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 compare the effects of 3 rehydration methods before blood donation on the prevention of on-site and delayed blood donation-related vasovagal response (VVR) . 【Methods】 From January to June 2021, 6 250 whole blood donors in 6 fixed blood donation sites signed informed consent and were divided into 198 clusters according to donor sites and dates, then they were randomly assigned to receive either oral rehydration salts (ORS), sugar water, or water group, and each drank 500 mL of ORS, sugar water or water within 20 minutes before blood donation. The researchers recorded the actual intervention accepted on site, and recorded the immediate VVR and related information. At rest after blood donation, donors submitted an electronic questionnaire containing socio-demographic information. At 48 hours after blood donation, the researchers called back every donor to record delayed VVR and related information. Logistic regression based on intention to treat (ITT) was used to analyze the difference of the incidence of VVR among the three groups, and the average treatment effect on treated (ATT) was calculated. PASS 2021was used to estimate the sample size and R (4.2.0) for statistical analysis. 【Results】 The cumulative incidence of blood donation-related VVR was 2.67% (2.29%-3.11%) among street whole blood donors under the 3 rehydration methods, in which, the incidence of immediate and delayed VVR was 1.02% (0.79%-1.31%) and 1.65% (1.36%-2.01%) respectively. ITT analysis found that ORS were more effective than water in reducing the incidence of delayed VVR【OR=0.59,95% CI[0.37,0.94]】.There was no significant difference in the incidence of immediate VVR between any two groups (P > 0.05), and there was no significant difference in the incidence of delayed VVR in the sugar water group compared with the water group (P > 0.05). There was a difference of -0.013 (【95% CI[-0.022, -0.004]】or -0.008【95% CI[-0.017, -0.000]】in the incidence of delayed VVR in the ORS group compared with water group or sugar water group, the difference was significant (P<0.05). The cumulative VVR of the three groups showed similar results to the delayed VVR. 【Conclusion】 Drinking ORS before blood donation is the most effective rehydration method to prevent delayed VVR. The next step is to establish the predictive model of delayed VVR to screen the susceptible population and provide them with ORS before blood donation, while other population can choose any liquid they like, thus achieving personalized blood donation-related VVR prevention and control.

Background::Hypertension and non-alcoholic fatty liver disease (NAFLD) share several pathophysiologic risk factors, and the exact relationship between the two remains unclear. Our study aims to provide evidence concerning the relationship between hypertension and NAFLD by analyzing data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 and Mendelian randomization (MR) analyses.Methods::Weighted multivariable-adjusted logistic regression was applied to assess the relationship between hypertension and NAFLD risk by using data from the NHANES 2017-2018. Subsequently, a two-sample MR study was performed using the genome-wide association study (GWAS) summary statistics to identify the causal association between hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and NAFLD. The primary inverse variance weighted (IVW) and other supplementary MR approaches were conducted to verify the causal association between hypertension and NAFLD. Sensitivity analyses were adopted to confirm the robustness of the results.Results::A total of 3144 participants were enrolled for our observational study in NHANES. Weighted multivariable-adjusted logistic regression analysis suggested that hypertension was positively related to NAFLD risk (odds ratio [OR] = 1.677; 95% confidence interval [CI], 1.159-2.423). SBP ≥130 mmHg and DBP ≥80 mmHg were also significantly positively correlated with NAFLD. Moreover, hypertension was independently connected with liver steatosis ( β = 7.836 [95% CI, 2.334-13.338]). The results of MR analysis also supported a causal association between hypertension (OR = 7.203 [95% CI, 2.297-22.587]) and NAFLD. Similar results were observed for the causal exploration between SBP (OR = 1.024 [95% CI, 1.003-1.046]), DBP (OR = 1.047 [95% CI, 1.005-1.090]), and NAFLD. The sensitive analysis further confirmed the robustness and reliability of these findings (all P >0.05). Conclusion::Hypertension was associated with an increased risk of NAFLD.

ObjectiveTo investigate the effect of human umbilical cord mesenchymal stem cells （hUCMSCs） in the treatment of mice with liver fibrosis and its mechanism. MethodsA total of 18 specific pathogen-free C57BL/6 mice， aged 6 weeks， were selected and divided into control group （n=6）， carbon tetrachloride （CCl₄） model group （CCl₄ group， n=6）， and hUCMSCs treatment group （MSC group， n=6） using a random number table. The mice in the CCl₄ group and the MSC group were given intraperitoneal injection of CCl₄ solution to establish a mouse model of liver fibrosis， while those in the control group were injected with the same dose of corn oil， and the mice in the MSC group were injected with hUCMSCs via the caudal vein during the injection of CCl₄. At the end of week 8， mouse serum was collected， and the mice were sacrificed to collect and fix the liver. Enzyme-linked immunosorbent assay was used to measure the levels of inflammatory factors； an automatic biochemical detector was used to measure liver function parameters； HE staining， Masson staining， Sirius Red staining， and α-SMA immunofluorescence assay were used to evaluate liver fibrosis. Hepatic stellate cells （HSCs） stimulated by TGF-β were co-cultured with hUCMSCs in the medium with or without chitinase-3 like-protein-1 （CHI3L1）， and Western blot was used to measure the expression levels of proteins. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsMasson staining and Sirius Red staining showed that the CCl₄ group had a significantly higher degree of fibrosis than the control group （both P<0.05）， and the MSC group had significant alleviation of fibrosis compared with the CCl₄ group （both P<0.05）. Compared with the control group， the CCl₄ group had significant increases in the levels of interleukin-1β， interleukin-6 （IL-6）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， and alkaline phosphatase （ALP） （all P<0.05）， and compared with the CCl₄ group， the MSC group had significant reductions in the levels of IL-6， AST， ALT， and ALP （all P<0.05）. The CCl₄ group had significantly higher expression levels of CHI3L1 and α-SMA than the control group and the MSC group （all P<0.05）. The cell culture experiment showed that the MSC+HSC group had a significantly higher expression level of Bax than the HSC group and the MSC+CHI3L1 group （both P<0.05）， suggesting that CHI3L1 reversed the pro-apoptotic effect of MSC on activated HSCs. ConclusionThis study shows that hUCMSCs can improve liver fibrosis in mice， possibly by inhibiting CHI3L1 to promote the apoptosis of HSCs.

Monopolar spindle 1, also known as threonine and tyrosine kinase (TTK), is a key component of spindle assembly checkpoint (SAC). It is considered to be a monitoring mechanism to ensure mitotic fidelity and genomic stability. TTK is overexpressed in a variety of malignant tumors, and patients with low expression of TTK tend to have a longer survival time, suggesting that it may be used as a biomarker for diagnosis and prognosis. Abnormal expression of TTK often impairs the function of SAC, resulting in irregular mitosis, increased aneuploidy and mitotic disaster, thus promoting the occurrence of tumors. Current studies have shown that TTK inhibitors can inhibit the proliferation of tumor cells and increase the sensitivity of tumor cells to therapy in combination with chemotherapy or radiotherapy to achieve sensitization and attenuated effects. This article will review the research and application of TTK and its inhibitors in malignant tumors.

Objective:To evaluate the feasibility of using a visual positioning system for both motion phantom and clinical quality control.Methods:A phantom experiment was conducted using the Dynamic Thorax Phantom from CIRS. Different ranges of motion were simulated to assess the discrepancies between camera-recorded positions and actual movements. Visual markers were also attached to the treatment bed and the collimator head, and their movements were simulated as part of the experiment. The experiment was repeated for three times. Discrepancies between system measurements and manual measurements were recorded and analyzed to assess the accuracy and reliability of the system.Results:In the motion phantom test, the deviation between the actual motion distance of the phantom and the system's recorded measurement was (0.18±0.07) mm. For linear motion analysis along the X, Y, and Z axes on the treatment table, the measurement errors were (0.14±0.08) mm, (0.15±0.09) mm, and (0.16±0.08) mm, respectively. Additionally, the measurement error in the rotational direction of the treatment couch was 0.18°±0.09°. For the rotational direction of the collimator head, the measurement error was 0.11°±0.02°. Conclusion:The system demonstrates good accuracy and stability, and has potential clinical application value.

BACKGROUND: The burden of esophageal cancer varies across different regions of the world. The aim of this study is to analyze the current burden of esophageal cancer in 185 countries in 2022 and to project the trends up to the year 2050. METHODS: We extracted data on primary esophageal cancer cases and deaths from the GLOBOCAN 2022 database, which includes data from 185 countries. Age-standardized incidence rates (ASIR) and mortality rates (ASMR) per 100,000 person-years were calculated by stratifying by Human Development Index (HDI) levels and regions. Considering changes in population size and age structure, we assumed that the risks of incidence and mortality remain constant at the levels of 2022 to forecast the number of new cases and deaths from esophageal cancer globally by 2050. RESULTS: In 2022, an estimated 511,054 people were diagnosed with esophageal cancer globally, and 445,391 died from the disease. The global ASIR and ASMR for esophageal cancer were 5.00 and 4.30 per 100,000, respectively. The highest rates were observed in East Africa (7.60 for incidence, 7.20 for mortality per 100,000), East Asia (7.60 for incidence, 5.90 for mortality per 100,000), Southern Africa (6.30 for incidence, 5.90 for mortality per 100,000), and South Central Asia (5.80 for incidence, 5.50 for mortality per 100,000). Among the 185 countries worldwide, esophageal cancer was among the top five causes of cancer incidence in 18 countries and among the top five causes of cancer mortality in 25 countries. In 2022, China had 224,012 new cases and 187,467 deaths from esophageal cancer, accounting for approximately 43.8% and 42.1% of the global total, respectively, which is higher than the proportion of China's population to the global population (17.9%). ASIR was 8.30 per 100,000, and ASMR was 6.70 per 100,000. The highest burden of esophageal cancer was in high HDI countries, with new cases and deaths accounting for 51.3% and 50.0% of the global total, respectively. The ASIR and ASMR were highest in the high HDI group (6.10 and 5.10 per 100,000, respectively), also exceeding the global averages. There was a trend of decreasing mortality to incidence ratio with increasing HDI, but no correlation was observed between HDI and ASIR or ASMR. In all regions worldwide, the incidence and mortality rates were higher in males than in females (with a male-to-female ASR ratio ranging from 1.10 to 28.7). Compared to 2022, it is projected that by 2050, the number of new esophageal cancer cases will increase by approximately 80.5%, and deaths will increase by 85.4% due to population growth and aging. CONCLUSIONS The burden of esophageal cancer remains heavy. Adopting a healthy lifestyle, including reducing tobacco and alcohol intake, avoiding moldy foods, and increasing intake of fresh fruits and vegetables, can help reduce the risk of stomach and esophageal cancer. In addition, the development and implementation of evidence-based and effective public health policies are critical to reducing the global disease burden of esophageal cancer.
Esophageal Neoplasms/mortality* ; Humans ; Male ; Incidence ; Female ; Middle Aged ; Global Health ; Aged ; Adult

Objective:To investigate the application of PDCA cycle management combined with "three-step" bedside teaching in respiratory nursing teaching.Methods:A total of 80 nursing students who studies in Department of Respiratory Medicine, Beijing Chaoyang Hospital Affiliated to Capital Medical University, were included as subjects, and they were divided into control group and observation group using a simple random number table, with 40 students in each group. The students in the control group received traditional teaching, while those in the observation group received PDCA cycle management combined with "three-step" bedside teaching. The two groups were compared in terms of the scores of theoretical knowledge, operation skills, and physical examination, comprehensive clinical nursing ability, and degree of satisfaction with teaching. SPSS 22.0 was used to perform the chi-square test and t-test. Results:The observation group had significantly higher scores of theoretical knowledge, operation skills, and physical examination than the control group ( P<0.05). Compared with the control group, the observation group had significantly higher scores of nursing consultation, physical examination, diagnosis, nursing measures, health consultation, humanistic care, organizational effectiveness, and overall evaluation ( P<0.05). The observation group had a significantly higher degree of satisfaction with teaching than the control group ( P<0.05). Conclusion:PDCA cycle management combined with "three-step" bedside teaching in respiratory nursing teaching can improve the assessment scores of theoretical knowledge, operation skills, and physical examination among nursing students, enhance their comprehensive clinical nursing abilities, and increase the degree of satisfaction.

Objective:To summarize the clinical data of Sun's procedure(total aortic arch replacement with frozen elephant trunk technique) in the treatment of complex aortic arch disease after previous cardiac surgery.Methods:From January 1, 2018 to December 31, 2020, a total of 55 patients underwent resternotomy Sun's procedure in the Aortic Surgery Center of Beijing Anzhen Hospital, including 41 males and 14 females, with a mean age of(45.4±12.7) years old, were retrospectively analyzed. The indications of primary cardiac surgery included type A aortic dissection, aortic root or ascending aortic aneurysm, heart valve surgery, and coronary heart disease. Indications for reoperation included residual aortic dissection larger than 55 mm in diameter, aortic aneurysm dilation, new type A aortic dissection, anastomotic leakage with symptoms, and pseudoaneurysm. All the operations were performed under general anesthesia and median resternotomy, total aortic arch replacement with the stented elephant trunk implantation and were performed by anterograde unilateral or bilateral cerebral perfusion.Results:There was no intraoperative death, and the postoperative mortality was 9.1%(5/55). The causes of death were 2 cases of low cardiac output, 1 case of respiratory failure, 1 case of cerebral complications, and 1 case of gastrointestinal bleeding. Except death, there were 2 cases of postoperative cerebral complications(2/50, 4%), 5 cases of spinal cord injury(transient paraplegia)(5/50, 10%), the median duration of ventilator use was 17 hours(14-42 h). Other postoperative complications included respiratory insufficiency requiring ventilatory support longer than 48 hours(8/50, 16%), renal insufficiency requiring temporary dialysis(2/50, 4%). The follow-up time was(25.9±11.2) months(10-47 months), during which 1 case died due to cerebral complication, 4 cases underwent total thoracoabdominal aorta replacement, and 1 case underwent anastomotic leakage repair.Conclusion:It is safe and effec to perform Sun's procedure(total aortic arch replacement with frozen elephant trunk technique) in the treatment of complex arch disease after previous cardiac surgery.

Objective:To investigate the differences in outcomes of surgical strategies and prognosis of patients with acute type A aortic dissection(ATAAD) during the period of COVID-19 Omicron variant epidemic compared with the non-epidemic period.Methods:Clinical data were retrospectively collected from ATAAD patients during the COVID-19 Omicron variant epidemic(December 7, 2022 to January 10, 2023) and during the non-epidemic period(December 7, 2019 to January 10, 2020) to compare the differences in surgical strategies, perioperative mortality, and perioperative complication rates in ATAAD patients during the two different periods.Results:There were 14 patients in the COVID-19 infected group and 43 patients in the control group. Patients in the infected group had a shorter mean aortic clamp time[(89.71±16.27)min vs.(110.09±28.99)min, P<0.01], a significantly higher postoperative mortality rate relative to the control group(21.43% vs. 2.33%, P=0.02), a significantly longer length of stay in the ICU(3 days vs. 2 days, P=0.04) and the duration of intubation time(34 h vs. 14 h, P<0.01), and the incidence of adverse events, mainly cerebral infarction, was higher in infected group(28.57% vs. 6.98%, P=0.03). Conclusion:During the COVID-19 Omicron variant strain epidemic, our center preferred a more conservative surgical strategy in COVID-19 infected patients. Although the COVID-19 infection increased the postoperative mortality and complication rate of ATAAD, patients still achieve a more satisfactory outcome. Therefore, surgical treatment should be timely performed for ATAAD patients.