Circulating tumor cells(CTCs)are cells that dissociate from the tumor tissue and enter the lymphatic system or bloodstream with close association with tumor metastasis and recurrence.CTCs contain complete pathological information,which can be extracted by isolation,enrichment,and analysis of the CTCs to guide cancer diagnosis and treatment,thereby significantly improving the monitoring efficiency and prognosis of cancer.Compared with tissue biopsy,liquid biopsy with CTCs as a biomarker enables specific and dynamic detection of tumor growth with a less painful experience.For detection of CTCs,the cells must be captured from body fluids,followed then by their release and enrichment.This review summaries the latest research progress in responsive isolation of CTCs(e.g.with light,dielectrophoresis,acoustophoresis and magnetophoresis),chemical isolation(specific molecules and topological structure)and responsive release(e.g.,light,electric,thermal,pH,enzyme responsiveness,and substrates break).Responsive isolation utilizes the differences in physical properties between CTCs and blood cells,while chemical isolation utilizes specific recognition mechanisms to capture the CTCs.These techniques result in low cell damage with a high specificity to facilitate further analysis.Currently,CTC detection has been applied for early diagnosis and prognostic assessment of multiple cancers including lung cancer,liver cancer,colorectal cancer,and prostate cancer.

Circulating tumor cells(CTCs)are cells that dissociate from the tumor tissue and enter the lymphatic system or bloodstream with close association with tumor metastasis and recurrence.CTCs contain complete pathological information,which can be extracted by isolation,enrichment,and analysis of the CTCs to guide cancer diagnosis and treatment,thereby significantly improving the monitoring efficiency and prognosis of cancer.Compared with tissue biopsy,liquid biopsy with CTCs as a biomarker enables specific and dynamic detection of tumor growth with a less painful experience.For detection of CTCs,the cells must be captured from body fluids,followed then by their release and enrichment.This review summaries the latest research progress in responsive isolation of CTCs(e.g.with light,dielectrophoresis,acoustophoresis and magnetophoresis),chemical isolation(specific molecules and topological structure)and responsive release(e.g.,light,electric,thermal,pH,enzyme responsiveness,and substrates break).Responsive isolation utilizes the differences in physical properties between CTCs and blood cells,while chemical isolation utilizes specific recognition mechanisms to capture the CTCs.These techniques result in low cell damage with a high specificity to facilitate further analysis.Currently,CTC detection has been applied for early diagnosis and prognostic assessment of multiple cancers including lung cancer,liver cancer,colorectal cancer,and prostate cancer.

Objective: The aim of this study was to investigate the effect of changes in nasal tip protrusion on the sense of upper lip protrusion in different populations and to provide a reference for the improvement of soft tissue beauty. Methods : Informed consent and portrait authorization were obtained from the model. A female model whose face met the criteria was selected, and a 3D model of her was obtained using a 3D stereo camera. Based on the original model, ZBRUSH2019 software was used to simulate changes in nose tip protrusion. Then, 9 segments of facial dynamic rotation videos were produced, and an electronic questionnaire was created through a questionnaire website to evaluate the effect of different nose tip protrusions on perceived upper lip protrusion. Randomly selected orthodontic patients, orthodontics professionals and general adults completed the electronic questionnaire. In the questionnaire, a Visual Analog Scale was used to evaluate the perceived degree of protrusion of the upper lip. The higher the score, the more prominent the upper lip of the model in the image. The questionnaire data were statistically analyzed using a generalized linear mixed model. Results : As the nasal tip position became progressively more retracted, the subjects' upper lip protrusion scores increased. Among male subjects, the results showed that the general population thought that the upper lip protrusion was higher than the patients did when the nasal tip protrusion was +6 mm and +4.5 mm (P = 0.023, P = 0.047). When the nasal tip protrusion was +6 mm, the scores of the general population were higher than those of the orthodontics professionals (P = 0.023). However, when the nasal tip variable was -6 mm, their score was lower than that of the patients (P = 0.003), and there was no significant difference in other retest distances between groups (P>0.05). Conclusion When the protrusion of the nasal tip decreased, the three groups experienced a visual illusion of upper lip protrusion. When the nasal tip protrusion is too large, the general population perceived the visual illusion of the upper lip protrusion as being more obvious.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVE: To investigate the association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth. METHODS: A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group (n=1 654) and euthyroid group (n=14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score＜3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del. RESULTS: The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment (β=0.057, 95%CI: 0.014-0.100, P=0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks (β=0.052, 95%CI: 0.001-0.103, P=0.044), 29-32 weeks (β=0.055, 95%CI: 0.004-0.107, P=0.035) and 36-40 weeks (β=0.068, 95%CI: 0.011-0.125, P=0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women. CONCLUSION The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.
Pregnancy ; Female ; Humans ; Pregnancy Trimester, First ; Iodide Peroxidase ; Cohort Studies ; Reproducibility of Results ; Fetal Development ; Fetal Weight ; Fetal Growth Retardation ; Ultrasonography, Prenatal

ObjectiveTo establish a population pharmacokinetic （PPK） model of teicoplanin in septic patients from Intensive Care Unit （ICU） and to explore its pharmacokinetic characteristics and related covariates. MethodsThe study included 66 septic patients hospitalized in the department of critical care medicine from November 2017 to February 2020. After intravenous dosing of teicoplanin in septic patients， the trough concentration of teicoplanin was determined by high performance liquid chromatography （HPLC） and the concentration-time data was analyzed by non-linear mixed effect model. The pharmacokinetic parameters and residual errors were evaluated. The influence of covariates on model parameters was tested by forward addition and backward elimination. The predictive performance of the final model was assessed by internal validation. ResultsA two-compartment model best described the teicoplanin concentration-time data. The PPK parameter estimates were central clearance of 0.45 L/min， peripheral clearance of 0.72 L/min， central volume of distribution of 39.74 L and peripheral volume of distribution of 152.41 L. Creatinine， total protein， and lactate were found to significantly affect central clearance of teicoplanin （P<0.05）. ConclusionThe two-compartment PPK model of teicoplanin established in this study could be used for individualized treatment in septic patients from ICU due to its good stability and high predictive accuracy.

Objective: To investigate the value of stool-based methylated SDC2 test in physical examination population for the screening of colorectal neoplasms. Methods: Using the prospective cohort study method, from December 2020 to November 2021, 2 107 participants from the First People's Hospital of Xiushui County, Jiangxi Province were enrolled, consisted of 1 012 males and 1 094 females, aged 20-90 years with the median age of 49 years old. Fresh stool samples were collected and SDC2 DNA methylation tests were carried out as the primary screening method. The participants with positive results were recommended to undergo colonoscopy, and those who were negative were followed up by telephone. The positive rate of screening, the compliance of colonoscopy, and the detection of colorectal lesions were analyzed by chi-square test. Combined the follow-up results of negative subjects, the value of SDC2 DNA methylation test for the screening of colorectal neoplasms was evaluated. Results: Among the 2 107 participants, 2 106 completed the SDC2 methylation test. 113 participants (5.4%) were positive. The positive rate of primary screening increased with age significantly (χ²=32.135, P<0.001). Out of 113 cases, 72 (63.7%) underwent colonoscopy examinations. Finally, 3 (4.2%) cases of colorectal cancer, 12 (16.7%) cases of advanced adenoma, 31 (43.1%) cases of non-advanced adenoma, and 16 (22.2%) cases of non-adenomatous polyp were detected. The positive predictive value (PPV) of stool-based SDC2 DNA methylation test for intestinal lesions and colorectal neoplasms were 86.1% and 63.9%, respectively. Among the 1 374 follow-up participants, the negative predictive value (NPV) of this test for intestinal lesions and colorectal neoplasms were 97.7% and 99.4%, respectively. Conclusion: Primary stool-based SDC2 DNA methylation test and subsequent colonoscopy examination can effectively find colorectal neoplasms. This strategy may be a potential tool for the screening of colorectal neoplasms in general risk population.
Male ; Female ; Humans ; Middle Aged ; Sensitivity and Specificity ; Prospective Studies ; Early Detection of Cancer/methods* ; Colorectal Neoplasms/diagnosis* ; Mass Screening/methods* ; Feces ; DNA Methylation ; Colonoscopy ; Physical Examination ; Syndecan-2/genetics*

ObjectiveTo investigate the causes of discontinuation of subcutaneous allergen immunotherapy （SCIT） in patients with allergic rhinitis （AR） and / or bronchial asthma （BA） in the Pearl River Delta region， and to improve the compliance of these patients. MethodsIt was a retrospective， multi-center real world study. Patients with AR and / or BA receiving SCIT in six hospitals in the Pearl River Delta region from January 2015 to December 2020 were recruited. The clinical data of all patients were collected， and the patients with abscission were followed up by telephone. ResultsIn this study， 1 244 patients who received SCIT were included. A total of 427 patients stopped SCIT before 3 years （34.3%）. Children， married patients and patients with positive family history of allergy and total immunoglobulin E （tIgE） > 200 U / mL showed relatively good compliance （P<0.05）， while more patients of AR alone stopped SCIT before 3 years than patients of AR complicated with BA （P<0.05）. Patients with high symptom score and drug score before treatment had better compliance （P<0.001）. A total of 279 cases （65.3%） of the non-adherence group were followed by telephone. The first three reasons for discontinuing treatment were the treatment did not achieve the expected effect （115 cases， 41.2%）， factors pertaining to learning and daily life （74 cases， 26.5%） and adverse reactions （29 cases， 10.4%）. The number of patients stopping SCIT decreased gradually with time； the proportion of patients who discontinued treatment due to adverse reactions in the first year of treatment was higher than that in the second and third years （P<0.05）. ConclusionFailure to achieve the expected effect was the primary reason for poor compliance of patients receiving SCIT and discontinuation mainly occurred on the early stage of the treatment. The supervision from family members is helpful to improve the compliance， suggesting that individualized measures need to be taken to reduce the loss of SCIT.

OBJECTIVE: To improve the collection efficiency of leukapheresis, explore relatively scientific and objective evaluation indicators for collection effect, and observe the effect of high-volume leukapheresis on blood cells and coagulation function. METHODS: A total of 158 times of high-volume leukapheresis were performed on 93 patients with hyperleukocytic leukemia by using continuous flow centrifugal blood component separator. 1/5-1/4 of total blood volume of the patients was taken as the target value of leukocyte suspension for single treatment. In addition, the total number of white blood cells (WBCs) subtracted, value of WBCs reduction, rate of WBCs reduction, decrease value of WBCs count, decrease rate of WBCs count, amount of hemoglobin (Hb) lost, value of Hb lost, decreased value of Hb, total number of platelet (PLT) lost, the value of PLT loss, and decrease value of PLT count were used to comprehensively evaluate the collection effect of leukapheresis and influence on Hb level and PLT count of the patients. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen (Fib) concentration were detected before and after treatment, and the effect of leukapheresis on coagulation function of the patients was observed. RESULTS: The volume of leukocyte suspension collected in a single treatment was 793.01±214.23 ml, the total number of WBCs subtracted was 353.25 (241.99-547.28)×10⁹, the value of WBCs reduction was 86.98 (63.05-143.43)×10⁹/L, the rate of WBCs reduction was 44.24 (28.37-70.48)%, decrease value of WBCs count was 65.73 (37.17-103.97)×10⁹/L, decrease rate of WBCs count was (35.67±23.08)%, the amount of Hb lost was 17.36 (12.12-24.94) g, the value of Hb lost was 4.31 (3.01-6.12) g/L, decreased value of Hb was 4.80 (-1.25-9.33) g/L, total number of PLT lost was 222.79 (67.03-578.31)×10⁹, the value of PLT loss was 54.45 (17.29-139.08)×10⁹/L, and decrease value of PLT count was 26.00 (8.38-62.50)×10⁹/L. Before and after a single treatment, the PT was 14.80 (13.20-16.98) s and 15.20 (13.08-16.90) s (z=-1.520, P>0.05), the aPTT was 35.20 (28.68-39.75) s and 35.40 (28.00-39.75) s (z=-2.058, P<0.05), the TT was 17.50 (16.30-18.80) s and 17.70 (16.70-19.10) s (z=-3.928, P<0.001), and the Fib concentration was 2.87±1.13 g/L and 2.64±1.03 g/L (t=7.151, P<0.001), respectively. CONCLUSION High-volume leukapheresis can improve the efficiency of leukapheresis while maintaining the relative stability of the patients' circulating blood volume. The degree of influence on the patients' Hb level, PLT count, Fib concentration, and comprehensive coagulation indicators reflecting the patients' intrinsic and cxtrinsic coagulation activity is within the body's compensation range.
Blood Coagulation Tests ; Fibrinogen ; Hemoglobins ; Humans ; Leukapheresis ; Leukemia

Objective:To investigate the dynamic expression of histone methyltransferase (enhance of zeste homolog 2, EZH2) in peripheral blood B lymphocytes (CD19 +B) and memory B lymphocytes (CD19 +CD27 +B) of septic patients and its value in predicting prognosis in sepsis. Methods:From June 2018 to January 2020, 48 septic patients in the Intensive Care Unit of Shanghai East Hospital were enrolled, and 40 healthy adult volunteers were recruited as healthy controls. Septic patients were divided into the non-survivors (18 cases) and the survivors (30 cases) according to whether the patients survived at 28 days. Blood samples were collected at day 1, 3 and 7, blood routine, IL-6 and blood gas analysis were collected, and SOFA and APACHE Ⅱ scores were counted. Flow cytometry was used to detect the positive rate and the mean fluorescence intensity of EZH2 on CD19 +B lymphocytes, and the positive rate of EZH2 on CD19 +CD27 +B lymphocytes at different time points. In the healthy controls, fasting was taken only once in the morning. ROC curve was drawn and the area under the curve (AUC) was calculated to evaluate the value of expression of EZH2 on CD19 +B lymphocytes and CD19 +CD27 +B lymphocytes in predicting the prognosis of septic patients. Results:(1) Compared with the healthy controls, the positive rate and average fluorescence intensity of EZH2 on CD19 +B lymphocytes and the positive rate of EZH2 expression on CD19 +CD27 +B lymphocytes were significantly increased at day 1, 2 and 3 in septic patients ( P<0.05). Over time, the expression of EZH2 in CD19 +B lymphocytes and CD19 +CD27 +B lymphocytes increased gradually ( P<0.05). (2) Compared with the survivors, the positive rate of EZH2 on CD19 +B lymphocytes of the non-survivors was increased at day 1, but the positive rate of EZH2 on CD19 +CD27 +B lymphocytes of the non-survivors was decreased at day 3 and 7 ( P<0.05). (3) The positive rate of EZH2 on CD19 +B lymphocytes, APACHE Ⅱ score, SOFA score and IL-6 level in septic patients at day 1 were independently associated with 28-day mortality. (4) The AUC of APACHEⅡ score was 0.907 (95% CI: 0.825-0.990), and the sensitivity and the specificity were 88.89% and 76.67%. The AUC of SOFA score was 0.831 (95% CI: 0.706-0.955), and the sensitivity and the specificity was 66.67% and 86.67%; The AUC of EZH2 positive rate on CD19 +B lymphocytes were 0.799 (95% CI: 0.657-0.941), and the sensitivity and specificity were 88.89% and 80.77%, respectively, the sensitivity was better than SOFA score, and the specificity was higher than APACHEⅡ score. Conclusions:The high expression of EZH2 on B lymphocytes in septic patients is associated with poor prognosis. Dynamic monitoring of EZH2 expression on B lymphocytes has certain predictive value for sepsis.