BACKGROUND:Umbilical cord mesenchymal stem cells(UMSCs)have been proven to have therapeutic effects on cartilage injury,and exosomes are the main carriers for UMSCs to exert therapeutic effects in vivo.Our research group previously found that lncRNA H19 is an important active molecule that mediates the activity of UMSCs-derived exosomes regulating chondrocytes.LncRNA H19 could adsorb miR-29b-3p to promote the proliferation and regeneration of chondrocytes,but its downstream mechanism is still unclear. OBJECTIVE:To reveal the specific mechanism of UMSCs in the treatment of cartilage injury from the perspective of exosomes and lncRNAs,so as to provide a new target for the treatment of cartilage injury. METHODS:UMSCs stably overexpressing lncRNA H19 were constructed.H19-Exos were extracted by ultra-centrifugation.The exosomes were identified by transmission electron microscopy,Nanosight,western blot assay and exosome uptake assay.The effect of miR-29b-3p overexpression and silencing on the TGF-β1/Smad3 pathway was detected by western blot assay,qPCR and dual luciferase reporter gene system.The biological effect of H19-Exos on cartilage regeneration was verified by the specific TGF-β1/Smad3 inhibitor in vitro and in vivo. RESULTS AND CONCLUSION:(1)H19-Exos showed a typical cup shape under an electron microscope,and the particle size was approximately 130 nm.H19-Exos expressed CD63,CD81 and TSG1010.(2)Overexpression of miR-29b-3p could down-regulate the mRNA and protein levels of TGF-β1 and Smad3,while silencing miR-29b-3p could up-regulate the mRNA and protein levels of TGF-β1/Smad3.(3)Dual-luciferase reporter gene system showed that miR-29b-3p had significant differences in the activities of downstream target genes TGF-β1 and Smad3.(4)The osteoarthritis models of rats were successfully established by injection of type II collagenase into the knee joint.H19-Exos significantly promoted cartilage regeneration.The specific TGF-β1/Smad3 inhibitor SB-431542 could block the biological effect of H19-Exos on cartilage regeneration in vitro and in vivo.(5)This study systematically demonstrated the promotion effect of UMSCs-derived exosomes highly expressing lncRNA H19 on cartilage regeneration,and the specific mechanism is that lncRNA H19 promotes cartilage regeneration by targeting miR-29b-3p/TGF-β1/Smad3 pathway.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective To investigate the correlation between claudin-5 level and the risk of hemor-rhagic transformation(HT)in elderly stroke patients after thrombolysis.Methods A total of 192 elderly stroke patients hospitalized in our department from February 2021 to October 2022 were recruited,and divided into HT group(32 cases,including 14 of parenchymal hematoma type and 18 of hemorrhagic cerebral infarction type)and non-HT group(160 cases)according to the results of head CT or MRI 48 h after thrombolysis.The clinical data and serum claudin-5 level were com-pared between the two groups.Multivariate logistic regression analysis was used to identify the in-fluencing factors of HT risk after thrombolysis in elderly stroke patients.Restricted cubic splines were drawn to analyze the correlation between claudin-5 level and HT risk after thrombolysis.Re-sults The HT group had higher proportion of atrial fibrillation,longer onset to thrombolysis time,higher baseline NIHSS score,and fasting blood glucose and claudin-5 levels than the non-HT group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that time from onset to thrombolysis(OR=2.589,95％CI:1.202-5.573,P=0.015),baseline NIHSS score(OR=1.415,95％CI:1.213-1.651,P=0.000),and fasting blood glucose(OR=1.552,95％CI:1.014-2.375,P=0.043)and claudin-5 levels(OR=1.174,95％CI:1.076-1.281,P=0.000)were risk factors for HT after thrombolysis in elderly stroke patients.Restricted cubic spline anal-ysis demonstrated that claudin-5 level had a nonlinear relationship with the risk of HT in the pa-tients after thrombolysis(x2=12.380,P=0.006).Conclusion Serum claudin-5 level is associated with HT after thrombolysis in elderly stroke patients,and shows a dose-response relationship with HT.

Objective:To analyze the clinical features and genetic etiology of 17 Chinese pedigrees affected with X-linked intellectual disability (XLID).Methods:Seventeen pedigrees affected with unexplained intellectual disability which had presented at Henan Provincial People′s Hospital from May 2021 to May 2023 were selected as the study subjects. Clinical data of the probands and their pedigree members were collected. Trio-whole exome sequencing (Trio-WES), Sanger sequencing and X chromosome inactivation (XCI) analysis were carried out. Pathogenicity of candidate variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics and co-segregation analysis.Results:The 17 probands, including 9 males and 8 females with an age ranging from 0.6 to 8 years old, had all shown mental retardation and developmental delay. Fourteen variants were detected by genetic testing, which included 4 pathogenic variants ( MECP2: c. 502C>T, MECP2: c. 916C>T/c.806delG, IQSEC2: c.1417G>T), 4 likely pathogenic variants ( MECP2: c. 1157_1197del/c.925C>T, KDM5C: c. 2128A>T, SLC6A8: c. 1631C>T) and 6 variants of uncertain significance ( KLHL15: c. 26G>C, PAK3: c. 970A>G/c.1520G>A, GRIA3: c. 2153C>G, TAF1: c. 2233T>G, HUWE1: c. 10301T>A). The PAK3: c.970A>G, GRIA3: c. 2153C>G and TAF1: c. 2233T>G variants were considered as the genetic etiology for pedigrees 12, 14 and 15 by co-segregation analysis, respectively. The proband of pedigree 13 was found to have non-random XCI (81: 19). Therefore, the PAK3: c. 1520G>A variant may underlie its pathogenesis. Conclusion:Trio-WES has attained genetic diagnosis for the 17 XLID pedigrees. Sanger sequencing and XCI assay can provide auxiliary tests for the diagnosis of XLID.

The red gene is the crystallization of the ideas and wisdom of the Chinese Communist Party’s century-long struggle, and plays an irreplaceable and decisive role in cultivating socialist hospital culture and medical professionals in the new era. The Chinese Academy of Medical Science (CAMS) Cancer Hospital has a distinctive red gene trait. For more than 60 years since its establishment, through the protection of the red gene inheritance carrier, the enrichment of the content and expression form of the red gene inheritance, and the exploration and demonstration of the role model in the red gene inheritance, it has always integrated the red gene inheritance into the whole process of hospital construction, development and spiritual culture cultivation, and has achieved remarkable results, accumulated rich practical experience, and provided a useful reference for the spiritual and cultural construction of public hospitals.

Objective:To explore the application value of two-dimensional speckle tracking imaging (2D-STI) in evaluating diaphragm function, and to compare the ability of 2D-STI and conventional diaphragm ultrasonography in diagnosing diaphragmatic dysfunction and evaluating disease severity in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods:A total of 58 AECOPD patients admitted to the First Affiliated Hospital of Xi′an Jiaotong University from January to October 2021 were retrospectively enrolled as AECOPD group, and 34 healthy subjects were recruited as control group during the same period. Repeatability test of diaphragmatic 2D-STI was performed. According to modified Medical Research Council (mMRC) dyspnea scores system and COPD Assessment Test (CAT), mMRC 0-1 and CAT<10 was classified as group A, mMRC≥2 and CAT≥10 was classified as group B. The baseline characteristics, conventional diaphragm ultrasonography parameters(thickening fraction and excursion) and 2D-STI parameters (longitudinal and radial strains) were compared between the AECOPD group and the control group, and the Spearman correlation between parameters of AECOPD group and forced expiratory volume in one second (FEV1) was analyzed. The differences of these parameters between group A and B were also compared. The ROC curve of conventional diaphragm ultrasonography parameters and 2D-STI parameters was plotted to differentiate group A from group B, and the diagnostic efficacy was evaluated.Results:Great intra- and inter-observer reproducibility was found for all diaphragmatic 2D-STI parameters, with ICCs above 0.80 for all measurements. The control group and the AECOPD group did not differ in age, sex and body mass index( P>0.05), whereas there were significant differences in smoking history, lung function, bilateral thickening fraction, excursion, longitudinal and radial strains( P<0.05). Compared with control group, patients in group A had a significant increase in diaphragm thickness ( P<0.05), while there was no significant difference in that between group B and control group ( P>0.05). The bilateral longitudinal strains, radial strains and thickening fraction of diaphragm were linearly correlated with FEV1 (right side rs=0.828, 0.794, 0.843, respectively; all P<0.001; left side rs=0.757, 0.704, 0.752, respectively; all P<0.001 ), while the correlation between excursion and FEV1 was not significant(right side rs=0.247, left side rs=0.253; all P>0.05). There were significant differences in bilateral longitudinal strains, radial strains and thickening fraction between group A and group B(all P<0.05), whereas there was no significant difference in excursion between the two groups ( P>0.05). ROC analysis showed bilateral longitudinal and radial strains had higher accuracy in distinguishing group A from group B than thickening fraction and excursion(right side AUCs 0.90, 0.84, 0.78 and 0.62, respectively; left side AUCs 0.85, 0.83, 0.77 and 0.62, respectively). Conclusions:2D-STI is a real-time noninvasive technique for diaphragm function assessment, which has high clinical value. Compared with conventional ultrasonography, 2D-STI shows more accuracy and effectiveness in diagnosing diaphragmatic dysfunction and evaluating disease severity of patients with AECOPD.

OBJECTIVE To explore the difference in chemical components of essential oil from medicinal part （rhizome）and non-medicinal parts （fibrous roots ，stems，and leaves ）of Atractylodes chinensis，and to preliminarily evaluate their antibacterial activity in vitro . METHODS The essential oil was extracted from three parts of A. chinensis by steam distillation ，and their chemical components and relative contents were analyzed and identified by gas chromatography -mass spectrometry （GC-MS）. The antibacterial activities of essential oil （5 mg/mL） from different parts against Staphylococcus aureus ，S. albus and Bacillus subtilis were determined by paper diffusion method . The correlation between chemical components in essential oil and antibacterial activity was analyzed . RESULTS A total of 60 chemical constituents were identified from the essential oilof rhizome ，fibrous roots ，stems and leaves of A. chinensis， mainly composed of terpenes ，sesquiterpenoids，alcohols and ketones. There were 8 kinds of common components in the essential oil of rhizome ，fibrous root and stem and leaves ，which were elementol ，cadinene，agarospirol，valencian citrine ， caryophyllin，β-sesquidiene，γ-eucalyptol and β-eucalyptol. A total of 26 components were identified from the essential oil of rhizome，of which the relative content of 4-benzaldehyde was the highest （31.56%）；a total of 21 components were identified from the essential oil of fibrous roots ，among which the relative content of β-eucalyptol was the highest （44.39%）；a total of 42 components were identified from the essential oil of stems and leaves ，among which the relative content of β-sesquidiene was the highest（14.83%）. The essential oil from different parts had certain antibacterial effect on S. aureus，S. albus and B. subtilis. The order of antibacterial effect was rhizome ＞fibrous roots ＞stem and leaves ；the relative contents of β-caryophyllene，α-humulene and modhephene were positively correlated with inhibitory effects of essential oil against S. aureus and B. subtilis（P＜0.05 or P＜0.01）. The relative contents of atractylone ，zingiberene and agarospirol were positively correlated with the inhibitory effect of essential oil against B. subtilis（P＜0.05 or P＜0.01）. CONCLUSIONS There are significant differences in the chemical composition and contents of essential oil from medicinal and non -medicinal parts of A. chinensis，and all of them have antibacterial activity in vitro .

Objective:To investigate the effect of anterior or posterior debridement on infections of the lumbar vertebral fusion with cage and pedical screw system.Methods:A total of 10 cases (3 males and 7 females, age 49.80±13.29 years) with infections in the lumbar fusion device were admitted from January 2013 to December 2019. The cases were diagnosed with deep infections after the preview surgery at 10.80±13.24 months, including 10 cases with 12 cages infections and 8 cases with screw system infections. 7 cases were done with debridement and removal of the cages via the anterior approach. And another 3 cases underwent posterior debridement and removal of lumbar fusion cages. The changes in laboratory examination such as WBC count, ESR, CRP, visual analogue scale (VAS) and Oswestry Disability Index (ODI) score were compared preoperatively, 2 months and 6 months postoperatively.Results:No patients were lost in the follow-up. The average follow-up time periods is 16.30±5.10 months (range 9-24 months). There was no significant difference in WBC count between 2 and 6 months after surgery compared with preoperation ( F=0.855, P=0.436). The ESR, CRP, VAS and ODI scores decreased in 2 months and 6 months after sugery, which has significant differences compared preoperation ( P<0.05). The abnormal signals in the lambar vertebral showed a gradual fading trend in the postoperative MRI. The completely fading time was 5.00±1.33 months (range 3-7 months). One-stage bone grafting was performed in 6 cases with 8 spaces via anterior approach, 5 cases with 7 spaces showed the intervertebral fusion after postoperative with 6.80±2.28 months (range 4-10 months), 1 case wirh 1 space was not fused. One-stage bone grafting was performed in 2 cases via posterior approach: 1 case was fused after postoperative and the other patient was not, which due to bone graft area infection. Postoperative bone graft displacement occurred with 1 case and 1 case with L 5 nerve root pulling injury during the operation. Conclusion:The fusion cage can be removed by debridement via posterior approach, but it is difficult to done the completely debridement, which the main reason is the obstruction of the posterior nerve and bone structure. Posterior approach also have risks of infection recurrence and nerve root injury. Cage removal via anterior approach was relatively easy and debridement was thoroughly, which has the risk of injury of important adjacent vessels.

OBJECTIVE: To explore the genetic basis for a fetus suspected for congenital nephrotic syndrome of Finland (CNF). METHODS: Genomic DNA was extracted from peripheral and umbilical cord blood samples derived from both parents and the fetus. Potential variants were detected by using next-generation sequencing. Suspected variants were confirmed by Sanger sequencing. RESULTS: The fetus was found to carry compound heterozygous variants c.1440+1G>A and c.925G>T of the NPHS1 gene, which were respectively inherited from its mother and father. CONCLUSION Identification of the compound heterozygous NPHS1 variants has enabled diagnosis of CNF in the fetus and genetic counseling for the affected family.
Female ; Fetus ; Finland ; Heterozygote ; Humans ; Membrane Proteins ; genetics ; Nephrotic Syndrome ; congenital ; diagnosis ; Pregnancy ; Prenatal Diagnosis

Objective: To explore the genetic basis for a fetus suspected for congenital nephrotic syndrome of Finland (CNF). Methods: Genomic DNA was extracted from peripheral and umbilical cord blood samples derived from both parents and the fetus. Potential variants were detected by using next-generation sequencing. Suspected variants were confirmed by Sanger sequencing. Results: The fetus was found to carry compound heterozygous variants c. 1440+ 1G>A and c. 925G>T of the NPHS1 gene, which were respectively inherited from its mother and father. Conclusion Identification of the compound heterozygous NPHS1 variants has enabled diagnosis of CNF in the fetus and genetic counseling for the affected family.