Background/Aims: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide and is driven by metabolic reprogramming that supports tumor growth and progression. A common missense genetic variant (rs2642438, p.A165T) in mitochondrial amidoxime reducing component 1 (MTARC1), identified as protective against liver disease, has been recently associated with lower prevalence of steatosis, cirrhosis, and HCC. However, the mechanistic role of MTARC1 in HCC is unclear. Therefore, we sought to decipher the role of MTARC1 in HCC. Methods: We investigated the role of MTARC1 in HCC by performing siRNA-mediated knockdown across human immortalized HCC cell lines (Hep3B2, HuH7, HepG2 and HepaRG) homozygous for the risk allele (p.A165) and by generating stable CRISPR-Cas9 knockout (KO) models. Next, we assessed the effect of MTARC1 loss on cell proliferation, migration, lipid metabolism, and fatty acid oxidation in vitro, as well as tumor aggressiveness in a subcutaneous xenograft mouse model. Additionally, we performed global proteomics in both in vitro and xenograft models. Results: Transient knockdown of MTARC1 p.A165 reduced proliferation in HCC cell lines. CRISPR-Cas9-mediated stable MTARC1 p.A165 KO in Hep3B2 cells led to decreased neutral lipid intracellular accumulation, enhanced β-oxidation and reduced cell migration. An MTARC1 KO xenograft model had reduced tumor volume. Proteomic analyses of both in vitro HCC cells and xenograft tumors revealed inhibition of oncogenic pathways and activation of anti-proliferative proteins. Conclusions Downregulation of MTARC1 p.A165 inhibits lipid accumulation, dampens tumor-promoting pathways and restricts tumor growth, highlighting MTARC1 as a promising therapeutic target for HCC.

ObjectiveTo investigate the value of liver stiffness measurement （LSM） and spleen stiffness measurement （SSM） measured by two-dimensional shear wave elastography （2D-SWE） in the diagnosis of severe portal hypertension （SPH） and high-risk varices （HRV）， and to provide a basis for noninvasive assessment of portal hypertension. MethodsA prospective study was conducted among 78 patients with cirrhotic portal hypertension who were treated in Liver Research Center of Beijing Friendship Hospital， Capital Medical University， from December 2019 to April 2023. According to hepatic venous pressure gradient （HVPG）， the patients were divided into 6 mmHg≤HVPG<12 mmHg group， 12 mmHg≤HVPG<20 mmHg group， and HVPG ≥20 mmHg group. All patients underwent gastroscopy and 2D-SWE within 1 week after HVPG measurement， and SWE-LSM and SWE-SSM measured by 2D-SWE were recorded. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. With HVPG and gastroscopy findings as the gold standard， the receiver operating characteristic （ROC） curve was plotted and the area under the ROC curve （AUC） was calculated to evaluate diagnostic performance， while the DeLong test was used for comparison of AUC. The Pearson or Spearman correlation analysis was used to investigate the correlation between variables， and the linear regression analysis and the Logistic regression analysis were used to investigate the influencing factors for HVPG and HRV. ResultsThe mean HVPG was 18.1±6.4 mmHg for the patients enrolled in this study， and HRV was observed in 62 patients （79.5%）. Both SWE-LSM and SWE-SSM were significantly positively correlated with HVPG （r=0.413 and 0.633， both P<0.001）， with an AUC of 0.812 and 0.902， respectively， in the diagnosis of HVPG≥12 mmHg and an AUC of 0.804 and 0.789， respectively， in the diagnosis of HVPG≥20 mmHg （all P>0.05）. The multivariate linear regression analysis showed that SWE-SSM was an independent influencing factor for HVPG （β=0.17， P<0.001）. In the diagnosis of HRV， only SWE-SSM showed a significant positive correlation with HRV （r=0.432， P<0.001）， with a better diagnostic performance than SWE-LSM in terms of AUC （0.808 vs 0.642， Z=2.775， P=0.006）. The multivariate Logistic regression analysis showed that platelet count was an independent influencing factor for HRV （odds ratio=0.97， P=0.014）. ConclusionSWE-SSM is closely correlated with both HVPG and HRV， showing a good performance in the diagnosis of SPH and HRV， and therefore， it is expected to become an effective noninvasive tool for assessing portal hypertension.

Objective To explore the functional impact of A-to-I editing in the seed region of miR-411 during post-myocardial infarction (MI) fibrosis and elucidate its therapeutic potential. Methods Integrating GEO database with myocardial RNA-seq data from MI mouse models, we identified dynamic A-to-I RNA editing in small noncoding RNAs across MI progression (1 day to 8 weeks post-MI). Four miRNAs exhibited differential editing rates between MI and controls, with miR-411 showing progressive editing enhancement at seed region position 4 (P＜0.01). This editing event was validated in both murine MI models and human heart failure specimens. Results The A-to-I editing ratio change of the 4th nucleotide in the seed region of miR-411 mainly occurs in cardiac fibroblasts rather than cardiomyocytes, and the editing at this site depends on ADAR2 rather than ADAR1. Edited miR-411 (ED-miR-411) diverged from wild-type miR-411 (WT-miR-411) in suppressing collagen-related pathways (extracellular matrix [ECM]-receptor interaction, collagen-containing ECM, ECM organization; P＜0.01) in cardiac fibroblasts. Mechanistically, dual-luciferase assays confirmed ED-miR-411 directly targeted the 3′UTR and suppressed expression of type Ⅱ transforming growth factor (TGF)-beta receptor (TGFBR2) and CD44, which were key drivers of TGF-β-mediated fibroblast activation. ED-miR-411 overexpression blunted TGF-β-induced collagen synthesis and myofibroblast proliferation (P＜0.05). In vivo, intramyocardial delivery of ED-miR-411 mimics at 1 week post-MI reduced fibrosis by 40% and improved ejection fraction by 15% (P＜0.01 vs controls), whereas WT-miR-411 showed no therapeutic effect. Conclusions A-to-I editing of miR-411 emerges as an endogenous anti-fibrotic mechanism by repressing TGFBR2 and CD44, thereby disrupting TGF-β signaling and ECM dysregulation. Our findings highlight ED-miR-411 as a novel RNA-based therapeutic candidate to mitigate post-infarction cardiac remodeling.

Objective:To investigate the efficacy and safety of anlotinib combined with GP (gemcitabine+cisplatin) regimen in the treatment of advanced triple-negative breast cancer refractory to anthracyclines and taxanes chemotherapy.Methods:A retrospective cohort study was conducted. Fifty two patients with advanced triple-negative breast cancer refractory to anthracyclines and taxanes chemotherapy in Affiliated Jiangyin Hospital of Nantong University from January 2019 to June 2022 were selected. According to follow-up treatment methods, they were divided into the treatment group of anlotinib combined with GP regimen (observation group) and the treatment group of GP regimen alone (control group), with 26 cases in each group. The short-term efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1 after 2 cycles of treatment, and the adverse reactions were assessed according to the Common Terminology Criteria for Adverse Events 4.0 after each treatment cycle. Kaplan-Meier method was used for analysis of progression-free survival (PFS) and overall survival (OS), and log-rank test was performed for inter group comparison. The scores of various dimensions of SF-36 quality of life scale before and after treatment were compared.Results:All 52 enrolled patients were able to evaluate the therapeutic effect. The objective response rate (ORR) of the observation group was 38.5% (10/26), and the disease control rate (DCR) was 84.6% (22/26). The ORR of the control group was 19.2% (5/26), and the DCR was 57.7% (15/26). The ORR and DCR of the observation group were higher than those in the control group, and the differences were statistically significant ( χ2 values were 10.82 and 7.18, respectively, both P < 0.05). The PFS [median PFS time, 5.4 months (95% CI: 5.0-5.8 months) vs. 3.9 months (95% CI: 3.6-4.2 months)] and OS [median OS time, 14.0 months (95% CI: 12.1-17.8 months) vs. 9.2 months (95% CI: 7.9-11.3 months)] of the observation group were better than those of the control group, and the differences were statistically significant (both P < 0.05). Compared with the control group, the incidence of hypertension [57.7% (15/26) vs. 3.8% (1/26)] and hand-foot syndrome [23.1% (6/26) vs. 0 (0/26)] in the observation group was higher (both P < 0.05), while there was no statistically significant difference in the incidence of nausea and vomiting, neutropenia, thrombocytopenia, anemia, bleeding, hyperbilirubinemia, fatigue, oral mucositis, and alopecia between the two groups (all P > 0.05). The scores of each dimension of the SF-36 quality of life scale in both groups of patients after treatment were higher than those before treatment (all P < 0.05), and the scores of each dimension in the observation group were higher than those in the control group after treatment (all P < 0.05). Conclusions:Anlotinib combined with GP regimen is effective in the treatment of advanced triple-negative breast cancer refractory to anthracyclines and taxanes chemotherapy, this regimen will not significantly increase the adverse reactions of chemotherapy and can improve the prognosis and the quality of life of patients.

Objective:To develop a laser-induced graphene (LIG)-based multimodal electrochemical sensor for monitoring the burn wound microenvironment and to evaluate its performance.Methods:This study was an experimental study. LIG three-electrode substrates were functionalized with L-lactate oxidase, polyaniline, and sortase A to fabricate lactate sensor, pH sensor, and bacterial sensor, respectively, thereby constituting the LIG-based multimodal electrochemical sensor. An electrochemical workstation was used to assess the electrochemical performance of the lactate sensor and bacterial sensor by cyclic voltammetry, with voltammetric response curves being plotted. An electrochemical workstation was used to assess the lactate sensor's response to lactate by chronoamperometry (with current-time curve being recorded and calibration curve being plotted during the test in the L-lactic acid solution with a molar concentration of 10-60 mmol/L), the pH sensor's response to pH by open-circuit potential measurement (with open-circuit potential-time curve being recorded and calibration curve being plotted during the test in the standard buffer solutions with pH values ranging from 3 to 8), and the bacterial sensor's response to bacteria by differential pulse voltammetry (with current-voltage curve being recorded and calibration curve being plotted during the test in gradient suspensions of Staphylococcus aureus ranging from 1×103-1×10? colony forming unit (CFU)/mL). The sample size for all the above experiments was 3. The correlation analysis was performed on the current value of the lactate sensor and the lactate concentration, the average value of steady-state open circuit potential of the pH sensor and the pH value, and the peak current value of the bacterial sensor and the bacterial concentration value. Each of the prepared standard test system solutions for lactate, pH value, and bacteria were all aliquoted into 30 samples. The lactate concentration, pH value, and bacterial concentration were determined by the lactate sensor and a L-lactate assay kit, the pH sensor and a precision pH meter, and the bacterial sensor and a microvolume spectrophotometer, respectively. Fifteen pairs of matched data were selected according to the random number table method for comparison, and the correlation analysis was performed on the measured values of each sensor and the reference values of the corresponding standard methods. Results:The voltammetric response curves showed that the lactate sensor and the bacterial sensor exhibited distinct oxidation peak currents at oxidation peak potentials of approximately 0.74 and 0.65 V, respectively. In the lactate sensor, the change in current after addition of phosphate buffered solution was (0.025±0.041) μA, which was significantly lower than that after addition of L-lactate solution (0.228±0.117) μA ( t=2.85, P<0.05). In the L-lactic acid solution with a molar concentration of 10-60 mmol/L, the current value of the lactate sensor was significantly linearly correlated with the lactate concentration ( r=0.98, P<0.05). In the standard buffer solutions with pH values ranging from 3 to 8, the average value of steady-state open circuit potential of the pH sensor was significantly linearly correlated with the corresponding pH values ( r=0.96, P<0.05). In gradient suspensions of Staphylococcus aureus ranging from 1×103 to 1×10? CFU/mL, the peak current value of the bacterial sensor was significantly linearly correlated with the logarithm of bacterial concentration ( r=0.95, P<0.05). There were no statistically significant differences between the lactate concentrations measured by the lactate sensor and by the L-lactate assay kit, pH values measured by the pH sensor and by the precision pH meter, and logarithmic bacterial concentrations measured by the bacterial sensor and by the microvolume spectrophotometer ( P>0.05), but there were significant positive correlations between the two (with r values of 0.97, 0.96, and 0.95, respectively, P<0.05). Conclusions:After functional modification, the developed LIG-based multimodal electrochemical sensor enables accurate monitoring of lactate concentration, pH value, and bacterial load in the burn wound microenvironment with the results being of high sensitivity and stability. This platform provides a reliable new approach for non-invasive monitoring of the critical indicators of burn wound microenvironment, which shows great prospects for clinical application.

Objective:To study the epidemiological characteristics and clinical diagnosis of human brucellosis in Qujing City, Yunnan Province.Methods:Through the Infectious Disease Reporting Information Management System of the China Disease Prevention and Control Information System, the basic information and clinical diagnostic data of brucellosis cases reported in Qujing City from January 2008 to December 2023 were retrospectively collected. Descriptive epidemiological methods were used to analyze the epidemic profile, three distribution characteristics (time, population, region), and diagnosis of brucellosis.Results:A total of 1 417 brucellosis cases were reported in Qujing City from 2008 to 2023, with no death. The annual average incidence of brucellosis was 1.49/100 000, with no cases reported in 2009 and 2010, and the highest incidence in 2023 (7.82/100 000). The incidence of brucellosis showed an increasing trend year by year (χ 2trend = 1 874.58, P < 0.001). The number of cases from June to November accounted for 61.54% (872/1 417). The majority of brucellosis cases were in the age group of 36 - 65 years old, accounting for 67.82% (961/1 417). Among them, there were 954 males and 463 females, with a gender ratio of 2.06 ∶ 1.00. Farmers were the main occupation, accounting for 84.33% (1 195/1 417). The cases were mainly distributed in Luliang County (621 cases), Xuanwei City (282 cases) and Shizong County (137 cases), accounting for 73.39% (1 040/1 417). The median interval between onset and diagnosis was 13 days, and the cases with intervals ≤7 d, 8 - 30 d, and ≥31 d accounted for 32.11% (455/1 417), 40.16% (569/1 417), and 27.73% (393/1 417), respectively. Totally 63.94% (906/1 417) of the cases were confirmed in medical institutions in Qujing City. Conclusions:The incidence of brucellosis in Qujing City is increasing year by year, with men, middle-aged and elderly people and farmers as the main population, summer and autumn as the peak period, and Luliang County, Xuanwei City and Shizong County as the high incidence areas. Most cases have an interval of less than 30 days between onset and diagnosis, and can be diagnosed within the jurisdiction.

Objective To investigate the diagnostic value of serum soluble growth stimulation expressed gene 2(sST2),decoy receptor 3(DcR3)and dynamic electrocardiogram(DCG)for asymptomatic myocardial ischemia(SMI).Methods Eighty-five patients with coronary heart disease were selected as observation subjects(the observation group).Sixty-one SMI patients were confirmed by coronary angiography(the SMI group).Among them,there were 24 cases with symptomatic myocardial ischemia(the symptomatic myocardial ischemia group).During the same period,84 patients with unexplained chest pain who were examined in our hospital and without coronary heart disease were selected as the control group.ELISA was applied to detect serum levels of sST2 and DcR3.ROC was used to analyze the diagnostic value of serum sST2,DcR3 and DCG for SMI.Multivariate Logistic regression was applied to analyze the influencing factors of SMI.Results The serum level of sST2 was higher in the observation group than that in the control group[(55.61±7.12)μg/L vs.(14.22±3.64)μg/L],while the level of DcR3 was lower than that in the control group[(0.68±0.11)μg/L vs.(1.24±0.21)μg/L](P＜0.05).The serum level of sST2 was higher in the SMI group than that in the symptomatic myocardial ischemia group[(59.28±7.12)μg/L vs.(46.28±8.15)μg/L],while the level of DcR3 was lower than that in the symptomatic myocardial ischemia group[(0.63±0.11)μg/L vs.(0.81±0.14)μg/L](P＜0.05).The heart rate of the SMI group was higher than that of the symptomatic myocardial ischemia group,and the duration of ischemia and the decrease in ST segment were lower than those of the symptomatic myocardial ischemia group(P＜0.05).ROC curve results showed that the AUC values of serum sST2,DcR3 and DCG alone and in their combination for diagnosing SMI in patients with coronary heart disease were 0.826,0.882,0.773,and 0.958,respectively,and the combined diagnosis of SMI was superior to individual diagnosis(Z=3.188,2.225,2.770,P＜0.05).sST2 and DcR3 were influencing factors of SMI occurrence(P＜0.05).Conclusion The increased serum sST2 and the decreased DcR3 are closely related to the occurrence of SMI,and the combination of serum sST2 and DcR3 with DCG has certain diagnostic value for SMI.

Objective:To study the epidemiological characteristics and clinical diagnosis of human brucellosis in Qujing City, Yunnan Province.Methods:Through the Infectious Disease Reporting Information Management System of the China Disease Prevention and Control Information System, the basic information and clinical diagnostic data of brucellosis cases reported in Qujing City from January 2008 to December 2023 were retrospectively collected. Descriptive epidemiological methods were used to analyze the epidemic profile, three distribution characteristics (time, population, region), and diagnosis of brucellosis.Results:A total of 1 417 brucellosis cases were reported in Qujing City from 2008 to 2023, with no death. The annual average incidence of brucellosis was 1.49/100 000, with no cases reported in 2009 and 2010, and the highest incidence in 2023 (7.82/100 000). The incidence of brucellosis showed an increasing trend year by year (χ 2trend = 1 874.58, P < 0.001). The number of cases from June to November accounted for 61.54% (872/1 417). The majority of brucellosis cases were in the age group of 36 - 65 years old, accounting for 67.82% (961/1 417). Among them, there were 954 males and 463 females, with a gender ratio of 2.06 ∶ 1.00. Farmers were the main occupation, accounting for 84.33% (1 195/1 417). The cases were mainly distributed in Luliang County (621 cases), Xuanwei City (282 cases) and Shizong County (137 cases), accounting for 73.39% (1 040/1 417). The median interval between onset and diagnosis was 13 days, and the cases with intervals ≤7 d, 8 - 30 d, and ≥31 d accounted for 32.11% (455/1 417), 40.16% (569/1 417), and 27.73% (393/1 417), respectively. Totally 63.94% (906/1 417) of the cases were confirmed in medical institutions in Qujing City. Conclusions:The incidence of brucellosis in Qujing City is increasing year by year, with men, middle-aged and elderly people and farmers as the main population, summer and autumn as the peak period, and Luliang County, Xuanwei City and Shizong County as the high incidence areas. Most cases have an interval of less than 30 days between onset and diagnosis, and can be diagnosed within the jurisdiction.

Objective:To study the effects of remimazolam on stress response index, T lymphocyte subsets and postoperative delirium in patients undergoing modified radical mastectomy.Methods:A total of 120 patients with breast cancer who underwent modified radical mastectomy in our hospital from Aug. 2024 to Dec. 2024 were separated into the control group (n=60, anesthetic induction and maintenance with Propofol) and the observation group (n=60, anesthetic induction and maintenance with remimazolam) according to random number table method, and the other anesthetic drugs were the same. The operation time, anesthesia recovery time, postoperative delirium and cognitive dysfunction of the two groups were observed, and the changes of stress response indexes and T lymphocyte subsets indexes at different time points were compared, and the adverse reactions after anesthesia were counted.Results:The incidence of postoperative delirium and cognitive dysfunction in the observation group was lower than that in the control group ( x2=4.62, 5.18, P < 0.05), and there was no statistically significant difference in operation time or anesthesia recovery time between the two groups ( t=0.43, 1.71, P > 0.05). The observation group had lower serum cortisol (Cor), norepinephrine (NE) and epinephrine (E) levels 30 min after anesthesia induction (T 1) and immediately after surgery (T 2) ( t=5.53, 6.71, 9.33, 6.74, 7.26, 8.77, P < 0.05), while the comparison of those indexes before surgery (T 0) and 12 h after surgery (T 3) showed no statistically significant difference ( t=1.19, 1.85, 0.90, 1.55, 1.64, 1.81, P > 0.05). The levels of CD3 +T, CD4 +T and CD4 +/CD8 + in the observation group were higher than those in the control group at T 1, T 2 and T 3 ( t=2.21, 4.94, 4.77, 4.44, 6.24, 7.07, 2.11, 2.56, 2.15, P < 0.05), and there was no statistically significant difference in those indexes between the two groups at T 0 ( t=0.76, 0.79, 1.51, P > 0.05). The incidence of adverse reactions after anesthesia showed no statistically significant difference between the two groups [25.00% (15/60) and 33.33% (20/60) ] ( χ2=1.008, P > 0.05) . Conclusion:The induction and maintenance of remimazolam anesthesia can effectively reduce the incidence of postoperative delirium and cognitive dysfunction in patients with modified radical mastectomy, relieve the body stress response of patients, and effectively reduce the influence of anesthesia on T lymphocytes.

Objective To investigate the diagnostic value of serum soluble growth stimulation expressed gene 2(sST2),decoy receptor 3(DcR3)and dynamic electrocardiogram(DCG)for asymptomatic myocardial ischemia(SMI).Methods Eighty-five patients with coronary heart disease were selected as observation subjects(the observation group).Sixty-one SMI patients were confirmed by coronary angiography(the SMI group).Among them,there were 24 cases with symptomatic myocardial ischemia(the symptomatic myocardial ischemia group).During the same period,84 patients with unexplained chest pain who were examined in our hospital and without coronary heart disease were selected as the control group.ELISA was applied to detect serum levels of sST2 and DcR3.ROC was used to analyze the diagnostic value of serum sST2,DcR3 and DCG for SMI.Multivariate Logistic regression was applied to analyze the influencing factors of SMI.Results The serum level of sST2 was higher in the observation group than that in the control group[(55.61±7.12)μg/L vs.(14.22±3.64)μg/L],while the level of DcR3 was lower than that in the control group[(0.68±0.11)μg/L vs.(1.24±0.21)μg/L](P＜0.05).The serum level of sST2 was higher in the SMI group than that in the symptomatic myocardial ischemia group[(59.28±7.12)μg/L vs.(46.28±8.15)μg/L],while the level of DcR3 was lower than that in the symptomatic myocardial ischemia group[(0.63±0.11)μg/L vs.(0.81±0.14)μg/L](P＜0.05).The heart rate of the SMI group was higher than that of the symptomatic myocardial ischemia group,and the duration of ischemia and the decrease in ST segment were lower than those of the symptomatic myocardial ischemia group(P＜0.05).ROC curve results showed that the AUC values of serum sST2,DcR3 and DCG alone and in their combination for diagnosing SMI in patients with coronary heart disease were 0.826,0.882,0.773,and 0.958,respectively,and the combined diagnosis of SMI was superior to individual diagnosis(Z=3.188,2.225,2.770,P＜0.05).sST2 and DcR3 were influencing factors of SMI occurrence(P＜0.05).Conclusion The increased serum sST2 and the decreased DcR3 are closely related to the occurrence of SMI,and the combination of serum sST2 and DcR3 with DCG has certain diagnostic value for SMI.