ObjectiveTo establish an ultra-performance liquid fingerprint and multi-components determination method for Naomaili granules. To evaluate the quality of different batches by chemometrics， and the anti-neuroinflammatory effects of water extract and main components of Naomaili granules were tested in vitro. MethodsThe similarity and common peaks of 27 batches of Naomaili granules were evaluated by using Ultra performance liquid chromatography （UPLC） fingerprint detection. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） technology was used to determine the content of the index components in Naomaili granules and to evaluate the quality of different batches of Naomaili granules by chemometrics. LPS-induced BV-2 cell inflammation model was used to investigate the anti-neuroinflammatory effects of the water extract and main components of Naomaili granules. ResultsThe similarity of fingerprints of 27 batches of samples was > 0.90. A total of 32 common peaks were calibrated， and 23 of them were identified and assigned. In 27 batches of Naomaili granules， the mass fractions of 14 components that were stachydrine hydrochloride， leonurine hydrochloride， calycosin-7-O-glucoside， calycosin，tanshinoneⅠ， cryptotanshinone， tanshinoneⅡ_A， ginsenoside Rb₁， notoginsenoside R₁， ginsenoside Rg₁， paeoniflorin， albiflorin， lactiflorin， and salvianolic acid B were found to be 2.902-3.498， 0.233-0.343， 0.111-0.301， 0.07-0.152， 0.136-0.228， 0.195-0.390， 0.324-0.482， 1.056-1.435， 0.271-0.397， 1.318-1.649， 3.038-4.059， 2.263-3.455， 0.152-0.232， 2.931-3.991 mg∙g^-1， respectively. Multivariate statistical analysis showed that paeoniflorin， ginsenoside Rg₁， ginsenoside Rb₁ and staphylline hydrochloride were quality difference markers to control the stability of the preparation. The results of bioactive experiment showed that the water extract of Naomaili granules and the eight main components with high content in the prescription had a dose-dependent inhibitory effect on the release of NO in the cell supernatant. Among them， salvianolic acid B and ginsenoside Rb₁ had strong anti-inflammatory activity， with IC₅₀ values of （36.11±0.15） mg∙L^-1 and （27.24±0.54） mg∙L^-1， respectively. ConclusionThe quality evaluation method of Naomaili granules established in this study was accurate and reproducible. Four quality difference markers were screened out， and eight key pharmacodynamic substances of Naomaili granules against neuroinflammation were screened out by in vitro cell experiments.

INTRODUCTION: Hydroxychloroquine (HCQ), originally an antimalarial drug, is currently used to treat multiple disorders, especially rheumatic diseases. Given its good efficacy and safety, HCQ is widely administered in pregnant patients. However, the safety profile of HCQ during pregnancy remains controversial due to limited research. In addition, HCQ has been reported to reduce preeclampsia in patients with systemic lupus erythematosus (SLE) and could potentially alleviate the symptom of preeclampsia. However, the clinical profile and molecular mechanism of HCQ in preeclampsia is yet to be fully understood. METHOD: We reviewed the literature on HCQ treatment in pregnancy with rheumatic diseases and preeclamp-sia in PubMed and Web of Science. We also discussed the safety of long-term therapy with HCQ during pregnancy. RESULTS: HCQ mainly modulates autoimmune response through inhibition of lysosomal function, toll-like receptor (TLR) signalling, nicotinamide adenine dinucleotide phosphate-mediated oxidative stress and autophagy. Benefits of HCQ in treating rheumatic diseases, including antiphospholipid syndrome, rheumatoid arthritis and Sjogren's syndrome during pregnancy, has been demonstrated in clinics. In particular, multiple clinical guidelines recommend HCQ as an indispensable therapeutic drug for pregnant patients with SLE. Additionally, it may potentially function in preeclampsia to improve clinical symptoms. CONCLUSION HCQ is effectively used for rheumatic diseases during pregnancy. The benefits of HCQ treatment in rheumatic diseases outweigh the risk of adverse reactions it induces in pregnant women.
Humans ; Hydroxychloroquine/pharmacology* ; Pregnancy ; Female ; Antirheumatic Agents/pharmacology* ; Rheumatic Diseases/drug therapy* ; Pregnancy Complications/drug therapy* ; Pre-Eclampsia/prevention & control* ; Lupus Erythematosus, Systemic/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Antiphospholipid Syndrome/drug therapy* ; Sjogren's Syndrome/drug therapy*

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

OBJECTIVES: To investigate the role of METTL3 and FOXO3 in anthracycline resistance in acute myeloid leukemia (AML) cells. METHODS: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptome sequencing (RNA-seq) were performed in anthracycline-resistant and sensitive HL60 and K562 cells with lentivirus-mediated knockdown or overexpression of METTL3 and FOXO3. TCGA and GSE6891 datasets were used for analysis of the clinical and gene expression data of AMI patients. FOXO3 expressions at the mRNA and protein levels in the transfected cells were detected with RT-qPCR and Western blotting, and the changes in cell proliferation and apoptosis were evaluated using CCK8 assay and flow cytometry; the expression of m⁶A-modified mRNA and mRNA stability of FOXO3 was detected analyzed using MeRIP-qPCR and RT-qPCR. Functional enrichment analysis of the differential genes in the transfected cells was performed. RESULTS: Differential gene analysis in anthracycline-resistant versus sensitive AML cells and in cells with METTL3 knockdown revealed the enrichment in FoxO and autophagy pathways (P<0.05), and the anthracycline-resistant cells showed significantly increased m⁶A modification of FOXO3. FOXO3 expression was positively correlated with METTL3 expression. METTL3 knockdown significantly reduced FOXO3 mRNA stability and its protein levels in anthracycline-resistant AML cells, which exhibited higher m6A-modified FOXO3 expression levels than their sensitive counterparts. Database analysis, Kaplan-Meier analysis and RT-qPCR results suggested that a high FOXO3 expression was associated with a poor prognosis of AML patients. In anthracycline-resistant AML cells expressing higher FOXO3 levels than the sensitive cells, lentivirus-mediated overexpression of FOXO3 significantly enhanced cell proliferation and suppressed cell apoptosis. Inhibiting autophagy using an autophagy inhibitor (Baf.A1) obviously enhanced the inhibitory effect of adriamycin on resistant AMI cells and cells overexpressing FOXO3. CONCLUSIONS METTL3 promotes FOXO3 expression via m6A modification, and FOXO3-driven autophagy contributes to anthracycline resistance in AML cells by enhancing cell proliferation and suppressing cell apoptosis.
Humans ; Forkhead Box Protein O3/genetics* ; Leukemia, Myeloid, Acute/genetics* ; Drug Resistance, Neoplasm ; Methyltransferases/genetics* ; Autophagy ; Anthracyclines/pharmacology* ; HL-60 Cells ; Apoptosis ; Cell Proliferation ; K562 Cells

Small cell lung cancer (SCLC) accounts for about 13%~17% of primary bronchial lung cancer. Due to its rapid growth rate, aggressive behavior, early metastasis and poor prognosis, about 70% of patients were diagnosed with extensive-stage (ES) disease. Although most ES-SCLC patients are sensitive to initial chemotherapy, local recurrence and distant metastasis develop in the short term. Immunotherapy has brought the dawn to overcome it. At present, immune checkpoint inhibitor combined with chemotherapy has become an important strategy as first-line therapy for ES-SCLC. Nevertheless, patients are still at a high risk of chest lesion recurrence after initial systemic therapy. Whether the addition of thoracic consolidation radiotherapy (TRT) can reduce chest lesion recurrence rate remains to be determined. In this review, we summarized the latest research progress in the mode of first-line chemotherapy combined with immunotherapy followed by TRT in ES-SCLC, aiming to provide reference for clinical practice.

Small cell lung cancer (SCLC) accounts for about 13%~17% of primary bronchial lung cancer. Due to its rapid growth rate, aggressive behavior, early metastasis and poor prognosis, about 70% of patients were diagnosed with extensive-stage (ES) disease. Although most ES-SCLC patients are sensitive to initial chemotherapy, local recurrence and distant metastasis develop in the short term. Immunotherapy has brought the dawn to overcome it. At present, immune checkpoint inhibitor combined with chemotherapy has become an important strategy as first-line therapy for ES-SCLC. Nevertheless, patients are still at a high risk of chest lesion recurrence after initial systemic therapy. Whether the addition of thoracic consolidation radiotherapy (TRT) can reduce chest lesion recurrence rate remains to be determined. In this review, we summarized the latest research progress in the mode of first-line chemotherapy combined with immunotherapy followed by TRT in ES-SCLC, aiming to provide reference for clinical practice.

Objective     To construct a radiomics model for identifying clinical high-risk carotid plaques. Methods     A retrospective analysis was conducted on patients with carotid artery stenosis in China-Japan Friendship Hospital from December 2016 to June 2022. The patients were classified as a clinical high-risk carotid plaque group and a clinical low-risk carotid plaque group according to the occurrence of stroke, transient ischemic attack and other cerebrovascular clinical symptoms within six months. Six machine learning models including eXtreme Gradient Boosting, support vector machine, Gaussian Naive Bayesian, logical regression, K-nearest neighbors and artificial neural network were established. We also constructed a joint predictive model combined with logistic regression analysis of clinical risk factors. Results    Finally 652 patients were collected, including 427 males and 225 females, with an average age of 68.2 years. The results showed that the prediction ability of eXtreme Gradient Boosting was the best among the six machine learning models, and the area under the curve (AUC) in validation dataset was 0.751. At the same time, the AUC of eXtreme Gradient Boosting joint prediction model established by clinical data and carotid artery imaging data validation dataset was 0.823. Conclusion     Radiomics features combined with clinical feature model can effectively identify clinical high-risk carotid plaques.

Objective     To identify the preoperative risk factors for prolonged mechanical ventilation (PMV) after pulmonary thromboendarterectomy (PTE). Methods    The clinical data of patients who underwent PTE from December 2016 to August 2021 in our hospital were retrospectively analyzed. The patients were divided into two groups according to the postoperative mechanical ventilation time, including a postoperative mechanical ventilation time≤48 h group (≤48 h group) and a postoperative mechanical ventilation time>48 h (PMV) group (>48 h group). Univariable and logistic regression analysis were used to identify the preoperative risk factors for postoperative PMV. Results    Totally, 90 patients were enrolled in this study. There were 40 patients in the ≤48 h group, including 30 males and 10 females, with a mean age of 45.48±12.72 years, and there were 50 patients in the >48 h group, including 29 males and 21 females, with a mean age of 55.50±10.42 years. The results showed that in the ≤48 h group, the median postoperative ICU stay was 3.0 days, and the median postoperative hospital stay was 15.0 days; in the >48 h group, the median postoperative ICU stay was 7.0 days, and the median postoperative hospital stay was 20.0 days. The postoperative PMV was significantly correlated with tricuspid annular plane systolic excursion (TAPSE) [OR=0.839, 95%CI (0.716, 0.983), P=0.030], age [OR=1.082, 95%CI (1.034, 1.132), P=0.001] and pulmonary vascular resistance (PVR) [OR=1.001, 95%CI (1.000, 1.003), P=0.028]. Conclusion    Age and PVR are the preoperative risk factors for PMV after PTE, and TAPSE is the preoperative protective factor for PMV after PTE.

ObjectiveTo explore the effect and possible mechanism of Shenqi Pills （肾气丸） on cognitive impairment and hippocampal glucose energy metabolism in type 2 diabetes mellitus （T2DM）. MethodsSixty C57BL/6 mice were randomly divided into control group， model group， rosiglitazone group and Shenqi Pills low-， medium- and high-dose groups， with 10 mice in each group. T2DM model was induced by a high-fat diet combined with intraperitoneal injection of streptozotocin in all the groups except for the control group. After successful modeling， the high-， medium-， and low-dose Shenqi Pills groups were given 2.08， 1.04， and 0.52 g/（kg·d） of Shenqi Pills granules by gavage respectively， while the rosiglitazone group was given 3 mg/（kg·d） of rosiglitazone tablets by gavage， and the control group and model group were gavaged with 10 ml/（kg·d） of distilled water， all for 8 consecutive weeks. The body weight and fasting blood glucose （FBG） level were recorded every two weeks. The Morris water maze test was performed on the 8th week of medication. After 8-week medication， oral glucose tolerance test （OGTT） and fasting insulin level were measured， hippocampal glucose energy metabolism-related products were quantitatively detected by liquid chromatography tandem mass spectrometry， and KEGG annotation analysis was performed. ResultsCompared to those measured at the same timepoints in the control group， the body mass on week 6 and 8， as well as the FBG level on week 2， 4， 6 and 8 in the model group increased； the blood glucose level at 0， 30， 60 and 120 minutes of the OGTT test increased， while fasting insulin level after 8-week medication decreased. The escape latency of the model group was significantly prolonged on the 3rd and 4th days， and the escape latency time increased， while the total swimming distance， platform quadrant residence time and the number of platform crossings decreased （P＜0.05 or P＜0.01）. Compared to those measured at the same timepoints in the model group， the body mass on week 6 in the low-dose Shenqi Pills group， on week 6 and 8 in the medium- and high-dose groups， and on week 8 in the rosiglitazone group were significantly reduced； the FBG levels in all the Shenqi Pills groups and rosiglitazone group on week 6 and 8 decreased， while fasting insulin levels increased. In the OGTT test， blood glucose in the medium-dose group of Shenqi Pills at all timepoints decreased； in the Morris water maze test， the escape latency period of the medium- and high-dose Shenqi Pills groups was shortened on the 3rd and 4th days， while the escape latency time was reduced， and the total swimming distance， platform quadrant residence time， and number of platform crossings increased in the medium-dose Shenqi Pills group （P＜0.05 or P＜0.01）.The medium-dose Shenqi Pills showed best effect， therefore it was selected for the targeted quantitative detection of metabolites. The medium-dose Shenqi Pills group could regulate the disorder of glucose metabolism in the hippocampus of T2DM mice， and 13 differential metabolites were found，up-regulating α-ketoglutarate and 3-phosphoglyceric acid， and down-regulating fumaric acid， glutamatic acid， lactatic acid， inosine， malic acid， adenine， fructose 1,6-diphosphate and others. KEGG annotation of differential metabolites suggested that Shenqi Pills was closely related to the regulation of glucose metabolism disorder and insulin resistance in the hippocampus region of T2DM model mice， as well as neurodegenerative diseases and ABC transport， hypoxia-inducible factor 1 （HIF）， forkhead transcription factor （FoXO） and cyclic adenosine monophosphate （cAMP） signaling pathways. ConclusionShenqi Pills can improve learning and memory abilities and cognitive impairment in T2DM mice， and may act its role by regulating glucose energy metabolism in the hippocampus of T2DM.