ObjectiveTo explore the mechanism of action of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata （CSFZ） in the treatment of acute-on-chronic liver failure （ACLF） through network pharmacology， molecular docking， and animal experiments. MethodsNetwork pharmacology was used to identify potential targets and related signaling pathways for the treatment of ACLF with CSFZ. Molecular docking was used to examine the binding activity of the core components with corresponding key targets. An ACLF rat model was established by subcutaneous and tail vein injections of bovine serum albumin combined with lipopolysaccharide （LPS） + D-galactosamine （D-GalN） intraperitoneal injection. A normal control group （NC）， a model group， a CSFZ group （CSFZ， 5.85 g·kg^-1）， and a hepatocyte growth-promoting granule group （HGFG， 4.05 g·kg^-1） were set up in this study. Pathological changes in rat liver tissue were observed using hematoxylin and eosin （HE） and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of interleukin-6 （IL-6）， B-cell lymphoma-2 （Bcl-2）， Caspase-3， and albumin （ALB）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to measure the mRNA and protein expression levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， phosphorylated PI3K （p-PI3K）， and phosphorylated Akt （p-Akt）. ResultsNetwork pharmacology screening identified 49 active ingredients of CSFZ， 103 action targets， and 3 317 targets related to ACLF. Among these， 74 targets overlapped with CSFZ drug targets. Key nodes in the protein-protein interaction （PPI） network included Akt1， tumor necrosis factor （TNF）， IL-6， Bcl-2， and Caspase-3. Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis identified multiple signaling pathways， with the PI3K/Akt signaling pathway being the most frequent. Molecular docking showed that the core components of the drug exhibited good binding activity with the corresponding key targets. Animal experiments confirmed that CSFZ significantly improved liver tissue pathological damage in ACLF rats， reduced the release of inflammatory factors and liver cell apoptosis， and upregulated the expression levels of the PI3K/Akt signaling pathway. ConclusionThrough network pharmacology， molecular docking， and in vivo experiments， this study confirms the effect of CSFZ in reducing liver cell inflammatory damage and inhibiting liver cell apoptosis. The specific mechanism may be related to its involvement in regulating the PI3K/Akt signaling pathway.

To investigate the clinical features and peripheral blood immune cell subsets ofelderly (≥60 years old) onset rheumatoid arthritis (EORA) patients.

[Objective] To investigate the functional differences and potential effects of chromatin spatial structure in patients with normal karyotype and complex karyotype multiple myeloma. [Methods] High-throughput chromosome conformational capture (Hi-C) analysis was performed on plasma cells of 1 case with 1q21 complex karyotype and 1 case with normal karyotype multiple myeloma, and the differences in three-dimensional genome structure between the two patients were analyzed, and the transcriptome characteristics of plasma cells were combined to investigate the differential features through gene functional enrichment. [Results] A/B switch occurred in 36% of the chromatin compartments in two cases, and 1 041 genes in patient with complex karyotype had B/A switch. About 3 500 topological association domains (TADs) were identified in each sample, and there was no significant difference. The number of loops identified in complex karyotype sample was 1 069, which was 1/6 of the normal sample, and there were significant differences in the number of three different types of loops, which to some extent reflected the loss of genome stability. Transcriptome analysis showed significant differences in expression profiles between the two patients, and a total of 6 150 differentially expressed genes (3 303 up-regulated genes and 2 847 down-regulated genes) were identified. [Conclusion] Compared with patient with normal karyotype, patient with 1q21 complex karyotype multiple myeloma exhibit significant changes in the spatial structure of plasma cell chromatin at different levels, which leads to changes in gene expression and activation of pathways related to cancer progression.

Objective:To analyze clinical characteristics of acromegaly patients who have discordant growth hormone(GH) or insulin-like growth factor-1(IGF-1) levels and evaluate impact of different GH cut-offs on discordance rate.Methods:A retrospective analysis was conducted on data from 66 acromegaly patients treated at Nanjing Drum Tower Hospital from November 2017 to March 2023. Patients were categorized based on the nadir GH(GHn) and IGF-1 levels at the last follow-up into four groups: controlled, high GH, high IGF-1, and active. Clinical and metabolic parameters were compared across these groups, and impact of different GHn and fasting growth hormone(GHf) cut-offs on discordance rate was evaluated.Results:No statistically significant differences were observed among groups in age, duration of follow-up, imaging characteristics(all P>0.05). High IGF-1 group had higher fasting insulin and homeostasis model assessment for β cell function compared to controlled and high GH group(all P<0.05), while these parameters did not differ between high GH and controlled group. High IGF-1 group had higher carboxy-terminal cross-linked telopeptide of type 1 collagen, osteocalcin and procollagen type 1 N-terminal propeptide compared to controlled and high GH group, but differences were not statistically significant(all P>0.05). These parameters also did not differ between high GH and controlled group. Discordance rate was not significantly different when GHn cut-offs was 1.0 μg/L or 0.4 μg/L(30.3% vs 21.3%, P=0.146). Compared to 2.5 μg/L, discordance rate was lower when GHf cut-off was 1.0 μg/L(39.4% vs 24.3%, P=0.041). Conclusion:The discordance rate in treated acromegaly patients during follow-up is approximately 30%. Different GH measurement timings and cut-offs significantly impact discordance rate. Patients with normal GH and elevated IGF-1 levels are at potential risk of active disease, and require closer follow-up. This study provides a valuable reference for treatment of patients with discordant GH and IGF-1 levels.

Objective:To evaluate the diagnostic value of 1, 3-β-D glucan (BDG), mannan IgM antibody (Mn-IgM) and mannan IgG antibody (Mn-IgG) in invasive candidiasis and to compare the differences in the diagnostic capability of serological markers used alone or in combination.Methods:Serum samples of 126 patients with invasive candidiasis and 104 healthy people who took physical examination during the same period were collected. BDG was detected by dynamic chromogenic method, and Mn-IgM and Mn-IgG were detected by ELISA. The sensitivity, specificity, positive predictive value, negative predictive value, Youden index, coincidence rate and Kappa value of the three serological markers used alone or in combination in the diagnosis of invasive candidiasis were analyzed and compared. The receiver operating characteristic (ROC) curves were drawn and the areas under the curves (AUCs) were calculated.Results:The levels of BDG, Mn-IgM and Mn-IgG in patients with invasive candidiasis were significantly higher than those in healthy people ( P<0.01). The sensitivity, specificity, Kappa value and AUC of BDG were 48.41%, 92.31%, 0.389 and 0.842. The sensitivity, specificity, Kappa value and AUC of Mn-IgM were 64.29%, 91.35%, 0.540 and 0.829. The sensitivity, specificity, Kappa value and AUC of Mn-IgG were 27.78%, 95.19%, 0.214 and 0.737. The sensitivity, specificity, Kappa value and AUC of BDG+ Mn-IgM were 76.19%, 88.46%, 0.637 and 0.921. The sensitivity, specificity, Kappa value and AUC of BDG+ Mn-IgG were 59.52%, 91.35%, 0.491 and 0.856. The sensitivity, specificity, Kappa value and AUC of Mn-IgM+ Mn-IgG were 69.84%, 90.38%, 0.588 and 0.891. The sensitivity, specificity, Kappa value and AUC of BDG+ Mn-IgM+ Mn-IgG were 80.16%, 88.46%, 0.679 and 0.922. Conclusions:The sensitivity of Mn-IgM was higher than that of BDG and Mn-IgG in the diagnosis of invasive candidiasis. When the serological biomarkers were used in combination, BDG+ Mn-IgM and BDG+ Mn-IgM+ Mn-IgG had relatively high Kappa value and AUC, showing high accuracy. The clinical diagnostic value of multiple serological biomarkers used in combination was significantly higher than that of any serological biomarkers used alone. Early combined detection and continuous monitoring of multiple serological biomarkers in patients with high risk of invasive candidiasis could be used clinically to adjust antifungal treatment strategies timely.

Objective: To investigate the effect of glycogen synthase kinase 3 β ( GSK-3 β) and its correlation with microtubule-associated protein 2 (MAP2) during cerebral hypoxia / reoxygenation (H / R) in zebrafish． Methods: The cerebral hypoxia / reoxygenation model of zebrafish was established．Healthy adult zebrafishes of the same size were divided into control group ( Control) ，hypoxia / reoxygenation group ( H / R) and hypoxia / reoxygenation + GSK-3 β inhibitor group (H / R + TDZD-8) for experiment．The brain tissues of zebrafish in each group were selected to determine the mRNA expressions of hypoxia inducible factor 1 αa and 1 αb (HiF-1αa and HIF-1 αb) at different reoxygenation time points by qRT-PCR , and the protein expression levels of HIF-1α , GSK-3 β , p-GSK-3 β (Ser 9) and MAP2 were detected by Western blot，TTC staining and TUNEL staining were used to detect cerebral infarction area and cell apoptosis ，and immunofluorescence was used to detect the distribution and expression of MAP2 in brain. Results: Compared with Control group，the mRNA levels of Hif-1αa and Hif-1 αb(P＜0. 01) and protein expression of Hif-1 α(P＜0. 01) increased in H / R group，the area of cerebral infarction (P ＜0. 01) and apoptotic cells(P ＜0. 01) increased，p-GSK-3 β ( Ser 9) / GSK-3 β ratio，MAP2 protein expression (P ＜0. 05) and immunofluorescence expression of MAP2 (P ＜0. 01 ) reduced ; Furthermore，TDZD-8 pretreatment could relieve the brain injury of H / R zebrafish by decreasing the infarct size and cell apoptosis，improving the ratio of p-GSK-3 β ( Ser 9 ) / GSK-3 β , and increasing the expression of MAP2． Conclusion Hypoxia / reoxygenation can cause brain neuron damage in zebrafish，and its mechanism may be related to inhibition of GSK-3 β phosphorylation and MAP2 expression．GSK-3 β specific inhibitor TDZD-8 can reverse the damage of brain neurons caused by hypoxia / reoxygenation by promoting the expression of P-GSK-3 β (Ser 9) and reducing MAP2 degradation.

Objective:To identify the clinical and pathological characteristics of adrenocortical carcinoma(ACC) with hypercortisolism and analyze the prognostic factors.Methods:Clinical data of ACC patients between January 2003 and December 2022 from Nanjing Drum Tower Hospital were collected retrospectively. Clinical and pathological characteristics were compared between ACC patients with hypercortisolism and nonfunctional ACCs. Kaplan-Meier method was used for survival analyses and Cox regression models were performed to analyze prognostic factors for ACC patients.Results:In 61 cases of ACC patients, the average age was (49.33±16.32) years. After a median follow-up of 77 months(95% CI 47.49-106.51 months), median overall survival and progression-free survival were 50 months(95% CI 20.44-79.56 months) and 29 months(95% CI 22.87-35.13 months), respectively. Among 36 patients with complete endocrinologic evaluations, 19(52.77%) were diagnosed with hypercortisolism. Compared with nonfunctional ACC, patients with hypercortisolism had more hypokalemia(42.11% vs 6.25%, P=0.022), capsular invasion(68.42% vs 25.00%, P=0.018), and distant metastases(73.68% vs 25.00%, P=0.007). Median overall survival and progression-free survival were significantly shorter than nonfunctional ACC(overall survival: 39 months vs 67 months, P=0.009; progression-free survival: 30 months vs 51 months, P=0.040) as well. Multivariate Cox regression analyses indicated that Ki67 index( HR=1.078, P=0.024) was an independent risk factor for overall survival. Hypercortisolism( HR=71.112, P=0.006), Ki67 index( HR=1.345, P=0.003), adjuvant therapy( HR=176.652, P=0.012), and operation( HR=0.020, P=0.003), were associated with disease progression. Conclusion:ACC accompanied by hypercortisolism is more prone to invasion and distant metastasis, resulting in shorter survival. Hypercortisolism is an independent prognostic factor for ACC patients.

Objective:To explore the pathological characteristics of adrenal masses based on various tumor diameter and unenhanced computed tomography(CT) attenuation value, and evaluate the value of the two parameters in the assessment of the benign and malignant nature of adrenal masses.Methods:The data of 1 367 patients who underwent adrenalectomy in Nanjing Drum Tower Hospital from January 2017 to October 2022 were retrospectively collected. The adrenal masses were divided into four groups according to tumor diameter and unenhanced CT attenuation value, and the clinical and histopathological characteristics of the four groups were compared respectively. Logistic regression was used to analyze the correlation between tumor diameter, non-contrast CT attenuation value and malignant adrenal masses, and receiver operating characteristic(ROC) curve was used to assess the diagnostic value of both in benign and malignant adrenal masses.Results:The proportion of adrenocortical carcinoma and other malignant tumors increased with the rise of tumor diameter or unenhanced CT attenuation value. After adjusting for age and gender, tumor diameter( OR=1.624, 95% CI 1.464-1.803, P<0.001) and unenhanced CT attenuation value( OR=1.108, 95% CI 1.079-1.138, P<0.001) were predictors of malignant adrenal masses. The tumor diameter and unenhanced CT attenuation value in diagnosing malignant adrenal masses had area under the ROC curve(AUC) of 0.838 and 0.892, respectively. With the optimal cut-off values of >3.4 cm and >30 HU, the sensitivity was 75.5% and 83.7%, and the specificity was 80.5% and 84.4%, respectively. The combination of tumor diameter >3.4 cm and unenhanced CT attenuation value >20 HU had an AUC of 0.927, with a sensitivity of 71.4% and a specificity of 90.1% in diagnosing malignant adrenal masses. Conclusions:Tumor diameter and unenhanced CT attenuation value has important significance in the differential diagnosis of benign and malignant adrenal masses. A combination of tumor diameter (>3.4 cm) and unenhanced CT attenuation value (>20 HU) demonstrates best diagnostic efficiency. Clinical application of this combined index can effectively diagnose malignant adrenal masses while avoiding unnecessary investigations or surgery.

Objective:To explore the safety and effectiveness of the application of sevoflurane inhalation sedation and analgesia during dressing changes in children with extensive burns.Methods:A prospective randomized controlled research was conducted. From March 2020 to January 2023, 216 children with extensive burns who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of Kunming Children's Hospital. According to the random number table, the children were divided into sevoflurane group and ibuprofen group, with 103 cases left in sevoflurane group (67 males and 36 females, aged 1 (1, 2) years), and 98 cases left in ibuprofen group (67 males and 31 females, aged 1 (1, 2) years) after the exclusion of several dropped-out children. Children in sevoflurane group received sevoflurane inhalation for sedation and analgesia during dressing changes, while those in ibuprofen group took oral ibuprofen for analgesia before dressing changes. The heart rate, mean arterial pressure (MAP), and percutaneous arterial oxygen saturation (SpO 2) of the children were monitored and recorded at 30 minutes before the start of dressing changes, immediately after debridement, and at 30 minutes after the completion of dressing changes. The face, legs, activity, cry, and consolability scale and Ramsay sedation scale were used to evaluate the pain intensity and degree of sedation, respectively, at 30 minutes before the start of dressing changes, immediately after debridement, and at 30 minutes after the completion of dressing changes. The duration of dressing changes and the total number of dressing changes during hospitalization were recorded. The Houston Pain Outcome Instrument questionnaire was used to assess the satisfaction of the dressing-changing surgeons and a family member of the child with the analgesic effects during the process of dressing change when the children were discharged from the hospital. The occurrence of adverse reactions such as respiratory depression and hypoxemia that occurred during the process of dressing change were monitored and recorded. Data were statistically analyzed with independent sample t test, analysis of variance for repeated measurement, Wilcoxon rank-sum test, chi-square test, and Fisher's exact probability test. Results:At 30 minutes before the start of dressing changes and 30 minutes after the completion of dressing changes, there were no statistically significant differences in heart rate, MAP, and SpO 2 between children in the two groups ( P>0.05). Immediately after debridement, compared with those in ibuprofen group, the heart rate and MAP of children in sevoflurane group were significantly decreased (with t values of 8.10 and 4.37, respectively, P<0.05), while the SpO 2 was significantly increased ( t=21.77, P<0.05). At 30 minutes before the start of dressing changes and 30 minutes after the completion of dressing changes, there were no statistically significant differences in the score of pain intensity and score of sedation degree between children in the two groups ( P>0.05). Immediately after debridement, compared with that in ibuprofen group, the score of pain intensity of children in sevoflurane group was significantly decreased, while the score of sedation degree was significantly increased (with t values of 42.87 and 72.45, respectively, P<0.05). The duration of dressing changes and the total number of dressing changes during hospitalization of patients in sevoflurane group were (18±3) min and (4.1±1.0) times, respectively, which were both significantly shorter than (26±7) min and less than (6.6±1.4) times in ibuprofen group, respectively (with t values of -4.44 and 14.17, respectively, P<0.05). Upon discharge, the satisfaction scores of dressing-changing surgeons and the family members of children with the analgesic effects during the process of dressing change in sevoflurane group were significantly higher than those in ibuprofen group (with t values of 44.23 and 36.55, respectively, P<0.05). There were no statistically significant differences in the incidence of respiratory depression, hypoxemia, hypotension, coughing, nausea, and vomiting during the process of dressing change between children in the two groups ( P>0.05). Conclusions:Application of sevoflurane inhalation during dressing changes in children with extensive burns can safely and effectively control pain and sedation, shorten the time for dressing change, with fewer adverse reactions. This method can be used for routine dressing change in pediatric burn wards.

Objective:To explore the value of adrenocorticotrophic hormone (ACTH) stimulation in adrenal vein sampling (AVS) with its effect on the sampling success rate and lateralization determination.Methods:The clinical data of 54 patients with primary aldosteronism (PA) who underwent AVS in Nanjing Drum Tower Hospital from July 2018 to June 2020 were collected retrospectively. Blood samples from bilateral adrenal veins were collected simultaneously at baseline and after ACTH stimulation. The selectivity index (SI), lateralization index (LI), and relative aldosterone secretion index (RASI) were examined.Results:The concentration of serum cortisol level in left and right adrenal vein and peripheral vein increased significantly after ACTH stimulation ( P<0.001). SI of left adrenal vein increased from 18.00 (2.29, 20.29) to 34.76 (12.10, 46.86) , and the SI of right adrenal vein increased from 26.61(5.24, 31.85) to 28.40 (27.65, 56.05, P<0.001). The bilateral vein sampling success rate increased from 80%(43/54) to 93%(50/54). LI decreased from 2.85(1.78, 6.20) at baseline to 2.45(1.40, 6.10) after ACTH stimulation without significant difference( P>0.05). Eleven patients who identified unilateral secretion at baseline demonstrated bilateral after ACTH stimulation, and the RASI of these patients decreased from 0.50 (0.38, 1.25 ) to 0.37 (0.22, 0.84, P=0.019). Conclusion:ACTH stimulation significantly increased SI and the AVS success rate in patients with PA: ACTH stimulation decreased the relative aldosterone secretion in the dominant side of some patients with aldosterone producing adenoma, thus reduced the proportion of identified unilateral PA.