Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation ; Adipose Tissue/immunology* ; Mice ; Male ; Humans ; Network Pharmacology ; Macrophages/immunology* ; Mice, Inbred C57BL ; Child ; Protein Interaction Maps/drug effects* ; Obesity/genetics* ; Inflammation/drug therapy*

Objective:To observe the effects of warm acupuncture on post-stroke cognitive impairment (PSCI) based on the theory of intestinal flora.Methods:A randomized controlled trial was conducted. 60 patients with PSCI in the Department of Acupuncture and Neurology of the First Affiliated Hospital of Xinjiang Medical University from October 2020 to June 2022 were selected as the observation objects, and were divided into 2 groups by random number table, with 30 cases in each group. On the basis of cognitive rehabilitation training, the treatment group was given warm acupuncture treatment, and the control group was given routine acupuncture treatment. 2 groups were treated for 4 weeks as 1 course, and a total of 4 courses were treated. Montreal cognitive assessment (MoCA) was used to assess patients' cognitive function before and after treatment, and mini-mental state examination (MMSE) was used to assess patients' intelligence level. The numbers of bifidobacteria and lactic acid bacteria in fecal samples were calculated, and plasma gamma-aminobutyric acid (GABA) levels were detected by ELISA to evaluate the clinical efficacy.Results:During the study, 1 case was lost in each of the two groups, and finally 29 cases were included in the curative effect statistics. The total effective rate was 79.3% (23/29) in the treatment group and 65.5% (19/29) in the control group, with statistical significance ( χ2=43.39， P<0.05). After treatment, MoCA score [(24.23±1.36) vs. (21.26±1.30), t=3.12] and MMSE score [(25.35±1.24) vs. (21.52±1.22), t=3.25] in the treatment group were higher than those in the control group ( P<0.05); Bifidobacterium [(9.20±1.25) LgCFU/g vs. (7.23±1.21) LgCFU/g, t=2.98], Lactic acid bacteria [(8.24±1.12) LgCFU/g vs. (6.25±1.22) LgCFU/g, t=2.92], and the level of GABA [(283.80±83.54) mmol/L vs. (264.76±61.38) mmol/L, t=10.54] were higher than those in the control group ( P<0.05 or P<0.01). Conclusion:Warm acupuncture and moxibustion can effectively regulate the number of intestinal beneficial bacteria in PSCI patients, increase the level of GABA, promote brain tissue repair and improve cognitive function.

Humans ; Diabetes Mellitus, Type 2/epidemiology* ; Air Pollution/adverse effects* ; Air Pollutants/toxicity* ; Risk Assessment ; Particulate Matter ; Environmental Exposure

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Adult ; Aged ; China/epidemiology* ; Cohort Studies ; Female ; Humans ; Male ; Metabolic Syndrome/etiology* ; Middle Aged ; Parks, Recreational/supply & distribution* ; Prevalence ; Residence Characteristics/statistics & numerical data* ; Rural Population/statistics & numerical data* ; Young Adult

Objective: To summarize the genetics and clinical phenotypes of epilepsy children with 2q24.3 microdeletion. Methods: All the patients with 2q24.3 microdeletion were retrospectively collected at the Pediatric Department of Peking University First Hospital from March 2017 to July 2022. The features of clinical manifestations, electroencephalogram (EEG), and neuroimaging were analyzed. Results: There were 13 patients with 2q24.3 microdeletion were included. All 13 patients had de novo copy number variation (CNV) with a deletion size ranged 0.18-7.31 Mb. The main pathogenic genes in the region were SCN3A, SCN2A, TTC21B, SCN1A and SCN9A genes. Among the 13 patients, 7 were boys, and 6 were girls. The onset age of epilepsy was 3.3(2.5, 6.0) months. Multiple seizure types were observed, including focal seizures in 13 patients, generalized tonic-clonic seizures (GTCS) in 6 patients, myoclonic seizures in 3 patients, epileptic spasm in 2 patients, and tonic seizures in 2 patients. Seizures were fever sensitivity in 9 patients. Status epilepticus was observed in 6 patients. One case had normal mental motor development and 12 cases had different degrees of developmental delay. Six patients had craniofacial abnormality, 1 had six-finger deformity of the right thumb, and 1 had multiple system abnormalities. EEG showed focal discharge in 3 cases, multifocal discharges in 5 cases, multifocal and generalized discharges in 1 case. Brain magnetic resonance imaging (MRI) showed enlargement of subarachnoid spaces in the frontal and temporal region in 4 patients, enlargement of lateral ventricle in 4 patients and delayed myelination of white matter in 1 patient. Dravet syndrome was diagnosed in 5 cases. The age at the last follow-up were 2.5(1.4,5.5) years, 1 patient was seizure free longer than 1 year, and 12 patients still had seizures. Conclusions: The epilepsy associated with 2q24.3 microdeletion is mainly induced by the deletion of SCN3A, SCN2A and SCN1A genes. The seizure onset age of 2q24.3 microdeletion related epilepsy was in infancy. Multiple seizure types are observed and the common seizure types include focal seizures and GTCS. Most patients have fever sensitivity and status epilepticus. Most patients have developmental delay. The phenotype of patients with deletion of SCN3A and SCN2A gene is more severe than that of patients with deletion of SCN1A gene only.
Humans ; Abnormalities, Multiple ; Chromosomes ; DNA Copy Number Variations ; Epilepsies, Myoclonic ; Epilepsy ; Fever ; NAV1.7 Voltage-Gated Sodium Channel ; Phenotype ; Retrospective Studies ; Seizures ; Status Epilepticus ; Chromosomes, Human, Pair 2

Objective: To analyze the genotypes and clinical phenotypes of patients with epilepsy associated with IQSEC2 gene variants. Methods: The genotypes, seizure types, electroencephalogram, neuroimage of 6 patients with IQSEC2 gene variants in the Department of Pediatrics, Peking University First Hospital from July 2019 to October 2021 were analyzed. Results: There were 5 males and 1 female. Six variants were de novo, including 2 frameshift variants (c.3801_3808dup/p.Q1270Rfs*130, c.1459_1460delAT/p.M487Vfs*2), 2 nonsense variants (c.3163C>T/p.R1055*, c.1417G>T/p.E473*), 1 in-frame deletion (c.2295_2297del/p.N765del) and 1 missense variant (c.2293A>G/p.N765D). Age at seizure onset ranged from 3 months to 2 years and 5 months. Multiple seizure types were observed, including epileptic spasms in 5 patients, focal seizures in 5 patients, tonic seizures in 3 patients, myoclonic seizures in 3 patients, atypical absence seizures in 2 patients and atonic seizures in 2 patients. All 6 patients showed global developmental delay before seizure onset. There were other clinical manifestations, including autistic features in 3 patients, microcephaly in 3 patients, dystonia in 2 patients and binocular esotropia in 1 patient. The electroencephalogram showed slow background activity and hypsarrhythmia in all 6 patients. Brain magnetic resonance imaging showed abnormal in 5 patients and normal in 1 patient. Five patients were diagnosed with infantile spasms. Among them, 4 patients had late-onset infantile spasms. One patient was unclassified developmental epileptic encephalopathy. The age of last follow-up ranged from 3 years and 2 months to 7 years and 2 months. All 6 patients still had seizures after multiple anti-seizure medications. Conclusions: The seizure onset of patients with IQSEC2 gene variants usually begins after 1 year of age. The common seizure types include epileptic spasms and focal seizures. Patients usually have a global developmental delay before seizure onset. IQSEC2 variants could be related to developmental and epileptic encephalopathy, and most patients are diagnosed with late onset infantile spasms. Epilepsy associated with IQSEC2 gene variants is usually refractory.
Female ; Male ; Child ; Humans ; Spasms, Infantile/genetics* ; Genotype ; Phenotype ; Epilepsy/genetics* ; Seizures ; Spasm ; Guanine Nucleotide Exchange Factors

Objective: To summarize the phenotypes of epilepsy in patients with MBD5 gene variants. Methods: A total of 9 epileptic patients, who were treated in the Department of Pediatrics, Peking University First Hospital from July 2016 to September 2021 and detected with MBD5 gene pathogenic variants, were enrolled. The features of clinical manifestations, electroencephalogram (EEG), and neuroimaging were analyzed retrospectively. Results: Among 9 patients, 6 were male and 3 were female. Age at seizure onset ranged from 5 to 89 months. Multiple seizure types were observed, including generalized tonic clonic seizures (GTCS) in 7 patients, myoclonic seizures in 5 patients, focal seizures in 5 patients, atypical absence seizures in 3 patients, atonic seizures in 2 patients, myoclonus absence seizures in 1 patient, epileptic spasms in 1 patient, and tonic seizures in 1 patient. There were 8 patients with multiple seizure types, 2 patients with sensitivity to fever and 5 patients with clustering of seizures. Two patients had a history of status epilepticus. All patients had developmental delay before seizure onset. Nine patients had obvious language delay, and 6 patients had autism-like manifestations. Five patients had slow background activity in EEG. Interictal EEG showed abnormal discharges in 9 patients. Brain magnetic resonance imaging (MRI) was normal in all patients. A total of 9 epileptic patients carried MBD5 gene variants, all of them were de novo variants. There were MBD5 gene overall heterozygous deletion in 1 patient, large fragment deletions including MBD5 gene in 3 patients and single nucleotide variations (c.300C>A/p.C100X, c.1775delA/p.N592Tfs*29, c.1759C>T/p.Q587X, c.150_151del/p.Lys51Asnfs*6, c.113+1G>C) in 5 patients. The age at last follow-up ranged from 2 years and 9 months to 11 years and 11 months. At the last follow-up, 2 patients were seizure-free for more than 11 months to 4 years 6 months, 7 patients still had seizures. Conclusions: The initial seizure onset in patients with MBD5 gene variants usually occurs in infancy. Most patients have multiple seizure types. The seizures may be fever sensitive and clustered. Developmental delays, language impairments, and autistic behaviors are common. MBD5 gene variants include single nucleotide variations and fragment deletions. Epilepsy associated with MBD5 gene variants is usually refractory.
Child ; Child, Preschool ; DNA-Binding Proteins/genetics* ; Electroencephalography ; Epilepsies, Myoclonic/genetics* ; Epilepsy/genetics* ; Female ; Fever ; Humans ; Infant ; Male ; Nucleotides ; Phenotype ; Retrospective Studies ; Seizures/genetics*

Objectives: To evaluate the therapeutic effects of unilateral/bilateral bone conduction hearing rehabilitation in patients with bilateral microtia accompanied with severe conductive hearing loss following staged auricle reconstruction and bonebridge implantation. Methods: Thirty-two patients, including 20 males and 12 females, with an average age of 11.8, who received surgical treatment in Peking Union Medical College Hospital (PUMCH) from March, 2016 to January, 2020 with bilateral microtia-atresia were included. Hearing thresholds, speech perception and high-resolution CT of the temporal bone were evaluated prior to surgery and individualized surgery plans (staged auricle reconstruction and bonebridge implantation) were made. Hearing thresholds and speech perception in quiet and noise (SNR = 5 dB) using unilateral Bonebridge were tested two weeks after the implantation surgery when the Bonebridge was activated and at 3^th, 6^th, 12^th month after activation. Hearing thresholds and speech perception were also tested at least three months after the activation of the Bonebridge under three conditions: unaided, unilateral Bonebridge, and bilateral bone conduction hearing devices (Bonebridge plus contralateral ADHEAR). The international hearing aid assessment questionnaire (IOI-HA) and Glasgow children's benefit questionnaire were used to evaluate the subjective benefits of the patients. SPSS 21.0 software was used for statistical analysis. Results: Among these 32 patients, nine were conducted Bonebridge implantation surgery before auricle reconstruction, six were simultaneously with auricle reconstruction and 17 were implanted after auricle reconstruction surgery. Compared with unaided, the mean hearing thresholds (0.5, 1, 2, and 4 kHz) and speech perception following unilateral BCHD and bilateral BCHD attachment were improved significantly (P<0.05 each). The speech perceptin in noise of bilateral BCHD was better than unilateral (P<0.05 each). The modified questionnaire revealed high levels of patient satisfaction following use of both unilateral and bilateral devices. Conclusions: Individulized surgical procedures involving auricle reconstruction and Bonebridge implantation are safe and effective for patients with bilateral microtia-atresia, solving both appearance and hearing problems. Speech perception in noise is better following bilateral BCHD than unilateral BCHD attachment.
Bone Conduction ; Child ; Congenital Microtia/surgery* ; Ear, External ; Female ; Hearing Aids ; Hearing Loss, Conductive/surgery* ; Humans ; Male ; Speech Perception

ObjectiveTo investigate the role of PI3K/Akt/eNOS signaling pathway in the protective effect of hydrogen sulfide（H₂S） on endothelial cell senescence induced by hydrogen peroxide （H₂O₂）. MethodsSenescence in human umbilical vein endothelial cells （HUVEC） was induced by 60 μmol/L H₂O₂ for 1 h， and the effects of NaHS on the senescence were examined by the expression of plasminogen activator inhibitor 1 （PAI-1） and senescence-associated β-galactosidase （SA-β-Gal） staining. Meanwhile，the expression of protein kinase B（Akt）， Phospho protein kinase B（p-Akt）， and endothelial nitric oxide synthase （eNOS） were examined by western blot， and the senescence-related parameters. The content of the nitric oxide （NO） was measured by nitrate reduction method. ResultsCompared with the control group， after being treated with 60 μmol/L H₂O₂， the number of SA-β-gal positive cells and the expression of PAI-1 were significantly increased. However， after pretreatment of NaHS， the expression of PAI-1， the ratio of SA-β-gal positive cells was significantly decreased， but the expression of p-Akt， eNOS and the NO concentration increased. ConclusionNaHS could reverse HUVEC senescence induced by H₂O₂， and this may be highly associated with PI3K/Akt/eNOS signaling pathway.