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.

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.

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 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.

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.

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.

Objective To investigate the population composition,seasonal dynamics,and infestation levels of cockroaches in Lanzhou,China,and to provide information for the scientific development of cockroach control strategies.Methods Monitoring was conducted at three locations using the sticky trap method.Habitats included farm product markets,catering establishments,hotels,hospitals,and residential areas.Results From 2016 to 2023,the average cockroach density was 0.77 insects per board,with an average infestation rate of 10.84%.Blattella germanica was the dominant species.Seasonal density of cockroaches showed an approximately unimodal distribution,peaking in September.The highest average density and infestation rates were observed in farm product markets.Conclusions Cockroach density and infestation levels in Lanzhou remained relatively low.A comprehensive prevention and control strategy focusing on environmental management in key areas should be implemented according to the seasonal fluctuations.

Objective To investigate the effect of remimazolam(Rem)on retinal ischemia-reper-fusion injury(RIRI)in rats and its regulatory mechanism on the high-mobility group box 1(HMGB1)/receptor for advanced glycation end products(RAGE)/nuclear factor-κB(NF-κB)signaling pathway.Methods Rats were randomly divided into Sham group,Model group,Rem-L group(low-dose Rem),Rem-M group(medium-dose Rem),Rem-H group(high-dose Rem),and high-dose Rem plus HMGB1 activator dexamethasone(DEX)group(Rem-H+DEX group),with 15 rats in each group.Except for the Sham group,RIRI model was established in the other groups by increasing in-traocular pressure.Hematoxylin and eosin(HE)staining was used to observe the changes in retinal tissue structure in each group.The TUNEL method was used to detect retinal tissue apoptosis.En-zyme-linked immunosorbent assay(ELISA)was performed to detect the expression levels of interleu-kin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in the serum of rats in each group.Kits were used to detect the levels of oxidative stress indicators,including superoxide dis-mutase(SOD),glutathione peroxidase(GSH-PX),and malondialdehyde(MDA).Western blot was used to detect the expression levels of hypoxia-related factors[hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor(VEGF)]and HMGB1/RAGE/NF-κB signaling pathway-related proteins in retinal tissue.Results Compared with the Sham group,the Model group showed severe retinal edema,a significant decrease in the number of ganglion cells,vacuolar changes in cells with disordered arrangement,and widened cell gaps.With increasing doses of Rem,the degree of retinal edema gradually decreased,the number of ganglion cells increased,and their arrangement became more orderly in RIRI rats.Compared with the Sham group,the Model group exhibited increased ret-inal cell apoptosis rate,serum levels of IL-1 β,IL-6,and TNF-α and increased expression levels of MDA,HMGB1,RAGE,NF-κB,HIF-1α and VEGF in retinal tissue,while the expression levels of SOD and GSH-PX decreased(P＜0.05).Compared with the Model group,the Rem-L,Rem-M,and Rem-H groups showed dose-dependent decreases in retinal cell apoptosis rate,serum levels of IL-1 β,IL-6,and TNF-α,and expression levels of MDA,HMGB1,RAGE,NF-κB,HIF-1α and VEGF in retinal tissue,with dose-dependent increases in the expression levels of SOD and GSH-PX(P＜0.05).Compared with the Rem-H group,the Rem-H+DEX group showed reversed trends in the above indicators.Conclusion Rem can inhibit the occurrence of RIRI in rats,and its mecha-nism of action may be related to the regulation of the HMGB1/RAGE/NF-κB signaling pathway.

Objective: To construct a hypertension risk prediction model for residents aged 18-79 years, so as to provide an assessment tool for early screening and prevention of hypertension in high-risk groups. Methods: The permanent residents aged 18-79 years from 6 townships (streets) in Fangshan District of Beijing Municipality were selected as the study subjects using a multi-stage stratified random sampling method from March to June 2023. Demographic information, lifestyle, body mass index (BMI), blood pressure, fasting blood glucose, and blood lipid were collected through questionnaire survey, physical examination, and laboratory tests. Subjects were randomly divided into training and validation sets at a 7∶3 ratio. The logistic regression model was used to screen the risk factors of hypertension, and a hypertension risk prediction nomogram was constructed. Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis were used to verify the discrimination, fit, and clinical application value of the model. Results: A total of 4 438 subjects were included, including 2 365 males (53.29%) and 2 073 females (46.71%), with a mean age of (44.99±14.90) years. The prevalence of hypertension was 35.29% (1 566 cases), and the standardized prevalence was 24.74%. The logistic regression model screened out 9 influencing factors of hypertension. The nomogram was established as ln[p/ (1-p)]= -2.873 + 0.935×40-<50 years + 1.463×50-<60 years + 1.908×60-<70 years + 2.346×70-79 years + 0.298×male-0.675×college degree or above + 0.384×smoking + 0.227×drinking + 0.572×overweight + 1.449×obesity + 0.557×heart rate ≥80 beats/min + 0.428×diabetes + 0.484×dyslipidemia. The area under the ROC curve of the validation set was 0.821 (95%CI: 0.798-0.843), and the calibration curve results showed that the calibration curve fitted the actual curve well. Decision curve analysis showed that the threshold probability was in the range of 0.10 to 0.70, and the model had good predictive value and clinical application value. Conclusion The nomogram based on age, gender, educational level, smoking, drinking, body mass index, heart rate, diabetes, and dyslipidemia can be used to predict the risk of hypertension among residents aged 18-79 years.