[The value of minimal residual disease and IKZF1 deletion for predicting prognosis in adult patients with B-cell acute lymphoblastic leukemia].

Objective: To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial. Methods: We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models. Results: The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD(3)) after induction therapy was independently associated with relapse risk (HR=2.535, 95%CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk (HR=1.869, 95%CI 1.034-3.379, P=0.039). Based on MRD(3) and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD(3)-negative and IKZF1 gene deletion-negative) and high-risk (MRD(3)-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % (P<0.001) and (61.6±8.3) % vs (25.5±6.5) % (P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS (HR=3.937, 95%CI 1.975-7.850, P<0.001) and CIR (HR=4.037, 95%CI 2.095-7.778, P<0.001) . Conclusion: The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.

[Study on sIgE distribution characteristics and the sensitization pattern of allergen in 1 161 patients with allergic diseases of respiratory tract in northwest China].

Objective: To explore the allergen map of patients with allergic diseases in northwest China, to investigate the distribution characteristics of serum specific Immunoglobulin E (sIgE) in different ages, genders, diseases and the sensitization patterns of allergens. Methods: This study is a cross-sectional study, a total of 1 161 patients with confirmed respiratory allergic diseases were selected retrospectively from outpatient or inpatient department of Gansu Provincial People's Hospital, Gansu Provincial Maternity and Child Care Hospital, General Hospital of Ningxia Medical University, Yinchuan Maternal and Child Health Care Hospital, Xijing Hospital, Air Force Military Medical University and Tumor Hospital of Inner Mongolia Autonomous Region from June 2019 to October 2022. HAIKE ALLEOS 2000 fluorescent magnetic particle chemiluminescence method was used to quantify their serum for 12 inhaled allergen-specific IgE. Chi square test or Fisher's exact test were used for comparison between count data groups (Bonferroni correction was used for further pairwise comparison in multiple groups, two-sided P<0.05/3=0.017 considered that the difference was statistically significant). Pearson correlation analysis was used for correlation of continuous numerical variables. Results: The positive detection rate of sIgE in 1 161 patients was 66.8%(776/1 161). The three highest positive rate of inhaled allergen were mugwort(599/1 161, 51.6%), French chrysanthemum(565/1 161, 48.7%) and dandelion(412/1 161, 35.5%). In different age groups, the highest positive rate of sIgE was 7-18 age group(379/513, 73.9%) while the lowest positive rate was 4-6 age group(222/370, 60.0%), the difference between groups was statistically significant(χ2=21.177, P<0.001). The sensitization peak of mugwort, French chrysanthemum, plantain, timothy, birch, dermatophagoides pteronyssinus, dermatophagoides farinae, cat epithelium, dog epithelium and German cockroach appeared in 7-18 age group. In different disease groups, the highest positive rate of sIgE was allergic rhinitis with asthma group (500/717, 69.7%) while the lowest positive rate was asthma group (76/144, 52.8%), the difference between groups was statistically significant(χ2=15.563, P<0.001). In different gender groups, the positive rate of sIgE in male (503/711, 70.7%) was higher than in female (273/450, 60.7%), the difference between groups was statistically significant(χ2=12.630, P<0.001). The multiple-sensitization rate was 86.9%(674/776) and the double-sensitization rate was 16.8%(130/776) in sIgE positive patients. Pearson correlation results showed that there was an extremely strong correlation between dandelion and French chrysanthemum(r=0.93,P<0.001). There was a strong correlation between mugwort and French chrysanthemum(r=0.64,P<0.001). In the co-sensitization analysis, the number of patients sensitized by mugwort, French chrysanthemum, dandelion, plantain and timothy accounted for 25.2%(170/674)of the total number of multiple sensitization. The number of patients sensitized by mugwort, French chrysanthemum and dandelion accounted for 58.3%(393/674)of the total number of multiple sensitization. The number of patients sensitized by mugwort, French chrysanthemum, dandelion and plantain accounted for 35.6%(240/674) of the total number of multiple sensitization. Conclusion: Mugwort, French chrysanthemum, dandelion are the major inhaled allergens in northwest China. The positive rate of sIgE was different in different ages, diseases and genders. The multiple-sensitization rate of allergen was high and there was a certain positive correlation between pollen allergen-specific IgE pairwise, suggesting that there may exist co-sensitization or cross-reactions among allergens.

[Evaluation of diagnostic efficacy of digital liquid chip method for detection of specific antineutrophil cytoplasmic antibodies].

To explore the clinical diagnostic efficacy of antineutrophil cytoplasmic antibody associated vasculitis (AAV) by comparing the consistency and coincidence rate of serum anti-myeloperoxidase (MPO) antibody and anti-protease 3 (PR3) antibody detected by digital liquid chip method (DLCM) and enzyme-linked immunosorbent assay (ELISA). To provide reference for the selection of detection methods of anti-MPO antibody and anti-PR3 antibody in clinical laboratory. This study is a cross-sectional study, a total of 307 cases of antineutrophil cytoplasmic antibodies were detected in the Department of Clinical Immunology, West China Hospital of Sichuan University from January to March 2021. The serum samples and related clinical information were collected. At the same time, the levels of anti-MPO antibody and anti-PR3 antibody in serum samples were detected by ELISA and DLCM, indirect immunofluorescence (IIF) was used to re-test the differential samples between the two methods. SPSS 26.0 was used to analyze the test results, Cohen's kappa coefficient analysis was used to compare the consistency of the two methods, and paired chi-square test was used to compare the sensitivity and specificity of the two methods to AAV. The results showed that the positive cases of anti-MPO antibody detected by ELISA and DLCM were 63 and 44, and the negative cases were 244 and 263; the positive cases of anti-PR3 antibody detected by ELISA and DLCM were 34 and 28, and the negative cases were 273 and 279. The results of anti-MPO antibody and anti-PR3 antibody detected by the two methods had good consistency and coincidence rate, in which the total coincidence rate of anti-MPO antibody was 92.51%, the positive coincidence rate was 66.67%, and the negative coincidence rate was 99.18%. The results of consistency analysis showed that kappa=0.741 had well consistency. The total coincidence rate of anti-PR3 antibody is 96.74%, the positive coincidence rate is 76.47%, and the negative coincidence rate is 99.27%. The consistency analysis results show that kappa=0.821 had strong consistency. The results of IIF re-test of differential samples showed that the coincidence rate between DLCM and IIF was higher. The results of comparative analysis of anti-MPO antibody and anti-PR3 antibody showed that the specificity of DLCM was better than that of ELISA, and its sensitivity was lower than that of ELISA. In conclusion, the results of anti-MPO antibody and anti-PR3 antibody detected by DLCM were consistent with those of ELISA. In the combined detection of anti-MPO antibody and anti-PR3 antibody, the specificity of DLCM is better than that of ELISA.

[A preliminary study on the establishment of trachea respiratory passage invaded by thyroid malignant tumor].

Objective: To investigate the establishment of trachea respiratory passage invided by advanced thyroid malignant tumor. Methods: Review of 14 cases with the establishment of trachea respiratory passage invided by advanced thyroid cancer was conducted who were treated at the Department of Otorhinolaryngology Head and Neck Surgery, Zhongda Hospital Southeast University between 2016 and 2020. There were 5 males and 9 females, aged from 24-79 years old. Shin grade was as follows，5 cases with Ⅱ grade, 6 with Ⅲ grade, and 3 with Ⅳ grade. Based on the conditions of tracheal compression and tumor extent, three types of managements were used: patients with the narrowest tracheal diameter>5 mm (8 cases with dyspnea Ⅰ-Ⅱ, Shin grade Ⅱ-Ⅲ) were applied with local surface anesthesia and conscious endotracheal intubation after sedation and analgesia; patients with the narrowest tracheal diameter with 4-5 mm (3 cases with dyspnea Ⅱ, Shin grade Ⅳ) needed tracheotomy with local anesthesia by supplying oxygen with a mask; patients with the narrowest tracheal diameter<4 mm (3 cases with dyspnea Ⅲ, Shin grade Ⅲ) needed tracheotomy with extracorporeal circulation. Results: Respiratory passages for general anesthesia were safely established in all 14 patients, of whom 12 cases with differentiated thyroid carcinoma were treated with surgery, and 2 cases with undifferentiated thyroid carcinoma and B-cell lymphoma was treated with tracheotomy and then treated with chemotherapy in the Oncology or Hematology Department. All patients were followed-up for 2-22 months and survived without tumors, but one patient with undifferentiated carcinoma survived for 3 months. Conclusion: Respiratory passage can be established quickly and safe in advanced thyroid malignant tumor. This provides a necessary safety for patients who are needed surgical treatment and also an opportunity for patients undergoing other treatments.

[Value of IgA antiphospholipid antibodies in diagnosis of the antiphospholipid syndrome].

Objective: To examine the prevalence of multiple antiphospholipid antibodies (aPL) subtypes in healthy people and antiphospholipid syndrome (APS) patients, and to assess the value of IgA-aPL in the diagnosis of APS. Methods: According to the 2006 Sydney International APS Classification Criteria, a total of 218 APS patients who were admitted to Peking Union Medical College Hospital or West China Hospital of Sichuan University from July to December 2019 were enrolled. Among them, 66 were males, and 152 were females, aged (44.5±15.4) years, including 148 primary APS patients and 70 secondary APS patients. Age-and gender-matched controls were collected at the same period at the ratio of 1∶1 with the APS cases. IgA/IgG/IgM anticardiolipin antibodies (aCL) and anti-ß2 glycoprotein I antibodies (aß2GPI) were detected by chemiluminescent immunoassay. The differences of indicators between groups were analyzed, and the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of IgA-aPL for APS. Results: The positivity of IgA-aCL and IgA-aß2GPI was 20.6% and 15.6% in the APS patients, while in the IgG/IgM-aCL or IgG/IgM-aß2GPI negative individuals, the isolated positivity of IgA-aCL and IgA-aß2GPI was only 2.3% and 0.9%, respectively. Accordingly, IgA-aCL and IgA-aß2GPI isolated positivity could be used to diagnose APS (P=0.216, 1, respectively). The area under the ROC curve (AUC) of IgG/IgM-aCL for APS diagnosis was 0.833, which was significantly better than that of IgG-aCL alone (AUC=0.776, P<0.001); while the AUC of IgA/IgG/IgM-aCL was 0.833, which could not further increase the diagnostic value for APS (P=0.287). As for aß2GPI, the diagnostic efficacy of combined IgG/IgM (AUC=0.875) or IgA/IgG/IgM (AUC=0.875) antibodies was not superior to IgG-aß2GPI used alone (AUC=0.869, both P>0.05). Besides, patients with IgA-aPL were more likely to have heart valve lesions and thrombocytopenia (both P<0.05). Conclusion: Based on the existing serological markers, such as lupus anticoagulant, IgG/IgM subtype of aCL and aß2GPI, testing IgA-aCL and IgA-aß2GPI cannot further improve the predictive value of APS. However, IgA-aPL is associated with clinical manifestations of APS, including heart valve lesions and thrombocytopenia.

[Analysis of cases with emergency thyroid surgery].

Objective: To investigate the clinical features of cases with emergency thyroid surgery. Methods: Nineteen cases treated with emergency thyroid surgery from May 2014 to May 2019 were analysed retrospectively, including 9 males and 10 females, aged from 24-79 years old. Among them, 6 cases had nodular goitres and 13 cases had thyroid malignancies. One case underwent tracheal stenting before operation. Emergency thyroid surgery was due to severe dyspnea in all cases. Treatment outcomes and prognoses of patients were evaluated. Results: All the 19 patients underwent general anesthesia with endotracheal intubation. One patient underwent extracorporeal membrane oxygenation(ECMO) and two patients underwent cardiopulmonary bypass. Six cases of nodular goitres underwent proximal thyroidectomy. Eight cases of malignant tumors underwent total thyroidectomy, six cases with invading the trachea underwent tracheal end-end anastomosis after partial tracheal resection, one case underwent tumor resection with sternal sternum approach, cervical and mediastinal lymph node dissection, total laryngectomy and tracheal low ostomy. Two cases with extensive involvement of malignant tumors were given a definite diagnosis and tracheostomy. Of three cases with malignant lymphoma, one underwent total thyroidectomy, and two were only given a definite diagnosis and tracheostomy. No complications such as hemorrhage, recurrent laryngeal nerve or parathyroid injury occurred after operation in all patients. With followed up for 6-50 months, except 2 cases died due to tumor progression, the rest were alive. Conclusions: Patients with obvious dyspnea caused by thyroid tumors have a high mortality rate and should be treated actively. Emergency surgery not only relieves respiratory obstruction and saves the lives of patients, but some patients can get a radical cure as well.

Accurate diagnosis of colorectal cancer based on histopathology images using artificial intelligence.

BACKGROUND: Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients' treatment. The current heavy workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses. METHODS: Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany. RESULTS: Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells. CONCLUSIONS: This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.

[Clinical analysis of carotid artery stenting with severe stenosis and extracranial distortion under proximal protection technique].

Objective: To investigate the feasibility, efficacy and safety of endovascular reconstruction of the carotid artery with severe stenosis and extracranial distortion under proximal protection. Methods: A retrospective analysis of 21 patients with severe carotid stenosis and extracranial distortion who were admitted to the Second Affiliated Hospital of Soochow University between January 2011 and August 2017, of which 16 patients were symptomatic stenosis with acute ischemic stroke. All the patients were treated with carotid artery stenting under (CAS) proximal protection technique, and assessed with the National Institutes of Health Stroke Scale (NIHSS) before the treatment and hospital discharge. The clinical outcome and vascular morphology were followed-up regularly after the treatment. Results: Twenty-one patients were successfully completed the CAS procedure under the proximal protection technique, the average blocking time was 241.0 (232.5-261.0) seconds. Nine patients received 1block attempt, 6 patients received 2 block attempts, and the other 6 patients received 3 block attempts. Three patients experienced transient ischemic attack (TIA) during the procedure, the maximum duration of TIA was 10 minutes. In 16 patients with symptomatic stenosis, there were no significant differences in NIHSS score before CAS procedure and hospital discharge (P>0.05). The residual stenosis rate of the carotid artery after stenting was(13±6)%, compared with preoperative (87±16)%, which appeared a significant difference (t=19.948, P<0.05). All the patients had no adverse events such as myocardial infarction, recurrent ischemic stroke and death in the follow-up period. Restenosis was assessed in 6 patients by DSA or CTA and no restenosis was found. Conclusion: Endovascular reconstruction of the carotid artery with severe stenosis and extracranial distortion under proximal protection technique has been proven as a safe and effective therapy.

[Altered regional brain activity of functional connectivity in patients with obstructive sleep apnea].

Objective: To investigate the changes of default mode network in subjects with obstructive sleep apnea (OSA) using functional connectivity (FC). Methods: Clinical data were collected from thirty-three subjects with OSA who went to the Zhongda Hospital, Southeast University, and twenty-nine normal controls were recruited from community from Jan 2016 to Jan 2018. The OSA group was divided into two subgroups according to apnea-hypopnea index (AHI) and the lowest oxygen saturation at night: 15 patients in the mild group and 18 in the moderate to severe group. Both of the two group subjects underwent functional magnetic resonance imaging scans, and their default network was extracted based on independent component analysis to compare the differences in FC. Results: Body Mass Index (BMI), AHI, oxygen desaturation index (ODI), mini-mental state examination (MMSE) and Epworth Sleepiness Scale (ESS) in the OSA group were significantly higher than those in the control group [(27.1±4.3) vs (22.2±2.7) kg/m(2), (29.5±22.1) vs (2.4±1.6) events/h, 19.5 (4.6, 39.1) vs 0.6 (0.2, 1.6) events/h, (27.5±1.5) vs (29.4±0.8) score, (8.6±3.3) vs (3.5±1.6) score] (all P<0.001). The OSA group showed an increase in left limbic lobe, left cingulate, left parietal lobe, left inferior parietal lobule; a decrease in bilateral temporal lobe, bilateral limbic lobe and parahippocampa gyrus, left frontal lobe in FC value, compared with the normal control group (all P<0.001). The moderated-severe group showed a significant increase in the left occipital lobe, bilateral cuneus, right parietal lobe; a decrease in the bilateral parietal lobe, inferior parietal lobule in FC value compared with the mild group (all P<0.01). Conclusions: The FC of default mode network in OSA group is disrupted, with parts of brain regions suffering injury,while parts of brain regions experiencing compensatory reaction. Additionally, the compensatory period translates to the decompensation period with disease progression in OSA group.