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Schizophrenia is a severe psychological disorder. The current diagnosis mainly relies on clinical symptoms and lacks laboratory evidence, which makes it very difficult to make an accurate diagnosis especially at an early stage. Plasma protein profiles of schizophrenia patients were obtained and compared with healthy controls using 4D-DIA proteomics technology. Furthermore, 79 DEPs were identified between schizophrenia and healthy controls. GO functional analysis indicated that DEPs were predominantly associated with responses to toxic substances and platelet aggregation, suggesting the presence of metabolic and immune dysregulation in patients with schizophrenia. KEGG pathway enrichment analysis revealed that DEPs were primarily enriched in the chemokine signaling pathway and cytokine receptor interactions. A diagnostic model was ultimately established, comprising three proteins, namely, PFN1, GAPDH and ACTBL2. This model demonstrated an AUC value of 0.972, indicating its effectiveness in accurately identifying schizophrenia. PFN1, GAPDH and ACTBL2 exhibit potential as biomarkers for the early detection of schizophrenia. The findings of our studies provide novel insights into the laboratory-based diagnosis of schizophrenia.
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Biomarcadores , Profilinas , Proteómica , Esquizofrenia , Esquizofrenia/metabolismo , Esquizofrenia/diagnóstico , Esquizofrenia/sangre , Humanos , Biomarcadores/sangre , Biomarcadores/metabolismo , Proteómica/métodos , Profilinas/metabolismo , Femenino , Masculino , Adulto , Estudios de Casos y Controles , Gliceraldehído-3-Fosfato Deshidrogenasa (Fosforilante)/metabolismo , Persona de Mediana Edad , Proteínas Sanguíneas/análisis , Proteoma/análisisRESUMEN
BACKGROUND: Early systemic anticoagulation (SAC) is a common practice in acute necrotizing pancreatitis (ANP), and its impact on in-hospital clinical outcomes had been assessed. However, whether it affects long-term outcomes is unknown. This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients. METHODS: During January 2013 and December 2018, ANP patients admitted within 7 days from the onset of abdominal pain were screened. The primary outcome was 90-day readmission after discharge. Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission. RESULTS: A total of 241 ANP patients were enrolled, of whom 143 received early SAC during their hospitalization and 98 did not. Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis (SVT) [risk ratio (RR) = 0.40, 95% CI: 0.26-0.60, P < 0.01] and lower 90-day readmission with an RR of 0.61 (95% CI: 0.41-0.91, P = 0.02) than those who did not. For the quality of life, patients who received early SAC had a significantly higher score in the subscale of vitality (P = 0.03) while the other subscales were all comparable between the two groups. Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57 (95% CI: 0.34-0.96, P = 0.04). Mediation analysis showed that SVT mediated 37.0% of the early SAC-90-day readmission causality. CONCLUSIONS: The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients, and reduced SVT incidence might be the primary contributor.
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Pancreatitis Aguda Necrotizante , Trombosis de la Vena , Humanos , Readmisión del Paciente , Estudios Retrospectivos , Pancreatitis Aguda Necrotizante/diagnóstico , Pancreatitis Aguda Necrotizante/tratamiento farmacológico , Calidad de Vida , Factores de Riesgo , Trombosis de la Vena/tratamiento farmacológico , Anticoagulantes/efectos adversosRESUMEN
OBJECTIVE: Functional dyspepsia (FD), which has a complicated pathophysiologic process, is a common functional gastrointestinal disease. Gastric hypersensitivity is the key pathophysiological factor in patients with FD with chronic visceral pain. Auricular vagal nerve stimulation (AVNS) has the therapeutic effect of reducing gastric hypersensitivity by regulating the activity of the vagus nerve. However, the potential molecular mechanism is still unclear. Therefore, we investigated the effects of AVNS on the brain-gut axis through the central nerve growth factor (NGF)/ tropomyosin receptor kinase A (TrkA)/phospholipase C-gamma (PLC-γ) signaling pathway in FD model rats with gastric hypersensitivity. MATERIALS AND METHODS: We established the FD model rats with gastric hypersensitivity by means of colon administration of trinitrobenzenesulfonic acid on ten-day-old rat pups, whereas the control rats were given normal saline. AVNS, sham AVNS, K252a (an inhibitor of TrkA, intraperitoneally), and K252a + AVNS were performed on eight-week-old model rats for five consecutive days. The therapeutic effect of AVNS on gastric hypersensitivity was determined by the measurement of abdominal withdrawal reflex response to gastric distention. NGF in gastric fundus and NGF, TrkA, PLC-γ, and transient receptor potential vanilloid 1 (TRPV1) in the nucleus tractus solitaries (NTS) were detected separately by polymerase chain reaction, Western blot, and immunofluorescence tests. RESULTS: It was found that a high level of NGF in gastric fundus and an upregulation of the NGF/TrkA/PLC-γ signaling pathway in NTS were manifested in model rats. Meanwhile, both AVNS treatment and the administration of K252a not only decreased NGF messenger ribonucleic acid (mRNA) and protein expressions in gastric fundus but also reduced the mRNA expressions of NGF, TrkA, PLC-γ, and TRPV1 and inhibited the protein levels and hyperactive phosphorylation of TrkA/PLC-γ in NTS. In addition, the expressions of NGF and TrkA proteins in NTS were decreased significantly after the immunofluorescence assay. The K252a + AVNS treatment exerted a more sensitive effect on regulating the molecular expressions of the signal pathway than did the K252a treatment. CONCLUSION: AVNS can regulate the brain-gut axis effectively through the central NGF/TrkA/PLC-γ signaling pathway in the NTS, which suggests a potential molecular mechanism of AVNS in ameliorating visceral hypersensitivity in FD model rats.
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Dispepsia , Estimulación del Nervio Vago , Animales , Ratas , Dispepsia/terapia , Factor de Crecimiento Nervioso/metabolismo , Fosfolipasa C gamma/metabolismo , Receptor trkA/genética , Receptor trkA/metabolismo , ARN Mensajero , Transducción de Señal , Tropomiosina/metabolismoRESUMEN
AIM: To compare the differences in the efficacy and safety of combination of intravitreal dexamethasone(Ozurdex)and ranibizumab or monotherapy of ranibizumab in eyes with macular edema secondary to retinal vein occlusion(RVO-ME).METHODS: Patients diagnosed with non-ischemic RVO-ME by fluorescein fundus angiography in our hospital from June 2020 to December 2022 were selected. All patients were initially treated with intravitreal injection of ranibizumab(0.5 mg), and 42 patients(42 eyes)who had central retinal thickness(CRT)≥300 μm after 2 wk were included. They were randomly divided into combined treatment group and monotherapy group. The combined treatment group(21 eyes)received Ozurdex intravitreal injection immediately, while the monotherapy group(21 eyes)was treated with ranibizumab intravitreal injection by 3+pro re nata(PRN). The changes of best corrected visual acuity(BCVA), CRT, and intraocular pressure before and at 2 wk, 1, 2, 3, 4, 5, and 6 mo after treatment were recorded, and the ocular or systemic complications were observed.RESULTS:The BCVA and CRT of all patients at 2 wk, 1, 2, 3, 4, 5, and 6 mo after treatment were significantly better than those before treatment(all P&#x003C;0.01). There were statistical significance in the BCVA and CRT between two groups at 2 and 3 mo after treatment(all P&#x003C;0.05). The most significant increase of BCVA in the combined treatment group occurred at 2 mo after treatment. The mean recurrence time of macular edema in the monotherapy group was 1.45±0.53 mo, with 4.21±0.78 injection times of ranibizumab. None of the patients showed serious complications after treatment. The most common complications in the combined treatment group were subconjunctival hemorrhage and elevated intraocular pressure, which were manageable with topical ocular hypotensive agents, and no patient required antiglaucoma or cataract surgery.CONCLUSION: Compared with monotherapy of ranibizumab, intravitreal injection of dexamethasone combined with ranibizumab can significantly improve the visual acuity and effectively reduce the macular edema in the treatment of RVO-ME, with a long duration of efficacy and less intravitreal injection of drugs.
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Objective:To compare the distribution differences of serum protein electrophoresis (SPE) among different gender and age individuals, and to explore the clinical application of SPE screening monoclonal gammopathy.Methods:A retrospective analysis was conducted based on the SPE results obtained from 533 989 cases enrolled from January 2018 to December 2019 at Zhongshan Hospital Affiliated to Fudan University. Among these patients, 435 479 inpatients were from departments of hematology, nephrology, spinal surgery, endocrinology, and rheumatology and immunology; and 98 510 were apparently healthy individuals. The distributions of albumin, α1 globulin, α2 globulin, β1 globulin, β2 globulin and γ globulin in different gender and age groups (≤20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90, ≥91 years old) were compared. A total of 10 014 cases were selected by immunofixation electrophoresis (IFE). The positive detection rates of different SPE bands and IFE bands were analyzed. The sensitivity and specificity of SPE methods were determined according to IFE results as the gold standard.Results:No significant difference was examined in the proportion of SPE bands between different genders ( P>0.05). There were statistically significant differences in the proportion of albumin bands between apparently healthy individuals and hospitalized patients at different ages (apparently healthy individuals: F=5.12, P<0.05, inpatients: F=4.18, P<0.05), and all of them decreased with the increase of age. The proportion of γ globulin bands increased with age (apparently healthy individuals: F=1.34, P<0.05; inpatients: F=1.24, P<0.05). The sensitivity of SPE was 69% (2 098/3 051), and the specificity was 97% (6 721/6 963). Compared with IFE method, the positive detection rate of monoclonal gammopathy was significantly different (χ2=5 049.94, P<0.05). The positive rate of monoclonal gammopathy in γ globulin region (21.11%, 2 114/10 014) was higher than that in β globulin region (3.28%, 328/10 014) (χ2=90.74, P<0.05) and β-γ globulin region (1.63%, 163/10 014) (χ2=44.34, P<0.05). IgG and IgM bands are common in γ globulin region. Among them, IgG-κ type accounted for 94.1% (995/1 058), IgG-λ type accounted for 94.8% (690/728), IgM-κ type accounted for 89.2% (222/249), IgM-λ accounted for 83.8% (62/74). IgA bands are common in β region, of which IgA-κ accounted for 49.8% (103/207) and IgA-λ accounted for 51.6% (149/289). The positive rate of monoclonal gammopathy of IgG-κ type was the highest (10.57%, 1 058/10 014), and the positive rate of monoclonal gammopathy of IgM-λ type was the lowest (0.74%, 74/10 014). Conclusions:With increasing age, the proportion of albumin band in SPE decreased and the proportion of γ globulin band increased. IgG and IgM type monoclonal gammopathy is mostly found in the gamma region, with a higher detection rate in IgG type. IgA type monoclonal gammopathy is mostly found in the β region, with a lower detection rate.
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Objective:To investigate the characteristics and distribution of monoclonal gammopathy in clinical patients.Methods:A total of 936 171 patients (508 449 males and 427 722 females) who received capillary zone electrophoresis in Zhongshan Hospital Affiliated to Fudan University from January 2012 to December 2021 were selected, from which 14 945 patients with abnormal bands were screened as the study subjects, including 10 173 males and 4 772 females and the age 21-102 (65±13) years old. According to the age, patients were divided into 8 groups: 21-30 years old (168 cases), 31-40 years old (405 cases), 41-50 years old (1 326 cases), 51-60 years old (3 068 cases), 61-70 years old (4 985 cases), 71-80 years old (3 288 cases), 81-90 years old (1 519 cases), and≥91 years old (186 cases). The diagnostic results of the 14 945 patients with abnormal bands were collected and were divided into tumor group (5 196 cases) and non-tumor disease group (9 749 cases) according to the presence of tumor. The distribution of abnormal bands in different gender, age, and disease groups were retrospectively analyzed. Among the 14 945 patients, 4 988 cases underwent immunofixation electrophoresis, excluding 336 negative cases and 412 cases of double clonal bands reaction, and 4 240 patients with monoclonal immunoglobulin (M protein) reaction were selected as the study subjects, including 2 794 males and 1 446 females aged 21-102 (67±12) years old. They were divided into 8 groups according to the age: 21-30 years old (18 cases), 31-40 years old (91 cases), 41-50 years old (364 cases), 51-60 years old (862 cases), 61-70 years old (1 455 cases), 71-80 years old (904 cases), 81-90 years old (486 cases), and≥91 years old (60 cases). The diagnostic results and immunoglobin subtypes (IgA-κ, IgA-λ, IgG-κ, IgG-λ, IgM-κ, IgM-λ, κ, λ) of patients were collected, and the distribution of monoclonal gammopathy in different gender, age and disease groups were retrospectively analyzed.Results:Among 936 171 patients, 14 945 cases showed abnormal bands in electropherograms with a detection rate of 1.60%; the detection rates of abnormal bands in males and females were 2.00% (10 173/508 449) and 1.12% (4 772/427 722), respectively, with a statistically significant difference ( P<0.01). There was a significant difference in the detection rate of abnormal bands among different age groups ( P<0.01); among them, the highest detection rate of abnormal band in group of ≥91 years old was 5.98%, and the ratio of male to female was 1.67∶1. Among the 14 945 cases of abnormal bands, patients aged 51-60, 61-70 and 71-80 accounted for 20.53% (3 068 cases), 33.36% (4 985 cases) and 22.00% (3 288 cases), respectively, and the differences among the age groups were statistically significant (χ 2=115.82, P<0.01). In the tumor group, the top 3 tumors with abnormal bands were plasmacytoma with 1 123 cases, lymphoma with 289 cases, and leukemia with 49 cases. The detection rate of abnormal bands in electropherograms of plasmacytoma was 89.92% (1 123/1 249), which was higher than that in lymphoma and leukemia [6.73% (289/4 296) and 6.40% (49/766), respectively, P<0.01]. Among 4 240 patients with positive M protein, the proportion of 51-60, 61-70 and 71-80 years old patients were 20.33% (862/4 240), 34.32% (1 455/4 240) and 21.32% (904/4 240), respectively, and the differences among age groups were statistically significant ( P<0.01). The results of M protein types showed that the proportion of IgG-κ type was the highest in both genders, with 32.28% (902/2 794) in males and 34.30% (496/1 446) in females. In the 21-30, 31-40, and 41-50 age groups, the proportion of IgG-λ was the highest, which were 38.89% (7/18), 36.26% (33/91) and 34.07% (124/364) in these groups respectively. However, the proportions of IgG-κ were the highest in either of the 51-60, 61-70, 71-80, 81-90 and ≥91 years old groups, which were 33.87% (292/862), 34.16% (497/1 455), 31.53% (285/904), 34.57% (168/486), 28.33% (17/60), respectively, and the differences among all age groups and gender groups had statistical significance ( P<0.01). Among patients with positive M protein in the tumor group, plasmacytoma accounted for 14.22% (603/4 240), followed by lymphoma 6.30% (267/4 240); among non-tumor diseases, M proteinemia accounted for the highest proportion (7.24%, 307/4 240), followed by pulmonary infection (5.47%, 232/4 240). Conclusions:The detection rate of abnormal bands in capillary zone electrophoresis may increase with age, and is higher in males than in females in the same age group; different malignant tumor diseases can also show abnormal bands in capillary zone electrophoresis, but they are still mainly hematological tumors. Among the positive results of M protein, 61-70 years old group accounts for the highest proportion; the most common type of monoclonal gammopathy is IgG type; in the age group of 21-50 years, the proportion of IgG-λ type is the highest; in the group of >50 years old, the proportion of IgG-κ type is the highest; in the diagnosis of positive monoclonal gammopathy, the top 3 diseases are all hematological diseases, including plasmacytoma, monoclonal gammopathies and lymphoma.
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Objective To explore the value of droplet digital polymerase chain reaction(ddPCR)in the etiological diagnosis of severe acute pancreatitis(SAP)patients with suspected bloodstream infection(BSI).Methods SAP patients admitted to the department of critical care medicine in a hospital July to September 2022 were enrolled.When BSI was suspected,venous blood was collected for both ddPCR detection and blood culture(BC)with antimi-crobial susceptibility testing(AST)simultaneously.The time required for two detection methods was recorded,and the detection results of ddPCR and BC were compared.The etiological diagnostic efficacy of ddPCR was calculated,and the correlation between the value of pathogen load detected by ddPCR and the level of infection parameters was explored.Results A total of 22 patients were included in the analysis,and 52 venous blood specimens were collec-ted for detection.BC revealed 17 positive specimens(32.7%)and 29 pathogenic strains,while ddPCR showed 41 positive specimens(78.8%)and 73 pathogenic strains.Detection time required for ddPCR was significantly lower than that of BC([0.16±0.03]days vs[5.92±1.20]days,P<0.001).Within the detection range of ddPCR and taking BC results as the gold standard,the sensitivity and specificity of ddPCR were 80.0%and 28.6%,respective-ly.With the combined assessment of BSI based on non-blood specimen microbial evidence within a week,the sensi-tivity and specificity of ddPCR detection increased to 91.9%and 76.9%,respectively.ddPCR detected resistance genes of blaKPC,blaNDM/IMP,VanA/VanM,and mecA from 19,9,6,and 5 specimens,respectively.Correlation analysis showed a positive correlation between pathogen load and levels of C-reactive protein as well as procalcitonin(r=0.347,0.414,P<0.05).Conclusion As a supplementary detection method for BC in BSI diagnosis,ddPCR has the advantages of higher sensitivity and shorter detection time,and is worthy of further exploration in clinical application.
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Objective:To investigate the value of three-dimensional reconstruction combined with serum carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) detection in the diagnosis and resectability evaluation of hilar cholangiocarcinoma (HCCA) before resectable lymph node metastasis.Methods:A total of 65 patients with suspected HCCA who were treated at Yiwu Central Hospital from June 2019 to June 2022 were included in the observation group. Thirty healthy people who concurrently underwent physical examinations in the same hospital were included in the control group. All participants underwent a CT three-dimensional reconstruction examination. Simultaneously, the automatic electrochemiluminescence immunoassay analyzer was used to measure serum levels of CA19-9 and CEA. The outcomes of percutaneous transhepatic cholangiography were used as the "gold standard". The consistency between CT three-dimensional reconstruction, CA19-9 detection, and CEA detection, either individually or combined, and the "gold standard" in the diagnosis of HCCA was evaluated.Results:Serum levels of CA19-9 and CEA in the observation group were (62.71 ± 10.63) U/mL and (62.71 ± 10.63) ng/mL, respectively, which were significantly higher than those in the control group [(12.37 ± 7.39) U/mL, (1.31 ± 0.97) ng/mL, t = 23.43, 11.59, both P < 0.05). The levels of CA19-9 [(71.69 ± 12.37) U/mL] and CEA [(8.89 ± 3.51) ng/mL] in patients with HCCA who had lymph node metastasis were significantly higher than those in patients with HCCA who had no lymph node metastasis [CA19-9 (56.78 ± 10.16) U/mL, CEA (6.45 ± 2.11) ng/mL, t = 4.14, 2.76, both P < 0.05].Compared with histopathological examination, the accuracy of CT three-dimensional reconstruction in typing was 85.00%. According to the "gold standard" diagnosis, CT three-dimensional reconstruction, CA19-9 detection, and CEA detection, alone and their combination, successfully detected HCCA in 22 cases (55.00%), 26 cases (65.00%), 31 cases (77.50%), and 38 cases (95.00%), respectively. The detection rate of HCCA was the highest when CT three-dimensional reconstruction, CA19-9 detection, and CEA detection were combined, and the difference was statistically significant ( χ2 = 18.15, P < 0.05). Compared with CT three-dimensional reconstruction (AUC: 0.808), CA19-9 detection (AUC: 0.721), and CEA detection (AUC: 0.703) individually, their combination (AUC: 0.913) had the highest value in the diagnosis of HCCA (all P < 0.05). Conclusion:CT three-dimensional reconstruction, CA19-9 detection, and CEA detection have a certain diagnostic value for HCCA, but the combination of CT three-dimensional reconstruction with the detection of serum levels of CA19-9 and CEA has a higher diagnostic value for HCCA, providing an effective reference for the preoperative evaluation of the resectability of HCCA in the clinic.
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ObjectiveTranscription factor NFE2 was observed abnormal expression in myeloproliferative neoplasm (MPN) patients. However, how NFE2 is transcriptionally regulated remains ambiguous. This study aims to explore the elements and molecular mechanisms involved in the transcriptional regulation of NFE2. MethodsActive enhancers were predicted by public NGS data and conformed experimentally via dual luciferase reporter assay. After that, PRO-seq and GRO-seq data was used to detect enhancer RNAs transcribed from these enhancers. RACE was utilized to clone the full length enhancer RNA (eRNA) transcripts, and RT-qPCR was used to measure their expression in different leukemia cell lines as well as the transcript levels during induced differentiation. Finally, to investigate the molecular function of the eRNA, overexpression and knockdown of the eRNA via lentivirus system was performed in K562 cells. ResultsWe identified three enhancers regulating NFE2 transcription, which located at -3.6k, -6.2k and +6.3k from NFE2 transcription start site (TSS) respectively. At the -3.6k enhancer, we cloned an eRNA transcript and characterized that as a lncRNA which was expressed and located in the nucleus in three types of leukemia cell lines. When this lncRNA was overexpressed, expression of NFE2 was upregulated and decreases of K562 cell proliferation and migration ability were observed. While knocking down of this lncRNA, the level of NFE2 decreases correspondingly and the proliferation ability of K562 cells increases accordingly. ConclusionWe identified an enhancer lncRNA that regulates NFE2 transcription positively and suppresses K562 cell proliferation.
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ObjectiveTo investigate the prevalence and influencing factors of overweight, obesity and central obesity among elderly residents in Xuhui District, and to analyze the epidemiological status of central obesity in elderly people with different body mass indexes. MethodsThe third round of health status and health service utilization monitoring data in Xuhui District was used. The information collected from questionnaire survey and physical examination were analyzed. SPSS 20.0 software was used for χ2 test, trend χ2 test and multinominal logistic regression analysis. Results5 096 survey subjects were included. The prevalence of overweight, general obesity, and central obesity in the residents aged 60 and above in Xuhui District were 34.3%, 6.5%, and 29.2%, respectively. There was gender difference in the rates of overweight, obesity, and central obesity among the residents. The overweight and central obesity rates in males were higher than those in females, while the obesity rate was lower than that in females (P<0.05). Multinominal logistic regression analysis showed that in comparison with the normal weight non-central obesity group drinking only at party (OR=1.729, 95%CI: 1.184‒2.525), and hypertension (OR=1.637, 95%CI: 1.305‒2.053), were highly associated with normal weight with central obesity. Aged 60‒ years (OR=1.589, 95%CI: 1.190‒2.120), aged 70‒ years (OR=1.763, 95%CI: 1.327‒2.342), male (OR=1.379, 95%CI: 1.134‒1.676), hypertension (OR=2.231, 95%CI: 1.878‒2.649), former smokers (OR=1.437, 95%CI: 1.027‒2.011), drinking at party only (OR=1.491, 95%CI: 1.107‒2.006), and drinking ≥3 times per week (OR=1.611, 95%CI: 1.116‒2.325), were highly associated with overweight combined with central obesity. Aged 60‒ years (OR=3.817, 95%CI: 2.251‒6.474), aged 70‒ years (OR=3.084, 95%CI: 1.838‒5.175), hypertension (OR=3.683, 95%CI: 2.753‒4.929), diabetes (OR=2.085, 95%CI: 1.511‒2.878), former smokers (OR=1.835, 95%CI: 1.043‒3.226), were highly associated with compound obesity. Central obesity was found in the elderly residents with different BMI categories, and the rate of central obesity increased with the increase of BMI grade. ConclusionThe prevalence of overweight, obesity and central obesity among the elderly aged 60 years and above in Xuhui District is not optimistic. Attention should be paid to the elderly under 80 years old who are with hypertension and/or diabetes, alcohol consumption, low educational level and not doing physical exercise. Especially for the central obesity population with normal BMI, measures should be taken to prevent and intervene the occurrence of obesity and related diseases.
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BACKGROUND: Ventricular septal defect (VSD) is the most common subtype of congenital heart disease. In the present study, we aimed to determine whether chromosome aberration was associated with the occurrence of VSD and evaluate the association of VSD size, location and chromosome aberration with adverse outcomes in the Chinese fetuses. METHODS: Fetuses with VSD and comprehensive follow-up data were included and evaluated retrospectively. Medical records were used to collect epidemiological data and foetal outcomes. For VSD fetuses, conventional karyotype and microarray analysis were conducted. After adjusting confounding factors by using multivariable logistic regression analyses, the association between chromosome variations and VSD occurrence was explored. The association between defect size, location and chromosome aberrations and adverse foetal outcomes was also investigated. RESULTS: Chromosome aberration was the risk factor for VSD occurrence, raising 6.5-fold chance of developing VSD. Chromosome aberration, peri-membranous site and large defect size of VSD were significant risk factors of adverse fetal outcome. Chromosome aberrations, including pathogenic copy number variations (CNVs) and variations of uncertain significance (VUS), were both risk factors, increasing the risk of the adverse fetal outcome by 55.9 times and 6.7 times, respectively. The peri-membranous site would increase 5.3-fold risk and defects larger than 5 mm would increase the 7.1-fold risk for poor fetal outcome. CONCLUSIONS: The current investigation revealed that chromosomal abnormalities, large defects, and the peri-membranous site were all risk factors for poor fetal outcomes. Our study also indicated that chromosome aberration was one of risk factors for the VSD occurrence.
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Variaciones en el Número de Copia de ADN , Defectos del Tabique Interventricular , Humanos , Estudios Retrospectivos , Factores de Riesgo , Feto , Defectos del Tabique Interventricular/epidemiología , Defectos del Tabique Interventricular/genética , Pronóstico , Aberraciones Cromosómicas , Análisis FactorialRESUMEN
AIMS: Diabetic cardiomyopathy (DC) is one of serious complications of diabetic patients. This study investigated the biological function of activating transcription factor 4 (ATF4) in DC. METHODS AND RESULTS: Streptozotocin-treated mice and high glucose (HG)-exposed HL-1 cells were used as the in vivo and in vitro models of DC. Myocardial infarction (MI) was induced by left coronary artery ligation in mice. Cardiac functional parameters were detected by echocardiography. Target molecule expression was determined by real time quantitative PCR and western blotting. Cardiac fibrosis was observed by haematoxylin and eosin and Masson's staining. Cardiac apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labelling. Activities of superoxide dismutase, glutathione peroxidase, and levels of malonic dialdehyde and reactive oxygen species were used to assess oxidative stress damage. Molecular mechanisms were evaluated by chromatin immunoprecipitation, dual luciferase assay, and co-immunoprecipitation. ATF4 was up-regulated in the DC and MI mice (P < 0.01). Down-regulation of ATF4 improved cardiac function as evidenced by changes in cardiac functional parameters (P < 0.01), inhibited myocardial collagen I (P < 0.001) and collagen III (P < 0.001) expression, apoptosis (P < 0.001), and oxidative stress (P < 0.001) in diabetic mice. Collagen I (P < 0.01) and collagen III (P < 0.01) expression was increased in MI mice, which was reversed by ATF4 silencing (P < 0.05). ATF4 depletion enhanced viability (P < 0.01), repressed apoptosis (P < 0.001), oxidative damage (P < 0.001), and collagen I (P < 0.001), and collagen III (P < 0.001) expression of HG-stimulated HL-1 cells. ATF4 transcriptionally activated Smad ubiquitin regulatory factor 2 (Smurf2, P < 0.001) to promote ubiquitination and degradation of homeodomain interacting protein kinase-2 (P < 0.001) and subsequently caused inactivation of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 pathway (P < 0.001). The inhibitory effects of ATF4 silencing on HG-induced apoptosis (P < 0.01), oxidative injury (P < 0.01), collagen I (P < 0.001), and collagen III (P < 0.001) expression were reversed by Smurf2 overexpression. CONCLUSIONS: ATF4 facilitates diabetic cardiac fibrosis and oxidative stress by promoting Smurf2-mediated ubiquitination and degradation of homeodomain interacting protein kinase-2 and then inactivation of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 pathway, suggesting ATF4 as a treatment target for DC.
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Diabetes Mellitus Experimental , Cardiomiopatías Diabéticas , Infarto del Miocardio , Animales , Ratones , Factor de Transcripción Activador 4/genética , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Cardiomiopatías Diabéticas/genética , Cardiomiopatías Diabéticas/metabolismo , Fibrosis , Hemo-Oxigenasa 1 , Proteínas QuinasasRESUMEN
Objective To investigate the treatment outcomes,prognosis,and risk factors of treatment failure of peritoneal dialysis associated peritonitis (PDAP) caused by Klebsiella pneumoniae,and thus provide clinical evidence for the prevention and treatment of this disease. Methods The clinical data of PDAP patients at four peritoneal dialysis centers from January 1,2014 to December 31,2019 were collected retrospectively.The treatment outcomes and prognosis were compared between the patients with PDAP caused by Klebsiella.pneumoniae and that caused by Escherichia coli.Kaplan-Meier method was employed to establish the survival curve of technical failure,and multivariate Logistic regression to analyze the risk factors of the treatment failure of PADP caused by Klebsiella pneumoniae. Results In the 4 peritoneal dialysis centers,1034 cases of PDAP occurred in 586 patients from 2014 to 2019,including 21 cases caused by Klebsiella pneumoniae and 98 cases caused by Escherichia coli.The incidence of Klebsiella pneumoniae caused PDAP was 0.0048 times per patient per year on average,ranging from 0.0024 to 0.0124 times per patient per year during 2014-2019.According to the Kaplan-Meier survival curve,the technical failure rate of Klebsiella pneumoniae caused PDAP was higher than that of Escherichia coli caused PDAP (P=0.022).The multivariate Logistic regression model showed that long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP (OR=1.082,95%CI=1.011-1.158,P=0.023).Klebsiella pneumoniae was highly sensitive to amikacin,meropenem,imipenem,piperacillin,and cefotetan,and it was highly resistant to ampicillin (81.82%),cefazolin (53.33%),tetracycline (50.00%),cefotaxime (43.75%),and chloramphenicol (42.86%). Conclusion The PDAP caused by Klebsiella pneumoniae had worse prognosis than that caused by Escherichia coli,and long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP.
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Diálisis Peritoneal , Peritonitis , Humanos , Klebsiella pneumoniae , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Diálisis Peritoneal/efectos adversos , Peritonitis/tratamiento farmacológico , Factores de Riesgo , Insuficiencia del Tratamiento , Escherichia coliRESUMEN
Objective To investigate the therapeutic effect of oral administration of deuterium depleted water on gastroenteritis induced by 131I radiation in thyroid cancer treatment. Methods Fifty patients with papillary thyroid cancer treated with 131I in the Department of Nuclear Medicine of Changshu No.2 People’s Hospital from May 2022 to February 2023 were divided into control group and experimental group (25 patients in each group). Data were continuously collected throughout the study duration. The control group was orally administrated omeprazole enteric-coated capsules and purified water at 660 mL tid for 5 days. The experimental group received the same basic treatment as the control group except that deuterium depleted water was used instead of purified water. The incidence and alleviation of 131I radiation-induced gastroenteritis were observed and compared between the two groups using the Fisher’s exact test and Kaplan-Meier analysis. Results The number of gastroenteritis cases from day 1 to day 5 after 131I administration was 2 (8%), 5 (20%), 2 (8%), 1 (4%), and 0 (0%), respectively, in the experimental group, and 2 (8%), 8 (32%), 4 (16%), 3 (12%), and 1 (4%), respectively, in the control group. The incidence of gastroenteritis was significantly different between the two groups (χ2=4.064, P=0.044). After 5 days of treatment, the overall response rate of patients in the experimental group was 96%, which was significantly higher than 76% in the control group (χ2=9.105, P=0.025). Conclusion Oral administration of deuterium depleted water is effective in the relief of clinical symptoms of 131I radiation-induced gastroenteritis in thyroid cancer treatment. The clinical application of deuterium depleted water should be further investigated.
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Objective:To compare the detection performance of serum free light chain (sFLC) in two platforms and evaluate the comparability of serum free light chain results in patients with multiple myeloma (MM).Methods:To evaluate the detection performance (repeatability, accuracy, linear range, reference range, interfering substances, etc.) of sFLC kit based on polyclonal antibodies. Spearman correlation analysis and Bland-Altman were used to analyze 214 sFLC results obtained on two detection platforms at the same time to evaluate the correlation between the results of the two methods and analyze the causes of methodological bias. 119 cases with aMM and 23 cases of disease control group (AL, WM, POEMS syndrome, MGUS, diffuse large B-cell lymphoma) initially diagnosed in the hematology department of Zhongshan Hospital of Fudan University from March 2020 to March 2021 were all included. A retrospective analysis was conducted to calculate the area under the curve of receiver operating characteristic (AUC-ROC) and obtain the optimal sensitivity and specificity cut-off points for the diagnosis of MM patients on monoclonal antibody platform.Results:Repeatability, accuracy, linear range, reference interval and anti-interfering capacity of the detection platform based on polyclonal antibodies were verified to meet clinical needs. The overall consistency of FLC/κ, FLC/λ and κ/λ ratios in two methods was 89.3%, 84.1% and 77.1% respectively; but the correlation results were highly heterogeneous. The correlation coefficient of FLC/κ R 2 was 0.922( P<0.001), while the correlation coefficients R 2of the FLC/λ and κ/λ ratios were only 0.349 and 0.441( P<0.001). After segment analysis, it was found that the correlation of FLC/λ was improved within the linear range and R 2 could rise to 0.78( P<0.001). Compared with monoclonal antibody platform, the vast majority points of FLC/κ fell within the 95% limit by Bland Altman analysis. While the results of FLC/λ on polyclonal antibody platform showed significant positive bias. The AUC of MM diagnosis on monoclonal antibody platform was 0.751 ( P=0.001), and the optimal cutoff value was 24.67. Conclusion:The overall consistency between the two platforms was good, but there were significant differences between the results, so they were not comparable and could not be interchanged. For monitoring the prognosis of patients with multiple myeloma, the same platform should be selected for testing.
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Objective:To explore the value of traditional Chinese medicine combined with 131I in the treatment of Graves hyperthyroidism. Methods:From March 2020 to July 2021, 90 patients (39 males, 51 females, age (33.2±7.0) years) with Graves hyperthyroidism who were diagnosed and treated in Changshu No.2 People′s Hospital were retrospectively analyzed. Patients were randomly divided into 3 groups ( n=30 in each group), including group A who received treatment of antithyroid drugs (ATD), group B who received treatment of traditional Chinese medicine, and group C who received treatment of 131I combined with traditional Chinese medicine. Thyroid function indicators and inflammatory indicators before treatment and 1, 3, and 6 months after treatment were determined, including free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid stimulating hormone (TSH) and TSH receptor antibody (TRAb), and C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). One-way analysis of variance and χ2 test were used to analyze data. Results:The levels of FT 3, FT 4, TSH, TRAb, CRP, IL-6 and TNF-α in group A, B and C before treatment and 1, 3, 6 months after treatment were significantly different ( F values: 193.27-906.11, all P<0.05). The total effective rate in group C (100.0%, 30/30) was significantly higher than that in group A (86.7%, 26/30) or group B (83.3%, 25/30; χ2 values: 8.24, 9.83, P values: 0.006, 0.037), while there was no significant difference between group A and group B ( χ2=3.02, P=0.124). The incidence of adverse reactions in group B (46.7%, 14/30) was significantly higher than that in group A (30.0%, 9/30; χ2=6.59, P=0.042). And the incidence of adverse reaction in group C (13.3%, 4/30) was significantly lower than that in group A or group B ( χ2 values: 12.05, 7.20, P values: 0.004, 0.038). Conclusion:The curative effect of 131I combined with traditional Chinese medicine is effective and reliable, suggesting that clinical researches should be carried out together and perfected.
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Objective:To systematically evaluate the effect of on-the-job training of primary health workers in Pukou District, Nanjing City by using the Kirkpatrick's four-level model of evaluation, and to provide a basis for the design of on-the-job training programs for primary health workers.Methods:A questionnaire was conducted to investigate the basic information, training status, and training effects of the staff in all primary medical and health service institutions in Pukou District. A total of 428 valid questionnaires were collected. SPSS 16.0 software was used for statistical analysis, binary or ordinal Logistic regression was used to screen related factors.Results:In the response evaluation, 49.6% (192/387) of trainees thought that it was meaningful to participate in the training; in the learning evaluation, 51.4% (220/428) understood the frontier knowledge of their profession; in the behavior evaluation, 40.3% (156/387) had widely used the content of the training; in the result evaluation, 41.3% (177/428) said that the quality of their work was very high. Comprehensively, training frequency, training duration, professional category and professional title were the influencing factors of training effect.Conclusion:Overall, the training effect of primary health workers is not satisfactory. In a word, increasing the frequency of training, enhancing health personnel's awareness of the importance of training, and extending the duration of training can effectively improve the training effect.
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Frontal fibrosing alopecia is a primary lymphocytic cicatricial alopecia, and is generally considered to be a subtype of lichen planopilaris due to similar histopathological changes. Its etiology is still unclear. With the deepening of research on this disease, more and more cases of frontal fibrosing alopecia have been reported in China and other countries. This review summarizes research progress in pathogenesis, clinical and pathological characteristics, and treatment of frontal fibrosing alopecia.
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Alkaloids are important active ingredients occurring in many traditional Chinese medicines, and alkaloid glycosides are one of their existence forms. The introduction of saccharide units improves the water solubility of alkaloid glycosides thus presenting better biological activity.Because of the low content in plants, alkaloid glycosides have been not comprehensively studied. In this study, ultrahigh performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry(UPLC-QTOF-MS/MS) was employed to identify and analyze the alkaloid glycosides in Coptis chinensis, Phellodendron chinense, Menispermum dauricum, Sinomenium acutum, Tinospora sagittata and Stephania tetrandra. The results showed that except Tinospora sagittata, the other five herbal medicines contained alkaloid glycosides. Furthermore, the alkaloid glycosides in each herbal medicine were identified based on UV absorption spectra, quasimolecular ion peaks in MS, fragment ions information in the MS/MS, and previous literature reports. A total of 42 alkaloid glycosides were identified. More alkaloid glycosides were identified in C. chinensis and Menispermum dauricum, and eleven in C. chinensis were potential new compounds. Furthermore, the alkaloid glycosides in the water extract of C. chinensis were coarsely se-parated by macroporous adsorption resin, purified by column chromatography with D151 cation exchange resin, ODS and MCI, combined with semi-preparative high performance liquid chromatography. Two new alkaloid glycosides were obtained, and their structures were identified by mass spectrometry and NMR data as(S)-7-hydroxy-1-(p-hydroxybenzyl)-2,2-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-6-O-β-D-glucopyranoside and(S)-N-methyltetrahydropalmatubine-9-O-β-D-glucopyranoside, respectively. This study is of great significance for enriching the information about the chemical composition and the in-depth development of C. chinensis. Meanwhile, it can provide a reference for rapid identification and isolation of alkaloid glycosides from other Chinese herbal medicines.
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Glicósidos/química , Medicina Tradicional China , Espectrometría de Masas en Tándem/métodos , Coptis chinensis , Medicamentos Herbarios Chinos/química , Alcaloides/análisis , Extractos Vegetales/química , Antineoplásicos , Plantas Medicinales/química , Agua , Cromatografía Líquida de Alta Presión/métodos , Coptis/químicaRESUMEN
The aim of this study is to investigate the effects of Gynostemma pentaphyllum dried with two different methods(air drying and heating) on inflammation in acute lung injury(ALI) mice in vivo and in vitro. Lipopolysaccharide(LPS) was sprayed into the airway of wild type C57BL/6J male mice to establish the model, and the drug was injected into the tail vein 24 h after modeling. Lung function, lung tissue wet/dry weight(W/D) ratio, the total protein concentration, interleukin 6(IL-6), IL-1β, and tumor necrosis factor-α(TNF-α) in the bronchoalveolar lavage fluid(BALF), and pathological changes of the lung tissue were used to evaluate the effects of different gypenosides on ALI mice. The results showed that total gypenosides(YGGPs) and the gypenosides substituted with one or two glycosyl(GPs_(1-2)) in the air-dried sample improved the lung function, significantly lowered the levels of IL-1β and TNF-α in BALF, and alleviated the lung inflammation of ALI mice. Moreover, GPs_(1-2) had a more significant effect on inhibiting NO release in RAW264.7 cells. This study showed that different drying methods affected the anti-inflammatory activity of G. pentaphyllum, and the rare saponins in the air-dried sample without heating had better anti-inflammatory activity.