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 analyze the efficacy and safety of modified associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in the treatment of patients with primary liver cancer.Methods:Clinical data of 83 patients with hepatocellular carcinoma (HCC) undergoing hemihepatectomy in the Department of Hepatobiliary and Pancreatic Tumor Surgery of Gansu Provincial Cancer Hospital between January 2022 and November 2023 were retrospectively analyzed, including 53 males and 30 females, aged (54.0±6.5) years. According to the treatment protocol, patients were divided into the control group ( n=41), in which patients underwent traditional ALPPS, and the observation group ( n=42), in which patients underwent modified ALPPS (occlusion of portal venous branch using vascular clips, combined with radiofrequency ablation for physical separation of the diseased lobe, without liver mobilization). The completion rate of staged surgery, interval between surgeries, future liver remnant (FLR) growth rate at 7 days after first-stage surgery, alanine transaminase (ALT) and aspartate transaminase (AST) levels at 5 days after fisrt-stage surgery, and postoperative complications (ascites, nausea, and vomiting, etc.) were compared between the groups. Results:The completion rate of staged surgery was 95.2% (40/42) in the observation group and 90.2% (37/41) in the control group ( χ2=0.62, P=0.431). The ALT and AST levels at 5 days after first-stage surgery were (550.4±86.0) U/L and (327.1±52.8) U/L in the observation group, respectively, which were significantly lower than those in the control group (861.6±106.3) U/L and (533.8±73.7) U/L, respectively ( t=13.13 and P<0.001, t=12.93 and P<0.001). The FLR growth rate were higher in the observation group than that in the control group [(80.4±10.3)% vs (49.3±5.7)%; t=13.13, P<0.001] and the interval between procedures were also shorter in the observation group (10.9±2.1 vs 22.4±4.8, d; t=9.65, P<0.001). The intraoperative blood loss of the first-stage surgery was lower in the observation group than that in the control group (350.5±45.2 vs 825.5±21.7, ml; t=21.43, P<0.001). The total complication rates after the first-stage surgery were 11.9% (5/42) in the observation group and 19.5% (8/41) in the control group, while after the second-stage surgery, the complication rates were 7.5% (3/40) and 18.9% (7/37), respectively, with no statistically significant differences ( χ2=0.65 and P=0.419, χ2=1.81 and 0.177, respectively). Conclusion:The modified ALPPS offers better postoperative liver function, reduced surgical trauma, accelerated FLR growth, and a shorter interval between procedures, demonstrating a favorable safety in the treatment of primary liver cancer.

Objectives:There is a lack of long-term follow-up study results on severe microvascular complications in a larger Chinese population with diabetes.This study aims to explore long-term impact of newly diagnosed diabetes(NDD)on the incidence and risk of severe microvascular complications.Methods:A total of 598 NDD and 493 normal glucose tolerance(NGT)subjects were included in this study in 1986.By questionnaire and systematic case review,the occurrence of severe microvascular complications,including severe diabetic retinopathy,severe diabetic nephropathy,and severe diabetic neuropathy,was followed up and collected over a period of 34 years.Results:The cumulative incidence of severe microvascular complications in the NDD population was 65.03%(95%CI:58.90%-70.48%)over 34 years,significantly higher than that in the NGT population(16.8%,95%CI:12.64%-20.11%).After adjusting for related risk factors,the risk of severe microvascular complications in the NDD population was 7.08 times than that of the NGT population(HR=7.08,95%CI:5.09-9.84,P<0.0001).Stratified analysis by sex showed that the cumulative incidence and risk of severe microvascular complications were slightly higher in male NDD population(68.02%,95%CI:57.27%-76.61%;HR=9.45,95%CI:5.78-15.47,P<0.0001)than in female NDD population(63.37%,95%CI:55.69%-70.09%;HR=5.86,95%CI:3.75-9.16,P<0.0001);however,the cumulative incidence increased more rapidly in women during the follow-up period of 10-25 years.Conclusions:The incidence and risk of severe microvascular complications in diabetes were significantly higher than those in the NGT population;and the incidence of severe vascular complications increased rapidly after the duration of diabetes exceeded 10 years,indicating that strict control of blood glucose in the early stage of diabetes is of vital importance.

Objectives:There is a lack of long-term follow-up study results on severe microvascular complications in a larger Chinese population with diabetes.This study aims to explore long-term impact of newly diagnosed diabetes(NDD)on the incidence and risk of severe microvascular complications.Methods:A total of 598 NDD and 493 normal glucose tolerance(NGT)subjects were included in this study in 1986.By questionnaire and systematic case review,the occurrence of severe microvascular complications,including severe diabetic retinopathy,severe diabetic nephropathy,and severe diabetic neuropathy,was followed up and collected over a period of 34 years.Results:The cumulative incidence of severe microvascular complications in the NDD population was 65.03%(95%CI:58.90%-70.48%)over 34 years,significantly higher than that in the NGT population(16.8%,95%CI:12.64%-20.11%).After adjusting for related risk factors,the risk of severe microvascular complications in the NDD population was 7.08 times than that of the NGT population(HR=7.08,95%CI:5.09-9.84,P<0.0001).Stratified analysis by sex showed that the cumulative incidence and risk of severe microvascular complications were slightly higher in male NDD population(68.02%,95%CI:57.27%-76.61%;HR=9.45,95%CI:5.78-15.47,P<0.0001)than in female NDD population(63.37%,95%CI:55.69%-70.09%;HR=5.86,95%CI:3.75-9.16,P<0.0001);however,the cumulative incidence increased more rapidly in women during the follow-up period of 10-25 years.Conclusions:The incidence and risk of severe microvascular complications in diabetes were significantly higher than those in the NGT population;and the incidence of severe vascular complications increased rapidly after the duration of diabetes exceeded 10 years,indicating that strict control of blood glucose in the early stage of diabetes is of vital importance.

Objective:To analyze the efficacy and safety of modified associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in the treatment of patients with primary liver cancer.Methods:Clinical data of 83 patients with hepatocellular carcinoma (HCC) undergoing hemihepatectomy in the Department of Hepatobiliary and Pancreatic Tumor Surgery of Gansu Provincial Cancer Hospital between January 2022 and November 2023 were retrospectively analyzed, including 53 males and 30 females, aged (54.0±6.5) years. According to the treatment protocol, patients were divided into the control group ( n=41), in which patients underwent traditional ALPPS, and the observation group ( n=42), in which patients underwent modified ALPPS (occlusion of portal venous branch using vascular clips, combined with radiofrequency ablation for physical separation of the diseased lobe, without liver mobilization). The completion rate of staged surgery, interval between surgeries, future liver remnant (FLR) growth rate at 7 days after first-stage surgery, alanine transaminase (ALT) and aspartate transaminase (AST) levels at 5 days after fisrt-stage surgery, and postoperative complications (ascites, nausea, and vomiting, etc.) were compared between the groups. Results:The completion rate of staged surgery was 95.2% (40/42) in the observation group and 90.2% (37/41) in the control group ( χ2=0.62, P=0.431). The ALT and AST levels at 5 days after first-stage surgery were (550.4±86.0) U/L and (327.1±52.8) U/L in the observation group, respectively, which were significantly lower than those in the control group (861.6±106.3) U/L and (533.8±73.7) U/L, respectively ( t=13.13 and P<0.001, t=12.93 and P<0.001). The FLR growth rate were higher in the observation group than that in the control group [(80.4±10.3)% vs (49.3±5.7)%; t=13.13, P<0.001] and the interval between procedures were also shorter in the observation group (10.9±2.1 vs 22.4±4.8, d; t=9.65, P<0.001). The intraoperative blood loss of the first-stage surgery was lower in the observation group than that in the control group (350.5±45.2 vs 825.5±21.7, ml; t=21.43, P<0.001). The total complication rates after the first-stage surgery were 11.9% (5/42) in the observation group and 19.5% (8/41) in the control group, while after the second-stage surgery, the complication rates were 7.5% (3/40) and 18.9% (7/37), respectively, with no statistically significant differences ( χ2=0.65 and P=0.419, χ2=1.81 and 0.177, respectively). Conclusion:The modified ALPPS offers better postoperative liver function, reduced surgical trauma, accelerated FLR growth, and a shorter interval between procedures, demonstrating a favorable safety in the treatment of primary liver cancer.

Objection:To evaluate the effects of the miniscrew supported removable palatal arch for maxillary molar distalization.Methods:33 patients with mild to moderate crowding teeth and maxillary protrusion were treated with the miniscrew supported remova-ble palatal arch.The lateral cephalograms and dental plaster models were taken at the beginning of the treatment(T0)and at the end of molar distalization(T1).The multicentre variables were measured and compared with statistical software.Results:Cephalometrics showed that the average distance(mm)of the firs molar distalization was 3.6(P＜0.001),molar distal tipping was 6°(P＜0.001)and molar intrusion(mm)was 0.6(P＜0.05).The measurements of right and left molar distalization on plaster models were 4.2 mm(P＜0.001)and 4.0 mm(P＜0.001)respectively,the width of dental arch was increased by 3.1 mm(P＜0.05).The data of distalization of the first molar showed no statistical difference between right and left side on plaster cast and between model and cephalometric meas-urements.On the right side the angle between the mesial-distal tips line and the middle line was increased by 1.6°(P＞0.05),on the left by 4.8°(P＜0.05).Conclusion:The none extraction therapy for mild to moderate crowding teeth and maxillary protrusion can be realized by miniscrew supported removable palatal arch distalization appliance.

Objective : To discuss the effectiveness and mechanism for movement of maxillary buccally transposed canines by using a door-shaped individualized dental archwire mechanic and to provide a reference for clinicians. Methods: Eight patients with unilateral maxillary transposed canines were enrolled. All patients were treated with door-shaped individualized archwires. Before treatment (T1) and after the crowns of the transposed canines were moved to the right buccal positions in the dental arch during the treatment (T2), orthopantomograms were taken both at T1 and T2 to compare the linear changes (distance changes of the crown and root apex) and angular changes to study the mechanisms of tooth movement. The probing depth and buccal crown height were measured using a periodontal probe to compare periodontal changes before treatment (T1) and after treatment (T3) between the transposed canines and contralateral canines. Results: All eight transposed canines were successfully brought back to their normal dental arch position but were made more buccal by using the door-shaped individualized dental archwire, with a mean of (11.5 ± 2.7) months. The average overall duration was (28.3 ± 4.7) months. The crown distance changes of the canines from T1 to T2 (8.1 mm) were greater than those of the root apexes (1.5 mm) (P<0.05). The mean angulation changes of the long axes of the canines were 17.5°. There was no significant difference in the depth of periodontal measurement and buccal crown height measurement between T1 and T3 (P>0.05). Conclusion The buccal movement of maxillary transposed canines under a door-shaped individualized dental archwire was effective and feasible. The movement pattern under this mechanism was controlled tipping.

Objective:To study the clinical characteristics and risk factors for hypertriglyceridemia-induced severe acute pancreatitis (HTG-SAP) complicated by acute kidney injury.Methods:The clinical data of HTG-SAP patients admitted to the Department of Critical Care Medicine of the Second Affiliated Hospital of Anhui Medical University from January 2014 to July 2022 were retrospectively collected, and divided into an AKI group and a non-AKI group according to whether AKI occurred. The general condition, laboratory data and clinical characteristics of the two groups were compared. Factors with statistically significant differences were screened for logistic regression analysis and a predictive model was constructed. We plotted the receiver operating characteristic curve and used the area under the curve (AUC) to evaluate the predictive ability of each predictor for HTG-SAP complicated with AKI.Results:A total of 91 patients were included, including 37 (40.7%) with AKI and 54 (59.3%) without AKI. The proportions of extrapancreatic infection, sepsis and multiple organ dysfunction syndrome, requiring mechanical ventilation, continuous renal replacement therapy (CRRT), retroperitoneal puncture, and surgical intervention were higher in the AKI group than in the non-AKI group (all P<0.05). The length of ICU stay, total length of hospitalization, and mortality rate in the AKI group were higher than those in the non-AKI group (all P<0.05). Multivariate logistic regression analysis showed that acute physiology and chronic health status scoreⅡ (APACHEⅡ) ( OR=2.069, 95% CI: 1.286-3.417, P=0.003), abdominal pressure ( OR=1.469, 95% CI: 1.108-1.958, P=0.007), and lactic acid ( OR=3.156, 95% CI: 1.013-9.831, P=0.047) were independent risk factors for AKI in HTG-SAP patients. The AUCs of the APACHEⅡ score, abdominal pressure, lactic acid level and combined prediction model were 0.951, 0.918, 0.837 and 0.986, respectively. Conclusions:Patients with HTG-SAP complicated with AKI were more likely to have complications related to extrapancreatic infection, sepsis and multiple organ dysfunction, and the proportion of mechanical ventilation, CRRT, retroperitoneal puncture and surgical intervention required during hospitalization was greater, the lengths of ICU stay and total hospital stay were longer, and the mortality rate was higher. APACHEⅡ score, abdominal pressure and lactic acid were independent risk factors for HTG-SAP concurrent AKI, and the prediction model established based on these three factors had higher value in predicting HGT-SAP concurrent AKI

Small interfering RNA(siRNA) has been the focus of attention in the field of drug development for its excellent properties such as efficiency, specificity and transient nature in treating diseases. However, the poor stability and low cellular uptake of naked siRNAs make it difficult for them to exert their gene silencing effects, a high-quality drug delivery system is needed to deliver them to target cells where they can function. Many nano delivery systems are no longer suitable for siRNA transport due to toxicity and drug loading problems, chitosan derivatives are beginning to receive widespread attention because of their high water solubility, safety and stability. This paper reviewed the research progress of chitosan derivatives as siRNA nano-delivery systems and provided a reference for researchers who are interested in the development of nano-delivery systems.

Objective:To study the clinical effect of different application times of antibiotics in patients with hypertriglyceridemic severe acute pancreatitis(HTG-SAP).Methods:The clinical data of 92 patients with HTG-SAP who were treated at the Department of Critical Care Medicine of the Second Affiliated Hospital of Anhui Medical University from January 2016 to February 2022 were analyzed retrospectively. There were 65 males and 27 females, aged (40.82±10.55) years old. These patients were divided into three groups based on the time of prophylactic use of antibiotics: the early prevention group (used within 72 h after admission, n=39), the delayed prevention group (used after 72 h after admission, n=30) and the nonprevention group ( n=23). The clinical data such as the general data, length of stay and all cause mortality rate of the three groups of patients were analyzed. Results:Compared with patients in the nonprevention group, the incidence rate of pancreatic/peripancreatic infection [10.0%(3/30) vs. 39.1%(9/23)] and the incidence rate of bloodstream infection [6.7%(2/30) vs. 34.8%(8/23)] in the delayed prevention group were significantly decreased (pancreas/peripancreatic infection: χ 2=6.31, P=0.012; bloodstream infection: χ 2=6.72, P=0.010). The infection rate of multiple/pan resistant bacteria in the early prevention group [23.1%(9/39)] was significantly higher than the nonprevention group [4.3%(1/23)] (χ 2=4.49, P=0.034). There were no significant differences in the all cause mortality rate, length of stay, duration of intensive care, hospitalization cost, incidence of intestinal fistula and retroperitoneal hemorrhage, and the proportion of patients requiring surgery among the 3 groups (all P>0.05). Conclusions:Pophylactic use of antibiotics within 72 h of hospital admission significantly reduced the incidence of pancreatic/peripancreatic infection and bloodstream infection in patients with HTG-SAP. There were no significant differences in the final prognosis among these patients with HTG-SAP treated with antibiotics at different times.