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.

INTRODUCTION: Visual impairment and obesity remain the major public health issues among school-age students in rural areas of China. Obesity is an underlying risk of vision problems. This study aimed to assess the association between visual impairment and body mass index (BMI) among school-age students in rural northwest China. METHODS: This study included 39,385 students from the 4 th to 9 th grade in rural northwest China. From 2018 to 2020, students underwent an assessment of visual acuity (VA) and completed a questionnaire on family demographics, and height and weight measurements. Multiple logistic regression analyses were used to analyse the data. RESULTS: The association between visual impairment and BMI groups was significant in the study population ( P = 0.002) and in different groups (at the different educational, provincial and national levels) ( P < 0.001, separately). Multiple logistic regression analyses revealed a positive relationship between visual impairment and obesity in the study population, including those attending primary school, Han students and the residents of Ningxia autonomous region. CONCLUSION The association between visual impairment and obesity was significant among school-age students in rural northwest China. There should be implementation of policies to address the problem about visual impairment and obesity among school-age students in rural areas.
Humans ; China/epidemiology* ; Body Mass Index ; Male ; Female ; Rural Population ; Vision Disorders/complications* ; Child ; Adolescent ; Students ; Surveys and Questionnaires ; Logistic Models ; Obesity/complications* ; Visual Acuity ; Cross-Sectional Studies

Objective:To explore the distribution of Traditional Chinese Medicine constitution among patients with impaired awareness of hypoglycemia (IAH) and identify risk factors for IAH in patients with diabetes mellitus, to develop a risk prediction model. The aim is to validate the models′ predictive accuracy to facilitate early prevention and treatment of IAH.Methods:A case control study employing convenience sampling model was conducted on 1351 hospitalized patients with diabetes mellitus in the endocrinology departments of Changshu Hospital Affiliated to Nanjing University of Chinese Medicine and Affiliated Hospital of Jiangsu University, between August 2021 and December 2023. Traditional Chinese medicine constitution types were determined using the Traditional Chinese Medicine Constitution Classification and Judgment (ZYYXH/T157-2009). Data were divided into training and test sets at a ratio of 7∶3. Two prediction models were developed: Model 1, a conventional IAH prediction model for patients with diabetes mellitus, and Model 2, an IAH prediction model for patients with diabetes mellitus incorporating traditional Chinese medicine constitution. Nomograms were drawn for both models. The Hosmer-Lemeshow goodness-of-fit test, calibration curve, receiver operating characteristic (ROC) curve, and area under the curve (AUC) were calculated to evaluate the effectiveness of models 1 and 2. The improvement in prediction performance between Models 1 and 2 was assessed using Delong test, AUC, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA).Results:The study included 1 283 patients with diabetes mellitus, including 578 males and 705 females, aged (59.61 ± 14.09) years. The incidence of IAH among patients with diabetes mellitus was 20.50% (263/1283), with yang deficiency constitution being the most prevalent traditional Chinese medicine constitution type, at 47.53% (125/263). Multivariate analysis revealed that age, body mass index, course of diabetes, neurological hypoglycemia symptoms, hypoglycemia symptoms and severe hypoglycemia history were the influencing factors of Model 1 (all P<0.05); age, body mass index, neurological hypoglycemic symptoms, hypoglycemic symptoms, history of severe hypoglycemia, and traditional Chinese medicine constitution were the influencing factors of Model 2 (all P<0.05). The Hosmer-Lemeshow goodness-of-fit test showed a good fit of Model 2 [training set ( χ2=8.48, P>0.05), test set ( χ2=3.92, P>0.05)]. The Delong test results showed that the AUC for Model 2 was 0.96 for both the training and test sets, significantly higher than the AUCs of the 0.90 and 0.91 for Model 1 ( Z=-7.27, -3.70, both P<0.01). Furthermore, NRI was 0.66 ( 95%CI 0.53-0.79, P<0.01) and IDI was 0.02 (95% CI 0.01-0.03, P<0.05) for Model 2. Comparative analysis of clinical utility demonstrated that the net benefit of Model 2 for predicting IAH in patients with diabetes mellitus surpassed that of Model 1 across threshold probabilities ranging from 5% to 100%. Conclusions:The study constructed a nomogram prediction model included traditional Chinese medicine constitution with good predictive performance for IAH in patients with diabetes mellitus, and is of significant clinical value for identifying high-risk IAH populations.IAH patients mainly have a biased constitution, indicating that medical staff can reduce the incidence of IAH by improving the patients′ constitution.

Objective:To explore the distribution of Traditional Chinese Medicine constitution among patients with impaired awareness of hypoglycemia (IAH) and identify risk factors for IAH in patients with diabetes mellitus, to develop a risk prediction model. The aim is to validate the models′ predictive accuracy to facilitate early prevention and treatment of IAH.Methods:A case control study employing convenience sampling model was conducted on 1351 hospitalized patients with diabetes mellitus in the endocrinology departments of Changshu Hospital Affiliated to Nanjing University of Chinese Medicine and Affiliated Hospital of Jiangsu University, between August 2021 and December 2023. Traditional Chinese medicine constitution types were determined using the Traditional Chinese Medicine Constitution Classification and Judgment (ZYYXH/T157-2009). Data were divided into training and test sets at a ratio of 7∶3. Two prediction models were developed: Model 1, a conventional IAH prediction model for patients with diabetes mellitus, and Model 2, an IAH prediction model for patients with diabetes mellitus incorporating traditional Chinese medicine constitution. Nomograms were drawn for both models. The Hosmer-Lemeshow goodness-of-fit test, calibration curve, receiver operating characteristic (ROC) curve, and area under the curve (AUC) were calculated to evaluate the effectiveness of models 1 and 2. The improvement in prediction performance between Models 1 and 2 was assessed using Delong test, AUC, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA).Results:The study included 1 283 patients with diabetes mellitus, including 578 males and 705 females, aged (59.61 ± 14.09) years. The incidence of IAH among patients with diabetes mellitus was 20.50% (263/1283), with yang deficiency constitution being the most prevalent traditional Chinese medicine constitution type, at 47.53% (125/263). Multivariate analysis revealed that age, body mass index, course of diabetes, neurological hypoglycemia symptoms, hypoglycemia symptoms and severe hypoglycemia history were the influencing factors of Model 1 (all P<0.05); age, body mass index, neurological hypoglycemic symptoms, hypoglycemic symptoms, history of severe hypoglycemia, and traditional Chinese medicine constitution were the influencing factors of Model 2 (all P<0.05). The Hosmer-Lemeshow goodness-of-fit test showed a good fit of Model 2 [training set ( χ2=8.48, P>0.05), test set ( χ2=3.92, P>0.05)]. The Delong test results showed that the AUC for Model 2 was 0.96 for both the training and test sets, significantly higher than the AUCs of the 0.90 and 0.91 for Model 1 ( Z=-7.27, -3.70, both P<0.01). Furthermore, NRI was 0.66 ( 95%CI 0.53-0.79, P<0.01) and IDI was 0.02 (95% CI 0.01-0.03, P<0.05) for Model 2. Comparative analysis of clinical utility demonstrated that the net benefit of Model 2 for predicting IAH in patients with diabetes mellitus surpassed that of Model 1 across threshold probabilities ranging from 5% to 100%. Conclusions:The study constructed a nomogram prediction model included traditional Chinese medicine constitution with good predictive performance for IAH in patients with diabetes mellitus, and is of significant clinical value for identifying high-risk IAH populations.IAH patients mainly have a biased constitution, indicating that medical staff can reduce the incidence of IAH by improving the patients′ constitution.

Background:The incidence of colorectal cancer(CRC)remains high in China.ITGBL1,an intergrin-like molecule,may play a significant role in the tumorigenesis and progression of CRC.Aims:To explore the expression of ITGBL1 in CRC tissues,and its clinical significance and effect on the biological function of CRC cells.Methods:Fifty-five paraffin embedding cancerous and paracancerous tissues from CRC patients undergoing surgical treatment were collected.Protein expression of ITGBL1 was detected by immunohistochemistry.The relationship between ITGBL1 expression and the clinicopathological characteristics of the CRC patients was analyzed.Furthermore,the sh-ITGBL1 lentiviral system was used to construct ITGBL1 knockdown stably-transformed HCT116 and RKO cells,then the ITGBL1 protein expression was detected by Western blotting.Effects of ITGBL1 knockdown on the proliferation of CRC cells were analyzed by CCK-8 assay and colony formation assay.Results:ITGBL1 was highly expressed in CRC tissues and cells.Expression of ITGBL1 was positively correlated with the infiltration depth,lymph node metastasis and the clinical stage of CRC(all P＜0.05),whereas no correlations were found between ITGBL expression and the gender,age,tumor size,tumor differentiation,and distant metastasis of CRC patients.Compared with the control group(sh-NC),ITGBL1 expression was significantly decreased in ITGBL1 knockdown(sh-ITGBL1)HCT116 and RKO cells,and the cell proliferation was significantly inhibited(all P＜0.05).Conclusions:Highly expressed ITGBL1 may be associated with the occurrence and development of CRC.ITGBL1 knockdown exerts a significant inhibitory effect on the proliferation of CRC cells.Therefore,ITGBL1 might be a potential biomarker,which is expected to be a new target for diagnosis and treatment of CRC.

Objective:To systematically review thrombosis risk prediction models associated with peripherally inserted central venous catheter (PICC) in adults and provide a basis for the clinical application of these models and the development of subsequent models.Methods:Databases such as CNKI, Wanfang, VIP, PubMed, CINAHL, Web of Science, and Ovid were searched to collect studies on thrombosis risk prediction models related to adult PICC, covering all entries from the inception of the databases until December 31, 2022. Two researchers independently screened the literature, extracted data, and assessed the risk of bias.Results:Nineteen studies were included. D-dimer was the most common predictive factor; only five studies underwent external validation, and six studies evaluated model calibration. All included studies exhibited high risk of bias, primarily due to methodological deficiencies in model development and validation processes; the combined area under the receiver operating characteristic curve for nine models was 0.80 (95% Confidence Interval: 0.75-0.85) .Conclusions:Research on thrombosis risk prediction models related to adult PICC is still in its developmental stage. Most of the known models perform well with comprehensive and easily obtainable predictive factors, yet they exhibit methodological shortcomings. Future research should focus on improving the methodological quality and external validation during model development and validation processes.

Background:The incidence of colorectal cancer(CRC)remains high in China.ITGBL1,an intergrin-like molecule,may play a significant role in the tumorigenesis and progression of CRC.Aims:To explore the expression of ITGBL1 in CRC tissues,and its clinical significance and effect on the biological function of CRC cells.Methods:Fifty-five paraffin embedding cancerous and paracancerous tissues from CRC patients undergoing surgical treatment were collected.Protein expression of ITGBL1 was detected by immunohistochemistry.The relationship between ITGBL1 expression and the clinicopathological characteristics of the CRC patients was analyzed.Furthermore,the sh-ITGBL1 lentiviral system was used to construct ITGBL1 knockdown stably-transformed HCT116 and RKO cells,then the ITGBL1 protein expression was detected by Western blotting.Effects of ITGBL1 knockdown on the proliferation of CRC cells were analyzed by CCK-8 assay and colony formation assay.Results:ITGBL1 was highly expressed in CRC tissues and cells.Expression of ITGBL1 was positively correlated with the infiltration depth,lymph node metastasis and the clinical stage of CRC(all P＜0.05),whereas no correlations were found between ITGBL expression and the gender,age,tumor size,tumor differentiation,and distant metastasis of CRC patients.Compared with the control group(sh-NC),ITGBL1 expression was significantly decreased in ITGBL1 knockdown(sh-ITGBL1)HCT116 and RKO cells,and the cell proliferation was significantly inhibited(all P＜0.05).Conclusions:Highly expressed ITGBL1 may be associated with the occurrence and development of CRC.ITGBL1 knockdown exerts a significant inhibitory effect on the proliferation of CRC cells.Therefore,ITGBL1 might be a potential biomarker,which is expected to be a new target for diagnosis and treatment of CRC.

Objective:To analyze the clinical efficacy of three-dimensional (3D) navigation-assisted percutaneous sacroiliac screw fixation in the treatment of Tile C1 pelvic fractures.Methods:A total of 12 patients with Tile C1 pelvic fractures who underwent percutaneous sacroiliac screw fixation assisted by 3D navigation in Liuzhou People's Hospital Affiliated to Guangxi Medical University from September 2019 to March 2022 were retrospectively analyzed. There were 8 males and 4 females, aged 43.08±16.93 years (range, 21-72 years). 24 patients with Tile C1 pelvic fractures who underwent fluoroscopy-assisted percutaneous sacroiliac screw internal fixation during the same period were selected as controls by pairing them according to age and sex in a ratio of 1:2. There were 15 males and 9 females, aged 45.75±11.69 years (range, 32-75 years). The operation time, intraoperative blood loss, number of screws, intraoperative fluoroscopy times, guide pin drilling times and pelvic function scores were compared between the two groups. The quality of pelvic fracture reduction was evaluated based on the Matta scoring criteria, the screw cut-out rate was calculated according to the Lonstein evaluation criteria, and the degree of postoperative heterotopic ossification was evaluated according to the Brooker grading system.Results:All patients were followed up for 18.1±4.7 months (range, 12-30 months). In the 3D navigation group, the operation time was 110.67±44.85 min, the number of intraoperative fluoroscopies was 24.42±9.94, and the number of guided needle drilling was 7.33±4.70, which was lower than 145.00±48.51 min, 75.75±29.47, and 13.92±5.78 in the fluoroscopically-assisted group, and the differences were statistically significant ( P<0.05). At the last follow-up, the Majeed pelvic function score of 3D navigation group was 89.08±3.89, and the excellent and good rate was 100% (12/12). The score of fluoroscopy-assisted group was 74.00±10.71, and the excellent and good rate was 79% (19/24). The difference was statistically significant ( χ2=10.23, P<0.001). The excellent and good rate of Matta grading was 92% (11/12) in the 3D navigation group and 79% (19/24) in the fluoroscopic assisted group, showing no significant difference between the two groups ( χ2=2.93, P=0.403). The screw cut-out rate and heterotopic ossification rate in the 3D navigation group were 17% (2/12) and 8% (1/12), which were lower than 71% (17/24) and 13% (3/24) in the fluoroscopy-assisted group, and the differences were statistically significant ( χ2=9.76, P=0.021; χ2=31.71, P<0.001). Conclusion:3D navigation-assisted percutaneous sacroiliac screw fixation for Tile C1 pelvic fractures can reduce the operation time and radiation exposure, improve the postoperative pelvic function, and reduce the incidence of screw cut-out and heterotopic ossification.

Objective:To explore the risk factors associated with the clinical progression of COVID-19 infection in kidney transplant(KT)recipients during the spread of Omicron variant and evaluate the effectiveness of anti-RNA virus agents in blocking the clinical progression of COVID-19 in these recipients.Methods:Retrospective analysis was conducted for the clinical data on COVID-19 infection in 232 KT recipients followed up from December 4, 2022 to January 31, 2023 at Department of Renal Transplantation, Organ Transplantation Center, Beijing Tsinghua Changgung Hospital.Inclusion criteria were age ≥18 years and stable kidney function without renal replacement therapy.The follow-up time was 30 days after COVID-19 infection.Based upon whether or not there was an infection of COVID-19, KT recipients were divided into two groups of infection(181 cases)and non-infection(51 cases). In infection group, recipients were further assigned into two sub-groups of disease progression(n=23)and stable(158 cases)according to whether or not there was a progression to severe disease.Various factors such as gender, age, body mass index(BMI), time after transplantation, underlying diseases(history of hypertension, diabetes mellitus, coronary heart disease & chronic lung disease), smoking history and dosing of anti-RNA virus agents were collected.Pearson χ2 test or Fisher's exact probability method was utilized for examining enumeration data while Mann-Whitney U test for measurement data.Univariate Logistic regression analysis was conducted and variables with P<0.05 were included into multifactorial Logistic regression analysis to identify independent risk factors for clinical progression of COVID-19 infection in KT recipients. Results:Among 232 KT recipients, infection rate of COVID-19 was 78.0%(181/232). The clinical classification was mild(112 cases), moderate(46 cases), severe(21 cases)and critical(n=2 cases). The severe rate was 12.7%(23/181). After infection with COVID-19, the proportion of KT recipients aged ≥65 years progressing from mild/moderate to severe was higher than those aged<65 years[38.5%(5/13)vs 10.7%(18/168)]. The difference was statistically significant( P=0.014); The proportion of diabetic KT recipients progressing from mild/moderate to severe was higher than those without diabetes[19.1%(13/68)vs 8.8%(10/113)]. The difference was statistically significant( P=0.045). Univariate Logistic analysis showed similar results.Age≥65 years( OR=5.21, 95% CI: 1.54-17.64, P=0.008)or diabetes mellitus( OR=2.44, 95% CI: 1.003-5.911, P=0.049)were the risk factors for COVID-19 infection recipients progressing from mild/moderate to severe disease.Multivariate Logistic analysis revealed that age ≥65 years( OR=4.03, 95% CI: 1.14-14.34, P=0.031)was an independent risk factor for COVID-19 infection recipients progressing from mild/moderate to severe.Among 181 cases of COVID-19 mild/medium infected patients, 18 cases received nimativir/ritonavir and 10 cases had azvudine for anti-RNA virus treatment.However, none of them progressed to severe; 153 cases did not use anti-RNA virus drugs and 23 cases(15.0%)progressed to severe disease and the difference was statistically significant( P=0.028). Among 23 severe cases, 14 cases received nirmatrelvir/ritonavir and 2 cases had azivudine for anti-RNA virus treatment.The former did not progress to critical disease while 1 case in the latter progressed to critical illness and death; 1/7 recipients not using anti-RNA virus agents progressed to critical illness and died while another 6 cases did not progress to critical illness. Conclusions:KT recipients aged ≥65 years or diabetes mellitus have a greater risk of progression from mild/moderate to severe disease after COVID-19 infection.Among them, age ≥65 years is an independent risk factor for patients with COVID-19 infection to progress from mild/moderate to severe.Antiviral treatment with nirmatrelvir/ritonavir or azivudine in KT recipients during mild/moderate stage of COVID-19 infection can significantly reduce the rate of severe disease.Treatment with Nirmatrelvir/Ritonavir is still effective in the severe stage.

Objective:To explore the differences of clinical features and surgical efficacy between the elderly and the middle-aged and young patients with meningiomas in the central cortex area.Methods:Forty-three elderly patients with meningiomas in the central cortex area (≥60 years old) and 63 middle-aged and young patients with meningiomas in the central cortex area (18-59 years old), accepted surgery in Department of Neurosurgery, Guangdong 999 Brain Hospital from January 2011 to December 2020, were chosen. The differences of symptom, gross tumor volume, peritumoral edema degrees, intraoperative blood loss, tumor resection degrees, complications, and hospital stays between the 2 groups were analyzed.Results:The elderly patients had significantly higher proportion of preoperative muscle strength decline, lower proportion of preoperative headache, larger preoperative tumor volume, more severe peritumoral edema degrees before and after surgery, small volume of intraoperative blood loss, and longer hospital stays compared with the middle-aged and young patients ( P<0.05). However, no significant differences in distributions of tumor resection Simpson grades, proportion of new neurological dysfunction, incidence of postoperative complications, and proportions of reoperations and tumor recurrence were noted between the 2 groups ( P>0.05). Significant difference in distributions of peritumoral edema degrees among patients with different WHO grades was noted in the elderly group ( P<0.05), and significant difference in distribution of peritumoral edema degrees among patients with different tumor volumes was noted in the middle-aged and young group ( P<0.05). Conclusions:Although differences in clinical characteristics exist between the elderly and the middle-aged and young patients with meningiomas in the central cortex area, no significant difference in surgical efficacy is noted between the 2 groups. The peritumoral edema degree in the elderly patients is related to tumor pathological grades, while that in middle-aged and young patients is related to tumor volumes.