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Introduction: Determining the causal relationship between polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) holds significant implications for GDM prevention and treatment. Despite numerous observational studies suggesting an association between PCOS and GDM, it remains unclear whether a definitive causal relationship exists between these two conditions and which specific features of PCOS contribute to increased incidence of GDM. Methods: The causal relationship between polycystic ovary syndrome (PCOS), its characteristic indices, and gestational diabetes mellitus (GDM) was investigated using a two-sample Mendelian randomization study based on publicly available statistics from genome-wide association studies (GWAS). The inverse-variance weighted method was employed as the primary analytical approach to examine the association between PCOS, its characteristic indices, and GDM. MR Egger intercept was used to assess pleiotropy, while Q values and their corresponding P values were utilized to evaluate heterogeneity. It is important to note that this study adopts a two-sample MR design where PCOS and its characteristic indices are considered as exposures, while GDM is treated as an outcome. Results: The study results indicate that there is no causal relationship between PCOS and GDM (all methods P > 0.05, 95% CI of OR values passed 1). The IVW OR value was 1.007 with a 95% CI of 0.906 to 1.119 and a P value of 0.904. Moreover, the MR Egger Q value was 8.141 with a P value of 0.701, while the IVW Q value was also 8.141 with a P value of 0.774, indicating no significant heterogeneity. Additionally, the MR Egger intercept was 0.0004, which was close to zero with a P value of 0.988, suggesting no pleiotropy. However, the study did find a causal relationship between several other factors such as testosterone, high-density lipoprotein, sex hormone-binding globulin, body mass index, waist-hip ratio, apolipoprotein A-I, number of children, diabetes illnesses of mother, father and siblings, hemoglobin A1c, fasting insulin, fasting blood glucose, years of schooling, and GDM based on the IVW method. Conclusion: We observed no association between genetically predicted PCOS and the risk of GDM, implying that PCOS itself does not confer an increased susceptibility to GDM. The presence of other PCOS-related factors such as testosterone, high-density lipoprotein, and sex hormone-binding globulin may elucidate the link between PCOS and GDM. Based on these findings, efforts aimed at preventing GDM in individuals with PCOS should prioritize those exhibiting high-risk features rather than encompassing all women with PCOS.
Subject(s)
Diabetes, Gestational , Polycystic Ovary Syndrome , Child , Pregnancy , Humans , Female , Diabetes, Gestational/genetics , Sex Hormone-Binding Globulin , Genome-Wide Association Study , Mendelian Randomization Analysis , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/genetics , Lipoproteins, HDL , TestosteroneABSTRACT
Objective:To investigate the characteristics of the nocturnal melatonin secretion concentration and circadian rhythm in patients with wake-up stroke (WUS).Methods:Patients with acute ischemia stroke (AIS) admitted to the Department of Neurology, the Second Affiliated Hospital of Soochow University from October 2019 to August 2022 were enrolled. They were divided into WUS group and non-WUS group. Saliva samples within one week after admission were collected (at 19∶00, 20∶00, 21∶00, 22∶00, and 23∶00) and melatonin concentration was measured. Melatonin secretion curve graph was drawn, dim light melatonin onset (DLMO) was calculated, and circadian rhythms were evaluated. The differences in endogenous circadian rhythms between the WUS group and the non-WUS group were compared. The relevant factors of WUS were determined by multivariate logistic regression analysis. Results:A total of 116 patients with AIS were included, with 79 males (68.1%), aged 59.9±10.3 years; 35 patients (30.2%) were WUS. Univariate analysis showed that there was a statistically significant difference in the infarct site between the WUS group and the non-WUS group ( P=0.019). At 21:00 ( P=0.004) and the average ( P=0.038) nighttime melatonin concentration in the WUS group were significantly lower than those in the non-WUS group, and DLMO showed a significant delay compared to the non-WUS group (21:28:08 vs. 20:57:57; P=0.015). Multivariate logistic regression analysis showed a significant independent correlation between DLMO delay and WUS (odds ratio 1.792, 95% confidence interval 1.123-2.858; P=0.014). Conclusion:Patients with WUS may have endogenous circadian rhythm delay, which is an independent risk factor for WUS.
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ObjectiveTo investigate the effects of epigallocatechin-3-gallate (EGCG) on learning and memory abilities of amygdala electrical kindling-induced epilepsy in rats and its mechanism. MethodMale SD rats were randomly divided into the normal group, model group, intervention group (model+25 mg·kg-1 EGCG), and EGCG group (25 mg·kg-1 EGCG). Rats in the EGCG group were only given EGCG intraperitoneal injection, those in the normal group were only given electrode implantation, and those in the other experimental groups were given amygdala electrical kindling stimulation to establish a chronic kindling epilepsy model. EGCG was injected intraperitoneally daily before electrical stimulation. Twenty-four hours after the last electrical stimulation, the escape latency and percentage of target quadrant were recorded by the Morris water maze. Twenty-four hours after the behavioral test, rats in each group were sacrificed by decapitation. The number of hippocampal neurons was observed by Nissl staining. The thickness of postsynaptic density in the hippocampus, synaptic cleft, length of active zone and the curvature of synaptic interface were observed by transmission electron microscopy (TEM). The expressions of synapse-related proteins synaptotagmin (Syt), postsynaptic density-95 (PSD-95) and Kalirin-7 in the hippocampus were examined by Western blot. ResultCompared with those in the normal group, the escape latency was significantly prolonged (P<0.05, P<0.01) and the target quadrant ratio was significantly decreased in the model group (P<0.05). The number of hippocampus neurons decreased significantly (P<0.01). The synaptic cleft of the hippocampus was widened significantly, and the length of active zone and the thickness of postsynaptic density were significantly decreased (P<0.05, P<0.01). The expressions of synapse-related proteins Syt, PSD-95 and Kalirin-7 in the hippocampus were significantly decreased (P<0.05,P<0.01). Compared with those in the model group, the escape latency was significantly shortened and the percentage of target quadrant was significantly increased in the intervention group (P<0.05, P<0,01). The number of hippocampal neurons significantly increased (P<0.01). The synaptic cleft of the hippocampus was significantly shortened, and the length of active zone and postsynaptic density were significantly increased (P<0.05, P<0.01). The expressions of synaptic related proteins Syt, PSD-95 and Kalirin-7 were significantly increased (P<0.05, P<0.01). ConclusionEGCG can effectively improve cognitive dysfunction after epilepsy. Its protective effect may be achieved by protecting the ultrastructure of hippocampal synapses and regulating the expressions of synapse-related proteins Syt, PSD-95 and Kalirin-7.
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BackgroundThe course of schizophrenia is prolonged, and patients have impaired social function and significantly reduced quality of life. Drug therapy combined with psychological therapy is particularly important for improving the quality of life of patients. Brief cognitive behavioral therapy (BCBT) has been widely applied in clinical practice, but current research on BCBT focuses more on improving patients' symptoms and lacks relevant reports on improving quality of life. ObjectiveTo evaluate the efficacy and influencing factors of BCBT combined with conventional treatment on improving the quality of life in patients with schizophrenia. MethodsA total of 210 patients who met the diagnostic criteria for schizophrenia in the International Classification of Diseases (10th edition) (ICD-10) and were followed up at the outpatient department of Beijing Anding Hospital Capital Medical University from August 2011 to December 2016 were selected. Using a random number table method, patients were divided into study group and control group, with 105 cases in each group. Both groups received routine treatment, and the research group received a total of 8 BCBT sessions for 12 weeks on this basis. At the baseline period and 12 weeks of treatment, 26 weeks of follow-up and 52 weeks of follow-up, Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance Scale (PSP) and World Health Organization Quality of Life Brief (WHOQOL-BREF) were used for evaluation. ResultsThe results of repeated measures analysis of variance showed that the time point effect and interaction effect of PANSS total score were statistically significant (F=118.783, 8.083, P<0.01).The time point effect, inter group effect and interaction effect of PSP total score were statistically significant (F=94.358, 4.048, 5.490, P<0.05 or 0.01). The time point effect, inter group effect and interaction effect of the total score of WHOQOL-BREF were all statistically significant (F=12.330, 4.168, 4.142, P<0.05 or 0.01) Binary Logistic regression analysis showed that the study group (OR=1.861, 95% CI: 1.004~3.448) and young age (OR=1.044, 95% CI: 1.001~1.088) were protective factors for improving quality of life of patients, while high PANSS baseline score (OR=0.972, 95% CI: 0.945~0.999) was a risk factor for improving quality of life of patients. ConclusionThe combination of BCBT and conventional treatment has an earlier onset of improvement in the quality of life of patients with schizophrenia, and long-term efficacy is superior to conventional treatment.[Funded by Research Projects Supported by Beijing Municipal Commission of Science and Technology (number, Z111107058811078); Capital Medical Development Fund Joint Research Project (number, 2009-1050); Beijing Hygienism and Health Science and Technology Achievements and Appropriate Technology Promotion Project (number, TG-2017-38); www.chictr.org.cn number: ChiCTR-TRC-13003709]
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Clinical prediction models play an important role in the field of medicine. These can help predict the probability of an individual suffering from disease, complications, and treatment outcomes by applying specific methodologies. Polycystic ovary syndrome (PCOS) is a common disease with a high incidence rate, huge heterogeneity, short- and long-term complications, and complex treatments. In this systematic review study, we reviewed the progress of clinical prediction models in PCOS patients, including diagnosis and prediction models for PCOS complications and treatment outcomes. We aimed to provide ideas for medical researchers and clues for the management of PCOS. In the future, models with poor accuracy can be greatly improved by adding well-known parameters and validations, which will further expand our understanding of PCOS in terms of precision medicine. By developing a series of predictive models, we can make the definition of PCOS more accurate, which can improve the diagnosis of PCOS and reduce the likelihood of false positives and false negatives. It will also help discover complications earlier and treatment outcomes being known earlier, which can result in better outcomes for women with PCOS.
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Polycystic Ovary Syndrome , Female , Humans , Polycystic Ovary Syndrome/drug therapy , Models, Statistical , PrognosisABSTRACT
Objective: To observe the characteristics of the evolution of liver indexes in patients with relapsed/refractory multiple myeloma (RRMM) treated with CAR-T-cells based on BCMA. Methods: Retrospective analysis was performed of patients with RRMM who received an infusion of anti-BCMA CAR-T-cells and anti-BCMA combined with anti-CD19 CAR-T-cells at our center between June 1, 2019, and February 28, 2023. Clinical data were collected to observe the characteristics of changes in liver indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) in patients, and its relationship with cytokine-release syndrome (CRS) . Results: Ninety-two patients were included in the analysis, including 41 patients (44.6%) in the group receiving a single infusion of anti-BCMA CAR-T-cells, and 51 patients (55.4%) in the group receiving an infusion of anti-BCMA combined with anti-CD19 CAR-T-cells. After infusing CAR-T-cells, 31 patients (33.7%) experienced changes in liver indexes at or above grade 2, which included 20 patients (21.7%) with changes in one index, five patients (5.4%) with changes in two indexes, and six patients (6.5%) with changes in three or more indexes. The median time of peak values of ALT and AST were d17 and d14, respectively, and the median duration of exceeding grade 2 was 5.0 and 3.5 days, respectively. The median time of peak values of TBIL and DBIL was on d19 and d21, respectively, and the median duration of exceeding grade 2 was 4.0 days, respectively. The median time of onset of CRS was d8, and the peak time of fever was d9. The ALT, AST, and TBIL of patients with CRS were higher than those of patients without CRS (P=0.011, 0.002, and 0.015, respectively). CRS is an independent factor that affects ALT and TBIL levels (OR=19.668, 95% CI 18.959-20.173, P=0.001). The evolution of liver indexes can be reversed through anti-CRS and liver-protection treatments, and no patient died of liver injury. Conclusions: In BCMA-based CAR-T-cell therapy for RRMM, CRS is an important factor causing the evolution of liver indexes. The evolution of liver indexes after CAR-T-cell infusion is transient and reversible after treatment.
Subject(s)
Humans , Antigens, CD19 , B-Cell Maturation Antigen/therapeutic use , Bilirubin , Immunotherapy, Adoptive , Liver , Multiple Myeloma/drug therapy , Retrospective Studies , T-LymphocytesABSTRACT
AIM To establish an HPLC-MS/MS method for the simultaneous content determination of pulegone,prim-O-glucosylcimifugin,5-O-methylvisammioside,columbianadin,saikosaponin a,saikosaponin d,ferulic acid,naringin,liquiritin and glycyrrhizic acid in Jingfang Granules.METHODS The analysis of methanol extract of this drug was performed on a 30℃thermostatic ZORBAX Eclipse Plus C18 column(2.1 mm×150 mm,1.8 μm),with the mobile phase comprising of methanol-0.1%formic acid flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS Ten constituents showed good linear relationships within their own ranges(r>0.996 5),whose average recoveries were 96.7%-98.8%with the RSDs of 0.9%-1.9%.CONCLUSION This rapid,simple,sensitive and specific method can be used for the quality control of Jingfang Granules.
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Objectve:To observe the change of functional connectivity(FC)characteristic and its correlation with cognitive flexibility in type 2 diabetes mellites(T2DM)patients with cognitive flexibility decreased.Methods:A retro-spective analysis was performed in 24 T2DM patients with cognitive flexibility decreased(T2DM+CD),34 T2DM pa-tients without cognitive flexibility decreased(T2DM-CD)and 31 healthy controls(HC).Wisconsin Card Sorting Test(WCST)and the Stroop Color Word Test(Stroop)were respectively used in three groups of subjects to assess cognitive flexibility and functional magnetic resonance imaging(fMRI)scans was used to assess the FC.The differences of cogni-tive flexibility were found between three groups of subjects.The differences of FC between the bilateral(Left and Right,L.and R.)striatum(ST)and the dorsolateral prefrontal cortex(dlPFC)were found between three groups of subjects.Further analysis was focused on the interactive effect of T2DM and cognitive flexibility on FC changes.Results:Com-pared with T2DM-CD and HC,the number of response administered,errors responses,perseverative response,and time in WCST of T2DM+CD were significantly increased,while the number of correct responses was decreased.In Stroop,the number of correct,word-color contradiction and correct word-color indifference in T2DM+CD were lower than HC.In T2DM+CD,FC between L.ST-L.dlPFC,R.ST-L.dlPFC and R.ST-R.dlPFC were decreased,and decreased FC between R.ST-R.dlPFC was associated with cognitive flexibility scale scores.There existed an interactive effect between T2DM and cognitive flexibility on FC changes.Conclusion:Decreased FC between ST and dlPFC is the neural mechanism of cognitive flexibility impairment in T2DM.
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Objective: To determine the optimal cutoff value of Epstein-Barr virus (EBV) DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease (PTLD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed. Through constructing the receiver operating characteristic (ROC) curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD. Results: A total of 94 patients were included, of whom 20 (21.3% ) developed PTLD, with a median onset time of 56 (40-309) d after transplantation. The median EBV value at the time of diagnosis of PTLD was 70,400 (1,710-1,370,000) copies/ml, and the median duration of EBV viremia was 23.5 (4-490) d. Binary logistic regression was used to analyze the peak EBV-DNA load (the EBV-DNA load at the time of diagnosis in the PTLD group) and duration of EBV viremia between the PTLD and non-PTLD groups. The results showed that the difference between the two groups was statistically significant (P=0.018 and P=0.001) . The ROC curve was constructed to calculate the Youden index, and it was concluded that the EBV-DNA load ≥ 41 850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD (AUC=0.847) , and the sensitivity and specificity were 0.611 and 0.932, respectively. The duration of EBV viremia of ≥20.5 d had diagnostic significance for PTLD (AUC=0.833) , with a sensitivity and specificity of 0.778 and 0.795, respectively. Conclusion: Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance, which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.
Subject(s)
Humans , Epstein-Barr Virus Infections/diagnosis , Herpesvirus 4, Human/genetics , Retrospective Studies , Viremia , Hematopoietic Stem Cell Transplantation/adverse effects , Lymphoproliferative Disorders/etiology , DNA, Viral , Viral LoadABSTRACT
Objective: To explore the incidence and clinical characteristics of engraftment syndrome (ES) after syngeneic hematopoietic stem cell transplantation (syn-HSCT) in patients with hematological diseases. Methods: The clinical data of 21 patients who received syn-HSCT at People's Hospital of Peking University from January 1994 to May 2018 were retrospectively analyzed. Results: Seven (33.3% ) of 21 patients developed ES. The onset of ES symptoms occurred at a median of 8 (range: 5-13) days after HSCT, and the diagnosis of ES occurred at a median of 10 (range: 7-14) days after HSCT. Steroids were administered immediately after the diagnosis of ES, the median time of symptom continuance was 2 (range: 1-5) days, and all patients showed complete resolution of ES symptoms. In the multivariate analysis, patients with acute myeloid leukemia and faster neutrophil reconstitution were the risk factors for ES (HR=15.298, 95% CI 1.486-157.501, P=0.022, and HR=17.459, 95% CI 1.776-171.687, P=0.014) . Meanwhile, there was no significant difference in the overall survival and disease-free survival between patients with ES and those without ES. Conclusion: A high incidence of ES was observed in syn-HSCT recipients. Moreover, the prognosis of ES was excellent.
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Humans , Retrospective Studies , Incidence , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Hematologic Diseases/complicationsABSTRACT
OBJECTIVE@#To evaluate the clinical efficacy and safety of decitabine combined with modified CAG regimen (D-CAG regimen) in patients aged ≥70 years with newly diagnosed acute myeloid leukemia (AML).@*METHODS@#The clinical data of 59 AML patients (≥70 years old) who were newly diagnosed and treated in the Hematology Department of the First Affiliated Hospital of Nanjing Medical University from November 2010 to June 2021 were retrospectively analyzed.@*RESULTS@#Among the 59 AML patients, 28 were males and 31 were females, with a median age of 74 (70-86) years. The complete remission (CR) rate was 69.4% (34/49), and the median duration of CR was 10.7 (0.6-125.4) months after 2 courses of D-CAG treatment. According to the British Medical Research Council (MRC) classification, there was only one patient in the favorable-risk group, and the CR rate was 71.8% (28/39) in the intermediate-risk group, and 55.6% (5/9) in the adverse-risk group, respectively. There was no statistical difference in the CR rate between the intermediate-risk and adverse-risk group. Referring to ELN 2017 genetic risk classification, CR rate was 88.2% (15/17) in the favorable-risk group, 45.5% (5/11) in the intermediate-risk group, and 66.7% (14/21) in the adverse-risk group. There was no significant difference in CR rate between the favorable-risk and adverse-risk categories, but both were significantly higher than that in the intermediate-risk group (P <0.05). Next-generation sequencing (NGS) analysis showed that 11 gene mutations with a frequency of more than 10%, including TET2 mutation (35.6%), ASXL1 mutation (30.5%), NPM1 mutation (28.8%), FLT3-ITD mutation (27.1%), DNMT3A mutation (22.0%), IDH1 mutation (15.3%), CEBPA single mutation (13.6%), TP53 mutation (13.6%), IDH2 mutation (11.9%), RUNX1 mutation (11.9%), and NRAS mutation (10.2%). There were no statistical differences in mutation frequency of these 11 genes between CR group and non-CR group. Compared with normal karyotypes, patients with complex karyotypes were more likely to develop TP53 mutations (P <0.001), while FLT3-ITD and DNMT3A mutations were more likely to occur in patients with normal karyotypes (P =0.04, P =0.047). The median follow-up, overall survival (OS), and event-free survival (EFS) of all the patients was 11.7 (1.5-128.2) months, 12.3 (1.5-128.2) months, and 8.5 (1.5-128.2) months, respectively. The median OS and EFS of CR patients were 19.8 and 13.3 months, respectively, which were significantly longer than 6.4 and 5.7 months in patients experiencing treatment failure (P < 0.001, P =0.009). In regard to genes with mutation frequency >10%, there were no statistical differences in CR rate, median OS, and median EFS between mutated and wild-type patients by Chi-square test and survival analysis. Univariate analysis showed that age, hemoglobin, lactate dehydrogenase, cytogenetics and CR were factors affecting prognosis, while multivariate analysis showed that only CR failure was an independent adverse prognostic factor for OS. The major adverse reactions to D-CAG regimen were grade 3-4 myelosuppression, pulmonary infection, and fever (infection focus was not identified).@*CONCLUSION@#D-CAG regimen is safe and effective in the treatment of AML patients ≥70 years old, and can partially improve the prognosis of elderly and high-risk patients.
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Aged , Male , Female , Humans , Aged, 80 and over , Decitabine/therapeutic use , Retrospective Studies , Cytarabine/therapeutic use , Prognosis , Mutation , Leukemia, Myeloid, Acute/geneticsABSTRACT
Objective:To investigate changes in expression of plasma soluble CD100 (sCD100) and membrane-bound CD100 (mCD100) on peripheral T cells in patients with herpes zoster, and to observe the regulatory effect of exogenous CD100 on CD8 + T cells. Methods:A total of 53 patients with herpes zoster attending the Zhumadian Central Hospital from July 2019 to April 2021 were enrolled, so were 25 age- and sex-matched healthy controls. Anticoagulated venous blood samples were collected, plasma and peripheral blood mononuclear cells were isolated, plasma sCD100 levels were detected by enzyme-linked immunosorbent assay, and mCD100 expression on CD4 + and CD8 + T cells was determined by flow cytometry. After the purification of CD8 + T cells, the secretion levels of cytotoxic molecules and cytokines by CD8 + T cells were measured and compared between herpes zoster patients and controls. Some purified CD8 + T cells from herpes zoster patients were stimulated with recombinant human CD100 and recombinant varicella-zoster virus glycoprotein, and the effect of recombinant human CD100 on the secretion of cytotoxic molecules and cytokines by CD8 + T cells was investigated. Comparisons between groups were conducted by t test. Results:Plasma sCD100 levels were significantly lower in the herpes zoster group (1.12 ± 0.23 ng/ml) than in the control group (1.31 ± 0.28 ng/ml, t = 2.97, P = 0.004), the proportion of mCD100 + CD8 + T cells was significantly higher in the herpes zoster group (17.41% ± 4.26%) than in the control group (14.69% ± 3.70%, t = 2.52, P = 0.014), and no significant difference in the proportion of mCD100 + CD4 + T cells was found between the two groups (2.52% ± 0.58% vs. 2.32% ± 0.56%, t = 1.27, P = 0.208). The herpes zoster group showed significantly decreased mRNA expression of perforin and granzyme B in, and lower secretion levels of perforin, granzyme B, interferon-γ and tumor necrosis factor-α by CD8 + T cells compared with the control group (all P < 0.05). After stimulation with recombinant human CD100, levels of perforin, granzyme B, interferon-γ and tumor necrosis factor-α in the culture supernatant of CD8 + T cells (43.68 ± 14.12, 126.8 ± 22.92, 12.79 ± 3.66, 310.0 ± 79.90 pg/ml, respectively ) were significantly higher than those in non-stimulated group (34.55 ± 10.78, 99.04 ± 10.44, 9.53 ± 2.00, 275.6 ± 68.04 pg/ml, respectively, all P < 0.05) . Conclusion:There was an imbalance between sCD100 and mCD100 expression in patients with herpes zoster, and exogenous sCD100 may enhance the cytotoxicity of CD8 + T cells in herpes zoster patients.
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Objective: To evaluate treatment responses, outcomes, and prognostic factors in adults with secondary acute myeloid leukemia (sAML) . Methods: Between January 2008 and February 2021, date of consecutive cases of younger than 65 years of adults with sAML were assessed retrospectively. Clinical characteristics at diagnosis, treatment responses, recurrence, and survival were evaluated. Logistic regression and Cox proportional hazards model were employed to determine significant prognostic indicators for treatment response and survival. Results: 155 patients were recruited, including 38, 46, 57, 14 patients belonging to t-AML, and AML with unexplained cytopenia, post-MDS-AML, and post-MPN-AML, respectively. In the 152 evaluable patients, the rate of MLFS after the initial induction regimen was 47.4%, 57.9%, 54.3%, 40.0%, and 23.1% in the four groups (P=0.076) . The total rate of MLFS after the induction regimen was 63.8%, 73.3%, 69.6%, 58.2%, and 38.5% (P=0.084) , respectively. Multivariate analysis demonstrated that male gender (OR=0.4, 95% CI 0.2-0.9, P=0.038 and OR=0.3, 95% CI 0.1-0.8, P=0.015) , SWOG cytogenetic classification into unfavorable or intermediate (OR=0.1, 95% CI 0.1-0.6, P=0.014 and OR=0.1, 95% CI 0.1-0.3, P=0.004) and receiving low-intensity regimen as induction regimen (OR=0.1, 95% CI 0.1-0.3, P=0.003 and OR=0.1, 95%CI 0.1-0.2, P=0.001) were typical adverse factors impacting the first CR and the final CR; PLT<45 × 10(9)/L (OR=0.4, 95%CI 0.2-0.9, P=0.038) and LDH ≥258 U/L (OR=0.3, 95%CI 0.1-0.7, P=0.005) were independent factors for CR. Among the 94 patients with achieving MLFS, 46 cases had allogeneic hematopoietic stem cell transplantation. With a median follow-up period of 18.6 months, the probabilities of relapse-free survival (RFS) and overall survival (OS) at 3 years were 25.4% and 37.3% in patients with transplantation, and in patients with chemotherapy, the probabilities of RFS and OS at 3-year were 58.2% and 64.3%, respectively. At the time of achieving MLFS, multivariate analysis revealed that age ≥46 years (HR=3.4, 95%CI 1.6-7.2, P=0.002 and HR=2.5, 95%CI 1.1-6.0, P=0.037) , peripheral blasts ≥17.5% at diagnosis (HR=2.5, 95%CI 1.2-4.9, P=0.010 and HR=4.1, 95%CI 1.7-9.7, P=0.002) , monosomal karyotypes (HR=4.9, 95%CI 1.2-19.9, P=0.027 and HR=28.3, 95%CI 4.2-189.5, P=0.001) were typical adverse factors influencing RFS and OS. Furthermore, CR after induction chemotherapy (HR=0.4, 95%CI 0.2-0.8, P=0.015) and transplantation (HR=0.4, 95%CI 0.2-0.9, P=0.028) were substantially linked to longer RFS. Conclusion: Post-MDS-AML and post-MPN-AML had lower response rates and poorer prognoses than t-AML and AML with unexplained cytopenia. In adults with male gender, low platelet count, high LDH, and SWOG cytogenetic classification into unfavorable or intermediate at diagnosis, and receiving low-intensity regimen as the induction regimen predicted a low response rate. Age ≥46 years, a higher proportion of peripheral blasts and monosomal karyotype had a negative effect on the overall outcome. Transplantation and CR after induction chemotherapy were greatly linked to longer RFS.
Subject(s)
Adult , Humans , Male , Middle Aged , Prognosis , Remission Induction , Retrospective Studies , Leukemia, Myeloid, Acute/drug therapy , Induction Chemotherapy , Recurrence , Hematopoietic Stem Cell TransplantationABSTRACT
Objective:To explore the comparative study of video laryngoscopy combined with bronchial blocker and video laryngoscopy combined with double-lumen tube in the teaching of endotracheal intubation in thoracic surgery in the standardized residency training of anesthesia.Methods:The trainees of the standardized residency training were randomly divided into control group and experimental group for clinical teaching, with 25 ones in each group. The experimental group was treated with visual laryngoscopy combined with bronchial blocker, while the control group was treated with visual laryngoscopy combined with double-lumen tube group. The intubation time, intubation success rate, positioning time, hemodynamic changes, and complication incidence during intubation, as well as student assessment results were recorded. GraphPad Prism 6.0 was used for t test and Chi-square test. Results:The time of endotracheal intubation [(95.3±10.1) vs. (137.5±13.5)] and positioning time [(100.8±11.7) vs. (155.4±15.3)] in the experimental group were both shorter than those of the control group ( P< 0.001), the hemodynamic changes in patients with immediate intubation were smaller ( P<0.001), the success rate of intubation was higher (92% vs. 68%) ( P<0.001), the complication incidence was lower ( P<0.001) and the students' performance was higher ( P<0.001). Conclusion:In the anesthesia teaching of thoracic surgery, bronchial blocker can reduce the time of endotracheal intubation, lower the hemodynamic changes during intubation, cut down the incidence of complications, improve the success rate of endotracheal intubation and enhance the confidence of students.
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Objective:To compare the efficacy of different antibacterial drugs combined in the treatment of adult brucellosis patients.Methods:Using a prospective design, 60 adult brucellosis patients admitted to the Affiliated Hospital of Jining Medical University from January 2018 to December 2021 were selected as the study subjects. They were randomly divided into an observation group ( n = 30) and a control group ( n = 30) using a random number table method. The observation group was treated with rifampicin combined with minocycline, and the control group was given rifampicin combined with doxycycline. The course of treatment in both groups was 6 weeks. The efficacy and clinical symptom disappearance time between the two groups, as well as the blood white blood cell count (WBC), alanine aminotransferase (ALT) levels, and serum interferon-γ (IFN-γ), interleukin-4 (IL-4) and interleukin-10 (IL-10) levels before and after treatment, and the occurrence of adverse reactions were compared. Results:The total effective rate of the observation group (96.67%, 29/30) was higher than that of the control group (73.33%, 22/30), with a statistically significant difference (χ 2 = 4.71, P = 0.030). The disappearance time of joint pain, hyperhidrosis, gastrointestinal reactions, and fever in the observation group were shorter than those in the control group, and the differences were statistically significant ( P < 0.05). After treatment, the blood WBC and ALT levels in both groups decreased compared to before treatment ( P < 0.05). After treatment, the blood WBC and ALT levels in the observation group were lower than those in the control group ( P < 0.001). The levels of serum IFN-γ and IL-10 were both decreased after treatment compared to before treatment in two groups, while IL-4 level increased compared to before treatment ( P < 0.05). The levels of serum IFN-γ and IL-10 in the observation group were lower than those of the control group, while IL-4 level was higher than that of the control group ( P < 0.001). The incidence of adverse reactions in the observation group (13.33%, 4/30) was lower than that in the control group (36.67%, 11/30), and the difference was statistically significant (χ 2 = 4.36, P = 0.037). Conclusion:The combination of rifampicin and minocycline in the treatment of adult brucellosis patients has good efficacy and can reduce serum IFN-γ and IL-10 levels and increase IL-4 level with few adverse reactions.
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Objective:To investigate the predictive value of vascular endothelial growth factor (VEGF) expression and microvascular density (MVD) for the depth of infiltration in early gastric cancer.Methods:The pathological tissues of 24 patients with early gastric cancer (early gastric cancer group), 23 patients with advanced gastric cancer (advanced gastric cancer group) and 10 patients with gastritis (gastritis group) who admitted to Fenyang Hospital Affiliated of Shanxi Medical University from January 2020 to January 2022 were retrospectively collected. Immunohistochemistry was used to detect VEGF expression and MVD in the lesion tissues of each group, and the correlation of VEGF expression and MVD in gastric cancer tissues with the clinicopathological characteristics of patients was analyzed. Postoperative pathological diagnosis was treated as the gold standard. The efficacy of VEGF and MVD in predicting the depth of infiltration in gastric cancer and early gastric cancer was assessed by using the receiver operating characteristic (ROC) curve.Results:The VEGF positive expression rate was 10.00% (1/10), 29.17% (7/24) and 78.26% (18/23) in gastritis group, early gastric cancer group and advanced gastric cancer group, respectively, and the MVD was (21±5) strips/field, (23±9) strips/field and (43±15) strips/field, respectively. The positive expression rate of VEGF and MVD were related with the tumor diameter [>2 cm vs. ≤2 cm:69.70% (23/33) vs. 14.29% (2/14), (39±15) strips/field vs. (20±8) strips/field] and infiltration depth of gastric cancer [intramucosal carcinoma vs. submucosal carcinoma vs. advanced gastric cancer: 26.31% (5/19) vs. 40.00% (2/5) vs. 78.26% (18/23), (20±7) strips/field vs. (36±3) strips/field vs. (43±15) strips/field] (all P > 0.01), while not related with gender, age, tumor location, differentiation degree (all P > 0.05). The ROC curve analysis showed that the area under the curve (AUC) of VEGF and MVD in predicting the depth of infiltration in gastric cancer was 0.716 (95% CI 0.581-0.828) and 0.711 (95% CI 0.573-0.823), respectively; the optimal cut-off value of VEGF and MVD was positive and 24.8 strips/field, with the sensitivity of 53.19%, 61.70%, and the specificity of 90.00% both. The AUC of VEGF and MVD in predicting the depth of infiltration in early gastric cancer was 0.596 (95% CI 0.414-0.760) and 0.506 (95% CI 0.330-0.681) , respectively; the optimal cut-off value of VEGF and MVD was positive and 32.5 strips/field, with the sensitivity of 29.17% , 70.83%, and the specificity of 90.00%, 0, respectively. Conclusions:VEGF expression and MVD are elevated with the increase of depth of gastric cancer infiltration, while the value of the combination of both in predicting the depth of infiltration in early gastric cancer is not high.
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In recent years, with the increasing understanding of the genetic mechanisms of hypertrophic cardiomyopathy, novel molecular-targeted drugs Mavacamten and Aficamten are two cardiac myosin inhibitors currently approved by the FDA for the treatment of hypertrophic obstructive cardiomyopathy. Both of them have a similar mechanism of action and can selectively bind to different variable sites of cardiac myosin to inhibit cardiac myosin, thus reducing myocardial hypercontractility. Relevant clinical studies have also shown that both drugs can reduce patients’ left ventricular outflow tract pressure gradient, the levels of N-terminal pro-B-type natriuretic peptide and cardiac troponin I as cardiac markers, and improve New York Heart Association (NYHA) cardiac function class. They are safe, have mild adverse reactions, and can be tolerated by patients. Compared to Mavacamten, Aficamten, as a structurally optimized product, has a shorter half-life and fewer drug-drug interactions, which is more conducive to drug- targeted dose titration.
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Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.
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Humans , Cytomegalovirus , Retrospective Studies , Cohort Studies , Prospective Studies , Cytomegalovirus Infections/prevention & control , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/prevention & control , Recurrence , Antiviral Agents/therapeutic useABSTRACT
BackgroundGender and age differences in the clinical manifestations of patients with bipolar disorder can affect the clinical diagnosis and treatment process. The current treatment effect of bipolar disorder in adolescents is not ideal, which has become the main reason for disability during the learning period. ObjectiveTo analyze the clinical features and medication therapy status of bipolar disorder in adolescents, and to provide references to support for personalized diagnosis and treatment. MethodsOn January 16, 2023, 1 169 patients with bipolar disorder who were hospitalized at Beijing Anding Hospital Affiliated Capital Medical University from January 1, 2014 to December 31, 2017 were retrospectively enrolled. Medical records were collected and analyzed to compare the clinical features among patients of different gender and age groups, and to explore the differences in medication use among patients of different genders in different types of seizures. ResultsMale patients reported a larger proportion of manic episodes, and a smaller proportion of depressive episodes than female patients (P<0.05).Female patients reported a larger proportion of non-suicidal self-harm behaviors than male patients (χ2=7.761, P<0.01).And patients in low-age group featured a larger proportion of mixed seizures, impulsive behaviors and family history of bipolar disorders along with a smaller proportion of manic episodes than those in high-age group (P<0.05 or 0.01). High-age group had a longer average length of hospital stay than low-age group (t=-2.930, P<0.01). In manic episode patients, males were found to have a larger proportion of valproate and atypical antipsychotic drug administration than females (P<0.01). Among atypical antipsychotic drugs, males accounted for a larger proportion of administration of risperidone and olanzapine (χ2=26.957) than females (P<0.05 or 0.01), while females constituted a larger proportion of administration of quetiapine (χ2=14.865) and aripiprazole than males (P<0.01). In depressive episode patients, females had a larger proportion of administration of olanzapine than males (P<0.01). In patients with mixed seizures, females occupied a larger proportion of administration of lithium carbonate than males (χ2=9.253, P<0.01), and males exhibited a larger proportion of administration of valproate than females (P<0.05). ConclusionDifferences have been shown in diagnostic classification and concomitant symptoms among adolescent bipolar disorder of different genders and ages. Furthermore, medications of lithium carbonate, valproate, atypical antipsychotic and other drugs differ by gender among adolescents of different subtypes of bipolar disorder. [Funded by Key Special Project of the National Key R&D Program of the Ministry of Science and Technology for "Major Chronic Non communicable Disease Prevention and Control Research" (number, 2017YFC1311101)]
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OBJECTIVE@#To establish a rapid detection and genotyping method for SARS-CoV-2 Omicron BA.4/5 variants using CRISPPR-Cas12a gene editing technology.@*METHODS@#We combined reverse transcription-polymerase chain reaction (RT-PCR) and CRISPR gene editing technology and designed a specific CRISPPR RNA (crRNA) with suboptimal protospacer adjacent motifs (PAM) for rapid detection and genotyping of SARS- CoV-2 Omicron BA.4/5 variants. The performance of this RT- PCR/ CRISPPR-Cas12a assay was evaluated using 43 clinical samples of patients infected by wild-type SARS-CoV-2 and the Alpha, Beta, Delta, Omicron BA. 1 and BA. 4/5 variants and 20 SARS- CoV- 2-negative clinical samples infected with 11 respiratory pathogens. With Sanger sequencing method as the gold standard, the specificity, sensitivity, concordance (Kappa) and area under the ROC curve (AUC) of RT-PCR/CRISPPR-Cas12a assay were calculated.@*RESULTS@#This assay was capable of rapid and specific detection of SARS- CoV-2 Omicron BA.4/5 variant within 30 min with the lowest detection limit of 10 copies/μL, and no cross-reaction was observed in SARS-CoV-2-negative clinical samples infected with 11 common respiratory pathogens. The two Omicron BA.4/5 specific crRNAs (crRNA-1 and crRNA-2) allowed the assay to accurately distinguish Omicron BA.4/5 from BA.1 sublineage and other major SARS-CoV-2 variants of concern. For detection of SARS-CoV-2 Omicron BA.4/5 variants, the sensitivity of the established assay using crRNA-1 and crRNA-2 was 97.83% and 100% with specificity of 100% and AUC of 0.998 and 1.000, respectively, and their concordance rate with Sanger sequencing method was 92.83% and 96.41%, respectively.@*CONCLUSION@#By combining RT-PCR and CRISPPR-Cas12a gene editing technology, we successfully developed a new method for rapid detection and identification of SARS-CoV-2 Omicron BA.4/5 variants with a high sensitivity, specificity and reproducibility, which allows rapid detection and genotyping of SARS- CoV-2 variants and monitoring of the emerging variants and their dissemination.