Patients with severe tumors do not refer to the patients with end-stage tumors,but rather to the patients with a performance status(PS)score between 2 and 4 in certain stages due to various reasons,such as acute or chronic comorbidities,tumor itself,or treatment-related adverse events.To these patients,there is a high probability of achieving survival benefit and/or improvement in PS scores after synergistic management of available life-support technologies and anti-tumor therapies based on dynamic and precise testing.Elderly patients with tumors frequently present with one or more chronic illnesses and have poor toler-ance and compliance to treatment.Moreover,their treatment regimens often lack high-quality clinical evidence,making them more susceptible to developing severe tumors.The management of severe tumors in the elderly is based on three basic diagnosis and treatment technologies:dynamic and precise detection,powerful life support technologies,and skillful application of current anti-tumor treatments.In specific clinical practice,the following 7 flexible and individualized treatment strategies should be adopted for different tumor types:1.concurrent management of cancer and comorbidities,2.upgrading and downgrading of anti-tumor drugs based on PS score,3.dynamic accurate detection,4.skillful combinations for increasing efficacy and reducing toxicity,5.complete overview,paying equal attention to systemic therapy and local therapy,6.safety first in medication for the elderly,7.multi-discipli-nary participation,individualized and comprehensive treatment.This article introduced the concept of severe tumors in the elderly and the associated management strategies,to increase awareness and provide feasible guidance for clinical practice.

Objective To investigate the relationship between the expression of programmed death ligand 1(PD-L1)and hypoxia inducible factor-1α(HIF-1 α)with the clinical pathological characteristics and prognosis of gastric cancer patients.Methods The cancer tissues of 100 gastric cancer patients who underwent radical gastrectomy at the First Hospital of Handan City from July 2019 to July 2020 were selected as the research subjects,and their adjacent tissues(normal tissues ≥ 5 cm from the cancer tissues)were as the control group.Immunohistochemical detection of PD-L1 and HIF-1 α was performed by SP method.Spearman correlation analysis was used to analyze PD-L1 and HIF-1 α in gastric cancer tissues.Kaplan-Meier method was used to analyze the 3-year survival relationship of gastric cancer patients.The influencing factors of prognosis and death in patients with gastric cancer were analyzed by univariate and multivariate Cox regression.Results Among 100 gastric cancer patients,52 were PD-L1 positive and 48 were negative;67 were HIF-1 α positive and 33 were HIF-1 α negative,the positive expression rates of PD-L1 and HIF-1α in gastric cancer tissues were 52.00％and 67.00％,respectively,which were obviously higher than those in adjacent tissues(11.00％、18.00％),the difference was statistically significant(P＜0.05).Spearman correlation analysis showed that the expression of PD-L1 was positively correlated with that of HIF-1α in gastric cancer tissues(r=0.730,P＜0.001).The expressions of PD-L1 and HIF-1α in patients with gastric cancer were correlated with TNM stage,lymph node metastasis and local invasion(P＜0.05).The 3-year overall survival rate of gastric cancer patients was 48.00％after surgery,and the 3-years survival rate of patients with positive expression of PD-L1 and HIF-1α were 28.85％and 31.34％,which were lower than those of patients with negative expression of PD-L1 and HIF-1α(68.75％and 81.82％)(Log rank x2=25.155,P＜0.001.Log rank x2=24.552,P＜0.001).Moreover,positive expression of PD-L1 and HIF-1α,TNM staging of Ⅲ-Ⅳ,lymph node metastasis,and local infiltration were independent risk factors for prognosis and death in gastric cancer patients(P＜0.05).Conclusion Both PD-L1 and HIF-1α are highly expressed in cancer tissues of gastric cancer patients,and they are positively correlated.They are also associated with clinical pathological features such as TNM staging,lymph node metastasis,and poor prognosis.

Background::Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-na?ve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-na?ve MM.Methods::This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-na?ve MM patients.Results::A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-na?ve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG +Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1) + DCs, IFN-responding DCs, MHCII + DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-na?ve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that "don’t eat me" -related genes and IFN-induced genes increase in treatment-na?ve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16 + monocytes/macrophages and expression level of CD16. Cell-cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-na?ve MM patients. Conclusions::Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.

Objective:To study the iodine nutrition status of children aged 8 to 10 and pregnant women and thyroid of children in Fushun City, Liaoning Province, and to provide data for formulation of prevention and control programs on iodine deficiency disorders in Fushun.Methods:In 2021, according to population probability proportional sampling method (PPS), 1 street (township) was selected from 7 districts and counties (Dongzhou District, Wanghua District, Dongzhou District, Xinfu District, Fushun County, Xinbin County and Qingyuan County) in Fushun City according to 5 directions (east, south, west, north and middle) and 1 primary school was selected from each street (township). Forty to 50 children aged 8 to 10 from each primary school and 20 pregnant women were selected from each street (township). Urine samples and salt samples of children and pregnant women were collected for urine iodine and salt iodine levels detection, and thyroid gland of children was examined to calculate the goiter rate. Urine iodine was determined by "Determination of Iodine in Urine Part 1: Method for Determination of Iodine in Urine by As 3+-Ce 4+ Eatalytic Spectrophotometry", salt iodine was determined by "General Test Method in Salt Industry - Determination of Iodine", and children's thyroid was examined by Doppler B-ultrasound. Children iodine nutrition criteria: urinary iodine median < 100 μg/L was iodine deficiency; 100 - < 200 μg/L was suitable for iodine; 200 - < 300 μg/L was more than the appropriate amount of iodine; ≥300 μg/L was iodine excess. Pregnant women iodine nutrition criteria: urinary iodine median < 150 μg/L was iodine deficiency; 150 - < 250 μg/L was suitable for iodine. 250 - < 500 μg/L was more than the appropriate amount of iodine; ≥500 μg/L was iodine excess. Criteria for iodized salt: 18 - 33 mg/kg was qualified iodized salt; < 5 mg/kg was non-iodized salt; 5 - < 18 or > 33 mg/kg was unqualified iodized salt. Results:A total of 1 647 children aged 8 to 10 years were selected, including 829 males and 818 females. The median urinary iodine of children was 203.4 μg/L. The median urinary iodine of children by district and county ranged from 151.6 to 232.4 μg/L, and the difference was statistically significant ( H = 24.227, P < 0.001). A total of 700 urine samples were collected from pregnant women. The median urine iodine was 164.7 μg/L. The median urine iodine of pregnant women by district and county ranged from 131.3 to 193.0 μg/L, and the difference was statistically significant ( H = 48.516, P < 0.001). A total of 2 347 salt samples were collected, including 2 329 iodized salt samples, with iodized salt coverage rate of 99.23% (2 329/2 347). There were 2 254 qualified iodized salt samples, and the rate of qualified iodized salt was 96.04% (2 254/2 347). There was no correlation between total urinary iodine level and salt iodine content ( r = 0.129, P > 0.05). The thyroid gland of 1 439 children was examined, and 25 children of them had goiter, with an enlargement rate of 1.74% (25/1 439), lower than the national standard for elimination of iodine deficiency disorders (< 5%), and the difference between counties and districts was statistically significant (χ 2 = 31.692, P < 0.01). Conclusion:The iodine nutrition of 8 to 10 years old children and pregnant women in Fushun City, Liaoning Province in 2021 is basically at an appropriate level, the rate of qualified iodized salt is high, and the goiter rate of children conforms to the national elimination standards of iodine deficiency disorders.

Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.
Animals ; Bone Regeneration ; Indoles ; Nanoparticles ; Osteogenesis ; Pharmaceutical Preparations ; Polymers ; Rats

Objective To explore the construction method and physicochemical properties of disulfide?bonded hyaluronic acid?functionalized sodium?meter probe for hepatocellular carcinoma, and its biological evaluation in vitro and feasibility of MRI. Methods Synthesis of hyaluronic acid?disulfide?bonded?poly ε?caprolactone (HA?SS?PCL) by disulfide?bonded alkynyl?terminated polycaprolacton (alkyne?SS?PCL) and azido?terminated hyaluronic acid (HA?N3) by clicking chemical reaction, then doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) were encapsulated in HA?SS?PCL core by dialysis method.HA?SS?PCL@DOX/SPIO was prepared and its particle size,DOX and SPIO loading rate were measured. With PBS as control group, the safety of HA?SS?PCL on human hepatocellular carcinoma cells HepG2 and normal liver cells LO2 was evaluated by the methylthiazolyl tetrazolium (MTT) assay, and the cytotoxicity of HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO on human hepatocellular carcinoma cells HepG2 was evaluated. Immunofluorescence and flow cytometry were used to observe the expression of CD44 receptor on the surface of HepG2 cells in HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO groups. Through in vitro MRI, PBS was used as the control group to observe the changes of T2 signal intensity of HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO groups when SPIO concentration was 10, 20, 40, 80 μg / ml. One way ANOVA test and t test were used. Results HA?SS?PCL@DOX / SPIO sodium?meter probes were successfully constructed. The particle size of HA?SS?PCL@DOX/SPIO was (126.9±6.3) nm,and they were spherical with uniform size. The loading rates of DOX and SPIO were 61.4% and 58.7%. MTT assay showed that the survival rate of HepG2 and LO2 cells was more than 80% even at 500 μg/ml of HA?SS?PCL, 66.6% in HA?PCL@DOX/SPIO group and 55.2% in HA?SS?PCL@DOX/SPIO group. Immunofluorescence and flow cytometry showed that HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO groups all have strong fluorescence, and the latter has stronger fluorescence intensity the former fluorescence intensity was 139.70±8.52,less than the latter 245.06±13.21. In vitro MRI showed that the T2 signal intensity of HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO was significantly lower than that of the control group (F values were 613.591 and 569.234,P=0.000), the latter decline rate was more significant. Conclusion The disulfide?bonded hyaluronic acid?functionalized sodium?meter probe for hepatocellular carcinoma has excellent physicochemical properties, good targeting and MRI functions on human hepatoma cell HepG2 at the cellular level in vitro.

Objective To preliminarily explore the anti?cancer efficiency of disulfide?bonded hyaluronic acid?functionalized targeted sodium?meter probe for hepatocellular carcinoma and the feasibility of MRI. Methods Twenty?one nude mice models of subcutaneous liver cancer transplantation were randomly divided into saline, hyaluronic acid?poly ε?caprolactone@ doxorubicin/superparamagnetic iron oxide (HA?PCL@DOX/SPIO) and HA?disulfide?bonded?PCL@DOX/SPIO (HA?SS?PCL@DOX/SPIO) groups, with 7 mice in each group. The experimental groups were injected with micelles at a dose of Fe 5 mg/kg through the tail vein, and the control group was injected with the same amount of saline via the tail vein. MRI was performed before and after injection (2 h, 4 h, 8 h). The T2 value of the region of interest (tumor) was measured and its decline rate was calculated. Twenty?one nude mice models of orthotopic liver cancer transplantation were randomly divided into saline group,HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO groups, with 7 mice in each group. The experimental groups were injected with micelles at a dose of DOX 2 mg/kg through the tail vein by three consecutive times a day apart, and the control group was injected with the same amount of saline through the tail vein. Continuous observation for 15 days to calculate tumor inhibition rate. One way ANOVA test was used. Results The T2 value of HA?SS?PCL@DOX/SPIO group decreased significantly after 2, 4 and 8 hours (P<0.05) than initial time, which was distinct compared with HA?PCL@DOX/SPIO group. The growth rate of tumor in HA?SS?PCL@DOX/SPIO and HA?PCL@DOX/SPIO groups was significantly lower than that in the control group (F=21.513,P<0.05). The former had the most obvious inhibitory effect on orthotopic liver cancer (47.7% and 28.2%). Conclusion Disulfide?bonded hyaluronic acid?functionalized targeted sodium?meter probe for hepatocellular carcinoma(HA?SS?PCL@DOX/SPIO) has high anti?cancer efficiency and imaging function at the animal level in vivo, and can be used to monitor the early therapeutic effect of tumor at the molecular imaging level.

Objective To investigate the application value of functional MRI in the differential diagnosis between breast mucinous carcinoma and phyllodes tumor(≥ 3 cm). Methods 55 cases of breast mucinous adeno-carcinoma and phyllodes tumors(≥ 3 cm)from January 2012 to December 2017 were retrospectively analyzed. MRI features of 20 mucinous carcinomas and 35 phyllodes tumors were analyzed,compared with pathology. Re-sults There were 20 cases of breast mucinous carcinoma in current study,including 14 cases of pure mucinous carcinoma and 6 cases of mixed mucinous carcinoma. There were 35 cases of phyllodes tumors,including 9 be-nign,18 borderline and 8 malignant cases. There was no significant difference in T1WI signal and enhancement mode between breast mucinous carcinoma and phyllodes tumors. There were significant differences in age,long di-ameter,morphology,lobulation,border,ADC value,EER,T2WI signal and TIC curve pattern(P < 0.05). The area under ROC(AUC)of ADC value and EER for breast mucinous adenocarcinoma and phyllodes tumor was 0.7036 and 0.8029,respectively. Conclusions Multi-model functional MRI can effectively distinguish breast mucinous adenocarcinoma from phyllodes tumor(≥ 3 cm),and EER is more accurate than ADC value.

Objective To investigate the CT findings and its pathological basis of gastrointestinal neuroendocrine tumors (GEP-NETs ). Methods The CT findings of 23 patients with GEP-NETs confirmed by pathology were analyzed retrospectively and compared with the pathological results.Results The GEP-NETs were found on CT in 20 patients,including focal gastrointestinal wall thickening in 4,mass formation in 6,and both in 10.The tumor diameter ranged from 0.9 cm to 5.2 cm with a mean value of (2.6±0.6)cm. Plain CT showed homogenous isodensity in 15 lesions,little necrosis with low density in 4,and hemorrhage with high density in 1. The dynamic contrast-enhanced CT showed the tumors with obvious enhancement in 16 cases and mild enhancement in 4 in arterial phase.In addition,serosa invasion was found in 7,enlargement of mesentery lymph node in 7,and liver metastases in 2.The pathol-ogy showed the location of submucosa and invasion of the tumors.Most small tumors had intact gastrointestinal mucosa,and some large ones had surface or infiltrated ulcer.Conclusion Some specific CT findings of GEP-NETs depend on its pathological character-istics.CT plays an important role in assessment of invasion extent and metastasis of the tumor.