Abelmoschi Corolla, the dried corolla of Abelmoschus manihot, has anti-inflammatory, antioxidant, and anti-fibrosis activities. Its chemical constituents mainly include flavonoids, organic acids, steroids, and polysaccharides. This study reviewed the research progress in the chemical constituents and pharmacological activities of Abelmoschi Corolla in recent 20 years. According to the concept of quality marker(Q-marker), the Q-markers of Abelmoschi Corolla were predicted from plant phylogeny, chemical constituent specificity, traditional efficacy, chemical constituent measurability, and absorbed constituents. The primary Q-markers for Abelmoschi Corolla were anticipated to include quercetin-3'-O-β-D-glucopyranoside, gossypetin-8-O-β-D-glucuronide, isoquercetin, myricetin,quercetin, and hyperoside, with the aim of providing reference data for improving the quality evaluation system of Abelmoschi Corolla.
Abelmoschus/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Flowers/chemistry* ; Humans ; Animals ; Quality Control ; Flavonoids/chemistry*

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

Objective:To discuss the clinical efficacy of recombinant human growth hormone(rhGH)in the treatment of the pediatric patients with growth hormone deficiency(GHD)and idiopathic short stature(ISS),and to clarify its clinical application value in the pediatric patients with short stature of different etiologies.Methods:The clinical data of 132 children with short stature who treated with rhGH from January 2018 to January 2023 were collected.They were divided into GHD group(n=70)and ISS group(n=62)based on different etiologies.The bone age,target height(TH),body mass index(BMI),height standard deviation score(HtSDS),changes in height standard deviation scores(ΔHtSDS)before treatment and 6 months after treatment,and growth velocity(GV)of the pediatric patients were calculated.Propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)were used to balance the confounding factors between the pediatric patients in two groups and the efficacy and safety of the pediatric patients in two groups were evaluated.Results:There were significant differences in whether children were full-term,bone age,bone age maturity,and TH of the pediatric patients between two groups(P<0.05).Compared with before treatment,the height and HtSDS of the pediatric patients in both GHD and ISS groups were significantly increased after treated for 6 months(P<0.05).Before matched by PSM,there were significant differences in full-term,bone age,bone age maturity,and TH of the pediatric patients between two groups(P<0.05).After matched by PSM,there were no significant differences in gender,region,term birth status,mode of delivery,feeding method,age,bone age,height,BMI,TH,and pretreatment HtSDS of the pediatric patients between two groups(P>0.05);the standardized mean difference(SMD)differences of covariates except for region were<0.2.After weighted by IPTW,there were no significant differences in gender,region,term birth status,mode of delivery,feeding method,age,bone age,height,BMI,TH,and pretreatment HtSDS of the pediatric patients between two groups(P>0.05);all SMD of covariates except for term birth status were<0.2.Before balancing covariates,after meatched by PSM matching,and after weighted by IPTW weighting compared with GHD group,the GV and ΔHtSDS of the pediatric patients in ISS group were slightly increased,but the difference was not significant(P>0.05).In terms of adverse reactions,2 cases(2.68%)of fasting hyperglycemia and 7 cases(10.00%)of hypothyroidism occurred in GHD group;3 cases(4.84%)of fasting hyperglycemia and 2 cases(3.23%)of hypothyroidism occurred in ISS group.Conclusion:rhGH can promote the height increase in the patients with GHD and ISS,and there is no significant difference in the height-increasing efficacy between GHD and ISS children.The incidence of adverse reactions is relatively low during treatment,indicating good overall safety.

The incidence of knee osteoarthritis(KOA)is in-creasing year by year,seriously affecting patients'health.Mes-enchymal stem cells are multipotent cells with multiple differen-tiation functions.The extracellular vesicles released by these cells can carry various"cargo"to corresponding cells and tis-sues,exerting biological functions.They have shown great clini-cal potential in the treatment of KOA.This study reviews the therapeutic effects and mechanisms of extracellular vesicles se-creted by mesenchymal stem cells from different tissues such as bone marrow,adipose tissue,and synovium in KOA.It is found that miRNA is an important biological component in exerting therapeutic effects.The study also discusses the research pro-gress of engineered extracellular vesicles in KOA,pointing out the current challenges in clinical application,such as standard-ized acquisition of extracellular vesicles and difficulties in targe-ted action,aiming to provide a certain reference for the basic re-search and clinical application of extracellular vesicle therapy for KOA.

Guillain-Barre syndrome rarely develops after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and only a few reports exist in China. Guillain-Barre syndrome is an acute and life-threatening condition that requires early diagnosis and treatment. A patient with acute myeloid leukemia underwent allogeneic HSCT for >5 months and gradually developed limb muscle weakness and limited eye movement after coexisting with delayed acute intestinal graft-versus-host disease. After the examination of cerebrospinal fluid and electromyography, the diagnosis of Guillain–Barre syndrome was confirmed. After a high-dose intravenous immunoglobulin (IVIg) treatment, muscle strength gradually recovered, and the prognosis was good.

The onset of myasthenia gravis (MG) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) seriously threatens the survival of patients, since it is acute, and is prone to rapid progression. Two patients with acute myeloid leukemia (AML), who had undergone allo-HSCT developed shortness of breath, and gradually developed cervical weakness and dyspnea. The acetylcholine receptor (AChR) antibody and neostigmine test enabled the diagnosis of MG. The condition of the patients improved after treatment with pyridostigmine bromide, glucocorticoids and rituximab.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To investigate the efficacy, safety and possible mechanisms of celecoxib as an adjunctive treatment for schizophrenia.Methods:90 schizophrenic inpatients at the second affiliated hospital of Xinxiang Medical College from April 2019 to October 2020 were recruited and randomly assigned to a placebo group or the celecoxib adjunctive treatment group using a random number table. In the placebo group, 46 patients (29 males, 17 females; aged 21-34, mean age 27.46±6.50 years) completed a 6-week follow-up. In the celecoxib group, 44 patients (32 males, 12 females; aged 21-39, mean age 30.52±8.69 years) completed a 6-week follow-up. The Positive and Negative Syndrome Scale (PANSS) was used to assess psychiatric symptoms in both groups. Changes in PANSS score at the end of the treatment were compared to evaluate the efficacy of celecoxib. Metabolic indicators such as weight, body mass index, waist circumference and plasm glucolipid, as well as cardiovascular indicators like blood pressure, electrocardiogram and routine blood tests, and adverse events were collected for the safety evaluation. Serum tumor necrosis factor-α (TNF-α), Interleukin-4 (IL-4) and interferon-γ (IFN-γ) were also tested. Pearson correlation analysis was used to explore the relationship between cytokine levels, PANSS score, PANSS reduction rate [(pre-treatment score-post-treatment score)/pre-treatment score×100%], and the safety measurements in the two groups, analyzing the role of inflammation in celecoxib adjunctive therapy.Results:The change of PANSS positive score at the end of the 6th week was significantly higher in the celecoxib adjuvant treatment group than in the placebo group (-8.00±6.12 vs -4.78±5.19, H=-0.55, P=0.009). The weight changes, body mass index, total cholesterol, and triglycerides over 6 weeks were significantly lower in the celecoxib group compared to the placebo group ( F=-7.37, -7.30, 2.56, -2.54; all P<0.05). No serious adverse events were found in celecoxib adjuvant therapy. In the placebo group, baseline TNF-α levels were positively correlated with baseline negative symptoms and PANSS reduction rate ( r=0.260 and 0.330, both P<0.05), and negatively correlated with the 6-week weight ( r=-0.311, P<0.05); baseline IL-4 levels were positively correlated with the 6-week PANSS total score and the 6-week PANSS negative score ( r=0.320 and 0.397, both P<0.05), and negatively correlated with PANSS reduction rate and 6-week blood glucose ( r=-0.316 and -0.331, both P<0.05); Six-week IFN-γ levels were negatively correlated with low-density lipoprotein levels ( r=-0.306, P<0.05). And no such correlation was found in celecoxib adjuvant group. Conclusion:Celecoxib adjunctive therapy can improve positive symptoms of schizophrenia without causing adverse reactions. Inflammatory state is related to schizophrenia symptoms, treatment efficacy and metabolic abnormalities.

Objectives:To investigate the association between single nucleotide polymorphisms (SNP) of indoleamine 2,3-dioxygenase( IDO) genes and schizophrenia (SZ) in a Chinese Han population. Methods:Using a case-control study method, 3 700 in-patients with SZ were recruited from January 2010 to December 2021 at the Second Affiliated Hospital of Xinxiang Medical University, and 8 580 healthy controls were recruited from surrounding communities in Xinxiang City. The patient group and control group were matched in gender and age. After collecting peripheral blood from all subjects and extracting genomic DNA, the sample DNA was genotyped using methods such as gene chips and amplification refractory mutation system. The association analysis between IDO gene SNPs and SZ was conducted using the online analysis tool SHEsis. The differences in IDO gene SNP genotype and allele frequency between the two groups were compared using chi-square test. Linkage disequilibrium analysis, haplotype analysis, and Hardy Weinberg equilibrium test were performed using Haploview v4.2 software. A multifactor dimensionality reduction software was used to evaluate the interaction between SNPs and SNP frequencies. Results:In the four SNP loci of IDO gene, there was a significant difference in genotype and allele frequency between the SZ patient and the health control at rs9657182 locus (χ 2=11.81, P=0.003;χ 2=5.54, P=0.019). After Bonferroni correction, the genotype difference at rs9657182 locus still showed statistical significance ( P=0.011). There were no statistically significant differences in genotype and allele frequency among the three SNP locis (rs7820268, rs4503083, and rs10109853). Further stratified by gender, there was no significant difference in genotype frequency between the two groups at the rs9657182. Haplotype analysis revealed that the haplotype of CC and TC (rs9657182 and rs7820268) were significantly different between the two groups (χ 2=3.93,4.78, P=0.048, 0.029). Conclusion:The rs9657182 locus of IDO gene may be a susceptible locus for SZ. The haplotype of CC and TC may be associated with the onset of SZ.