OBJECTIVE: To investigate the effects of thymoquinone on the proliferation of acute myeloid leukemia (AML) cells and its molecular mechanism, so as to provide theoretical basis for the basic research on the anti-leukemia of traditional Chinese medicine. METHODS: The HL-60 and THP-1 cells were treated with thymoquinone at different concentration gradients, cell proliferation was detected by CCK-8 method, morphological changes were detected by Wright-Giemsa method, apoptosis was detected by Annexin V/PI double staining flow cytometry, and apoptosis and signal pathway protein expression were detected by Western blot. Real-time quantitative fluorescence PCR and Western blot were used to detect the expression changes of high mobility family members of SRY-related proteins (SOX). RESULTS: Thymoquinone inhibited the malignant proliferation of HL-60 and THP-1 cells, up-regulated the expression of pro-apoptotic protein Bax, down-regulated the expression of anti-apoptotic protein Bcl-2 and Survivin, and hydrolyzed Caspase-3 to induce the apoptosis of HL-60 and THP-1 cells. Thymoquinone could also significantly down-regulate the phosphorylation of PI3K, Akt and mTOR, and inhibit the malignant biological characteristics of HL-60 and THP-1 cells by inhibiting the activation of PI3K/Akt/mTOR pathway. After thymoquinone intervention in HL-60 and THP-1 cells, the expression of SOX2 and SOX4 could be down-regulated significantly. At low concentration ( < 10 μmol/L), the expression of SOX12 was weakly affected by thymoquinone. With increasing concentration, the expression of SOX12 could be down-regulated, however, thymoquinone had no effect on SOX11 expression. CONCLUSION Thymoquinone can inhibit the proliferation of AML cells, and its mechanism may be related to inhibiting the activation of PI3K/Akt/mTOR signaling pathway, regulating the expression of apoptotic proteins and core members of SOX family.
Humans ; Benzoquinones/pharmacology* ; Cell Proliferation/drug effects* ; Leukemia, Myeloid, Acute/metabolism* ; Apoptosis/drug effects* ; HL-60 Cells ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Cell Line, Tumor ; Phosphatidylinositol 3-Kinases/metabolism* ; THP-1 Cells

Objective To explore the clinical characteristics and treatment scheme of periprosthetic joint infection(PJI)caused by Cutibacterium avidum(C.avidum).Methods The diagnosis and treatment process of a patient with PJI caused by C.avidum was summarized,and relevant literatures in the database were retrieved for review.Results A 65-year-old female patient with body mass index(BMI)of 31.1 kg/m2 underwent left humeral head prosthesis replacement surgery following a left proximal humerus fracture.Ten months after the surgery,the pa-tient exhibited poor wound healing and oozing,along with limited movement of the left shoulder joint,and was diag-nosed infection following shoulder arthroplasty.Patient underwent debridement of the infected lesion and removal of the prosthesis.The tissue,bone cement and prosthesis were cultured for C.avidum.Four literatures were re-trieved and screened,a total of 30 patients with PJI(28 cases hip joint infection and 2 cases shoulder joint infection)caused by C.avidum were reported through literature retrieval,and 78.6％(n=22)total hip arthroplasty(THA)surgeries were performed using direct anterior approach(DAA).The positive rate of preoperative joint fluid culture was 71.4％,29 cases underwent surgical combined with sensitive antimicrobials treatment.Except for one patient who had repeated infection and underwent three surgeries,other patients had a good prognosis.Conclusion PJI caused by C.avidum is mostly seen in THA patients who are obese and undergo DAA,with a few cases reported after shoulder arthroplasty.The high sensitivity of preoperative joint fluid culture provides an important basis for the development of surgical strategies and anti-infection protocols.

Amorphous solid dispersion (ASD) is one of the most effective formulation approaches to enhance the water solubility and oral bioavailability of poorly water-soluble drugs. However, maintenance of physical stability of amorphous drug is one of the main challenges in the development of ASD. Crystallization is a process of nucleation and crystal growth. The nucleation is the key factor that influences the physical stability of the ASD. However, a theoretical framework to describe the way to inhibit the nucleation of amorphous drug is not yet available. We reviewed the methods and theories of nucleation for amorphous drug. Meanwhile, we also summarized the research progress on the mechanism of additives influence on nucleation and environmental factors on nucleation. This review aims to enhance the better understanding mechanism of nucleation of amorphous drug and controlling over the crystal nucleation during the ASD formulation development.

Aim To study the effect of emetine on in-sulin secretion through glucagon-like peptide-1 receptor(GLP-1R).Methods Isolating rat islets were used to carry out insulin secretion experiment.Islets were incubated with different concentrations of emetine(2,10,50 μmol·L-1),different concentrations of glu-cose solution(2.8,11.1,16.7 mmol·L-1)or spe-cific GLP-1R antagonist Exendin(9-39).The amount of insulin secretion in the supernatant of each group was determined by an enzyme-linked radioimmunoas-say.Small molecule compounds were docked to GLP-1R(PDB code:5NX2)using SYBYL-X2.0 software.Results Emetine could promote insulin secretion in high glucose(11.1 mmol·L-1)in a dose-dependent manner.In low glucose(2.8 mmol·L-1),insulin secretion did not change after intervention of emetine.But in high glucose(11.1,16.7 mmol·L-1),insu-lin secretion significantly increased under the treatment of emetine in a glucose-dependent manner.The doc-king score of emetine and GLP-1R was Total Score=6.82,C Score=5,indicating that emetine had a good binding affinity with GLP-1R.Using Exendin(9-39)to block GLP-1R,the insulinotropic effect of emetine was reduced.Conclusion Emetine could promote in-sulin secretion,which is related to the activation of GLP-1R.

OBJECTIVE: To establish a new digital polymerase chain reaction (dPCR) system for the detection of BCR-ABL fusion gene in patients with chronic myeloid leukemia (CML), and explore its analytical performance and clinical applicability in the detection of BCR-ABL^p190/210/230. METHODS: A new dPCR system for detecting BCR-ABL^p190/210/230 was successfully developed, and its sensitivity difference with qPCR and improvement of drug side effects in patients with CML during drug reduction or withdrawal were compared. RESULTS: Among 176 samples, qPCR and dPCR showed high consistency in the sensitivity of detecting BCR-ABL (82.39%), and the positive rate of dPCR was about 5 times higher that of qPCR (20.45% vs 3.98%). During follow-up, blood routine (25% vs 10%), kidney/liver/stomach (25% vs 20%) and cardiac function (10% vs 0) were significantly improved after drug reduction or withdrawal in patients with initial dPCR negative compared with before drug reduction or withdrawal. CONCLUSIONS This new dPCR detection system can be applied to the detection of BCR-ABL^p190/210/230. It has better consistency and higher positive detection rate than qPCR. Drug withdrawal or dose reduction guided by dPCR has a certain effect on improving drug side effects.
Humans ; Fusion Proteins, bcr-abl/genetics* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis* ; Polymerase Chain Reaction ; Drug-Related Side Effects and Adverse Reactions ; Reverse Transcriptase Polymerase Chain Reaction

Objective:To investigate the influence of rosuvastatin combined ticagrelor on therapeutic effect,cardiac func-tion and inflammatory factor levels in patients with acute myocardial infarction(AMI).Methods:A total of 288 AMI pa-tients admitted in our hospital were randomly and equally divided into rosuvastatin group(received rosuvastatin therapy)and combined treatment group(received rosuvastatin combined with ticagrelor).After two-month treatment,therapeu-ticeffect,cardiac function,inflammatory index levels and incidence rate of adverse reaction were compared between two groups.Results:Total effective rate of combined treatment group was significantly higher than that of rosuvastatin group(96.53%v.s 86.81%,P=0.003).Compared with before treatment,there were significant improvements in cardiac function and inflammatory factor levels in two groups after treatment,P=0.001 al.l Compared with rosuvastatin group af-ter treatment,there were significant reductions in left ventricular end-diastolic diameter(LVEDd)[(44.86±5.25)mmv.s(30.94±4.02)mm],left ventricular end-systolic diameter(LVESd)[(28.83±3.02)mmv.s(21.27±2.86)mm],interventricular septal thickness(IVST)[(9.82±1.51)mmv.s(9.09±1.46)mm],levels of interleukin-6(IL-6)[(4.62±0.68)pg/mlv.s(3.85±0.59)pg/ml]and tumor necrosis factor-α(TNF-α)[(1.25±0.22)pg/mlv.s(0.93±0.18)pg/ml],and significant rise in 6 min walking distance(6MWD)[(398.63±50.58)m v.s(436.35±52.03)m]and LVEF[(54.11±6.32)%v.s(60.24±7.88)%]in combined treatment group,P=0.001 al.l There was no signif-icant difference in total incidence rate of adverse reactions during treatment between two groups,P=0.444.Conclusion:The combination of rosuvastatin and ticagrelor possesses significant therapeutic effect in the treatment of AMI patient.s It can improve cardiac function and reduce levels of inflammatory factors with good safety.

Objective To study the effect of dexmedetomidine (DEX), an α2- adrenoceptor agonist, on the pain-related anxiety-like and depression-like behaviour induced by complete Freund' s adjuvant (CFA) injection and its possible regulatory mechanism. Methods Thirty-six ICR female mice were randomly divided into normal saline (NS) group, CFA group and DEX + CFA group, n = 12 for each group. Chronic inflammatory pain model was established by subcutaneous injection of 10 μl CFA into the right hind limb of mice. DEX + CFA group mice were injected intraperitoneally with 0.025 mg/kg DEX 30 minutes before nociceptive behavior test, and once a day for 7 days. Von-frey fiber was used to evaluate the threshold of mechanical pain in mice, n = 12 for each group. The anxiety-like behavior of mice were detected by open field test, n = 12 for each group. Sucrose preference, tail suspension test and forced swimming test were used to detected the depression-like behavior of mice, n = 12 for each group. The expression of adrenergic receptor β2 (ADRB2), Brain-derived neurotrophic factor (BDNF), tyrosine kinase B receptor (TrkB), and glutamate receptors 1 (GluR1) and GluR2 were detected by Western blotting, n = 8 for each group. Immunohistochemical staining was used to detect the expression of recombinant doublecortin(DCX), which is a marker of newborn neurons in the hippocampus, n = 4 for each group. Results Compared with the NS group, the mechanical threshold of mice on the 1st, 3rd and 7th day after CFA injection decreased significantly (P < 0.05); But there was no significant difference between DEX + CFA group and CFA group (P>0.05). Compared with the NS group, the time spent in the inner ares (P<0.01), number of entering the central grid area (P<0.01) and distance travelled in the inner area (P<0.01) of CFA group mice reduced significantly, while the time (P<0.01), numbers (P < 0.05) and distance (P < 0.05) of DEX + CFA group mice entering the central grid area enhanced significantly. The result of depression-like behavior tests showed that the sucrose preference percentage (P < 0.05) reduced significantly in CFA group when compared with NS group, and the immobility time increased significantly in tail suspension test (P<0.01) and forced swimming test (P< 0.001) in CFA mice when compared with NS group, while DEX intervention could significantly increase the sucrose preference scores (P<0.05) and decreased the immobility time in tail suspension test (P<0.05) and forced swimming test (P<0.05). The result of Western blotting showed that compared with the NS group, the levels of ADRB2 (P<0.0010), BDNF (P < 0.001), TrkB (P < 0.01), GluR1 (P < 0.001) and GluR2 (P < 0.001) in the hippocampus of CFA group were significantly decreased, while DEX intervention could significantly increase the expression of ADRB2 (P<0.05), BDNF (P < 0.001), TrkB (P < 0.001), GluR1 (P < 0.001) and GluR2 (P < 0.001). Immunohistochemical result showed that compared with the NS group, the average absorbance (AA) of DCX decreased significantly in hippocampus of CFA group (P<0.05), but increased significantly in DEX+CFA group (P < 0.05). Conclusion Dexmedetomidine may promote hippocampal neurogenesis through upregulated the expression of BDNF-TrkB, thus improving CFA-induced anxiety-like and depression-like behaviors in mice.

Objective: To analyze the morbidity and mortality trends of thyroid cancer in China from 1990 to 2019, explore the causes of the trends, and predict morbidity and mortality in the future. Methods: The morbidity and mortality data of thyroid cancer in China from 1990 to 2019 were collected from the 2019 Global Burden of Disease database. The Joinpoint regression model was used to describe the change trends. Based on the morbidity and mortality data from 2012 to 2019, a grey model GM (1,1) was constructed to predict the trends in the next ten years. The model was tested by the posterior error method and residual test method. Results: In all populations, men and women, the AAPC values of the crude morbidity rates were 4.15% (95%CI: 3.86%-4.44%, P<0.001), 5.98% (95%CI: 5.65%-6.31%, P<0.001) and 3.23% (95%CI: 2.94%-3.53%, P<0.001) respectively, the AAPC values of age-standardized morbidity rates were 2.47% (95%CI: 2.12%-2.83%, P<0.001), 3.98% (95%CI: 3.68%-4.29%, P<0.001), 1.65% (95%CI: 1.38%-1.93%, P<0.001), the AAPC values of crude mortality rates were 2.09% (95%CI: 1.92%-2.25%, P<0.001), 3.68% (95%CI: 3.45%-3.90%, P<0.001), 0.60% (95%CI: 0.50%-0.71%, P<0.001). The age-standardized mortality rates in men showed a fluctuating trend of first decrease (1990-1994), then increase (1994-2012), and then decrease (2012-2019) (AAPC=1.35%, 95%CI: 1.16%-1.53%, P<0.001). The age-standardized mortality rate in women continuously decreased (AAPC=-1.70%, 95%CI: -1.82%- -1.58%, P<0.001). The GM (1,1) models can be used for medium and long-term predictions. The results of the residual test show that the average relative error values of all models are less than 10.00%, the prediction accuracy values are more than 80.00%, and the prediction effects are good. The results of the posterior error method show that all the prediction results are good except the qualified prediction of the age-standardized morbidity rate in men. In 2029, the crude morbidity rates would increase to 3.57/100 000, 2.78/100 000, and 4.40/100 000, respectively, and the age-standardized incidence rates would increase to 2.38/100 000, 1.89/100 000, and 2.88/100 000, respectively, the crude mortality rates would increase to 0.57/100 000, 0.62/100 000 and 0.53/100 000, and the age-standardized mortality rates would decrease to 0.33/100 000, 0.42/100 000 and 0.27/100 000 in all population, men and women in China. Conclusions: The overall, gender- specific age-standardized mortality rates showed downward trends in the last decade or so, and the prediction results showed that it might further decline. However, the crude morbidity rates, age-standardized and crude mortality rates have been on the rise, and the population aging is becoming increasingly serious in China, which requires close attention and targeted prevention and control measures.
Male ; Humans ; Female ; Morbidity ; Thyroid Neoplasms/epidemiology* ; Aging ; China/epidemiology*

At present, there are disadvantages with the detection for occupational hazard factors, such as insufficient monitoring data, poor timeliness, weak representativeness, long detection cycles, and inability to continuously monitor. Taking advantages of internet of things technology, an online monitoring platform for occupational hazard factors has been designed. The platform collects the concentration (intensity) of hazard factors through sensors, transmits the occupational hazards data collected online in realtime. The online monitoring cloud center for occupational hazard factors processes and analyzes online monitoring data in realtime, stores the hazard factors data to form database management, and provides user application services to form an intelligent online monitoring service model for occupational hazard factors. Based on the online monitoring platform of occupational hazard factors, multi-level government health supervision departments and employers can grasp the status of hazard factors in real time, which is conducive to improving the level of occupational hazard supervision.
Internet of Things ; Internet

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens