[Multicenter evaluation of minimal residual disease monitoring in early induction therapy for treatment of childhood acute lymphoblastic leukemia].

Objective: To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL). Methods: This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children's Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors. Results: Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×109/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively (χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant (χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively (χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%,χ2=4.13,P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%,χ2=4.06,P=0.044;(58.3±18.6)% vs. (85.7±3.2)%,χ2=9.44,P=0.002). Multivariate analysis showed that age (OR=0.58, 95%CI 0.35-0.97) and white blood cell count at first diagnosis (OR=0.43, 95%CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 (OR=0.55,95%CI 0.31-0.97), ETV6-RUNX1 fusion gene (OR=0.13,95%CI 0.03-0.54), MLL gene rearrangement (OR=2.55,95%CI 1.18-5.53) and white blood cell count at initial diagnosis (OR=0.52,95%CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions: The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

[Transperineal targeted prostate puncture combined with rapid pathological examination in the diagnosis of prostate cancer].

Exploring the clinical value of multiparametric magnetic resonance (Mp-MRI)-cognitive fusion method of targeted transperineal prostate puncture combined with rapid pathological diagnosis. Patients with suspected prostate cancer admitted to our hospital from 2022.01 to 2023.05 were selected as the study subjects, and Mp-MRI was performed and the suspected lesions were scored by the Prostate Imaging Reporting and Data System (PI-RADS). The enrolled patients were randomly divided into the transperineal prostate targeted puncture plus rapid pathology group (experimental group) and the transperineal prostate systematic combined targeted puncture plus conventional pathology group (control group), and the positive puncture rate, pathological findings, and complications were analyzed to compare the differences between the two groups. A total of 100 patients were enrolled, 53 in the experimental group [age 55-89 years, (73.17±7.79) years; tPSA 7.01-100 µg/L, mean 21.34 (12.38, 44.42) µg/L]and 47 in the control group [age 60-87 years, (71.96±7.07) years; tPSA 6.11-98.82 µg/L, mean 18.77 (9.04, 38.09) µg/L], and there was no significant difference between the two groups in the diagnostic positivity rate of overall PCa and clinically significant PCa (P>0.05); there was no significant difference in the highest Gleason score of pathological tissues between the two groups (P>0.05); the number of cases of medically induced sarcoid hematuria in the experimental group were significantly reduced compared with the control group (P<0.05). In terms of biopsy pain score (VAS), patients in the experimental group experienced less pain than those in the control group (P<0.05). The Mp-MRI-cognitive fusion method of transperineal targeted prostate puncture combined with rapid frozen section pathological examination can provide rapid and accurate pathological results, reduce the chance of post-puncture complications, and alleviate the pain caused by puncture sampling, which has high clinical value.

[Study on primary screening technique for children with autism spectrum disorder].

To explore screening tools for children with autism spectrum disorder (ASD), which are convenient for primary hospitals, it can provide basic data for formulating ASD prevention policies. This was a cross-sectional study by cluster sampling. Huyi District and Xincheng District were extracted for investigation in Xi'an City. From July 2021 to September 2022, all children aged from 3 months to 36 months who live in the two districts were subjected to primary screening. The child care physician used the routine screening tool "warning signs checklist for screening psychological, behavioral and developmental problems of children" and cartoon pictures of "early high-risk warning signs of autism", the children who were positive in the initial screening were referred to the district level maternal and child health hospital for re-screening, and those who were positive in the re-screening were referred to Xi 'an Children's Hospital for diagnosis. The results showed that a total of 17 905 children aged from 3 months to 36 months were initially screened in the two districts, including 10 588 children aged from 18 months to 36 months, 50 children who were positive in the initial screening and 50 children who were re-screened. 23 children (18 boys and 5 girls) were diagnosed with ASD. The prevalence rate of ASD in children was 2.17‰ (95% confidence interval:1.29‰-3.06‰). 42 children were positive for "warning signs checklist" at the preliminary screening, and 19 were confirmed as ASD. 27 children were positive for "cartoon pictures" in the preliminary screening, and 23 were confirmed with ASD. The "cartoon pictures" in the preliminary screening and diagnosis of consistent rate was higher than the "warning signs checklist", two kinds of screening methods comparison were statistically significant difference in the odds of consistent (χ2=11.01, P=0.001). In conclusion, relying on the three-level network of maternal and child health care, it is conducive to the whole process management of screening and diagnosis of children with ASD, and to guide the formulation of prevention policies. The cartoon pictures of "early high-risk warning signs of autism" can assist the identification of children with ASD based on the "warning signs checklist", which is simple, effective and suitable for promotion in the community health care.

[Clinicopathological analysis of superior mediastinal lymph node metastases in medullary thyroid carcinoma].

Objective: To investigate the clinicopathological characteristics of superior mediastinal lymph node metastases (sMLNM) in medullary thyroid carcinoma (MTC). Methods: This retrospective analysis enrolled the patients who were treated for sMLNM of MTC in our hospital from May 2012 to January 2021. All patients were suspected of sMLNM due to preoperative imaging. According to the pathological results, the patients were divided into two groups named sMLNM group and the negative superior-mediastinal-lymph-node group. We collected and analyzed the clinical features, pathological features, pre- and post-operative calcitonin (Ctn), and carcinoembryonic antigen (CEA) levels of the two groups. Logistic regression analysis was used to analyze risk factors, and receiver operation characteristic (ROC) curves were drawn to determine the optimal cut-off values of preoperative Ctn and preoperative CEA for predicting sMLNM. Results: Among the 94 patients, 69 cases were in the sMLNM group and 25 cases were in the non-SMLNM group. Preoperative Ctn level (P=0.003), preoperative CEA level (P=0.010), distant metastasis (P=0.022), extracapsular lymph node invasion (P=0.013), the number of central lymph node metastases (P=0.002) were related to sMLNM, but the multivariate analysis did not find any independent risk factors. The optimal threshold for predicting sMLNM by pre-operative Ctn is 1500 pg/ml and AUC is 0.759 (95% CI: 0.646, 0.872). The sensitivity, specificity, positive predictive value, and negative predictive value of diagnosis are 61.2%, 77.3%, 89.1%, 39.5%, respectively. In patients who underwent mediastinal lymph node dissection through transsternal approach, the metastatic possibility of different levels from high to low were level 2R (82.3%, 28/34), level 2L (58.8%, 20/34), level 4R (58.8%, 20/34), level 3 (23.5%, 8/34), level 4L (11.8%, 4/34). Postoperative complications occurred in 41 cases (43.6%), and there was no perioperative death in all cases. 14.8% (12/81) of the patients achieved biochemical complete response (Ctn≤12 pg/ml) one month after surgery, 5 of these patients were in sMLNM group. Conclusions: For patients who have highly suspicious sMLNM through imaging, combining with preoperative Ctn diagnosis can improve the accuracy of diagnosis, especially for patients with preoperative Ctn over 1 500 pg/ml. The superior mediastinal lymph node dissection for the primary sternotomy should include at least the superior mediastinal levels 2-4 to avoid residual lesions. The strategy of surgery needs to be cautiously performed. Although the probability of biochemical cure in sMLNM cases is low, nearly 40% of patients can still benefit from the operation at the biochemical level.

[Correlation of micropapillary patten, cribriform pattern and retraction clefting of endocervical adenocarcinoma with the Silva classification system and prognosis].

Objective: To investigate the relationship between micropapillary patten, cribriform pattern and retraction clefting of HPV associated endocervical adenocarcinoma and Silva classification and prognosis; and to validate the application and clinical significance of Silva system in endocervical adenocarcinoma. Methods: Cases of endocervical adenocarcinoma from January 2009 to November 2017 were selected from the Second Hospital of Jilin University and followed up. The morphologic characteristics of Silva classification, micropapillary patten, cribriform pattern and retraction clefting were observed and recorded. Inferential analysis was performed to compare clinicopathological variables data between pattern subgroups. Results: The study included 120 patients (ranging from 26 to 73 years) with an average age of (48.0±9.1)years. Silva A, B and C accounted for 9.2% (11/120), 18.3% (22/120) and 72.5% (87/120), respectively. Cases with micropapillary pattern accounted for 25.8%(31/120), of which six cases were Silva B and 25 cases were Silva C. Cases with cribriform pattern accounted for 53.3%(64/120), including three cases of Silva A, 17 cases of Silva B and 44 cases of Silva C. Retraction clefting occurred in 28.3%(34/120) cases, all were Silva C. The three morphologic features were associated with lymph node metastasis (P<0.05). Univariate analysis showed that micropapillary pattern was related to prognosis of endocervical carcinoma (P<0.05), while cribriform pattern, retraction clefting and Silva classification showed no correlation with overall survival and disease-free survival. Conclusions: The suggestion is revising the Silva C criteria by adding papillary patten and retraction clefting as factors and expanding the Silva pattern system to include more histologic variants. The Silva system is helpful to select appropriate operation before surgery, but its prognostic value requires further evaluation.

[Analysis of surgical strategy for pediatric papillary thyroid carcinoma with low-intermediate risk].

Objective: To explore the feasibility and rationality of lobectomy in the treatment of pediatric thyroid papillary carcinoma (PTC) with low-intermediate risk. Methods: The clinicopathological features and follow-up data of pediatric PTC with low-intermediate risk were reviewed from March 2000 to December 2018 in Cancer Hospital of Chinese Academy of Medical Sciences. The correlations between different surgical procedures and prognoses were evaluated. Propensity score matching(PSM) was used to adjust for risk factors, and the difference in prognoses between the total thyroidectomy (TT) group and the lobectomy (LT) group was compared. Results: A total of 140 patients were included in the study, including 36 males and 104 females. The age range was from 6-year-old to 18-year-old. There were 43 low-risk patients and 97 intermediate-risk patients. The median follow-up time was 87.5 months, ranging from 8 to 241 months, and 20 patients (14.3%) showed recurrence during the follow-up period. Univariate analysis showed that N1b, extrathyroidal extension, the number of lymph node metastasis>5, the ratio of lymph node metastasis≥0.19, and radioactive iodine treatment were risk factors for recurrence (all P value below 0.05), but multivariate analysis showed that only the ratio of lymph node metastasis≥0.19 (HR=8.69, 95%CI=1.08-70.21, P=0.043) was an independent risk factor for recurrence. There was no significant difference in the 5-year recurrence free survival rates between TT group and LT group before propensity score matching (82.8% vs. 86.5%, χ2=0.219, P=0.640) and after propensity score matching (89.6% vs. 90.4%, χ2=0.099, P=0.753). Conclusion: There is no significant difference in recurrence-free survival between TT group and LT group. Lobectomy is feasible for selective pediatric PTC with low-intermediate risk.

[Study on the expression of microRNA-1825 in serum of pre-operative and post-operative patients with breast cancer].

By measuring the relative expression level of miR-1825 in serum of pre-operative and post-operative patients with breast cancer and healthy subjects, the clincal value of miR-1825 for pre-operative and post-operative breast cancer patients was evaluated.The serum of pre-operative breast cancer patients(n=92), post-operative breast cancer patients(n=64) and healthy subjects(n=60) were collected from General Hospital of Southern Theatre Command of PLA from October 2018 to March 2021. Real-time quantitative PCR was used to detect the relative expression of miR-1825 in the serum of breast cancer patients and healthy controls. The clinicopathological data were used to analyze the correlation between the expression level of miR-1825 and serum tumor markers level. The receiver operating characteristic curve (ROC) was used to evaluate the diagnosis value of breast cancer with miR-1825, CA15-3. Mann-Whitney U test was used for comparisons between two groups,and Kruskal-Wallis H test was used for multiple group comparisons. The correlation between miR-1825 and CEA, CA15-3, CA-125 expression were analyzed using Spearman correlation test.The relative expression level of miR-1825 in serum of pre-operative patients with breast cancer 1.290(0.705, 1.793) was significantly higher than that of healthy controls 0.18(-0.876, 0.725), but decreased after surgery and chemotherapy -0.080(-0474, 0.405). The analysis of clinicopathological characteristics found that the expression level of miR-1825 was higher in patients with stage Ⅲ-Ⅳ, low degree of tissue differentiation, and tumor larger than 2 cm[stageⅠ-Ⅱ:0.975(0.458, 1.380), stageⅢ-Ⅳ: 1.955(1.663, 2.535), U=98.000, P<0.001;low degree of tissue differentiation:1.685(1.448, 2.143), high/medium degree of tissue differentiation:0.700(0.395, 0.898), U=15.500, P<0.001; tumor smaller than 2 cm:0.935(0.438, 1.370), tumor larger than 2 cm:1.915(1.580, 2.288), U=215.500, P<0.001].Spearman analysis result showed that the expression of serum miR-1825 in breast cancer patients was linearly correlated with the expression of CEA (r=0.274, P=0.008) and CA15-3 (r=0.587, P<0.001); ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. When using one biomarker to discriminate pre-operation and post-operation patients,miR-1825 had the best diagnostic efficiency,with an area under the ROC curve(AUC) of 0.914(95%CI: 0.872-0.956). miR-1825 may become a potential serum marker for the diagnosis of breast cancer and monitoring of therapeutic efficacy.

Effects of CAR structure and culture conditions on memory CAR-T cells.

Adoptive CAR T cell therapy (chimeric antigen receptor T-Cell) has received increasing attention in recent years; however, its efficacy is undesirable and differs from person to person. Understanding how to overcome this obstacle is important to improve therapy. Infusion of poorly differentiated CAR-CD62L+ T cells, such as T memory stem cell populations, leads to enhanced T cell implantation, expansion, and persistence, which ultimately leads to more stable tumour regression. Here, we reviewed emerging findings demonstrating that CAR structure and cell culture conditions can influence CAR T cell differentiation and antitumour efficacy.

Elevated CISD2 expression predicts poor diagnosis and promotes invasion and migration of prostate cancer cells.

OBJECTIVE: To explore roles of CDGSH iron-sulfur domain-containing protein 2 (CISD2) in the progression of prostate cancer (PCa) cells, and relationships between CISD2 expression and the prognosis and clinical pathological parameters in PCa patients. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) analysis and Western blot analysis were used to detect the CISD2 expression in PCa tissues and cells. CISD2 siRNA was used to inhibit the CISD2 expression. Kaplan-Meier method and Log rank analysis were performed to determine survival analysis while Chi-square test was performed to analyze the association between CISD2 and clinicopathological parameters of PCa patients. Transwell assay and wound healing assay was conducted to examine the invasion and migration ability of PCa cells, respectively. RESULTS: CISD2 was up-regulated in PCa tissues and cells, and showed positive association with the poor prognosis, T stage, lymphatic invasion, prostate-specific antigen (PSA) level, and distant metastasis of PCa patients. Besides, we found that inhibition of CISD2 significantly impaired the migration and invasion ability of PCa cells. CONCLUSIONS: The paper demonstrated that CISD2 could act as a new target for the diagnosis and treatment of PCa patients.

[Spondyloenchondrodysplasia with immune dysregulation: a case report and literature review].

Objective: To analyze the clinical characteristics of spondyloenchondrodysplasia with immune dysregulation (SPENCDI). Methods: The clinical manifestations, laboratory examinations, treatment and genetic analysis of a patient diagnosed with SPENCDI who was admitted to the Department of Pediatrics in Peking Union Medical College Hospital in October 2016 were analyzed. Then literature review was done after searching articles in PubMed and several Chinese databases with the key words "spondyloenchondrodysplasia with immune dysregulation" up to the date of November 2017. Results: A 12-year-old girl was admitted to local hospital for complaint of "recurrent fever over one month" in October 2016. She was diagnosed with type Ⅱ autoimmune hepatitis for abnormal liver function, elevated immunoglobulin G, positive anti-liver-kidney microsomal antibody and medium to severe interface hepatitis verified by liver biopsy. Systemic lupus erythematosus was also suspected based on positive antinuclear antibody and anti-dsDNA antibody, decreased complements, reduced white blood cells and hemoglobin. Methylprednisolone and azathioprine were started based on the diagnosis. However, she experienced mycoplasma pneumoniae and suspected fungal infections during the treatment. Detailed history revealed the history of developmental retardation since birth, and cerebral palsy diagnosed when she was 2 years old. She also underwent surgery at the age of eight for eversion of her right foot. Based on the abnormal findings of immune system, skeleton and nervous system, certain primary immunodeficiency disease was speculated. Gene sequencing was performed, which revealed compound heterozygous mutations in ACP5 gene (NM_001111035.2) (c.798dupC, p. S267Lfs*20, paternal; c.716G>A, p. G239D, maternal). With X-ray of the vertebrae showed multiple platyspondyly, the diagnosis was corrected as SPENCDI and type Ⅱ autoimmune hepatitis. Then she was treated with prednisone (60 mg/d) and mycophenolate mofetil (1.5 g/d). All symptoms resolved on 3-month follow-up, with normalized activity indexes of autoimmune hepatitis and systemic lupus erythematosus. A total of 25 articles (1 Chinese, 24 English) were reviewed, with 74 SPENCDI patients reported. The most common manifestations were skeletal abnormalities (74/74, 100%), autoimmune diseases (47/74, 63.5%), dwarfism (45/74, 60.8%), and nervous system symptoms (25/74, 33.8%). A few patients with simple spondyloenchondrodysplasia were treated with growth hormone, and those who with autoimmune diseases were treated with immunosuppressants, all of whom were improved to certain extent. Conclusions: Vertebral and metaphyseal dysplasia, nervous system symptoms, and strong predisposition to autoimmune diseases are the hallmarks of SPENCDI. SPENCDI should be considered in dwarf with or without autoimmune diseases or nervous system symptoms.

[Dye-tattooing under ultrasound guidance in preoperative localization of neck recurrences from thyroid cancer].

Objective: To evaluate the efficacy and safety of the application of dye-tattooing under ultrasound guidance in preoperative localization of neck recurrences from thyroid cancer. Methods: Between October 2014 to September 2016, 25 patients with 34 lesions were enrolled. There were 22 cases of papillary thyroid carcinoma and three cases of medullary thyroid carcinoma, all of which could not be detected by computed tomography. Surgeons located the recurrent lesions using dye-tattooing under ultrasound guidance along with radiologist three days before the operation. Results: All lesions were successfully located (100%), 32 of which were located directly and two of which were located indirectly. Postoperative pathological examination confirmed 25 metastases of papillary thyroid carcinoma, two metastases of medullary thyroid carcinoma, and seven cases of false positives. The accuracy of ultrasound diagnosis was 79.4%. After 15 months of follow-up, neither tumor residual nor recurrences was detected according to imaging tests. Conclusions: Dye-tattooing under ultrasound guidance represents a reliable and safe method for localization of neck recurrences from thyroid cancer. The cooperation between experienced surgeons and radiologists will be crucial to successful location.

[Clinical analysis of secondary cervical lymph node dissection in papillary thyroid carcinoma].

Objective: To investigate the value of secondary cervical lymph node dissection in papillary thyroid carcinoma (PTC). Methods: PTC patients with recurrence re-operated in a previously dissected area at our hospital during 2000-2016 were included in this analysis. Patients were divided according to the operative interval of 6 months. The level and number of lymph node metastasis and the number of lymph node dissection were analyzed to calculate the ratio of lymph node metastasis. Results: A total of 336 PTC patients received 360 side lateral cervical lymph nodes dissection. The ratio of recurrence in unilateral lateral neck is 92.9%(312/336). The ratio of recurrence in multiple levels (more than two regions) were 47.5% (171/360). The recurrence ratio of level Ⅱ, Ⅲ, Ⅳ and Ⅴ were 55.6%(200/360), 44.2%(159/360), 59.7%(215/360) and 10.3%(37/360), respectively. Lymph node metastases were inclined to level Ⅱ (33.6%) and Ⅳ (35.8%). The mean number of lymph node dissection and metastasis in the group of operative interval ≤ 6 months was 26.56 per case and 4.37 per case, respectively. The mean number of lymph node dissection and metastasis in the group of operative interval >6 months was 16.80 per case and 3.20 per case, respectively. The number of lymph node dissection and metastasis between these two groups were significantly different (P=0.001, P<0.001). Conclusions: Lymph node metastasis of PTC patients with secondary cervical lymph node dissection are inclined to level Ⅱ and level Ⅳ. Moreover, multi-level metastasis is not rare. Level Ⅱ and level Ⅳ require more attention in the first operation. Most of the patients undergo reoperation because of residual lymph nodes from the previous treatment. Normalization and completeness of the initial dissection are particularly important to PTC patients.

[Clinical features of postoperative cervical lymph nodes recurrence in papillary thyroid carcinoma].

Objective: To analyse the postoperative metastasis or recurrence of cervical lymph nodes in individual neck levels for papillary thyroid carcinoma and to evaluate the outcomes and complications of re-surgery. Methods: A retrospective cohort study of 259 patients who underwent lymph node dissection for PTC relapse from January 2010 to June 2011. Lymph node metastases in each of neck levels were detected, postoperative complications were evaluated, and the patients were followed up with examining thyroglobulin levels to assess the therapeutic effect.Continuous variables were compared with t test.Categorical variables were compared with Fisher's exact test. Results: Lymph node metastasis was found in 259 cases and lymph node metastasis rates in levels Ⅱ, Ⅲ, Ⅳ, Ⅴ and Ⅵ were 43.2%, 50.2%, 45.6%, 8.1% and 59.1% respectively. In 44 cases received the neck dissection of level Ⅱ, the metastasis rates in the levels Ⅱa and Ⅱb were respectively (52.3% vs 18.2%, P=0.887). Recurrence in unilateral lateral neck was more common than that in bilateral lateral neck (73.1% vs 20.6%, P<0.001). The lymph nodes in lateral neck were more likely to metastasize than those in central region (80.7% vs 59.1%, P<0.001). There were 47 cases (18.1%) had postoperative complications, including 10 cases with permanent hypocalcemia. Conclusions: The scope of re-operation for neck metastasis or recurrence in papillary thyroid carcinoma should include the dissection of levels Ⅱ-Ⅳ and Ⅵ. The incidence of postoperative complications for re-surgery is high, and re-surgery should be performed by experienced surgeon.

[Preparation of chaperone-antigen peptide vaccine derived from human gastric cancer stem cells and its immune function].

Objective: To explore the method of extracting chaperone antigen peptide complexes from gastric cancer stem cells and its immune function. Methods: Gastric cancer stem cells and gastric cancer cells were screened by low temperature ultrasonic lysis. After salting out and dialysis, the lysate supernatant was processed with SDS-PAGE to analyze the expression of chaperone antigen peptide complexes, and then was separated and purified with CNBr-activated SepharoseTM 4B. Reverse high pressure liquid chromatography (HPLC), SDS-PAGE and Western blotting were used to analyze the purity and nature of the acquired albumen. Lymphocyte proliferation assay and lymphocytotoxicity assay were used to ditermine the immunological activity of the chaperone-antigen peptide complexes. Results: The chaperone antigen peptide complexes of gastric cancer stem cells were prepared and identified successfully, of which the main components were the antigen peptides of HSP60, HSP70, HSP90 and HSP110. 0.75 µg and 1.00 µg HSP70-antigen peptide and 1.00 µg HSP90-antigen peptide activated lymphocytes significantly. Their A(490) values were 0.26±0.03, 0.45±0.05 and 0.32±0.04, respectively, while the corresponding doses of HSP60-antigen peptide and HSP110-antigen peptide did not activate lymphocytes. The killing rates of 1.00 µg HSP70-antigen peptide and 1.00 µg HSP70 were (45.0±2.0)% and (16.0±2.0)%, respectively, showing a significant difference (P=0.012). Similarly, the killing rates of 1.00 µg HSP90-antigen peptide and 1.00 µg HSP90 were (36.0±5.0)% and (13.0±4.0)%, respectively, also showing a significant difference (P=0.048). Conclusions: The amount of chaperone antigen peptide complexes in gastric cancer cells is extremely low, but it is obviously increased in gastric cancer stem cells. After purification, the chaperone antigen peptide complexes with high purity can be prepared. The extracted chaperone antigen peptide complexes have stronger immunogenicity, and can be used to make tumor vaccine in vitro, which may have a good application value in the targeted therapy of gastric cancer.

[Hyper-IgE syndromes].

A hyper-IgE syndrome is a rare immunodeficiesncy disease, often accompanied by high serum IgE. It often characterized by facial features, repeated skin infections, eczema and pulmonary infection, including autosomal dominant HIES (AD-HIES) and autosomal recessive HIES (AR-HIES). AR-HIES is caused by mutations in STAT3, which is presented as connective tissue, bone, vascular disease, and high brain white matter signal. AD-HIES is mainly caused by mutations in DOCK8 and TYK2, which is presented as severe viral infection and poor prognosis. The treatment for Hyper-IgE syndromes is mainly to control infection, skin care and other symptomatic treatment, if necessary, should be done as early as possible hematopoietic stem cell transplantation. This article reviews the clinical manifestations, pathogenesis and treatment of high IgE syndrome.

[Treatment of liver cancer in vitro and in mice by monoclonal antibody targeting epithelial specific antigen-positive liver cancer stem cells in combination with cisplatin].

OBJECTIVE: To investigate the biological characteristics of monoclonal antibodies against human liver cancer stem cells and its therapeutic effect in combination with cisplatin in the treatment of hepatocellular carcinoma. METHODS: Cell culture in serum-free medium and PKH26 staining were used to determine the existence of cancer stem cells in human liver Bel7402-V3 cell line. The co-expression of antigen recognized by monoclonal antibody (McAb) 15D2 and epithelial specific antigen (ESA) and PKH26-positive cells in the Bel7402-V3 cells were detected by immunofluorescence assay. Serum-free suspension culture was used to detect the self-renewal ability of 15D2-positive Bel7402-V3 cells sorted by flow cytometry and the effect of 15D2 on the self-renewal ability of Bel7402-V3 cells. The effect of 15D2 on cisplatin resistance in the cells was examined by CCK8 method. The inhibitory effect of 15D2 combined with cisplatin on the transplanted tumor growth in mice was also observed. RESULTS: Single PKH26-positive cells were observed in the Bel7402-V3 cell spheroids cultured for 11 days. Immunofluorescence assay showed that the 15D2-recognized antigen could be conjugated with PKH26 and ESA and co-localized on Bel7402-V3 cells. The spheroid formation rate of 15D2-positive cells in serum-free medium was significantly higher than that of 15D2-negative cells [(30.4±3.4)% vs. (8.8±1.8)%, P<0.01]. The cisplatin resistance of 15D2-positive cells was obviously higher than that of 15D2-negative cells (IC50: 1.014 µmol/L vs. 0.365 µmol/L). McAb 15D2 significantly suppressed the spheroid formation of Bel7402-V3 cells, with an inhibition rate of 37.5%. McAb 15D2 also notably inhibited the cisplatin resistance of Bel7302-V3 cells. The IC50 was 0.211 µg/ml in the 15D2 group and 0.325 µg/ml in the control group. The mouse experiment showed that the tumor growth rates of 50 mg/kg, 25 mg/kg and 12.5 mg/kg 15D2-treatment groups were 82.6%, 71.4% and 60.0%, respectively; that of the 50 mg/kg 15D2 + cisplatin group was 91.0%, and that of the cisplatin monotherapy was 56.7%. CONCLUSION: McAb 15D2 is a functional monoclonal antibody targeting liver cancer stem cells, which could be a potential monoclonal antibody drug for the stem cell-targeted therapy of liver cancer.

TGF-ß signaling links E-cadherin loss to suppression of nucleotide excision repair.

E-cadherin is a cell adhesion molecule best known for its function in suppressing tumor progression and metastasis. Here we show that E-cadherin promotes nucleotide excision repair through positively regulating the expression of xeroderma pigmentosum complementation group C (XPC) and DNA damage-binding protein 1 (DDB1). Loss of E-cadherin activates the E2F4 and p130/107 transcription repressor complexes to suppress the transcription of both XPC and DDB1 through activating the transforming growth factor-ß (TGF-ß) pathway. Adding XPC or DDB1, or inhibiting the TGF-ß pathway, increases the repair of ultraviolet (UV)-induced DNA damage in E-cadherin-inhibited cells. In the mouse skin and skin tumors, UVB radiation downregulates E-cadherin. In sun-associated premalignant and malignant skin neoplasia, E-cadherin is downregulated in association with reduced XPC and DDB1 levels. These findings demonstrate a crucial role of E-cadherin in efficient DNA repair of UV-induced DNA damage, identify a new link between epithelial adhesion and DNA repair and suggest a mechanistic link of early E-cadherin loss in tumor initiation.