Analyzing the methanation thermodynamic feasibility of steel plant byproduct gases.

To improve the utilization of byproduct gases in the steel plant, the coke oven gas (COG) methanation combined with blast furnace gas (BFG) and basic oxygen furnace gas (BOFG) was proposed in viewpoint of economy and environment. The optimization mathematics model based on Gibbs free energy minimization was established to predict the thermodynamic feasibility of the proposed methanation. To solve the proposed model, the convenient method was implemented by using the Gibbs module in Aspen Plus software. Effects of operation parameters on the methanation performance were revealed to identify the optimized conditions. To reduce the solid carbon concentration, it was found that the optimized conditions of temperature, pressure and stoichiometric number were 650 °C, 30 bar and 3.0, respectively. Moreover, it was discovered that 10 mol% of BFG or BOFG could be mixed into COG to obtain the maximum methane yield. In addition, it was testified that there were the good agreements between calculated results and industrial and published data, which indicated that the proposed methanation was thermodynamically feasible. Therefore, the simple and easy method was developed to evaluate the methanation operating conditions from the aspect of thermodynamic equilibrium, which provided the basic process conditions of byproduct gases methanation to enhance the steel plant efficiency and reduce carbon emissions.

Nanoplastic propels diet-induced NAFL to NASH via ER-mitochondrial tether-controlled redox switch.

Nonalcoholic steatohepatitis (NASH) is multifactorial that lifestyle, genetic, and environmental factors contribute to its onset and progression, thereby posing a challenge for therapeutic intervention. Nanoplastic (NP) is emerged as a novel environmental metabolism disruptor but the etiopathogenesis remains largely unknown. In this study, C57BL/6 J mice were fed with normal chow diet (NCD) and high-fat diet (HFD) containing 70 nm polystyrene microspheres (NP). We found that dietary-derived NP adsorbed proteins and agglomerated during the in vivo transportation, enabling diet-induced hepatic steatosis to NASH. Mechanistically, NP promoted liver steatosis by upregulating Fatp2. Furthermore, NP stabilized the Ip3r1, and facilitated ER-mitochondria contacts (MAMs) assembly in the hepatocytes, resulting in mitochondrial Ca2+ overload and redox imbalance. The redox-sensitive Nrf2 was decreased in the liver of NP-exposed mice, which positively regulated miR26a via direct binding to its promoter region [-970 bp to -847 bp and -318 bp to -176 bp]. NP decreased miR26a simultaneously upregulated 10 genes involved in MAMs formation, lipid uptake, inflammation, and fibrosis. Moreover, miR26a inhibition elevated MAMs-tether Vdac1, which promoted the nucleus translocation of NF-κB P65 and Keap1 and functionally inactivated Nrf2, leading to a vicious cycle. Hepatocyte-specific overexpressing miR26a effectively restored ER-mitochondria miscommunication and ameliorated NASH phenotype in NP-exposed and Keap1-overexpressed mice on HFD. The hepatic MAM-tethers/Nrf2/miR26a feedback loop is an essential metabolic switch from simple steatosis to NASH and a promising therapeutic target for oxidative stress-associated liver damage and NASH.

Effect of Liuwei Dihuang Tang on ferroptosis pathway in retinal tissue of aging model rats / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the effects of Liuwei Dihuang Tang on the expression levels of ferritin, recombinant solute carrier family 7 member 11(SLC7A11), glutathione(GSH), and glutathione peroxidase 4(GPX4)in retinal of aging model rats.METHODS: A total of 45 SD rats were randomly divided into a blank group, a model group, and a traditional Chinese medicine(TCM)group, with 15 rats in each group. The blank group was intraperitoneally injected with physiological saline, while the model group and TCM group were intraperitoneally injected with D-galactose [500 mg/(kg·d)]. At the same time, the TCM group was orally administered with Liuwei Dihuang Tang [6.75 g/(kg·d)], while the blank group and model group were orally administered with equal volume of physiological saline for 8 consecutive wk. The expression levels of ferritin, SLC7A11, GSH, and GPX4 in the retinal tissues of rats in each group were detected.RESULTS: The expression of ferritin in the retinal tissue of the model group was increased compared to the blank group(P<0.05), while the expression of GSH, SLC7A11, and GPX4 was reduced(P<0.05). The expression of GSH, SLC7A11, and GPX4 in the retina tissue of rats in the TCM group was higher than that in the model group(P<0.05).CONCLUSIONS: Liuwei Dihuang Tang may exert a delaying effect on retinal aging by regulating the ferroptosis pathway.

Activation of cGAS-STING signaling pathway promotes liver fibrosis and hepatic sinusoidal microthrombosis.

Inflammation plays an essential role in the development liver fibrosis.The Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) is a central cytoplasmic DNA sensor which can recognize cytoplasmic DNA, known to trigger stimulator of interferon genes (STING) and downstream proinflammatory factors. Here, we investigated the role of cGAS-STING signaling pathway in the pathogenesis of liver fibrosis.Differentially expressed genes (DEGs) in human liver tissue were identified using RNA-Seq analysis. As models of liver fibrosis, chronic Carbon tetrachloride (CCl4) exposure were applied in cGAS-knockout mice. LX-2 cells were co-cultured with human liver sinusoidal endothelial cells (LSECs) to explore the underlying mechanisms of hepatic sinusoidal microthrombosis in an inflammatory microenvironment. The endoscopic ultrasound-guided portal vein pressure gradient (EUS-PPG) method was used to analyze the associations between hepatic sinusoidal microthrombosis and PPG in patients with liver fibrosis and portal hypertension (PTH). The RNA-seq analysis results showed that DEGs were enriched in inflammation and endothelial cell activation. The upregulation of the cGAS-STING signaling exacerbated liver fibrosis and intrahepatic inflammation. It also exacerbated LSECs impairment and increased the contribution of hepatic sinusoidal microthrombosis to liver fibrosis in vivo and in vitro. Prothrombotic mediators and proinflammatory factors were associated with PPG in patients with liver fibrosis and portal hypertension. Therefore, activating cGAS-STING signaling pathway promotes liver fibrosis and hepatic sinusoidal microthrombosis, which may lead to increased portal vein pressure.

The ubiquitin-binding protein MdRAD23D1 mediates drought response by regulating degradation of the proline-rich protein MdPRP6 in apple (Malus domestica).

RAD23 (RADIATION SENSITIVE23) proteins are a group of UBL-UBA (ubiquitin-like-ubiquitin-associated) proteins that shuttle ubiquitylated proteins to the 26S proteasome for breakdown. Drought stress is a major environmental constraint that limits plant growth and production, but whether RAD23 proteins are involved in this process is unclear. Here, we demonstrated that a shuttle protein, MdRAD23D1, mediated drought response in apple plants (Malus domestica). MdRAD23D1 levels increased under drought stress, and its suppression resulted in decreased stress tolerance in apple plants. Through in vitro and in vivo assays, we demonstrated that MdRAD23D1 interacted with a proline-rich protein MdPRP6, resulting in the degradation of MdPRP6 by the 26S proteasome. And MdRAD23D1 accelerated the degradation of MdPRP6 under drought stress. Suppression of MdPRP6 resulted in enhanced drought tolerance in apple plants, mainly because the free proline accumulation is changed. And the free proline is also involved in MdRAD23D1-mediated drought response. Taken together, these findings demonstrated that MdRAD23D1 and MdPRP6 oppositely regulated drought response. MdRAD23D1 levels increased under drought, accelerating the degradation of MdPRP6. MdPRP6 negatively regulated drought response, probably by regulating proline accumulation. Thus, "MdRAD23D1-MdPRP6" conferred drought stress tolerance in apple plants.

Tumor-associated macrophages-derived exo-let-7a promotes osteosarcoma metastasis via targeting C15orf41 in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) immune environment is complexed and the immune factors-related to OS progression need to be explored. Tumor-associated macrophages (TAMs) are regarded as immune suppressive and tumor-promoting cells. However, the underlying mechanisms through which TAMs function are still fragmentary. Here, we aim to explore the underlying mechanisms by which TAMs regulate OS progression. METHODS: TAMs from OS tissues were isolated by flow cytometry. Exosomes derived from TAMs were separated using ultracentrifugation and western blotting. Transmission electron microscopy (TEM), and flow cytometry were constructed to characterize TAMs-derived exosomes. Additionally, the differential MicroRNAs (miRNAs) and genes were detected through RNA sequencing, and further validated using real-time PCR (RT-PCR). OS cell metastasis ability was assessed using transwell invasion and scratch wound healing assays. MiRNAs mimic and lentiviral vectors were utilized to explore the effects on OS progression. RESULTS: Exosome secreted by TAMs accelerated the OS metastasis. Let-7a level was upregulated in TAMs derived exosomes, which downregulated C15orf41 by targeting 3'-untranslated region (UTR). Furthermore, overexpressing let-7a enhanced invasion and migration by blocking the transcription of C15orf41. In consistent, up-regulating let-7a promoted OS progression and made the prognosis to be worse, which can be reversed by C15orf41 overexpression. CONCLUSION: This study highlighted the critical role of TAMs-derived exosomes in OS progression and explored the potential value of the let-7a/C15orf41 axis as an indicator or target for OS.

The Prognostic Value of a lncRNA Risk Model Consists of 9 m6A Regulator-Related lncRNAs in Hepatocellular Carcinoma (HCC).

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Although the RNA modification N6-methyladenine (m6A) has been reported to be involved in HCC carcinogenesis, early diagnostic markers and promising personalized therapeutic targets are still lacking. In this study, we identified that 19 m6A regulators and 34 co-expressed lncRNAs were significantly upregulated in HCC samples; based on these factors, we established a prognostic signal of HCC associated with 9 lncRNAs and 19 m6A regulators using LASSO Cox regression analysis. Kaplan-Meier survival estimate revealed correlations between the risk scores and patients' OS in the training and validation dataset. The ROC curve demonstrated that the risk score-based curve has satisfactory prediction efficiency for both training and validation datasets. Multivariate Cox's proportional hazard regression analysis indicated that the risk score was an independent risk factor within the training and validation dataset. In addition, the risk score could distinguish HCC patients from normal non-cancerous samples and HCC samples of different pathological grades. Eventually, 232 mRNAs were co-expressed with these 9 lncRNAs according to GSE101685 and GSE112790; these mRNAs were enriched in cell cycle and cell metabolic activities, drug metabolism, liver disease-related pathways, and some important cancer related pathways such as p53, MAPK, Wnt, RAS and so forth. The expression of the 9 lncRNAs was significantly higher in HCC samples than that in the neighboring non-cancerous samples. Altogether, by using the Consensus Clustering, PCA, ESTIMATE algorithm, LASSO regression model, Kaplan-Meier survival assessment, ROC curve analysis, and multivariate Cox's proportional hazard regression model analysis, we established a prognostic marker consisting of 9 m6A regulator-related lncRNAs that markers may have prognostic and diagnostic potential for HCC.

Combination of acupuncture and medication for dry eye complicated with computer vision syndrome: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical efficacy of acupuncture, Chinese medication and combination of acupuncture and medication in the treatment of dry eye complicated with computer vision syndrome (CVS).@*METHODS@#A total of 152 patients with dry eye complicated with CVS were randomly divided into an acupuncture-medication group (38 cases, 1 case was removed), an acupuncture group (38 cases, 1 case dropped off), a Chinese medication group (38 cases, 1 case was removed), and a western medication group (38 cases, 1 case dropped off). In the western medication group, sodium hyaluronate eye drop combined with esculin and digitalis glycosides eye drop were used. In the acupuncture group, acupuncture was applied at bilateral Taiyang (EX-HN 5)， Cuanzhu (BL 2), Fengchi (GB 20), Qimen (LR 14) , and Hegu (LI 4) etc., once a day. In the Chinese medication group, Yiqi Congming decoction formula ganule was given orally, one dose a day. In the acupuncture-medication group, acupuncture combined with Yiqi Congming decoction formula granule were used. All groups were treated for 14 d. The non-invasive first tear film break-up time (NIBUT f), non-invasive average tear film break-up time (NIBUT av), tear meniscus height (TMH), ocular surface disease index (OSDI) score, and CVS symptom score were compared between the patients of each group before and after treatment.@*RESULTS@#After treatment, the NIBUT f, NIBUT av, and TMH were increased compared with those before treatment in the patients of the 4 groups (P<0.01); the NIBUT f and NIBUT av in the acupuncture-medication group and the acupuncture group were higher than those in the Chinese medication group and the western medication group (P<0.05), and the TMH in the acupuncture-medication group and the Chinese medication group were higher than those in the acupuncture group and the western medication group (P<0.05). After treatment, the OSDI scores, the various scores and total scores of CVS (except for head symptom score in the western medication group) were decreased compared with those before treatment in the patients of the 4 groups (P<0.01). The OSDI score, total score, eye symptom score, and body symptom score of CVS in the acupuncture-medication group were lower than those in the acupuncture group, the Chinese medication group, and the western medication group (P<0.01, P<0.05), the head symptom score of the acupuncture-medication group was lower than that in the western medication group (P<0.05), and the CVS physical symptom scores and mental cognitive symptom scores of the acupuncture-medication group and the acupuncture group were lower than those in the Chinese medication group and the western medication group (P<0.05).@*CONCLUSION@#Acupuncture has advantages in improving NIBUT f, NIBUT av, and CVS physical symptoms and cognitive symptoms, and the Chinese medication has advantage in improving TMH. The combination of acupuncture and Chinese medication has better effects compared with monotherapy.

Analysis on the current situation of clinical blood fees exemption for blood donors and their family members in Henan / 中国输血杂志

【Objective】 To analyze the current situation of direct exemption of clinical blood fess for voluntary blood donors and their family members in Henan Province, in order to improve and fully implement the policy. 【Methods】 According to the policy on blood fees exemption issued by China and Henan Province in 2019,the data of hospitals in 18 prefecture-level cities in Henan from 2020 to 2021 were continuously collected from the system of clinical blood fees exemption,including the way of exemption,the number of people (times) of exemption,exemption amount, the proportion of blood fees exemption and the total exemption rate. The experience gained in the past two years after the implementation of the policy was summarized,and the existing problems and causes were analyzed. 【Results】 The rates of direct exemption of blood fees in Henan Province in 2020 and 2021 were 34.53% (8 709/25 221) and 71.68%(23 587/32 906) (P<0.05) ,respectively. In 2021, the direct exemption rate of blood fees in 18 cities was 6.20% (83/1 370) to 88.50% (1 332/1 505) [ (47.35±41.15)%],and increased month by month from 43.19% (1 183/2 507) in January to 83.15% (2 097/2 522) in August, then remained stable at a similar level to August from September to December, with 83.43% (2 744/3 289) in December as the highest for the year. 【Conclusion】 The implementation of the policy of blood fees exemption showed significant effectiveness, which has effectively promoted the development of voluntary blood donation in Henan. However, there is still room for improving the policy in some cities, which is expected to further increase the direct exemption rate of the city and the whole province.

Research progress of MicroRNA in hypertension and its target organ damage / 中国药理学通报

Hypertension is a risk factor for a variety of cardiovascular diseases, which is an important public health problem in the world today. MiRNAs are a class of highly conserved non-coding small RNAs. In recent years, studies have found that miRNAs are involved in the occurrence and development of hypertension through a variety of ways, causing damage to the important target organs of hypertension, such as heart, brain and kidney. This article reviews the research progress of miRNA in hypertension in recent years, in order to clarify its role in the process of hypertension and target organ damage, and provide ideas for exploring new therapeutic targets of hypertension.

Qiju Dihuangtang Combined with Chinese Medicine Fumigation in Treatment of Dry Eye and Its Effect on Levels of Tear IL-6 and MMP-9 / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Qiju Dihuangtang combined with Chinese medicine fumigation in the treatment of dry eye and its effect on the levels of interleukin-6 （IL-6） and matrix metalloproteinase-9 （MMP-9） in tears. MethodA total of 120 patients with dry eye of liver-kidney Yin deficiency syndrome who were treated in the Department of Ophthalmology， The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine（TCM） from october 2019 to october 2021 were randomized into the observation group and control group. The control group was given sodium hyaluronate eye drops， and the observation group was treated with sodium hyaluronate eye drops， Qiju Dihuangtang， and Chinese medicine fumigation. The treatment lasted 30 days for both groups. The changes of ocular surface disease index （OSDI）， TCM syndrome score， tear secretion （SIT）， tear film breaking up time （BUT）， corneal fluorescein staining （FL）， and tear interleukin-6 （IL-6） and matrix metalloproteinase-9 （MMP-9） were observed. ResultAfter the treatment， the total effective rate was 90.0% （54/60） in the observation group and 75.0% （45/60） in the control group （χ2=4.675， P<0.05）. After treatment， the OSDI score and TCM syndrome score were lower than those before treatment in both groups （P<0.05）， and lower in the observation group than in the control group （P<0.05）. After treatment， the SIT and BUT were higher （P<0.05） and FL score was lower （P<0.05） than those before treatment in both groups. After treatment， the improvement of the above indicators in the observation group was better than that in the control group （P<0.05）. After treatment， the levels of IL-6 and MMP-9 were lower than those before treatment in both groups （P<0.05）， and lower in the observation group than in the control group （P<0.05）. ConclusionQiju Dihuangtang combined with Chinese medicine fumigation can effectively improve subjective symptoms， promote tear secretion， prolong BUT， enhance corneal epithelial repair， and reduce the levels of tear IL-6 and MMP-9 in the treatment of dry eye.

Clinical Efficacy of Compound Tripterygium wilfordii Preparation（Xinfeng Capsules） in Improving Immune Inflammation of Rheumatoid Arthritis Due to Spleen Deficiency and Dampness Exuberance Based on Apriori Algorithm and Random Walk Model / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Xinfeng capsules on immunoinflammatory indicators in patients with rheumatoid arthritis （RA） due to spleen deficiency and dampness exuberance. MethodA total of 102 patients were randomly divided into control group and observation group according to the random number table method， with 51 cases in each group. All patients were treated with methotrexate tablets， while those in the observation group received additional Xinfeng capsules. The course of treatment in both groups was 12 weeks. The 28-joint disease activity score （DAS28）， visual analogue scale （VAS） scores， morning stiffness time， erythrocyte sedimentation rate （ESR）， high-sensitivity C-reactive protein （hs-CRP）， rheumatoid factor （RF）， anti-cyclic citrullinated peptide （anti-CCP） antibody， vascular endothelial growth factor （VEGF）， and serum amyloid A （SAA） of the two groups before and after treatment were compared. The efficacy and incidence of adverse events were compared between the two groups. The Apriori association rule model and random walk model were constructed to evaluate the effect of Xinfeng capsules in improving hs-CRP， ESR， RF， SAA， VEGF， and anti-CCP. ResultThere were no dropouts in this study. There was no statistical difference in the indicators between the two groups before treatment. After 12 weeks of treatment， the total effective rate in the observation group was 90.19% （46/51）， which was higher than 74.51% （38/51） in the control group （χ2＝4.320，P<0.05）. DAS28， VAS score， and morning stiffness time in the observation group were improved compared with those in the control group （P<0.05）. Apriori association rule model results showed that the application of Xinfeng capsules in the observation group had a strong correlation with the reduction of RF， ESR， hs-CRP， SAA， and VEGF. The results of the random walk model showed that the improvement coefficients of hs-CRP， ESR， RF， SAA， and VEGF in the observation group were all better than those of the control group， and the improvement coefficient of anti-CCP in the control group was better than that of the observation group. The improvement degree of hs-CRP， ESR， RF， SAA， and VEGF in the observation group was superior to that of the control group （P<0.05）. The incidence of adverse reactions in the observation group was lower than in the control group （χ2＝4.057，P<0.05）. ConclusionOn the basis of the treatment with methotrexate tablets， Xinfeng capsules can effectively improve the immunoinflammatory level in RA due to spleen deficiency and dampness exuberance and reduce the incidence of adverse reactions.

Genetic analysis of a child with Pitt-Hopkins syndrome due to a novel variant of TCF4 gene derived from low percentage maternal mosaicism / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a child with Pitt-Hopkins syndrome.@*METHODS@#A child who had presented at the Medical Genetics Center of Gansu Provincial Maternal and Child Health Care Hospital on February 24, 2021 and his parents were selected as the study subjects. Clinical data of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing. Karyotype analysis was also carried out for the child, and her mother was subjected to ultra-deep sequencing and prenatal diagnosis upon her subsequent pregnancy.@*RESULTS@#The clinical manifestations of the proband included facial dysmorphism, Simian crease, and mental retardation. Genetic testing revealed that he has carried a heterozygous c.1762C>T (p.Arg588Cys) variant of the TCF4 gene, for which both parents had a wild-type. The variant was unreported previously and was rated as likely pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (ACMG). Ultra-deep sequencing indicated that the variant has a proportion of 2.63% in the mother, suggesting the presence of low percentage mosaicism. Prenatal diagnosis of amniotic fluid sample suggested that the fetus did not carry the same variant.@*CONCLUSION@#The heterozygous c.1762C>T variant of the TCF4 gene probably underlay the disease in this child and has derived from the low percentage mosaicism in his mother.

Serosurvey for SARS-CoV-2 among blood donors in Wuhan, China from September to December 2019

The emerging of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 pandemic. The first case of COVID-19 was reported at early December in 2019 in Wuhan City, China. To examine specific antibodies against SARS-CoV-2 in biological samples before December 2019 would give clues when the epidemic of SARS-CoV-2 might start to circulate in populations. We obtained all 88,517 plasmas from 76,844 blood donors in Wuhan between 1 September and 31 December 2019. We first evaluated the pan-immunoglobin (pan-Ig) against SARS-CoV-2 in 43,850 samples from 32,484 blood donors with suitable sample quality and enough volume. Two hundred and sixty-four samples from 213 donors were pan-Ig reactive, then further tested IgG and IgM, and validated by neutralizing antibodies against SARS-CoV-2. Two hundred and thirteen samples (from 175 donors) were only pan-Ig reactive, 8 (from 4 donors) were pan-Ig and IgG reactive, and 43 (from 34 donors) were pan-Ig and IgM reactive. Microneutralization assay showed all negative results. In addition, 213 screened reactive donors were analyzed and did not show obviously temporal or regional tendency, but the distribution of age showed a difference compared with all tested donors. Then we reviewed SARS-CoV-2 antibody results from these donors who donated several times from September 2019 to June 2020, partly tested in a previous published study, no one was found a significant increase in S/CO of antibodies against SARS-CoV-2. Our findings showed no SARS-CoV-2-specific antibodies existing among blood donors in Wuhan, China before 2020, indicating no evidence of transmission of COVID-19 before December 2019 in Wuhan, China.

Analysis of genotypes on 850 newborns with SLC26A4 single-allele mutation and the phenotypes of those with second variant / 中华耳鼻咽喉头颈外科杂志

Objective: To clarify the phenotypes of the newborns with SLC26A4 single-allele mutation in deafness genetic screening and second variant; to analyze the SLC26A4 genotype and hearing phenotype. Methods: 850 newborns born in Beijing from April 2015 to December 2019 were included and there were 468 males and 382 females. They received genetic deafness screening for 9 or 15 variants, with the result of SLC26A4 single-allele mutation. Firstly, three step deafness gene sequencing was adopted in this work, i.e., the first step was "SLC26A4 gene whole exons and splice sites" sequencing; the second step was "SLC26A4 gene promoter, FOXI1 gene and KCNJ10 gene whole exons" sequencing; and the third step was detection for "SLC26A4 gene copy number variation". Secondly, we collected the results of newborn hearing screening for all patients with the second mutation found in the three step test, and conducted audiological examinations, such as acoustic immittance, auditory brainstem response and auditory steady state response. Thirdly, for novel/VUS mutations, we searched the international deafness gene database or software, such as DVD, ClinVar and Mutation Taster, to predict the pathogenicity of mutations according to the ACMG guideline. Lastly, we analyzed the relationship between genotype and phenotype of newborns with SLC26A4 single allele mutation. Results: Among 850 cases, the median age of diagnosis was 4 months. In the first step, 850 cases were sequenced. A total of 32 cases (3.76%, 32/850) of a second variants were detected, including 18 cases (2.12%, 18/850) with identified pathogenic variants; 832 cases were sequenced and 8 cases of KCNJ10 gene missense variants were detected among the second step. No missense mutations in the FOXI1 gene and abnormal SLC26A4 gene promoter were detected; the third step sequencing results were all negative. Genotypes and hearing phenotypes included 18 cases combined with the second clear pathogenic variant, 16 cases (16/18) referred newborn hearing screening and 2 cases (2/18) passed in both ears; degree of hearing loss consisted of 18 profound ears (18/36), 13 severe ears (13/36) and 5 moderate ears (5/36); audiogram patterns comprised 17 high frequency drop ears (17/36), 14 flat ears (14/36), 3 undistinguished ears (3/36), and 2 U shaped ears (2/36); 11 cases underwent imaging examination, all of which were bilateral enlarged vestibular aqueduct. As for 22 cases of other genotypes, all passed neonatal hearing screening and the hearing diagnosis was normal, including 9 cases with VUS or possibly novel benign variants, 8 cases with KCNJ10 double gene heterozygous variants, and 5 cases with double heterozygous variants. Conclusions: The probability of individuals with SLC26A4 single-allele variant who merge with a second pathogenic variant is 2.12%, all of which are SNV, which can provide scientific basis for the genetic diagnosis and genetic counseling of SLC26A4 variants. Those who have merged with second pathogenic variant are all diagnosed with sensorineural hearing loss. Patients with KCNJ10 gene mutations do not manifest hearing loss during the infancy, suggesting the need for further follow-up.

Advances in cancer vaccines for immunotherapy of prostate cancer / 中南大学学报(医学版)

Prostate cancer is currently one of the most common malignancies that endanger the lives and health of elderly men. In recent years, immunotherapy, which exploits the activation of anti-cancer host immune cells to accomplish tumor-killing effects, has emerged as a new study avenue in the treatment of prostate cancer. As an important component of immunotherapy, cancer vaccines have a unique position in the precision treatment of malignant tumors. Monocyte cell vaccines, dendritic cell vaccines, viral vaccines, peptide vaccines, and DNA/mRNA vaccines are the most often used prostate cancer vaccines. Among them, Sipuleucel-T, as a monocyte cell-based cancer vaccine, is the only FDA-approved therapeutic vaccine for prostate cancer, and has a unique position and role in advancing the development of immunotherapy for prostate cancer. However, due to its own limitations, Sipuleucel-T has not been widely adopted. Meanwhile, owing to the complexity of immunotherapy and the specificity of prostate cancer, the remaining prostate cancer vaccines have not shown good clinical benefit in large randomized phase II and phase III trials, and further in-depth studies are still needed.

Analysis of genotypes and phenotypes of three children with Cornelia de Lange syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and results of genetic testing in three children with Cornelia de Lange syndrome (CdLS).@*METHODS@#Clinical data of the children and their parents were collected. Peripheral blood samples of the pedigrees were collected for next generation sequencing analysis.@*RESULTS@#The main clinical manifestations of the three children have included growth delay, mental retardation, peculiar facies and other accompanying symptoms. Based on the criteria proposed by the International Diagnostic Consensus, all three children were suspected for CdLS. As revealed by whole exome sequencing, child 1 has harbored NIPBL gene c.5567_5569delGAA insTAT missense variant, child 2 has harbored SMC1A gene c.607A>G missense variant, and child 3 has harbored HDAC8 gene c.628+1G>A splicing variant. All of the variants were de novo in origin.@*CONCLUSION@#All of the children were diagnosed with CdLS due to pathogenic variants of the associated genes, among which the variants of NIPBL and HDAC8 genes were unreported previously. Above finding has enriched the spectrum of pathogenic variants underlying CdLS.

Clinical translational research and application prospects of mesenchymal stem cells in periodontal tissue regeneration / 中华口腔医学杂志

Periodontitis is an oral infectious disease that occurs in the tooth supporting tissues, which damages the soft and hard tissues of the periodontium and eventually results in tooth mobility and loss. Traditional clinical treatment can effectively control the periodontal infection and inflammation. However, as the therapeutic effect depending on the local condition of periodontal defect and the systemic factors of patients, it's hard to achieve satisfactory and stable periodontal tissue regeneration for damaged periodontal tissues. Recently, as a promising therapeutic strategy in periodontal regeneration, mesenchymal stem cells (MSC) play an important role in modern regenerative medicine. Combined with the clinical translational researches of MSC in periodontal tissue engineering and the research results of our group in the past decade, it is summarized and explained the mechanism of MSC promoting periodontal regeneration, the preclinical and the clinical transformation researches as well as the future application prospects of MSC in periodontal regeneration therapy in this paper.

Outcome of surgical repair for aortic coarctation with coexisting descending aortic aneurysm in adult patients / 中华心血管病杂志

Objective: To evaluate the efficacy of surgical treatment of aortic coarctation combined with descending aortic aneurysm in adult patients. Methods: This is a retrospective cohort study. Adult patients with aortic coarctation who were hospitalized in Beijing Anzhen Hospital from January 2015 to April 2019 were enrolled. The aortic coarctation was diagnosed by aortic CT angiography, and the included patients were divided into the combined descending aortic aneurysm group and the uncomplicated descending aortic aneurysm group based on descending aortic diameter. General clinical data and surgery-related data were collected from the included patients, and death and complications were recorded at 30 days after surgery, and upper limb systolic blood pressure was measured in all patients at discharge. Patients were followed up after discharge by outpatient visit or telephone call for their survival and the occurrence of repeat interventions and adverse events, which included death, cerebrovascular events, transient ischemic attack, myocardial infarction, hypertension, postoperative restenosis, and other cardiovascular-related interventions. Results: A total of 107 patients with aortic coarctation aged (34.1±15.2) years were included, and 68 (63.6%) were males. There were 16 cases in the combined descending aortic aneurysm group and 91 cases in the uncomplicated descending aortic aneurysm group. In the combined descending aortic aneurysm group, 6 cases (6/16) underwent artificial vessel bypass, 4 cases (4/16) underwent thoracic aortic artificial vessel replacement, 4 cases (4/16) underwent aortic arch replacement+elephant trunk procedure, and 2 cases (2/16) underwent thoracic endovascular aneurysm repair. There was no statistically significant difference between the two groups in the choice of surgical approach (all P>0.05). In the combined descending aortic aneurysm group at 30 days after surgery, one case underwent re-thoracotomy surgery, one case developed incomplete paraplegia of the lower extremity, and one case died; and the differences in the incidence of endpoint events at 30 days after surgery were similar between the two groups (P>0.05). Systolic blood pressure in the upper extremity at discharge was significantly lower in both groups compared with the preoperative period (in the combined descending aortic aneurysm group: (127.3±16.3) mmHg vs. (140.9±16.3) mmHg, P=0.030, 1 mmHg=0.133 kPa; in the uncomplicated descending aortic aneurysm group: (120.7±13.2) mmHg vs. (151.8±26.3) mmHg, P=0.001). The follow-up time was 3.5 (3.1, 4.4) years. There were no new deaths in the combined descending aortic aneurysm group, no transient ischemic attack, myocardial infarction or re-thoracotomy surgery, and one patient (1/15) suffered cerebral infarction and 10 patients (10/15) were diagnosed with hypertension. The differences in the occurrence of endpoint events during postoperative follow-up were similar between the two groups (P>0.05). Conclusion: In experienced centers, long-term prognosis of patients with aortic coarctation combined with descending aortic aneurysm is satisfactory post surgical intervention.

GPRC5B protects osteoarthritis by regulation of autophagy signaling

Osteoarthritis (OA) is one of the most common chronic diseases in the world. However, current treatment modalities mainly relieve pain and inhibit cartilage degradation, but do not promote cartilage regeneration. In this study, we show that G protein-coupled receptor class C group 5 member B (GPRC5B), an orphan G-protein-couple receptor, not only inhibits cartilage degradation, but also increases cartilage regeneration and thereby is protective against OA. We observed that Gprc5b deficient chondrocytes had an upregulation of cartilage catabolic gene expression, along with downregulation of anabolic genes in vitro. Furthermore, mice deficient in Gprc5b displayed a more severe OA phenotype in the destabilization of the medial meniscus (DMM) induced OA mouse model, with upregulation of cartilage catabolic factors and downregulation of anabolic factors, consistent with our in vitro findings. Overexpression of Gprc5b by lentiviral vectors alleviated the cartilage degeneration in DMM-induced OA mouse model by inhibiting cartilage degradation and promoting regeneration. We also assessed the molecular mechanisms downstream of Gprc5b that may mediate these observed effects and identify the role of protein kinase B (AKT)-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Thus, we demonstrate an integral role of GPRC5B in OA pathogenesis, and activation of GPRC5B has the potential in preventing the progression of OA.