Ineffective Group Research Articles

Clinical Features and Influencing Factors for the Prognosis of Patients With Sudden Deafness.

BackgroundsStudies on risk factors influencing the prognosis of patients with sudden onset deafness are lacking.MethodsFrom March 2018 to March 2021, 500 patients, from the Tongde Hospital in Zhejiang Province, with sudden onset deafness were enrolled. We collected clinical information from the hospital medical records, including certain demographic characteristics, information related to sudden-onset deafness, and laboratory parameters. Univariate and multivariate analyses were performed to determine independent prognostic risk factors for patients with sudden deafness. Additionally, we also employed orthogonal partial least squares discriminant analysis (OPLS-DA) to analyze the data of these enrolled patients.ResultsThe baseline clinical characteristics of the enrolled patients were analyzed. Based on their prognoses, the included patients were divided into the overall effective and ineffective groups. Between these two groups, the univariate and multivariate analyses were performed. Age, type of hearing curve at the initial diagnosis, acute phase, and sudden deafness site were found to be independently associated with the prognoses of patients with sudden deafness (all P < 0.05). Through the OPLS-DA, the sudden deafness site was found to be an indicator with the highest predictive power.ConclusionsAge, type of hearing curve at the initial diagnosis, acute phase, and sudden deafness site were all independently correlated with the prognoses of patients with sudden deafness and, therefore, need to be emphasized.

Clinical Value of PLR, MLR, and NWR in Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer.

Objective The clinical value of platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-white blood cell ratio (NWR) in predicting the prognosis of patients with locally advanced gastric cancer after neoadjuvant chemotherapy (NACT) was studied. Methods A total of 131 patients with locally advanced gastric cancer treated with neoadjuvant chemotherapy in our hospital from May 2015 to June 2018 were selected as the study subjects, and all were treated with neoadjuvant chemotherapy. The relationship between the values of PLR, MLR, and NWR and the efficacy of neoadjuvant chemotherapy and clinical staging was analyzed; all patients were followed up for 3 years. Patients were divided into death group and survival group according to the survival of patients. The predictive value of PLR, MLR, and NWR values for patients' prognosis was analyzed, and the survival rates of patients with different PLR, MLR, and NWR values were compared. Results The effective rate of neoadjuvant chemotherapy in patients with locally advanced gastric cancer was 62.60% (82/131), and the PLR, MLR, and NWR values in the effective group were lower than those in the ineffective group (P < 0.05). The AUC of combined PLR, MLR, and NWR in evaluating the efficacy of neoadjuvant chemotherapy was greater than that of PLR and NWR alone (P < 0.05). The PLR value of patients with stage IIIa, IIIb, and IIIc was greater than that of patients with stage II, the MLR value of patients with stage IIIb and IIIc was greater than that of patients with stage II and IIIa, and the NMR value of patients with stage IIIc was greater than that of patients with stage II, IIIa, and IIIb (P < 0.05). PLR, MLR, and NWR values were positively correlated with clinical stage (P < 0.05). The PLR, MLR, and NWR values in the survival group were lower than those in the death group (P < 0.05). The AUC of combined PLR, MLR, and NWR in predicting the prognosis of patients was greater than that of MLR and NWR alone (P < 0.05). The survival rate of patients with PLR ≥ 162.11 (36.21%) was lower than that of patients with PLR < 162.11 (80.82%), and the survival rate of patients with MLR ≥ 0.31 (42.86%) was lower than that of patients with MLR < 0.31 (74.67%), and the survival rate of patients with NWR ≥ 0.62 (45.00%) was lower than that of patients with NWR < 0.62 (74.65%) (P < 0.05). Conclusions PLR, MLR, and NWR values are correlated with clinical stage, and the combined detection has value in evaluating the clinical efficacy of neoadjuvant chemotherapy and predicting the prognosis of patients with locally advanced gastric cancer.

Constraints in Operationalizing FPOs in Punjab and Strategies to Mitigate Them

Background: Majority of the Farmer in Punjab is of small holders and these farmers face a lot of problems in the process of inputs as well as output marketing. In order to provide solutions to the marketing problems of the such small holder farmers the union government came up with the idea of strengthening or initiating the formation of self-help groups, farmer interest groups, farmer cooperatives and clubs etc. for further integrating these entities into the farmer Producer Organisations (FPOs). Methods: For this study data were collected from 150 randomly selected respondents belonging to functional as well as non-functional FPOs. Garrett’s ranking technique was used to identify the most important constraints faced in the process of running FPOs. Result: This study attempted to identify the constraints in the process of operationalizing the FPOs in Punjab and it was found that managerial, socio-psychological, economic and marketing constraints were the major ones. Moreover, lack of trust, cooperation, financial crunch, lack of business management skills, unequal work delegation, ineffective group leadership, delayed payments were the major constraints. Mitigation strategies adopted by the executives of the FPOs were transparency of records, strong association with resource institutes, participatory decision making, efficient conflict management etc. The suggestions of the respondents for making FPOs more vibrant and sustainable were accountability of the resource institutes, capacity buildings of the stakeholders, dissemination of awareness about the functioning of FPOs among the members etc.

Prediction of clinical efficacy of subcutaneous immunotherapy for Artemisia sieversiana pollen allergic rhinitis by serum metabolomics

Specific immunotherapy is the only effective etiological treatment for allergic rhinitis, but subcutaneous immunotherapy has a slow onset and poor compliance. Predicting the clinical efficacy of subcutaneous immunotherapy in advance can reduce unnecessary medical costs and resource waste. This study aimed to identify metabolites that could predict the efficacy of subcutaneous immunotherapy on seasonal allergic rhinitis by serum metabolomics. Patients (n=43) with Artemisia sieversiana pollen allergic rhinitis were enrolled and treated with subcutaneous immunotherapy for one year. Patients were divided into the ineffective group (n=10) and effective group (n=33) according to the therapeutic index. Serum samples were collected before treatment. Metabolomics was determined by liquid chromatography-mass spectrometry combined with gas chromatography-mass spectrometry and analyzed differential compounds and related metabolic pathways. A total of 129 differential metabolites (P<0.05) were identified and 4 metabolic pathways, namely taurine and hypotaurine metabolism, pentose and glucuronate interconversions, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism, were involved. Some metabolites, such as hypotaurine, taurine, and l-alanine, have the potential to become predictive biomarkers for effective subcutaneous immunotherapy.

Prediction of Antidepressant Efficacy by Cognitive Function in First-Episode Late-Life Depression: A Pilot Study.

The response rate of treatment for late-life depression (LLD) is only 25–60%. The cognitive impairment associated with LLD often affects the effectiveness of antidepressants and may has the potential ability to predict response. This study seeks a biomarker for baseline cognitive function to predict efficacy of antidepressants. Sixty patients diagnosed with LLD received escitalopram or sertraline treatment for 8 weeks. Clinical symptom was measured using Hamilton Depression Rating Scale-17 (HAMD-17) and cognitive function was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Trail Making Test (TMT) before and after 8-week treatment. Patients were divided into treatment effective group (TE) and treatment ineffective group (TI) according to reduction rate in scores of HAMD-17 after treatment. Thirty-eight matched healthy controls (HC) were assessed using RBANS and TMT. There was significant decrease of score of RBANS and increase of score of TMT in patients with LLD compared with HC. Regression analysis revealed that change in HAMD-17 score was significantly positively associated with baseline score of picture naming, figure copy, digit span, and delayed memory. The preliminary findings suggested that working memory, attention, visuospatial, language function, and delayed memory should be examined further as a means of providing the useful objective biomarkers of treatment response.Clinical Trials Registration[www.ClinicalTrials.gov], identifier [ChiCTR2100042370].

Diagnostic and Prognostic Significance of microRNA-208a in Acute Myocardial Infarction.

Objective To determine the prognostic and diagnostic significance of microRNA-208a (miR-208a) in acute myocardial infarction (AMI). Methods Totally, 84 AMI patients hospitalized in our hospital between Jan. 2019 and Feb. 2021 were enrolled as the patient group (Pat group), and 50 healthy individuals over same time span as the control group (Con group). qRT-PCR assay was carried out to quantify serum miR-208a in the patients and receiver-operating characteristic (ROC) curves for analysing its diagnostic value in AMI patients and its predictive value in clinical efficacy and adverse events in the patients after therapy. The changes of miR-208a and clinical indexes ((lactate dehydrogenase (LDH), creatine kinase (CK) as well as Creatine kinase-MB (CK-MB)) in the patients before and after therapy were evaluated. Pearson's test was adopted to analyse the associations of miR-208a with clinical indexes. Additionally, the target genes of miR-208a were forecasted. Results The patient group showed a higher miR-208a level than the control group (p < 0.05), and the area under the curve (AUC) of miR-208a in diagnosing AMI was >0.9. After therapy, patients presented notable decreases in serum miR-208a, LDH, CK, and CK-MB (all p < 0.05). Serum miR-208a presented positive associations with LDH, CK, as well as CK-MB both before and after therapy (all p < 0.05). Before therapy, the ineffective group presented a higher miR-208a level than the effective group (p < 0.05), and miR-208a had an AUC of 0.784 in forecasting efficacy. Additionally, the group with adverse events presented a higher miR-208a level than the group without them before therapy (p < 0.05), and miR-208a had an AUC of 0.713 in forecasting adverse events. According to enrichment analysis, the target genes of miR-208a were bound up with signal pathways of cellular senescence, MTOR and Wnt. Conclusion With high expression in AMI cases, miR-208a is a promising potential biomarker for diagnosis and prognosis forecasting of AMI.

Efficacy of Nerve Root Block for the Treatment of Lumbar Spinal Canal Stenosis in Adults Older Than 80 Years of Age.

Background: Patients with advanced lumbar spinal canal stenosis (LCS) often prefer non-operative treatment owing to decreased physiological function and comorbidities. Although the therapeutic value of selective nerve root block (SNRB) for LCS is confirmed, there are few reports of its effectiveness in the elderly. We investigated the efficacy of SNRB for LCS in patients over 80 years of age.Methods: The subjects were 112 patients aged over 80 years (mean age: 84 years; 45 men and 67 women ) with medication-resistant LCS without cauda equina syndrome who underwent SNRB. Cases with acute-onset lumbar disc herniation were excluded. We retrospectively investigated and compared the presence or absence of surgery, effect of SNRB, number of procedures, duration of disease, and magnetic resonance imaging findings. Patients who could avoid the surgery by SNRB were defined as the effective group. Patients whose symptoms were not relieved by SNRB and who underwent surgery and those whose symptoms were not relieved but who continued conservative treatment were defined as the ineffective group. A total of one to seven SNRBs were performed in both groups, and the same spine surgeon performed the entire procedure from SNRB to surgery.Results: There were 86 nonoperative patients (69 effective cases) and 26 operative patients; the overall rate of effectiveness was 61% (69/112 patients). The area of the spinal canal at the responsible level was 108.63 mm2 in the effective group compared with 77.06 mm2 in the ineffective group. This was significantly narrower in the ineffective group (p=0.0094). There was no significant difference in the duration of illness, number of blocks, or hernia complication rate between the groups. No patient experienced severe neuralgia that may have been caused by neuropathy during SNRB.Discussion: Our outcome showed that more than 60% of older patients with LCS showed symptomatic improvement with SNRB. SNRB can be performed relatively safely in the elderly and appears to be a favorable treatment option for older patients with various risks, such as poor general condition.Conclusions: Multiple sessions of SNRB may provide older patients with symptomatic improvement and may be an option for treatment.

Circulating C-X-C Motif Ligand 13 as a Biomarker for Early Predicting Efficacy of Subcutaneous Immunotherapy in Children With Chronic Allergic Rhinitis.

BackgroundC-X-C motif ligand 13 (CXCL13) and B cell-activating factor (BAFF) are proven to be involved in inflammatory diseases, but their role in allergic rhinitis (AR) remains unclear. The aim of this study was to investigate the role of serum CXCL13 and BAFF in AR and their clinical values as objective biomarkers to predict the efficacy of subcutaneous immunotherapy (SCIT).MethodsWe prospectively recruited 90 children with AR treated with SCIT and collected their serum specimens before SCIT. One-year follow-up was conducted for all patients, and they were categorized into effective and ineffective groups based on efficacy. The serum concentrations of CXCL13 and BAFF were detected and compared between the two groups. A validation cohort of 52 responders and 26 non-responders were further assessed for both cytokines and serum CXCL13 and BAFF levels were assayed by enzyme-linked immunosorbent assay (ELISA).ResultsEighty children completed the follow-up schedule, and 56 children were categorized into the effective group and 24 children into the ineffective group. The serum levels of CXCL13 in the effective group were clearly higher than those in the ineffective group (P < 0.05). Receiver operating characteristic (ROC) curves revealed the potential values of CXCL13 as a biomarker in predicting the response of SCIT. Further, in the validation cohort, ELISA results demonstrated that serum CXCL13 levels were increased in responders than non-responders (P < 0.05). ROC curves showed good accuracy of serum CXCL13 in predicting the efficacy of SCIT.ConclusionOur discovery–validation study demonstrated that circulating CXCL13 might serve as a novel biomarker to predict the outcome of SCIT in childhood AR. The findings indicated that CXCL13 was involved in the pathological mechanisms of AR and made help to the fundamental therapeutic mechanism of SCIT.

Relationship between sexual function improvement and treatment satisfaction by TRT in LOH patients

ABSTRACT Introduction In the treatment of LOH (late-onset hypogonadism) syndrome, TRT (testosterone replacement therapy) is effective for various LOH related symptoms including sexual function. However, among Japanese population, sexual desire is not always strong in elderly men. Even if the patients do not have opportunities of sexual intercourse, TRT may still be beneficial for other symptoms derived from LOH syndrome. Objectives To examine patients’ satisfaction by TRT, we examined the relationship between TRT effect on sexual function and whole treatment satisfaction in our patient cohort. Methods Patients who have LOH symptoms and low serum free-testosterone (FT) levels were diagnosed as LOH syndrome. FT was diagnosed as “low” when &amp;lt;8.5pg/ml, while diagnosed as “borderline” when 8.5-11.8pg/ml. For TRT, testosterone enanthate 250mg/2-4weeks was given for more than 6 months. SHIM (Sexual Health Inventory for Men) score and our original questionnaire asking whether they are satisfied with the treatment were examined. Results Median patients’ age was 54 years (n=95). Before treatment, total testosterone was 4.5±1.8ng/ml and free testosterone was 6.2±2.3pg/ml. The majority of chief complaint before treatment were psychological or somatic symptoms. After treatment, SHIM score showed significant improvement in all questions of 1 to 5, and total SHIM score increased from 6.4 to 9.4. The number of patients who have few opportunities for sexual intercourse (0 point for SHIM Q3.4.5) decreased from 66% to 48% after treatment. Using the questionnaire for patients’ satisfaction, 71% were classified into the effective group. The number of patients who still had few opportunities of sexual intercourse after treatment was 39% in the effective group and 71% in the ineffective group. Conclusions From the point of patient satisfaction, TRT for LOH syndrome was effective in 71% of patients. Almost 40 percent of the patients who were satisfied with the treatment answered that there were few opportunities of sexual intercourse even after treatment. The improvement in sexual function may not be always required in a cohort of our patient population. Disclosure Work supported by industry: no.

Long-term outcomes of testosterone replacement therapy for patients with late-onset hypogonadism syndrome

ABSTRACT Introduction and Objective Testosterone replacement therapy (TRT) is effective for patients with late onset hypogonadism (LOH) syndrome. However, treatment compliance of long-term TRT for LOH syndrome patients remains unclear. We investigated the long-term outcomes of TRT for patients with LOH syndrome. Methods Forty-two patients (age: mean 55.9, SD 10.2) were diagnosed and then underwent TRT using testosterone enanthate between January 2010 and December 2014 at our hospital. We investigated long-term compliance of TRT, changes of subjective data, i.e. aging male symptom (AMS score) and, international index of erectile function (IIEF5), and objective data, i.e. free testosterone level and, serum PSA level, retrospectively. This study was approved by the Ethics Committee of our facility (Approval No.3043). Results At the time of TRT initiation, AMS score (mean, as mentioned below) was 55.1 (SD 10.1) points, IIEF5 was 7.9 (SD 3.8) points, free testosterone level was 5.8 (SD 1.9) pg/ml, and serum PSA level was 1.3 (SD 1.6) ng/ml. The duration of TRT was 27.7 (SD 29.4) months. Dose of testosterone enanthate was 183.1 (SD 69.2) mg/4weeks. AMS score and IIEF5 were significantly improved after TRT. Adverse events (AE) occurred in 9.6% of the patients, but these were no severe AE. TRT continuation rate was 50.0% at 12 months, 40.5% at 24 months, 35.7% at 36 months, and 33.3% at 48 months. In addition, there was a significantly higher rate in the group with severe AMS scores than in mild-moderate groups. In the discontinuation group of 25 patients (59.5%), the duration of treatment was significantly longer in the improvement group than in the ineffective group. Conclusions Testosterone replacement therapy for late onset hypogonadism syndrome is a safe and effective long-term treatment. The treatment continuation analysis showed that patients with severe AMS scores and better effect of TRT requested long-term treatment. Disclosure Work supported by industry: no.

Association of lymphocyte subsets with efficacy and prognosis of immune checkpoint inhibitor therapy in advanced non-small cell lung carcinoma: a retrospective study

BackgroundImmune checkpoint inhibitors (ICIs) have achieved promising effects in patients with non-small cell lung cancer (NSCLC). However, not all patients with NSCLC benefit from immunotherapy. There is an urgent need to explore biomarkers that could predict the survival outcomes and therapeutic efficacy in advanced NSCLC patients treated with immunotherapy. In this study, we aimed to assess the changes in peripheral blood lymphocyte subsets and their association with the therapeutic efficacy and clinical prognosis of advanced NSCLC patients treated with immunotherapy.MethodsA total of 276 patients with advanced NSCLC were enrolled. Peripheral blood lymphocyte subsets including CD4+ T cells, CD8+ T cells, CD4+/CD8+ ratio, NK cells, Tregs and B cells were collected before any treatment, before immunotherapy or chemotherapy, and after 4 cycles of immunotherapy or chemotherapy. T-test was used to analyze the factors influencing lymphocyte subsets and their changes before and after therapy. Logistic regression was used to plot ROC curves and analyze the relationship between lymphocyte subsets and therapeutic efficacy. Log-rank test and Cox regression model were used to evaluate the relationship between lymphocyte subsets and progression-free survival (PFS).ResultsGender, distant metastasis, and EGFR mutation status are known to affect the proportion of peripheral blood lymphocyte subsets in patients with advanced NSCLC. The proportions of CD4+ T cells, CD8+ T cells, Tregs and B cells were found to decrease after chemotherapy as compared to the baseline. The proportion of CD4+ T cells, CD8+ T cells, CD4+/CD8+ ratio, NK cells and Tregs were higher after immunotherapy than after chemotherapy. Compared to the baseline, the effective group showed significant increase in the proportions of CD4+ T cells, CD4+/CD8+ ratio, NK cells and Tregs, and the number of CD8+ T cells was significantly lower in the peripheral blood after 4 cycles of immunotherapy. On the contrary, the ineffective group did not show any significant differences in the above parameters. Baseline CD4+ T cells and NK cells were independent predictors of immunotherapy efficacy and PFS. Baseline Tregs were independent predictor of immunotherapy efficacy.ConclusionImmune checkpoint inhibitors induced changes in the proportion of peripheral blood lymphocyte subsets in patients that responded well to immunotherapy. The levels of the different lymphocyte subsets could serve as valuable predictive biomarkers of efficacy and clinical prognosis for NSCLC patients treated with immunotherapy.

Relationship between gut microbiome characteristics and the effect of nutritional therapy on glycemic control in pregnant women with gestational diabetes mellitus.

The purpose of this study was to explore the relationship between the characteristics of gut microbiome and the effect of medical nutrition therapy (MNT) on glycemic control in pregnant women with gestational diabetes mellitus (GDM). Seventy-four pregnant women newly diagnosed with GDM received MNT for one-week. The effect of glycemic control was evaluated by fasting and 2-hour postprandial blood glucose; and stool samples of pregnant women were collected to detect the gut microbiome before and after MNT. We used a nested case-control study design, with pregnant women with GDM who did not meet glycemic standards after MNT as the ineffective group and those with an age difference of ≤5 years, matched for pre-pregnancy body mass index (BMI) 1:1, and meeting glycemic control criteria as the effective group. Comparison of the gut microbiome characteristics before MNT showed that the ineffective group was enriched in Desulfovibrio, Aeromonadales, Leuconostocaceae, Weissella, Prevotella, Bacillales_Incertae Sedis XI, Gemella and Bacillales, while the effective group was enriched in Roseburia, Clostridium, Bifidobacterium, Bifidobacteriales, Bifidobacteriaceae, Holdemania and Proteus. After treatment, the effective group was enriched in Bifidobacterium and Actinomycete, while the ineffective group was enriched in Holdemania, Proteus, Carnobacteriaceae and Granulicatella. In conclusion, the decrease in the abundance of characteristic gut microbiome positively correlated with blood glucose may be a factor influencing the poor hypoglycemic effect of MNT in pregnant women with GDM. Abundance of more characteristic gut microbiome negatively correlated with blood glucose could help control blood glucose in pregnant women with GDM.

Screening of Prognostic Biomarkers for Stereotactic Body Radiation Therapy in Primary Liver Cancer.

ObjectiveSo far there are still no effective immediate-early markers for assessing the efficacy of Stereotactic Body Radiation Therapy (SBRT). To find effective biomarkers for accurate assessment of the efficacy of SBRT in patients with primary liver cancer, we conducted this study including retrospective part and prospective part.Material and Methods589 patients with primary liver cancer were included at Ruikang Hospital affiliated to Guangxi Medical University from January 2012 to December 2018. Follow-up was conducted, clinical information and a total of 17 patients with 51 blood samples (before SBRT, before discharge and 2 months after SBRT) were collected. mRNAs profiles on 2 patients with 6 blood samples were detected by high-throughput sequencing, followed by qPCR verification on 15 patients with 45 blood samples.ResultsThe commonly used serum biomarkers such as AFP, CEA, and CA125 shown low prognostic value in distinguishing survival group and death group, indicated by low AUC (less than .7) and Youden indexes (less than .5). Based on high-throughput sequencing of test group and qPCR detection of another verification group, we found 16 up-regulated and 12 downregulated genes after SBRT. Among them, ADIPOR1 and EPB42 showed significantly different between effective and ineffective group after SBRT, ROC suggested that based on the optimal threshold of .5838, ADIPOR1 shown a sensitivity of 100% and a specificity of 83.33% to distinguish effective from ineffective group. And EPB42 had a sensitivity of 75% and a specificity of 100% at the optimal threshold of 1.3817. In addition, GSEA showed that high expression of ADIPOR1 was mainly related to Mismatch repair, Circadian rhythm, Protein processing in endoplasmic reticulum, DNA replication, and Fanconi anemia pathways.ConclusionADIPOR1 in whole blood is a promising candidate to act as prognostic biomarker for predication of SBRT outcomes in primary liver cancer patients.

Pharmacokinetic study of anti-human T-cell porcine immunoglobulin combined with cyclosporine A immunosuppressive therapy in patients with severe aplastic anemia

目的研究抗人T细胞猪免疫球蛋白（p-ATG）在重型再生障碍性贫血（SAA）患者的药物代谢特点。方法2017年2月至2017年12月纳入接受p-ATG联合环孢素A（CsA）免疫抑制治疗的SAA患者，p-ATG剂量为20 mg·kg−1·d−1，持续12 h静脉给药，连续5 d。应用三抗体夹心ELISA方法检测p-ATG血药浓度，药代动力学分析软件拟合，计算相关参数并绘制药物代谢曲线。随访记录不良事件并评估治疗后6个月血液学反应。结果入组16例接受p-ATG治疗的SAA患者，女8例，男8例，中位年龄22（12～49）岁，中位体重62.5（37.5～82.0）kg。其中14例可进行p-ATG药代动力学评价。p-ATG在体内分布为二室模型，平均药物浓度峰值时间（Tmax）为（5.786±2.486）d，平均峰浓度（Cmax）为（616±452）mg/L，平均半衰期（T1/2）为（10.479±8.242）d。平均药物浓度时间曲线下面积［AUC（0-t）］为（5.807±3.236）mg/L·d。14例患者治疗后6个月8例获得血液学反应，有效组与无效组患者AUC（0-t）分别为（7.50±3.26）mg/L·d对（4.50±2.18）mg/L·d，Cmax分别为（627±476）mg/L对（584±382）mg/L。结论连续5 d输注后p-ATG血药浓度达峰值，后缓慢下降，半衰期10.479 d，用药后60 d体内检测到残存药物浓度。尚不能得出药物代谢与疗效及不良反应的关系。

Distinct brain structural-functional network topological coupling explains different outcomes in tinnitus patients treated with sound therapy.

Topological properties, which serve as the core of the neural network, and their couplings can reflect different therapeutic effects in tinnitus patients. We hypothesized that tinnitus patients with different outcomes after sound therapy (narrowband noise) would have distinct brain network topological alterations. Diffusion tensor imaging and resting‐state functional magnetic resonance imaging (fMRI) were prospectively performed in 60 patients with idiopathic tinnitus and 57 healthy controls (HCs). Graph‐theoretical network analyses of structural connectivity (SC), functional connectivity (FC), and SC and FC coupling were performed. Associations between clinical performance and graph‐theoretical features were also analyzed. Treatment was effective (effective group; EG) in 28 patients and ineffective (ineffective group; IG) in 32 patients. For FC, the patients in the EG showed higher local efficiency than patients in the IG. For SC, patients in both the EG and IG displayed lower normalized characteristic path length, characteristic path length, and global efficiency than the HCs. More importantly, patients in the IG had higher coupling than the HCs, whereas there was no difference in coupling between patients in the EG and HCs. Additionally, there were significant associations between the SC features and clinical performance in patients in the EG. Our findings demonstrate that tinnitus patients exhibited significant brain network topological alterations, especially in the structural brain network. More importantly, patients who demonstrated different curative effects showed distinct SC‐FC topological coupling properties. SC‐FC coupling could be an indicator that could be used to predict prognoses in patients with idiopathic tinnitus before sound therapy.

Deep Learning-Based Electrocardiograph in Evaluating Radiofrequency Ablation for Rapid Arrhythmia.

This study is aimed at analyzing the important role of deep learning-based electrocardiograph (ECG) in the efficacy evaluation of radiofrequency ablation in the treatment of tachyarrhythmia. In this study, 158 patients with rapid arrhythmia treated by radiofrequency ablation were divided into effective treatment group (142 cases) and ineffective treatment group (16 cases). ECG examination was performed on all patients, and the indicators of ECG examination were quantified by the deep learning-based convolutional neural network model. The indicators of ECG examination of the effective treatment group and the ineffective treatment group were compared. The results showed that compared with the ineffective treatment group, the end-systolic volume (ESV), end-diastolic volume (EDV), end-systolic volume index (ESVI), and end-diastolic volume index (EDVI) of the effective treatment group were significantly decreased, and the left ventricular ejection fraction (LVEF) was significantly increased (P < 0.05). After radiofrequency ablation, the ventricular rate of patients in the effective treatment group was significantly lower than that of the ineffective treatment group at 12 h and 24 h after treatment (P < 0.05). In addition, compared with patients in the ineffective treatment group, the QT dispersion of the ECG in the effective treatment group was significantly higher (P < 0.05). The accuracy, specificity, and sensitivity of ECG in evaluating the therapeutic effect of patients with tachyarrhythmia were 86.81%, 84.29%, and 77.27%, respectively. The area under the curve was determined as 0.798 according to the receiver operating characteristic (ROC) curve of the subjects. In summary, indicators of ECG examination based on deep learning can provide auxiliary reference information for the efficacy evaluation of radiofrequency ablation in the treatment of tachyarrhythmia.

Association Between Antidepressant Efficacy and Interactions of Three Core Depression-Related Brain Networks in Major Depressive Disorder.

BackgroundThe central executive network (CEN), salience network (SN), and default mode network (DMN) are the three most studied depression-related brain networks. Many studies have shown that they are related to depression symptoms and treatment effects. However, few studies have related these three networks and their activity frequency bands to depressive symptoms and treatment efficacy.MethodsSixty-six medication-free patients with major depressive disorder (MDD) were enrolled. Magnetoencephalography (MEG) was administered at baseline to calculate imaging indicators such as the power and functional connectivity (FC) of each brain network. The Hamilton Rating Score for Depression (HRSD-17) was assessed at baseline and weekly for 4 weeks. Pearson correlation and receiver operating characteristic curves (ROC) analyses were used to explore the relationship between brain imaging indicators and antidepressant efficacy.ResultsThe difference between therapeutically effective and ineffective groups was mainly manifested in the beta power of the SN. The FC of beta waves between the three networks was related to antidepressant efficacy, with ROC analysis results of AUC = 0.794, P = 0.004, sensitivity = 76.7%, and specificity = 81.8%.LimitationsThe sample size was small and a healthy control group was not available.ConclusionsThe interaction between the three networks is related to antidepressant efficacy and the relief of depressive symptoms.

Utility of GPR68 and TIL in TPF-induced chemotherapy and prognosis evaluation in middle-advanced hypopharyngeal squamous cell carcinoma

Objective: To evaluate the roles of G Protein-Coupled Receptor 68 (GPR68) and tumor infiltrating lymphocytes (TIL) in TPF-(paclitaxel, cisplatin and 5-fluorouracil) induced chemotherapy for middle-advanced hypopharyngeal squamous cell carcinomas. Methods: A total of 31 patients with middle-advanced hypopharyngeal squamous cell carcinoma before TPF-inducted chemotherapy were enrolled from September 2012 to November 2017 in Beijing Tongren Hospital, Capital Medical University, including 28 males and 3 females, aged 43 to 71 years old. The expression of GPR68 and tumor infiltrating CD4+and CD8+T cells before chemotherapy was detected by immunohistochemical staining, and the relationships between GPR68 expression and clinical features, chemotherapy efficacy and overall survival (OS) were analyzed using t-test. Results: After 3 cycles of chemotherapy, there were 4, 14, 10 and 3 patients respectively with complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). The positive rates of GPR68 and CD8 were 25% and 40% respectively in the effective group (CR+PR), while 50% and 15% in the ineffective group (SD+PD), with statistically significant differences between two groups (t=5.17 and 12.86,P<0.001). Linear regression analysis showed that GPR68 was negatively correlated with CD8+T cells (r=-0.64,P<0.001). There was no significant correlation between the CD4 expression and TPF efficacy (P>0.05). The mean OS was 12.5 months in patients with high-expressed GPR68 and 25.0 months in patients with low-expressed GPR68, with a statistically significant difference (P=0.005). And mean OS was 25.0 months in patients with high-expressed CD8 and 14.5 months in low-expressed CD8, with a statistically significant difference (HR=2.58, P=0.019). Cox regression analysis showed that GPR68 and CD8+T cells were significant prognostic factors (OR(95%CI)=3.27(2.46-5.97) and 1.53(0.78-1.82), all P<0.05), while CD4 had no significant effect on prognosis (P>0.05). Conclusion: GPR68 and CD8+T cells are expected to be biomarkers for evaluating the efficacy and prognosis of TPF-induced chemotherapy in patients with middle-advanced hypopharyngeal squamous cell carcinoma.

Relationship between right ventricular geometry and function parameters and tricuspid annuloplasty efficacy

Abstract Funding Acknowledgements Type of funding sources: None. INTRODUCTION The prevalence of untreated moderate and severe functional tricuspid regurgitation (TR) eventually leads to heart failure and is associated with poor prognosis. Therefore, tricuspid annuloplasty (TA) is offered as a first-line treatment for significant functional TR. However, studies to investigate factors leading to recurrent TR after TA are still scarce. AIM The aim is to investigate the relationship between right ventricular (RV) geometry and function parameters and recurrent TR after TA. METHODS Prospective observational cohort study enrolled patients with moderate or severe functional TR caused by left heart valvular disease who underwent surgical tricuspid valve (TV) repair. The dominant pathology was severe mitral regurgitation. Patients with ischemic heart disease (assessed by coronary angiography) were excluded from the analysis. The current study included 60 patients with full sets of preoperative 2D and 3D echocardiographic parameters. Echocardiographic quantification included the following parameters: the RV and RA geometry, functional (velocity of the tricuspid annular systolic motion [S’] and RV fractional area change [FAC], tricuspid annular plane systolic excursion [TAPSE] and RV ejection fraction (EF)). The severity of TR was measured quantitatively according to the recent ESC guidelines. Patients were divided into two groups according to the outcomes of TA: effective (38 pts.) and ineffective (22 pts.) TV repair. Effective TA was considered if TR 1 year after surgery was mild, while ineffective – TR was moderate or severe (recurrent TR). The statistical analysis was performed using SPSS statistical software, univariate logistic regression was used. RESULTS In 60 patients of current analysis 67% were female, mean age was 67 ± 9 years. The odds ratio for risk of ineffective TA are shown in Table 1. Age, gender, body mass index, left ventricular (LV) functional, as well as left atrial parameters did not differ between effective and ineffective TA groups. When analysing echocardiographic parameters in univariate logistic regression, RV and RA geometry, TV annulus diameter had predictive value for ineffective TA. Preoperative effective regurgitant orifice area (EROA) did not differ significantly between two groups (ineffective TA vs. effective TA; 31 [60] mm2 vs. 24 [17] mm2, p = 0.308 respectively). Meanwhile, none of the RV functional parameters were significant. CONCLUSION Recurrent moderate or severe functional tricuspid regurgitation after tricuspid annuloplasty is associated with preoperative tricuspid annulus size, RA and RV geometry, but not with changes of RV function. Abstract Figure.

Analysis of the tumor microenvironment in ineffective patients of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma.

468 Background: Atezolizumab plus bevacizumab (Atezo + Bev) has been the standard treatment for frontline systemic therapy in advanced hepatocellular carcinoma (HCC). Immune check point inhibitors and its combination therapies are completely ineffective in some population of patients based on previous reports in several other malignancies. Regarding the results of a phase III trial (IMbrave 150) and several reports from real world practice, ̃20% of patients were determined to be progression disease (PD) as the best radiological response to Atezo + Bev in patients with advanced HCC. In this study, we analyzed the tumor microenvironment using tumor biopsy samples obtained before starting Atezo + Bev to clarify the mechanism of resistance to Atezo + Bev in patients with advanced HCC. Methods: This study enrolled patients with advanced HCC treated with Atezo + Bev at Chiba University Hospital between October 2020 and April 2021. We defined an ineffective group as patients with PD within 2 months according to RECIST version 1.1. The analysis of the tumor microenvironment in this study was performed using the nCounter PanCancer IO 360TM Panel. Results: Of 56 patients who initiated Atezo + Bev during the study period, biopsy samples with a sufficient amount of tumor tissue for analysis were obtained from 30 patients by percutaneous needle biopsy immediately before administering Atezo + Bev. According to radiological assessments, 7 and 23 patients were classified as ineffective and effective groups, respectively. Comparing baseline characteristics of the two groups, the rate of alpha fetoprotein (AFP) ≥ 400 ng/mL was significantly higher in the ineffective group (ineffective group: 85.7%; effective group: 34.8%; p = 0.031). According to gene expression analyses, 101 of 775 genes were differentially expressed between the two groups. Gene set enrichment analysis showed that antigen presentation, cytokine and chemokine signaling, cytotoxicity, immune cell adhesion and migration, and interferon signaling had a lower expression in the ineffective group. Conversely, a higher expression of cell proliferation signaling was observed in the ineffective group. In this cohort, the expression of Wnt signaling showed no significant difference between the two groups. We calculated the cytolytic activity based on the expression of granzyme A and perforin 1, and it was significantly lower in the ineffective group (6.1 in the effective group and 5.3 in the ineffective group, p = 0.013). Conclusions: Analysis of the tumor microenvironment found differences of several gene expressions and those of signaling between the ineffective and effective groups of Atezo + Bev in patients with advanced HCC. The ineffectiveness of Atezo + Bev is due to the reduced action of T cell infiltration and its immune response to tumor.