Analysis of Influencing Factors and Strategies for Premature Breast Development in Female Children based on Logistic Regression Analysis: A Randomized Double-blind Controlled Clinical Trial.

Objective: To investigate and analyze the influencing factors of simple early breast development in girls, to discover the dangers and triggers of PT conversion to ICPP, and the time point of transformation in order to detect and prevent the occurrence of transformation in advance and reduce the incidence of idiopathic central precocious puberty. Ensure children's physical and mental health and normal growth and development. Methods: A total of 50 children with PT admitted to our hospital from April 2019 to December 2020 were included in the study group, and 50 children with physical examination during the same period were selected as the control group. All children were tested for vitamin D, androstenedione, dehydroepiandrosterone, 17-hydroxyprogesterone, leptin, IGF-I., and IGFBp-3 at 3, 6, 9 and 12 months after the diagnosis of PT. Results: Vitamin D levels decreased in the child, indicating that vitamin D deficiency was closely related to the age of breast development in ICPP girls and may be related to serum P-FSH, P-LH and E2 levels. Increased levels of IGFBp-3 indicate that these indicators are involved in the onset of ICPP. Children have a higher BMI, watch idol dramas or play mobile games longer, often eat snacks containing preservatives, have a fishy diet, are more irritable and sensitive, and dry stools are also risk factors affecting the early development of simple breasts in girls. Conclusion: The influencing factors leading to simple, early breast development in girls include vitamin D, androstenedione, dehydroepiandrosterone, 17-hydroxyprogesterone, leptin, IGF-I., IGFBp-3, and should be combined with the progression of breast Tanner staging (complete regression, recurrent, and persistent), height growth rate, bone age, Uterine and ovarian B ultrasound, sex hormones, etc., warn of the conversion of PT to ICPP, and ensure children's physical and mental health and normal growth and development.

Exploration of potential active ingredients and mechanism of action of Xihuang pill-medicated serum against glioma based on HPLC-Q-TOF-MS/MS, network pharmacology and experimental verification / 药学学报

Qualitative analysis of the ingredients absorbed into blood and their metabolites of Xihuang pill (XHP) were conducted using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) technology. Network pharmacology was used to explore the potential anticancer mechanisms of the ingredients against glioma, and their specific mechanisms were validated through molecular docking and experimental verification. SD rats were intragastrically administered with XHP, and rat serum samples were collected. Ingredients absorbed into blood and their metabolites were identified based on the retention time of chromatographic peaks, accurate molecular mass, characteristic fragment ions, and comparisons with reference substances and literature data. PharmMapper and SwissTarget Prediction databases were used to obtain the targets of the XHP-medicated serum, while GeneCards, OMIM, PharmGKB, TTD, and DrugBank databases were used to obtain glioma disease targets. The "component-target" network relationship diagram was constructed using Cytoscape 3.9.1 software. The protein-protein interaction (PPI) network diagram was constructed using the STRING database, and the targets were analyzed using GO and KEGG analyses. Molecular docking was used to verify the binding ability of core targets with their corresponding compounds in XHP-medicated serum. The potential mechanism of the anti-glioma effect of 11-keto-β-boswellic acid (KBA), a representative component of XHP-medicated serum, was verified using CCK-8 and Western blot assays. A total of 40 compounds were identified in the XHP-medicated serum, including 28 prototype components and 12 metabolites. The network pharmacology results showed that elemonic acid, 3-acetyl-β-boswellic acid, KBA, α-boswellic acid, and other 5 compounds might be the active ingredients of XHP-medicated serum in the treatment of glioma. Glutathione reductase (GSR), glucose-6-phosphate dehydrogenase (G6PD), ATP-citrate lyase (ACLY), aldo-keto reductase family 1 member B1 (AKR1B1) and glutaredoxin (GLRX) were identified as key targets, involving pathways such as glutathione metabolism and the pentose phosphate pathway. Further cell experiments showed that KBA significantly inhibited the proliferation of T98G cells with an IC50 of 30.96 μmol·L-1, and KBA (30 μmol·L-1) significantly downregulated the protein expression levels of GSR in T98G cells. In summary, XHP-medicated serum may exert its anti-glioma effect by regulating GSR and G6PD-targeted pathways involved in glutathione metabolism. These results provide valuable evidence for further investigating the mechanism of XHP in treating glioma. The animal welfare and experimental procedures were approved by the Ethical Committee of Laboratory Animals at Nanjing University of Chinese Medicine (approval No. ACU221001).

Asperuloside Promotes Apoptosis of Cervical Cancer Cells through Endoplasmic Reticulum Stress-Mitochondrial Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum (ER) stress and mitochondrial pathway.@*METHODS@#Different doses (12.5-800 µg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration (IC50) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78 (GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid (4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside.@*RESULTS@#Asperuloside of 325, 650, and 1300 µg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells (P<0.01). All doses of asperuloside significantly increased intracellular ROS levels, reduced mitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions (P<0.01). In addition, 10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis (P<0.05), and 650 µg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation, decreased apoptosis and cleaved-caspase-3, -4 and GRP78 protein expressions (P<0.05).@*CONCLUSION@#Our study revealed the role of asperuloside in cervical cancer, suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.

Quantification of hetero-cyclic amines from different categories of braised beef by optimized UPLC-TQ-XS/ESI method.

This research work has developed and optimized a sensitive analytical method for separation and quantification of heterocyclic amines (HCAs) mainly including PhIP, Harman, Norharman, IQ, MeIQ, AαC, MeAαC and Trp-P-2 by optimizing UPLC-TQ-XS using electrospray ionization source (ESI+) on ACQUITY UPLC® BEH C18 column in <7 min, from braised beef sample matrix. Meanwhile, modified HCAs extraction by modifying QuEChERS (quick, easy, cheap, efficient, rugged and safe) technique and revisited with solid phase extraction (SPE) for HCAs purification, instead using traditional QuEChERS salts. Moreover, optimized pH conditions of HCA extracts before purification, for better extraction recoveries. Furthermore, this method was validated in terms of method validation parameters. Lastly, simulation of real braised beef model provided the minimum formation of HCAs by optimizing cooking parameters and precursors in a cooking system. Therefore, this method could be applied simultaneously on braised beef matrix either marketed or home cooked for HCAs analysis.

Interpretation for indications of metabolic and bariatric surgery released by ASMBS and IFSO in 2022 / 中华胃肠外科杂志

With the increasing number of obese patients worldwide, metabolic and bariatric surgery (MBS) has quickly become an effective way to treat obesity and related metabolic diseases such as type 2 diabetes, hypertension, lipid abnormalities, etc. Although MBS has become an important part of general surgery, there is still controversy regarding the indications for MBS. In 1991, the National Institutes of Health (NIH) issued a statement on the surgical treatment of severe obesity and other related issues, which continues to be the standard for insurance companies, health care systems, and hospital selection of patients. The standard no longer reflects the best practice data and lacks relevance to today's modern surgeries and patient populations. After 31 years, in October 2022, the American Society for Metabolic and Bariatric Surgery (ASMBS) and the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO), the world's leading authorities on weight loss and metabolic surgery, jointly released new guidelines for MBS indications, based on increasing awareness of obesity and its comorbidities and the accumulation of evidence of obesity metabolic diseases. In a series of recommendations, the eligibility of patients for bariatric surgery has been expanded. Specific key updates include the following: (1) MBS is recommended for individuals with BMI≥35 kg/m2, regardless of the presence, absence, or severity of co-morbidities; (2) MBS should be considered for individuals with metabolic diseases and BMI 30.0-34.9 kg/m2; (3) the BMI threshold should be adjusted for the Asian population:: BMI≥25 kg/m2 suggest clinical obesity, and BMI ≥ 27.5 kg/m2 population should consider MBS; (4) Appropriately selected children and adolescents should be considered for MBS.

Investigation on medical security and quality of life of migrant workers with pneumoconiosis / 中华劳动卫生职业病杂志

Objective: To investigate and understand the medical security and quality of life of migrant workers with pneumoconiosis, so as to provide scientific basis for the prevention and control countermeasures of migrant workers with pneumoconiosis and targeted poverty alleviation. Methods: Using a stratified random sampling method, 200 migrant workers diagnosed with pneumoconiosis at the Shandong Academy of Occupational Health and Occupational Medicine from January 2016 to December 2021 were selected as the observation group, while 200 non migrant workers diagnosed with pneumoconiosis were selected as the control group. St. George's Respiratory Questionnaire (SGRQ) and Pneumoconiosis Questionnaire were used to collect and compare information on the age, working age of dust exposure, economic sources, employment status, income, medical security and quality of life of two groups of patients. Results: The age of migrant worker pneumoconiosis patients in the observation group was (58.1±8.1) years old, and the working age of dust exposure was (19.3±10.1) years. The main source of income was children support (85.5%, 171/200), employment status was mainly wait for employment or unemployed (69.0%, 138/200), personal monthly income was mainly non income (90.0%, 180/200), and family annual income was mainly less than 10000 yuan (48.0%, 96/200). The average personal annual medical expenditure of 5000-<10000 yuan accounted for 42.0% (84/200). The age of pneumoconiosis patients in the control group was (59.2±8.9) years old, and the working age of dust exposure was (20.2±10.5) years. The main source of income was retirement pension or salary (99.0%, 198/200), with retirement as the main employment status (66.0%, 132/200), the main personal monthly income was 2000-<4000 yuan (61.5%, 123/200), the main family annual income was 20000-<40000 yuan (44.0%, 88/200), and the average personal annual medical expenditure was mostly non-expenditure (92.0%, 184/200). There were statistically significant differences in the distribution of economic sources, employment status, personal monthly income, family annual income and average personal annual medical expenditure between the two groups (P<0.001). The main type of insurance for the observation group was rural cooperative medical care (68.5%, 137/200), and 87.0% (174/200) had no medical reimbursement and a proportion less than 50%. There were statistically significant differences in insurance type and medical reimbursement proportion between the two groups (P<0.001). The respiratory symptoms, activity ability, daily life influence and total quality of life scores of pneumoconiosis patients in the observation group were significantly higher than those in the control group, the differences were statistically significant (P<0.001) . Conclusion: Migrant workers with pneumoconiosis have low income, high medical expenditure, low medical reimbursement proportion and poor quality of life. Therefore, it is necessary to draw high attention from relevant departments and provide timely attention and assistance to improve the quality of life of migrant workers with pneumoconiosis.

A case of corrosive digestive tract and lung injury caused by ingestion of pipeline dredging agent / 中华劳动卫生职业病杂志

Ingestion of corrosive substances can severely burn the upper digestive tract leading to bleeding or perforation, and may even be life-threatening. Less commonly, damage to the trachea and bronchi is involved. In this paper, a case of corrosive digestive tract injury and lung injury after oral administration of pipeline dredging agent (the main components are hydroxide, sodium carbonate, sodium hypochlorite, etc.) was analyzed. After active rescue treatment, the patient died of massive hemoptysis. It is suggested that serious complications may occur after ingestion of corrosive substances. Timely diagnosis and reasonable medical management are needed to improve the level of recognition and treatment of such diseases.

Effect of miR-125b on T Cell Activation in Aplastic Anemia by Targetting B7-H4 / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of miR-125b on T cell activation in patients with aplastic anemia (AA) and its molecular mechanism.@*METHODS@#A total of 30 AA patients were enrolled in department of hematology, Binzhou Medical University Hospital from January 2018 to October 2021, as well as 15 healthy individuals as healthy control (HC) group. Peripheral blood mononuclear cells (PBMCs) were isolated, in which the levels of miR-125b and B7-H4 mRNA were detected by RT-qPCR. Immunomagnetic beads were used to separate naive T cells and non-naive T cells from AA patients and healthy people to detect the levels of miR-125b and B7-H4 mRNA. Lentivirus LV-NC inhibitor and LV-miR-125b inhibitor were transfected into cells, and T cell activation was detected by flow cytometry. The dual-luciferase reporter gene assay was used to detect the targetting relationship between miR-125b and B7-H4. RT-qPCR and Western blot were used to detect the levels of miR-125b, CD40L, ICOS, IL-10 mRNA and B7-H4 protein.@*RESULTS@#Compared with HC group, the expression of miR-125b was up-regulated but B7-H4 mRNA was down-regulated in PBMCs of AA patients (P <0.05), and the proportions of CD4+CD69+ T cells and CD8+CD69+ T cells in PBMCs of AA patients were higher (P <0.05). The expression of miR-125b was significantly up-regulated but B7-H4 mRNA was down-regulated in both naive T cells and non-naive T cells of AA patients (P <0.05), and non-naive T cells was more significant than naive T cells (P <0.05). Compared with NC inhibitor group, the expression of miR-125b was significantly decreased, the expression level of CD69 on CD4+ and CD8+ T cells in PBMCs was also significantly decreased, while the luciferase activity was significantly increased after co-transfection of miR-125b inhibitor and B7-H4-3'UTR-WT in the miR-125b inhibitor group (P <0.05). Compared with NC inhibitor group, the mRNA and protein levels of B7-H4 were significantly increased in the miR-125b inhibitor group (P <0.05). Compared with miR-125b inhibitor+shRNA group, the expression levels of CD69 on CD4+ and CD8+ T cells were significantly increased, and the levels of CD40L, ICOS and IL-10 mRNA were also significantly increased in the miR-125b inhibitor+sh-B7-H4 group (P <0.05).@*CONCLUSION@#MiR-125b may promote T cell activation by targetting B7-H4 in AA patients.

Research advances in genetic polymorphisms in Kawasaki disease / 中国当代儿科杂志

Kawasaki disease (KD) is a systemic inflammatory vascular disorder that predominantly affects children and is the leading cause of acquired heart disease in children. Although the etiology of this disease remains unclear, genome-wide association and genome-wide linkage studies have shown that some susceptible genes and chromosomal regions are associated with the development and progression of KD. With the advancement of high-throughput DNA sequencing techniques, more and more genomic information related to KD is being discovered. Understanding the genes involved in the pathogenesis of KD may provide novel insights into the diagnosis and treatment of KD. By analyzing related articles and summarizing related research advances, this article mainly discusses the T cell activation-enhancing genes that have been confirmed to be closely associated with the development and progression of KD and reveals their association with the pathogenesis of KD and coronary artery lesions.

25G pars plana vitrectomy combined with Dexamethasone intravitreal implants for the treatment of vitreous hemorrhage and diabetic macular edema secondary to proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical effect of 25G pars plana vitrectomy(PPV)combined with dexamethasone intravitreal implant(DEX)on the treatment of vitreous hemorrhage and diabetic macular edema(DME)secondary to proliferative diabetic retinopathy(PDR).METHODS: Prospective clinical case study. A total of 40 patients(40 eyes)with vitreous hemorrhage and DME secondary to PDR who treated in Tianjin Eye Hospital from July 2020 to January 2022 were included in the study. All eyes underwent 25G PPV and cataract phacoemulsification. The patients were randomly divided into PPV group(20 eyes)and PPV+DEX group(20 eyes). Best corrected visual acuity(BCVA), intraocular pressure, and central macular thickness(CMT)of the patients before and 1, 3, 6mo after the operation were compared.RESULTS: All patients were followed up for 6mo. The BCVA of the patients in the PPV+DEX group improved better than that of the PPV group at 1, 3 and 6mo after surgery(P&#x003C;0.05). CMT of the PPV+DEX group was lower than that of the PPV group at 1mo after operation(P&#x003C;0.05). Retinal neovascularization or CMT regression with less than 5% was found in 8 eyes in the PPV group, who were supplemented with anti-vascular endothelial growth factor, while it was found in only 1 eye in the PPV+DEX group(P&#x003C;0.05).CONCLUSION: PPV combined with DEX could yield synergies, which provide better therapeutic effect for the patients with vitreous hemorrhage and DME secondary to PDR.

Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures (version 2023) / 中华创伤杂志

Hip fractures are among the most common fractures in the elderly, presenting to be a leading cause of disability and mortality. Surgical treatment is currently the main treatment method for hip fractures. The incidence of perioperative malnutrition is increased after hip fractures in the elderly due to the comorbidities, decreased basal metabolic rate, accelerated protein breakdown, weakened anabolism and surgical stress. However, malnutrition not only increases the incidence of postoperative complications, but also leads to increased mortality, indicating an important role of perioperative nursing management of nutrition for the elderly patients with hip fractures. At present, there still lacks scientific guidance and application standards on perioperative nursing management of nutrition for the elderly patients with hip fractures. Therefore, the Orthopedic Nursing Committee of Chinese Nursing Association and the Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures ( version 2023) according to evidence-based medical evidences and their clinical experiences. Fourteen recommendations were made from aspects of nutrition screening, nutrition assessment, nutrition diagnosis, nutrition intervention and nutrition monitoring to provide guidance for perioperative nursing management of nutrition in elderly patients with hip fractures.

Dissecting the role of subicular circuit in temporal lobe epilepsy / 中国药理学与毒理学杂志

OBJECTIVE Epilepsy is considered a cir-cuit-level dysfunction associated with imbalanced excita-tion-inhibition,it is therapeutically necessary to identify key brain regions and related circuits in epilepsy.The subic-ulum is an essential participant in epileptic seizures,but the circuit mechanism underlying its role remains largely elusive.METHODS Here we deconstruct the diversity of subicular circuits in mouse models of epilepsy.Fiber pho-tometry was used to detect intrinsic activities of subicular PV,SST-positive interneurons and CaMK Ⅱ α-positive pyramidal neurons.Optogenetics and chemogenetics were used to selectively active or inactive subicular neu-rons or their projecting terminals.We also used in vivo and in vitro electrophysiology to record membrane charac-teristics of single neuron in distinct sub-regions of the subiculum.Finally,single pulse test was used to detect synaptic transmission strength between the subiculum and its downstream target.RESULTS First,we found that two majority of subicular interneurons,which inner-vate local pyramidal neurons to constrain their excitability,PV and SST-positive neurons showcase distinct calcium dynamics during hippocampal seizures.This could be attributed to distinct neural inputs from para-hippocampal regions of these two neuronal types.During epileptogen-esis,PV and SST neurons undergo different circuit reor-ganization patterns,that is,remarkable increase of exter-nal input to subicular PV neurons are seen after seizures,while SST cells receive decimated neural input.As their downstream targets,excitatory subicular pyramidal neu-rons are also intrinsically activated during hippocampal seizures.Moreover,we found that the subiculum hetero-geneously controls the generalization of hippocampal sei-zures by projecting to different downstream regions.No-tably,anterior thalamus projecting subicular neurons bidi-rectionally mediate seizures,while entorhinal cortex-pro-jecting subicular neurons act oppositely in seizure modu-lation.These two subpopulations are structurally and functionally dissociable.An intrinsically enhanced hyper-polarization-activated current and robust bursting intensity in anterior thalamus-projecting neurons facilitate synaptic transmission,thus contributing to the generalization of hippocampal seizures.CONCLUSION These results demonstrate that subicular neurons and circuits have diverse roles in epilepsy,suggesting the necessity to pre-cisely target specific subicular circuits for effective treat-ment of epilepsy.

The relationship between neuroticism and professional identity in nursing students during internship: the moderating role of mindfulness / 中国实用护理杂志

Objective:This study aimed to investigate the present status of professional identity in internship nursing students and to find the moderate role of mindfulness in the relationship between neuroticism and professional identity.Methods:This was a cross sectional investigation. From October to December 2021, 819 internship nursing students from four hospitals of Shandong Province were invited to participate in the study and to finish a questionnaire survey including the general information questionnaire, Professional Identity Questionnaire for Nurse Students (PIQNS), the Big Five Inventory(BFI) and Mindful Attention Awareness Scale (MAAS).Results:The average score of PIQNS was (61.41 ± 11.59). Pearson correlation analysis showed that professional identity was negatively associated with neuroticism ( r=-0.405, P<0.01) and positively associated with mindfulness ( r=0.301, P<0.01). Neuroticism was negatively associated with mindfulness ( r=-0.439, P<0.01). The hierarchical regression showed that mindfulness level could moderate the correlation between neuroticism and professional identity. Furthermore, the Johnson-Neyman technique revealed that the moderating role was significant only when the positive level was greater than 47.085. Conclusions:The professional identity of internship nursing students deserves attention. Mindfulness level could moderate the correlation between neuroticism and professional identity. It is suggested that clinical managers to carry out targeted training, to enhance the professional identity of internship nursing students during internship.

Three cases of neonatal pericardial effusion related to umbilical venous catheterization / 中华实用儿科临床杂志

A retrospective case review was conducted of 3 cases with umbilical venous catheterization(UVC) related pericardial effusions in the Neonatal Intensive Care Unit of Zhongnan Hospital of Wuhan University from December 2020 to April 2022.All 3 cases were preterm infants with gestational ages of 33 + 4, 31 and 27 + 6 weeks, respectively.UVC was inserted routinely in 24 hours after birth.Three neonates developed tachycardia or bradycardia, dyspnea, decreased oxygen saturation and muffled heart sound at the 1 st to 4 th day after catheterization.Echocardiography indicated pericardial effusion, so the 3 neonates underwent pericardiocentesis and drainage.Among the 3 neonates, 2 cases improved and have good prognosis, 1 case died.UVC can cause pericardial effusion, which occurs mostly in the early stage after catheterization.Pericardial effusion and tamponade should be considered when patients show unexplained sudden clinical deterioration after catheterization, such as dyspnea, cyanosis, tachycardia or bradycardia, etc.Once diagnosed, umbilical vein catheter should be removed in time and pericardiocentesis and drainage should be performed for decompression.Early diagnosis and intervention can effectively improve the prognosis.

Clinical Impact of Drug Adherence of Tyrosine Kinase Inhibitors in Children with Ph-Positive Acute Lymphoblastic Leukemia / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to explore the impact of ABL1–tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients’ prognosis from TKIs intake practices. @*Materials and Methods@#Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated. @*Results@#Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged ≤ 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia. @*Conclusion@#TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age ≤ 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age ≤ 10 years, which may result in an inferior achievement of relevant treatment milestones.

Rapid determination of microbial contamination of Bupleurum chinense DC. decoction slices by ATP bioluminescence technology combined with statistical analysis methods / 药学学报

This study focuses on the microbial quality control of the Chinese herbal decoction pieces. In view of the shortcomings of traditional culture methods such as slow detection speed and inability to detect unculturable microorganisms, a new method based on ATP bioluminescence technology combined with statistical analysis methods was established to rapidly predict and quantitatively detect the total aerobic microbial count (TAMC) and total yeast and mold count (TYMC) contaminated Bupleurum chinense DC. decoction pieces. Based on the optimized ATP bioluminesence detection system, accurate detection of pure bacterial solution of Escherichia coli, Bacillus subtilis and Staphylococcus aureus can be achieved, with detection limits of 47.86, 89.13 and 1 862.09 CFU·mL-1, respectively. The detection time was 6.5 h, and the detection cost was as low as 2 yuan/time. The upper and lower warning limits of TAMC were determined by the misjudgment rates of 10% and 20%, respectively. And the warning limit of TYMC was determined by the misjudgment rate of 20%. The proposed crossing method could quickly predict the amount of microbial contamination in Bupleurum chinense DC. decoction pieces. The constructed partial least squares regression (PLSR) model could accurately quantify the quantity of microbial contamination in Bupleurum chinense DC. decoction pieces. The optimal PLSR prediction model for TAMC had a correction coefficient (R2) of 0.826, a root mean square error of correction set (RMSEE) of 0.468 and a root mean square error of cross-validation set (RMSECV) of 0.465. The R2, RMSEE and RMSECV in the prediction model of TYMC were 0.778, 0.543 and 0.541, respectively. The aim of this study is to establish a kind of rapid detection method and prediction models for the microbial limit of traditional Chinese medicine and Chinese herbal decoction pieces, and to provide a more convenient and sensitive detection technology for the microbial quality process control of traditional Chinese medicine products.

The Ubiquitin Ligase SMURF1 Catalyzes the Polyubiquitination of ADAR1 / 中国生物化学与分子生物学报

It is known that SMAD specific E3 ubiquitin protein ligase 1 (SMURF1) mediates autophagy through its E3 ubiquitin ligase activity, but the ubiquitinated substrates of SMURF1 need to be further explored. In this paper, the interacting proteins of SMURF1 in THP-1 cells were captured and identified by co-immunoprecipitation (Co-IP) combined with mass spectrometry. It was found that SMURF1 could physically bind to 222 proteins in THP-1 cells, and Adenosine deaminase acting on RNA 1 (ADAR1) had a higher peptide binding score. SMURF1 overexpression vectors were constructed and transfected into HEK-293T cells, then Co-IP and Western blotting assays verified the interaction between exogenous SMURF1 and endogenous ADAR1. qRT-PCR and Western blotting assays were carried out after transfecting SMURF1 overexpression vectors in HEK-293T cells, which identified that overexpression of SMURF1 attenuated the protein levels of ADAR1 (P<0. 05). However, there was no significant difference in the mRNA level of ADAR1. HEK-293T cells with normal and overexpressing SMURF1 were treated with cycloheximide (CHX), respectively, and Western blotting assays showed a shortened half-life of ADAR1 after overexpression of SMURF1 (P < 0. 05). Furthermore, overexpression of SMURF1 increased the polyubiquitination level of ADAR1 as detected by Co-IP and Western blot (P<0. 05). After the proteasome inhibitor (MG132) treatment, the Western blotting assay was performed to demonstrate that the negative regulatory effect of SMURF1 on ADAR1 was weakened after the proteasome degradation pathway was attenuated (P<0. 05). This study shows that SMURF1 interacts with ADAR1, catalyzes the polyubiquitination of ADAR1 and mediates its degradation through the proteasome pathway, which provides a theoretical basis for exploring the various biological functions of SMURF1 by affecting the stability of ADAR1.

Effect of Atglistatin on PA-induced VSMCs proliferation and ATGL expression / 中国临床药理学与治疗学

AIM: With building a proliferation model of PA-induced VSMC, the effect of ATGL, a key fat metabolism enzyme, on the phenotype transformation of VSMC was preliminarily explored. METHODS: 40 μmol/L Atglistatin was added to the proliferation model of VSMC induced by PA (50 μmol/L, 100 μmol/L, and 200 μmol/L, respectively) at separately administered concentrations, and cell viability and cell proliferation were detected by CCK-8 and EDU; cell migration ability was detected by scratch assay; oil red staining was used to detect the accumulation of lipid droplets in VSMC was detected by oil red staining; the effects of PA on ATGL as well as the effects of smooth muscle contraction phenotype proteins were examined by Western blot. RESULTS: PA at a concentration of 100 μmol/L could significantly induce VSMC proliferation, promote lipophagy and increase lipid droplet accumulation in VSMC; meanwhile, Atglistatin could exacerbate these changes caused by PA and increase lipid droplet accumulation in VSMC. CONCLUSION: Atglistatin exacerbates PA-induced VSMC proliferation and increases VSMC lipid droplet accumulation, and exacerbates transformation of proliferative phenotype of VSMC.

Mediation of mitochondrial translocator protein by tanshinone ⅡA in apoptosis of HepG2 cells / 中国药理学通报

Aim To investigate the role of mitochondrial translocator protein(TSPO)in the apoptosis of HepG2 cells induced by tanshinone IIA(Tan II A)and the involved mechanism. Methods Following the HepG2 cells treated with Tan ⅡA at 2.5, 5 and 10 μmol·L-1, the cell viability was determined by MTT assay, and intracellular ATP content was determined by luciferin-luciferase method. Oxygen utilization was measured polarographically with a Clark oxygen electrode. Cell apoptosis was determined by Hoechst 33342 staining and flow cytometry. The mitochondrial membrane potential was assessed with JC-1 staining. The intracellular distribution of TSPO was examined by TSPO immunostaining, and the expressions of TSPO, Cyto C, caspase-3, caspase-9 were determined by immunoblotting analysis. Results Tan II A inhibited the proliferation of HepG2 cells in a dose-and time-dependent manner. The treatment with Tan II A inhibited ATP production and oxygen utilization of mitochondria. In addition, Tan ⅡA enhanced TSPO expression and accumulation in nuclei and up-regulated the expression of Cyto C, caspase-3 and caspase-9. Conclusions Tan II A induces the apoptosis of HepG2 cells, which may be related to the TSPO-mediated mitochondrial dysfunction.

Research progress of reversion multi-drug resistance in tumor by berberine / 中国药理学通报

Tumor is a kind of disease with high morbidity, high mortality and poor prognosis. Chemotherapy is the main treatment of tumor, but the problem of chemotherapy resistance is becoming increasingly prominent, so finding ways to overcome chemotherapy resistance and improve the therapeutic effect has become an urgent problem to be solved. At present, with the development of research, the anti-tumor effect of some traditional Chinese medicine has attracted extensive attention. Berberine, traditionally used in the treatment of digestive system diseases, has been proved to have the effect of anti-tumor and reversing tumor multi-drug resistance. This review summarizes the recent researches on the reversion multi-drug resistance in tumor by berberine, in order to explore the means to improve the therapeutic effect and prognosis of tumor drug resistance.