Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

Objective:To investigate the effects of sampling methods on pathological assessment of resected non-small cell lung cancer (NSCLC) specimen with tumor maximum diameter >3 cm after neoadjuvant therapy.Methods:NSCLC patients with a large tumor (diameter >3 cm) that were resected after neoadjuvant therapy from June 2020 to July 2023 were retrospectively collected in the Department of Pathology, Shanghai Pulmonary Hospital, Shanghai, China. Sampling methods of the tumor bed were performed in accordance with the international and Chinese experts recommendations for resection specimens following neoadjuvant therapy (recommended sampling method, RSM), and all remaining tumor bed lesions were completely sampled after recommended sampling (complete sampling method, CSM). The difference of pathological response assessment of residual viable tumor (RVT) between RSM and CSM was examined.Results:A total of 90 cases were identified and analyzed, including 39 cases of squamous cell carcinoma and 51 cases of adenocarcinoma, treated with neoadjuvant therapy including chemotherapy in 22 cases (24.4%), targeted therapy in 14 cases (15.6%), and chemoimmunotherapy in 54 cases (60.0%). There were 62 males and 28 females with an average age of (62.7±17.9) years. The average tumor maximum diameter was 4.3 cm (range, 3.1-8.0 cm). The average number of sampled blocks was 8 blocks (range, 5 to 16) and 15 blocks (range, 8 to 36) per case by RSM and CSM, respectively. According to the definition of major pathological response (MPR) in which RVT is ≤10%, the numbers of patients with MPR were 34 cases by RSM and 30 cases by CSM, respectively. Four cases showed inconsistent RVT between the two methods, including one case of squamous cell carcinoma and three cases of adenocarcinoma. The RVT of the four inconsistent cases was 7%, 7%, 5% and 9% (MPR by RSM), and 15%, 15%, 15% and 20% (non-MPR by CSM), respectively. The kappa values of MPR consistency evaluated by the two sampling methods were 0.893 for all cases, 0.906 for squamous cell carcinoma cases and 0.751 for adenocarcinoma cases. According to MPR cut-off of 65% for invasive primary adenocarcinoma, 24 cases and 20 cases achieved MPR by RSM and CSM, respectively. Of the four inconsistent cases, the RVT by RSM was 60% in three cases and 65% in one case (MPR), whereas the RVT by CSM was 70% in three cases and 75% in one case (non-MPR). The kappa value of the two sampling methods was 0.741.Conclusions:There is high consistency between RSM and CSM in the pathological assessment of post-treatment responses in resected NSCLC specimens with tumor maximum diameter larger than 3 cm. When the percentage of RVT cells is close to MPR, re-evaluation of the specimen is required and CSM may be necessary to accurately evaluate the degree of pathological remission, assist in clinical postoperative treatment, and predict patient prognosis.

Objective:To investigate the effects of sampling methods on pathological assessment of resected non-small cell lung cancer (NSCLC) specimen with tumor maximum diameter >3 cm after neoadjuvant therapy.Methods:NSCLC patients with a large tumor (diameter >3 cm) that were resected after neoadjuvant therapy from June 2020 to July 2023 were retrospectively collected in the Department of Pathology, Shanghai Pulmonary Hospital, Shanghai, China. Sampling methods of the tumor bed were performed in accordance with the international and Chinese experts recommendations for resection specimens following neoadjuvant therapy (recommended sampling method, RSM), and all remaining tumor bed lesions were completely sampled after recommended sampling (complete sampling method, CSM). The difference of pathological response assessment of residual viable tumor (RVT) between RSM and CSM was examined.Results:A total of 90 cases were identified and analyzed, including 39 cases of squamous cell carcinoma and 51 cases of adenocarcinoma, treated with neoadjuvant therapy including chemotherapy in 22 cases (24.4%), targeted therapy in 14 cases (15.6%), and chemoimmunotherapy in 54 cases (60.0%). There were 62 males and 28 females with an average age of (62.7±17.9) years. The average tumor maximum diameter was 4.3 cm (range, 3.1-8.0 cm). The average number of sampled blocks was 8 blocks (range, 5 to 16) and 15 blocks (range, 8 to 36) per case by RSM and CSM, respectively. According to the definition of major pathological response (MPR) in which RVT is ≤10%, the numbers of patients with MPR were 34 cases by RSM and 30 cases by CSM, respectively. Four cases showed inconsistent RVT between the two methods, including one case of squamous cell carcinoma and three cases of adenocarcinoma. The RVT of the four inconsistent cases was 7%, 7%, 5% and 9% (MPR by RSM), and 15%, 15%, 15% and 20% (non-MPR by CSM), respectively. The kappa values of MPR consistency evaluated by the two sampling methods were 0.893 for all cases, 0.906 for squamous cell carcinoma cases and 0.751 for adenocarcinoma cases. According to MPR cut-off of 65% for invasive primary adenocarcinoma, 24 cases and 20 cases achieved MPR by RSM and CSM, respectively. Of the four inconsistent cases, the RVT by RSM was 60% in three cases and 65% in one case (MPR), whereas the RVT by CSM was 70% in three cases and 75% in one case (non-MPR). The kappa value of the two sampling methods was 0.741.Conclusions:There is high consistency between RSM and CSM in the pathological assessment of post-treatment responses in resected NSCLC specimens with tumor maximum diameter larger than 3 cm. When the percentage of RVT cells is close to MPR, re-evaluation of the specimen is required and CSM may be necessary to accurately evaluate the degree of pathological remission, assist in clinical postoperative treatment, and predict patient prognosis.

Background::Essential tremor (ET) and Parkinson’s disease (PD) are common movement disorders. ET-PD syndrome is characterized by the occurrence of PD in patients with a previous history of ET, which may be an independent phenotype distinct from PD. This study aims to identify clinical characteristics and subtypes in ET-PD.Methods::A total of 93 newly diagnosed ET-PD patients and 93 newly diagnosed PD patients matched for age, sex, education, and disease duration of PD were selected using propensity score matching analysis. The K-means cluster analysis was performed for 11 variables derived from the ET-PD group, and cluster profiles were established through statistical analysis of demographic and clinical variables.Results::The ET-PD group consisted of a high number of patients with a family history of ET exhibiting evident tremor with milder hypokinesia and postural instability symptoms, as compared to the PD group. Through the cluster analysis, two clusters of ET-PD patients were identified. The ET-PD cluster 1 ( n = 34) had a shorter ET duration before PD onset, lower number of patients with a family history of ET, higher unified PD rating scale instability scores, higher non-motor symptoms scores (non-motor symptoms scale D1 scores, Hamilton depression scale scores, Hamilton anxiety scale scores, and PD sleep scale-2 scores), and higher Chinese version of the PD questionnaire-39 scores relative to the ET-PD cluster 2 ( n = 59). Conclusion::ET-PD patients had significantly different characteristics for motor symptoms as compared to PD patients, and may be distinctly divided into two clinical subtypes, namely, the ET-PD complex type and the ET-PD simple type.

Objective:To investigate the attribution therapy on self-efficacy and physical function among patients with rheumatoid arthritis, and provide reference for functional rehabilitation of patients.Methods:A total of 72 rheumatoid arthritis patients of Rheumatology Department of Henan Province Orthopaedic Hospital were divided into experimental group ( n=36) and control group ( n=36) by random digits table method. The control group received routine nursing, while experimental group implemented attribution therapy for 6 times. Before and after 3 months of intervention, the intervention effect was assessed by using Health Assessment Questionnaire (HAQ), Clinical Disease Activity Index (CDAI), morning stiffness time as well as Arthritis Self-efficacy Scale (ASES), respectively. Results:After intervention, the scores of HAQ, CDAI were 0.62 ± 0.23, 9.52 ± 3.15, morning stiffness time were (31.76 ± 5.80) minutes in the experimental group, significantly lower than those in the control group (0.91 ± 0.33, 12.41 ± 2.70) points and (35.91 ± 7.90) minutes. The differences were statistically significant ( t=4.09, 4.04, 2.46, all P<0.05). The scores of self-efficacy pain subscale, self-efficacy function subscale, self-efficacy other symptoms subscale and total ASES scores were 6.58 ± 1.20, 5.88 ± 1.36, 6.67 ± 1.90 and 6.30 ± 0.81, significantly higher than those in the control group (5.97 ± 0.76, 5.18 ± 1.24, 5.59 ± 1.73 and 5.59 ± 0.74), the differences were statistically significant ( t values were 2.21-3.77, P<0.05). Conclusions:Attribution therapy can effectively alleviate physical function and promote self-efficacy of patients with rheumatoid arthritis.

During a radiological or nuclear emergency, iodine thyroid blocking is an urgent protection action to prevent or reduce the absorption of radioactive iodine by thyroid. Although potassium iodide (KI) administration is recommended by WHO guidelines for iodine prophylaxis following nuclear accidents and is also widely implemented in most national guidelines, the scientific evidence for the guidelines lacks as the guidelines are mostly based on expert opinions and recommendations. This paper introduces the development and revision of WHO guidelines for iodine thyroid blocking published in 1989 and 1999, as well as the revision methods and main recommendations of the guidelines published in 2017, which supports the use of iodine thyroid blocking during a radiological or nuclear emergency.

OBJECTIVE: To explore the genetic basis for a child with multiple malformation and growth retardation. METHODS: The child was subjected to low-coverage massively parallel copy number variation sequencing (CNV-seq) based on next generation sequencing (NGS) technique. RESULTS: G-banding karyotyping analysis has found no abnormality in the boy and his parents. CNV-seq analysis discovered that the child has carried a heterozygous 4.36 Mb deletion (24 020 000-28 380 000) at 7p15.3p15.1. The same deletion was not found in either parent. The deletion has encompassed 28 OMIM genes including HOXA13, CYCS, DFNA5, HOXA11 and HOXA2. Among these, HOXA13 has been associated with distal limb deformity, hypospadias and cryptorchidism. HOXA1, HOXA3 and HOXA4 are involved in the formation of cardiac primordia and primordial tube, and HOXA2 is involved in the development of auditory system. The clinical phenotype of the child was consistent with that of 7p15 deletion syndrome. CONCLUSION Haploinsufficiency of HOXA1, HOXA2, HOXA3, HOXA4 and HOXA13 genes may underlie the clinical phenotype of the child, which is comparable to 7p15 deletion syndrome.

Objective To observe regular monitoring in patients with chronic myeloid leukemia (CML) who received tyrosine kinase inhibitor (TKI), and to analyze its influencing factors. Methods A total of 857 patients with CML in Henan Tumor Hospital from October 2012 to October 2016 were collected. Patients were told to receive regular monitoring after receiving TKI treatment, including blood routine, bone marrow, BCR-ABL fusion gene and chromosomes. All patients were divided into good and poor compliance groups according to regular monitoring. Chi-square test was used to compare ABL kinase domain mutations rate and mortality between two groups. TKI species, level of education, duration from diagnosis to treatment, teaching times, sites of follow-up, convenience of transportation, annual income and gender were recorded respectively, and the factors affecting regular monitoring were analyzed by using single and multiple factor analysis. Results There were 390 and 467 patients in good and poor compliance groups respectively. Treatment failure rate was 19.49％ (76/390) and 25.91％ (121/467) in good and poor compliance groups respectively, the mutation rate was 28.95％ (22/76) and 7.44％ (9/121) respectively. The difference of ABL kinase domain mutation in patients with treatment failure of both groups was statistically significant (χ 2 =16.287, P < 0.01). The mortality was 0.77％ (3/390) in good compliance group, and 2.78％ (13/467) in poor compliance group, and the difference was statistically significant (χ 2 = 4.543, P = 0.033). The single factors analysis showed that TKI species, level of education, duration from diagnosis to treatment, teaching times, sites of follow-up, convenience of traffic and annual income were related with regular monitoring (all P < 0.05). Multiple-factor analysis showed that inconvenient transportation (β = 1.56, 95％ CI 1.74-3.74, P = 0.014), low education level (β = 1.67, 95％ CI 0.81-3.12, P = 0.041) and low income (β = 2.87, 95％ CI 1.31-4.51, 95％CI 1.74-3.74, P = 0.011) were independent factors for poor compliance in regular monitoring. In the result detection, 56 fusion genes fluctuated. Conclusions CML patients who received regular monitoring have a low treatment failure rate and mortality. Inconvenient transportation, low education level and low outcome are independent risk factors for regular monitoring. The single monitoring result can not prompt treatment effect, and thus it needs to review and monitor for many times.

Objective To detect and analyze the percentages of CD4+T, CD8+T and invariant na-ture killer T ( iNKT) cells as well as iNKT subsets in different tissues and organs of non-obese diabetic (NOD)/LtJ mice before the onset and in the early and late stages of type 1 diabetes (T1D) for better under-standing the immune function in different disease stages. Methods Female NOD/LtJ mice were selected as experimental subjects. Their fasting blood glucose levels were measured by blood glucose meter. Glycosuria and blood glucose level ≥11. 1 mmol/L in two consecutive detections were used as the diagnostic criteria of T1D. These mice were divided into three groups as follows: non-onset, early stage and late stage groups. Changes in food and water intake, glucose level in the urine, body weight, mental state, fur color and urine volume were recorded. Percentages of CD4+T, CD8+T and iNKT cells and ratios of subsets in peripheral blood, thymus, spleen, liver and inguinal lymph nodes were detected by flow cytometry (FACS). Results (1) Compared with the non-onset and the early stage groups, mice in the late stage group were apathetic and had rough hair. Moreover, significantly increased water and food intake and urine output (P<0. 05) and de-creased body weight, thymus index, spleen index and the absolute lymphocyte counts of spleen, liver and thymus (P<0. 05) were observed in the late stage group. (2) Compared with the non-onset group, the early stage group showed significantly increased percentages of CD4+T cells in spleen, liver, thymus and inguinal lymph nodes (P<0. 05). Compared with the early stage group, the late stage group showed decreased per-centages of CD4+T cells in liver, thymus, inguinal lymph nodes and peripheral blood (P<0. 05). Compared with the non-onset group, the percentages of CD8+T cells in the early stage group were significantly increased in spleen and thymus, but reduced in inguinal lymph nodes (P<0. 05). Compared with the early stage group, the percentages of CD8+T cells in late stage group were significantly reduced in liver and thymus, but increased in inguinal lymph nodes (P<0. 05). (3) The percentages of iNKT cells in liver and inguinal lymph nodes of mice in the early stage group were significantly higher than those of the non-onset group (P<0. 05). The percentages of iNKT cells in peripheral blood and liver of mice in the late stage group were sig-nificantly lower than those of the early stage group (P<0. 05). No significant difference in the percentages of iNKT cells in spleen and thymus was found among the three groups (P>0. 05). (4) Compared with the non-onset group, the percentages of iNKT1 subset in thymus in the early and late stage groups were significantly increased, while the percentages of iNKT2 subset were significantly decreased (P<0. 05). No significant difference in the percentages of iNKT1 and iNKT2 subsets in spleen, liver and inguinal lymph nodes was found among the three groups (P>0. 05). (5) The percentages of iNKT2 subset in spleen, liver and ingui-nal lymph nodes were significantly lower than those of the iNKT1 subset in the three groups (P<0. 05). The percentage of iNKT2 subset in thymus was significantly higher than that of iNKT1 subset in the non-onset group (P<0. 05). (6) Compared with the non-onset and the late stage groups, the early stage group showed significantly increased levels of IFN-γ, IL-4 and IL-17A and up-regulated ratio of IFN-γ/IL-4 (P<0. 05). Compared with the non-onset and the early stage groups, the late stage group showed significantly increased IL-6 level (P<0. 05). Compared with the non-onset group, IL-10 level in the other two groups was in-creased, especially in the late stage group (P<0. 05). No significant difference in IL-2 level was found among the three groups (P>0. 05). Conclusion Increased percentages of iNKT cells and iNKT1 subset in NOD/LtJ mice with early stage of T1D might be involved in the development of T1D.

Objective: To establish the method for determination of titanium dioxide in the air of workplace by inductivehy coupled plasma optical emission spectrometry (ICP-OES) . Methods: The titanium dioxide was collected by filter membrane and then digested by microwave digestion apparatus in the mixed solvents (HNO₃∶HF∶H₂O=4∶1∶1) , dilutedto 25 ml and detected by ICP-OES. Results: The sampling efficiency was higher than 95%; the linearity of ICP-OES was good at the range of 10-500 μg/ml, the minimum quantitation concentration was 0.72 mg/m³ (as collecting 150 L air sample) , the maximum quantitation concentration was 21.7 mg/m³ (as collecting 960 L air sample) , the recovery was ranged from 99.0%-102.0%, the RSD of intra- and inter-batch precision were 0.5%-3.2% and 1.7%-3.5%, respectively. Conclusion The sampling method and determination method meet the requirements of guide for establishing occupational health standards-part 4: determinatin methods of air chemicals in workplace (GBZ/T 210.4-2008) , and areapplys to the collection and determination of TiO₂ in the air of workplace.