Implantation of Adipose-Derived Mesenchymal Stromal Cells (ADSCs)-Lining Prosthetic Graft Promotes Vascular Regeneration in Monkeys and Pigs

BACKGROUND@#Current replacement procedures for stenosis or occluded arteries using prosthetic grafts have serious limitations in clinical applications, particularly, endothelialization of the luminal surface is a long-standing unresolved problem.METHOD: We produced a cell-based hybrid vascular graft using a bioink engulfing adipose-derived mesenchymal stromal cells (ADSCs) and a 3D bioprinting process lining the ADSCs on the luminal surface of GORE-Tex grafts. The hybrid graft was implanted as an interposition conduit to replace a 3-cm-long segment of the infrarenal abdominal aorta in Rhesus monkeys. @*RESULTS@#Complete endothelium layer and smooth muscle layer were fully developed within 21 days post-implantation, along with normalized collagen deposition and crosslinking in the regenerated vasculature in all monkeys. The regenerated blood vessels showed normal functionality for the longest observation of more than 1650 days. The same procedure was also conducted in miniature pigs for the interposition replacement of a 10-cm-long right iliac artery and showed the same long-term effective and safe outcome. @*CONCLUSION@#This cell-based vascular graft is ready to undergo clinical trials for human patients.

Construction and application of a management process for enteral nutrition-associated diarrhea in postoperative esophageal cancer patients / 中华护理杂志

Objective To explore the application effect of enteral nutrition-related diarrhea in postoperative esophageal cancer patients.Methods Based on literature search and expert meeting,a management process for enteral nutrition-associated diarrhea in postoperative esophageal cancer patients was constructed.A convenience sampling method was used to select a total of 68 patients with enteral nutrition-related diarrhea after esophageal cancer surgery admitted to the thoracic surgery department of a tertiary A cancer hospital in Jiangsu Province.Among them,patients admitted from January 2022 to December 2022 were set as an experimental group.The experimental group was implemented the management process for enteral nutrition-associated diarrhea in postoperative esophageal cancer patients.Those admitted from January 2021 to December 2021 were set as a control group with routine nursing.Then,the time of stopping diarrhea,the King's of Stool Chart(KSC-Tr)diarrhea score,and abnormal incidence of nutrition-related indexes,electrolytes abnormalities(low sodium,low potassium,and low calcium)were compared between 2 groups.Results The time of stopping diarrhea,KSC diarrhea score after 3 days of intervention and the time to achieve target feeding volume of the experimental group were lower than those in the control group,and the difference was statistically significant(P＜0.05).There were no significant differences in hemoglobin,albumin,prealbumin after 3 days of intervention,the incidence of electrolyte abnormalities(low sodium,low potassium,and low calcium)after 3 days of intervention,and the BMI index after 7 days of intervention between 2 groups(P＞0.05).Conclusion The management process for enteral nutrition-associated diarrhea in postoperative esophageal cancer patients can reduce the time of diarrhea,improve the severity of diarrhea,and shorten the time to achieve the target feeding,but has no significant change in the incidence of electrolyte abnormalities.

The biological function and mechanism of IDH1 gene in intrahepatic cholangiocarcinoma cell HuCCT1 / 解放军医学杂志

Objective To explore the role and possible molecular mechanism of Isocitrate dehydrogenase 1(IDH1)gene in proliferation and migration of intrahepatic cholangiocarcinoma(iCCA)cell HuCCT1.Methods HuCCT1 cells with IDH1 gene knockout(HuCCT1IDH1-/-)were constructed by CRISPR/Cas9 gene editing technology.To investigate the capacities of proliferation,migration and invasion of HuCCT1WT(HuCCT1 cells with wild-type IDH1 gene)and HuCCT1IDH1-/-cells,assays of CCK-8,clone formation,scratch and transwell were performed.Western blotting was used to detect the expression levels of epithelial-mesenchymal transition(EMT)associated proteins E-cadherin,N-cadherin,Vimentin,MMP-9,Wnt3a and β-catenin in two groups of cells.The transcriptome sequencing data of HuCCT1WT and HuCCT1IDH1-/-cells were analyzed by bioinformatics methods,Western blotting was used to verify the expression of signaling pathway-related proteins.Results Compared with HuCCT1WT cells,HuCCT1IDH1-/-cells showed the number of proliferation and clone formation significantly reduced(P<0.05),the proportion of cells blocked in G2/M phase was significantly increased(P<0.01),the rate of scratch healing was significantly decreased(P<0.01),and the number of migrated cells(P<0.001)and invaded cells(P<0.05)was significantly reduced.qRT-PCR assay showed that the expression levels of IDH1,Vimentin,MMP-9 and genes related to the regulation of G2/M cycle proliferation,Cyclin A2,Cyclin B1 and CDK1 mRNA were down-regulated in HuCCT1IDH1-/-cells(P<0.05),and the expression of CDH1 mRNA encoding E-cadherin was up-regulated(P<0.01);Western blotting assay showed that the expression level of E-cadherin in HuCCT1IDH1-/-cells was significantly increased(P<0.05),and the expression level of N-cadherin,Vimentin and MMP-9 protein was significantly decreased(P<0.05)than that in HuCCT1WT cells.Data of transcriptome sequencing revealed 1476 differentially expressed genes(DEGs)between two groups of HuCCT1 cells.Go enrichment analysis showed the DEGs were significantly enriched in cell biological processes associated with inflammatory response,cell signaling and cell metabolism.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis suggested that the DEGs may be involved in some signaling pathways such as Wnt,MAPK,Rap1,Hippo and TNF,which are closely related to the regulation of proliferation and invasion of tumor cells.Western blotting verification results showed that compared with HuCCT1WT cells,the relative expression of Wnt3a and β-catenin proteins of HuCCT1IDH1-/-cells was significantly decreased(P<0.05).Conclusions IDH1 gene may participate in the control of biological functions of HuCCT1 cells,including cell proliferation,migration,invasion and epithelial mesenchymal transition.The mechanism may be related to the activation of the Wnt/β-catenin signaling pathway.

Advances in antitumor research of bifunctional small molecule inhibitors targeting heat shock protein 90 / 药学学报

The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.

Value of total bilirubin rebound rate and total bilirubin clearance rate in evaluating the prognosis of severe drug-induced liver injury after artificial liver support therapy / 临床肝胆病杂志

Objective To investigate the value of total bilirubin rebound rate (TBRR), total bilirubin clearance rate (TBCR), and TBCR after 1 week of treatment (ΔTBCR) in evaluating the short-term prognosis of patients with severe drug-induced liver injury (DILI) after artificial liver support therapy. Methods A retrospective analysis was performed for 203 patients with severe DILI who received artificial liver support therapy in Tianjin Third Central Hospital from September 2013 to December 2021, and general information, biochemical parameters, and clinical classification were collected. The patients were divided into improved group and unhealed group according to the prognosis at discharge, and Model for End-Stage Liver Disease (MELD) score, TBRR, TBCR, and ΔTBCR were calculated. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic (ROC) curve was plotted to investigate the value of assessment indices in predicting the prognosis of patients, and the Kaplan-Meier method was used to investigate the difference in the length of hospital stay in the context of different assessment indices. Results Compared with the unhealed group, the improved group had significantly lower age ( t =-2.762, P < 0.05), white blood cell count ( Z =-3.184, P < 0.05), total bilirubin ( t =-2.809, P < 0.05), conjugated bilirubin ( t =-2.739, P < 0.05), international normalized ratio ( Z =-2.357, P < 0.05), MELD score ( t =-3.090, P < 0.05), and TBRR ( t =-4.749, P < 0.05), as well as significantly higher albumin ( t =2.198, P < 0.05), prothrombin time activity ( t =2.018, P < 0.05), TBCR ( t =2.166, P < 0.05), and ΔTBCR ( t =9.549, P < 0.05). MELD score, TBRR, TBCR, and ΔTBCR had an area under the ROC curve (AUC) of 0.656, 0.727, 0.611, and 0.879, respectively, and ΔTBCR had a better predictive value than TBRR ( Z =3.169, P =0.001 5). The optimal cut-off value was 22.5% for TBRR (with a sensitivity of 94.6% and a specificity of 45.2%) and 27.4% for ΔTBCR (with a sensitivity of 77.7% and a specificity of 86.5%). ΔTBCR showed a good predictive value in different clinicopathological types, with extremely high sensitivity (91.4%) and specificity (100.0%) in evaluating the treatment outcome of patients with mixed-type DILI after artificial liver support therapy. Conclusion TBRR and ΔTBCR have a higher value than MELD score in evaluating the short-term prognosis of patients with severe DILI after artificial liver support therapy, among which ΔTBCR has a higher predictive value.

The analysis of features of first-onset neuromyelitis optica spectrum disease within 1 year after delivery / 中华预防医学杂志

To explore the clinical features and influencing factors of first-onset neuromyelitis optica spectrum disease (NMOSD) within 1 year after delivery. A single center, observational cohort study was used to retrospectively analyze 12 patients with first-onset NMOSD within 1 year after delivery hospitalized in the Department of Neurology of Beijing Tong Ren Hospital from June 2015 to June 2018(short as the postpartum onset group). 12 patients with first-onset NMOSD without 1 year after delivery hospitalized in our department during the same period were selected (short as the control group). The results showed the next recurrence interval in the postpartum onset group was longer than the control group [the postpartum onset group: (6.1±3.5) years, the control group: (1.6±1.5) years, t=3.622,P=0.005], the times of relapses were less than the control group [the postpartum onset group: (1.8±1.4) times, the control group:4.0 (3.0, 7.3) times, Z=-3.122,P=0.002], and expanded disability status scale (EDSS) of the last follow-up was lower than the control group [the postpartum onset group: 3.0(2.3, 3.9), the control group: 4.5(4.0, 6.0), Z=-3.358,P=0.001] with statistically significant differences. The recurrence rates of 1 year, 3 years and 5 years in the postpartum onset group (0%, 16.7%, 33.3%) were lower than control group (58.3%, 83.3%, 91.7%) with statistically significant differences (χ2=8.000,P=0.014;χ2=10.667,P=0.003; χ2=8.711,P=0.009). After the second delivery, the recurrence rate in postpartum onset group was 100% (n=3) and in control group was 50%(n=2), but the difference was not statistically significant (χ2=2.100,P=0.429). In the postpartum onset group, combination of autoimmune disease was consistent with positive in serum AQP-4 antibody moderately (Kappa=0.5, P=0.046). Positive in other autoimmune antibodies were consistent with positive in serum AQP-4 antibody moderately (Kappa=0.5, P=0.046). Combination of autoimmune disease were consistent with positive in serum other autoimmune antibodies well (Kappa=0.667, P=0.021). In conclusion, the first-onset NMOSD within 1 year after delivery have longer next recurrence interval, less times of relapses, lower relapse rate, better long-term prognosis of central nervous system, and they have trend to suffering from recurrent after the second delivery. For the females, combined with autoimmune disease or autoimmune antibody, who are ready for pregnancy, could detect serum AQP-4; if serum AQP-4 positive, they are recommended to prevent the occurrence of NMOSD after delivery.

The analysis of features of first-onset neuromyelitis optica spectrum disease within 1 year after delivery / 中华预防医学杂志

To explore the clinical features and influencing factors of first-onset neuromyelitis optica spectrum disease (NMOSD) within 1 year after delivery. A single center, observational cohort study was used to retrospectively analyze 12 patients with first-onset NMOSD within 1 year after delivery hospitalized in the Department of Neurology of Beijing Tong Ren Hospital from June 2015 to June 2018(short as the postpartum onset group). 12 patients with first-onset NMOSD without 1 year after delivery hospitalized in our department during the same period were selected (short as the control group). The results showed the next recurrence interval in the postpartum onset group was longer than the control group [the postpartum onset group: (6.1±3.5) years, the control group: (1.6±1.5) years, t=3.622,P=0.005], the times of relapses were less than the control group [the postpartum onset group: (1.8±1.4) times, the control group:4.0 (3.0, 7.3) times, Z=-3.122,P=0.002], and expanded disability status scale (EDSS) of the last follow-up was lower than the control group [the postpartum onset group: 3.0(2.3, 3.9), the control group: 4.5(4.0, 6.0), Z=-3.358,P=0.001] with statistically significant differences. The recurrence rates of 1 year, 3 years and 5 years in the postpartum onset group (0%, 16.7%, 33.3%) were lower than control group (58.3%, 83.3%, 91.7%) with statistically significant differences (χ2=8.000,P=0.014;χ2=10.667,P=0.003; χ2=8.711,P=0.009). After the second delivery, the recurrence rate in postpartum onset group was 100% (n=3) and in control group was 50%(n=2), but the difference was not statistically significant (χ2=2.100,P=0.429). In the postpartum onset group, combination of autoimmune disease was consistent with positive in serum AQP-4 antibody moderately (Kappa=0.5, P=0.046). Positive in other autoimmune antibodies were consistent with positive in serum AQP-4 antibody moderately (Kappa=0.5, P=0.046). Combination of autoimmune disease were consistent with positive in serum other autoimmune antibodies well (Kappa=0.667, P=0.021). In conclusion, the first-onset NMOSD within 1 year after delivery have longer next recurrence interval, less times of relapses, lower relapse rate, better long-term prognosis of central nervous system, and they have trend to suffering from recurrent after the second delivery. For the females, combined with autoimmune disease or autoimmune antibody, who are ready for pregnancy, could detect serum AQP-4; if serum AQP-4 positive, they are recommended to prevent the occurrence of NMOSD after delivery.

Research progress on triterpenoids of Betula plants / 药学学报

The secondary metabolites of plants are important sources of natural drugs. Betula plants have abundant pharmacological value, complex mechanism and wide applications, which are closely related to the triterpenoids of theirs. Triterpenoids in Betula species are mainly divided into dammarane-type, ocotillol-type, oleanane-type, lupane-type and cycloaltunane-type. The extracts of Betula species have varieties of activities such as anti-tumor, anti-inflammatory, anti-oxidant, anti-bacterial, etc. And the biosynthetic pathways of triterpenoids after 2,3-oxidosqualene are split into four branches of dammarenediol-II, lupeol, cycloartenol and amyrin according to the different oxidosqualene cyclases. This review summarizes the chemical constituents, pharmacological activities and biosynthetic pathways of triterpenoids in Betula plants. It provides a reference for the research and development of new drugs and the production of these triterpenoids in microbial cell factories by synthetic biology methods.

Construction of hiPSC-derived Excitatory Neural Network-like Tissue / 中山大学学报(医学科学版)

ObjectiveTo construct a neural network-like tissue with the potential of synaptic formation in vitro by seeding human induced pluripotent stem cell-derived neural precursor cells （hiPSC-NPCs） on decellularized optic nerve （DON）， so as to provide a promising approach for repair of nerve tissue injury. MethodsThrough directional induction and tissue engineering technology， human induced pluripotent stem cells （hiPSCs） and 3D DON scaffolds were combined to construct neural network-like tissues. Then the hiPSCs were directionally induced into human neural precursor cells （hNPCs） and neurons. Immunofluorescence staining was used to identify cell differentiation efficiency. 3D DON scaffolds were prepared. Morphology and cytocompatibility of scaffolds were identified by scanning electron microscopy and Tunnel staining. Induced hiPSC-NPCs were seeded on DON scaffolds. Immunofluorescence staining， scanning electron microscopy， transmission electron microscopy and patch clamp were used to observe the morphology and functional identification of constructed neural network tissues. Results①The results of immunofluorescence staining suggested that most of hiPSC-NPCs differentiated into neurons in vitro. We had successfully constructed a neural network dominated by neurons. ② The results of scanning electron microscopy and immunohistochemistry suggested that a neural network-like tissue with predominating excitatory neurons in vitro was successfully constructed. ③The results of immunohistochemical staining， transmission electron microscopy and patch clamp indicated that the neural network-like tissue had synaptic transmission function. ConclusionA neural network-like tissue mainly composed of excitatory neurons has been constructed by the combination of natural uniform-channel DON scaffold and hiPSC-NPCs， which has the function of synaptic transmission. This neural network plays a significant role in stem cell derived replacement therapy， and offers a promising prospect for repair of spinal cord injury （SCI） and other neural tissue injuries.

Research on classification method of multimodal magnetic resonance images of Alzheimer's disease based on generalized convolutional neural networks / 生物医学工程学杂志

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Neuroimaging based on magnetic resonance imaging (MRI) is one of the most intuitive and reliable methods to perform AD screening and diagnosis. Clinical head MRI detection generates multimodal image data, and to solve the problem of multimodal MRI processing and information fusion, this paper proposes a structural and functional MRI feature extraction and fusion method based on generalized convolutional neural networks (gCNN). The method includes a three-dimensional residual U-shaped network based on hybrid attention mechanism (3D HA-ResUNet) for feature representation and classification for structural MRI, and a U-shaped graph convolutional neural network (U-GCN) for node feature representation and classification of brain functional networks for functional MRI. Based on the fusion of the two types of image features, the optimal feature subset is selected based on discrete binary particle swarm optimization, and the prediction results are output by a machine learning classifier. The validation results of multimodal dataset from the AD Neuroimaging Initiative (ADNI) open-source database show that the proposed models have superior performance in their respective data domains. The gCNN framework combines the advantages of these two models and further improves the performance of the methods using single-modal MRI, improving the classification accuracy and sensitivity by 5.56% and 11.11%, respectively. In conclusion, the gCNN-based multimodal MRI classification method proposed in this paper can provide a technical basis for the auxiliary diagnosis of Alzheimer's disease.

Dupilumab for Treatment of Food-Dependent, Exercise-Induced Anaphylaxis: Report of One Case / 中国医学科学杂志(英文版)

Food-dependent, exercise-induced anaphylaxis (FDEIA) is a potentially life-threatening disorder that often occurs with exercise, and patients typically have eaten a specific food within hours before disease onset. This disease is exceedingly rare, with a prevalence of 0.02%. No well-recognized prevention or treatment strategy has been available for FDEIA except avoiding triggers strictly. Here we report an 11-year-old boy with a history of recurrent anaphylaxis of unknown etiology more than 10 times within two years. As the anaphylactic symptoms had not been controlled after traditional treatments, the patient was given subcutaneous injection of dupilumab seven times within 33 weeks. During dupilumab treatments, the patient was exposed to culprit mushrooms plus exercises at least twice a month but without notable anaphylaxis. Thus, Dupilumab may improve the allergic reactions in FDEIA patients.

Clinical features of 23 neonates infected with Omicron variant of severe acute respiratory syndrome coronavirus 2 / 中国当代儿科杂志

OBJECTIVES@#To summarize the clinical features of neonates infected with Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).@*METHODS@#The medical data of 23 neonates with Omicron variant of SARS-CoV-2 infection admitted to the City North Campus of Urumqi First People's Hospital from October to December 2022 were retrospectively reviewed.@*RESULTS@#All 23 infants had a history of exposure to confirmed caregivers with SARS-CoV-2 infection after birth, and none of them was vertically transmitted. Clinical classification: 5 cases of asymptomatic infection, 18 cases of mild infection, and no cases of moderate, severe, or critically ill. The first symptoms were fever in 13 cases, cough in 3 cases, nasal congestion in 1 case, and diarrhea in 1 case. Blood white blood cell counts decreased in 2 cases, and C-reactive protein increased in 1 case. Seven infants underwent chest X-ray examination due to cough or shortness of breath, and one of which showed focal exudative changes, while the rest showed no abnormal changes. All infants were discharged after symptomatic treatment and the median hospital stay was 6 days. The duration of nucleic acid positivity of SARS-CoV-2 was negatively correlated with N gene Ct values and ORF1ab gene Ct values (rs=-0.719 and -0.699, respectively; P<0.05). One month after discharge, all infants had no symptoms or signs of nucleic acid re-positivity.@*CONCLUSIONS@#The clinical manifestations are usually mild or asymptomatic in neonates infected with SARS-CoV-2 Omicron variant. The lower the Ct values of the N and ORF1ab genes of SARS-CoV-2, the longer the duration of nucleic acid positivity. Neonates infected with SARS-CoV-2 Omicron variant can have a good prognosis after symptomatic treatment.

Construction and effect evaluation of management process of Da Vinci robotic surgical instrument based on bar code / 中国实用护理杂志

Objective:To establish and effect evaluate of management process of Da Vinci robotic surgical instrument based on bar code, and evaluate its application effect.Methods:This study was a randomized controlled trial using convenient sampling method. A total of 172 Da Vinci robotic surgeries from Jiangsu Cancer Hospital from September to November 2020 were selected as the control group, and 118 Da Vinci robotic surgeries from September to November 2021 were selected as the observation group. The control group adopted the traditional Da Vinci surgical instrument management mode, while the observation group adopted the management mode of Da Vinci surgical instrument based on bar code. The incidence of management problems related to Da Vinci surgical instruments, the number of reported adverse events of instruments rate and the impact of staff work effect were compared between two groups.Results:The incidence rates of non-traceable information, counting error, usage charge and bar code irregularity were 9.3% (11/118), 0, 0.8% (1/118) and 2.5% (3/118), respectively, which were lower than 26.7% (46/172), 17.4% (30/172), 12.2% (21/172) and 16.9% (29/172) of the control group. The differences were statistically significant ( χ2 values were 12.89-24.68, all P<0.01). The reporting rate of device adverse events in the control group was 0, and the observation group was 4.2% (5/118), and the difference between the two groups was statistically significant ( χ2=7.42, P<0.05). The number of sterilization package turnover sets in the observation group was 2(2, 3), which was lower than 2(2, 4) of the control group, and the difference was statistically significant ( Z=-2.50, P<0.05). The average amount of pre-purchased surgical instruments per surgical instrument in the observation group was 7 858.0 (6 712.1, 14 119.9), which was lower than that of the control group of 7 858.0 (7 858.0, 2 0385.0), and the difference was statistically significant ( Z=-2.97, P<0.05). Conclusions:The management process of Da Vinci Xi robotic surgical instrument based on bar code can reduce the incidence of related management problems, increase the reporting rate of adverse events, improve the work efficiency of the management of mechanical arm to optimize hospital of reusable medical equipment management level, thus further ensure medical safety and improve medical quality.

Characteristics of new corneal biomechanical parameters in different degrees of myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the characteristics of new corneal biomechanical parameters in different degrees of myopia and analyze the correlation of the new parameter stress-strain index(SSI).METHODS: A cross-sectional study was conducted on 366 adult patients(718 eyes)with different degrees of myopia who received treatment at the First Affiliated Hospital of Dali University from October 2021 to November 2021, aged 18-50 years, and the spherical equivalent(SE)was -0.50～-16.75D. The axial length(AL)of the eye was measured by IOL master, and the new corneal biomechanical parameters, central corneal thickness(CCT)and intraocular pressure(IOP)were measured by corneal visualization Scheimpflug technology(Corvis ST). The subjects were categorized into low myopia, moderate myopia and high myopia groups according to SE. The data were analyzed by ANOVA and Pearson correlation.RESULTS: The ratio of the thinnest corneal thickness to horizontal thickness change rate(ARTh)and SSI were statistically significant(P&#x0026;#x003C;0.001), while the remaining parameters were not statistically significant(P&#x0026;#x003E;0.05). SSI was positively correlated with age(r=0.102, P=0.006), SE(r=0.361, P&#x0026;#x003C;0.001), IOP(r=0.175, P&#x0026;#x003C;0.001), CCT(r=0.098, P=0.009), SPA1(r=0.182, P&#x0026;#x003C;0.001), negatively correlated with AL(r=-0.331, P&#x0026;#x003C;0.001), IR(r=-0.545, P&#x0026;#x003C;0.001)and had no correlation with other corneal biomechanical parameters(P&#x0026;#x003E;0.05).CONCLUSION: With the increase of myopia degree and the elongation of the axial length, the SSI value becomes smaller and the corneal hardness decreases. SSI may be a helpful corneal biomechanical indicator for future research on myopia.

Progress in research of risk prediction of non-syndromic oral clefts using genetic information / 中华流行病学杂志

Non-syndromic oral cleft (NSOC), a common birth defect, remains to be a critical public health problem in China. In the context of adjustment of childbearing policy for two times in China and the increase of pregnancy at older childbearing age, NSOC risk prediction will provide evidence for high-risk population identification and prenatal counseling. Genome-wide association study and second generation sequencing have identified multiple loci associated with NSOC, facilitating the development of genetic risk prediction of NSOC. Despite the marked progress, risk prediction models of NSOC still faces multiple challenges. This paper summarizes the recent progress in research of NSOC risk prediction models based on the results of extensive literature retrieval to provide some insights for the model development regarding research design, variable selection, model-build strategy and evaluation methods.

Status of fungal sepsis among preterm infants in 25 neonatal intensive care units of tertiary hospitals in China / 中华儿科杂志

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.

Role of CD4+NKG2D+ T cells in the disease activity of juvenile idiopathic arthritis / 中国当代儿科杂志

OBJECTIVES@#To study the expression levels of CD4+NKG2D+ T cells and NKG2D soluble ligands, the soluble MHC class I chain-related molecules A and B (sMICA/sMICB) in the active stage and stable stage of juvenile idiopathic arthritis (JIA) and their role in the disease activity of JIA.@*METHODS@#Nineteen children with systemic JIA and 20 children with articular JIA who were diagnosed in Children's Hospital of Chongqing Medical University from November 2019 to December 2021 were enrolled in this prospective study. Six healthy children were enrolled as the control group. After peripheral blood samples were collected, ELISA was used to measure the levels of sMICA and sMICB, and flow cytometry was used to measure the percentage of CD4+NKG2D+ T cells. Systemic Juvenile Arthritis Disease Activity Score-27 (sJADAS-27)/Juvenile Arthritis Disease Activity Score-27 (JADAS-27) was used to evaluate the disease activity in children with JIA. The Pearson correlation analysis and the receiver operating characteristic (ROC) curve were used to assess the role of CD4+NKG2D+ T cells, sMICA and sMICB in the disease activity of JIA.@*RESULTS@#The active systemic JIA and active articular JIA groups had a significant increase in the percentage of CD4+NKG2D+ T cells compared with the control group and their corresponding inactive JIA group (P<0.05). The JIA groups had significantly higher levels of sMICA and sMICB than the control group (P<0.05), and the active articular JIA group had a significantly higher level of sMICB than the stable articular JIA group (P<0.05). In the children with JIA, the percentage of CD4+NKG2D+ T cells and the levels of sMICA and sMICB were positively correlated with sJADAS-27/JADAS-27 disease activity scores (P<0.05). The ROC curve analysis showed that sMICB had an area under the curve of 0.755 in evaluating the disease activity of JIA, with a specificity of 0.90 and a sensitivity of 0.64.@*CONCLUSIONS@#The percentage of CD4+NKG2D+ T cells and the levels of sMICA and sMICB increase in children with JIA compared with healthy children and are positively correlated with the disease activity of JIA, suggesting that CD4+NKG2D+ T cells and NKG2D ligands can be used as potential biomarkers for evaluating the disease activity of JIA.

The Molecular Mechanism of LncRNA HOTAIR Regulating the Proliferation, Invasion and Migration of Lymphoma Cells through Target Gene miR-20a-5p / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of lncRNA HOTAIR on the proliferation, invasion and migration of lymphoma cells through target gene miR-20a-5p and its molecular mechanism.@*METHODS@#After synthesizing HOTAIR siRNA and siRNA NC plasmids, they were transfected into lymphoma Raji cells, respectively. The expression of HOTAIR mRNA was detected by RT-qPCR. The proliferation, invasion and migration of lymphoma Raji cells were detected by CCK-8 assay, Transwell assay and cell scratch healing assay, respectively. The target gene of lncRNA HOTAIR was predicted by miRcode software, and the relationship between HOTAIR and target gene was analyzed by dual luciferase assay. After synthesis of miR-20a-5p inhibitor and inhibitor NC, Raji cells were transiently transfected. The expression of miR-20a-5p was detected by RT-qPCR, and the effects of down-regulation of miR-20a-5p on the proliferation, invasion and migration of Raji cells were analyzed. The overexpression plasmid of lncRNA HOTAIR and miR-20a-5p mimics were transfected into Raji cells simultaneously to analyze the proliferation, invasion and migration ability of Raji cells. After overexpression or down-regulation of miR-20a-5p, the expression of JAK/STAT3 signaling pathway related proteins was analyzed.@*RESULTS@#HOTAIR expression in Raji cells was decreased after transfection of HOTAIR siRNA (P<0.01), and miR-20a-5p expression was also decreased after transfection of miR-20a-5p inhibitor (P<0.01). HOTAIR had a targeting and negative regulation relationship with miR-20a-5p (r=-0.826). Silencing HOTAIR promoted the expression of miR-20a-5p and inhibited the proliferation, invasion and migration of Raji cells. Down-regulation of miR-20a-5p expression promoted the proliferation, invasion and migration of Raji cells. Effect of HOTAIR overexpression on the proliferation, invasion and migration of Raji cells could be reversed by up-regulation of miR-20a-5p. Down-regulation of miR-20a-5p expression activated the intracellular JAK/STAT3 signaling pathway.@*CONCLUSION@#HOTAIR affects the proliferation, invasion and migration of lymphoma cells by targeting miR-20a-5p, and its mechanism may be related to the activation of JAK/STAT3 signaling pathway.

Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C / 药物分析学报

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Effect of exercise on cancer-related cognitive impairment in breast cancer patients:a Meta-analysis / 现代临床护理

Objective To evaluate the intervention effect of exercise on cancer related cognitive impairment of breast cancer patients,and to provide evidence-based evidence for the choices of rehabilitation programs for cognitive impairment.Methods The PubMed,Embase,Web of Science,Cochrane Library,Joanna Briggs Institute Library(JBI),CINAHL,CNKI,Wanfang,VIP and CBM were searched by computer for randomized controlled trials on the impact of exercise on cancer-related cognitive impairment in patients with breast cancer.The retrieval time limit was from the establishment of the database to October 2022.The quality of the included studies was evaluated according to Cochrane Handbook 5.1.0.RevMan5.4 was used for meta-analysis.Results A total of 18 publications including 1310 patients were included.The results showed that exercise could improve self-reported cancer-related cognitive impairment[SMD=0.33,95%CI(0.21,0.46),P<0.001],executive function[SMD=-0.27,95%CI(-0.42,-0.11),P<0.001]and attention[SMD=-0.37,95%CI(-0.60,-0.14),P<0.01],alleviate cancer-related fatigue[SMD=-0.56,95%CI(-0.79,-0.34),P<0.001],and reduce depression[SMD=-0.73,95%CI(-1.17,-0.30),P<0.001],but it has no significant effect on the memory of patients with breast cancer[SMD=0.05,95%CI(-0.16,0.27),P=0.64].Conclusion Exercise can improve the self-reported cancer-related cognitive impairment,executive function and attention of breast cancer patients,alleviate cancer-related fatigue,reduce depression,but it has no significant effect on improving memory,which still needs further verification.