The aim of this study is to investigate the regulation of Kaixin San-medicated serum(KXS-MS) on autophagy induced by Aβ_(25-35) in SH-SY5Y cells. The SH-SY5Y cell model of Aβ_(25-35)(25 μmol·L~(-1))-induced injury was established, and different concentrations of KXS-MS were added into the culture media of cells, which were then incubated for 24 h. Cell viability was measured by the methyl thiazolyl tetrazolium(MTT) assay. The protein levels of microtubule-associated protein 1 light chain 3(LC3)Ⅰ, LC3Ⅱ, protein kinase B(Akt), p-Akt, mammalian target of rapamycin(mTOR), and p-mTOR were assessed by Western blot. Furthermore, the combination of rapamycin(Rapa)/3-methyladenine(3-MA) and low concentration of KXS-MS was added to the culture medium of SH-SY5Y cells injured by Aβ_(25-35), and the cell viability and the expression levels of the above proteins were determined. The results showed that Aβ_(25-35) decreased the cell viability, up-regulated the expression levels of LC3Ⅱ and LC3Ⅱ/LC3Ⅰ, and down-regulated the expression levels of p-Akt, p-mTOR, p-Akt/Akt, and p-mTOR/mTOR. Compared with the Aβ_(25-35) model group, KXS-MS treatment attenuated Aβ_(25-35)-induced injury and enhanced the survival of SH-SY5Y cells. Meanwhile, KXS-MS down-regulated the LC3Ⅱ/LC3Ⅰ level and up-regulated the p-Akt/Akt and p-mTOR/mTOR levels. Compared with the low-concentration KXS-MS group, Rapa did not affect the cell survival and the levels of p-Akt and p-Akt/Akt, while it up-regulated the levels of LC3Ⅱ and LC3Ⅱ/LC3Ⅰ and down-regulated the levels of p-mTOR and p-mTOR/mTOR. 3-MA significantly reduced the cell survival rate and p-Akt, p-Akt/Akt level in the KXS-MS group, while it had no significant effect on the levels of LC3Ⅱ, LC3Ⅱ/LC3Ⅰ, p-mTOR, and p-mTOR/mTOR. The above results indicate that KXS-MS exhibits protective effects against Aβ_(25-35)-induced damage in SH-SY5Y cells by up-regulating Akt/mTOR activity to inhibit autophagy.
Humans ; Autophagy/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Amyloid beta-Peptides/toxicity* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Cell Line, Tumor ; Cell Survival/drug effects* ; Peptide Fragments/toxicity* ; Microtubule-Associated Proteins/genetics*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

AIM: To investigate the efficacy and safety of orthokeratology combined with 0.01% atropine solution in adolescents with myopia.METHODS: A total of 100 adolescent myopic patients(100 right eyes)who received treatment at the Department of Ophthalmology, People's Hospital of Hengshui from January 2019 to January 2022 were enrolled. All patients were divided into two groups based on the patient's preferences and randomized controlled principles: control group(n=50)and experimental group(n=50). Patients in the control group received orthokeratology alone, while those in the experimental group received orthokeratology in combination with 0.01% atropine solution. Treatment data for both groups were collected at 1, 3, 6, 9 and 12mo after treatment. The observed indicators included refraction, corneal curvature, axial length(AL), central corneal thickness(CCT), pupil diameter(PD), lipid layer thickness(LLT), break-up Time(BUT), root-mean-square of higher-order aberration(RMSh), subfoveal choroidal thickness(SFCT), corneal endothelial cell density(CD), and hexagonal cell ratio(HEX). The adverse reactions experienced during follow-up period were also observed and recorded.RESULTS: After 12mo of treatment, the refraction, corneal curvature, and AL in the experimental group were -2.42±0.17D, 38.89±1.18D and 25.44±0.23mm, respectively, which were significantly better than the control group(-2.56±0.19D, 40.12±1.65D and 25.54±0.19 mm, all P<0.05). The CCT of the experimental group(538±33 μm)was lower than that of the control group(545±41 μm), while the PD of the experimental group was higher than that of the control group(6.38±0.38 mm vs. 6.12±0.37 mm, P<0.05). LLT and BUT in the experimental group was 61.14±8.41 nm and 9.24±2.05s, respectively, which were significantly higher than those in the control group(56.14±7.22 nm and 7.27±1.99s, all P<0.05). RMSh in the experimental group was lower than that of the control group(0.73±0.21 μm vs. 0.85±0.12 μm, P<0.05), and SFCT in the experimental group was significantly higher than that of the control group(289±55 μm vs. 282±59 μm, P<0.05). Additionally, after 12mo of treatment, there was no significant difference in CD and HEX between the experimental group and the control group(all P>0.05). The main adverse reactions of both groups during treatment period were photophobia, anaphylaxis, conjunctivitis and keratitis, but there was no significant difference between the two groups(all P>0.05).CONCLUSION: Compared to orthokeratology alone, the combination of orthokeratology and 0.01% atropine solution effectively prevents and improves the development of adolescent myopia without increasing the incidence of adverse reactions.

ObjectiveTo explore the mechanism of Dendrobium huoshanense in the treatment of gastric ulcer （GU） based on network pharmacology and in vivo experiment. MethodThe active components of D. huoshanense were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and literature， and the targets of the components were screened from TCMSP and SwissTargetPrediction. GU-related genes were retrieved from GeneCards， Online Mendelian Inheritance in Man （OMIM）， and DisGeNET. Thereby， the common targets of the disease and the medicinal were yielded and the protein-protein interaction （PPI） network was constructed， followed by Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment. According to the predicted results， hematoxylin-eosin （HE） staining， immunohistochemistry， enzyme-linked immunosorbent assay （ELISA）， Western blot， and real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） were used to validate the effects of D. huoshanense on acetic acid-induced GU in rats. ResultA total of 63 active components of D. huoshanense and 37 target genes of D. huoshanense for the treatment of GU were screened out. PPI network analysis yielded several possible core anti-GU targets of D. huoshanense. They influenced the development of GU by acting on signaling pathways such as phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， hypoxia inducible factor-1 （HIF-1）， tumor necrosis factor （TNF）， and nuclear factor-κB （NF-κB）， and various biological processes. The in vivo experiment showed that D. huoshanense significantly reduced the levels of inflammatory factors such as interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and TNF-α in the serum of model rats （P<0.05， P<0.01）， increased gastric blood flow （GBF） at the ulcer margin， raised the expression of epidermal growth factor （EGF） and epidermal growth factor receptor （EGFR） at the ulcer margin （P<0.01）， significantly down-regulated protein and mRNA expression of PI3K and Akt， and up-regulated protein and mRNA expression of phosphatase and tensin homolog deleted on chromosome ten （PTEN） in the gastric tissues of GU rats （P<0.01）. ConclusionThrough regulating EGFR/PI3K/Akt signaling pathway， D. huoshanense can inhibit tissue inflammation， increase gastric microcirculatory blood flow at the ulcer margin， and promote cell proliferation and repair of damaged gastric mucosa.

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

Artemisia indica is an important medicinal plant in the Asteraceae family, but its molecular genetic information has been rarely reported. In this study, the chloroplast genome of A. indica was sequenced, assembled, and annotated by the high-throughput sequencing technology, and its sequence characteristics, repeat sequences, codon usage bias, and phylogeny were analyzed. The results showed that the length of the chloroplast genome for A. indica was 151 161 bp, which was a typical circular four-segment structure, including two inverted repeat regions(IRs), a large single-copy(LSC) region, and a small single-copy(SSC) region, with a GC content of 37.47%. A total of 132 genes were annotated, and 114 were obtained after de-duplication, including 80 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. Fifty long repeat sequences and 191 SSRs were detected in the chloroplast genome of A. indica, and SSRs were mainly single nucleotides. Codon usage bias analysis showed that leucine was the most frequently used amino acid(10.77%) in the chloroplast genome, and there were 30 codons with relative synonymous codon usage(RSCU)>1 and all ended with A/U. The phylogenetic tree constructed based on the chloroplast genomes of the 19 species from the Asteraceae family showed that A. indica and A. argyi were closest in the genetic relationship, and Artemisia species clustered into separate evolutionary branches. The results of this study are expected to provide a theoretical basis for the genetic diversity and resource conservation of Artemisia medicinal plants.
Genome, Chloroplast ; Phylogeny ; Artemisia/genetics* ; Codon/genetics* ; Base Composition ; Plants, Medicinal/genetics*

OBJECTIVE: To explore the predictors of hematologic responses of non-transfusion-dependent β-thalassemia (NTDT) to thalidomide. METHODS: 33 patients with NTDT who treated with thalidomide in the 923rd Hospital of the Joint Logistics Support Force of the People's Liberation Army from May 2016 to June 2019 were included in the study. The basic data, hematological indexes, degree of treatment response and genetic background of the patients were analyzed. RESULTS: The baseline fetal hemoglobin (HbF) level of main responders (MaR) was significantly higher than that of minor responders (MiR) and no responders (NR) (P=0.001). And the baseline HbF level was positively correlated with hemoglobin increment after treatment (r=0.601). Genetic background analysis showed that the frequencies of the genotype CT of HBG2 rs7482144 (P=0.031), the genotypes CT/CC (P=0.030) and the minor allele C (P=0.015) of HBS1L-MYB rs9399137, the genotypes AT/TT (P=0.030) and the minor allele T (P=0.028) of HBS1L-MYB rs4895440, the genotypes AG/GG (P=0.030) and the minor allele G (P=0.028) of HBS1L-MYB rs4895441 (P=0.030) in MaR group were significantly higher than those in MiR and NR groups. Comparing the area under the ROC curve (AUC) of the above indicators to predict the main response, the results demonstrated that the predictive value of baseline HbF level was significantly better than rs7482144 (0.91 vs 0.72, P=0.003), rs9399137 (0.91 vs 0.74, P=0.022), rs4895440 (0.91 vs 0.74, P=0.023) and rs4895441 (0.91 vs 0.74, P=0.023), but there was no significant difference in the predictive value between combined single nucleotide polymorphisms (SNPs) (0.91 vs 0.88, P=0.658）and baseline HbF combined SNPs (0.91 vs 0.97, P=0.132). The AUC value of baseline HbF predicting the efficacy of thalidomide as the main response was 0.91, the cut-off value was 27.4%, the sensitivity was 100%, and the specificity was 58.3% (P=0.001). CONCLUSION The hematologic response of NTDT to thalidomide is variable and complex. Compared to genetic background, baseline HbF may be a simpler and more efficient tool to predict efficacy response.
Fetal Hemoglobin/genetics* ; Humans ; MicroRNAs ; Polymorphism, Single Nucleotide ; Repressor Proteins/genetics* ; Thalidomide/therapeutic use* ; beta-Thalassemia/genetics*

Objective: To investigate the efficacy and safety of infliximab (IFX) therapy for children with Kawasaki disease. Methods: Sixty-eight children with Kawasaki disease who received IFX therapy in Children's Hospital of Fudan University from January 2014 to April 2021 were enrolled. The indications for IFX administration, changes in laboratory parameters before and after IFX administration, response rate, drug adverse events and complications and outcomes of coronary artery aneurysms (CAA) were retrospectively analyzed. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Results: Among 68 children with Kawasaki disease, 52 (76%) were males and 16 (24%) were females. The age of onset was 2.1 (0.5, 3.8) years. IFX was administered to: (1) 35 children (51%) with persistent fever who did not respond to intravenous immunoglobulin (IVIG) or steroids, 28 of the 35 children (80%) developed CAA before IFX therapy; (2) 32 children (47%) with continuous progression of CAA; (3) 1 child with persistent arthritis. In all cases, IFX was administered as an additional treatment (the time from the onset of illness to IFX therapy was 21 (15, 30) days) which consisted of second line therapy in 20 (29%), third line therapy in 20 (29%), and fourth (or more) line therapy in 28 (41%). C-reactive protein (8 (4, 15) vs. 16 (8, 43) mg/L, Z=-3.38, P=0.001), serum amyloid protein A (17 (10, 42) vs. 88 (11, 327) mg/L, Z=-2.36, P=0.018) and the percentage of neutrophils (0.39±0.20 vs. 0.49±0.21, t=2.63, P=0.010) decreased significantly after IFX administration. Fourteen children (21%) did not respond to IFX and received additional therapies mainly including steroids and cyclophosphamide. There was no significant difference in gender, age at IFX administration, time from the onset of illness to IFX administration, the maximum coronary Z value before IFX administration, and the incidence of systemic aneurysms between IFX-sensitive group and IFX-resistant group (all P>0.05). Infections occurred in 11 cases (16%) after IFX administration, including respiratory tract, digestive tract, urinary tract, skin and oral infections. One case had Calmette-Guérin bacillus-related adverse reactions 2 months after IFX administration. All of these adverse events were cured successfully. One child died of CAA rupture, 6 children were lost to follow up, the remaining 61 children were followed up for 6 (4, 15) months. No CAA occurred in 7 children before and after IFX treatment, while CAA occurred in 54 children before IFX treatment. CAA regressed in 23 (43%) children at the last follow-up, and the diameter of coronary artery recovered to normal in 10 children. Conclusion: IFX is an effective and safe therapeutic choice for children with Kawasaki disease who are refractory to IVIG or steroids therapy or with continuous progression of CAA.
Child ; Coronary Aneurysm/etiology* ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Infant ; Infliximab/adverse effects* ; Male ; Mucocutaneous Lymph Node Syndrome/drug therapy* ; Retrospective Studies