Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Objective:To investigate the ultrasonographic features of medullary thyroid carcinomas (MTCs) of different sizes and supply valid information for separating MTCs from papillary thyroid carcinomas (PTCs).Methods:There were 87 patients with MTC and 220 patients with PTC detected by ultrasonography and confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital from June 2018 to March 2022. Nodules were divided into the large nodule group (the maximum diameter of the tumor was＞1 cm) and the small nodule group (the maximum diameter of the tumor was ≤1 cm). There were 97 cases in the small nodule group, including 28 cases of MTC and 69 cases of PTC. There were 210 cases in the large nodule group, including 59 cases of MTC and 151 cases of PTC. After stratification by thyroid nodules, ultrasonographic features of thyroid nodules and metastatic lymph nodes, preoperative serum calcitonin (CT) and carcinoembryonic antigen (CEA) levels were compared between MTC and PTC patients.Results:In the small nodule group, the proportion of MTCs exhibiting hypoecho, smooth margins, and having blood flow signals was higher than that of PTCs, with statistically significant differences (all P＜0.05). In the large nodule group, the proportion of MTCs showing cystic solidity, hypoecho, smooth margins, blood flow, and the type Ⅳvascular distribution was higher than PTCs, and the difference of calcification type between them was also statistically significant (all P＜0.05). In contrast, the differences in the number of lesions and aspect ratio between MTCs and PTCs were not statistically significant regardless of nodule size (all P＞0.05). In the small nodule group,6 metastatic lymph nodes of medullary thyroid carcinoma (LNM-MTC) and 11 metastatic lymph nodes of papillary thyroid carcinoma (LNM-PTC) were correctly diagnosed by ultrasound, respectively. The diagnostic compliance rate of ultrasound was 78.6% (22/28) and 78.3% (54/69), respectively, with no statistically significant difference ( P=0.973). In the large nodule group, 28 LNM-MTC and 11 LNM-PTC were correctly diagnosed by ultrasound, respectively. The diagnostic compliance of ultrasound was 88.1% (52/59) and 73.5% (111/151), respectively, which was statistically significant ( P=0.022). Among them, 82.1% of LNM-MTC and 56.6% of LNM-PTC showed abnormal blood flow signals, with a statistically significant difference ( P=0.016). There were significant differences in preoperative serum CT and CEA levels of different sizes of MTCs (all P＜0.05). Conclusions:Different sizes of MTCs require diverse demonstrative criteria. Abnormal blood flow signal is of great significance in the diagnosis of LNM-MTC. Within the absence of ultrasonic characteristics, preoperative serum CT test can provide confidence for the diagnosis of MTC.

Objective:To investigate the ultrasonographic features of medullary thyroid carcinomas (MTCs) of different sizes and supply valid information for separating MTCs from papillary thyroid carcinomas (PTCs).Methods:There were 87 patients with MTC and 220 patients with PTC detected by ultrasonography and confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital from June 2018 to March 2022. Nodules were divided into the large nodule group (the maximum diameter of the tumor was＞1 cm) and the small nodule group (the maximum diameter of the tumor was ≤1 cm). There were 97 cases in the small nodule group, including 28 cases of MTC and 69 cases of PTC. There were 210 cases in the large nodule group, including 59 cases of MTC and 151 cases of PTC. After stratification by thyroid nodules, ultrasonographic features of thyroid nodules and metastatic lymph nodes, preoperative serum calcitonin (CT) and carcinoembryonic antigen (CEA) levels were compared between MTC and PTC patients.Results:In the small nodule group, the proportion of MTCs exhibiting hypoecho, smooth margins, and having blood flow signals was higher than that of PTCs, with statistically significant differences (all P＜0.05). In the large nodule group, the proportion of MTCs showing cystic solidity, hypoecho, smooth margins, blood flow, and the type Ⅳvascular distribution was higher than PTCs, and the difference of calcification type between them was also statistically significant (all P＜0.05). In contrast, the differences in the number of lesions and aspect ratio between MTCs and PTCs were not statistically significant regardless of nodule size (all P＞0.05). In the small nodule group,6 metastatic lymph nodes of medullary thyroid carcinoma (LNM-MTC) and 11 metastatic lymph nodes of papillary thyroid carcinoma (LNM-PTC) were correctly diagnosed by ultrasound, respectively. The diagnostic compliance rate of ultrasound was 78.6% (22/28) and 78.3% (54/69), respectively, with no statistically significant difference ( P=0.973). In the large nodule group, 28 LNM-MTC and 11 LNM-PTC were correctly diagnosed by ultrasound, respectively. The diagnostic compliance of ultrasound was 88.1% (52/59) and 73.5% (111/151), respectively, which was statistically significant ( P=0.022). Among them, 82.1% of LNM-MTC and 56.6% of LNM-PTC showed abnormal blood flow signals, with a statistically significant difference ( P=0.016). There were significant differences in preoperative serum CT and CEA levels of different sizes of MTCs (all P＜0.05). Conclusions:Different sizes of MTCs require diverse demonstrative criteria. Abnormal blood flow signal is of great significance in the diagnosis of LNM-MTC. Within the absence of ultrasonic characteristics, preoperative serum CT test can provide confidence for the diagnosis of MTC.

Objective:To explore the diagnostic value of strain ultrasonic elastography (SUE) supported by Image Pro Plus (IPP) software in distinguishing benign and malignant Breast Imaging Reporting and Data System (BI-RADS) category 4 nodules.Methods:The clinical and ultrasound imaging data of 192 female patients with BI-RADS category 4 nodules diagnosed by breast ultrasound in Tianjin Medical University Cancer Institute and Hospital from January 2020 to January 2021 were retrospectively analyzed. One nodule was selected for each patient, and a total of 192 nodules were analyzed. The ultrasound images and SUE images of each nodule were acquired before surgery, followed by BI-RADS classification scoring and SUE scoring. The IPP software was applied to outline the region of interest of all nodules, and the software automatically counted the SUE area ratio (SUE-IPP-AR) of all nodules. Using pathological diagnosis as the gold standard, SUE-IPP scoring was performed based on the optimal cut-off value of SUE-IPP-AR for distinguishing benign and malignant nodules according to receiver operating characteristic (ROC) curve. The efficacy of BI-RADS classification, SUE score, SUE-IPP score, and SUE-IPP+BI-RADS combined score in the differentiation of benign and malignant breast nodules were analyzed by ROC curve. Kappa coefficient was used to assess inter-observer agreement for SUE and SUE-IPP-AR.Results:Of the 192 nodules, 58 were benign nodules and 134 were malignant nodules diagnosed by pathology. These nodules were classified by BI-RADS, with 46 nodules in BI-RADS category 4A, 57 nodules in BI-RADS category 4B and 89 nodules in BI-RADS category 4C. SUE images 1-6 level were 12, 14, 41, 51, 42, and 32 nodules, respectively. ROC curve analysis showed that the optimal cut-off value of SUE-IPP for determining benign and malignant BI-RADS category 4 breast nodules was 58% [area under the curve (AUC) = 0.729, sensitivity 73%, specificity 69%]. The AUC of SUE-IPP+BI-RADS combined score for determining benign and malignant nodules was the largest (0.871), which was higher than that of BI-RADS score (AUC = 0.829, Z = 2.51, P = 0.012), SUE-IPP score (AUC = 0.729, Z = 3.56, P < 0.001) and SUE score (AUC = 0.695, Z = 4.37, P < 0.001). The sensitivity of SUE-IPP+BI-RADS combined score ≥ 3 points for diagnosing malignant nodules was 86.6%, while the specificity was 82.8%. Therefore, SUE-IPP+ BI-RADS score had the best efficacy for determining benign and malignant nodules. There was good agreement between sonographer with more than 5 years of experience and those with less than 5 years of experience in applying SUE to diagnose breast malignant nodules (Kappa = 0.768, 95% CI 0.711-0.825), and very good diagnostic agreement in applying SUE-IPP (Kappa = 0.946, 95% CI 0.919-0.974). Conclusions:SUE-IPP can improve the diagnostic ability for BI-RADS category 4 breast malignant nodules and can be used as an adjunct to ultrasound diagnosis.

As one of the most important components of caveolae, caveolin-1 is involved in caveolae-mediated endocytosis and transcytosis pathways, and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal transduction. In recent years, the relationship between the expression level of caveolin-1 in the tumor microenvironment and the prognostic effect of tumor treatment and drug treatment resistance has also been widely explored. In addition, the interplay between caveolin-1 and nano-drugs is bidirectional. Caveolin-1 could determine the intracellular biofate of specific nano-drugs, preventing from lysosomal degradation, and facilitate them penetrate into deeper site of tumors by transcytosis; while some nanocarriers could also affect caveolin-1 levels in tumor cells, thereby changing certain biophysical function of cells. This article reviews the role of caveolin-1 in tumor prognosis, chemotherapeutic drug resistance, antibody drug sensitivity, and nano-drug delivery, providing a reference for the further application of caveolin-1 in nano-drug delivery systems.

The dynamic or flowing tumor cells just as leukemia cells and circulating tumor cells face a microenvironment difference from the solid tumors, and the related targeting nanomedicines are rarely reported. The existence of fluidic shear stress in blood circulation seems not favorable for the binding of ligand modified nanodrugs with their target receptor. Namely, the binding feature is very essential in this case. Herein, we utilized HSPC, PEG-DSPE, cholesterol and two

Although high-efficiency targeted delivery is investigated for years, the efficiency of tumor targeting seems still a hard core to smash. To overcome this problem, we design a three-step delivery strategy based on streptavidin-biotin interaction with the help of c(RGDfK), magnetic fields and lasers. The ultrasmall superparamagnetic iron oxide nanoparticles (USIONPs) modified with c(RGDfK) and biotin are delivered at step 1, followed by streptavidin and the doxorubicin (Dox) loaded nanosystems conjugated with biotin at steps 2 and 3, respectively. The delivery systems were proved to be efficient on A549 cells. The co-localization of signal for each step revealed the targeting mechanism. The external magnetic field could further amplify the endocytosis of USPIONs based on c(RGDfK), and magnify the uptake distinctions among different test groups. Based on photoacoustic imaging, laser-heating treatment could enhance the permeability of tumor venous blood vessels and change the insufficient blood flow in cancer. Then, it was noticed that only three-step delivery with laser-heating and magnetic fields realized the highest tumor distribution of nanosystem. Finally, the magnetism/laser-auxiliary cascaded delivery exhibited the best antitumor efficacy. Generally, this study demonstrated the necessity of combining physical, biological and chemical means of targeting.

Objective The dynamic changes of hematopoietic function of bone marrow in patients with renal anemiabefore and after treatment and the curative effect of drug treatment were discussed through the detection of the related parameters of the red blood cell.Methods Reticulated red cells using Mindray-6900 automatic blood cell analyzer,54 cases of renal anemia patients were divided into three groups,respectively for renal function of compensatory group,renal function insufficiency decompensation group and renal failure group,and 45 cases of normal healthy group for comparison analysis were used to detect the reticulocyte percentage (RET),immature red blood cell index (IRF),red blood cell (RBC) count,hemoglobin (HB),serum creatinine (CR) and blood urea nitrogen (BUN) were detected before and after treatment of red blood cell hematocrit (HCT) and RET,and through the correction formula to calculatethe net knits red blood cell production index (RPI).The results were compared and analyzed.Results RET in renal failure compensatory group and renal failure group was significantly higher than that of the control group (P＜0.05);IRF％ in renal insufficiency compensatory group was significantly lower than that of control group (P＜0.05).and renal failure compensatory group and renal failure group were significantly higher than those of the control group (P＜0.05);RBC,Hb levels with the levels of bun and Cr increased significantly reduced,in kidney function not full decompensated group was significantly lower than that of control group (P＜0.05).and with the severity of the kidney was decreased gradually.Renal insufficiency compensatory group before and after treatment with HCT(％),Ret(％),HFR(％),MFR(％),RPI the difference was statistically significant (t=2.103,2.062,2.079,2.354,2.368;all P＜0.05),LFR (％) showed no significant difference (t=1.812,P＞ 0.05);renal insufficiency decompensation group before and after treatment with HCT(％),Ret(％),HFR(％),MFR(％),LFR(％),HFR showed significant differences (t =2.228,2.172,2.894,2.185,2.023,2.455;all P＜ 0.05);renal failure group HCT (％),Ret (％),HFR(％),MFR(％) HFR was statistically significant differences before and after the treatment (t=2.148,2.351,2.642,2.086,2.686;all P＜0.05),LFR(％) showed no significant difference (t=1.921,P＞0.05).The ROC area of IRF％ waslarger than other hematological indexes,and its diagnostic sensitivity and specificity were 88.4 ％ and 80.2 ％,respectively,when the critical value was 22.3 ％.Conclusion Reticulocyte erythrocyte parameters can effectively assist physicians in renal anemia patients for diagnosis and treatment,especially the IRF％ and RPI is net woven red cells more sensitive,and the index can more accurately reflect the growth of hematopoietic function of bone marrow and erythroid,worthy of clinical application.

Objective Analyze the relationship between high sensitivity C‐reactive protein (hs‐CRP) ,homocysteine (Hcy) ,D‐di‐mer (D‐D) levels and atherosclerosis (AS) .Methods A total of 92 patients with AS were analyzed retrospectively ,including acute coronary syndrome (ACS) group with 61 cases ,stable angina pectoris (SAP) group with 31 cases .According to the result of coro‐nary artery plaque CT detection was further divided into plaque group ,non plaque group ,stable plaque subgroup ,and unstable plaque subgroup .Meanwhile 42 healthy subjects were selected as control group .The levels of the three indicators were compared . Results The serum hs‐CRP ,Hcy and plasma D‐D concentration in the ACS group and SAP group were significant higher than those of the control group (P< 0 .05) ,and those of the ACS group were significant higher than those of the SAP group(P< 0 .05) . The serum hs‐CRP ,Hcy and plasma D‐D concentration in the plaque group were significant higher than those of the non plaque group ,those in the unstable plaque subgroup were significant higher than those of the stable plaque subgroup(P< 0 .05) .The serum hs‐CRP ,Hcy and plasma D‐D concentration of the ACS patients were all correlated positively .Conclusion Serum hs‐CRP ,Hcy and plasma D‐D levels are closely related to the development of AS ,the combined detection of three indexes is value for the prevention , treatment and prognosis of AS .

The aimed of this study was to prepare stabilized thiomers to overcome the poor stability character of traditional thiomers. Poly(acrylic acid)-cysteine (PAA-Cys) was synthesized by conjugating cysteine with poly(acrylic acid) and poly(acrylic acid)-cysteine-6-mercaptonicotinic acid (PAA-Cys-6MNA, stabilized thiomers) was synthesized by grafting a protecting group 6-mercaptonicotinic acid (6MNA) with PAA-Cys. The free thiol of PAA-Cys was determined by Ellmann's reagent method and the ratio of 6MNA coupled was determined by glutathione reduction method. The study of permeation enhancement and stabilized function was conducted by using Franz diffusion cell method, with fluorescein isothiocyanate dextran (FD4) used as model drug. The influence of polymers on tight junctions of Caco-2 cell monolayer was detected with laser scanning confocal fluorescence microscope. The results indicated that both PAA-Cys and PAA-Cys-6MNA could promote the permeation of FD4 across excised rat intestine, and the permeation function of PAA-Cys-6MNA was not influence by the pH of the storage environment and the oxidation of air after the protecting group 6MNA was grafted. The distribution of tight junction protein of Caco-2 cell monolayer F-actin was influenced after incubation with PAA-Cys and PAA-Cys-6MNA. In conclusion, stabilized thiomers (PAA-Cys-6MNA) maintained the permeation function compared with the traditional thiomers (PAA-Cys) and its stability was improved. The mechanism of the permeation enhancement function of the polymers might be related to their influence on tight junction relating proteins of cells.