Detachable string magnetically controlled capsule endoscopy for the noninvasive diagnosis of esophageal diseases:A prospective,blind clinical study

BACKGROUND Traditional esophagogastroduodenoscopy(EGD),an invasive examination method,can cause discomfort and pain in patients.In contrast,magnetically controlled capsule endoscopy(MCE),a noninvasive method,is being applied for the detection of stomach and small intestinal diseases,but its application in treating esophageal diseases is not widespread.AIM To evaluate the safety and efficacy of detachable string MCE(ds-MCE)for the diagnosis of esophageal diseases.METHODS Fifty patients who had been diagnosed with esophageal diseases were pros-pectively recruited for this clinical study and underwent ds-MCE and conven-tional EGD.The primary endpoints included the sensitivity,specificity,positive predictive value,negative predictive value,and diagnostic accuracy of ds-MCE for patients with esophageal diseases.The secondary endpoints consisted of visualizing the esophageal and dentate lines,as well as the subjects'tolerance of the procedure.RESULTS Using EGD as the gold standard,the sensitivity,specificity,positive predictive value,negative predictive value,and diagnostic accuracy of ds-MCE for esophageal disease detection were 85.71%,86.21%,81.82%,89.29%,and 86%,respectively.ds-MCE was more comfortable and convenient than EGD was,with 80%of patients feeling that ds-MCE examination was very comfortable or comfortable and 50%of patients believing that detachable string v examination was very convenient.CONCLUSION This study revealed that ds-MCE has the same diagnostic effects as traditional EGD for esophageal diseases and is more comfortable and convenient than EGD,providing a novel noninvasive method for treating esophageal diseases.

Nonalcoholic fatty liver disease:Updates in noninvasive diagnosis and correlation with cardiovascular disease

Nonalcoholic fatty liver disease(NAFLD)refers to the accumulation of fat(mainly triglycerides)within hepatocytes.Approximately 20%-30%of adults in the general population in developed countries have NAFLD;this trend is increasing because of the pandemicity of obesity and diabetes,and is becoming a serious public health burden.Twenty percent of individuals with NAFLD develop chronic hepatic inflammation[nonalcoholic steatohepatitis(NASH)],which can be associated with the development of cirrhosis,portal hypertension,and hepatocellular carcinoma in a minority of patients.And thus,the detection and diagnosis of NAFLD is important for general practitioners.Liver biopsy is the gold standard for diagnosing NAFLD and confirming the presence of NASH.However,the invasiveness of this procedure limits its application to screening the general population or patients with contraindications for liver biopsy.The development of noninvasive diagnostic methods for NAFLD is of paramount importance.This review focuses on the updates of noninvasive diagnosis of NAFLD.Besides,we review clinical evidence supporting a strong association between NAFLD and the risk of cardiovascular disease because of the cross link between these two disorders.

Evaluation of the diagnostic efficacy of noninvasive diagnosis in patients with chronic viral hepatitis B complicated with nonalcoholic fatty liver disease and significant liver fibrosis

Objective:To evaluate the diagnostic efficacy of chronic viral hepatitis B(CHB)with significant liver fibrosis(S2)in patients with nonalcoholic fatty liver disease(NAFLD)by using noninvasive diagnosis and their combined models,and to explore their clinical features.Methods:A total of 104 inpatients with CHB diagnosed and complicated with NAFLD(hepatic steatosis suggested by liver biopsy)were retrospectively collected from January 2018 to January 2023 in the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University.Liver biopsy was performed in all patients.General data,laboratory test results,liver hardness(LSM),FIB-4,APRI,GGT/PLT,AST/PLT and other results of patients were collected and grouped according to different fibrosis stages(S)to explore the clinical and pathological characteristics of patients with<S2 and S2 stages.Receiver operating characteristic curve was used to evaluate the diagnostic value of LSM,FIB-4,APRI,GGT/PLT,AST/PLT and their combined models in patients with significant liver fibrosis in CHB patients with NAFLD.Results:Among the 104 patients,there were 55 patients had S1 fibrosis,32 patients had S2 fibrosis,11 patients had S3 fibrosis and 6 patients had S4 fibrosis.Patients had<S2 fibrosis,ALT 33.75±17.15 U/L,AST 24.00(19.77,29.00)U/L,inflammation above G2 stage accounted for 92.72%,GGT/PLT 0.07(0.10,0.15),AST/PLT 0.09(0.10,0.15),LSM 8.70(6.80,10.10)kPa,FIB-41.07±0.51,APRI 0.26(0.22,0.28).In patients S2 fibrosis,ALT 42.14±21.39 U/L,AST 29.04(24.00,40.32)U/L,inflammation above G2 stage accounted for 97.95%,GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26),GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26).LSM 11.80(8.50,16.65)kPa,FIB-41.39±0.72,APRI 0.35(0.26,0.66),the difference between the two groups was statistically significant(P<0.05).The area under the receiver operator characteristic curves of the subjects of LSM,FIB-4,APRI,GGT/PLT and AST/PLT were 0.716,0.623,0.669,0.644 and 0.669(P<0.05),respectively.In the combined model,the area under the receiver operator characteristic curves of LSM combined with FIB-4,LSM combined with APRI,LSM combined with GGT/PLT and LSM combined with AST/PLT were 0.712,0.719,0.715 and 0.719,respectively(P<0.05).Conclusion:Although the currently commonly used Noninvasive diagnosis of liver fibrosis has certain diagnostic efficacy for significant liver fibrosis in CHB complicated with NAFLD,it cannot replace liver biopsy.Noninvasive Diagnosis can be used as an auxiliary method for regular clinical evaluation of liver biopsy.

Four-dimensional flow magnetic resonance imaging for noninvasive diagnosis of clinically significant portal hypertension and high-risk gastroesophageal varices in patients with cirrhosis

Introduction:Noninvasive diagnoses of clinically significant portal hypertension(CSPH)and high-risk gastroesophageal varices are clinically relevant but challenging.Four-dimensional(4D)flow magnetic resonance imaging(MRI)provides comprehensive flow information and is a promising alternative.This study evaluated the efficacy of 4D flow MRI as a noninvasive method for diagnosing CSPH and high-risk varices in patients with liver cirrhosis.Methods:This prospective study enrolled consecutive patients diagnosed with liver cirrhosis at a tertiary referral center between October 2020 and March 2021.Each participant underwent abdominal 4D flow MRI.Hemodynamic parameters within the portal vein,including the average and peak flow velocities,normalized flow volume(Q_(normal)),and regurgitant fraction(R%),were extracted and compared between healthy individuals and patients with CSPH and between participants with high-and low-risk varices.Subsequently,these parameters were incorporated into a logistic regression(LR)model refined using L1 regularization and validated using five-fold cross-validation.The diagnostic efficacy was evaluated using receiver operating characteristic(ROC)curves.Results:Eighty-two participants were enrolled(71 patients diagnosed with liver cirrhosis and 11 healthy individuals serving as controls).Among hemodynamic parameters,patients with CSPH exhibited a notable increase in Q_(normal)of 0.66±0.19 ml*m^(2)/[cycle*kg](P=0.001)and an R%of 1.98(2.05)(P=0.002).Similarly,patients with high-risk varices showed a higher Q_(normal)of 0.61±0.15 ml*m^(2)/[cycle*kg](P<0.001)and R%of 1.88(2.81)(P=0.006).ROC analysis revealed an area under the curve(AUC)for Q_(normal)of 0.93 and 0.91 for R%for diagnosing CSPH,while the LR model showcased a superior AUC of 0.95.For high-risk varices,Q_(normal)and R%showed AUC values of 0.75 and 0.70,respectively,whereas the LR model showed a higher AUC of 0.84.Conclusion:As a noninvasive imaging modality,4D flow MRI exhibits considerable potential for the diagnosis of CSPH and high-risk gastroesophageal varices;thus,it may minimize the reliance on invasive procedures in patients with cirrhosis.

Noninvasive beam diagnosis based on the TM_(010)mode

A resonant cavity based on the TM_(010)mode is an effective tool for noninvasive beam characterization. This technique has the advantages of a high signal-to-noise ratio, compact structure, and is related to multiple parameters compared with other beam monitors. In this study, high-precision measurements of the bunch charge, arrival time, bunch length, and energy parameters based on the TM_(010)mode are discussed. A cavity beam arrival time monitor(BAM) utilizing a phase cavity has been widely used in many facilities. Regarding bunch-length measurements, the influence of the beam energy, beam offset,and longitudinal spectrum on the TM_(010)mode are carefully considered to reduce errors, and the theoretical resolution of two cavities with different frequencies is analyzed. Owing to the dependence of the beam velocity of the beam loss factor, this method can also be used for the detection low beam energy using two cavities with the same frequency but different cavity lengths. A set of three cavities with different lengths and frequencies of 1.902 and 11.424 GHz is presented for measuring the four aforementioned parameters.

Noninvasive Prenatal Diagnosis of Fetal Sex by Single-cell PEP-PCR Method

A new method for noninvasive prenatal diagnosis of fetal sex was developed by using single cell PEP PCR techniques. Micromamipulation techniques were used to obtain single fetal cells from 273 maternal blood samples. The genome of single cells was preamplified by PEP and SRY genes were analyzed by PCR method. The SRY genes of 149 samples were detected by the new method among 153 samples carrying male fetus, while 119 out of 120 samples carrying female fetus were proved negative for SRY genes. The sensitivity and specificity of the new method were 97.39 % and 99.17 % respectively and the correct rate was 98.17 %. The new method has the advantage of high sensitivity and specificity in noninvasive prenatal diagnosis of fetal sex and provides the basis of other researches such as sex linked inherited diseases.

Clinical application of oral contrast-enhanced ultrasound in evaluating the preoperative T staging of gastric cancer

BACKGROUND Oral contrast-enhanced ultrasound(OCEUS)is widely used in the noninvasive diagnosis and screening of gastric cancer(GC)in China.AIM To investigate the clinical application of OCEUS in evaluating the preoperative T staging of gastric cancer.METHODS OCEUS was performed before the operation,and standard ultrasound images were retained.The depth of infiltration of GC(T-stage)was evaluated according to the American Joint Committee on Cancer 8th edition of the tumor-nodemetastasis staging criteria.Finally,with postoperative pathological staging as the gold standard reference,the sensitivity,specificity,negative predictive value,positive predictive value,and diagnostic value of OCEUS T staging were evaluated.RESULTS OCEUS achieved diagnostic accuracy rates of 76.6%(T1a),69.6%(T1b),62.7%(T2),60.8%(T3),88.0%(T4a),and 88.7%(T4b),with an average of 75.5%.Ultrasonic T staging sensitivity exceeded 62%,aside from T1b at 40.3%,while specificity was over 91%,except for T3 with 83.5%.The Youden index was above 60%,with T1b and T2 being exceptions.OCEUS T staging corresponded closely with pathology in T4b(kappa>0.75)and moderately in T1a,T1b,T2,T3,and T4a(kappa 0.40-0.75),registering a concordance rate exceeding 84%.CONCLUSION OCEUS was effective,reliable,and accurate in diagnosing the preoperative T staging of GC.As a noninvasive diagnostic technique,OCEUS merits clinical popularization.

Diagnostic role of transient elastography in patients with autoimmune liver diseases:A systematic review and meta-analysis

BACKGROUND Noninvasive methods have been developed to detect fibrosis in many liver diseases due to the limits of liver biopsy.However,previous studies have focused primarily on chronic viral hepatitis and nonalcoholic fatty liver disease.The diagnostic value of transient elastography for autoimmune liver diseases(AILDs)is worth studying.AIM To compare the diagnostic accuracy of imaging techniques with serum biomarkers of fibrosis in AILD.METHODS The PubMed,Cochrane Library and EMBASE databases were searched.Studies evaluating the efficacy of noninvasive methods in the diagnosis of AILDs[autoimmune hepatitis(AIH),primary biliary cholangitis(PBC)and primary sclerosing cholangitis(PSC)]were included.The summary area under the receiver operating characteristic curve(AUROC),diagnostic odds ratio,sensitivity and specificity were used to assess the accuracy of these noninvasive methods for staging fibrosis.RESULTS A total of 60 articles were included in this study,and the number of patients with AIH,PBC and PSC was 1594,3126 and 501,respectively.The summary AUROC of transient elastography in the diagnosis of significant fibrosis,advanced fibrosis and cirrhosis in patients with AIH were 0.84,0.88 and 0.90,respectively,while those in patients with PBC were 0.93,0.93 and 0.91,respectively.The AUROC of cirrhosis for patients with PSC was 0.95.However,other noninvasive indices(aspartate aminotransferase to platelet ratio index,aspartate aminotransferase/alanine aminotransferase ratio,fibrosis-4 index)had corresponding AUROCs less than 0.80.CONCLUSION Transient elastography exerts better diagnostic accuracy in AILD patients,especially in PBC patients.The appropriate cutoff values for staging advanced fibrosis and cirrhosis ranged from 9.6 to 10.7 and 14.4 to 16.9 KPa for PBC patients.

Analysis of sEMG signal for KOA classification

The sEMG signals are collected from the vastus lateralis,vastus medialis,biceps femoris,and semitendinosus of lower extremity during level walking among control subjects and knee osteoarthritis (OA) patients,the latter including mild,moderate and severe degree.The 5-fold cross-validation is used to measure the accuracy of the proposed analysis algorithm on collected sEMG recordings.For comparison,the more classical feature vectors of form factor,degree of skewness,kurtosis,and wavelet entropy are also tested.In experiment,the normalized energy ratio and marginal spectrum ratio achieve larger accuracy than the other features for all the four muscular groups.Moreover the accuracy of vastus medialis and biceps femoris are larger than that of vastus lateralis and semitendinosus.These results suggest that the normalized energy ratio and marginal spectrum ratio via the analysis of knee sEMG signals by HHT can server as characteristic parameters to easily classify osteoarthritis with noninvasive method.The more important muscular groups for maintaining the knee joint function are medialis and biceps femoris;as a result of that they should be exercise especially for rehabilitation.

Noninvasive Diagnostic Technique for Nonalcoholic Fatty Liver Disease Based on Features of Tongue Images

Objective:To investigate a new noninvasive diagnostic model for nonalcoholic fatty liver disease(NAFLD) based on features of tongue images.Methods:Healthy controls and volunteers confirmed to have NAFLD by liver ultrasound were recruited from China-Japan Friendship Hospital between September 2018 and May 2019,then the anthropometric indexes and sampled tongue images were measured.The tongue images were labeled by features,based on a brief protocol,without knowing any other clinical data,after a series of corrections and data cleaning.The algorithm was trained on images using labels and several anthropometric indexes for inputs,utilizing machine learning technology.Finally,a logistic regression algorithm and a decision tree model were constructed as 2 diagnostic models for NAFLD.Results:A total of 720 subjects were enrolled in this study,including 432 patients with NAFLD and 288 healthy volunteers.Of them,482 were randomly allocated into the training set and 238 into the validation set.The diagnostic model based on logistic regression exhibited excellent performance:in validation set,it achieved an accuracy of 86.98%,sensitivity of 91.43%,and specificity of 80.61%;with an area under the curve(AUC) of 0.93 [95% confidence interval(CI) 0.68–0.98].The decision tree model achieved an accuracy of 81.09%,sensitivity of 91.43%,and specificity of 66.33%;with an AUC of 0.89(95% CI 0.66–0.92) in validation set.Conclusions:The features of tongue images were associated with NAFLD.Both the 2 diagnostic models,which would be convenient,noninvasive,lightweight,rapid,and inexpensive technical references for early screening,can accurately distinguish NAFLD and are worth further study.

Reproductive management through integration of PGD and MPS-based noninvasive prenatal screening/diagnosis for a family with GJB2-associated hearing impairment

A couple with a proband child of GJB2 （encoding the gap junction protein connexin 26）-associated hearing impairment and a previous pregnancy miscarriage sought for a reproductive solution to bear a healthy child. Our study aimed to develop a cus- tomized preconception-to-neonate care trajectory to fulfill this clinical demand by integrating preimplantation genetic diagno- sis （PGD）, noninvasive prenatal testing （NIPT）, and noninvasive prenatal diagnosis （N1PD） into the strategy. Auditory and ge- netic diagnosis of the proband child was carried out to identify the disease causative mutations. The couple then received in-vitro-fertilization treatment, and eight embryos were obtained for day 5 biopsy. PGD was performed by short-tandem-repeat linkage analysis and Sanger sequencing of GJB2 gene. Transfer of a GJB2c.235delC heterozygous embryo resulted in a sin- gleton pregnancy. At the 13th week of gestation, genomic DNA （gDNA） from the trio family and cell-free DNA （cfDNA） from maternal plasma were obtained for assessment of fetal chromosomal aneuploidy and GJB2 mutations. NIPT and NIPD showed the absence of chromosomal aneuploidy and GJB2-associated disease in the fetus, which was later confirmed by inva- sire procedures and postnatal genetic/auditory diagnosis. This strategy successfully prevented the transmission of hearing im- pairment in the newborn, thus providing a valuable experience in reproductive management of similar cases and potentially other monogenic disorders.

Sequential ultrasound molecular imaging for noninvasive identification and assessment of non-alcoholic steatohepatitis in mouse models

Background and objective:Noninvasive non-alcoholic steatohepatitis(NASH)assessment is a clinical challenge to the management of non-alcoholic fatty liver disease.We aim to develop diagnostic models based on sequential ultrasound molecular imaging(USMI)for the noninvasive identification of NASH in mouse models.Methods:Animal experiments were approved by the Animal Ethics Committee of South China Agricultural University.Forty-nine C57BL/6 mice were divided into normal control,non-alcoholic fatty liver,NASH,and hepatitis groups.Sequential USMI was implemented using CD36-targeted microbubbles(MBs-CD36)and intercellular adhesion molecule-1(ICAM-1)-targeted microbubbles(MBs-ICAM-1)to visualize hepatic steatosis and inflammation.The targeting signal of USMI was quantified as the normalized intensity difference(NID)with the destruction-replenishment method.Correlation analysis was conducted between the NID-MBs-CD36 and pathological steatosis score and between the NID-MBsICAM-1 and pathological inflammation score.Finally,diagnostic models combining NID-MBs-CD36 with NID-MBs-ICAM-1 were established for NASH diagnosis.Results:MBs-CD36 and MBs-ICAM-1 were successfully prepared and used for sequential USMI in all mice.NID-MBs-CD36 values increased with the progression of steatosis,while NID-MBs-ICAM-1 values increased in parallel with the progression of inflammation.A strong positive correlation was identified between NID-MBs-CD36 and pathological steatosis grade(r_(s)=0.9078,P<0.0001)and between NIDMBs-ICAM-1 and pathological inflammation grade(r_(s)=0.9071,P<0.0001).Among various sequential USMI-based diagnostic models,the serial testing model showed high diagnostic performance in detecting NASH,with 95%sensitivity,97%specificity,95%positive predictive values,97%negative predictive values,and 96%accuracy.Conclusions:Sequential USMI using MBs-CD36 and MBs-ICAM-1 allows noninvasive grading of hepatic steatosis and inflammation.Sequential USMI-based diagnostic models hold great potential in the noninvasive identification of NASH.

Urinary analysis based on surface-enhanced Raman scattering for the noninvasive screening of lung cancer

We developed a reliable simple analysis of adenosine,creatinine and other nucleosides(cytidine and guanosine)with single measurement based on surface-enhanced Raman spectroscopy(SERS)using DSP-AuNPs with Cu^(2+)ions probe and applied it to achieve noninvasive screening of lung cancer.The gold nanoparticles(AuNPs)were modified with 3,3′-dithiodipropionic acid di(N-hydroxysuccinimide ester)(DSP),which could react with above mentioned molecules followed with the aggregation of AuNPs at the presence of Cu^(2+),thus form the plasmonic hot spots to dramatically increase their fingerprint Raman signal.The probe of DSP-AuNPs was applied for the detail analysis of urinary adenosine of healthy people and lung cancer patients.The SERS measurement indicated a higher concentration of urinary adenosine for lung cancer patients than that of healthy people,which was consistent with the results measured by high-performance liquid chromatography(HPLC).In combination of Raman spectroscopy with the orthogonal partial least squares discriminant analysis(OPLS-DA)model,we are able to discriminate the lung cancer patients from healthy people with the urinary test.The results indicated that besides of adenosine,other metabolites including uric acid,guanine and creatinine may also be the potential tumor markers in urine for the noninvasive lung cancer diagnosis.Such a method paves a way for the noninvasive cancer screening and it can be further modified for the detection of other molecules on medical diagnosis.

Application and progress of the detection technologies in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)has a very high incidence and fatality rate,and in most cases,it is already at an advanced stage when diagnosed.Therefore,early prevention and detection of HCC are two of the most effective strategies.However,the methods recommended in the practice guidelines for the detection of HCC cannot guarantee high sensitivity and specificity except for the liver biopsy,which is known as the“gold standard”.In this review,we divided the detection of HCC into pre-treatment diagnosis and post-treatment monitoring,and found that in addition to the traditional imaging detection and liver biopsy,alpha fetoprotein(AFP),lens culinaris-agglutinin-reactive fraction of AFP(AFP-L3),protein induced by vitamin K absence or antagonist-II(PIVKA-II)and other biomarkers are excellent biomarkers for HCC,especially when they are combined together.Most notably,the emerging liquid biopsy shows great promise in detecting HCC.In addition,lactic dehydrogenase(LDH),suppressor of cytokine signaling(SOCS)and other relevant biomarkers may become promising biomarkers for HCC post-treatment monitoring.Through the detailed introduction of the diagnostic technology of HCC,we can have a detailed understanding of its development process and then obtain some enlightenment from the diagnosis,to improve the diagnostic rate of HCC and reduce its mortality.

Advances on circulating fetal DNA in maternal plasma

The discovery of cell-free fetal DNA in maternal plasma in 1997 has opened up new possibilities for noninvasive diagnosis. By RT-PCR, circulating fetal DNA can be detected in the plasma of pregnant women, even in the first trimester of pregnancy, and thus can be used for noninvasive prenatal diagnosis of sex-linked disorders, the RhD status of fetuses, and single gene disorders such as beta-thalassaemia, congenital adrenal hyperplasia, and achondroplasia. In addition, quantitative aberrations of circulating fetal DNA may indicate various pregnancy-associated disorders, including preeclampsia, preterm labor and fetal trisomy 21.