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Digital polymerase chain reaction(dPCR)is a PCR technology that realizes accurate quantification of single-copy nucleic acid molecules by dividing the reaction system into tens of thousands of independent PCR reaction units for single-molecule-level amplification and integrating Poisson distribution.Due to its single-copy sensitivity and accurate quantification without the need of standard curves,dPCR has been widely used in disease diagnosis.By introducing technologies such as stepped emulsification and three-dimensional imaging,dPCR has been greatly improved in terms of accuracy,multiplexability and turnaround time,significantly enhancing its performance in clinical disease diagnosis.Based on this,this paper traced the technological development history of dPCR,gave an overview of its application in detection of tumors,infections and other diseases,and further discussed the challenges and opportunities of the development of dPCR,with the aim of providing a reference for the development and utilization of dPCR in the future,and promoting the high-quality development of molecular technology in clinical testing.
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Objective To investigate the correlation between the manual compression on injection point and the incidence of subcutaneous bleeding after subcutaneous injection of low molecular weight heparin(LMWH)in elderly patients with coronary artery disease.Methods A total of 131 elderly patients with coronary artery disease,who received subcutaneous injection of LMWH after percutaneous coronary intervention(PCI)at the Affiliated Nanjing Hospital of Nanjing Medical University of China between January 2019 and December 2021,were enrolled in this study.According to whether the manual compression on the injection point was employed or not after the injection of LMWH,the patients were divided into the study group(n=67)and the control group(n=64).The operation process of subcutaneous injection of LMWH was carried out in accordance with the"Supervision Standard for Nursing Quality of Hypodermic Injection of Low Molecular Weight Heparin"which was included in the norms formulated by authors'hospital.For the patients of the study group,the injection point was manually pressed for 3-5 min after the injection of LMWH,the manually-used force was to press the skin down for 1cm deep.The incidence of subcutaneous bleeding was compared between the two groups.Results In the study group and the control group,the incidence of subcutaneous ecchymosis was 9.0%and 7.8%respectively,the incidence of subcutaneous hard tubercle was 4.5%and 1.6%respectively,the differences between the two groups were not statistically significant(both P＞0.05).The patient's age,gender,abdominal circumference and body mass index(BMI)carried no obvious correlation with the subcutaneous bleeding after LMWH injection(P＞0.05),while a statistically significant correlation existed between the abdominal wall fat thickness and the subcutaneous bleeding(P＜0.05),which could be used as an independent predictor for the occurrence of subcutaneous bleeding after LMWH injection.Conclusion No obvious correlation exists between the manual compression on injection point and the incidence of subcutaneous bleeding in elderly patients with coronary artery disease after subcutaneous injection of LMWH,therefore,no compression manipulation,used as a hemostatic measure,is required after subcutaneous injection of LMWH.The abdominal wall fat thickness is an independent predictor for subcutaneous bleeding after injection of LMWH.Standard operation procedures should be strictly followed so as to avoid the occurrence of subcutaneous bleeding after injection of LMWH.(J Intervent Radiol,2024,32:77-81)
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In healthy individuals,there is a favourable balance between commensal and potentially patho-genic bacteria.When the balance is broken,the host might suffer from gastrointestinal cancer.Studies have shown that high-fat diet can alter the composition of gastrointestinal microbiota,gastrointestinal microbiota may promote gastrointestinal cancer by affecting metabolites of gastrointestinal microbiota,leading to loss of gastrointestinal barrier function,suppressing anti-tumor immunity,etc.In this work,we will summary the current knowledge on relations and possible mechanisms of high-fat diet-associated gastrointestinal microbiota and gastrointestinal cancer.To provide new ideas for the treatment of gastrointestinal cancer.
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Objective:To evaluate the short-term efficacy and safety of 3D printing patient-matched artificial vertebral body in clinical research and application.Methods:A total of 12 patients with spinal tumors were enrolled 7 males (58.33%) and 5 females (41.67%), aged from 18 to 65 years old in The First Affiliated Hospital of Air Force military Medical University (hereinafter referred to as Xijing Hospital) and Peking University people's Hospital from September 2021 to July 2022. The spinal vertebra defect were restored by using 3D printing patient-matched artificial vertebral body after tumor resection. All patients who accepted TES and 3D printing patient-matched artificial vertebral body implantation were included according to the inclusion and exclusion criteria. The bone interface fusion was evaluated by the imaging fusion criteria of Brantigan and Steffee at 3 and 6 months after operation, the curative effect was evaluated by comparing Japanese Orthopaedic Association (JOA) score at 3 and 6 months after operation, visual analogue scale (VAS) 3 months after operation and intervertebral height at 3 and 6 months after operation with those before operation, and the safety was evaluated by adverse event recording.Results:All 12 patients completed the operation successfully, and the operation sites were thoracic vertebrae in 6 cases (50%), thoracolumbar in 3 cases (25%) and lumbar vertebrae in 3 cases (25%). All patients were followed up. The mean follow-up time was 23.92±3.23 months (range, 19-29 months). No tumor recurrence or metastasis was observed during this period. All patients were followed up at 15 days, 3 months and 6 months after operation. During the 6-month follow-up, X ray results showed that interface of bone and the vertebral body were fused in all of the 12 patients, and the effective rate of fusion was 100%. The 95% confidence interval is calculated to be (75.6%-100%). Six months after operation, the improvement rate of JOA score was excellent in 10 cases, good in 1 case, poor in 1 case, and the excellent and good rate was 91.66%. The preoperative VAS score was 4.08 ±2.47, and during the 3-month follow-up, the VAS score was improved to 1.83 ±1.59. Compared with the preoperative VAS score, the difference was statistically significant ( t=2.635, P=0.023). The intervertebral height before operation, 15 days after operation, 3 months after operation and 6 months after operation were 32.75 (25.94, 68.20), 41.09 (30.55, 70.20), 40.70 (30.23, 67.83) and 40.74 (30.23, 67.08), respectively, and there was no statistically significant difference (χ 2=0.768, P=0.857). No implant-related adverse events occurred after operation. Conclusion:The 3D printing patient-matched artificial vertebral body used in this study has satisfactory short-term efficacy and safety in the reconstruction of spinal stability after spinal tumor resection.
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Objective:To investigate the effect of five-element music therapy combined with meridian-based acupoint massage timed according to qi circulationon on negative emotions and sleep quality in older adults with chronic heart failure. Methods:A total of 112 older adult patients with chronic heart failure who received treatment at The Affiliated Hospital of Hangzhou Normal University between January 2022 and June 2023 were included in this study. They were randomly divided into a control group ( n = 56) and a study group ( n = 56) using the random number table method. Based on conventional treatment, the control group received five-element music therapy, while the intervention group underwent a combination of five-element music therapy and meridian-based acupoint massage timed according to qi circulation. Before and after the intervention, a comparison was made between the two groups in terms of the scores of the Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), and various dimensions of the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Additionally, the sleep outcome and patient satisfaction were also compared between the two groups. Results:After intervention, the scores of the HAMA and HAMD in the study group were (11.29 ± 2.48) points and (12.48 ± 3.36) points, respectively. In contrast, the control group had scores of (15.93 ± 3.35) points and (16.50 ± 4.32) points, respectively. After intervention, the scores of the HAMA and HAMD scales in both the study and control groups demonstrated a significant reduction in comparison with their respective pre-intervention scores [study group: (20.13 ± 5.18) points, (23.95 ± 8.97) points, control group: (19.36 ± 5.45) points, (23.79 ± 7.61) points, t = 15.35, 10.24, 5.65, 8.93, all P < 0.001). After intervention, the scores of the HAMA and HAMD scales in the study group were significantly lower than those in the control group ( t = -8.34, -5.49, both P < 0.001). After intervention, the scores of the PSQI in the study and control groups were (7.05 ± 0.96) points and (9.91 ± 1.28) points, respectively. After intervention, the scores of PSQI in both the study and control groups demonstrated a significant reduction compared with their respective pre-intervention scores [study group: (12.98 ± 2.21) points, control group: (12.50 ± 2.48) points, t = 24.68, 9.79, both P < 0.05]. After intervention, the score of the PSQI in the study group was significantly lower than that in the control group ( t = 13.34, P < 0.05). Based on the scores across various dimensions of the MLHFQ, it was observed that after intervention, the scores of emotional, physical, and other domains in both the study and control groups [study group: (9.36 ± 2.29) points, (16.95 ± 3.80) points, (18.50 ± 2.33) points; control group: (12.93 ± 2.00) points, (19.98 ± 3.98) points, (20.04 ± 2.24) points] decreased significantly compared with their pre-intervention scores [study group: (15.57 ± 1.55) points, (26.23 ± 4.63) points, (21.18 ± 2.50) points, control group: (16.09 ± 1.87) points, (25.32 ± 4.40) points, (21.57 ± 2.69) points, t = 21.66, 18.55, 8.44, 11.29, 11.73, 4.61, all P < 0.001]. After intervention, the scores of emotional, physical, and other domains in the study group were significantly lower than those in the control group ( t = -8.79, -4.13, -3.56, all P < 0.05). Patient satisfaction in the study group was superior to that that in the control group [98.21% (55/56) vs. 87.50% (49/56), χ2 = -3.09, P < 0.05]. Total effective rate of intervention on sleep in the study group was significantly higher than that in the control group [92.86% (52/56) vs. 78.57% (44/56), χ2 = -2.09, P < 0.05]. Conclusion:Five-element music therapy combined with meridian-based acupoint massage timed according to qi circulationon in the treatment of chronic heart failure in older adults can effectively alleviate negative emotions, improve the quality of life and sleep, and increase patient satisfaction with nursing care.
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BackgroundThe incidence of mental disorders is steadily increasing. However， antipsychotic medications， commonly used in treatment， can lead to drug-induced amenorrhea in female patients. This side effect significantly reduces medication adherence and increases the risk of disease recurrence. Therefore， addressing drug-induced amenorrhea in female patients has become an urgent problem requiring effective solutions. ObjectiveTo explore the efficacy and safety of traditional Chinese medicine compound in treating antipsychotic-induced amenorrhea， so as to provide guidance for the treatment of this condition using traditional Chinese medicine compound. MethodsOn September 4， 2022， a computerized search was conducted on across multiple databases， including China National Knowledge Infrastructure， VIP Database， Wanfang Database， China Biomedical Literature Database， PubMed， Cochrane Library and Embase， and randomized controlled trials （RCT） of traditional Chinese medicine compound in treating antipsychotic-induced amenorrhea were collected. The quality of the included literature was assessed using Cochrane 5.3 bias risk assessment tool. Meta-analysis was performed to assess the total effective rate， cure rate， incidence of adverse reactions and recurrence rate using RevMan 5.3. ResultsUltimately， 22 RCT involving 1 879 patients were included. Meta-analysis results showed that the total effective rate （RR=1.29， 95% CI： 1.16~1.44） and cure rate （RR=1.62， 95% CI： 1.45~1.80） of traditional Chinese medicine compound or its combination with western medicine in treating antipsychotic-induced amenorrhea were significantly higher compared to western medicine alone. Moreover， the incidence of adverse reactions （RR=0.56， 95% CI： 0.41~0.76） and recurrence rate （RR=0.16， 95% CI： 0.06~0.42） were significantly lower than those of western medicine alone. ConclusionTraditional Chinese medicine compound may offer benefits in ameliorating antipsychotic-induced amenorrhea and its safety is better than simple western medicine treatment.
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Objective @#To investigate the mechanism by which Erastin affects ferroptosis in lung fibroblasts.@*Methods@#Mouse lung fibroblasts (C57/B6⁃L) were treated with varying concentrations of the iron death inducer Erastin, Cell viability was assessed using the cell counting Kit⁃8 (CCK⁃8) assay. Oxidative stress levels were visualize using a fluorescence microscope , and the expression of proteins related to the mitogen⁃activated protein kinase (MAPK) signaling pathway was analyzed using Western blot. Additionally , the p38 and extracellular regulated protein kinase (ERK) inhibitors SB203580 and U0126 were employed to further elucidate the mechanism by which Erastin induces iron death in lung fibroblasts. @*@#At a concentration of 100 μmol/L , Erastin effectively in⁃duced ferroptosis in lung fibroblasts , leading to an upregulation of oxidative stress. Furthermore , the phosphoryla⁃tion levels of p38 and ERK proteins in the MAPK pathway were elevated (P < 0. 05) . The addition of SB203580 and U0126 inhibitors resulted in a significant reduction in oxidative stress levels and a notable increased in cell actiivity in lung fibroblasts (P < 0. 05) . @*@#It can be concluded that Erastin induces ferroptosis in lung fibroblasts , potentially through the mediation of oxidative stress via the MAPK signaling pathway.
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Chikusetsusaponin IVa (CsIVa) is a natural active monomer of triterpene saponins in the Chinese herbal medicine of Panax japonicus, which has anti-inflammatory, anti-tumor and other effects. However, its function and mechanism in triple negative breast cancer (TNBC) remain unclear. This study investigated the inhibitory effect and mechanisms of CsIVa on the proliferation of triple negative breast cancer cell line MDA-MB-231. In this study, we found that CsIVa could significantly inhibit the proliferation of MDA-MB-231 cells and eliminate its potential toxic effect on normal breast cells (MCF-10A). The transcriptome sequencing results showed that the inhibition of proliferation of MDA-MB-231 cells by CsIVa was closely related to cell cycle and the pathway regulating cell cycle. Further studies confirmed that CsIVa blocked the cell cycle in G2/M phase by down-regulating the expression of cyclin dependent kinase 1 (CDK1), cyclin B1 and up-regulating the expression of cyclin dependent kinase inhibitor 1A (p21). Moreover, CsIVa can block cell cycle through inhibiting PI3K/AKT signal pathway. In conclusion, CsIVa regulates the expression of cell cycle related proteins (p21, CDK1, cyclin B1) via inhibiting the activity of PI3K/AKT signaling pathway, blocks TNBC cell cycle, and thus exerts its anti-tumor activity.
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Radiation enteritis is a kind of intestinal radiation injury in patients with pelvic and retroperitoneal malignancies after radiotherapy, and its occurrence and development process are very complicated. At present, studies have confirmed that intestinal microecological imbalance is an important factor in the formation of this disease. Abdominal radiation causes changes in the composition of the flora and a decrease in its diversity, which is mainly manifested by a decrease in beneficial bacterial species such as Lactobacilli and Bifidobacteria. Intestinal dysbacteriosis aggravates radiation enteritis, weakens the function of the intestinal epithelial barrier, and promotes the expression of inflammatory factors, thereby aggravating the occurrence of enteritis. Given the role of the microbiome in radiation enteritis, we suggest that the gut microbiota may be a potential biomarker for the disease. Treatment methods such as probiotics, antibiotics, and fecal microbiota transplantation are ways to correct the microbiota and may be an effective way to prevent and treat radiation enteritis. Based on a review of the relevant literature, this paper reviews the mechanism and treatment of intestinal microbes in radiation enteritis.
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Objective To analyze the status and trend for the mortality and DALY rates of child growth failure (CGF) in children aged < 5 years in China from 1990 to 2019, so as to provide a scientific basis for CGF prevention and control. Methods The mortality and DALY rates of CGF in children aged < 5 years from 1990 to 2019 were obtained from GBD 2019. The changes of these indicators with the years in China , the United States, Japan, Russia, India and the global were compared and analyzed. Results In 2019, the mortality of child wasting, child stunting and child underweight in children aged < 5 years in China were 9.62/100 000, 1.23/100 000, and 1.29/100 000 respectively, the mortality rates were 867.50/100 000 , 129.23/100 000 , and 112.87/100 000 rescpectively, higher than those of the United States, Japan, and Russia, and far lower than those of India and the global. The disease burden of three types of CGF were all higher in males than females, and higher in children aged < 1 years than children aged 1-4 years. From 1990 to 2019, the mortality and DALY rates of CGF in children aged < 5 years in China decreased from 300.41/100 000 and 26 445.38/100 000 to 10.49/100 000 and 943.57/100 000, respectively. China had the largest drop rate compared with all analyzed countries. As for children aged < 5 years in China, the DALY rate of lower respiratory infection ranked first in all the diseases caused by CGF. Conclusion From 1990 to 2019, the disease burden of CGF in children aged < 5 years has shown a significant decrease in China , but it is still far behind the developed countries. In the future, more attention should be paid to the problems of child growth in hope of reducing the mortality and DALY rates of CGF.
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Objective: To analyze associated factors and adverse pregnancy outcomes of postpartum hemorrhage in the caesarean section of puerperae with different types of placenta previa. Methods: This retrospective research was a case-control study. Puerperae with cesarean section of placenta previa from January 2019 to December 2020 in Women's Hospital, School of Medicine, Zhejiang University were collected and divided into the<1 000 ml control group or ≥1 000 ml postpartum hemorrhage group according to the amount of blood loss during cesarean section. Differences in continuous variables were analyzed by t-test and categorical variables were analyzed by χ2 test. The risk factors of postpartum hemorrhage were analyzed by logistic multivariate regression. Results: A total of 962 puerperae were enrolled with 773 cases in the control group and 189 cases in the postpartum hemorrhage group. The incidence of gestational weeks, gravidity, parity, induced abortion, placental accreta and preoperative hemoglobin<110 g/L was significantly different between two groups in different types of placenta previa (P<0.001). Logistic multivariate regression model analysis showed that the independent risk factors of postpartum hemorrhage in the caesarean section of low-lying placenta included placental accreta (OR=12.713, 95%CI: 4.296-37.625), preoperative hemoglobin<110 g/L (OR=2.377, 95%CI: 1.062-5.321), and prenatal vaginal bleeding (OR=4.244, 95%CI: 1.865-9.656). The independent risk factors of postpartum hemorrhage in the caesarean section of placenta previa included once induced abortion (OR=2.789, 95%CI:1.189-6.544), induced abortion≥2 (OR=2.843, 95%CI:1.101-7.339), placental accreta (OR=6.079, 95%CI:3.697-9.996), HBsAg positive (OR=3.891, 95%CI:1.385-10.929), and placental attachment to the anterior uterine wall (OR=2.307, 95%CI:1.285-4.142). The rate of postpartum hemorrhage and premature delivery in puerperae with placenta previa was higher than that in puerperae with low-lying placenta (P<0.001). Conclusions: The associated factors of postpartum hemorrhage in puerperae with different types of placenta previa are different. Placenta accreta is the common risk factor of postpartum hemorrhage in puerperae with low-lying placenta and placenta previa.
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Female , Pregnancy , Humans , Cesarean Section , Postpartum Hemorrhage/surgery , Pregnancy Outcome , Retrospective Studies , Case-Control Studies , Placenta Previa/surgery , Placenta , Risk FactorsABSTRACT
Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.
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Animals , Humans , Squamous Cell Carcinoma of Head and Neck/therapy , Heterografts , Photothermal Therapy , Biomimetics , Disease Models, Animal , Head and Neck Neoplasms/therapy , Cell Line, Tumor , Tumor MicroenvironmentABSTRACT
The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
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Animals , Mice , Antiviral Agents/pharmacology , COVID-19 , Hepatitis B virus , Interferon Type I/metabolism , SARS-CoV-2/drug effects , Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitorsABSTRACT
We constructed and optimized the plasmid DNA (pDNA) Opt-S encoding the gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, using poly (lactic-co-glycolic acid) copolymer (PLGA) as a delivery carrier for pDNA. PLGA-pDNA NPs were loaded by nanoprecipitation and its properties in vitro were preliminary evaluated. The results showed that the prepared PLGA-pDNA NPs were regular morphology, clear edges, with an average particle size of (184.2 ± 2.4) nm, polydisperse index (PDI) of 0.093 ± 0.013, zeta potential of (-68.10 ± 0.36) mV, and encapsulation rate of (98.92 ± 0.22)%. The PLGA-pDNA NPs were stable at -20 ℃ for 7 months and could protect pDNA against nuclease degradation. And they also exhibited sustained release of pDNA in vitro. The PLGA-pDNA NPs have low cytotoxicity and high safety. In addition, in vitro transfection experiments showed that the SARS-CoV-2 S gene could enter cells and be expressed. These results indicate that PLGA-pDNA NPs non-viral gene vector have simple preparation process and good performance, which are expected to provide a new idea for the research and development of SARS-CoV-2 vaccine.
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To explore the methods of the explicitation of implicit knowledge and the construction of knowledge graph on moxibustion in medical case records of ZHOU Mei-sheng's Jiusheng. The medical case records data of Jiusheng was collected, the frequency statistic was analyzed based on Python3.8.6, complex network analysis was performed using Gephi9.2 software, community analysis was performed by the ancient and modern medical case cloud platform V2.3.5, and analysis and verification of correlation graph and weight graph were proceed by Neo4j3.5.25 image database. The disease systems with frequency≥10 % were surgery, ophthalmology and otorhinolaryngology, locomotor, digestive and respiratory systems. The diseases under the disease system were mainly carbuncle, arthritis, lumbar disc herniation and headache. The commonly used moxibustion methods were fumigating moxibustion, blowing moxibustion, direct moxibustion and warming acupuncture. The core prescription of points obtained by complex network analysis included Yatong point, Zhiyang(GV 9), Sanyinjiao(SP 6), Dazhui(GV 14), Zusanli(ST 36), Lingtai(GV 10), Xinshu(BL 15), Zhijian point and Hegu(LI 4), which were basically consistent with high-frequency points. A total of 6 communities were obtained by community analysis, corresponding to different diseases. Through the analysis of correlation graph, 13 pairs of strong association rule points were obtained. The correlation between Zhiyang(GV 9)-Dazhui(GV 14) and Yatong point-Lingtai(GV 10) was the strongest. The acupoints with high correlation with Yatong point were Zhiyang(GV 9), Lingtai(GV 10), Dazhui(GV 14), Zusanli(ST 36) and Sanyinjiao(SP 6). In the weight graph of the high-frequency disease system, the relationship of the first weight of the surgery system disease was fumigating moxibustion-carbuncle-Yatong point, and the relationship of the first weight of the ophthalmology and otorhinolaryngology system disease was blowing moxibustion-laryngitis-Hegu (LI 4). The results of correlation graph and weight graph are consistent with the results of data mining, which can be used as an effective way to study the knowledge base of moxibustion diagnosis and treatment in the future.
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Humans , Moxibustion , Carbuncle , Pattern Recognition, Automated , Acupuncture Therapy , Acupuncture PointsABSTRACT
Objective: To explore the clinical features and prognosis of children with histiocytic necrotizing lymphadenitis (HNL). Methods: The clinical data of 118 children with HNL diagnosed and treated in the Department of Rheumatology and Immunology of Children's Hospital, Capital Institute of Pediatrics from January 2014 to December 2021 were retrospectively analyzed. The clinical symptoms, laboratory examination, imaging examination, pathological findings, treatment and follow-up were analyzed. Results: Among the 118 patients, 69 were males and 49 were females. The age of onset was 10.0 (8.0, 12.0) years, ranging from 1.5 to 16.0 years. All the children had fever lymph node enlargement, blood system involvement in 74 cases (62.7%), skin injury in 39 cases (33.1%). The main manifestations of laboratory examination were increased erythrocyte sedimentation rate in 90 cases (76.3%), decreased hemoglobin in 58 cases (49.2%), decreased white blood cells in 54 cases (45.8%) and positive antinuclear antibody in 35 cases (29.7%). Ninety-seven cases (82.2%) underwent B-mode ultrasound of lymph nodes, showing nodular lesions with low echo in the neck; 22 cases (18.6%) underwent cervical X-ray and (or) CT; 7 cases (5.9%) underwent cervical magnetic resonance imaging. Lymph node biopsy was performed in all 118 cases, and the pathological results did not support malignant diseases such as lymphoma or Epstein-Barr virus infection, suggesting HNL. Fifty-seven cases (48.3%) recovered without treatment, 61 cases (51.7%) received oral steroid therapy, and 4 cases (3.4%) received indomethacin as anal stopper. The 118 cases were followed up for 4 (2, 6) years, ranging from 1 to 7 years, 87 cases (73.7%) had one onset and did not develop into other rheumatological diseases, and 24 cases (20.3%) had different degrees of recurrence, 7 cases (5.9%) had multiple system injuries, and all of the tested autoantibodies were positive for medium and high titers. All of them developed into other rheumatic immune diseases, among which 5 cases developed into systemic lupus erythematosus and 2 cases developed into Sjogren's syndrome; 7 cases were given oral steroid therapy, including 6 cases plus immunosuppressant and 2 cases receiving methylprednisolone 20 mg/kg shock therapy. Conclusions: The first-onset HNL portion is self-healing, hormone-sensitive and has a good prognosis. For HNL with repeated disease and multiple system injury, antinuclear antibody titer should be monitored during follow-up, and attention should be paid to the possibility of developing into other rheumatological diseases, with poor prognosis.
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Female , Male , Humans , Child , Histiocytic Necrotizing Lymphadenitis/drug therapy , Antibodies, Antinuclear , Epstein-Barr Virus Infections , Retrospective Studies , Herpesvirus 4, Human , Prognosis , SteroidsABSTRACT
Aldolase B (ALDOB), a glycolytic enzyme, is uniformly depleted in clear cell renal cell carcinoma (ccRCC) tissues. We previously showed that ALDOB inhibited proliferation through a mechanism independent of its enzymatic activity in ccRCC, but the mechanism was not unequivocally identified. We showed that the corepressor C-terminal-binding protein 2 (CtBP2) is a novel ALDOB-interacting protein in ccRCC. The CtBP2-to-ALDOB expression ratio in clinical samples was correlated with the expression of CtBP2 target genes and was associated with shorter survival. ALDOB inhibited CtBP2-mediated repression of multiple cell cycle inhibitor, proapoptotic, and epithelial marker genes. Furthermore, ALDOB overexpression decreased the proliferation and migration of ccRCC cells in an ALDOB-CtBP2 interaction-dependent manner. Mechanistically, our findings showed that ALDOB recruited acireductone dioxygenase 1, which catalyzes the synthesis of an endogenous inhibitor of CtBP2, 4-methylthio 2-oxobutyric acid. ALDOB functions as a scaffold to bring acireductone dioxygenase and CtBP2 in close proximity to potentiate acireductone dioxygenase-mediated inhibition of CtBP2, and this scaffolding effect was independent of ALDOB enzymatic activity. Moreover, increased ALDOB expression inhibited tumor growth in a xenograft model and decreased lung metastasis in vivo. Our findings reveal that ALDOB is a negative regulator of CtBP2 and inhibits tumor growth and metastasis in ccRCC.
Subject(s)
Humans , Carcinoma, Renal Cell/genetics , Fructose-Bisphosphate Aldolase/metabolism , Co-Repressor Proteins/metabolism , Transcription Factors/genetics , Kidney Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, NeoplasticABSTRACT
Objective@#To examine the effect of SiO2 exposure on the airway surface microenvironment and NIMA-related kinase 7 (NEK7)/nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome in rats.@*Methods@#Twenty-four specific pathogen-free male rats of the SD strain were randomly divided into the control group and the model group, of 12 rats in each group. Rats in the model group were given SiO2 suspensions through disposable tracheal intubation perfusion to model silicosis in rats, while rats in the control group was perfused with the same amount of physiological saline. The pH value and glucose level were measured in the rat bronchoalveolar lavage fluid (BALF) 14 and 28 days after modeling. Lung tissues were stained with HE and Masson and the distribution of inflammatory cells and the deposition of pulmonary interstitial collagens were observed in lung tissues under a light microscope. The expression of transforming growth factor β1 (TGF-β1), collagen type Ⅰ(ColⅠ), collagen type Ⅲ (Col Ⅲ), interleukin-1β (IL-1β), NLRP3, N-terminal domain of Gasdermin D (GSDMD-NT), caspase-1, and NEK7 was quantified in lung specimens using immunohistochemistry.@*Results@# Lower pH values were measured in rat BALF in the model group than in the control group 14 [(6.38±0.05) vs. (6.68±0.08), P<0.05] and 28 days after modeling [(6.63±0.14) vs. (6.86±0.05), P<0.05], while higher glucose levels were seen in the model group than in the control group 14 [(0.39±0.06) vs. (0.31±0.04) mg/dL, P<0.05] and 28 days after modeling [(0.39±0.08) vs. (0.31±0.06) mg/dL, P<0.05]. HE and Masson staining showed mild to moderate alveolitis and pulmonary fibrosis in rats 14 days post-exposure to SiO2, and showed moderate to severe alveolitis and pulmonary fibrosis 28 days post-exposure. Immunohistochemistry detected higher TGF-β1, ColⅠ, Col Ⅲ, IL-1β, NLRP3, GSDMD-NT, caspase-1 and NEK7 expression in rat lung tissues in the model group than in the control group (all P<0.05). @*Conclusions@#SiO2 exposure may cause changes in rat airway surface microenvironment, including BALF acidification and elevated glucose. Pyroptosis induced by activation of NEK7-associated NLRP3 inflammasome may be an important mechanism of pulmonary fibrosis caused by silicosis.
ABSTRACT
The study identified the blood-entering components of Sijunzi Decoction after gavage administration in rats by UPLC-Q-TOF-MS/MS, and investigated the mechanism of Sijunzi Decoction in treating Alzheimer's disease by virtue of network pharmacology, molecular docking, and experimental verification. The blood-entering components of Sijunzi Decoction were identified based on the mass spectra and data from literature and databases. The potential targets of the above-mentioned blood-entering components in the treatment of Alzheimer's disease were searched against PharmMapper, OMIM, DisGeNET, GeneCards, and TTD. Next, STRING was employed to establish a protein-protein interaction(PPI) network. DAVID was used to perform the Gene Ontology(GO) annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape 3.9.0 was used to carry out visual analysis. AutoDock Vina and PyMOL were used for molecular docking of the blood-entering components with the potential targets. Finally, the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway enriched by the KEGG analysis was selected for validation by animal experiments. The results showed that 17 blood-entering components were detected in the serum samples after administration. Among them, poricoic acid B, liquiritigenin, atractylenolide Ⅱ, atractylenolide Ⅲ, ginsenoside Rb_1, and glycyrrhizic acid were the key components of Sijunzi Decoction in treating Alzheimer's disease. HSP90AA1, PPARA, SRC, AR, and ESR1 were the main targets for Sijunzi Decoction to treat Alzheimer's disease. Molecular docking showed that the components bound well with the targets. Therefore, we hypothesized that the mechanism of Sijunzi Decoction in treating Alzheimer's disease may be associated with the PI3K/Akt, cancer treatment, and mitogen-activated protein kinase(MAPK) signaling pathways. The results of animal experiments showed that Sijunzi Decoction significantly attenuated the neuronal damage in the hippocampal dentate gyrus area, increased the neurons, and raised the ratios of p-Akt/Akt and p-PI3K/PI3K in the hippocampus of mice. In conclusion, Sijunzi Decoction may treat Alzheimer's disease by activating the PI3K/Akt signaling pathway. The findings of this study provide a reference for further studies about the mechanism of action and clinical application of Sijunzi Decoction.
Subject(s)
Animals , Mice , Rats , Proto-Oncogene Proteins c-akt , Network Pharmacology , Alzheimer Disease/drug therapy , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases/genetics , Tandem Mass Spectrometry , Drugs, Chinese Herbal/pharmacologyABSTRACT
Objective:To study the incidence and risk factors of early hyperglycemia in extremely preterm infants (EPIs).Methods:From January 2018 to December 2021, EPIs with gestational age (GA) <28 w born in our hospital and admitted to the neonatal department were retrospectively studied. According to the occurrence of early hyperglycemia (within 1 w after birth), the infants were assigned into hyperglycemia group and non-hyperglycemia group. Univariate and logistic regression were used to analyze the risk factors of early hyperglycemia in EPIs.Results:A total of 218 cases of EPIs were enrolled, including 70 (32.1%) in the hyperglycemia group and 148 (67.9%) in the non-hyperglycemia group. The incidence of early hyperglycemia in EPIs with GA<25 w was 10/20 and 11/16 in EPIs with birth weight (BW) ≤700 g. The GA and BW of the hyperglycemia group were significantly lower than the non-hyperglycemia group ( P<0.05). More infants in the hyperglycemia group had 1-min and 5-min Apgar≤7 than the non-hyperglycemia group ( P<0.05). Logistic regression analysis showed that increased BW ( OR=0.995, 95% CI 0.993~0.997, P<0.05) was a protective factor for early hyperglycemia in EPIs, while male gender ( OR=2.512,95% CI 1.232~5.123, P<0.05), vasoactive drug use during the first week of life ( OR=2.687, 95% CI 1.126~6.414, P<0.05), maternal hypertension during pregnancy ( OR=14.735, 95% CI 1.578~137.585, P<0.05) were risk factors for early hyperglycaemia in EPIs. Conclusions:Early hyperglycemia are common among EPIs. Low BW, male gender, vasoactive drug use during the first week of life and maternal hypertension during pregnancy may increase the risk of early hyperglycemia.