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.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

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.

Tuberculosis is a highly infectious disease that poses a significant threat to public health, particularly in resource-limited regions where its incidence remains high. In 2022, the World Health Organization (WHO) released the WHO Consolidated Guidelines on Tuberculosis. Module 4: Treatment- Tuberculosis Care and Support, aimed at improving the quality of care and treatment for tuberculosis patients. This guideline outlines the multifaceted challenges faced by tuberculosis patients during treatment and offers evidence-based intervention strategies. It highlights key areas such as psychological support, nutritional management, and social care. This paper provides an interpretation of the main contents of the guideline to offer evidence-based practice guidance for healthcare providers, and to support clinical staff in delivering targeted patient care interventions.

Objective:To investigate the relationship among seminal oxidation-reduction potential(nORP),sperm DNA frag-mentation(DFI)and semen parameters in patients with varicocele.Methods:Clinical data of 522 patients treated in the reproduc-tive andrology clinic of the Northern Theater General Hospital from November 2023 to December 2023 were retrospectively analyzed,in-cluding 435 men of childbearing age and 87 men of infertile age.The patients were divided into the varicocele group(n=116)and non-varicocele group(n=406)according to clinical diagnosis.The differences of seminal plasma nORP,DFI,sperm high DNA stain ability(HDS)and semen parameters were analyzed between the two groups.The relationship among general clinical data,seminal plasma nORP,semen parameters,DFI and HDS in patients with varicocele were further analyzed.According to the severity of varico-cele,the patients were divided into three groups,including mild,moderate and severe.And the differences of seminal plasma nORP and semen parameters,DFI and HDS among all groups were analyzed.The differences of seminal plasma nORP,semen parameters,DFI and HDS were compared between the varicocele and non-varicocele groups.Results:The total sperm count,sperm concentra-tion,progressive motility sperm percentage(PR％)and normal sperm morphology rate(NSMR)in patients with varicocele were sig-nificantly lower than those in control group(P＜0.05).And seminal plasma nORP,DFI and HDS in patients with varicocele were sig-nificantly higher than those in control group(P＜0.05).Seminal plasma nORP in patients with varicocele was significantly negatively correlated with total sperm,sperm concentration and NSMR(P＜0.05),and significantly positively correlated with DFI and HDS(P＜0.05).There were significant differences in nORP,total sperm count,sperm concentration,PR％,DFI and HDS among mild,moderate and severe varicocele groups(P＜0.05).Seminal plasma nORP,sperm concentration,PR％and DFI in severe group were significantly lower than those in mild and moderate groups(P＜0.05).Sperm count and HDS in severe group were significantly lower than those in mild group(P＜0.05).In infertile patients,seminal plasma nORP,DFI and HDS in varicocele group were significantly higher than those in control group(P＜0.05).And PR％in varicocele group was significantly lower than that in control group(P＜0.05).Conclusions:Seminal plasma nORP in patients with varicocele may be an important marker of oxidative stress affecting DFI and semen parameters.

Objective:To investigate the predictive value of anti-Müllerian hormone (AMH) on the outcome of microscopic testicular sperm extraction (micro-TESE) in patients with non-mosaic Klinefelter syndrome (KS) of the clinical data and to identify effective predictors for successful micro-TESE.Methods:A retrospective case-control study was conducted on the clinical data of 118 non-mosaic KS patients treated at the Center for Reproductive Medicine of the First Affiliated Hospital of Zhengzhou University between May 2018 and September 2023. Patients were divided into two groups based on whether sperm were successfully retrieved via micro-TESE: the sperm retrieved group ( n=45) and the no sperm retrieved group ( n=73). Differences between the two groups were compared, and multivariate logistic regression analysis was used to identify factors influencing sperm retrieval. Changes in testicular volume and sex hormone levels before and after surgery were also assessed. Results:The sperm retrieval rate was 38.1% (45/118). Patients in the sperm retrieved group were significantly younger [(26.93±3.80) years] than those in the no sperm retrieved group [(28.27±3.92) years, P=0.029], and the AMH level was significantly higher [0.44 (0.18, 1.13) μg/L] than that in the no sperm retrieved group [0.10 (0.03, 0.22) μg/L, P<0.001]. AMH was identified as an independent predictor of micro-TESE outcome in non-mosaic KS patients ( OR=7.867, 95% CI: 2.727-27.242, P=0.001). The area under the receiver operating characteristic curve was 0.802 (95% CI: 0.722-0.883), and the optimal reference threshold for AMH was ≥0.265 μg/L. Postoperatively, testosterone levels decreased significantly by a median of 0.27 μg/L ( P=0.019), while luteinizing hormone levels increased by a median of 2.08 U/L ( P=0.049), with a more significant decline in testosterone levels observed in the no sperm retrieved group by a median of 0.29 μg/L ( P=0.022). Conclusion:AMH can predict successful micro-TESE in non-mosaic KS patients, with higher AMH levels indicating a higher likelihood of success.

Objective:To explore the correlation between serum ferritin(SF)levels and the efficacy of platelet transfusion in patients with malignant hematological diseases.Methods:Patients with malignant hematological diseases who received repeated transfusions of apheresis platelets in Department of Hematology of Aerospace Center Hospital in 2023 were selected.The platelet corrected count increment(CCI)was used to evaluate the efficacy of platelet transfusion.The correlations between sex,age,disease type,transplantation history,red blood cell transfusion history,and SF level and the efficacy of platelet transfusion were analyzed.Results:A total of 87 patients were included,with a cumulative 326 person-times platelet transfusions.As suggested by one-way analysis of variance,compared with the patients in the age groups of 24-45 years old and 46-66 years old,the patients in the age group of 2-23 years old had a better efficacy of platelet transfusion(P=0.004,P=0.004).There was no significant difference in the efficacy of platelet transfusion between the patients in the age group of 24-45 years old and those in the age group of 46-66 years old(P=0.876).Compared with the patients who had a history of red blood cell transfusion within 3 days,the patients without a history of red blood cell transfusion within 3 days had a better efficacy of platelet transfusion(P＜0.001).Compared with the groups with SF levels of 1.44-2.78 ng/L and＞2.78 ng/L,the group with SF levels＜1.44 ng/L had a better efficacy of platelet transfusion(P=0.028,P＜0.001).Compared with the group with SF levels＞2.78 ng/L,the group with SF levels of 1.44-2.78 ng/L had a better efficacy of platelet transfusion(P=0.001).After adjusting for age and the history of red blood cell transfusion,the transfusion efficacy of the group with SF levels＜1.44 ng/L was better than that of the groups with SF levels of 1.44-2.78 ng/L and＞2.78 ng/L(P=0.021,P＜0.001);Compared with the group with SF levels＞2.78 ng/L,the group with SF levels of 1.44-2.78 ng/L had a better efficacy of platelet transfusion(P=0.001).Both univariate and multivariate linear regression models showed that SF levels were negatively correlated with the efficacy of platelet transfusion(P＜0.001).Conclusion:There is a negative correlation between SF levels and the efficacy of platelet transfusion in patients with malignant hematological diseases.Detection of SF levels may provide guidance for predicting the efficacy of platelet transfusion.

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