BACKGROUND:Tumor stem cels are found to be involved in the recurrence, metastasis and drug resistance of the tumor.
OBJECTIVE:To explore the relationship between cel activity and multidrug resistance of CD44+CD24-/low breast cancer stem cels.
METHODS:CD44+CD24-/low breast cancer stem cels sorted from multidrug resistant breast cancer cel line MCF-7/ADR were detected as percentage using flow cytometry. P-gp fluorescence intensity of the cel membrane and MDR mRNA expression in sorted cels and MCF-7/ADR were detected using flow cytometry and RT-PCR, respectively.
RESULTS AND CONCLUSION: After sorting by flow cytometry, the proportion of CD44+CD24-/low breast cancer stem cels was more than 90%, indicating that the sorted cels could meet the needs of the subsequent experiment. CD44+CD24-/low cel subsets exhibited stronger ability to form microspheres than non- CD44+CD24-/low cel subsets. The P-gp fluorescence intensity and MDR mRNA expression of CD44+CD24-/low cels were significantly higher than those of MFC-7/ADR cel line (P < 0.05). These experimental findings suggest that CD44+CD24-/low breast cancer stem cels sorted from MCF-7/ADR cel lines have a strong ability to form cel microspheresin vitro, and significantly raise the level of P-gp protein and MDR mRNA expression, which may be one of the causes of multidrug resistance.

Objective This study is designed to explore the regulation of carboxyamidotriazole(CAI)on inflammatory factors in vitro and its underlying mechanisms.Methods Peritoneal macrophages were incubated with different concentrations(5～40 μmol/L),and then cell viabilities were evaluated by MTT assay.Cells were pretreated with CAI(5～40 μmol/L),LPS was then added,and celia were incubated for 18 h.NO and TNF-α levels were determined with Griess reagent and ELISA kit,respectively.The iNOS expression and NF-κB activation were detected by Western blot method.Results The rat peritoneal macrophage viability was not affected at the concentrations of CAI used.CAI(5～40 μmol/L)was found to reduce NO(P＜0.01,P＜0.001)and TNF-α production(P＜0.05,P ＜ 0.01)in a dose-dependent manner.CAI was also found to inhibit the LPS-induced expression of iNOS and degradation of IκBα in rat peritoneal macrophages.Conclusion The findings from the present study suggest that CAI has suppressive effect on iNOS expression,and this inhibitory effect was found to be associated with NF-κB inactivation via the blockade of IκBα phosphorylation.

Objective To discuss the protection of parathyroid and application of nano-carbon suspen-sion in thyroid surgery .Methods 80 cases were randomly divided into 2 groups:the experimental group which were injected nano-carbon into thyroid during thyroidectomy , and the control group without any injection .Results There were 5 cases with hypocalcemia and 5 cases with PTH decrease in the experimental group , and there were 15 cases and 14 cases respectively in the control group .Pathological results showed that misresection of par-athyroids occurred in 6 cases of the control group(11 parathyroid glands)were while it didn't happen in the experi-mental group .Conclusion Nano-carbon can help to identify and protect the parathyroid , decreasing the proba-bility of parathyroid gland damage during thyroid surgery .

Objective To evaluate the probability of siblings identification in Identifiler system by using the software of automatic analysis.Methods Using the software of automatic analysis in siblings jdentification.STP genetic typing of 151 pairs of full siblings and 31224 pairs of unrelated individuals from manual simulation were analyzed in 15 STR loci of ldentifiler system.Results Kin probability(W_(FS))of 39.07% full siblings were more than 99.999% while W_(FS) of unrelated individual pairs were 0% .W_(FS) of 60.93% full siblings and 21.3% unrelated individual pairs were all at the range from 99.999% to 1% .W_(FS) of 78.7% unrelated individual pairs 0% full siblings individuals were less than 1% .Therefore,there were notability difference between full siblings and unrelated individual pairs.In addition,testing of 15 STR loci of Identifiler system,it suggested that the pair were siblings when the locus number of the entirely-same is not less than 5 or that of the entirely-different is not more than 1,and that the pair were unrelated individuals when the locus number of the entirely-different is not less than 6 or that of the entirely-8alne is not more than 1.Conclusion The software of automatic analysis and the Identifiler system call be used to siblings identification.

Objective:To evaluate the systemic absorption and safety of multiple doses of topical tazarotene/betamethasone dipropionate cream in healthy subjects and patients with psoriasis.Methods:From September 2008 to April 2009, 12 healthy subjects collected from Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College were randomly and equally divided into tazarotene 0.15%/betamethasone dipropionate 0.15% cream group and tazarotene 0.2%/betamethasone dipropionate 0.2% cream group; these subjects were instructed to apply 0.03 g of the test drug per day on each of the 4 body sites, including the flexor aspects of bilateral forearms, waist and back, for 7 consecutive days, and venous blood samples were obtained before, and 1, 3, 5 and 7 days after the start of drug application. From October 2010 to August 2011, 60 patients with non-cephalic psoriasis collected from the Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College were randomly divided into 3 groups at a ratio of 3∶1∶1, i.e., tazarotene 0.05%/betamethasone dipropionate 0.05% cream group ( n = 36) and tazarotene 0.05% gel group ( n = 12) topically treated with a cream vehicle in the morning and the test drug at night, and betamethasone dipropionate 0.05% cream group ( n = 12) topically treated with the test drug twice a day (once in the morning and again in the evening) ; the treatment lasted 6 consecutive weeks, and venous blood samples were collected before, and 2, 4 and 6 weeks after drug application. Liquid chromatography-tandem mass spectrometry was performed to determine the concentrations of tazarotenic acid and betamethasone in plasma. During the trial, adverse events in the subjects were recorded, routine blood and urine examinations were carried out, and liver and kidney function were evaluated before and after treatment. Results:The plasma concentrations of tazarotenic acid and betamethasone in the 12 healthy subjects were below the lower limit of quantitation (0.04 μg/L) after 1-, 3-, 5- and 7-day treatment. After the consecutive treatment, tazarotenic acid and betamethasone were detected in 2 (5.56%) and 4 (11.11%) patients respectively at week 2, 4 or 6 in the tazarotene 0.05%/betamethasone dipropionate 0.05% cream group, and the highest plasma concentrations of tazarotenic acid and betamethasone were 0.112 and 0.201 μg/L respectively; in the betamethasone dipropionate 0.05% cream group, betamethasone was detected in 2 of 12 patients, and the highest plasma concentration of betamethasone was 0.112 μg/L. No test drug-related systemic adverse reactions or laboratory abnormalities were observed in any of the healthy subjects or patients.Conclusion:Multiple doses of topical tazarotene/betamethasone dipropionate cream has advantages of little systemic absorption, no long-term accumulation and good systemic safety.

Objective To evaluate the efficacy and safety of chocolate balloon assisted drug-coated balloon(DCB)angioplasty for the treatment of TASC Ⅱ type C/D femoropopliteal artery lesions.Methods The clinical data of 58 patients with TASC Ⅱ type C/D femoropopliteal artery lesions treated with chocolate balloon +DCB or plain balloon+DCB at Fuwai Central China Cardiovascular Hospital from January 2021 to October 2022 were retro-spectively analyzed.A total of 27 cases were assigned to the observation group(chocolate balloon + DCB)and 31 cases tothe control group(plain balloon + DCB).The rate of dissection and the clinical outcomes between the two groups were compared.Results The technical success rates of the observation and control groups were 88.9%and 80.6%,respectively.The rates of dissection,flow-limiting dissection,and bailout stenting were significantly lower in the observation group than of the control group(all P<0.05).Postoperative clinical symptoms of patients in both groups improved significantly compared with the preoperative period.The 12-month cumulative primary patency rate of the observation group was significantly higher than that of the control group(P<0.05).There was no significant difference in the 12-month cumulative freedom from clinically driven-target lesion revascularization rate between the two groups(P>0.05).Conclusion Chocolate balloonassisted DCB angioplasty was safe and effective for TASC Ⅱ type C/D femoropopliteal artery lesions.It reduced the rates of dissection and bailout stenting,and had better near-term outcomes than plain balloon + DCB.

Objective:To investigate the efficacy of excimer laser atherectomy (ELA) combined with drug-coated balloon (DCB) in the treatment of femoropopliteal arteriosclerosis obliterans (ASO) and its influencing factors.Methods:The clinical data of patients with femoropopliteal ASO treated by ELA combined with DCB from July 2019 to March 2022 were retrospectively analyzed, including technical success rate, ankle-brachial index(ABI), primary patency rate and freedom from target lesion revascularization (TLR) rate. Cox regression was applied to analyze the risk factors affecting the decline in the rate of primary patency and freedom from TLR.Results:All 82 patients were treated with ELA+DCB. The technical success was 91.5%. The post-operative ABI (0.73±0.13) was significantly higher than preoperative ABI (0.39±0.11) ( t=35.26, P<0.001). The 24-month cumulative primary patency and TLR-free rates were 64.1% and 76.8%, respectively. Lesion length>15 cm ( HR=2.57, P=0.047) and severe calcification ( HR=3.26, P=0.021) were associated with loss of primary patency. Having diabetes ( HR=5.24, P=0.010) and a single postoperative outflow tract ( HR=4.18, P=0.008) were associated with a decrease in TLR-free rates. Conclusions:ELA combined with DCB for femoropopliteal ASO is safe and has good intermediate efficacy. Lesion length>15 cm and severe calcification were independent risk factors for primary patency rate, and diabetes and a single postoperative outflow tract were independent risk factors for TLR-free rate.

Abstract: The new generation of artificial intelligence technology, represented by deep learning, has emerged as a crucial driving force in the advancement of new drug research and development. This article creatively proposes a workflow named “Molecular Factory” for the design and optimization of drug molecules based on artificial intelligence technology. This workflow integrates intelligent molecular generation models, high-performance molecular docking algorithms, and accurate protein-ligand binding affinity prediction methods. It has been integrated as a core module into DrugFlow, a one-stop drug design software platform, providing a comprehensive set of mature solutions for the discovery and optimization of lead compounds. Utilizing the “Molecular Factory” module, we conducted the research of second-generation inhibitors against Menin that can combat drug resistance. Through the integration of computational and experimental approaches, we rapidly identified multiple promising compounds. Among them, compound RG-10 exhibited the IC50 values of 9.681 nmol/L, 233.2 nmol/L, and 40.09 nmol/L against the wild-type Menin, M327I mutant, and T349M mutant, respectively. Compared to the positive reference molecule SNDX-5613, which has entered Phase II clinical trials, RG-10 demonstrated significantly enhanced inhibitory activity against the M327I and T349M mutants. These findings fully demonstrate the unique advantages of the "Molecular Factory" technology in practical drug design and development scenarios. It can rapidly and efficiently generate high-quality active molecules targeting specific protein structures, holding significant value and profound implications for advancing new drug discovery.

Objective To evaluate the efficacy and safety of laser-assisted balloon angioplasty(LABA)in treating patients with infrapopliteal arterial occlusion complicated by critical limb ischemia(CLI).Methods The clinical data of patients with infrapopliteal artery occlusion complicated by CLI,who were admitted to the Fuwai Central China Cardiovascular Hospital to receive LABA(LABA group)or balloon angioplasty alone(BA group)between January 2019 and December 2021,were retrospectively analyzed.The incidence of perioperative complications and postoperative clinical efficacy were compared between the two groups.Results A total of 32 patients received LABA therapy and 40 patients received BA alone.The technical success rate,the postoperative ankle-brachial index(ABI),the numerical value of postoperative ABI value deducting preoperative ABI value,the postoperative 24-month continuous improvement rate of clinical symptoms and the primary patency rate of target vessels in the LABA group were remarkably higher than those in the BA group(all P＜0.05).No procedure-related target vessel perforation,amputation,or death occurred in both groups.No statistically significant differences in the target vessel dissection,distal embolism,remedial stenting,and postoperative 24-month amputation-free survival existed between the groups(all P＞0.05).Conclusion For the infrapopliteal arterial occlusion complicated by CLI,LABA therapy is clinically safe and effective,and its mid-term efficacy is superior to BA alone.

Objective:To investigate the risk factors for retrograde type A dissection (RTAD) associated with thoracic endovascular aortic repair (TEVAR) which provided the basis for clinical risk stratification and treatment decision.Methods:The clinical data of 1 688 patients with thoracic aortic disease who underwent TEVAR in our center from January 2004 to December 2019 were retrospectively analyzed. The pathological classification included aortic dissection (1 592 cases) and other thoracic aortic diseases (96 cases). Univariate analysis and categorical multiple logistic regression analysis were used to explore the risk factors for the development of RTAD during or after TEVAR.Results:A total of 18 cases of RTAD were found, with an overall incidence of 1.1% (18/1 688), all of which occurred in aortic dissection group. After adjusting for confounding factors, multivariate logistic regression analysis showed that the incidence of RTAD was significantly decreased(OR=0.27,95%CI 0.07-0.96, P=0.043) when the oversize of stentgraft was 11%-20%, the oversize of stentgraft was ≤10% as the control group, and the difference was statistically significant( P<0.05). The ascending aorta diameter was <40 mm as the control group, and there was no significant difference in the incidence of RTAD between the ≥40 mm group and the control group(OR=2.71,95%CI 0.94-7.84, P=0.065). Conclusions:Aortic dissection is more likely to develop RTAD than other thoracic aortic diseases. A proper stentgraft oversizing ratio could reduce the probability of RTAD. That is to say that a too low stentgraft oversizing ratio is not recommended.