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ABSTRACT Purpose: The regulatory effect of microRNA on diseases has been confirmed. This study aimed to evaluate the expression of microRNA-210-3p in age-related cataracts and assess the effect of abnormal miR-210-3p expressions on H2O2-induced SAR01/04 cells. Methods: Reverse-transcription quantitative polymerase chain reaction method was performed to assess the levels of miR-210-3p in aqueous humor samples. Receiver operating characteristic analysis was employed to assess the discrimination ability of miR-210-3p between patients with age-related cataracts and healthy people, and Pearson correlation analysis was used to identify the correlation between miR-210-3p and oxidative stress indices such as superoxide dismutase, glutathione peroxidase, malonaldehyde. Cell counting kit-8 assay and Transwell assay were used to estimate the biological function of H2O2-induced age-related cataract cell model. The levels of oxidative stress indices such as superoxide dismutase, glutathione peroxidase, and malonaldehyde were measured to evaluate the degree of oxidative stress damage in the age-related cataract cell model. The relationship between miR-210-3p and its target gene was verified by luciferase reporter gene analysis. Results: The miR-210-3p expression was elevated in the aqueous humor of patients with age-related cataracts. A high miR-210-3p expression showed a high diagnostic value for age-related cataracts and was significantly associated with the level of oxidative stress markers in patients with age-related cataracts. The inhibition of miR-210-3p can reverse oxidative stress stimulation and adverse effects on H2O2-induced cell function. Conclusions: The results suggested that miR-210-3p could promote cell viability, cell migration, and oxidative stress by targeting autophagy-related gene 7 in in vitro age-related cataract cell model.
RESUMO Objetivo: O efeito regulador do microRNA em doenças tem sido confirmado, e este artigo tentou avaliar a expressão do microRNA-210-3p na catarata relacionada à idade e avaliar o efeito da expressão anormal do miR-210-3p em células SAR01/04 induzidas por H2O2. Métodos: O método de transcrição reversa seguida de reação em cadeia da polimerase (RT-PCR) quantitativa foi realizado para avaliar os níveis de miR-210-3p em amostras de humor aquoso. Análise de características operacionais do receptor foi feita para avaliar a capacidade de discriminação do miR-210-3p entre pacientes com catarata relacionada à idade e pessoas saudáveis. A análise de correlação de Pearson identificou a correlação do miR-210-3p e índices de estresse oxidativo, como superóxido dismutase, glutationa peroxidase, malonaldeído. O ensaio de contagem de células kit-8 (cck-8) e o ensaio no sistema Transwell foram utilizados para estimar a função biológica do formato de células de catarata relacionada com a idade induzida por H2O2. Os níveis de índices de estresse oxidativo como superóxido dismutase, glutationa peroxidase e malonaldeído foram detectados para avaliar o grau de dano do estresse oxidativo em formato de células de catarata relacionada à idade. A relação entre miR-210-3p e seu gene alvo foi verificada por análise do gene repórter luciferase. Resultados: A expressão miR-210-3p foi elevada no humor aquoso de pacientes com catarata relacionada à idade. A expressão miR-210-3p altamente expressiva mostrou alto valor diagnóstico para catarata relacionada à idade e foi significativamente associado ao nível de marcadores de estresse oxidativo em pacientes com catarata relacionada à idade. A inibição de miR-210-3p pode reverter a estimulação do estresse oxidativo e os efeitos adversos da função celular induzida por H2O2. Conclusões: Esses dados sugeriram que a expressão miR-210-3p poderia promover a viabilidade celular, migração celular e estresse oxidativo ao direcionar genes ATG 7 relacionados à autofagia em modelo in vitro de células de catarata relacionadas à idade.
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Objective@#To explore the relationship between cumulative family risk and depression symptoms at 2 and 4 year follow up among children and adolescents, so as to provide reference basis for promoting the mental health of children and adolescents.@*Methods@#Data were acquired from the China Family Panel Studies (CFPS) project in 2016(T1), 2018 (T2), and 2020 (T3), which included 730 children and adolescents, their families and parents. The measurement tools included the Cumulative Family Risk Scales and Center for Epidemiologic Studies Depression Scale (CES-D). Chi square test and Logistic regression were used to analyze the relationship between cumulative family risk and depression symptoms among children and adolescents.@*Results@#The detection rates of moderate and above depression symptoms among children and adolescents at T1, T2, and T3 were 14.4%, 15.9%, and 24.5%, respectively. The prevalence of depression symptoms of children and adolescents at T2 was higher in females (19.8%) than males (12.5%)( χ 2=7.28 ,P <0.01). Logistic regression analyses showed that the cumulative family risk at T1 positively predicted depression symptoms of children and adolescents at T1, T2, and T3( OR =1.73, 1.32, 1.38, P ＜0.05).@*Conclusions@#The cumulative family risk has a long lasting impact on depressive symptoms among children and adolescents after 2 and 4 years. Family and schools should pay attention to the changes in depression among children and adolescents,and provide timely intervention and assistance to promote their mental health development.
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@#Objective To investigate the effect of intravenous analgesia with a wireless or traditional analgesia pump system in thoracoscopic lung resection. Methods Patients who used the patient-controlled intravenous analgesia after thoracoscopic lung resection between June 2016 and June 2021 were enrolled in the study. They were allocated into a wireless pump group (a ZigBee-based wireless analgesia pump system collecting data automatically) and a traditional analgesia pump group. Perioperative analgesia management followed the routine standard operation protocol of Shanghai Chest Hospital. The patients’ numeric rating scale (NRS) for pain and postoperative nausea and vomiting (PONV) scores were collected for analysis from the Anesthesia Information Record System. The incidence of postoperative analgesia insufficiency (defined as NRS≥4 points) within 48 h, the incidence of PONV within 24 h, and the 48 h completion rate of analgesia pump infusion were compared. Results A total of 59 431 patients were collected, including 24 855 males and 34 576 females, 17 209 patients in the wireless pump group, and 42 222 patients in the traditional analgesia pump group. The incidence of analgesia insufficiency within 48 h after operation (3.75% vs. 4.98%, P=0.007), the incidence of PONV within 24 h after operation (13.60% vs. 16.70%, P=0.030) in the wireless pump group were lower than those in the traditional analgesia pump group. The 48 h completion rate of analgesia pump infusion in the wireless pump group was higher than that in the traditional analgesia pump group (83.40% vs. 71.90%, P<0.001). The wireless pump group could monitor the pressing times and use of the analgesia pump, while the traditional analgesia pump group could not record the relevant data. Conclusion Compared with the traditional analgesia pump, the wireless analgesia management system may be convenient for timely, accurate and individualized management, and has good analgesic effect and low incidence of adverse reactions, and may be more suitable for perioperative analgesia management.
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Objective:To analyze the development prospect of ChatGPT in the field of medical research management and the feasibility of application.Methods:The literature was reviewed and analyzed.Results:This paper describes the application of ChatGPT involving the orderly promotion of medical scientific research projects, the working mode of scientific research managers, and the development of scientific research management platform.Conclusions:The development of ChatGPT makes it have its unique advantages in medical scientific research management, but also has some shortcomings, which need to be reasonably understood and scientifically applied.
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This article reported a male neonate with lethal mitochondrial trifunctional protein deficiency (MTPD) caused by compound heterozygous variations in the HADHB gene. The patient presented with poor milk intake complicated by abnormal myocardial enzymes within 24 h after birth and was transferred to the Children's Hospital of Nanjing Medical University on day 4. Physical examination revealed no obvious abnormalities on admission. Laboratory examination showed increased creatine kinase isoenzyme and cardiac troponin levels, and electrocardiogram suggested sinus tachycardia and low QRS voltage in limb leads. Blood screening for metabolic abnormalities showed high levels of tetradecenyl carnitine and various 3-hydroxycarnitines. Heterozygous mutations of c.739C>T(p.Arg247Cys) and c.607C>T(p.Arg203Ter,272) were detected in the HADHB gene in the boy, which were pathogenic variants included in the Human Gene Mutation Database. Followed up to three months of age, the boy was readmitted to hospital due to poor milk intake for one week and poor response for 2 d after catching a cold. After admission, he quickly developed multiple organs dysfunction such as heart failure and respiratory failure, and then died. Lethal MTPD is rare with no effective treatment and poor prognosis. Lethal MTPD should be highly suspected when unexplained cardiomyopathy, hypoglycemia, acidosis and other metabolic abnormalities appear in the neonatal period, and an early diagnosis could be confirmed with genetic testing in the neonatal period.
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Objective:To investigate the counteractive effect of mouse dermal fibroblasts (MdFBs) during their adipogenic differentiation against Staphylococcus aureus infection, and to explore its mechanisms. Methods:MdFBs were obtained from newborn C57BL/6 mice, and their adipogenic differentiation was induced by culture in an adipogenic medium for 48 hours. Real-time fluorescence-based quantitative PCR (RT-PCR) was performed to determine the mRNA expression of cathelicidin antimicrobial peptide (CAMP) on days 0-6 during the adipogenic differentiation of MdFBs, and Western blot analysis to determine the protein expression of CAMP in the culture supernatant of MdFBs during their adipogenic differentiation. MdFBs were divided into 4 groups: co-stimulation group stimulated by S. aureus suspensions and cultured in an adipogenic medium, adipogenic control group cultured in an adipogenic medium, S. aureus-stimulation group stimulated by S. aureus suspensions and cultured in a common medium, and control group stimulated by phosphate-buffered saline and cultured in a common medium; Western blot analysis and RT-PCR were conducted to determine the protein and mRNA expression of CAMP. S. aureus (5 × 10 4 CFU/ml) was cultured with the culture supernatant of MdFBs after 5-day adipogenic differentiation (adipogenic group), and the growth activity was evaluated every 2 hours during 10 - 24 hours after the start of co-culture; S. aureus cultured with the culture supernatant of MdFBs in a common medium served as the normal control group, and that cultured with cell-free culture supernatant served as the negative control group. Differences between groups were assessed using unpaired t-test or analysis of variance. Results:Significant differences were observed in the relative mRNA expression of CAMP among different time points (days 0, 1, 2, 4, and 6) during the adipogenic differentiation of MdFBs (1.14 ± 0.74, 68.04 ± 12.72, 683.12 ± 38.06, 1 390.68 ± 226.21, 454.57 ± 204.12, F = 50.08, P < 0.001) ; the CAMP mRNA expression was significantly higher on days 1, 2, 4, and 6 than on day 0 ( t = 9.09, 31.03, 10.63, 3.85, respectively, all P < 0.05), and showed an initial rise and subsequent fall during days 0 - 6. The CAMP protein expression in the culture supernatant of MdFBs peaked on days 2-5 and subsequently decreased. Significant differences were observed in the mRNA and protein expression of CAMP among the control group, S. aureus-stimulation group, adipogenic control group and co-stimulation group (mRNA: 0.08 ± 0.02, 0.38 ± 0.10, 0.49 ± 0.11, 0.80 ± 0.03, respectively, F = 43.25, P < 0.05; protein: 0.433 ± 0.176, 0.574 ± 0.176, 1.007 ± 0.176, 1.217 ± 0.176, respectively, F = 46.79, P < 0.05), and the relative mRNA and protein expression of CAMP was significantly higher in the co-stimulation group than in the adipogenic control group, S. aureus-stimulation group and control group (all P < 0.05). At 10 hours during culture, the growth activity of S. aureus was significantly lower in the adipogenic group (0.053 ± 0.015) than in the normal control group and negative control group (0.109 ± 0.015, 0.106 ± 0.015, t = 11.30, 13.26, respectively, both P < 0.05) ; during 10 - 24 hours, the growth activity of S. aureus also showed a significant decrease in the adipogenic group compared with the normal control group and negative control group (all P < 0.05) . Conclusion:MdFBs secreted CAMP during the adipogenic differentiation, and could inhibit the proliferation of S. aureus.
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Objective:To investigate the effect of Candida albicans ( C. albicans) on pyroptosis of murine bone marrow-derived macrophages (BMDMs) . Methods:Live-cell imaging was used to observe morphologic changes of in vitro C. albicans-infected BMDMs (multiplicity of infection [MOI] = 50) so as to evaluate whether pyroptosis occurred. Cultured BMDMs were divided into a control group and a C. albicans group, which were treated with phosphate-buffered saline and C. albicans suspensions respectively for 6 hours; then, real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of NOD-like receptor pyrin domain containing 3 (NLRP3), interleukin (IL) -1β and IL-18, and Western blot analysis to determine the protein expression and cleavage levels of NLRP3, caspase-1 and gasdermin D (GSDMD). BMDMs were cultured with C. albicans suspensions for different durations (0, 10, 15, 20, and 25 hours), and enzyme-linked immunosorbent assay was conducted to detect secretion levels of IL-1β and IL-18. Cultured wild-type BMDMs and GSDMD-knockout BMDMs were treated with C. albicans suspensions for 15 minutes, and then rates of phagocytosis of C. albicans by wild-type BMDMs and GSDMD-knockout BMDMs were estimated by flow cytometry; after 6-hour treatment with C. albicans, flow cytometry and lactate dehydrogenase (LDH) release assay were performed to assess mortality rates of wild-type BMDMs and GSDMD-knockout BMDMs. In addition, some wild-type BMDMs and GSDMD-knockout BMDMs were separately divided into blank control group, control group, maximum enzyme activity-sample control group, IL-1β alone group, C. albicans alone group, and IL-1β + C. albicans group, and cell mortality rates were detected by the LDH release assay after treatment with IL-1β and/or C. albicans. Statistical analysis was carried out by using unpaired t test, Kruskal-Wallis test, analysis of variance, and other statistical methods. Results:After in vitro treatment with C. albicans, swelling and ballooning with large bubbles blowing from the plasma membrane occurred in BMDMs, suggesting the occurrence of cell pyroptosis; compared with the control group, the C. albicans group showed significantly increased mRNA expression levels of NLRP3 and IL-1β after 6-hour treatment with C. albicans ( t = 13.02, 17.51, respectively, P = or < 0.001), but no significant change in the IL-18 mRNA expression level ( P = 0.486), and Western blot analysis showed that C. albicans could increase the expression of NLRP3 inflammasomes, as well as cleaved caspase-1 and GSDMD. After the treatment with C. albicans for different durations (0, 10, 15, 20, and 25 hours), the secretion level of IL-1β by BMDMs gradually increased over time ( H = 12.90, P = 0.012), while the secretion level of IL-18 did not significantly change ( F = 0.48, P = 0.753), and the secretion level of IL-1β was significantly lower in the GSDMD-knockout BMDM group than in the wild-type BMDM group ( F = 24.22, P = 0.008). After 15-minute in vitro treatment with C. albicans, the phagocytosis rate of C. albicans was significantly lower in the GSDMD-knockout BMDM group (50.3% ± 1.10%) than in the wild-type BMDM group (58.53% ± 1.19%, t = 5.09, P = 0.007) ; after 6-hour treatment with C. albicans, the cell mortality rate was significantly higher in the GSDMD-knockout BMDM group than in the wild-type BMDM group (flow cytometry: 38.40% ± 0.50% vs. 34.37% ± 0.52%, t = 4.72, P = 0.009; LDH release assay: 22.52% ± 0.18% vs. 12.48% ± 0.15%, t = 42.36, P < 0.001) ; the cell mortality rates of wild-type BMDMs and GSDMD-knockout BMDMs both significantly decreased in the IL-1β + C. albicans groups compared with the C. albicans groups (both P < 0.001) . Conclusion:Pyroptosis could be induced in murine BMDMs after C. albicans infection, which promotes the release of IL-1β and may reduce the mortality rate of macrophages by improving their immune activity.
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Aim To investigate the potential mechanism of osthole promoting autophagy in cervical cancer HeLa cells. Methods HeLa cells were treated with various concentrations of Osthole(0,10,20,40,80,160,240,320 mg·L-1). MTT was used to detect cell vitality. Transmission electron microscopy(TEM)was used to observe the morphology of HeLa cells after osthole intervention. Mondane sulfonyl cadaverine(MDC)staining was used to dectect the level of autophagy. Western blot was employed to analyze the expression levels of mitochondrial protein MFN1 and DPR1. JC-1 flourescence probe was applied to detect mitochondrial membrane potential. Flow cytometry was used to deteminet the release of reactive oxygen species(ROS). A transplanted tumor model of cervical cancer was established in vivo in nude mice. Western blot was used to detect the protein expression levels of PINK1,Parkin and LC3Ⅱ/. Results Osthole could inhibit the proliferation of HeLa cells significantly. Transmission electron microscopy showed that typical autophagosomes were formed in HeLa cells after osthole intervention. The fluorescence intensity of MDC was enhanced. The expression of mitochondrial fusion protein MFN1 was down-regulated after HeLa cells pretreated with osthole,and mitochondrial fission protein DRP1 was up-regulated. Mitochondrial membrane potential decreased. ROS production of HeLa cells was increased by flow cytometry,which could be reversed by autophagy inhibitor 3-MA. Tumor weight in nude mice was inhibited by osthole obviously,which might restrain cervical cancer. Western blot result indicated that the key factors of mitochondrial autophagy PINK1,Parkin and LC3Ⅱ/ratio were up-regulated in HeLa cells. Conclusions Osthole could induce autophagy in HeLa cells and its mechanism may be related to ROS production and PINK1/Parkin pathway.
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Objective To explore the inhibitory effects and mechanisms of benzodiazepines on Helicobacter pylori (Hp).Methods The Hp international standard strain ATCC43504 was treated with benzodiazepines diazepam,midazolam,and remimazolam,respectively.The treatments with amoxicillin and clarithromycin were taken as the positive controls,and that with water for injection as the negative control.The inhibition zone of each drug was measured by the disk diffusion method.The minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of each drug against Hp were determined.Hp suspension was configured and treated with diazepam and midazolam,respectively.The bacterial suspension without drug added was used as the control group.The concentration of K+ in each bacterial suspension was measured by an automatic biochemical analyzer before drug intervention(T0)and 1(T1),2(T2),3(T3),4(T4),5(T5),6(T6),and 7 h(T7)after intervention.Hp urease was extracted and treated with 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,2 MIC midazolam,1 mg/ml acetohydroxamic acid,and water for injection,respectively.The time required for the rise from pH 6.8 to pH 7.7 in each group was determined by the phenol red coloring method.Results The inhibition zones of diazepam,midazolam,remimazolam,amoxicillin,clarithromycin,and water for injection against Hp were 52.3,42.7,6.0,72.3,60.8,and 6.0 mm,respectively.Diazepam and midazolam showed the MIC of 12.5 μg/ml and 25.0 μg/ml and the MBC of 25 μg/ml and 50 μg/ml,respectively,to Hp.The concentrations of K+ in the diazepam,midazolam,and control groups increased during T1-T7 compared with those at T0(all P<0.01).The concentration of K+ in diazepam and midazolam groups during T1-T4 was higher than that in the control group(all P<0.01).The time of inhibiting urease activity in the 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,and 2 MIC midazolam groups was(39.86±5.11),(36.52±6.65),(38.58±4.83),(39.25±6.19),(36.36±4.61),and(35.81±6.18)min,respectively,which were shorter than that in the acetohydroxamic acid group(all P<0.01)and had no significance differences from that in the water for injection group(all P>0.05).Conclusion Diazepam and midazolam exerted inhibitory effects on Hp,which may be related to the cleavage of Hp cells rather than inhibiting urease.
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Midazolam , Helicobacter pylori , Urease , Claritromicina/farmacologia , Benzodiazepinas/farmacologia , Diazepam/farmacologia , Amoxicilina , Água , Antibacterianos/farmacologiaRESUMO
【Objective】 To investigate the association between the long-stranded non-coding ribonucleic acid (lncRNA) MRAK088388 and allergic asthma in children. 【Methods】 A total of 15 healthy children and 15 children with asthma were monitored for disease progression over a 2-year period. Blood samples were collected from patients during the chronic phase of the disease for lncRNA/mRNA expression microarray analysis. Competing endogenous RNA networks (MRAK088388/miR-30a/ATG5) were identified by bioinformatics analysis. In vitro cultured bronchial epithelial (16HBE) cells were used to quantify gene and associated protein expression levels by real-time fluorescent quantitative polymerase chain reaction (qPCR) and protein blotting, respectively. Cell Counting Kit-8 and transwell assays were used to assess the proliferation and migration of 16HBE cells and verify the effects of MRAK088388, miR-30a and ATG5 on asthma. 【Results】 Six lncRNA-miRNA-mRNAs were identified by correlation analysis. By qRT-PCR analysis, MRAK088388/miR-30a/ATG5 was selected to construct the ceRNA network in this study. mRAK088388 and ATG5 expressions were high in the peripheral blood of children with asthma, while the expression of miR-30a was low (P<0.05). The expression level of E-cadherin was significantly higher in 16HBE cells after si-MRAK088388+TGF-β1 group, while the expression levels of Vimentin and α-SMA were significantly lower (P<0.05), indicating that knockdown of MRAK088388 inhibited the epithelial mesenchymal transition in 16HBE cells. Compared with si-NC+ TGF-β1 group, the cell morphology of si-MRAK088388+TGF-β1 group was similar to that of the control group, indicating that MRAK088388 knockdown attenuated TGF-β1-induced cell morphological changes; in addition, MRAK088388 knockdown inhibited TGF-β1-induced proliferation and migration of 16HBE cells. MRAK088388 was confirmed by qPCR and protein blotting to promote the progression of childhood asthma by targeting the miR-30a/ATG5 axis. 【Conclusion】 Childhood asthma is associated with the MRAK088388/miR-30a/ATG5 axis, and MRAK088388 is involved in the process of childhood allergic asthma by negatively regulating miR-30a expression and regulating elevated ATG5 expression levels to affect bronchial epithelial cell mesenchymal transition, proliferation, and migration.
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With the implementation of the "BRAIN initiative" in various countries, neuroethical governance has become an important concern of the international community. After ten years of development, the "BRAIN initiative" in the United States has formed a relatively complete ethical governance system. By interpreting the strategic report of the "BRAIN initiative" in the United States, analyzing its basic framework of ethical governance, dissecting its governance practice mechanism, and conducting research from the aspects of top-level design and construction, regulatory model innovation, promoting public participation, enhancing international dialogue, and improving soft and hard regulations, this paper provided some reference and thoughts for the ethical governance of the "BRAIN initiative" in China.
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@#Based on our previous work, the study herein designed and synthesized eight glycoconjugates of natural product harmine (14a-14h)by introducing a cyclohexylmethyloxyl group at its C7 position and coupling a methyl-2-amino-β-D-glucopyranoside to the N9 position through different lengths of alkyl chains.In vitro anti-tumor activity screening and structure-activity relationship studies showed that the antitumor activity of the conjugates increased with the lengthening of the alkyl chain in the linker.Compound 14h exhibited significantly better proliferative inhibitory activity against MDA-MB-231 breast cancer cells than harmine.As compared to harmine, the introduction of the carbohydrate moiety improved the water solubility of compound 14h and enhanced its tumor cell selectivity through the Warburg effect.Mechanism of action studies revealed that compound 14h induced apoptosis and G0/G1 cell cycle arrest in MDA-MB-231 cells, and inhibited tumor cell migration by interfering with epithelial-mesenchymal transition process.This study provides a new approach for the development of antitumor drugs based on harmine.
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OBJECTIVE To compare the efficacy of different enteral nutrition （EN） drugs for severe acute pancreatitis （SAP） and their gastrointestinal tolerance. METHODS A total of 118 SAP patients admitted to the Pancreatic Center of Jiangsu Provincial People’s Hospital from January 1， 2022 to June 30， 2023 were collected and divided into short-peptide EN drugs （SP） group （41 cases）， dietary fiber-free intact protein EN drugs （TP-MCT） group （40 cases） and dietary fiber-containing intact protein EN drugs （TPF-DM） group （37 cases） according to the types of EN. All three groups of patients were given continuous pumps of EN drugs via nasal feeding for 24 hours， with a target energy dose of 25-30 kcal/kg. The blood nutritional indexes [albumin （ALB）， total protein （TP）， hemoglobin （Hb）， globulin （GLB）]， inflammation indexes [white blood cells （WBC）， percentage of neutrophils （N%）， procalcitonin （PCT）， C-reactive protein （CRP）， interleukin-6 （IL-6）]， clinical outcomes indexes [time of stay in the intensive care unit （ICU）， length of hospital stay， duration of resuming oral diet， the rate of cases without improvement， mortality rate] and the occurrence of gastrointestinal tolerance were collected from 3 groups before medication and 7 d after medication. RESULTS After treatment， ALB and TP in 3 groups were significantly higher than before treatment （P＜0.05）； CRP and N% of 3 groups， PCT of TP-MCT group and IL-6 of SP group were significantly lower than corresponding group before medication （P＜ 0.05）； PCT of TP-MCT group and IL-6 of SP group were significantly lower than those of other two groups at corresponding period （P＜0.05）. There were no statistical significances in ALB， TP， CRP or N% among the three groups after medication， and in Hb， GLB or WBC among the three groups before and after treatment （P＞0.05）. There was no significant difference in clinical outcome indexes among 3 groups （P＞0.05）. The incidence of gastrointestinal adverse reactions in the TP-MCT group was the lowest （32.50%）， and significantly lower than those in the SP group （46.34%） and TPF-DM group （48.65%） （P＜0.05）. CONCLUSIONS Different EN preparations can improve the nutritional status and reduce the inflammatory response in SAP patients to different extents， among which SP and TP-MCT are more effective， and TP-MCT shows the better gastrointestinal tolerance.
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Bacteremia induced by periodontal infection is an important factor for periodontitis to threaten general health. P. gingivalis DNA/virulence factors have been found in the brain tissues from patients with Alzheimer's disease (AD). The blood-brain barrier (BBB) is essential for keeping toxic substances from entering brain tissues. However, the effect of P. gingivalis bacteremia on BBB permeability and its underlying mechanism remains unclear. In the present study, rats were injected by tail vein with P. gingivalis three times a week for eight weeks to induce bacteremia. An in vitro BBB model infected with P. gingivalis was also established. We found that the infiltration of Evans blue dye and Albumin protein deposition in the rat brain tissues were increased in the rat brain tissues with P. gingivalis bacteremia and P. gingivalis could pass through the in vitro BBB model. Caveolae were detected after P. gingivalis infection in BMECs both in vivo and in vitro. Caveolin-1 (Cav-1) expression was enhanced after P. gingivalis infection. Downregulation of Cav-1 rescued P. gingivalis-enhanced BMECs permeability. We further found P. gingivalis-gingipain could be colocalized with Cav-1 and the strong hydrogen bonding between Cav-1 and arg-specific-gingipain (RgpA) were detected. Moreover, P. gingivalis significantly inhibited the major facilitator superfamily domain containing 2a (Mfsd2a) expression. Mfsd2a overexpression reversed P. gingivalis-increased BMECs permeability and Cav-1 expression. These results revealed that Mfsd2a/Cav-1 mediated transcytosis is a key pathway governing BBB BMECs permeability induced by P. gingivalis, which may contribute to P. gingivalis/virulence factors entrance and the subsequent neurological impairments.
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Animais , Ratos , Bacteriemia/metabolismo , Barreira Hematoencefálica/microbiologia , Caveolina 1/metabolismo , Cisteína Endopeptidases Gingipaínas/metabolismo , Permeabilidade , Porphyromonas gingivalis/patogenicidade , Transcitose , Fatores de Virulência/metabolismoRESUMO
OBJECTIVE@#To explore the effect of facet joint degeneration in adjacent segments on the incidence of adjacent segment disease (ASD) after lumbar fusion and fixation.@*METHODS@#A retrospective analysis was performed on 138 patients who underwent L5S1 posterior lumbar interbody fusion (PLIF) from June 2016 to June 2019. Patients were divided into a degeneration group (68 cases) and a non-degenerative group (70 cases) based on the presence or absence of L4,5 facet joint degeneration before surgery (graded using the Weishaupt standard). Age, gender, body mass index (BMI), follow-up time, and preoperative L4,5 intervertebral disc degeneration (graded using the Pfirrmann standard) were collected for both groups. Clinical outcomes were evaluated using the visual analogue scale (VAS) and Oswestry disability index (ODI) at 1 and 3 months after surgery. The incidence and time of ASD after surgery were analyzed.@*RESULTS@#There were no significant differences between the two groups in age, gender, BMI, follow-up time, or preoperative L4,5 intervertebral disc degeneration. Both groups showed significant improvement in VAS and ODI at 1 and 3 months after surgery (P<0.001), with no significant difference between the groups(P>0.05). However, there was a statistically significant difference in the incidence and timing of ASD between the groups (P<0.05). The degeneration group had 2 cases of ASD in gradeⅠdegeneration, 4 cases of ASD in gradeⅡdegeneration, and 7 cases of ASD in grade Ⅲ degeneration. There was a statistically significant difference between the number of patients with grade Ⅲ degeneration and those with gradesⅠandⅡASD (P<0.0167, Bonferroni correction).@*CONCLUSION@#Preoperative degeneration of adjacent articular processes will increase the risk of ASD after lumbar fusion fixation, whereas gradeⅢ degeneration will further increase the risk.
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Humanos , Degeneração do Disco Intervertebral/cirurgia , Articulação Zigapofisária/cirurgia , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Vértebras Lombares/cirurgia , Espondilose , Resultado do TratamentoRESUMO
OBJECTIVE@#To investigate the effect of body mass index (BMI) on the short-term effectiveness of high tibial osteotomy (HTO) in the treatment of varus knee arthritis.@*METHODS@#The clinical data of 84 patients (84 knees) with varus knee arthritis treated with HTO between May 2016 and August 2020 were retrospectively analyzed. According to BMI, the patients were divided into normal group (32 patients in group A, BMI<25 kg/m 2), overweight group (27 patients in group B, BMI>30 kg/m 2), and obese group (25 patients in group C, BMI>30 kg/m 2). The BMI of groups A, B, and C were (23.35±0.89), (26.65±1.03), and (32.05±1.47) kg/m 2, respectively. There was no significant difference ( P>0.05) in gender, age, surgical side, disease duration, and preoperative Hospital for Special Surgery (HSS) score, visual analogue scale (VAS) score, knee range of motion, and hip-knee-ankle angle (HKA) between groups. The operation time, intraoperative dominant blood loss, and the decrease of hemoglobin on the 3rd day after operation were recorded and compared between groups. The improvement of knee joint function and pain status were evaluated by knee joint HSS score, knee range of motion, and VAS score before and after operation, and measuring the HKA of patients on X-ray film. During the follow-up, the X-ray films of the knee joint were reexamined to observe the position of the internal fixator and the healing of osteotomy.@*RESULTS@#All patients completed the operation successfully and were followed up 8-40 months (mean, 19.3 months). There was no significant difference in follow-up time, operation time, intraoperative dominant blood loss, and the decrease of hemoglobin on the 3rd day after operation between groups ( P>0.05). No operative complications such as severe vascular or nerve injury occurred. After operation, deep venous thrombosis of lower extremities occurred in 1 case in groups A and B respectively, and fat liquefaction of surgical incision occurred in 2 cases in group C. There was no significant difference in the incidence of perioperative complications between groups (3.1% vs. 3.7% vs. 8.0%) ( P=0.689). During the follow-up, there was no bone nonunion, plate fracture or loosening. At last follow-up, HSS score, VAS score, knee range of motion, and HKA significantly improved in the 3 groups when compared with those before operation ( P<0.05), but there was no significant difference in the differences of the above indexes between groups before and after operation ( P>0.05).@*CONCLUSION@#BMI does not affect the short-term effectiveness of HTO in the treatment of varus knee arthritis. HTO can be selected for overweight and obese patients after standard medical treatment is ineffective.
Assuntos
Humanos , Osteoartrite do Joelho/cirurgia , Índice de Massa Corporal , Sobrepeso , Estudos Retrospectivos , Resultado do Tratamento , Articulação do Joelho/cirurgia , Obesidade/complicações , Osteotomia , Perda Sanguínea CirúrgicaRESUMO
Objective Primary ovarian small cell carcinoma of pulmonary type (SCCOPT) is a rare ovarian tumor with a poor prognosis. The platinum-based chemotherapy is the standard treatment. However, there is little research on the clinical characteristics of SCCOPT and the potential benefits of other treatments due to its low incidence. The study aims to investigate clinicopathological characteristics and treatment of SCCOPT.Methods We summarized the clinical, imaging, laboratorical and pathological characteristics of 37 SCCOPT cases, in which 6 cases were admitted to the Gansu Provincial Hospital from the year of 2008 to 2022 and 31 cases reported in 17 English and 3 Chinese literatures.Results The median age of the studied SCCOPT cases (n=37) was 56.00 (range, 22-80) years. Almost 80% of them had a stage Ⅲ or Ⅳ tumor. All patients underwent an operation and postoperative chemotherapy. Nevertheless, all cases had a poor prognosis, with a median overall survival time of 12 months. Immunohistochemically, the SCCOPT of all patients showed positive expressions of epithelial markers, such as CD56 and sex-determining region of Y chromosome-related high-mobility-group box 2 (SOX-2), and negative expressions of estrogen receptor, progesterone receptor, vimentin, Leu-7, and somatostatin receptor 2. The tumor of above 80% cases expressed synaptophysin. Only a few cases expressed neuron-specific enolase, chromogranin A, and thyroid transcription factor-1. Conclusions SCCOPT had a poor prognosis. SOX-2 could be a biomarker to be used to diagnose SCCOPT.
Assuntos
Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Pequenas/patologia , Carcinoma Epitelial do Ovário , Neoplasias Ovarianas/terapia , PrognósticoRESUMO
Diabetic kidney disease is an important microvascular complication of diabetes and the leading cause of end-stage renal disease. Its pathological characteristics mainly include epithelial mesenchymal transition(EMT) in glomerulus, podocyte apoptosis and autophagy, and damage of glomerular filtration barrier. Transforming growth factor-β(TGF-β)/Smad signaling pathway is specifically regulated by a variety of mechanisms, and is a classic pathway involved in physiological activities such as apoptosis, proliferation and differentiation. At present, many studies have found that TGF-β/Smad signaling pathway plays a key role in the pathogenesis of diabetic kidney disease. Traditional Chinese medicine has significant advantages in the treatment of diabetic kidney disease for its multi-component, multi-target and multi-pathway characteristics, and some traditional Chinese medicine extracts, traditional Chinese medicines and traditional Chinese medicine compound prescription improve the renal injury of diabetic kidney disease by regulating TGF-β/Smad signaling pathway. This study clarified the mechanism of TGF-β/Smad signaling pathway in diabetic kidney disease by expounding the relationship between the key targets of the pathway and diabetic kidney disease, and summarized the research progress of traditional Chinese medicine in the treatment of diabetic kidney disease by interfering with TGF-β/Smad signaling pathway in recent years, to provide reference for drug research and clinical treatment of diabetic kidney disease in the future.
Assuntos
Humanos , Nefropatias Diabéticas/genética , Medicina Tradicional Chinesa , Rim/patologia , Fator de Crescimento Transformador beta/metabolismo , Transdução de Sinais , Transição Epitelial-Mesenquimal , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Diabetes Mellitus/genéticaRESUMO
In order to comprehensively evaluate the quality of Viticis Fructus, this study established HPLC fingerprints and evaluated the quality of 24 batches of Viticis Fructus samples from different species by similarity evaluation and multivariate statistical analysis(PCA, HCA, PLS-DA). On this basis, an HPLC method was established to compare the content differences of the main components, including casticin, agnuside, homoorientin, and p-hydroxybenzoic acid. The analysis was performed on the chromatographic column(Waters Symmetry C_(18)) with a gradient mobile phase of acetonitrile(A)-0.05% phosphoric acid solution(B) at the flow rate of 1 mL·min~(-1) and detection wavelength of 258 nm. The column temperature was 30 ℃ and the injection volume was 10 μL. The HPLC fingerprint of 24 batches of Viticis Fructus samples was established with 21 common peaks, and nine peaks were identified. Similarity analysis was carried out based on chromatographic data of 24 batches of chromatographic data of Viticis Fructus, and the results showed that except for DYMJ-16, the similarity of Vitex trifolia var. simplicifolia was ≥0.900, while that of V. trifolia was ≤0.864. In addition, the similarity analysis of two different species showed that the similarity of 16 batches of V. trifolia var. simplicifolia was 0.894-0.997 and that of the eight batches of V. trifolia was between 0.990 and 0.997. The results showed that the similarity of fingerprints of these two species was different, but the similarity between the same species was good. The results of the three multivariate statistical analyses were consistent, which could distinguish the two different species. The VIP analysis results of PLS-DA showed that casticin and agnuside contributed the most to the distinction. The content determination results showed that there was no significant difference in the content of homoorientin and p-hydroxybenzoic acid in Viticis Fructus from different species, but the content of casticin and agnuside was significantly different in different species(P<0.01). The content of casticin was higher in V. trifolia var. simplicifolia, while agnuside was higher in V. trifolia. The findings of this study show that there are differences in fingerprint similarity and component content of Viticis Fructus from different species, which can provide references for the in-depth study of the quality and clinical application of Viticis Fructus.
Assuntos
Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta Pressão/métodos , Frutas/química , Vitex/químicaRESUMO
Under the national policy background of traditional Chinese medicine（TCM）registration review and approval reform， TCM preparations in medical institutions（hereinafter referred to as medical institution preparations） have human use experience， conform to the characteristics of TCM clinical practice， and have advantages in the research and development of innovative Chinese medicines. Therefore， the research and development mode based on clinical experience prescription-medical institution preparations-innovative Chinese medicines has attracted widespread attention from the industry. However， in the process of development and use of medical institution preparations， there are generally clinical problems that restrict their transformation into innovative Chinese medicines， resulting in a relatively weak collection basis of human use experience and insufficient clinical evidence for supporting the research and development of new TCM medicines. In this paper， on the basis of sorting out the supporting regulations and relevant technical requirements of human use experience， and analyzing the clinical problems restricting the transformation of medical institution preparations， it provides suggestions for medical institutions to carry out high-quality research on human use experience of preparations in the process of TCM clinical practice from the aspects of continuously exploring clinical value， improving the construction of information system， focusing on the TCM clinical practice and giving full play to the advantages of discipline cooperation. By realizing the whole life cycle management of medical institution preparations based on three-combination evaluation evidence system， we can promote the transformation of medical institution preparations into innovative Chinese medicines.