US ($5847 vs. $75,671). CONCLUSION There are clear differences in trauma center capacity (number of patients treated), pre-hospital transport time, age distribution of injured patients, injury mechanisms, injury sites, whether emergency thoracotomy is performed, hospital costs, and length of stay between the 2 trauma centers in China and America. Understanding these differences can help us further recognize the characteristics of Eastern and Western trauma patients.
Humans ; China/epidemiology* ; Trauma Centers/statistics & numerical data* ; Retrospective Studies ; United States/epidemiology* ; Male ; Female ; Wounds and Injuries/therapy* ; Middle Aged ; Adult ; Injury Severity Score ; Length of Stay/statistics & numerical data* ; Treatment Outcome

Objective:To compare the differences in clinical characteristics among the patients at clinical high risk for bipolar disorder(CHR-BD),the patients with bipolar disorder(BD),and the healthy controls(HC)at low risk,and to provide the basis for the diognasis and treatment of CHR-BD.Methods:For the first time,the BD risk criteria and prospective structured assessment tools were jointly used in outpatients aged 16-30 years,and 43 CHR-BD patients were included to ensure the accuracy of the assessment.Meanwhile,33 BD patients and 32 HC subjects were also enrolled.The clinical symptoms,neurocognitive function,and global functional levels of the subjects in the three groups were evaluated using observer-rated and self-rated tools.The CHR-BD and BD groups were combined,and Logistic regression analysis was used to identify the independent influencing factors related to diagnostic status;Pearson or Spearman correlation analysis was used to analyze the correlations between the global functional levels and the symptoms or neurocognitive characteristics of the patients in CHR-BD and BD groups.Results:There were statistically significant differences in the scores of symptom and global functional level scales among HC,CHR-BD,and BD groups(P<0.05).Compared with HC group,the scores of mood symptoms(anxiety,depression,and mania/hypomania),psychotic symptoms,total affective temperament questionnaire scores,and some dimensions(cyclothymic,depressive,irritable,and anxious temperaments)in CHR-BD and BD groups were significantly increased(P<0.001),while the global functional levels were significantly decreased(P<0.001).Compared with BD group,the lowest global functional level score in the past year in CHR-BD group was significantly increased(P=0.022),while the current global functional level score was significantly decreased(P=0.005).No significant differences were observed in neurocognitive function scores among the three groups(P>0.05).The lowest global functional level score in the past year was an independent influencing factor for BD diagnosis[odds ratio(OR)=0.952,95%confidence interval(CI):0.917-0.988,P=0.010].In both CHR-BD and BD patients,the current global functional levels were negatively correlated with depressive(r=-0.417,P=0.005;r=-0.617,P<0.001)and anxiety symptoms(r=-0.360,P=0.018;r=-0.506,P=0.003).In BD patients,the current global functional level was negatively correlated with lifetime manic/hypomanic symptoms(r=-0.360,P=0.039),psychotic symptoms(r=-0.502,P=0.003),and affective temperament scores(r=-0.479,P=0.005),while the lowest global functional level in the past year was negatively correlated with lifetime manic/hypomanic symptoms(r=-0.391,P=0.024).Conclusion:CHR-BD patients share similar mood symptom characteristics with BD patients,and their global functional levels are negatively correlated with depressive and anxiety symptoms.BD patients exhibit worse lowest global functional levels in the past year,and their global functional levels are negatively correlated with manic/hypomanic symptoms.

Objective:To discuss the effects of kallikrein 5(KLK5)overexpression on the proliferation,invasion and cisplatin(DDP)sensitivity of cervical cancer cells,and to clarify its mechanism.Methods:Western blotting method was used to verify the stable transfection and overexpression of KLK5 in the cervical cancer cell(ME180-OE-KLK5).The cervical cancer ME180-NC-KLK5 and ME180-OE-KLK5 cells in logarithmic growth phase were subcutaneously inoculated into the nude mice to establish the subcutaneous xenograft models.After successful modeling,the mice were randomly divided into normal saline control group(NC-KLK5+0.9％NaCl group),DDP treatment group(NC-KLK5+DDP group),KLK5 overexpression group(OE-KLK5+0.9％NaCl group)and KLK5 overexpression combined with DDP group(OE-KLK5+DDP group),with 5 mice in each group.The nude mice in NC-KLK5+DDP group and OE-KLK5+DDP group were given intraperitoneal injection of DDP at a dose of 5 mng·kg-1;the nude mice in NC-KLK5+0.9％NaCl group and OE-KLK5+0.9％NaCl group were given intraperitoneal injection of normal saline at a dose of 0.01 mL·g-1.The body weights of nude mice were measured every 2 d,and the long diameter and short diameter of the tumors were recorded to calculate the tumor volume and plot the tumor growth curve.At 24 h after the last administration on day 14,the nude mice were sacrificed,and the tumors were dissected and weighed.HE staining method was used to observe the pathomorphology of tumor tissue in the nude mice in various groups;immunohistochemistry staining method was used to observe the expression levels of KLK5,Ki67 and matrix metalloproteinase-9(MMP-9)proteins in the tumor tissues of the nude mice in various groups.Results:Compared with ME180-NC-KLK5 cells,the expression level of KLK5 protein in ME180-OE-KLK5 cells was increased(P＜0.05).In the first week after subcutaneous xenograft inoculation,the nude mice in various groups showed good feeding and activity status,and their body weights gradually increased.The drug administration phase started from the second week.During the drug treatment period,the feeding and activity status as well as body weight of the nude mice in NC-KLK5+0.9％NaCl group showed no significant changes compared with the first week;compared with NC-KLK5+0.9％NaCl group,the nude mice in NC-KLK5+DDP group began to show loss of appetite,no increase in body weight,and decreased activity.During the drug treatment period in the third week,the feeding and activity status of the nude mice in NC-KLK5+0.9％NaCl group showed no significant changes compared with the second week,while they began to show no increase in body weight;compared with NC-KLK5+0.9％NaCl group,the feeding and activity status of the nude mice in NC-KLK5+DDP group were significantly weakened,and their body weights decreased.Compared with NC-KLK5+0.9％NaCl group,the volume of xenograft tumor in NC-KLK5+DDP group was decreased(P＜0.01);compared with NC-KLK5+DDP group,the volume of xenograft tumor OE-KLK5+DDP group was significantly increased(P＜0.001);compared with NC-KLK5+0.9％NaCl group,the volume of xenograft tumor of the nude mice in OE-KLK5+0.9％NaCl group was increased(P＜0.001);compared with OE-KLK5+0.9％NaCl group,the volume of xenograft tumors in the nude mice in OE-KLK5+DDP group showed no statistically significant difference(P＞0.05).Compared with NC-KLK5+0.9％NaCl group,the weight of xenograft tumor of the nude mice in NC-KLK5+DDP group was decreased(P＜0.05);compared with NC-KLK5+DDP group,the weight of xenograft tumors of the nude mice in OE-KLK5+DDP group was significantly increased(P＜0.001);compared with NC-KLK5+0.9％NaCl group,the weight of xenograft tumor of the nude mice in OE-KLK5+0.9％NaCl group was increased(P＜0.001);compared with OE-KLK5+0.9％NaCl group,the weight of xenograft tumors of the nude mice in OE-KLK5+DDP group showed no statistically significant difference(P＞0.05).Compared with NC-KLK5+0.9％NaCl group,the xenograft tumor cells of the nude mice in OE-KLK5+0.9％NaCl group showed greater nuclear heterogeneity;the xenograft tumor cells of the nude mice in OE-KLK5+DDP group and NC-KLK5+DDP group showed cytomorphological changes,manifested as nuclear pyknosis and fragmentation,reduced cell volume,and the appearance of necrosis and apoptosis.Compared with NC-KLK5+DDP group,the degree of necrosis in xenograft tumor of the nude mice in OE-KLK5+DDP group was more pronounced.Compared with NC-KLK5+0.9％NaCl group,the expression levels of KLK5,Ki67 and MMP-9 proteins in xenograft tumor tissue of the nude mice in NC-KLK5+DDP group were decreased(P＜0.05);compared with NC-KLK5+DDP group,the expression levels of KLK5,Ki67,and MMP-9 proteins in xenograft tumor tissue of the nude mice in OE-KLK5+DDP group were increased(P＜0.001);compared with NC-KLK5+0.9％NaCl group,the expression levels of KLK5,Ki67 and MMP-9 proteins in xenograft tumor tissue of the nude mice in OE-KLK5+0.9％NaCl group were increased(P＜0.001);compared with OE-KLK5+0.9％NaCl group,the expression levels of KLK5,Ki67 and MMP-9 in xenograft tumor tissue of the nude mice in OE-KLK5+DDP group showed no statistically significant differences(P＞0.05).Conclusion:KLK5 overexpression can promote the growth of subcutaneous xenograft tumors of cervical cancer ME 180 cells treated with DDP,up-regulate the expressions of Ki67 and MMP-9 in the xenograft tumor tissue,and reduce the sensitivity of the xenograft tumor to DDP.

Objective To analyze the spatiotemporal evolution patterns of mortality and disease burden of smoking-related prostate cancer(PCa)from 1990 to 2021 and to predict the future trends,so as to provide evidence-based insights for optimizing regional PCa prevention policies and smoking cessation interventions.Methods Based on data from the Global Burden of Disease Study(GBD)2021,annual mortality,disability-adjusted life years(DALYs),years of life lost(YLLs),years lived with disability(YLDs),and age-standardized rates(ASRs)for PCa across 204 countries and 21 regions from 1990 to 2021 were obtained.Estimated annual percentage change(EAPC)was used to assess the disease burden and mortality of smoking-related PCa across global,regional,socio-demographic index(SDI),and age groups.An autoregressive integrated moving average(ARIMA)model was employed to predict trends in these indicators up to 2050.Results In 2021,smoking-related PCa caused 12 992 global deaths,a 30.74％increase compared to 1990.However,from 1990 to 2021,the global age-standardized mortality rate(ASMR),age-standardized DALYs rate(ASDR),age-standardized YLDs rate(ASYR),and age-standardized YLLs rate(ASLR)for smoking-related PCa declined,with EAPCs being-1.43(95％CI:-1.77--1.12),-1.39(95％CI:-1.66--1.12),-0.41(95％CI:-0.67--0.15)and-1.51(95％CI:-1.78--1.23).In 2021,the region with the highest number of deaths from PCa was Asia(4663 deaths),followed by Europe(4647 deaths),and Oceania had the lowest number of deaths(9 deaths).From 1990 to 2021,the mortality rate of PCa in most regions generally showed a downward trend.High SDI regions showed the most significant declines in ASMR,ASDR,and ASLR[EAPCs:-3.17(95％CI:-3.31--3.02),-2.91(95％CI:-3.02--2.83),and-3.22(95％CI:-3.35--3.09)].For ASYR,only high-SDI regions exhibited a decline,whereas low-middle-SDI regions saw the largest increase[EAPC:1.26(95％CI:1.19-1.33)].In 2021,the number of PCa deaths was more concentrated in the age groups of 70-74 and 75-79,with 2312 and 2278 deaths,respectively.From 1990 to 2021,ASMR,ASDR,and ASLR showed an overall downward trend,EAPC were-2.84(95％CI:-3.21--1.83),-2.77(95％CI:-3.13--1.75),and-2.84(95％CI:-3.14--1.71),with the most significant decline observed in individuals aged 35-39.Projections to 2050 indicated continuing declines in all burden metrics,which would stabilize in later years.Conclusion Despite a global decline in smoking-related PCa burden over the past three decades,significant regional disparities persist,with low-and middle-income countries facing ongoing challenges.Implementing stricter tobacco control policies is critical to mitigating smoking-related health risks.