Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Aim To investigate the effects of total fla-vonoids of Chuzhou chrysanthemum(TFCC)on the activity and migration of rat brain artery endothelial cells under hypoxia/reoxygenation(H/R)injury,as well as the relationship between TFCC's effects and vascular endothelial growth factor receptor 2(VEGFR2).Methods Primary rat brain artery endo-thelial cells were cultured,the H/R model of cells was constructed,VEGFR2 inhibitor SU5416(10 μmol·L-1)was used and a cell transfection model was estab-lished.The cell activity was detected by CCK-8,and the cell migration was detected by scratch method and Transwell assay.Results TFCC(30,90,270 mg·L-1)significantly increased the activity and migration ability of rat brain artery endothelial cells with H/R in-jury,the use of VEGFR2 blocker SU5416 and transfec-tion of VEGFR2 siRNA could significantly inhibit the enhanced activity and migration ability of TFCC on cer-ebral vascular endothelial cells in rats with H/R inju-ry.Conclusions TFCC promotes the activity and mi-gration ability of rat brain artery endothelial cell with H/R injury,and its mechanism is related to VEGFR2.

Objective:To explore the application effect of comprehensive exercise program led by specialized nurses in patients with coronary heart disease(CHD)and type 2 diabetes mellitus(T2DM).Methods:We enrolled 386 CHD+T2DM patients admitted in Provincial Hospital Affiliated to Fuzhou University between April and December 2022.The patients were divided into control group(n=193)and intervention group(n=193)according to the order of their admission.The patients in control group received routine treatment and follow-up,while those in the in-tervention group received additional individualized exercise rehabilitation program led by specialized nurses.Both groups were intervened for 24 weeks.Levels of blood glucose[fasting blood glucose(FBG),glycosylated hemoglo-bin A1c(HbA1c)],blood lipids[low density lipoprotein cholesterol(LDL-C),total cholesterol(TC)],left ven-tricular ejection fraction(LVEF)and 6min walking distance(6MWD)were compared between two groups at dis-charge and six months after discharge.Results:Compared with patients in control group after 6-month interven-tion,those in intervention group had significant lower FBG[(5.30±0.97)mmol/L vs.(5.52±1.04)mmol/L],HbA1c[(5.60±0.65)％vs.(5.78±0.95)％],LDL-C[(1.88±0.52)mmol/L vs.(2.01±0.48)mmol/L],TC[(3.85±0.82)mmol/L vs.(4.04±0.75)mmol/L],and significant higher LVEF[(59.67±4.84)％ vs.(57.22±6.45)％]and 6MWD[(504.66±75.21)m vs.(487.75±56.16)m](P＜0.05 or＜0.01).Conclusion:Special-ized nurse-led exercise rehabilitation program could effectively control blood glucose and lipid levels,improve heart function,exercise endurance and prognosis in patients with type 2 diabetes mellitus and coronary heart disease.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Objective To identify biomarkers that characterize its bitter-cold properties of Scutellaria Radix on the basis of evaluating its cold and hot properties,as well as possible metabolic pathways and related targets;To explore its molecular mechanism.Methods Totally 40 mice were randomly divided into a control group and a treatment group,and were orally administered with normal saline and Scutellaria Radix decoction,respectively,for 4 consecutive days.The cold and hot plate differential method was used to evaluate the cold and hot tendencies of the mice;UPLC-MS/MS technology was used to analyze mouse blood samples,differential metabolites were screened using principal component analysis,partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis methods,and metabolic pathway analysis was performed;network modular analysis of differential metabolites was performed using Cytoscape 3.9.0 software to identify potential molecular targets.Results On the second day of administration,the anal temperature of mice in the treatment group decreased significantly compared to the control group(P<0.01);in the cold and hot tendency test,the mice in the treatment group showed an overall increase in high-temperature tendency and a higher proportion of high-temperature zone retention.There was a statistically significant difference(P<0.01,P<0.05)between the treatment group and the control group on the 2nd and 3rd day of treatment;the pattern recognition analysis of serum metabolome data showed that the serum samples of the treatment group and the control group could be completely separated,and a total of 14 differential metabolites were screened out;metabolic pathway analysis identified 16 related pathways,including unsaturated fatty acid biosynthesis,linoleic acid metabolism,citric acid cycle(TCA cycle),arachidonic acid metabolism,glycine,serine and threonine metabolism,steroid hormone biosynthesis,etc.;a total of 16 modules were obtained through network modular analysis,among which the arachidonic acid metabolism pathway and linoleic acid metabolism pathway modules were larger;the nodal degree values of arachidonic acid and linoleic acid were greater than the mean,involving arachidonic acid metabolism and linoleic acid metabolism pathways;by screening 26 genes associated with the cytochrome P450 enzyme system were obtained.Conclusion Scutellaria Radix may regulate the body's energy metabolism,achieve its biological effects,and characterize its medicinal properties by intervening in metabolic pathways such as arachidonic acid and linoleic acid.

Function-preserving surgery for gastric cancer is a treatment strategy aimed at improving postoperative function while ensuring oncological safety. By preserving important anatomical structures such as the cardia, pylorus, and vagus nerve, as well as key functions like digestion, secretion, emptying, and anti-reflux, this approach aims to minimize the negative impact on patients' postoperative quality of life. With the widespread application of neoadjuvant treatment and the continuous improvement in the efficacy of anti-tumor drugs, the application and indications for functional-preserving surgery may further expand. This article reviews the current status and future prospects of function-preserving surgery for gastric cancer, focusing on its main types, applications after neoadjuvant therapy, and the exploration of new technologies.

Function-preserving surgery for gastric cancer is a treatment strategy aimed at improving postoperative function while ensuring oncological safety. By preserving important anatomical structures such as the cardia, pylorus, and vagus nerve, as well as key functions like digestion, secretion, emptying, and anti-reflux, this approach aims to minimize the negative impact on patients' postoperative quality of life. With the widespread application of neoadjuvant treatment and the continuous improvement in the efficacy of anti-tumor drugs, the application and indications for functional-preserving surgery may further expand. This article reviews the current status and future prospects of function-preserving surgery for gastric cancer, focusing on its main types, applications after neoadjuvant therapy, and the exploration of new technologies.

Aim To investigate the effects of total fla-vonoids of Chuzhou chrysanthemum(TFCC)on the activity and migration of rat brain artery endothelial cells under hypoxia/reoxygenation(H/R)injury,as well as the relationship between TFCC's effects and vascular endothelial growth factor receptor 2(VEGFR2).Methods Primary rat brain artery endo-thelial cells were cultured,the H/R model of cells was constructed,VEGFR2 inhibitor SU5416(10 μmol·L-1)was used and a cell transfection model was estab-lished.The cell activity was detected by CCK-8,and the cell migration was detected by scratch method and Transwell assay.Results TFCC(30,90,270 mg·L-1)significantly increased the activity and migration ability of rat brain artery endothelial cells with H/R in-jury,the use of VEGFR2 blocker SU5416 and transfec-tion of VEGFR2 siRNA could significantly inhibit the enhanced activity and migration ability of TFCC on cer-ebral vascular endothelial cells in rats with H/R inju-ry.Conclusions TFCC promotes the activity and mi-gration ability of rat brain artery endothelial cell with H/R injury,and its mechanism is related to VEGFR2.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objective:To explore the application effect of comprehensive exercise program led by specialized nurses in patients with coronary heart disease(CHD)and type 2 diabetes mellitus(T2DM).Methods:We enrolled 386 CHD+T2DM patients admitted in Provincial Hospital Affiliated to Fuzhou University between April and December 2022.The patients were divided into control group(n=193)and intervention group(n=193)according to the order of their admission.The patients in control group received routine treatment and follow-up,while those in the in-tervention group received additional individualized exercise rehabilitation program led by specialized nurses.Both groups were intervened for 24 weeks.Levels of blood glucose[fasting blood glucose(FBG),glycosylated hemoglo-bin A1c(HbA1c)],blood lipids[low density lipoprotein cholesterol(LDL-C),total cholesterol(TC)],left ven-tricular ejection fraction(LVEF)and 6min walking distance(6MWD)were compared between two groups at dis-charge and six months after discharge.Results:Compared with patients in control group after 6-month interven-tion,those in intervention group had significant lower FBG[(5.30±0.97)mmol/L vs.(5.52±1.04)mmol/L],HbA1c[(5.60±0.65)％vs.(5.78±0.95)％],LDL-C[(1.88±0.52)mmol/L vs.(2.01±0.48)mmol/L],TC[(3.85±0.82)mmol/L vs.(4.04±0.75)mmol/L],and significant higher LVEF[(59.67±4.84)％ vs.(57.22±6.45)％]and 6MWD[(504.66±75.21)m vs.(487.75±56.16)m](P＜0.05 or＜0.01).Conclusion:Special-ized nurse-led exercise rehabilitation program could effectively control blood glucose and lipid levels,improve heart function,exercise endurance and prognosis in patients with type 2 diabetes mellitus and coronary heart disease.