Objective To establish quality evaluation method of Andrographis paniculata standard decoction by UPLC. Methods 21 batches of Andrographis paniculata standard decoctions were prepared according to the standardization method of TCM decoction pieces. The UPLC characteristic chromatograms analysis method was established. With andrographolide as a reference, quantitative analysis of multi-components by single marker （QAMS） was established for new neoandrographolide, 14 deoxyandrographolide and dehydrated andrographolide. The results were compared with the external standard method （ESM） to determine the accuracy of the method. Results Similarity Evaluation System for Chromatographic Fingerprint of TCM （2012 edition） was used to analyze and compare the characteristic chromatograms, and seven common peaks were determined and five were identified including luteolin-7-O-β-D-glucuronide, andrographolide, neoandrographolide, 14-deoxyandrographolide and dehydroandrographolide. The RSDs of content results of each component by QAMS and ESM were all within 3%. Conclusion The determination method was reliable and accurate, which could be used to reflect the intrinsic quality of Andrographis paniculata standard decoction comprehensively and provide the basis for the quality evaluation of Andrographis paniculata formula granules and other preparations.

OBJECTIVE: To evaluate the prognosis of septic right ventricular dysfunction (SRVD) based on bedside ultrasound and explore its risk factors. METHODS: A prospective observational study was conducted involving septic and septic shock patients admitted to the intensive care unit (ICU) of the General Hospital of Ningxia Medical University from February 2021 to January 2022. Tricuspid annular plane systolic excursion (TAPSE) was measured by M-mode ultrasound within 24 hours after ICU admission. According to the results of TAPSE, the subjects were divided into SRVD group (TAPSE < 16 mm) and non-SRVD group (TAPSE ≥ 16 mm). The gender, age, occurrence of septic shock, underlying diseases, source of patients, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, maximal body temperature within 24 hours after ICU admission, location and number of infections, duration of mechanical ventilation, and 28-day mortality were collected. Hemodynamic parameters, organ function indexes, oxygen therapy parameters and arterial blood gas analysis indexes were recorded within 24 hours after ICU admission. The differences of the above indexes between the two groups were compared. Binary multivariate Logistic regression analysis was used to screen out the independent risk factors for SRVD, and a nomogram of SRVD risk factors was drawn. RESULTS: 116 patients with sepsis and septic shock were enrolled, of which 24 (20.7%) had SRVD and 92 (79.3%) had no SRVD. Compared with the non-SRVD group, the patients in the SRVD group had higher emergency transfer and infection site ≥ 2 ratio, APACHE II score, SOFA score, higher cardiac troponin I (cTnI), myoglobin (Mb), MB isoenzyme of creatine kinase (CK-MB), N-terminal pro-brain natriuretic peptide (NT-proBNP), serum creatinine (SCr), arterial blood lactic acid (Lac) and lower left ventricular ejection fraction (LVEF), platelet count (PLT) within 24 hours after ICU admission, and higher proportion of norepinephrine application and continuous renal replacement therapy (CRRT). Binary multivariate Logistic regression analysis showed that LVEF [odds ratio (OR) = 0.918, 95% confidence interval (95%CI) was 0.851-0.991, P = 0.028], PLT (OR = 0.990, 95%CI was 0.981-0.999, P = 0.035), SCr (OR = 1.008, 95%CI was 1.001-1.016, P = 0.025), and the usage of norepinephrine (OR = 15.198, 95%CI was 1.541-149.907, P = 0.020) were independent risk factors for SRVD in patients with sepsis and septic shock. Based on the above four independent risk factors, a nomogram of SRVD risk factors was drawn. The results showed that the score was 64 when LVEF was 0.50, 18 when SCr was 100 μmol/L, 85 when PLT was 100×10⁹/L, and 39 when norepinephrine was used. When the total score reached 253, the risk of SRVD was 88%. Compared with non-SRVD group, the duration of mechanical ventilation in SRVD group was slightly longer [hours: 80.0 (28.5, 170.0) vs. 47.0 (10.0, 135.0), P > 0.05], and the 28-day mortality was significantly higher [41.7% (10/24) vs. 21.7% (20/92), P < 0.05]. CONCLUSIONS Patients with sepsis may have right ventricular dysfunction, impaired renal function and increased mortality in the early stage. The decrease in LVEF and PLT, the increase in SCr and the application of norepinephrine are independent risk factors for SRVD in patients with sepsis.
Humans ; Prognosis ; Ventricular Dysfunction, Right/diagnostic imaging* ; Risk Factors ; Prospective Studies ; Intensive Care Units ; Shock, Septic ; Male ; Ultrasonography ; Female ; Sepsis/complications* ; Middle Aged ; Point-of-Care Systems ; Aged ; Logistic Models ; APACHE

Microglia are specialized immune cells in the brain, primarily responsible for clearing debris and responding to inflammation. One of the pathological features of Alzheimer's disease (AD) is the extensive activation of immune system in the brain, and the dynamic changes and dysfunction of microglia could become key factors for AD progression. This article reviews the research progress of regulated effect of microglial on AD pathology, and summarizes its potential value in AD treatment, in order to provide theoretical basis for exploring new therapeutic strategies and intervention targets for AD.

Objective:To investigate the expression of miR-1243 and long non-coding RNA (lncRNA) HULC in papillary thyroid carcinoma (PTC) tissues, and their relationships with clinicopathological features and postoperative prognosis of patients.Methods:A total of 116 PTC patients treated in the Second Hospital of Nanjing from August 2021 to August 2023 were selected. The expression levels of miR-1243 and lncRNA HULC in PTC tissues and adjacent normal tissues were detected by real-time fluorescent quantitative polymerase chain reaction (PCR). The differences in the expression levels of miR-1243 and lncRNA HULC between PTC tissues and adjacent normal tissues, as well as among PTC tissues with different clinical features and different prognoses, were analyzed. Receiver operating characteristic (ROC) curve was used to analyze the value of miR-1243 in predicting postoperative recurrence of PTC patients.Results:The relative expression level of miR-1243 in PTC tissues was significantly lower than that in adjacent normal tissues ( P<0.05), while the relative expression level of lncRNA HULC was higher than that in adjacent normal tissues ( P<0.05). The relative expression level of lncRNA HULC in PTC tissues of patients with tumor diameter ≥2 cm, tumor node metastasis (TNM) stage Ⅲ-Ⅳ, and lymph node metastasis was higher than that in patients with tumor diameter <2 cm, TNM stage Ⅰ-Ⅱ, and no lymph node metastasis (all P<0.05). The relative expression level of miR-1243 in PTC tissues of patients with TNM stage Ⅲ-Ⅳ and lymph node metastasis was lower than that in patients with TNM stage Ⅰ-Ⅱ and no lymph node metastasis (all P<0.05). There was no significant correlation between the expression of miR-1243 and lncRNA HULC in PTC tissues ( r=0.129, P=0.167). All patients were followed up for 12 months, and 20 patients had postoperative recurrence. The proportion of TNM stage Ⅲ-Ⅳ in recurrent patients was 70.00%(14/20), which was higher than that in non-recurrent patients [29.17%(28/96), P<0.05], and the relative expression level of miR-1243 was lower than that in non-recurrent patients ( P<0.05). There was no significant difference in the relative expression level of lncRNA HULC between recurrent and non-recurrent patients ( P>0.05). The area under the ROC curve of miR-1243 relative expression level in predicting postoperative recurrence of PTC patients was 0.809(95% CI: 0.711-0.907, P<0.05), with a cut-off value of 1.17, sensitivity of 65.00% and specificity of 87.50%. Conclusions:The expression of miR-1243 is down-regulated and lncRNA HULC is up-regulated in PTC tissues, and both are related to clinicopathological features such as lymph node metastasis and TNM stage. Among them, the expression of miR-1243 is related to postoperative recurrence.

Objective To investigate the application value of late gadolinium enhancement(LEG)at cardiac MRI in predicting ventricular arrhythmia(VA)events in patients after implantation of ICD.Methods A retrospective analysis was performed on 16 patients at high risk of sudden cardi-ac death after ICD implantation and LEG examination in the First and the Sixth Medical Centers of Chinese PLA General Hospital from June 2020 to March 2024.According the occurrence of VA events receiving appropriate ICD therapy during the follow-up period,they were divided into post-operative VA group(7 cases)and non-VA group(9 cases).The correlation of clinical baseline fea-tures and LEG features with VA events was analyzed.Results The ratios of transmural enhance-ment and myocardial medium enhancement were obviously higher in the VA group than the non-VA group(71.4％vs 11.1％,P=0.035;85.7％vs 22.2％,P=0.041).Multivariate logistic regres-sionanalysis showed that transmural enhancement(OR=5.000,95％CI:0.150-166.589,P=0.368)and myocardial medium enhancement(OR=7.000,95％CI:0.217-226.005,P=0.272)were not independent factors influencing VA occurrence.ROC curve analysis indicated that the combined prediction of transmural enhancement and myocardial media enhancement and the pre-diction of transmural enhancement alone had better diagnostic efficacy(P＜0.05).Conclusion LEG has clinical value in predicting postoperative VA events in patients after ICD implantation.

Kirsten rat sarcoma viral oncogene homolog(KRAS)protein inhibitors are a promising class of thera-peutics,but research on molecules that effectively penetrate the blood-brain barrier(BBB)remains limited,which is crucial for treating central nervous system(CNS)malignancies.Although molecular generation models have recently advanced drug discovery,they often overlook the complexity of bio-logical and chemical factors,leaving room for improvement.In this study,we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug effi-cacy and drug absorption properties.Our approach utilizes a variational autoencoder(VAE)generative model integrated with reinforcement learning for multi-objective optimization.This method specifically aims to enhance BBB permeability(BBBp)while maintaining high-affinity substructures of KRAS in-hibitors.To support this,we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models.Additionally,we introduce two novel metrics,the knowledge-integrated reproduction score(KIRS)and the composite diversity score(CDS),to assess structural performance and biological relevance.Retrospective validation with KRAS inhibitors,AMG510 and MRTX849,demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications.This study provides a robust framework for accelerating the structural enhancement of lead compounds,advancing the drug development process across diverse targets.

Objective To investigate the expression of microRNA-873-5p(miR-873-5p)and C-X-C motif chemokine ligand 16(CXCL16)in thyroid cancer tissue and their relationship with pathological parameters and prognosis.Methods A total of 125 patients with thyroid cancer who underwent surgery at Nanjing Sec-ond Hospital from January 2018 to June 2019 were selected as the research subjects.Some cancer tissues and corresponding adjacent tissues of the patients were collected,and the expressions of miR-873-5p and CXCL16 mRNA were detected by real-time fluorescence quantitative polymerase chain reaction.The binding sites of miR-873-5p and CXCL16 were predicted through the online database.Pearson correlation was used to analyze the correlation between miR-873-5p and CXCL16 mRNA expression,and the correlation between miR-873-5p,CXCL16 mRNA expression and pathological parameters.According to the median expression of miR-873-5p and CXCL16 mRNA in thyroid cancer tissues,they were classified as high expression and low expression.The survival curves of patients with high and low expression of miR-873-5p and CXCL16 mRNA were plotted by the Kaplan-Meier method.Taking the survival status of patients with thyroid cancer as the dependent varia-ble,Cox regression was used to determine the relationship between the expressions of miR-873-5p and CX-CL16 mRNA and the death of patients with thyroid cancer.Results The expressions of miR-873-5p and CX-CL16 mRNA in thyroid cancer tissues were 0.83±0.12 and 1.54±0.25,respectively,and those in adjacent tissues were 1.13±0.15 and 0.98±0.13,respectively,the differences were statistically significant(t=-18.160,21.089).P＜0.001).Pearson correlation analysis showed that the expression of miR-873-5p and CXCL16 mRNA in thyroid cancer tissues was negatively correlated(r=-0.722,P＜0.001).The expression of miR-873-5p in thyroid cancer tissues was negatively correlated with pathological type,TNM stage and lymph node metastasis(r=-0.510,—0.262,-0.315,P＜0.05).The expression of CXCL16 mRNA was positively correlated with pathological type,TNM stage and lymph node metastasis(r=0.593,0.275,0.314,P＜0.05).The Kaplan-Meier survival curve showed that the 5-year overall survival rate of patients with high expression of miR-873-5p was higher than that of patients with low expression of miR-873-5p.The 5-year o-verall survival rate of patients with high expression of CXCL16 mRNA was lower than that of patients with low expression of CXCL16 mRNA,and the difference was statistically significant(x2=11.328,10.514,all P=0.001).miR-873-5p≥0.84 was an independent protective factor for death in patients with thyroid cancer,and CXCL16 mRNA≥1.55 was an independent risk factor for death in patients with thyroid cancer(P＜0.05).Conclusion The expressions of miR-873-5p and CXCL16 mRNA in thyroid cancer tissues are related to patho-logical parameters and prognosis,and may become prognostic markers for patients with thyroid cancer.

Objective:To investigate the feasibility and clinical effects of ultra early enteral nutrition (≤24 h) in critically ill children supported by extracorporeal membrane oxygenation (ECMO).Methods:A retrospective cohort study was conducted. Clinical data of 43 critically ill children who received ECMO support in the pediatric intensive care unit (PICU) of Shanghai Children′s Hospital from January 2016 to December 2023 were collected, including general information, nutritional support modalities, and enteral nutrition tolerance. Based on the timing of enteral nutrition initiation, patients were divided into the within 24 h enteral nutrition group and the after 24 h enteral nutrition group. Nutritive indicators, nutritional intake, duration of ECMO support, duration of mechanical ventilation duration, and mortality rates were compared between the 2 groups using the two independent sample t test, Mann-Whitney U test, χ2 test and Fisher′s exact test. Results:Among the 43 children, 25 were male and 18 were female, with an age of 47 (18, 97) months. There were no statistically significant differences between the within 24 h enteral nutrition group (21 cases) and the after 24 h enteral nutrition group (22 cases) in terms of age, body mass index Z score, total protein, albumin, hemoglobin levels before ECMO support, duration of ECMO support, duration of mechanical ventilation, length of PICU stay, number of enteral nutrition intolerance events, number of enteral nutrition interruption, or mortality rate (all P>0.05). The protein intake adequacy rate during ECMO support was higher in the within 24 h enteral nutrition group than in the after 24 h enteral nutrition group (0 (0, 21%) vs. 0 (0, 0), U=175.00, P<0.05). Conclusions:Ultra early enteral nutrition is safe for children supported by ECMO. Initiating enteral nutrition within 24 h can increase the proportion of days with adequate protein intake in ECMO children without increasing the occurance of enteral nutrition intolerance or interruptions.

OBJECTIVE: To investigate the effectiveness of tibial transverse transport (TTT) in treating Wagner grade 3-4 type 2 diabetic foot ulcers and analyze dynamic changes in immunoglobulin levels. METHODS: The clinical data of 68 patients with Wagner grade 3-4 type 2 diabetic foot ulcers treated with TTT between May 2022 and September 2023 was retrospectively analyzed. The cohort included 49 males and 19 females, aged 44-91 years (mean, 67.3 years), with 40 Wagner grade 3 and 28 grade 4 ulcers. The duration of type 2 diabetes ranged from 5 to 23 years, with an average of 10 years. The number of wound healing cases, healing time, amputation cases, death cases, and complications were observed and recorded. Serum samples were collected at 6 key time points [1 day before TTT and 3 days, 7 days (the first day of upward transverse transfer), 14 days (the first day of downward transverse transfer), 21 days (the first day after the end of transfer), 36 days (the first day after the removal of the transfer device)], and the serum immunoglobulin levels were detected by flow cytometry including immunoglobulin G (IgG), IgA, IgM, IgE, complement C3 (C3), C4, immunoglobulin light chain κ (KAP), immunoglobulin light chain λ (LAM). RESULTS: All the 68 patients were followed up 6 months. Postoperative pin tract infection occurred in 3 cases and incision infection in 2 cases. Amputation occurred in 5 patients (7.4%) at 59-103 days after operation, and 8 patients (11.8%) died at 49-77 days after operation; the wounds of the remaining 55 patients (80.9%) healed in 48-135 days, with an average of 80 days. There was no recurrence of ulcer, peri-osteotomy fracture, or local skin necrosis during follow-up. The serum immunoglobulin levels of 55 patients with wound healing showed that the levels of IgG and IgM decreased significantly on the 3rd and 7th day after operation compared with those before operation ( P<0.05), and gradually returned to the levels before operation after 14 days, and reached the peak on the 36th day. IgA levels continued to decrease with time, and there were significant differences at all time points when compared with those before operation ( P<0.05). The level of IgE significantly decreased at 21 days after operation compared with that before operation ( P<0.05), while it was higher at other time points than that before operation, but the difference was not significant ( P>0.05). The level of C3 showed a clear treatment-related increase, which was significantly higher on the 7th, 14th, and 21st days after operation than that before operation ( P<0.05), and the peak appeared on the 14th day. The change trend of C4 level was basically synchronous with that of C3, but the amplitude was smaller, and the difference was significant at 7 and 14 days after operation compared with that before operation ( P<0.05). There was no significant difference in KAP/LAM between different time points before and after operation ( P>0.05). CONCLUSION TTT can accelerate wound healing, effectively treat diabetic foot ulcer, and reduce amputation rate, and has definite effectiveness. The potential mechanisms of TTT in the treatment of diabetic foot ulcers include the dynamic regulation of IgG, IgA, IgM, and IgE levels to balance the process of inflammation and repair, and the periodic increase of C3 and C4 levels may promote tissue cleaning, angiogenesis, and anti-infection defense.
Humans ; Male ; Female ; Middle Aged ; Aged ; Diabetic Foot/immunology* ; Wound Healing ; Adult ; Retrospective Studies ; Aged, 80 and over ; Treatment Outcome ; Tibia/transplantation* ; Diabetes Mellitus, Type 2/complications* ; Amputation, Surgical ; Immunoglobulins/blood* ; Immunoglobulin G/blood*

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent