BACKGROUND: Osteoarthritis (OA) is a prevalent joint disorder that significantly impairs quality of life among elderly individuals because of chronic pain and physical disability. As the global burden of OA continues to rise, novel therapeutic strategies are urgently needed. Kaempferide (KA), a flavonoid derived from traditional Chinese herbal medicine, is known for its anti-inflammatory properties. However, the effect of KA on the progression of OA has not been well investigated. This study aimed to explore the therapeutic potential of KA in an OA model and investigate the underlying mechanisms via transcriptomic sequencing. METHODS: An in vitro OA model was established using SW1353 cells treated with interleukin-1 beta (IL-1β) and different concentrations of KA (30, 60, or 90 μmol/L) for 24 h. The anti-inflammatory effects of KA were assessed using quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blotting. In vivo , a papain-induced OA rat model was used to evaluate the therapeutic effects of KA through histological and behavioral analyses. Transcriptomic sequencing was performed to explore the differentially expressed genes (DEGs) and related signaling pathways. Statistical analysis was conducted using one-way analysis of variance. RESULTS: KA significantly increased cell viability in the OA chondrocyte model and downregulated the expression of inflammatory cytokines and cartilage degradation markers, with the greatest reduction observed at 90 μmol/L. In vivo , KA treatment mitigated cartilage degradation and improved gait behavior in OA rats. Transcriptomic analysis revealed substantial modulation of DEGs, implicating the hypoxia-inducible factor-1 (HIF-1) signaling pathway as a key mechanism. Further blocking and rescue experiments revealed that KA regulated key molecules within the HIF-1 pathway, specifically interferon-gamma (IFN-γ) and hypoxia-inducible factor 1-alpha (HIF-1α), confirming their critical roles in mediating the therapeutic effects of KA. CONCLUSION KA inhibited the progression of OA by targeting the HIF-1 signaling pathway, reducing inflammation, and cartilage degradation.
Animals ; Osteoarthritis/metabolism* ; Signal Transduction/drug effects* ; Rats ; Rats, Sprague-Dawley ; Humans ; Male ; Hypoxia-Inducible Factor 1/metabolism* ; Interleukin-1beta

OBJECTIVE: To explore the genetic etiology of a child with Renpenning syndrome (RS), and review the literature on the clinical characteristics and gene mutations of RS. METHODS: A child with RS (patient 1) who was diagnosed and treated in the Pediatric Intensive Care Unit of the Third Affiliated Hospital of Zhengzhou University in November 2023 was selected as the research object. The medical history, family history, physical examination, cerebrospinal fluid examination, echocardiography, brain magnetic resonance imaging (MRI), brain magnetic resonance angiography, cardiac coronary CT angiography and intelligence quotient (IQ) score of child 1 were retrospectively collected. Peripheral venous blood samples were collected from patient 1, his parents, sister and brother, respectively. Genomic DNA was extracted from the child and his family members, and Trios-whole exome sequencing (Trios-WES) was performed. Sanger sequencing was used to verify the pedigree. Bioinformatics softwares (Mutation Taster, REVEL, SIFT, PolyPhen-2, GERP++, SWISS-MODEL) were applied. The pathogenicity of the detected variants was rated according to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Classification of Genetic Variants (hereinafter referred to as the ACMG Guidelines). "PQBP1 gene" "Renpenning syndrome" "PQBP1 gene" "Renpenning syndrome" were used as keywords in Chinese and English, respectively. Case reports of patients with RS caused by PQBP1 gene variants were retrieved from Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed database. The clinical features and gene variants of RS caused by PQBP1 gene variants were summarized and analyzed. This study was reviewed by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Approval No. 2024-334-01). RESULTS The patient 1, a 12-year-old boy, was admitted to the hospital due to fever and disturbance of consciousness. Cerebrospinal fluid test showed viral encephalitis caused by human herpesvirus 7 infection. The main clinical manifestations were unusual facies (microcephaly, long narrow face, microphthalmos, superior oblique palpebral fissure, hypertelorism of inner canthus, bulbous nasal columella) and mental retardation. Auxiliary examination showed than patient 1 had atrial septal defect, nodular heterotopia in the posterior horn of the left ventricle, angiodysplasia, and low IQ. The disease began in infancy, and there was no family history of related diseases. A hemizygous deletion, c.459_462del (p.Arg153SerfsTer41), was identified in exon 5 of the PQBP1 gene in patient 1, which was inherited from his mother by Sanger sequencing. The results of bioinformatics analysis showed that the mutation was harmful. This variant was rated as pathogenic (PVS1+PS4+PM2_Supporting+PP3) according to ACMG Guidelines. According to the literature search strategy set in this study, a total of 13 cases of RS were retrieved, involving 16 cases of RS patient caused by PQBP1 gene mutation (patients 2-17), including patient 1, a total of 17 cases of RS. Among the 17 patients, 16 male patients had hemizygous mutations in the X chromosome PQBP1 gene, and 1 female patient had heterozygous mutations, including 12 deletion frameshift nonsense mutations, 3 point missense mutations, and 2 duplication mutations. Except for two fetuses, all patients had special facial features and low IQ to varying degrees. Ten patients had abnormal development of one or more organs such as eyes, heart, brain, etc. CONCLUSION: The main clinical manifestations of RS are developmental delay, long narrow face, bulbous nose, microcephaly, and may be accompanied by heterotopia of gray matter of ventricle and congenital heart disease. The c.459_462del (p.Arg153SerfsTer41) variant of the PQBP1 gene is the genetic basis of patient 1 in this study.
Humans ; Male ; Mutation ; Pedigree ; Child ; DNA-Binding Proteins/genetics* ; Nuclear Proteins/genetics* ; Female ; Exome Sequencing

OBJECTIVE: To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. METHODS: The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). RESULTS: Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a "cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. CONCLUSION The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.
Humans ; Male ; Female ; Child, Preschool ; Infant ; Child ; Olivopontocerebellar Atrophies/genetics* ; Arginine-tRNA Ligase/genetics* ; Mutation ; Cerebellar Diseases

Objective To explore the clinical features of methylmalonic acidemia (MMA) in children admitted to the pediatric intensive care unit, to help improve our understanding of MMA. Methods The clinical data of 21 patients with MMA admitted to our PICU from December 2012 to August 2016 were analyzed. Diagnosis were confirmed by gas chromatography-mass spectrometry, GC/MS. Results twenty-four of 158 suspected cases were confirmed as having organic acidemia diseases including 21 cases of MMA, one case of propionic acidemia, one case of urea cycle disorders, and one case of glutaric acidemia. The main clinical manifestations were feeding difficulty, malnutrition (13 cases), developmental retardation (12 cases), lethargy (10 cases), tricuspid severe reflux and pulmonary hypertension (1 case), hydrocephaly (5 cases), muscular dystonia (three cases with hypertonia, and four with hypotonia), convulsion (7 cases), apnea, sobbing respiration (10 cases), chromatosis (6 cases), anemia (13 cases), edema (6 cases), thrombocytopenia (6 cases), hematuria and proteinuria (2 cases). Five cases gave up therapy before diagnosis was made. Sixteen cases received the treatment with Vitamin B12 and supplementation of L-carnitine. Seven cases gave up after treatment without effect or deterioration of condition. Eight cases were vitamin B12-responsive, and one case was vitamin B12-nonresponsive. The follow-up for a period ranging from three months to two years, among eight vitamin B12-responsive cases, 6 cases showed a favorable outcome with apparent improvement, one case had no symptom and one patient died from severe pneumonia. Vitamin B12-nonresponsive case was still alive. Conclusions The clinical manifestations of MMA are non-specific. Urine organic acid analysis is critical to early diagnosis of MMA in high-risk patients. Timely diagnosis and appropriate long-term treatment are essential to improve the prognosis of the disease.

Objective To evaluate the role of T?type calcium channels in up?regulation of spinal Ca2+∕calmodulin?dependent protein kinase Ⅱ ( CaMKⅡ) expression in rats with neuropathic pain. Meth?ods Forty?eight male Sprague?Dawley rats, weighing 230-270 g, in which intrathecal catheters were suc?cessfully implanted, were divided into 4 groups ( n=12 each) using a random number table: sham opera?tion group (group S), neuropathic pain group (group NP), normal saline group (group NS), and T?type calcium channel blocker mibefradil group ( group M ) . The model of neuropathic pain was established by chronic compression of the dorsal root ganglion ( DRG) . Normal saline 20μl and mibefradil 200μg ( dilu?ted to 20μl in normal saline) were injected intrathecally at 5 days after compression of the DRG in NS and M groups, respectively. Before intrathecal catheter implantation ( T1 ) , before compression of the DRG ( T2 ) , at 5 days after compression of the DRG and before intrathecal administration ( T3 ) , and at 30, 60, 120 and 240 min after intrathecal administration ( T4?7 ) , the mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal latency ( TWL) were measured. The rats were sacrificed after the last measure?ment of the pain threshold at T7 , and the lumbar enlargement segments of the spinal cord were harvested for determination of CaMKⅡ expression by Western blot. Results Compared with group S, the MWT was significantly decreased, and TWL was significantly shortened at T3?7 , and the expression of spinal CaMKⅡ was significantly up?regulated in NP and M groups (P<0.05). Compared with group NP, the MWT wassignificantly increased, and TWL was significantly prolonged at T4?6, and the expression of spinal CaMKⅡwas significantly down?regulated in group M (P<0.05), and no significant change was found in the parame?ters mentioned above in group NS (P>0.05). Conclusion T?type calcium channels are opened, the intra?cellular free calcium ion concentrations are increased, and activated spinal CaMKⅡ is involved in the de?velopment of neuropathic pain in rats.

Objective To evaluate the effects of sevoflurane on the expression of heparanase ( HPA) and fascin in lung carcinoma cells of mice. Methods Mouse LLC cells were inoculated in the culture plate. After being cultured for 24 h, the cells were equally and randomly divided into 4 groups using a random number table: control group ( group CC) , 1% sevoflurane group ( group Sev1 ) , 2% sevoflurane group ( group Sev2 ) , and 3% sevoflurane group ( group Sev3 ) . Cells in Sev1-3 groups were exposed to 1%, 2% and 3% sevoflurane, respectively, for 4 h, while cells in group CC were not exposed to sevoflurane, and all the cells were then cultured for another 24 h in an incubator. The invasion of cells was determined by Transwell invasion assay, and the invaded cells were counted. The migration of cells was determined by wound healing assay, and cell migration rates were calculated. The expression of HPA and fascin in cells was detected by Western blot. Results Compared with group CC, the number of invaded cells and cell migration rates were gradually decreased, and the expression of HPA and fascin was gradually down?regulated with increasing concentrations of sevoflurane in Sev1-3 groups. Conclusion The mechanism through which sevoflurane inhibits the metastasis of mouse lung carcinoma cells is associated with down?regulated expression of HPA and fascin.

ObjectiveTo investigate the role of T-type calcium channel in the spinal neurotoxicity of intrathecal (IT) lidocaine in rats.MethodsForty-eight adult male SD rats in which IT catheter was successfully implanted,weighing 230-270 g,were randomly divided into 4 groups ( n =12 each):dimethyl sulfoxide (DMSO)group (group D),lidocaine group (group L),mibefradil + lidocaine group (group M),normal saline + lidocaine group (group N).Another 12 rats served as control group (group C).DMSO and 10％ lidocaine 20μl were injected intrathecally in groups D and L respectively.After mibefradil 200 μg/10μl and normal saline 10 μl were injected intrathecally in groups M and N respectively,10％ lidocaine 20 μl was injected intrathecally in the two groups.The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured before IT injection and at 2,4,8 and 12 h and 1,2,3,4 and 5 d after IT injection (T0-9).Four rats were sacrificed at T6 in each group and their lumbar enlargements were removed for microscopic examination.ResultsCompared with group C,no significant change in MWT and TWL was found at each time point in group D,MWT was significantly increased at T1-8 and TWL was significantly prolonged at T1-7 in groups L and N,and MWT was significantly increased at T1-6 and TWL was significantly prolonged at T1-6 in group M ( P ＜ 0.05 ).Compared with groups L and N,MWT was significantly decreased at T1-4 and TWL was significantly shortened at T1-4 in group M ( P ＜ 0.05).Pathological injury was significantly reduced in group M as compared with groups L and N.ConclusionT-type calcium channel is involved in the spinal neurotoxicity of IT lidocaine in rats.

Objective To investigate the relationship between the neuroprotective effect of epigallocatechin gallate ( EGCG ) for PC12 cells induced by 1-methyl-4-phenyl-pyridinium ( MPP+ ) and activating nuclear factor-related factor 2 ( NRF2 ).Methods Well differentiated PC12 cells treated with MPP+ were used as the in vitro cell models,and PC12 cells were pretreated with different concentrations of EGCG.MTT assay was used to investigate the cell viability.Western blot was used to observe the expression of NRF2 in cells and distribution in the nucleus and the cytoplasm.Real-time PCR was used to observe the antioxidant enzymes,HO-1 and NQO1 mRNA expression.Results Pretreatment of PC12 cells with different concentrations of EG CG for an hour could restore cell viability.Western blot showed that expression of NRF2 in cells treated with MPP+ for 24 hours was increased 148％ +5％ compared with the control group (t =6.102,P ＜0.01 ).The level of NRF2 in EGCG pretreated group was 188％ + 6％ compared with the control group(t =11.172,P ＜0.01 ).Moreover the NRF2 protein level in the nuclear was also increased.Western blot showed that the NRF2 protein level in the nuclear was 258％ +2％ compared with the control group (t =21.995,P ＜ 0.01 ).Further research found U 120,an inhibitor of ERK,could inhibit the effect of EGCG.The levels of NRF2 in both samples were 148％ ± 15％ and 158％ ± 1％ compared with their respective control groups(t =6.118,8.058,both P ＜0.01 ).In accordance with the NRF2 data,real-time PCR indicated that the levels of HO-1 and NQO1 mRNA expression increased obviously in the group pretreated with EGCG.Likewise,U120 could also inhibit HO-1 and NQO1 mRNA expression induced by EGCG.Conclusions EGCG can repair oxidative damage to PC12 cells induced by MPP+.The protective effect may be related through the ways to activate ERK-NRF2 and induce downstream of antioxidant enzyme expression,such as HO-1 and NQO1.

OBJECTIVE: To treat superficial hemangioma in children according to the local blood flow. METHODS: A total of 98 children with superficial hemangiomas admitted to our hospital from January 2005 to June 2009, and their clinical data were analyzed. RESULTS: According to the local blood flow velocity, 98 children were treated with injections or injection plus surgical treatment, respectively. Ninety-four children (95.9%) were cured. CONCLUSION Injection therapy is effective for children with superficial hemangioma, but we should arrange individualized treatment according to the local blood flow in children.
Adolescent ; Bleomycin ; administration & dosage ; analogs & derivatives ; Child ; Child, Preschool ; Female ; Glucocorticoids ; administration & dosage ; Hemangioma ; blood supply ; therapy ; Humans ; Infant ; Injections, Intralesional ; Male ; Regional Blood Flow ; Skin Neoplasms ; blood supply ; therapy

Objective To investigate the clinical diagnosis and treatment of children's relapsesable intussusception by Peutz-Jeghers syndrome.Methods 5 cases of relapsesable intussusception result from Peutz-Jeghers syndrome which confirmed by operation and pathological diagnosis in children were analyzed retrospectively.Results All patients were diagnosed definitely by operation and pathological diagnosis and recovered well postoperatively.Conclusions Treated with the intussusception and resected polypus is effect to Peutz-Jeghers syndrome because it caused intussusception recurred easily,and patients should be followed up and examined regularly.