Objective:To investigate the effects of PD-1 monoclonal antibody therapy on the peripheral and local immune microenvironment of patients with microsatellite instability-high(MSI-H)rectal cancer.Methods:Samples of peripheral blood and tumor biopsy were collected from a patient with MSI-H rectal cancer before and after PD-1 monoclonal antibody treatment.The samples were dissociated into single-cell suspensions using a combination of enzymatic and mechanical methods.Immune-related marker expression on peripheral and tumor-infiltrating im-mune cells was analyzed using single-cell mass cytometry(CyTOF).Results:According to the results of CyTOF analysis,CD45+immune cells in the peripheral blood and tumor tissues were categorized into 39 and 34 cell subsets,respectively,before and after PD-1 monoclonal antibody treatment(the correlation is unclear and ambiguous).After PD-1 monoclonal antibody treatment,differences were observed in the relative abundance of immune cell subsets:B cells significantly decreased in the peripheral blood,while B cells and γδT cells significantly increased in the tumor tissue;neutrophils significantly decreased,and the proportion of CD4+TEM cells in T cell subsets significantly increased,whereas CD4+Treg cells significantly decreased.Additionally,there were differences in the expression of immune-related markers in multiple immune cell subsets in both peripheral blood and tumor tissues,with CCR6 showing a significant increase in expression across all subsets,while ICOS and PD-1 expressions in T cell subsets were significantly reduced(the specific tissues for these cells or factors are unclear).Conclusion:After PD-1 monoclonal antibody treatment in MSI-H rectal cancer,changes occurred in the composition of immune cells and the expression of immune-related markers in both peripheral blood and tumor tissues.This study reveals the dynamic adjustment of the immune microenvironment and provides important evidence for understanding the therapeutic mechanism of PD-1 monoclonal antibodies.

Zona Incerta ; Prefrontal Cortex ; Fear ; Neural Pathways

Objectives: To summarize the clinical phenotypes and the variation spectrum of ATP7B gene in Chinese children with Wilson's disease (WD) and to investigate their significance for early diagnosis. Methods: Retrospective analysis was performed on the clinical data of 316 children diagnosed as WD in Guangzhou Women and Children's Medical Center during the period from January 2010 to June 2021. The general situations, clinical manifestations, lab test results, imaging examinations, and ATP7B gene variant characteristics were collected. The patients were divided into asymptomatic WD group and symptomatic WD group based on the presence or absence of clinical symptoms at the time that WD diagnosis was made. The χ² test, t test or Mann-Whitney U test were used to compare the differences between groups. Results: Among the 316 children with WD, 199 were males and 117 were females, with the age of 5.4 (4.0, 7.6) years at diagnosis; 261 cases (82.6%) were asymptomatic with the age of 4.9 (3.9, 6.4) years; whereas 55 cases (17.4%) were symptomatic with the age of 9.6 (7.3, 12.0) years. The main symptoms invloved liver, kidney, nervous system, or skin damage. Of all the patients, 95.9% (303/316) had abnormal liver function at diagnosis; 98.1% (310/316) had the serum ceruloplasmin lever lower than 200 mg/L; 97.7% (302/309) had 24-hour urine copper content exceeding 40 μg; only 7.4% (23/310) had positive corneal K-F rings, 8.2% (23/281) had abnormal MRI signals in the lenticular nucleus, and all of them had symptoms of damage in liver, kidney or nervous system. Compared with the group of symptomatic WD, asymptomatic group had higher levels of serum alanine aminotransferase and lower levels ceruloplasmin and 24-hour urine copper [(208±137) vs. (72±78) U/L, (55±47) vs. (69±48) mg/L, 103 (72, 153) vs. 492 (230, 1 432) μg; t=9.98, -1.98, Z=-4.89, all P<0.001]. Among the 314 patients completing genetic sequencing, a total of 107 mutations in ATP7B gene were detected, of which 10 are novel variants, and 3 cases (1.0%) had large heterozygous deletion (exons 10 to exon 11) in ATP7B gene. The percentage of missense mutation in asymptomatic WD children was significantly higher than that in symptomatic WD (81.5% (422/518) vs. 69.1% (76/110), χ²=8.47, P<0.05). WD patients carrying homozygous variant of c.2 333G>T had significantly low levels of ceruloplasmin than those not carrying this variant ((23±5) vs. (61±48) mg/L, t=-2.34, P<0.001). Conclusions: The elevation of serum ALT is an important clue for early diagnosis of WD in children, while serum ceruloplasmin and 24-hour urine copper content are specific markers for early diagnosis of WD. In order to confirm the diagnosis of WD, it is necessary to combine the Sanger sequencing with multiplex ligation-dependent probe amplification or other testing technologies.
Ceruloplasmin/metabolism* ; Child ; Child, Preschool ; Copper/metabolism* ; Copper-Transporting ATPases/genetics* ; Female ; Hepatolenticular Degeneration/genetics* ; Humans ; Male ; Mutation ; Phenotype ; Retrospective Studies

OBJECTIVE: To explore the association between postoperative C-reactive protein (CRP) levels and the occurrence of postoperative atrial fibrillation in patients undergoing cardiopulmonary bypass surgery. METHODS: We retrospectively analyzed the data of 550 patients undergoing cardiopulmonary bypass surgery in our hospital from September, 2018 to May, 2021, and after screening against the exclusion criteria, 363 patients were selected for further analysis. Univariate analysis was used to analyze the correlation of age and early postoperative CRP level with the occurrence of postoperative atrial fibrillation, and Chi-square test was used to explore the correlation of gender, disease type, and comorbidity with postoperative atrial fibrillation followed by multivariate analysis of the data using a binary logistic regression model. RESULTS: The 363 patients enrolled in this study included 247 with valvular disease, 42 with aortic dissection, 37 with coronary heart disease, and 37 with congenital heart disease, with a median postoperative CRP level of 88.65 mg/L and a median age of 57 years (range 5-77 years). Postoperative atrial fibrillation occurred in 101 (27.82%) of the patients, who were subsequently divided into atrial fibrillation group and sinus group. Univariate and multivariate correlation analyses showed that early postoperative elevation of CRP level was an important factor contributing to the occurrence of postoperative atrial fibrillation. CONCLUSION Early postoperative elevation of CRP level is associated with the occurrence of atrial fibrillation following cardiopulmonary bypass surgery.
Adolescent ; Adult ; Aged ; Atrial Fibrillation/etiology* ; C-Reactive Protein/analysis* ; Cardiopulmonary Bypass/adverse effects* ; Child ; Child, Preschool ; Coronary Artery Bypass ; Humans ; Middle Aged ; Postoperative Complications/epidemiology* ; Retrospective Studies ; Risk Factors ; Young Adult

Ophiopogonis Radix is an important Yin-nourishing drug in traditional Chinese medicine(TCM), with the effects of nourishing Yin, promoting fluid production, clearing away heart-fire, and relieving restlessness. It is widely used in clinical practice due to its multiple chemical components and pharmacological effects. The technique "mapping knowledge domains" is an effective tool to quantitatively and objectively visualize the development frontiers and trends of certain disciplines. In this study, TCM research papers related to Ophiopogonis Radix were retrieved from Web of Science(WoS) and CNKI, and the research institutions, journals, and keywords involved were visualized and analyzed using the scientometric software CiteSpace. The co-occurrence network of related research on Ophiopogonis Radix was constructed, and the Ophiopogonis Radix-disease-target network was plotted using Cytoscape 3.8.2. The hot topics in Chinese and English papers were analyzed and the shortcomings in the research on Ophiopogonis Radix were summed up. Furthermore, the development trends were discussed. A total of 1 403 Chinese papers and 292 English papers were included in this study. The analysis of research institutions showed that Beijing University of Chinese Medicine and China Pharmaceutical University were the two research institutions with the largest numbers of papers published. The analysis of journals showed that Hebei Journal of Traditional Chinese Medicine and Journal of Asian Natural Products Research were the two journals with the highest numbers of papers concerning Ophiopogonis Radix. The keyword analysis showed that the research contents of Chinese papers focused on the analysis of medication regularity and clinical observation trials, while the English papers focused on component analysis and pharmacological investigation. Data mining and apoptosis-based pharmacological mechanism might be the research trends in the future.
China ; Data Mining ; Humans ; Medicine, Chinese Traditional ; Plant Roots ; Publications

Objective:To explore the changes of sympathetic and parasympathetic activity in children with chest pain and/or chest distress of unknown cause based on their plasma catecholamine and heart rate variability indexes, and to analyze the predictive value of each index in diagnosing pediatric sympathetic excitation-related chest pain and/or chest distress by used receiver operating characteristics (ROC) curve analysis.Methods:Fifty-seven children who complained of unexplained chest pain and/or chest distress and had no organic diseases according to routine examinations in the Chengdu Women′s and Children′s Hospital from June 2017 to June 2019 were enrolled in the study group.There were 22 males and 35 females, aged 5-15 years old[(8.40±0.35) years old]. Meanwhile, 54 healthy children in the same period were enrolled in the healthy control group, including 21 males and 33 females, aged 5-15 years old (8.87±0.36) years old]. The disease history enquiring, physical examination, chest X-ray, 12-lead electrocardiogram, echocardiogram, blood routine test and biochemical test excluded the organic heart, lung, digestive tract and chest wall diseases in both groups.Their blood samples were collected to detect catecholamine and they were monitored by dynamic electrocardiogram.SPSS 25.0 software was used for statistical analysis and ROC curve analysis.Results:The study group exhibited higher dopamine, adrenaline and norepinephrine levels than those in the healthy control group[(0.83±0.04) nmol/L vs.(0.54±0.03) nmol/L, (0.76±0.04) nmol/L vs.(0.56±0.03) nmol/L and(3.59±0.18) nmol/L vs.(2.51±0.15) nmol/L], and the differences were statistically significant( t=4.906, 3.611, 4.596, all P<0.01). The levels of standard deviation of NN intervals, standard deviation of all mean 5-minutes NN intervals, standard deviation of all NN intervals for all 5-minute segments of 24 hours, root mean squared successive difference and proportion of NN 50 in the total number of NN intervals in the study group were lower than those in the healthy control group [(110.49±2.81) ms vs.(132.13±2.55) ms, (86.37±3.26) ms vs.(118.96±2.00) ms, (33.46±2.21) ms vs.(68.91±1.29) ms, (37.63±1.22) ms vs.(48.93±1.75) ms and(17.37±1.45)% vs.(22.22±1.61)%], and the differences were statistically significant( t=-5.710, -8.419, -13.862, -5.354, -2.245, all P<0.05). The area under the curve of plasma dopamine, adrenaline and norepinephrine in the diagnosis of pediatric sympathetic excitation-related chest pain and/or chest distress were 0.753, 0.689 and 0.746, respectively, higher than that of all heart rate variability indexes. Conclusions:Children′s unexplained chest pain and/or chest distress is highly related with autonomic nervous dysfunction (increased sympathetic activity and decreased parasympathetic activity). The level of plasma catecholamine can be used to reflect the changes of sympathetic activity in these children and diagnose sympathetic excitation-related chest pain and/or chest distress.Psychological counseling and relaxation therapy are supposed to be effective in redu-cing sympathetic activity, improving subjective symptoms and elevating their quality of life.

Objective: To analyse the clinical history, laboratory tests and pathological data of a patient who suffered from novel coronavirus pneumonia(COVID-19) and provide reference for the clinical treatment of similar cases. Methods: Data of clinical manifestation, laboratory examination, bronchoscopy, echocardiography and cardiopulmonary pathological results were retrospectively reviewed in a case of COVID-19 with rapid exacerbation from mild to critical condition. Results: This patient hospitalized at day 9 post 2019 novel coronavirus(2019-nCoV) infection, experienced progressive deterioration from mild to severe at day 12, severe to critical at day 18 and underwent extracorporeal membrane oxygenation(ECMO) and continuous renal replacement therapy(CRRT) as well as heart lung transplantation during day 28-45 post infection, and died at the second day post heart and lung transplantation. The patient had suffered from hypertension for 8 years. At the early stage of the disease, his symptoms were mild and the inflammatory indices increased and the lymphocyte count decreased continuously. The patient's condition exacerbated rapidly with multi-organ infections, and eventually developed pulmonary hemorrhage and consolidation, pulmonary hypertension, right heart failure, malignant ventricular arrhythmias, liver dysfunction, etc. His clinical manifestations could not be improved despite viral RNAs test results became negative. The patient underwent lung and heart transplantation and finally died of multi organ failure at the second day post lung and heart transplantation. Pathological examination indicated massive mucus, dark red secretions and blood clots in bronchus. The pathological changes were mainly diffused pulmonary hemorrhagic injuries and necrosis, fibrosis, small vessel disease with cardiac edema and lymphocyte infiltration. Conclusions: The clinical course of severe COVID-19 can exacerbate rapidly from mild to critical with lung, liver and heart injuries.
Betacoronavirus ; COVID-19 ; Coronavirus Infections/pathology* ; Fatal Outcome ; Hemorrhage/virology* ; Humans ; Lung/pathology* ; Myocardium/pathology* ; Pandemics ; Pneumonia, Viral/pathology* ; Retrospective Studies ; SARS-CoV-2

Background:Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD).The study is to evaluate the efficacy and safety of tACS treating MDD.Methods:This is an 8-week,double-blind,randomized,placebo-controlled study.Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min,77.5-Hz,15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4),following a 4-week observation period (week 8).The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8.Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17,the proportion of participants having improvement in the clinical global impression-improvement,the change in HDRS-17 score (range,0-52,with higher scores indicating more depression) over the study,and variations of brain imaging and neurocognition from baseline to week 4.Safety will be assessed by vital signs at weeks 4 and 8,and adverse events will be collected during the entire study.Discussion:The tACS applied in this trial may have treatment effects on MDD with minimal side effects.