AIM: To investigate the changes in serum levels of trefoil factor 1(Tff1)and bone morphogenetic protein 4(BMP4)in patients with diabetic retinopathy, and to evaluate their diagnostic value for diabetic retinopathy.METHODS: From January 2022 to January 2024, 186 patients with type 2 diabetes were selected as the study group and divided into a retinopathy subgroup(52 cases)and a non-retinopathy subgroup(134 cases)based on the presence of retinopathy. Another 186 healthy volunteers who underwent physical examinations during the same period were chosen as the control group. Serum Tff1 and BMP4 levels were measured using the enzyme-linked immunosorbent assay(ELISA). Pearson analysis was used to assess the correlation between serum Tff1, BMP4 levels, and clinical data. Multivariate Logistic regression analysis was performed to identify factors influencing the development of retinopathy in type 2 diabetic patients. Receiver operating characteristic(ROC)curve analysis was conducted to evaluate the diagnostic value of serum Tff1 and BMP4 levels for retinopathy in type 2 diabetic patients.RESULTS: Compared to the control group, serum Tff1 levels were lower and BMP4 levels were higher in both retinopathy and non-retinopathy subgroups(all P<0.05). Specifically, serum Tff1 levels were lower and BMP4 levels were higher in the retinopathy subgroup than in the non-retinopathy subgroup(all P<0.05). Pearson analysis revealed that Tff1 levels in type 2 diabetes patients were negatively correlated with disease duration, glycated hemoglobin levels, and triglyceride levels, while BMP4 levels were positively correlated(all P<0.05). Multivariate Logistic regression analysis identified type 2 diabetes duration, glycated hemoglobin, triglycerides, Tff1, and BMP4 as influencing factors for retinopathy development in type 2 diabetes patients(all P<0.05). ROC curve analysis showed that the combined diagnosis of serum Tff1 and BMP4 had an area under the curve(AUC)of 0.901, which was significantly higher than that of Tff1 alone(Z=2.069, P=0.039)and BMP4 alone(Z=2.072, P=0.038).CONCLUSION: Serum Tff1 levels are decreased and BMP4 levels are increased in patients with diabetic retinopathy, and the combined detection of these two markers offers high diagnostic value for diabetic retinopathy.

This paper aims to discuss the construction and promotion strategy of medical care capacity framework based on the core literacy of palliative care， combining domestic and foreign research and clinical status. The research results show that it is particularly important to construct a framework of medical care competence based on palliative care. The core competencies required for palliative care include the ability to comprehensively evaluate and formulate personalized programs， effective communication skills， interdisciplinary teamwork skills， and the ability to continuously learn and improve themselves. The quality of care can be further improved if the above abilities are incorporated into the framework of medical care ability based on palliative care. However， there are a series of problems in the process of constructing the framework of palliative medical care capacity， such as difficult implementation of policy support， poor professionalism of talent team， single and irregular service model， low social acceptance， and difficult interdisciplinary cooperation and resource integration. After a detailed analysis of the problems， this paper puts forward the countermeasures to construct the framework of caring ability literacy based on palliative care. Effective countermeasures such as increasing policy support， cultivating comprehensive talents， developing diversified palliative care models， improving social recognition， and strengthening interdisciplinary cooperation and resource integration can effectively improve the core literacy and professional ability of medical care personnel， and then promote the development and improvement of palliative care services. In-depth discussion of the above contents can provide scientific reference for building a care model and literacy framework with palliative care as the core.

Objective:To investigate the levels of serum high mobility group box (HMGB) 2 and HMGB3 and clinical significance in patients with non-small cell lung cancer (NSCLC) .Methods:A total of 137 NSCLC patients admitted to the First Affiliated Hospital of Xi'an Medical University from January 2020 to January 2022 were selected as the NSCLC group, and another 90 cases who underwent healthy medical checkups during the same period were selected as the healthy group. Serum HMGB2 and HMGB3 levels were compared between the two groups. The relationship between serum HMGB2 and HMGB3 levels and the clinical and pathological characteristics of NSCLC patients was analyzed. NSCLC patients were divided into a good prognosis group ( n=86) and a poor prognosis group ( n=51) according to the prognosis, and the clinical data of the two groups were compared. Multivariate logistic regression was used to analyze the influencing factors of the prognosis of NSCLC patients. Receiver operator characteristic (ROC) curve was used to analyze the predictive value of serum HMGB2 and HMGB3 on the prognosis of NSCLC patients. Results:Serum HMGB2 [ (6.35±1.66) ng/ml vs. (2.58±0.76) ng/ml, t=20.19, P<0.001] and HMGB3 [ (2.48±0.56) ng/ml vs. (1.09±0.13) ng/ml, t=23.13, P<0.001] levels in NSCLC group were higher than those in healthy group. Serum HMGB2 and HMGB3 levels of NSCLC patients with a history of smoking ( t=2.80, P=0.006; t=5.04, P<0.001), lymph node metastasis ( t=3.53, P=0.001; t=4.02, P<0.001), and TNM stage Ⅲ-Ⅳ ( t=2.58, P=0.011; t=3.82, P<0.001) were significantly higher than those of patients with no history of smoking, no lymph node metastasis, and TNM stage Ⅰ-Ⅱ. The serum levels of HMGB2 [ (7.80±1.83) ng/ml vs. (5.49±1.56) ng/ml, t=7.85, P<0.001] and HMGB3 [ (2.91±0.78) ng/ml vs. (2.23±0.43) ng/ml, t=6.58, P<0.001) ] in the poor prognosis group were higher than those in the good prognosis group, and the proportion of patients with lymph node metastasis ( χ2=4.81, P=0.028), history of smoking ( χ2=11.67, P=0.001), and TNM stage Ⅲ-Ⅳ ( χ2=6.18, P=0.013) was significantly higher than that in the good prognosis group. Multivariate logistic regression analysis showed that lymph node metastasis ( OR=1.96, 95% CI: 1.14-3.36, P=0.015), smoking history ( OR=2.02, 95% CI: 1.33-3.06, P=0.001), TNM stage ( OR=2.28, 95% CI: 1.35-3.86, P=0.002), HMGB2 ( OR=2.01, 95% CI: 1.40-2.91, P<0.001), and HMGB3 ( OR=1.99, 95% CI: 1.25-3.15, P=0.003) levels were independent influencing factors of prognosis of NSCLC patients. ROC curve analysis showed that the area under the curve (AUC) of serum HMGB2 and HMGB3 alone and in combination to predict the prognosis of NSCLC patients were 0.833, 0.862 and 0.922, respectively, and the AUC predicted by the combination was significantly higher than that predicted by serum HMGB2 ( Z=2.44, P=0.015) and HMGB3 ( Z=2.54, P=0.011) alone. Conclusion:Serum HMGB2 and HMGB3 levels are up-regulated in NSCLC patients and are closely associated with poor prognosis, and the combined detection of the two has certain predictive efficacy for prognosis of NSCLC patients.

Objective To investigate the effect of sirtuin 3(SIRT3)on the oxidative stress response and hypoxia inducible factor-1α(HIF-1α)expression in lung cancer cells through reactive oxygen species(ROS)under hypoxic conditions and its mechanism.Methods Human non-small cell lung cancer A549 cells were exposed to hypoxia for 0 h,12 h,24 h and 48 h.The mRNA and protein expressions of HIF-1α and SIRT3 were detected by RT-PCR and Western blot to determine the optimal time of hypoxia induction.A549 cells were divided into 5 groups:control group,hypoxia group,hypoxia+ROS inhibitor n-acetylcysteine(NAC)group,hypoxia+(SIRT3 overexpression)SIRT3-OE group and hypoxia+SIRT3-OE+NAC group.Cell proliferation was detected by MTT assay.Cell apop-tosis was detected by flow cytometry.The mRNA and protein expressions of HIF-1 α and SIRT3 in each group were detected by RT-PCR and Western blot.ROS content in each group was detected by flow cytometry.The contents of malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in the cells of each group were detected by biochemical kits.Results The optimal induction time of hypoxia was 24 h.Compared with the control group,the apoptosis rate,SIRT3 mRNA and protein levels,SOD and GSH contents in the hypoxia group signifi-cantly decreased(P＜0.01),the cell proliferation ability,HIF-1 α mRNA and protein levels,ROS and MDA con-tent in cells significantly increased(P＜0.01).Compared with the hypoxia group,the apoptosis rate,SIRT3 mR-NA and protein levels,SOD and GSH contents in the hypoxia+NAC and hypoxia+SIRT3-OE groups increased(P＜0.05),the cell proliferation ability,HIF-1 α mRNA and protein levels,ROS and MDA content in cells de-creased(P＜0.05).Compared with the hypoxia+NAC group,the apoptosis rate,SIRT3 mRNA and protein lev-els,SOD and GSH contents in the hypoxia+SIRT3-OE+NAC group significantly increased(P＜0.01),the cell proliferation ability,HIF-1 α mRNA and protein levels,ROS and MDA content in cells significantly decreased(P＜0.01).Conclusion Under hypoxic conditions,SIRT3 can promote cell apoptosis and inhibit lung cancer pro-gression by mediating ROS to inhibit oxidative stress response and HIF-1 α expression in lung cancer cells.

OBJECTIVE To analyze the dose-adjusted concentrations of Posaconazole oral suspension in patients undergoing hematopoietic stem cell transplantation （HSCT） and their influential factors. METHODS Data were collected from hospitalized HSCT patients admitted to the First Affiliated Hospital of Shandong First Medical University （Shandong Provincial Qianfoshan Hospital） from January 2021 to April whtwhm@yeah.net 2023 who took Posaconazole oral suspension for the prevention of invasive fungal disease （IFD） and received blood concentration of posaconazole. The rate of concentration attainment and clinical failure rate of posaconazole for the prevention of IFD were evaluated， and one-way and multiple linear regression analyses were performed for the influential factors of dose-adjusted concentrations （C0/D） of posaconazole. RESULTS A total of 44 patients were enrolled； the mean C0 of posaconazole in patients was （0.99±0.94） µg/mL， and 20 patients had a C0≥0.7 μg/mL， with a concentration attainment rate of 45.45% for the prevention of IFD； 13 cases were clinical failures， with a clinical failure rate of 29.55%. Of 24 patients who did not achieve C0/D of posaconazole for IFD prophylaxis， one patient was a clinical failure despite timely dose adjustment of posaconazole in seven patients； seven of the thirteen patients who did not undergo dose adjustment were clinical failures； and the remaining four patients were switched to other antifungal agents. The results of univariate analysis showed that gender， body mass index （BMI）， renal function， combined use of sodium phenytoin， omeprazole and metoclopramide had a significant effect on the C0/D of posaconazole （P＜0.05）； the results of multivariate linear regression analysis showed that gender， BMI and combined use of sodium phenytoin were the independent factors affecting the C0/D of posaconazole （P＜0.05）. CONCLUSIONS Significant individual differences are reflected in the blood concentration of Posaconazole oral suspension； gender， BMI and combined use of sodium phenytoin are independent factors affecting the C0/D of posaconazole.

Objective:To investigate the factors affecting the accuracy of electronic portal imaging device (EPID)-based in vivo dose verification in radiotherapy for patients with lung and esophageal cancers, and to recommend the workflow and specifications for the application of the in vivo dose verification. Methods:This study randomly selected 32 patients who received radiotherapy for esophageal and lung cancers at the Department of Radiation Oncology, Jinhua Municipal Central Hospital from May to August 2022, including 14 lung cancer cases and 18 esophageal cancer cases. Using a uRT-linac 506c linear accelerator, these patients were treated according to the dynamic intensity-modulated radiotherapy (dIMRT) and EPID-based In vivo dose verification ( In vivo EPID) plans developed with the uRT-TPOIS planning system. The In vivo dose verification performed during the treatment included 238 fractions of In vivo EPID and 80 fractions of image-guided radiotherapy (IGRT) for the lung cancer cases, as well as 414 fractions of In vivo EPID and 105 fractions of IGRT for the esophageal cancer cases. The 2D γ passing rate for each irradiation field was obtained according to the set threshold value. Furthermore, fractioned irradiation fields with γ-passing rates below the threshold value were analyzed, and primary factors decreasing the γ-passing rate were further analyzed by combining the online CT images and 3D reconstruction-derived dose. Results:For lung and esophageal cancers, the mean γ-passing rates were 95.1% ± 5.7% and 96.5% ± 4.5%, respectively at 3 mm/5%; 91.5% ± 8.4% and 92.2% ± 4.9%, respectively at 3 mm/3%, and 79.1% ± 14.7% and 83.7% ± 8.2%, respectively at 2 mm/2%, indicating no statistically significant differences between two cancers ( P > 0.05). The average γ passing rate for beam orientations near 0°/180° (Group A) was higher than those near 90°/270° (Group B) 3 mm/5%: Z = -25.4, P < 0.05; 3 mm/3%: Z = -26.8, P < 0.05). The IGRT correction of setup errors significantly improved the γ passing rates (96.3% ± 5.1% and 96.4% ± 4.9%, respectively at 3 mm/5%, Z = -5.50, P < 0.05; 92.3% ± 8.0% and 91.3% ± 7.7%, respectively at 3 mm/3%, Z = -9.54, P < 0.05). The results of In vivo dose verification were affected by changes in the volumes and motion of tumors and normal tissues, radiotherapy positioning, and adequacy of pre-treatment preparation. Conclusions:EPID-based In vivo dose verification during radiotherapy can avoid incorrect irradiation. However, it is necessary to standardize the workflow of the EPID-based In vivo dose verification to avoid the decrease in the γ passing rate caused by artificial factors.

【Objective】 To investigate the transfusion ratio of plasma to RBC suspension during DIC caused by sever postpartum hemorrhage, so as to improve the clinical blood transfusion protocol. 【Methods】 A total of 82 parturients, who gave birth in our obstetrics department from January 2008 to December 2019 and treated successfully for DIC due to sever postpartum hemorrhage, were selected for the study. According to the plasma/RBC suspension ratio range (from 0.4 to 2.0) during DIC rescue, the included population was divided into four groups according to the ratio interval of 0.4: Group 1: 0.4~0.8 (13 people, median 0.7), Group 2 : 0.8~1.2(30 people, median 1.0), Group 3: 1.2~1.6(30 people, median 1.3), and Group 4: 1.6~2.0 (9 people, median 1.8). The general conditions, way of delivery, number of uterine artery perfusion embolization and surgical operations performed in the 4 groups were recorded. Once spontaneous postpartum hemorrhage occurred, blood cell analysis and coagulation function examinations were carried out every 1 to 2 hours until the condition was stable. The 24-hour blood loss, transfusion units of RBC suspension, fresh frozen plasma(FFP), platelet apheresis and fibrinogen during DIC and throughout the rescue of 4 groups were recorded and compared. Locally Weighted Regression (Lowess) method was applied to analyze the nonlinear association between the plasma/RBC suspension ratio and the duration of DIC, according to the duration of DIC in 4 groups. 【Results】 1) The shortest duration of DIC (326.15 min) was observed in DIC patients transfused with a plasma/ red blood cell suspension ratio=1.8. The duration of DIC (min) in the four groups were 505.21±259.53, 435.67±307.18, 420.93±259.43, and 247.86±215.77, respectively (P<0.05). 2) The coagulation indexes PT(s), INR, APTT(s) and Fib(g/L) gradually recovered between 2.9~13.9 h after transfusion in all four groups, especially in group 4 (median plasma/RBC suspension ratio of 1.8), whose changes were most pronounced in PT, INR, and Fib at 4.3 h, 2.9 h, and 5 h, respectively (P<0.05). 【Conclusion】 Fresh frozen plasma should be given as early as possible during blood transfusion treatment of DIC rescue. The increase of the ratio of plasma/RBC suspension is beneficial to the early recovery of DIC, and the optimal ratio of plasma to RBC suspension is 1.8.

Objective:To explore the effects of interpregnancy interval (IPI) on pregnancy outcomes of subsequent pregnancy.Methods:A multicenter retrospective study was conducted in 21 hospitals in China. Information of age, height, pre-pregnancy weight, IPI, history of diseases, complications of pregnancy, gestational age of delivery, delivery mode, and pregnancy outcomes of the participants were collected by consulting medical records of pregnant women who had two consecutive deliveries in the same hospital during 2011 to 2018. The participants were divided into 4 groups according to IPI:<18 months, 18-23 months, 24-59 months and ≥60 months. According to the WHO′s recommendation, with the IPI of 24-59 months group as a reference, to the effects of IPI on pregnancy outcomes of subsequent pregnancy were analyzed. Stratified analysis was further carried out based on age, history of gestational diabetes mellitus (GDM), macrosomia, and premature delivery, to explore the differences in the effects of IPI on pregnancy outcomes among women with different characteristics.Results:A total of 8 026 women were included in this study. There were 423, 623, 5 512 and 1 468 participants in <18 months group, 18-23 months group, 24-59 months group and ≥60 months group, respectively. (1) The age, pre-pregnancy body mass index (BMI), history of cesarean section, GDM, gestational hypertension and cesarean section delivery rate of <18 months group, 18-23 months group, 24-59 months group and ≥60 months group were gradually increased, and the differences were statistically significant ( P<0.05). (2) After adjusting for potential confounding factors, compared with women in the IPI of 24-59 months group, the risk of premature delivery, premature rupture of membranes, and oligohydramnios were increased by 42% ( OR=1.42, 95% CI: 1.07-1.88, P=0.015), 46% ( OR=1.46, 95% CI: 1.13-1.88, P=0.004), and 64% ( OR=1.64, 95% CI: 1.13-2.38, P=0.009) respectively for women in the IPI≥60 months group. No effects of IPI on other pregnancy outcomes were found in this study ( P>0.05). (3) After stratified by age and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of oligohydramnios for women with advanced age ( OR=2.87, 95% CI: 1.41-5.83, P=0.004); and <18 months could increase the risk of premature rupture of membranes for women under the age of 35 ( OR=1.59, 95% CI: 1.04-2.43, P=0.032). Both the risk of premature rupture of membranes ( OR=1.58, 95% CI: 1.18-2.13, P=0.002) and premature delivery ( OR=1.52, 95% CI: 1.07-2.17, P=0.020) were significantly increased in the IPI≥60 months group. After stratified by history of GDM and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would lead to an increased risk of postpartum hemorrhage for women with a history of GDM ( OR=5.34, 95% CI: 1.45-19.70, P=0.012) and an increased risk of premature rupture of membranes for women without a history of GDM ( OR=1.44, 95% CI: 1.10-1.90, P=0.009). After stratified by history of macrosomia and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months could increase the proportion of cesarean section for women with a history of macrosomia ( OR=4.11, 95% CI: 1.18-14.27, P=0.026) and the risk of premature rupture of membranes for women without a history of macrosomia ( OR=1.46, 95% CI: 1.12-1.89, P=0.005). After stratified by history of premature delivery and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of premature rupture of membranes for women without a history of premature delivery ( OR=1.47, 95% CI: 1.13-1.92, P=0.004). Conclusions:Both IPI≥60 months and <18 months would increase the risk of adverse pregnancy outcomes in the subsequent pregnancy. Healthcare education and consultation should be conducted for women of reproductive age to maintain an appropriate IPI when they plan to pregnant again, to reduce the risk of adverse pregnancy outcomes in the subsequent pregnancy.

Purpose: C5α receptor 1 (C5ΑR1) is associated with the development of various human cancers. However, whether it is involved in the development of hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) is poorly understood. We explored the expression, biological role, and associated mechanisms of C5AR1 in HBV-related hepatoma cells. Materials and Methods: The expression of C5ΑR1 mediated by HBV and HBV core protein (HBc) was detected in hepatoma cells. The function of nuclear factor кB (NF-κB) pathway in HBc-induced C5AR1 expression was assessed. The roles of C5ΑR1 in the activation of intracellular signal pathways, the upregulation of inflammatory cytokines, and the growth and migration of hepatoma cells mediated by HBc, were investigated. The effect of C5α in the development of HCC mediated by C5AR1 was also measured. Results: C5ΑR1 expression was increased in HBV-positive hepatoma cells. Dependent on HBc, HBV enhanced the expression of C5ΑR1 at the mRNA and protein levels. Besides, HBc could promote C5ΑR1 expression via the NF-κB pathway. Based on the C5ΑR1, HBc facilitated the activation of JNK and ERK pathways and the expression and secretion of interleukin-6 in hepatoma cells. Furthermore, C5ΑR1 was responsible for enhancing the growth and migration of hepatoma cells mediated by HBc. Except these, C5α could promote the malignant development of HBc-positive HCC via C5AR1. Conclusion We provide new insight into the mechanisms of hepatocarcinogenesis mediated by HBc. C5ΑR1 has a significant role in the functional abnormality of hepatoma cells mediated by HBc, and might be utilized as a potential therapeutic target for HBV-related HCC.

Purpose: C5α receptor 1 (C5ΑR1) is associated with the development of various human cancers. However, whether it is involved in the development of hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) is poorly understood. We explored the expression, biological role, and associated mechanisms of C5AR1 in HBV-related hepatoma cells. Materials and Methods: The expression of C5ΑR1 mediated by HBV and HBV core protein (HBc) was detected in hepatoma cells. The function of nuclear factor кB (NF-κB) pathway in HBc-induced C5AR1 expression was assessed. The roles of C5ΑR1 in the activation of intracellular signal pathways, the upregulation of inflammatory cytokines, and the growth and migration of hepatoma cells mediated by HBc, were investigated. The effect of C5α in the development of HCC mediated by C5AR1 was also measured. Results: C5ΑR1 expression was increased in HBV-positive hepatoma cells. Dependent on HBc, HBV enhanced the expression of C5ΑR1 at the mRNA and protein levels. Besides, HBc could promote C5ΑR1 expression via the NF-κB pathway. Based on the C5ΑR1, HBc facilitated the activation of JNK and ERK pathways and the expression and secretion of interleukin-6 in hepatoma cells. Furthermore, C5ΑR1 was responsible for enhancing the growth and migration of hepatoma cells mediated by HBc. Except these, C5α could promote the malignant development of HBc-positive HCC via C5AR1. Conclusion We provide new insight into the mechanisms of hepatocarcinogenesis mediated by HBc. C5ΑR1 has a significant role in the functional abnormality of hepatoma cells mediated by HBc, and might be utilized as a potential therapeutic target for HBV-related HCC.