Objective:To discuss the effect of erythritol on glucose and lipid metabolism in the body,and to clarify the mechanism of erythritol affecting liver metabolism based on metabonomics.Methods:The male ICR mice were randomly divided into normal group,sucrose group(2％sucrose),low dose of erythritol(1％erythritol)group,medium dose of erythritol(2％erythritol)group,and high dose of erythritol(4％erythritol)group,with 10 mice in each group.The corresponding concentrations of sucrose and erythritol solutions were prepared and placed in water bottles,and the mice were allowed to drink and eat freely for 12 consecutive weeks;the body mass,food intakes,and water intakes of the mice in various groups were measured.Commercial kits were used to detect the serum triglyceride(TG),total cholesterol(TC),and blood glucose levels of the mice in various groups;the liver indexes of the mice were calculated.Ultra performance liquid chromatography-orbitrap exactive mass spectrometry(UPLC-OE-MS)non-targeted metabonomics was used to detect the liver metabolites of the mice normal group and high dose of erythritol group;bioinformatics analysis was used to screen the differential liver metabolites between the two groups with variable importance in projection(VIP)＞1 and adjusted P＜0.05;Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed to investigate the functional roles of the differential liver metabolites.Results:Compared with normal group,there were no significant differences in the body mass,food intake,liver index,and blood lipid levels of the mice in various groups(P＞0.05);compared with normal group,the blood glucose level of the mice in high dose of erythritol group was significantly increased(P＜0.01).The metabonomics analysis of the liver tissues of the mice in two groups identified 1 144 metabolites,mainly including lipids and lipid-like molecules(17.39％),organic acids and derivatives(10.87％),organic heterocyclic compounds(5.80％),and organic oxygen compounds(5.07％).Compared with normal group,there were 138 differential liver metabolites in the mice in high dose of erythritol group,among which 112 metabolites were up-regulated and 26 metabolites were down-regulated.The KEGG signal pathway enrichment analysis results showed that the differential metabolites were mainly enriched in metabolism,steroid hormone biosynthesis,cortisol synthesis and metabolism,and Cushing's syndrome pathways;the further topological analysis of the metabolic pathways results showed that the differential metabolites were mainly involved in sphingolipid metabolism,tricarboxylic acid cycle,riboflavin metabolism,steroid hormone biosynthesis,and purine metabolism signal pathways.Conclusion:Long-term intake of high dose of erythritol can increase the blood glucose level in the mice,and the mechanism may be that it affects the tricarboxylic acid cycle by interfering with riboflavin metabolism and interferes with sphingolipid metabolism,leading to impairment of the blood glucose control system.

Objective:To evaluate the effectiveness of a mobile extracorporeal cardiopulmonary resuscitation (ECPR) team in treating cardiac arrest (CA) in the mountainous regions of southwest Zhejiang Province, and to provide clinical insights for ECPR in patients with prolonged low blood flow time in such areas.Methods:A retrospective analysis was conducted on 55 CA patients treated with ECPR at Lishui People's Hospital from June 2020 to June 2024. These patients were compared with 55 CA patients treated with ECPR in urban areas during the same period. The mobile team from our center established ECMO support at county-level hospitals before transferring patients to our hospital's ECMO treatment center for further care. General patient data and blood gas analysis results before and 2 hours after ECPR were collected. Clinical data differences between the two groups were compared, and factors influencing patient prognosis were analyzed using univariate and multivariate Cox regression analyses.Results:The average age of the patients was (52.45 ± 15.66) years, with an average low blood flow time of 151.42 ± 49.31 minutes. The 30-day survival rate was 23.64%, and the rate of good neurological recovery was 18.18%. Although the survival rate and good neurological function rate were lower than those of ECPR patients in urban areas, the differences were not statistically significant ( P > 0.05). Univariate Cox analysis revealed that defibrillation rhythm, low blood flow time, pH before and after ECMO, blood lactate levels before and after ECMO, and hemoglobin significantly influenced the prognosis of ECPR patients ( P < 0.05). Multivariate Cox analysis identified post-ECMO pH ( HR = 0.037) and post-ECMO blood lactate levels ( HR = 1.078) as independent prognostic factors for ECPR patients ( P < 0.05). Conclusions:Despite the longer low blood flow time in CA patients from mountainous areas, the mobile ECPR team can effectively enhance the treatment success rate of these patients through ECPR.

Objective:To investigate the endoscopic combined serological diagnosis strategy for G1 and G2 gastric neuroendocrine neoplasms (G-NENs), and to evaluate the safety, short-term, and long-term efficacy of two endoscopic treatment procedures: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).Methods:This study retrospectively analyzed the clinical data of 100 consecutive patients with G-NENs who were hospitalized at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2011 to October 2023. These patients underwent endoscopic treatment, and propensity score matching (PSM) was used to compare clinicopathological characteristics, as well as short-term and long-term efficacy of lesions in the EMR group and ESD group before and after treatment.Results:Among the 100 patients with G-NENs, the median age was 54 years old. Before surgery, 29 cases underwent endoscopic combined serological examination, and 24 of them (82.2%) had abnormally elevated plasma chromogranin A. The combined diagnostic strategy for autoimmune atrophic gastritis (AIG) achieved a diagnostic accuracy of 100%(22/22). A total of 235 G-NEN lesions were included, with 84 in the ESD group and 151 in the EMR group. The median size of the lesions in the ESD group (5.0 mm) was significantly larger than that in the EMR group (2.0 mm, P＜0.001). Additionally, the ESD group had significantly more lesions with pathological grade G2[23.8%(20/84) vs. 1.3%(2/151), P＜0.001], infiltration depth reaching the submucosal layer [78.6%(66/84) vs. 51.0%(77/151), P＜0.001], and more T2 stage compared to the EMR group[15.5%(13/84) vs. 0.7%(1/151), P＜0.001]. After PSM, 49 pairs of lesions were successfully matched between the two groups. Following PSM, there were no significant differences in the en bloc resection rate [100.0%(49/49) vs. 100.0%(49/49)], complete resection rate [93.9%(46/49) vs. 100.0%(49/49)], and complication rate [0(0/49) vs. 4.1%(2/49)] between the two groups. During the follow-up period, no recurrence or distant metastasis was observed in any of the lesions in both groups. Conclusions:The combination of endoscopy and serology diagnostic strategy has the potential to enhance the accuracy of diagnosing G1 and G2 stage G-NENs and their background mucosa. Endoscopic resection surgery (EMR, ESD) is a proven and safe treatment approach for G1 and G2 stage G-NENs.

Objectives:To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions.Methods:Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set ( n=284) and a validation set ( n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training ( n=243), validation ( n=105), and test ( n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results:We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression ( P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions:Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.

Objective:To investigate the mechanism of Wenjing Decoction in the treatment of hepatic fibrosis through network pharmacological methods, and conducting animal experiments to verify the core targets.Methods:The TCMSP database platform was used to screen the active components and related targets of Wenjing Decoction, and the Uniprot database was used to obtain the target genes corresponding to the active components of Wenjing Decoction. The network diagram of "Chinese materia medica-compound-target" was constructed in Cytoscape 3.7.2, and the GeneCards database was used to search liver fibrosis related targets. String database was used to construct a protein interaction network (PPI) to screen the core components and key targets of liver fibrosis, and GO analysis and KEGG pathway enrichment were performed. Animal experiments were conducted to verify the results of the analysis. 10 mice were selected as the blank group, and the remaining 45 rats were induced with carbon tetrachloride induced liver fibrosis model. After modeling, 40 successfully modeled rats were divided into model group and Wenjing Decoction high, medium-, and low-dosage groups using a random number table method, with 10 rats in each group. Wenjing Decoction high, medium-, and low-dosage groups were orally administered with 1.5×3.18, 3.18, and 0.5×3.18 g/kg Wenjing Decoction, respectively. The blank group was orally administered with equal volume distilled water once a day for 8 consecutive weeks. HE staining was used to observe the histopathological and morphological changes in the liver of rats. The serum GPT and GOT levels of rats were detected using a fully automated biochemical analyzer, and the expressions of TNF, AKT, and IL-6 proteins in rat liver tissue was detected using Western Blot.Results:A total of 188 active components of Wenjing Decoction were obtained, and the active components with higher degree values were β-sitosterol, quercetin, naringenin, etc. 799 liver fibrosis gene targets were collected, and the core target genes of the PPI network were TNF, AKT, IL6, etc. The key anti-hepatic fibrosis related pathways were obtained by GO function and KEGG analysis, including pathway in cancer, TNF, PI3K-Akt and other signalling pathways. Results of animal experiments showed that there were obvious inflammatory infiltration, collagen fibre and pseudo lobe generation in the liver tissue of rats in the model group, and the levels of inflammation and fibrosis in the liver tissue of rats in the Wenjing Decoction high, medium-, and low-dosage groups were improved to different degrees compared with that of the model group; compared with the model group, the levels of serum GPT and GOT decreased ( P<0.05); the protein expressions of TNF, AKT and IL6 in the Wenjing Decoction high, medium-, and low-dosage groups decreased ( P<0.05). Conclusion:Wenjing Decoction may exert anti-liver fibrosis effects by intervening in TNF, AKT, IL6 targets, regulating cancer pathways, TNF, PI3K Akt and other signaling pathways.

Objective:To investigate the endoscopic combined serological diagnosis strategy for G1 and G2 gastric neuroendocrine neoplasms (G-NENs), and to evaluate the safety, short-term, and long-term efficacy of two endoscopic treatment procedures: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).Methods:This study retrospectively analyzed the clinical data of 100 consecutive patients with G-NENs who were hospitalized at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2011 to October 2023. These patients underwent endoscopic treatment, and propensity score matching (PSM) was used to compare clinicopathological characteristics, as well as short-term and long-term efficacy of lesions in the EMR group and ESD group before and after treatment.Results:Among the 100 patients with G-NENs, the median age was 54 years old. Before surgery, 29 cases underwent endoscopic combined serological examination, and 24 of them (82.2%) had abnormally elevated plasma chromogranin A. The combined diagnostic strategy for autoimmune atrophic gastritis (AIG) achieved a diagnostic accuracy of 100%(22/22). A total of 235 G-NEN lesions were included, with 84 in the ESD group and 151 in the EMR group. The median size of the lesions in the ESD group (5.0 mm) was significantly larger than that in the EMR group (2.0 mm, P＜0.001). Additionally, the ESD group had significantly more lesions with pathological grade G2[23.8%(20/84) vs. 1.3%(2/151), P＜0.001], infiltration depth reaching the submucosal layer [78.6%(66/84) vs. 51.0%(77/151), P＜0.001], and more T2 stage compared to the EMR group[15.5%(13/84) vs. 0.7%(1/151), P＜0.001]. After PSM, 49 pairs of lesions were successfully matched between the two groups. Following PSM, there were no significant differences in the en bloc resection rate [100.0%(49/49) vs. 100.0%(49/49)], complete resection rate [93.9%(46/49) vs. 100.0%(49/49)], and complication rate [0(0/49) vs. 4.1%(2/49)] between the two groups. During the follow-up period, no recurrence or distant metastasis was observed in any of the lesions in both groups. Conclusions:The combination of endoscopy and serology diagnostic strategy has the potential to enhance the accuracy of diagnosing G1 and G2 stage G-NENs and their background mucosa. Endoscopic resection surgery (EMR, ESD) is a proven and safe treatment approach for G1 and G2 stage G-NENs.

Objectives:To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions.Methods:Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set ( n=284) and a validation set ( n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training ( n=243), validation ( n=105), and test ( n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results:We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression ( P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions:Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.

Objective:To explore the measurement method and its diagnostic performance based on MRI and CT measurement of vertebral bone density in patients to predict proximal junctional kyphosis after degenerative scoliosis surgery.Methods:Retrospectively included patients who underwent long-segment fixation and fusion surgery at the Department of Orthopedics, West China Hospital of Sichuan University from January 2010 to December 2020 and had complete preoperative whole-spine X-rays, CT, MRI and other imaging examination results, and were followed up on schedule. 68 cases of adult degenerative scoliosis, 16 male, 52 women, aged 66.87±6.65 years (range, 54-80 years). The patients were measured based on preoperative lumbar spine MRI T 1WI bone quality score (vertebral bone quality score, VBQ) and CT-based Hounsfield (HU) value, and the patients were divided into postoperative proximal junction kyphosis group or non-proximal junction kyphosis group based on the results of postoperative imaging examinations. The age, gender, BMI, comorbidities, lumbar spine VBQ score, L 1 CT HU value and various imaging parameters before and after surgery were compared between the two groups of patients, including pelvic incident, lumbar lordosis, sagittal vertical axis, pelvic tilt, sacral slope, pelvic incidence-lumbar lordosis, T 1 pelvic angle, Upper instrumented vertebrae screw angle, etc. The receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic efficacy, sensitivity and specificity of VBQ score, HU value and their combined indicators. Results:Seventeen cases were included in the PJK group and 51 cases in the non-PJK group. The preoperative VBQ and HU values of the PJK group were 3.10±0.43 and 99.76±16.34 respectively, while those of the non-PJK group were 2.62±0.37 and 115.27±13.46 respectively. The differences were statistically significant ( t=3.896, P<0.001; t=4.482, P<0.001). The area under curve (AUC) of VBQ was 0.773 [95% CI(0.633, 0.914)], the sensitivity and specificity are 82.4% and 70.6% respectively, the AUC of HU value was 0.814 [95% CI(0.680, 0.949)], the sensitivity and specificity are 76.5% and 76.5% respectively. The AUC of the two combined indicators was 0.895 [95% CI(0.795, 0.995)], and the sensitivity and specificity were 94.1% and 82.4% respectively. The maximum Youden index and the critical value were respectively, VBQ value 0.530, 2.895, HU value 0.530, 110.0, the combined index 0.765, 0.734. Conclusion:Both VBQ and L 1 HU value can accurately predict proximal junctional kyphosis after degenerative scoliosis surgery. The accuracy of HU value was slightly higher than that of VBQ value. The diagnosis accuracy of the combined index was the highest.

This article reports a case of acute kidney injury (AKI) following near drowning with reduced urine output as the main manifestation. The patient was a 37-year-old middle-aged man. His renal function deteriorated sharply after accidentally falling into the water, and renal pathology showed acute tubular injury. After hemodialysis treatment, urine output increased significantly, and renal function and proteinuria improved significantly. AKI following near drowning lacks typical clinical manifestations and is prone to delayed diagnosis and treatment. The patients with a history of near drowning should be followed up to determine whether they are complicated by AKI.

Objective:To study the mechanism of Herba Hedyotidis against liver fibrosis based on network pharmacology. Methods:Based on TCMSP database and Uniprot database, the effective components and target genes of Herba Hedyotidis were screened. Target genes of liver fibrosis were screened by GeneCards and OMIM database, and the "disease-component-target" network map was constructed by Cytoscape 3.8.2 software. Protein interaction network was constructed by STRING database, and the Cytoscape 3.8.2 software was used to screen the core target out. The core targets were analyzed by gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Experimental verification was performed to the analysis results. A hepatic fibrosis model was established by intraperitioneal imjection of 40% carbon tetrachloride oil solution in rats that were then divided into the model control group and the Herba Hedyotidis group by randomized number table table, with 10 rats in each group. Ten normal rats were used as the normal control group. The Herba Hedyotidis group were injected 2.7 g/kg herb aqueous extract by intragastric administration, once a day, for 4 weeks; and the normal and model control group were given the same volume distilled water for gavage. The serum GPT, GOT, Alb and liver pathologic changes were observed. The serum expressions of IL-6, IL-1β and TGF-β1 were detected by ELISA. The expressions of PI3K, Akt, HIF-1α and VEGF were detected by Western blot. Results:5 effective components and 118 targets of Herba Hedyotidis in the treatment of hepatic fibrosis were obtained. Stigmasterol, β-sitosterol and quercetin were the most effective components with high moderate value. The moderate targets were VEGF, EGFR, HIF-1α and IL-6. The core genes of PPI network were HIF-1α, IL-6, etc. GO enrichment analysis showed that RNA transcription, protein binding and other processes may be affected. KEGG pathway enrichment analysis showed that significant enrichment pathways were cancer pathway, hepatitis B pathway, PI3K/Akt, HIF pathway and so on. Animal experimental results showed that compared with model group, liver histopathology was improved significantly, the content of GPT, GOT, IL-6, IL-1β and TGF-β1 decreased ( P<0.01), the content of Alb increased ( P<0.01), and the protein expressions of PI3K, Akt, HIF-1α and VEGF in liver tissue were down-regulated ( P<0.01). Conclusion:The Herba Hedyotidis exerts functions of anti-hepatic fibrosis through acting on the targets of VEGF, EGFR, HIF-1α and IL-6, regulating the PI3K/Akt, HIF-1 pathways, and has anti-inflammatory, anti-angiogenesis, anti-tumor and other biological functions.