Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

Objective:To analyze the clinicopathological features of solitary papillary thyroid isthmus carcinoma (SPTIC) and the therapeutic effect and prognosis of different surgical methods.Methods:A total of 161 patients with SPTIC who underwent surgical treatment in the Department of Thyroid Surgery of the First Hospital of Jilin University from Dec. 2012 to Oct. 2021 were selected. Gender, age, body mass index and pathology of the patients were collected and the clinicopathological characteristics of SPTIC were analyzed. They were divided into three groups according to different surgical methods: group A underwent isthmic excision, group B underwent extended isthmic excision, and group C underwent total thyroidectomy. There were 47 patients in group A (8 males and 39 females with an average age of 42.6±9.1 years), 50 patients in group B (11 males and 39 females with an average age of 45.3±11.3 years), and 64 patients in group C (10 males and 54 females with an average age of 46.9±11.4 years). The clinicopathological features and therapeutic effect of the three groups were compared by ANOVA, multiple local rank sum test, χ2 test or Fisher's exact probability method, and the recurrence rate and recurrence free survival (RFS) of the three groups were compared after a follow-up of 6 to 126 months. Results:Among the 161 patients with SPTIC, 132 (82.0%) were female, 130 (80.7%) were younger than 55 years old, BMI (25.1±3.6) kg/m 2, 124 (77.0%) were combined with capsule invasion. There were 53 cases (32.9%) with central lymph node metastasis (CLNM). Subgroup analysis showed that the proportion of males in patients with tumor diameter > 1 cm, the proportion of patients with BMI≥26.0 kg/m 2, the rate of capsular invasion, the rate of extrandular invasion and the rate of CLNM were higher (30.0% vs. 14.0%, P=0.023; 60.0% vs. 33.9%, P=0.004; 97.5% vs. 70.2%, P< 0.001; 42.5% vs. 9.9%, P<0.001; 50.0% vs. 27.3%, P=0.008) ; The CLNM rate was higher in male patients with BMI≥26.0 kg/m 2 and tumor diameter > 1 cm (28.3% vs. 13.0%, P=0.017; 52.8% vs. 34.3%, P=0.024; 37.7% vs. 18.5%, P=0.008). Compared with groups A and B, group C had longer hospitalization days, higher hospitalization costs, longer operation time, more postoperative drainage flow and higher incidence of postoperative hypoparathyroidism, and the differences were statistically significant (all P< 0.05). Groups A and B were similar in all aspects, with no statistical significance ( P> 0.05 for all). During the follow-up, 3 patients in both group A and B relapsed, while no patients in group C relapsed, and there were no statistically significant differences in the recurrence rate ( P=0.059) or RFS ( P=0.082) among the three groups. Conclusions:The majority of SPTIC were microcarcinomas, but the incidence of tumor combined with capsule invasion was higher, and the tumor size of more than 1 cm was more invasive (capsule invasion rate and extrathyroid invasion rate were higher). SPTIC should be treated as conservatively as possible (isthmic excision or enlarged isthmic excision) .

Objective To investigate the diagnosis and treatment strategy of the portal vein complications in children undergoing split liver transplantation. Methods The clinical data of 88 pediatric recipients who underwent split liver transplantation were retrospectively analyzed. Intraoperative anastomosis at the bifurcating site of the portal vein or donor iliac vein bypass anastomosis was performed depending on the internal diameter and development of the recipient's portal vein. A normalized portal venous blood stream monitoring was performed during the perioperative stage. After operation, heparin sodium was used to bridge warfarin for anticoagulation therapy. After portal vein stenosis or thrombosis was identified with enhanced CT or portography, managements including embolectomy, systemic anticoagulation, interventional thrombus removal, balloon dilatation and/or stenting were performed. Results Among the 88 recipients, a total of 10 children were diagnosed with portal vein complications, of which 4 cases were diagnosed with portal vein stenosis at 1 d, 2 months, 8 months, and 11 months after surgery, and 6 cases were diagnosed with portal vein thrombosis at intraoperative, 2 d, 3 d (n=2), 6 d, and 11 months after surgery, respectively. One patient with portal vein stenosis and one patient with portal vein thrombosis died perioperatively. The fatality related to portal vein complications was 2% (2/88). Of the remaining 8 patients, 1 underwent systemic anticoagulation, 2 underwent portal venous embolectomy, 1 underwent interventional balloon dilatation, and 4 underwent interventional balloon dilatation plus stenting. No portal venous related symptoms were detected during postoperative long term follow up, and the retested portal venous blood stream parameters were normal. Conclusions The normalized intra- and post-operative portal venous blood stream monitoring is a useful tool for the early detection of portal vein complications, the early utilization of useful managements such as intraoperative portal venous embolectomy, interventional balloon dilatation and stenting may effectively treat the portal vein complications, thus minimizing the portal vein complication related graft loss and recipient death.

The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.

Objective: To systematically evaluate the incidence and influencing factors of depression in family caregivers of Alzheimer's disease (AD) patients, so as to provide the basis for the prevention and treatment of depression among the family caregivers of AD patients. Methods: Publications pertaining to depression in family caregivers of AD patients were retrieved from CNKI, Wanfang Data, PubMed and other databases from the time of their establishment to June 15, 2023. The evaluation criteria recommended by the Agency for Healthcare Research and Quality (AHRQ) and the Newcastle-Ottawa Scale were used to assess the quality of cross-sectional and cohort studies, respectively. Stata 16.0 and Revman 5.4 softwares were used to conduct a meta-analysis on the incidence and influencing factors of depression in family caregivers of AD patients. Sensitivity analysis and publication bias assessment were also performed on the results. Results: A total of 2 324 articles were retrieved, and ultimately 14 articles were included, with a total sample size of 8 313 individuals. There were 6 high-quality articles and 8 moderate-quality articles. Meta-analysis showed that the incidence of depression in family caregivers of AD patients was 37.5% (95%CI: 30.2%-45.1%). Factors associated with depression included patients' high degree of dementia (OR=1.718, 95%CI: 1.059-2.789), patients' low scores on Activities of Daily Living Scale (OR=1.344, 95%CI: 1.059-1.706), patients' psychobehavioral abnormalities (OR=1.248, 95%CI: 1.155-1.348), long duration of caregiving (OR=1.998, 95%CI: 1.637-2.437), less involvement of other family members in caregiving (OR=1.597, 95%CI: 1.237-2.061), low educational level (OR=1.191, 95%CI: 1.044-1.359), poor caregiving skills (OR=3.060, 95%CI: 2.257-4.149), poor self-rated health (OR=2.536, 95%CI: 1.114-5.771) and social support (OR=0.424, 95%CI: 0.232-0.774). The results of depression incidence demonstrated good stability with no significant publication bias. However, publication bias was observed in the influencing factors for depression, which were patients' high degree of dementia and patients' low scores on Activities of Daily Living Scale. Conclusions The incidence of depression in family caregivers of AD patients ranges from 30.2% to 45.1%. It is primarily influenced by the severity of patients' symptoms and ability to perform daily activities, and caregivers' educational level, caregiving skills, health status, caregiving duration and social support.

Objective To analyze the influence of intraoperative blood glucose fluctuation and postoperative insulin resistance(IR)on postoperative cognitive dyfunction(POCD)in elderly patients undergoing thoracoscopic radical resection of lung cancer under general anesthesia.Methods A total of 352 elderly patients undergoing thoracoscopic radical resection of lung cancer under general anesthesia were collected and divided into the POCD group(n=84)and the non-POCD group(n=268).The covariates between the two groups were balanced by propensity score matching method(PSM).Eighty-four cases in each group were successfully matched.The data between the two groups before and after PSM were compared.After PSM,receiver operating characteristic(ROC)curve of blood glucose fluctuation amplitude for predicting POCD was drawn,and patients were divided into the low-level blood glucose fluctuation group(n=97)and the high-level blood glucose fluctuation group(n=71)according to the cut-off value.According to the existence of postoperative IR,patients were divided into the IR group(n=53)and the non-IR group(n=115).Then,incidences of POCD between groups were compared.Logistic regression was used to analyze the influencing factors of POCD.Results Before PSM,the POCD group had older age,higher blood glucose fluctuation amplitude,IR ratio,operation time,anesthesia time,propofol dosage,remifentanil dosage and sufentanil dosage in anesthesia maintenance period than those in the non-POCD group(P＜0.05).The POCD group had higher blood glucose fluctuation amplitude and IR ratio than those in the non-POCD group after PSM(P＜0.05).After PSM,the incidences of POCD in the high-level blood glucose fluctuation group and the IR group were higher than those in the low-level blood glucose fluctuation group and the non-IR group(P＜0.05).Logistic regression analysis showed that higher intraoperative blood glucose fluctuation(OR=9.140,95%CI:4.338-19.257)and postoperative IR(OR=4.034,95%CI:1.163-13.991)were risk factors of POCD.Conclusion The risk of POCD in elderly patients undergoing thoracoscopic radical lung cancer surgery under general anesthesia is increased in patients with higher intraoperative blood glucose fluctuation and postoperative IR.

The early diagnosis of Alzheimer′s disease (AD) has long been a challenge in the field of medicine. In recent years, research on blood biomarkers of AD has flourished, which holds significant promise for advancing the early diagnosis, monitoring, and early intervention of AD. With the new generation of ultra-sensitive detection techniques, a series of studies have successfully validated core biomarkers, non-specific biomarkers, and other relevant biomarkers of AD in blood. However, the use of blood-based biomarkers for the diagnosis and prediction of AD still faces some challenges related to accuracy and robustness. This article compiles and analyzes the advances, strengths, and limitations of each type of biomarkers, and provides several potential strategies to address these challenges.

Objective:To explore the correlation between serum 1, 5-anhydroglucitol (1, 5-AG) and mild cognitive impairment (MCI) in elderly patients with type 2 diabetes mellitus (T2DM).Methods:A total of 160 patients with T2DM aged 60-75 years old who visited the First Hospital of Hebei Medical University from May 2021 to July 2022 were selected. According to the Montreal cognitive assessment (MoCA), all patients were divided into T2DM with MCI group (T2DM+ MCI group, n=81) and T2DM without MCI group (T2DM group, n=79). All research subjects were tested for glycated hemoglobin A1c (HbA1c), serum 1, 5-AG, serum β-amyloid peptide 42 (Aβ42), and blood biochemical indicators.SPSS 25.0 statistical software was used for data analysis. The t test, Mann-Whitney U test and χ2 test were used to compare the two groups. Binary Logistic regression analysis was used to examine the relevant influencing factors. Results:(1) Compared with T2DM group, patients in T2DM+ MCI group had significantly higher age, systolic pressure and HbA1c(all P<0.05).The level of 1, 5-AG in T2DM+ MCI group was significantly lower than that in T2DM group( (15.65±2.56 )μg/mL, (18.17±3.72 )μg/mL, P<0.01), and the level of Aβ42 was higher than that of T2DM group (2.95 (3.36) pg/mL, 1.91 (2.48) pg/mL, P<0.05). (2) Binary Logistic regression analysis results showed that HbA1c( β=0.230, OR=1.259, 95% CI=1.010-1.568, P=0.040) and Aβ42( β=0.188, OR=1.206, 95% CI=1.033-1.409, P=0.018) were the independent risk factors for MCI in elderly patients with T2DM, while 1, 5-AG ( β=-0.240, OR=0.786, 95% CI=0.698-0.886, P<0.001) was the protective factor for MCI. Conclusion:There is a positive correlation between serum 1, 5-AG and cognitive function, and the decrease of 1, 5-AG level was associated with the increased risk of MCI in elderly patients with T2DM.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.