Value of sonoelastography for diagnosis of breast non-mass lesions and comparison with BI-RADS: A systematic review and meta-analysis.

BACKGROUND: Not all the breast lesions were mass-like, some were non-mass-like at ultrasonography. In these lesions, conventional ultrasonography had a high sensitivity but a low specificity. Sonoelastography can evaluate tissue stiffness to differentiate malignant masses from benign ones. Then what about the non-mass lesions? The aim of this study was to evaluate the current accuracy of sonoelastography in the breast non-mass lesions and compare the results with those of the American College of Radiology breast Imaging-Reporting and Data System (BI-RADS). METHODS: An independent literature search of English medical databases, including PubMed, Web of Science, Embase & MEDLINE (Embase.com) and Cochrane Library, was performed by 2 researchers. The accuracy of sonoelastography was calculated and compared with those of BI-RADS. RESULTS: Fourteen relevant studies including 1058 breast non-mass lesions were included. Sonoelastography showed a pooled sensitivity of 0.74 (95% CI: 0.70-0.78), specificity of 0.89 (95% CI: 0.85-0.91), diagnostic odds ratio (DOR) of 25.22 (95% CI: 17.71-35.92), and an area under the curve of 0.9042. Eight articles included both sonoelastography and BI-RADS. The pooled sensitivity, specificity, DOR and AUC were 0.69 versus 0.91 (P < .01), 0.90 versus 0.68 (P < .01), 19.65 versus 29.34 (P > .05), and 0.8685 versus 0.9327 (P > .05), respectively. CONCLUSIONS: Sonoelastography has a higher specificity and a lower sensitivity for differential diagnosis between malignant and benign breast non-mass lesions compared with BI-RADS, although there were no differences in AUC between them.

Comparison of artificial intelligence, elastic imaging, and the thyroid imaging reporting and data system in the differential diagnosis of suspicious nodules.

Background: Ultrasound is widely used for detecting thyroid nodules in clinical practice. This retrospective study aimed to assess the diagnostic efficacy of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS), S-Detect, and elastography of the carotid artery for suspicious thyroid nodules and to determine the complementary value of artificial intelligence and elastography. Methods: Between January 2021 and November 2021, 101 consecutive patients with 138 thyroid nodules were enrolled in The First Hospital of China Medical University. All nodules were evaluated using ACR-TIRADS categories (TR), S-Detect, and elastography, and then the diagnostic performance of the different methods and the combined assessment were compared. The inclusion criteria were the following: (I) TR3, TR4, and TR5 nodules, which were defined as "suspicious nodules"; (II) patients who had surgical or cytopathological results after ultrasound examination; and (III) voluntary enrollment in this study. Meanwhile, the exclusion criteria were the following: (I) TR1 and TR2 nodules, (II) patients who had undergone fine-needle aspiration before ultrasound examination, and (III) inconclusive cytologic findings. Results: A total of 71 patients (12 men and 59 women) with 94 suspicious thyroid nodules (42 benign nodules and 52 malignant nodules) were finally included in this study. S-Detect had a significantly better sensitivity than did ACR-TIRADS [S-Detect: 98.1%, 95% confidence interval (CI): 89.7-100.0%; ACR-TIRADS: 84.6%, 95% CI: 71.9-93.1%; P=0.036], but its specificity was much lower (S-Detect: 19.0%; 95% CI: 8.6-34.1%; ACR-TIRADS: 40.5%, 95% CI: 25.6-56.7%; P=0.032). The accuracy was not significantly different between S-Detect (62.8%; 95% CI: 52.2-72.5%) and ACR-TIRADS (64.9%; 95% CI: 54.4-74.5%) (P=0.761). The elasticity contrast index (ECI) was not definitively useful in identifying suspicious thyroid nodules (P=0.592). Compared with the use of ACR-TIRADS and S-Detect alone, the specificity (45.2%; 95% CI: 29.8-61.3%), positive predictive value (65.2%; 95% CI: 52.4-76.5%), accuracy (66.0%; 95% CI: 55.5-75.4%), and the area under the receiver operating characteristic curve (0.640; 95% CI: 0.534-0.736) of their combination were higher but not significantly so. Conclusions: At present, S-Detect cannot replace manual diagnosis, and the value of elastography of the carotid artery in diagnosing suspected thyroid nodules remains unclear.

Electroacupuncture Zusanli (ST36) Relieves Somatic Pain in Colitis Rats by Inhibiting Dorsal Root Ganglion Sympathetic-Sensory Coupling and Neurogenic Inflammation.

Referred somatic pain triggered by hyperalgesia is common in patients with inflammatory bowel disease (IBD). It was reported that sprouting of sympathetic nerve fibers into the dorsal root ganglion (DGR) and neurogenic inflammation were related to neuropathic pain, the excitability of neurons, and afferents. The purpose of the study was to explore the potential and mechanism of electroacupuncture (EA) at Zusanli (ST36) for the intervention of colon inflammation and hyperalgesia. Sprague-Dawley (SD) was randomly divided into four groups, including control, model, EA, and sham-EA. Our results showed EA treatment significantly attenuated dextran sulfate sodium- (DSS-) induced colorectal lesions and inflammatory cytokine secretion, such as TNF-α, IL-1ß, PGE2, and IL-6. EA also inhibited mechanical and thermal pain hypersensitivities of colitis rats. Importantly, EA effectively abrogated the promotion effect of DSS on ipsilateral lumbar 6 (L6) DRG sympathetic-sensory coupling, manifested as the sprouting of tyrosine hydroxylase- (TH-) positive sympathetic fibers into sensory neurons and colocalization of and calcitonin gene-related peptide (CGRP). Furthermore, EA at Zusanli (ST36) activated neurogenic inflammation, characterized by decreased expression of substance P (SP), hyaluronic acid (HA), bradykinin (BK), and prostacyclin (PGI2) in colitis rat skin tissues corresponding to the L6 DRG. Mechanically, EA treatment reduced the activation of the TRPV1/CGRP, ERK, and TLR4 signaling pathways in L6 DRG of colitis rats. Taken together, we presumed that EA treatment improved colon inflammation and hyperalgesia, potentially by suppressing the sprouting of sympathetic nerve fibers into the L6 DGR and neurogenic inflammation via deactivating the TRPV1/CGRP, ERK, and TLR4 signaling pathways.

NETO2 promotes melanoma progression via activation of the Ca2+/CaMKII signaling pathway / 医学前沿

Melanoma is the most aggressive cutaneous tumor. Neuropilin and tolloid-like 2 (NETO2) is closely related to tumorigenesis. However, the functional significance of NETO2 in melanoma progression remains unclear. Herein, we found that NETO2 expression was augmented in melanoma clinical tissues and associated with poor prognosis in melanoma patients. Disrupting NETO2 expression markedly inhibited melanoma proliferation, malignant growth, migration, and invasion by downregulating the levels of calcium ions (Ca2+) and the expression of key genes involved in the calcium signaling pathway. By contrast, NETO2 overexpression had the opposite effects. Importantly, pharmacological inhibition of CaMKII/CREB activity with the CaMKII inhibitor KN93 suppressed NETO2-induced proliferation and melanoma metastasis. Overall, this study uncovered the crucial role of NETO2-mediated regulation in melanoma progression, indicating that targeting NETO2 may effectively improve melanoma treatment.

Efficacy of omalizumab in the treatment of chronic urticaria patients with poor response to antihistamines: a single-center retrospective study / 中华皮肤科杂志

Objective:To investigate the efficacy and safety of omalizumab in the treatment of chronic urticaria (CU) patients with poor response to H1 antihistamines.Methods:CU patients, who showed poor response to H1 antihistamines and received omalizumab treatment, were collected from the Department of Dermatology, Xiangya Hospital, Central South University from June 2020 to June 2021. The efficacy of omalizumab was evaluated by using the 7-day urticaria activity score (UAS7) and urticaria control test (UCT) score at weeks 4, 12 and 24 after the start of treatment. The t-test, chi-square test, and Pearson correlation analysis were used to analyze the relationship between the clinical characteristics and efficacy. Results:A total of 121 CU patients who met the inclusion criteria and had relatively complete medical records were included in this study, including 54 males (44.63%) and 67 females (55.37%) , and their ages ranged from 13 to 70 years (39.88 ± 14.36 years) ; 88 patients were diagnosed with chronic spontaneous urticaria (72.73%) , 10 with chronic inducible urticaria (8.26%) , and 23 with chronic spontaneous urticaria accompanied by chronic inducible urticaria (19.01%) . At week 4 after the start of omalizumab treatment, the response rate was 50.86% (59/116) , and the complete response rate was 25.86% (30/116) ; at week 12, the response rate was 78.26% (54/69) , and the complete response rate was 34.78% (24/69) ; at week 24, the response rate was 64.71% (22/34) , and the complete response rate was 23.53% (8/34) . At week 4, CU patients with baseline serum total IgE levels of < 40 IU/ml had a lower response rate (26 cases, 30.77%) than those with baseline serum total IgE levels of ≥ 40 IU/ml (61 cases, 65.57%; χ2 = 8.93, P = 0.004) . Correlation analysis showed that the age at treatment, age at onset, allergic diseases, concomitant symptoms, baseline erythrocyte sedimentation rates, and baseline C-reactive protein levels were significantly correlated with the UCT scores (all P < 0.05) , while the course of disease, clinical types, serum total IgE levels, peripheral blood counts, dermatology life quality index scores, and UAS7 scores were not significantly correlated with the UCT scores. Among the 121 CU patients, 8 (6.61%) reported mild to moderate adverse reactions. Conclusion:Omalizumab could effectively improve clinical symptoms and signs of CU patients with poor response to H1 antihistamines, and was well tolerated;omalizumab treatment may be more beneficial to patients without allergic comorbidities such as allergic rhinitis, without concomitant symptoms such as angioedema, and with lower erythrocyte sedimentation rates and C-reactive protein levels.

circ_0092315 Promotes Proliferation and Invasion of Papillary Thyroid Carcinoma Cells via Regulating microRNA-1256/High Mobility Group A2 axis / 中国医学科学院学报

Objective To investigate the role and mechanism of circ_0092315 in the proliferation and invasion of papillary thyroid carcinoma cells. Methods The expression of circ_0092315 in papillary thyroid carcinoma cells was examined by real-time fluorescence quantitative PCR.The proliferation and invasion of TPC-1 cells was assessed by CCK-8 and Transwell assays.The protein level of high mobility group A2 (HMGA2) was determined by Western blotting.The regulatory relationship of circ_0092315,microRNA-1256 (miR-1256),and HMGA2 was explored by bioinformatics tools,dual-luciferase reporter assay,real-time fluorescence quantitative PCR,and Western blotting. ++++Results circ_0092315 was overexpressed in papillary thyroid carcinoma cells (all P<0.001).circ_0092315 promoted the proliferation and invasion of TPC-1 cells (all P<0.001).The transfection of si-circ_0092315 up-regulated the expression of miR-1256 (P<0.001),and miR-1256 inhibitor up-regulated the protein level of HMGA2 (P<0.001). ++++Conclusion circ_0092315 is overexpressed in TPC-1 cells and it promotes the proliferation and invasion of TPC-1 cells by regulating the miR-1256/HMGA2 axis.

UGT1A1 gene mutations in Chinese Dong neonates in Sanjiang, Guangxi / 中国当代儿科杂志

OBJECTIVES@#To study the characteristics of UGT1A1 gene mutations in Dong neonates in Sanjiang County of Liuzhou and its association with the pathogenesis of hyperbilirubinemia in Dong neonates.@*METHODS@#A prospective analysis was performed on 84 neonates who were diagnosed with unexplained hyperbilirubinemia in the Department of Neonatology, Sanjiang County People's Hospital, from January 2021 to January 2022. Sixty healthy neonates born during the same period were enrolled as the control group. Peripheral blood genomic DNA was extracted for both groups, and UGT1A1 exon 1 was amplified by PCR and sequenced.@*RESULTS@#In the case group, 33 neonates were found to have G71R missense mutation, with a mutation rate of 39%. The case group had a significantly higher frequency of A allele than the healthy control group (21% vs 10%, P<0.05). The risk of hyperbilirubinemia in Dong neonates carrying G71R missense mutation was 2.588 times as high as that in healthy neonates carrying wild-type UGT1A1 gene (P<0.05). Hardy-Weinberg equilibrium testing showed that the UGT1A1 G71R locus was in genetic equilibrium in both groups (P>0.05).@*CONCLUSIONS@#UGT1A1 G71R mutation is a high-frequency gene mutation type in Dong neonates in Sanjiang County, and G71R missense mutation is associated with hyperbilirubinemia in Dong neonates.

Evaluation of Enzyme Inhibitory Activity of Flavonoids by Polydopamine-Modified Hollow Fiber-Immobilized Xanthine Oxidase.

In this study, a polydopamine (PDA)-modified hollow fiber-immobilized xanthine oxidase (XOD) was prepared for screening potential XOD inhibitors from flavonoids. Several parameters for the preparation of PDA-modified hollow fiber-immobilized XOD, including the dopamine concentration, modification time, XOD concentration and immobilization time, were optimized. The results show that the optimal conditions for immobilized XOD activity were a dopamine concentration of 2.0 mg/mL in 10.0 mM Tris-HCl buffer (pH 8.5), a modification time of 3.0 h, an XOD concentration of 1000 µg/mL in 10.0 mM phosphate buffer (pH 7.5) and an immobilization time of 3.0 h. Subsequently, the enzymatic reaction conditions such as the pH value and temperature were investigated, and the enzyme kinetics and inhibition parameters were determined. The results indicate that the optimal pH value (7.5) and temperature (37 °C) of the PDA-modified hollow fiber-immobilized XOD were consistent with the free enzyme. Moreover, the PDA-modified hollow fiber-immobilized XOD could still maintain above 50% of its initial immobilized enzyme activity after seven consecutive cycles. The Michaelis-Menten constant (Km) and the half-maximal inhibitory concentration (IC50) of allopurinol on the immobilized XOD were determined as 0.25 mM and 23.2 µM, respectively. Furthermore, the PDA-modified hollow fiber-immobilized XOD was successfully applied to evaluate the inhibitory activity of eight flavonoids. Quercetin, apigenin, puerarin and epigallocatechin showed a good inhibition effect, and their percentages of inhibition were (79.86 ± 3.50)%, (80.98 ± 0.64)%, (61.15 ± 6.26)% and (54.92 ± 0.41)%, respectively. Finally, molecular docking analysis further verified that these four active compounds could bind to the amino acid residues in the XOD active site. In summary, the PDA-modified hollow fiber-immobilized XOD is an efficient method for the primary screening of XOD inhibitors from natural products.

Preparation of a zirconium terephthalate metal-organic framework coated magnetic nanoparticle for the extraction of berberine prior to high-performance liquid chromatography analysis.

In this study, a zirconium terephthalate metal-organic framework-coated magnetic nanoparticle (UiO-66@PA@PEI@Fe3 O4 ) was synthesized for the extraction of berberine prior to high-performance liquid chromatography analysis. The phytic acid, which could be grafted onto the magnetic nanoparticle through electrostatic interaction with the abundant amino groups of polyethylenimine, possesses outstanding metal ion coordination ability for the immobilization of metal-organic frameworks UiO-66. The physicochemical properties of the obtained nanoparticle were thoroughly investigated by a series of characterization techniques. Then, the factors that will affect the extraction efficiency and recovery of berberine were investigated. Results indicated that the material had good stability and reusability, and high adsorption capacity (50.01 mg/g) to berberine through single-layer adsorption. In addition, a molecular docking study indicated that the interactions between the material and berberine were mainly π-π stacking and hydrophobic interaction. Finally, the material was successfully applied to the extraction of berberine in Rhizoma Coptidis and Cortex Phellodendri extracts with the recoveries of 76.1% and 71.6%, respectively.

Adsorbed hollow fiber immobilized tyrosinase for the screening of enzyme inhibitors from Pueraria lobata extract.

In this study, a method based on adsorbed hollow fiber immobilized tyrosinase (TYR) was developed to screening potential TYR inhibitors from Pueraria lobate extract. Kojic acid and ranitidine were used as positive and negative control to verify the reliability of the proposed method, respectively. Several significant parameters of the screening process, including the amount of P. lobata extract, adsorption time and incubation time, were optimized. After investigating the repeatability of the developed method, seven potential active compounds in P. lobata extract were successfully detected and their chemical structures were tentatively identified by liquid chromatography - mass spectrometry analysis. Furthermore, the inhibitory activity of four identified compounds on TYR was tested in vitro, and three of them, namely, puerarin, puerarin-6″-O-xyloside and puerarin apioside were verified to have good TYR inhibitory activity with IC50 value of 478.5, 513.8, and 877.3 µM, respectively. In addition, the molecular docking results indicated that these compounds could bind to the amino acid residues in TYR catalytic pocket. These results proved that the proposed method is a feasible approach for screening of TYR inhibitors from plant extract.

Selective Ferroptosis Inhibitor Liproxstatin-1 Attenuates Neurological Deficits and Neuroinflammation After Subarachnoid Hemorrhage / 神经科学通报·英文版

Ferroptosis is a form of iron-dependent regulated cell death. Evidence of its existence and the effects of its inhibitors on subarachnoid hemorrhage (SAH) is still lacking. In the present study, we found that liproxstatin-1 protected HT22 cells against hemin-induced injury by protecting mitochondrial functions and ameliorating lipid peroxidation. In in vivo experiments, we demonstrated the presence of characteristic shrunken mitochondria in ipsilateral cortical neurons after SAH. Moreover, liproxstatin-1 attenuated the neurological deficits and brain edema, reduced neuronal cell death, and restored the redox equilibrium after SAH. The inhibition of ferroptosis by liproxstatin-1 was associated with the preservation of glutathione peroxidase 4 and the downregulation of acyl-CoA synthetase long-chain family member 4 as well as cyclooxygenase 2. In addition, liproxstatin-1 decreased the activation of microglia and the release of IL-6, IL-1β, and TNF-α. These data enhance our understanding of cell death after SAH and shed light on future preclinical studies.

Effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia: a multicenter study in Hubei Province, China / 中国当代儿科杂志

OBJECTIVES@#To study the effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia.@*METHODS@#A retrospective analysis was performed on the medical data of the neonates with asphyxia who were admitted to 52 hospitals in Hubei Province of China from January to December, 2018 and had blood glucose data within 12 hours after birth. Their blood glucose data at 1, 2, 6, and 12 hours after birth (with an allowable time error of 0.5 hour) were recorded. According to the presence or absence of brain injury and/or death during hospitalization, the neonates were divided into a poor prognosis group with 693 neonates and a good prognosis group with 779 neonates. The two groups were compared in the incidence of glucose metabolism disorders within 12 hours after birth and short-term prognosis.@*RESULTS@#Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of neonates from secondary hospitals (48.5% vs 42.6%, @*CONCLUSIONS@#Recurrent hyperglycemia in neonates with asphyxia may suggest poor short-term prognosis, and it is necessary to strengthen the early monitoring and management of the nervous system in such neonates.

Epidemic Characteristics of the Novel Coronavirus Delta Variant in Guangzhou and Grid Crowd Management Based on Public Security Forensic Perspective / 法医学杂志

Abstract： Objective To analyze the first epidemic spread of the novel coronavirus Delta variant in China based on public security forensic perspective, investigate its transmission characteristics, contributing factors, and epidemiologic research experience, and provide a reference for the prevention and control of the epidemic caused by the novel coronavirus variant. Methods Based on the information that public security forensic experts obtained from front-line epidemiologic research, the gender, age, place of residence, transmission route and infectivity of the coronavirus disease 2019 （COVID-19） confirmed cases, asymptomatic infected persons and their close contacts in Guangzhou caused by the novel coronavirus Delta variant were analyzed. The basic reproduction number （R0） during this epidemic in Guangzhou was calculated. Results Among the 153 cases infected with novel coronavirus Delta variant in the epidemic, 63 cases were male and 90 cases were female, their age ranging from 1 to 92 years, with a median age of 49 years. The main route of transmission was close contact, including dining together, co-living, and close contact in the same residential building. There were 31 cases of family clusters, 25 of which were in Liwan District. The epidemic lasted from May 26 to May 29, and the R0 remained above 4.0. After May 30, R0 began to decline and remained below 1.0 from June 7. Conclusion The novel coronavirus Delta variant is highly infectious, the crowd is generally susceptible to infection and family cluster cases are easy to occur. So, it is necessary to precisely prevent and control this strain. Public security forensic experts have both medical literacy and criminal investigation capabilities, they can play a more professional role in epidemic prevention and control.

HIF / 中南大学学报(医学版)

OBJECTIVES@#To analyze the expressions and distributions of hypoxia-inducible factor-1α (HIF-1α), CD147, and glucose transporter 1 (GLUT1) in epidermis from psoriasis vulgaris and normal people, and to explore the associations among these proteins and their roles in hypoxic HaCaT cell line.@*METHODS@#The expression levels of HIF-1α, CD147, and GLUT1 were determined by immunohistochemistry staining in skin biopsies from 48 psoriasis vularis patients and 33 healthy subjects. Cobalt chloride (CoCl@*RESULTS@#HIF-1α, CD147, and GLUT1 were highly expressed and the glycolytic capacity was increased in lesions of psoriasis vulgaris; HIF-1α upregulated the expression of CD147 and GLUT1, increased the lactate production and decreased the ATP level in CoCl@*CONCLUSIONS@#Glycolytic capacity increases in the injured keratinocytes of psoriasis vulgaris, suggesting that HIF-1α, CD147, and GLUT1 are associated with glycolysis, which can be considered as the promising targets for psoriasis therapy.

FOXC1 Knockdown Reverses Gefitinib Resistance in Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#Lung cancer is the malignant tumor with the highest incidence and mortality in China, among which non-small cell lung cancer (NSCLC) accounts for about 80%. Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeted therapy has been playing an important role in treatment of NSCLC. However, unavoidable therapeutic resistance significantly limits the clinical efficacy of EGFR-TKI. As a key member of the forkhead box protein family, FOXC1 is aberrantly expressed in NSCLC and involved in NSCLC progression. The aim of this work is to investigate the effect and potential mechanism of FOXC1 on gefitinib resistance in NSCLC.@*METHODS@#Western blot was performed to assess the expression of FOXC1 protein in HCC827/GR cells. Immunohistochemistry (IHC) assays were performed in human NSCLC tissues with gefitinib resistance. HCC827/GR cells were transfected with shRNA specifically targeting FOXC1 mRNA and stable cell lines were established. The effects of FOXC1 on cell viability and apoptosis were analyzed using a new methyl thiazolyl tetrazolium assay (MTS assay) and flow cytometry. Self-renewal ability was determined by mammosphere-formation analysis. Quantitative real-time PCR (qRT-PCR) and Western blot were employed to detect the expression of SOX2, Nanog, OCT4 and CD133. Flow cytometry analysis were further used to detect the level of CD133. IHC assays were used to detect the levels of SOX2 and CD133 in NSCLC tissues with genfitiinb resistance. Correlations of the expressions of FOXC1, CD133 and SOX2 with each other in lung adenocarcinoma samples were analyzed based on The Cancer Genome Atlas (TCGA) database.@*RESULTS@#The expression of FOXC1 is significantly increased in HCC827/GR cells compared with HCC827 cells (P<0.05). IHC results showed FOXC1 was highly expressed in NSCLC tissues with gefitinib resisitance. Knockdown of FOXC1 significantly increased the sensitivity of HCC827/GR cells to gefitinib. The cell viability was decreased and the apoptosis was promoted (P<0.05). Moreover, FOXC1 knockdown apparently inhibited the expression of SOX2 and CD133, and decreased the mammosphere-formation capacity in HCC827/GR cells. In NSCLC tissues with gefitinib resistance, the expressions of SOX2 and CD133 were significantly higher compared with gefitinib-sensitive tissues (P<0.01). Meanwhile, the expressions of FOXC1, CD133 and SOX2 with each other were positively correlated (P<0.05).@*CONCLUSIONS@#FOXC1 could increase gefitinib resitance in NSCLC, by which mechanism is related to the regulation of cancer stem cell properties.

Antithrombotic effect and action mechanism of Salvia miltiorrhiza and Panax notoginseng herbal pair on the zebrafish.

BACKGROUND: Salvia miltiorrhiza (Danshen, DS) and Panax notoginseng (Sanqi, SQ) are famous traditional Chinese herbs, and their herbal pair (DS-SQ) has been popular used as anti-thrombotic medicines. However, there is still a lack of sufficient scientific evidence to illustrate the optimum combination ratio of these two herbs as well as its action mechanisms. The purpose of this study is to investigate the anti-thrombotic effects of DS-SQ on zebrafish and explore its possible action mechanism. METHODS: Firstly, the chemical components in DS-SQ extract were analyzed by LC-ESI-MS/MS. Then, a phenylhydrazine (PHZ)-induced zebrafish thrombosis model was developed for evaluating the anti-thrombotic effects of DS-SQ extracts with different combination ratios and their nine pure compounds. Followed, Real-time quantitative PCR (RT-qPCR) assays were performed to investigate the potential antithrombotic mechanisms of DS-SQ. RESULTS: Thirty-three components were tentatively identified by LC-MS analysis. DS-SQ at the ratio of 10:1 presented the best anti-thrombotic effect, and rosmarinic acid, lithospermic acid and salvianolic acid B of DS showed good anti-thrombotic activity on zebrafish thrombosis model. The RT-qPCR assays indicated that DS-SQ (10:1) could cure the PHZ-induced thrombosis by downregulating the expression of PKCα, PKCß, fga, fgb, fgg and vWF in zebrafish. CONCLUSIONS: DS-SQ with the combination ratio of 10:1 showed optimum anti-thrombotic effect on PHZ-induced zebrafish thrombosis model, which provided a reference for reasonable clinical applications of DS-SQ herbal pair.

Controlling Nutritional Status (CONUT) Score as a New Indicator of Prognosis in Patients With Hilar Cholangiocarcinoma Is Superior to NLR and PNI: A Single-Center Retrospective Study.

BACKGROUND: Currently, many nutritional indicators, including controlling nutritional status score (CONUT), can be used to assess a patient's nutritional status and have been reported as reliable predictors of multiple malignancies. However, the value of CONUT score in predicting postoperative outcomes in patients with hilar cholangiocarcinoma has not been explored. In this study, its predictive value will be discussed and compared with the known predictors the neutrophil lymphocyte ratio (NLR) and prognostic nutritional index (PNI). METHODS: Preoperative CONUT scores, PNI and NLR levels of 94 Hilar cholangiocarcinoma (HCCA) patients who underwent radical-intent resection of hepatobiliary surgery in our hospital from March 2010 to April 2019 were retrospectively collected and analyzed. They were grouped according to their optimal cutoff value and the prognostic effects of patients in each group were compared respectively. RESULTS: CONUThigh was more frequent in patients with Clavien-Dindo classification of ≥IIIa (P = 0.008) and Bile leakage presence (P = 0.011). Kaplan-Meier curves analyzing the relationship between CONUT, PNI, and NLR values and HCCA patient survival (including total survival (OS) and recurrence-free survival (RFS) showed significant differences between groups (P <0.001). Meanwhile, multi-factor analysis found that Degree of cure, PNI, NLR, and preoperative CONUT score were independent prognostic factors for OS and RFS. The predictive power of CONUT score was higher than that of NLR and PNI based on time-dependent receiver operating Characteristic (ROC) analysis and the net reclassification index (NRI) and integrated discriminatory index (IDI) values (P < 0.05). CONCLUSION: CONUT score may be of some clinical reference value in evaluating postoperative prognosis of HCCA patients.

Follow-up of NSCLC patients with first-generation EGFR-TKI resistance using third-generation EGFR-TKI / 中国医师杂志

Objective:To analyze the clinical efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced NSCLC.Methods:We collected 23 cases of NSCLC advanced patients, who were treated in the affiliated Cancer Hospital of Guangzhou Medical University from January 2015 to March 2020. And these 23 cases of patients with first-generation EGFR-TKIs resistance were treated with the third-generation EGFR-TKI drugs. We analyzed their clinicopathological characteristics, studied their therapeutic effects, and followed up their progression-free survival (PFS).Results:It is showed that 16 of 23 cases (69.56%) were got local progression and 7 of 23 cases (31.43%) were found with systemic progression. Briefly, the median PFS of the 23 patients was 17.5 months. A total of 7 cases occurred rashes after taking EGFR-TKI, and 3 cases got abnormal liver function. Fortunately, they were all improved after symptomatic treatments. Additionally, no bone marrow suppression (granulocytes, neutropenia, thrombocytopenia, anemia) and digestive tract reactions (nausea, vomiting, diarrhea) were occurred in 23 cases of NSCLC patients. The mental and physical improvement of EGFR-TKI in the third generation of 19 patients was more obvious than that in the first generation of EGFR-TKI. Among them, 15 cases showed more obvious lesion shrinkage after third-generation EGFR-TKI treatment. 4 patients with GGO had cleaner disappearance than that of the first-generation EGFR-TKI.Conclusions:Compared with traditional chemotherapy, the first-generation EGFR-TKI resistance treatment with three-generation EGFR-TKI treatment has better efficacy with reduced toxic and side effects, and significantly improved the life quality of advanced NSCLC patients.

Clinical significance of multidisciplinary team collaboration for the treatment of hip fractures in the elderly / 中华老年医学杂志

Objective To investigate the clinical value of multidisciplinary team collaboration (MDT)for the treatment of hip fractures in elderly patients.Methods A total of 157 elderly patients with hip fractures meeting inclusion and exclusion criteria were admitted into our department from 1st September 2015 to 31st December 2017.The patients were randomly divided into the traditional treatment group and the MDT group.The differences in treatment time,cost,postoperative outcomes and postoperative Harris hip function score were compared between the two groups.Results The preoperative length of stay,total hospitalization time and the time of antibiotic use after operation were shorter in the MDT treatment group than in the traditional treatment group (all P ＜0.05).Total costs of treatment and costs for bed,laboratory examinations,and nursing were lower in the MDT treatment group than in the traditional treatment group(all P＜0.05).The off-bed activity time after operation was earlier in the MDT treatment group with femoral neck fractures [(5.36 ± 1.56)d vs.(10.07±2.26)d,P =0.002]than in the traditional treatment group with intertrochanteric fracture patients [(30.26 ± 3.01) d vs.(42.28 ± 3.52) d,P =0.017].Harris hip function score was higher in the MDT treatment group than in the traditional treatment group at 3 and 6 months after surgery (P ＜ 0.05).Conclusions As compared with the traditional treatment mode,MDT treatment mode can shorten the preoperative stay in bed,the length of hospital stay after surgery and the off-bed activity time after operation,reduce hospitalization costs and postoperative complications,and can promote the recovery of hip joint function in elderly hip fracture patients.

Expression of Smo in pancreatic cancer CD44+CD24+cells and construction of a lentiviral expression vector to silence Smo.

The present study focused on the roles of members of the Hedgehog (Hh) signaling pathway in the maintenance of malignant biological characteristics, such as tumorigenesis, similar to that of pancreatic tumor cells. Cluster of differentiation (CD)44+CD24+/CD44-CD24- cells were isolated from three different pancreatic cancer cell lines by flow cytometry. Among the three pancreatic cancer cell lines, the SW1990 cell line exhibited the highest percentage of CD44+CD24+ cells, which accounted for 39.9% of the total. The expression of members of the Hh signaling pathway in CD44+CD24+/CD44-CD24- cells was detected using reverse transcription-polymerase chain reaction and western blot analysis. The results demonstrated that members of the Hh signaling pathway were differentially expressed in CD44+CD24+ cells compared with CD44-CD24-, normal pancreatic duct cells and unsorted SW1990 cells. In addition, lentiviral expression vectors expressing Smoothened (Smo) small interfering RNA (siRNA) were constructed. Following transfection with the lentiviral expression vectors, Smo expression was markedly reduced in CD44+CD24+ cells. The present study represents a preliminary investigation into the biological characteristics of CD44+CD24+ pancreatic cancer cells.