ß-Elemene enhances erlotinib sensitivity through induction of ferroptosis by upregulating lncRNA H19 in EGFR-mutant non-small cell lung cancer.

Nearly half of all Asian non-small cell lung cancer (NSCLC) patients harbour epidermal growth factor receptor (EGFR) mutations, and first-generation EGFR tyrosine kinase inhibitors (TKIs) are one of the first-line treatments that have improved the outcomes of these patients. Unfortunately, 20% of these patients can not benefit from the treatment. The basis of this primary resistance is poorly understood. Therefore, overcoming EGFR-TKI primary resistance and maintaining the efficacy of TKIs has become a key issue. ß-Elemene, a sesquiterpene compound extracted from Curcuma aromatica Salisb. (wenyujing), has shown potent antitumor effects. In this research, we found that ß-elemene combined with erlotinib enhanced the cytotoxicity of erlotinib to primary EGFR-TKI-resistant NSCLC cells with EGFR mutations and that ferroptosis was involved in the antitumor effect of the combination treatment. We found that lncRNA H19 was significantly downregulated in primary EGFR-TKI-resistant NSCLC cell lines and was upregulated by the combination treatment. Overexpression or knockdown of H19 conferred sensitivity or resistance to erlotinib, respectively, in both in vitro and in vivo studies. The high level of H19 enhanced the cytotoxicity of erlotinib by inducing ferroptosis. In conclusion, our data showed that ß-elemene combined with erlotinib could enhance sensitivity to EGFR-TKIs through induction of ferroptosis via H19 in primary EGFR-TKI-resistant lung cancer, providing a promising strategy to overcome EGFR-TKI resistance in NSCLC patients.

Objective Assessment of Visual Field Defects Caused by Optic Chiasm and Its Posterior Visual Pathway Injury.

OBJECTIVES: To investigate the characteristics and objective assessment method of visual field defects caused by optic chiasm and its posterior visual pathway injury. METHODS: Typical cases of visual field defects caused by injuries to the optic chiasm, optic tracts, optic radiations, and visual cortex were selected. Visual field examinations, visual evoked potential (VEP) and multifocal visual evolved potential (mfVEP) measurements, craniocerebral CT/MRI, and retinal optical coherence tomography (OCT) were performed, respectively, and the aforementioned visual electrophysiological and neuroimaging indicators were analyzed comprehensively. RESULTS: The electrophysiological manifestations of visual field defects caused by optic chiasm injuries were bitemporal hemianopsia mfVEP abnormalities. The visual field defects caused by optic tract, optic radiation, and visual cortex injuries were all manifested homonymous hemianopsia mfVEP abnormalities contralateral to the lesion. Mild relative afferent pupil disorder (RAPD) and characteristic optic nerve atrophy were observed in hemianopsia patients with optic tract injuries, but not in patients with optic radiation or visual cortex injuries. Neuroimaging could provide morphological evidence of damages to the optic chiasm and its posterior visual pathway. CONCLUSIONS: Visual field defects caused by optic chiasm, optic tract, optic radiation, and visual cortex injuries have their respective characteristics. The combined application of mfVEP and static visual field measurements, in combination with neuroimaging, can maximize the assessment of the location and degree of visual pathway damage, providing an effective scheme for the identification of such injuries.

Spectrum of ß-Thalassemia Mutations in Some Areas of Guangxi Zhuang Autonomous Region of Southern China: A Study on a Pediatric Population Aged 0-15 Years.

ß-Thalassemia (ß-thal), one of the most common form of single-gene inheritable blood diseases in the world, is highly prevalent in southern China, especially in the Guangxi Zhuang Autonomous Region. To update the ß-thal mutation spectrum in this region, we performed hematological and genetic analyses on 888 ß-thal major (ß-TM), ß-thal intermedia (ß-TI) and ß-thal carrier patients, aged 0-15 years old, from different parts of Guangxi Province. We identified 55 genotypes and 18 ß-thal mutations. The codons 41/42 (-TTCT) (HBB: c.126_129delCTTT) (43.97%), codon 17 (A>T) (HBB: c.52A>T) (25.43%), -28(A>G) (HBB: c.-78A>G) (8.18%), IVS-II-654 (C>T) (HBB: c.316-197C>T) (7.85%) and codon 26 (G>A) (HBB: c.79G>A) (5.02%) were the five most common, accounting for more than 90.0%. The results of our study are providing an up-to-date ß-thal mutation spectrum in the 0-15-year-old pediatric population, which will help genetic counseling and prevention of ß-TM in mainland China's most endemic region, Guangxi Zhuang Autonomous Region.

Fatigue in chronic hepatitis B patients is significant and associates with autonomic dysfunction.

BACKGROUND: Fatigue is an important clinical finding in patients with chronic hepatitis virus infection. However, studies assessing fatigue in patients with chronic hepatitis B (CHB) are very limited. This study aimed to quantify the severity of fatigue in patients with CHB, to determine whether perceived fatigue reflects impairment of functional ability, and to explore potential causes. METHODS: A total of 133 patients with histologically proven CHB and 59 community controls were assessed using the fatigue impact scale (FIS). RESULTS: The degree of fatigue was significantly higher in patients with CHB than in controls (mean (range) FIS 24.9 (0-91) vs. 15.7 (0-31), p < 0.001). Fatigue experienced by patients with CHB was similar to that in primary biliary cirrhosis (PBC) (n = 20) (FIS 22.2 vs. 20.9, p = 0.28). No association was found between FIS and biochemistry and histological parameters of liver disease severity. Significant associations were found between fatigue severity and cognitive impairment (r = 0.39, p < 0.001), daytime somnolence (r = 0.32, p < 0.001), scores of the Chronic Liver Disease Questionnaire (r = - 0.31, p < 0.001), and autonomic symptoms (r = 0.43, p < 0.001). The level of autonomic symptom was the only factor independently associated with the degree of fatigue. CONCLUSION: Fatigue is a significant problem of functional ability impairment in CHB and similar in degree to that in PBC patients. Fatigue in patients with CHB appears to be unrelated to the severity of liver disease but is associated with significant autonomic symptoms.

Two new steroidal saponins from the roots of Cynanchum limprichtii.

As a part of our continuing research for bioactive constituents from Cynanchum limprichtii Schltr., two new C21 steroidal glycosides limproside A (1) and limproside B (2) were isolated from the roots of Cynanchum limprichtii. Their structures were elucidated on the basis of 1D- and 2D-NMR spectroscopic data as well as HR-ESI-MS analysis. The cytotoxicity of two compounds against two selected human cancer cell lines was assayed.

An Inexpensive Digital Image Analysis Technique for Liver Fibrosis Quantification in Chronic Hepatitis B Patients.

BACKGROUND AND AIM: Quantitative digital imaging analysis to evaluate liver fibrosis is accurate, but its clinical use is limited by its high cost and lack of standardization. We aimed to validate an inexpensive digital imaging analysis technique for fibrosis quantification in chronic hepatitis B patients. MATERIAL AND METHODS: In total, 142 chronic hepatitis B patients who underwent liver biopsy and analysis of serum fibrosis markers were included. Images of Sirius red stain sections were captured and processed using Adobe Photoshop CS3 software. The percentage of fibrosis (fibrosis index) was determined by the ratio of the fibrosis area to the total sample area, expressed in pixels, and calculated automatically. RESULTS: A strong correlation between the fibrosis index and the Ishak, Metavir, and Laennec histological staging systems were observed (r = 0.83, 0.86, and 0.84, respectively; < 0.001). The cutoff value associated with cirrhosis was 7.7% with an area under the receiver operating characteristic curve (AUROC) of 0.95 (95% confidence interval [CI], 0.92-0.99, p < 0.001). Furthermore, the fibrosis index yielded a cutoff value of 8.9% (AUROC, 0.74; 95% CI, 0.66-0.86), 12% (AUROC, 0.84; 95% CI, 0.75-0.93), and 14% (AUROC, 0.97; 95% CI, 0.92-1.0) for the diagnosis of cirrhosis 4a, 4b, and 4c, respectively. No serum markers or fibrosis models were correlated with the fibrosis index in Metavir F2-F4. CONCLUSIONS: The present digital imaging analysis technique is reproducible and available worldwide, allowing its use in clinical practice, and can be considered as a complementary tool to traditional histological methods.

[Research of genes expression related to ginsenosides biosynthesis by methyl jasmonic acid in ginseng hair roots].

In order to obtain the expression of ginsenoside biosynthetic pathway related enzyme gene in ginseng hairy root under the control of elicitors, methyl jasmonate (MeJA) was added exogenously as elicitors. Ginseng hairy root clones induced by 4-year-old ginseng root was used as material, total saponin content in ginseng hairy root before and after MeJA treatment was determined by vanillin-sulfuric acid colorimetry, Meanwhile, relative expression of squalene synthase genes, squalene epoxidase genes, oxidized squalene cyclase genes, dammarenediol synthase genes, ß-amyrin synthase genes, cycloartenol synthase genes before and after MeJA treatment were determined by Real-time PCR. The optimum conditions of MeJA which added to ginseng hairy root were obtained, the optimum additional concentration was 6×10⁻4 µmol•L⁻¹, the optimum additional time was 22 d, and the optimum action time was 5 d. The addition of MeJA could improve the enzymatic activity of peroxidase (PPD), catalase (CAT) and peroxidase (PPD) in ginseng hairy root. The expression of SQS，SQE，OSC，DS and ß-AS genes of ginsenoside biosynthetic pathway increased significantly after MeJA treatment, while the change of CAS gene expression were not significant. The expression of key enzyme SQS，SQE，OSC，DS and ß-AS genes in ginsenoside biosynthetic pathway was consistent with the changes of PPD，CAT，PPO enzymatic activity.

RhoB/ROCK mediates oxygen-glucose deprivation-stimulated syncytiotrophoblast microparticle shedding in preeclampsia.

Increased circulating syncytiotrophoblast microparticles (STBMs) are often associated with preeclampsia (PE) but the molecular mechanisms regulating STBM shedding remain elusive. Experimental evidence has shown that actin plays a key role in STBM shedding and that Rho/ROCK is important in regulating actin rearrangement. To investigate the role of RhoB/ROCK-regulated actin arrangement in STBM shedding in PE, chorionic villous explants were prepared from placenta of patients with normotensive or PE pregnancies and BeWo cells were fused to imitate syncytiotrophoblasts. The oxygen-glucose deprivation (OGD) conditions were applied to imitate the pathophysiology of PE in vitro. The results showed that RhoB and ROCK were activated in the preeclamptic placenta, accompanied by increased actin polymerization and decreased outgrowing microvilli. In villous tissue cultures or BeWo cells, OGD activated RhoB, ROCK1 and ROCK2 and promoted STBM shedding and actin stress fibers formation. In BeWo cells, RhoB overexpression activated ROCK1 and ROCK2, leading to F-actin redistribution and STBM shedding and the OGD-induced actin polymerization and STBM shedding could be reversed by RhoB or ROCK knockdown. These results reveal that RhoB and ROCK play a key role in PE by targeting STBM shedding through actin rearrangement and that RhoB/ROCK intervention may be a potential therapeutic strategy for PE.

Dust mite allergen Der f 4: Expression, characterization, and IgE binding in pediatric asthma.

BACKGROUND: House dust mite hypersensitivity affects millions of people worldwide, and although many allergens produced by house dust mite species have been identified, some of the less potent allergens remain to be studied. METHODS: The full-length cDNA encoding the group 4 allergen of the house dust mite species Dermatophagoides farinae (Der f 4) was generated through degenerate primer-based PCR, 5' RACE, and 3' RACE, and the cDNA fragment was cloned into an expression vector for nucleotide sequencing. Following codon optimization and removal of the signal peptide sequence, the mature gene fragment was subcloned into pET-28b (+) and transfected into E. coli BL21 cells for expression. The recombinant protein was purified by nickel affinity chromatography, identified by SDS-PAGE, Western blotting, and MALDI-TOF, and tested by ELISA for IgE reactivity with sera from individuals with asthma. Bioinformatics analyses were used to identify features of Der f 4. RESULTS: SDS-PAGE and Western blotting of the codon-optimized expression product showed a specific band. The mature recombinant Der f 4 was characterized as a stable and hydrophilic 57.9-kDa protein, and its secondary structure comprised alpha helix (25.3%), extended strand (22.51%), and random coils (52.19%). The structure of the recombinant protein was consistent with that of α-amylase. Among 27 pediatric asthma patients, 40.74% exhibited reactivity to rDer f 4 by ELISA. CONCLUSIONS: This initial cloning and characterization of the Der f 4 allergen serves as a foundation for future studies into the clinical importance and application of this protein for house dust mite allergy.

Two new lignans from the aerial part of Vitex negundo.

A new phenyldihydronaphthalene-type lignan, (3R,4S)-6-hydroxy-4-(4-hydroxy- 3-methoxyphenyl)-5,7-dimethoxy-3,4-dihydro-2-naphthaldehyde-3a-O-ß-d-glucopyranoside (1), and a new phenylnaphthalene-type lignan, 6,7,4'-trihydroxy-3'-methoxy-2,3- cycloligna-1,4-dien-2a,3a-olide (2), along with 10-known lignan derivatives (3-12) were isolated from the aerial part of Vitex negundo var. heterophylla. Their structures were established by comprehensive 1D- and 2D-NMR spectroscopic analyses.

[Progress in the molecular genetic mechanism of gonadoblastoma].

Gonadoblastoma (GB), a rare in situ germ cell tumor derived from sex cord and germ cells, is closely associated with gonadal dysgenesis. About 80% of GB individuals exhibit 46, XY female phenotype while the others are 45, XY and 46, XX with disorders of sex development. Moreover, 35% of GB can eventually develop into malignant tumors, such as seminoma and dysgerminoma tumors. The molecular genetic mechanism of GB remains to be fully uncovered due to phenotypic and genetic heterogeneity. Increasing studies show that the formation of GB is closely related to genes regulating sexual differentiation and determination (e.g., SRY, WT1, SOX9, Foxl2, TSPY, etc), and is affected by the interaction of genetic and epigenetic regulation. Here we describe the clinical and pathological features, diagnosis and treatment of GB, and also summarize the molecular genetic and epigenetic mechanisms underlying the gonadal abnormalities that lead to GB. We analyze and construct the common gene regulatory networks related to the development of GB, and describe some obstacles and deficiencies in current studies to provide innovative perspectives on further studying the pathological and molecular mechanisms of GB.

[Effect of Shengjiang Xiexin Decoction on the Repair of Damaged Rat Intestinal Mucosa after Irinotecan Chemotherapy].

OBJECTIVE: To explore the effect of Shengjiang Xiexin Decoction (SXD) on the intestinal mucosal and functional cells of rats after irinotecan (CPT-11) chemotherapy. METHODS: Totally 24 healthy Sprague-Dawley (SD) male rats were divided into three groups, the normal control group, the CPT-11 group, the SXD combined CPT-11 group according to random digit table, 8 in each group. CPT-11 was injected at the daily dose of 150 mg/kg to rats in the CPT-11 group and the SXD combined CPT-11 group from the caudal vein on the 4th day, once daily for 2 successive days to duplicate delayed diarrhea model. Equal volume of normal saline was injected to rats in the normal control group from the caudal vein. SXD at 2 g/mL (10 g/kg body weight) was administered to rats in the SXD combined CPT-11 group by gastrogavage for 9 successive days. Deionized water was administered to rats in the CPT-11 group and the normal control group. Diarrhea was observed at 48, 60, 72, 84, 96, and 108 h to calculate the incidence rate of diarrhea. Meanwhile, scoring for diarrhea was performed by referring methods of Akinobu Kurita. Rats were killed on day 10, ileum, cecum, and colon tissues were collected and fixed in 10% formalin solution. HE staining was performed. Intestinal mucosa injuries were graded under light microscope according to the criterion of Chiu's score. The expressions of goblet cells and Paneth cells were observed by PAS stain. Enteroendocrine cells were observed by immunohistochemical CgA staining. Positive cells were counted and cumulative optical density (IOD) analyzed by Image-Pro-Plus 6.0. RESULTS: No diarrhea occurred in rats of the normal control group at each time point. The incidence rate of diarrhea was 75.0% (6/8) at 48 h, 100.0% (8/8) at 60 h, 100.0% (8/8) at 72 h, 87.5% (7/8) at 84 h, 75.0% (6/8) at 96 h, and 75.0% (6/8) at 108 h in the CPT-11 group. The incidence rate of diarrhea was 25.0% (2/8) at 48 h, 50.0% (4/8) at 60 h, 12.5% (1/8) at 72 h, 0.0% (0/8) at 84 h in the SXD combined CPT-11 group. Compared with the same group at 60 h, scores for diarrhea at 48, 84, 96, and 108 h obviously decreased in the CPT-11 group, and scores for diarrhea at 48, 72, 84, 96, and 108 h obviously decreased in the SXD combined CPT-11 group (P < 0.05, P < 0.01). Compared with the same group at 72 h, scores for diarrhea at 84, 96, and 108 h obviously decreased in the CPT-11 group (P < 0.05, P < 0.01). Compared with the normal control group, scores for diarrhea increased in the CPT-11 group at each time point (P < 0.01); grading of ileum, cecum, and colon mucosal tissues increased (P < 0.05, P < 0.01); expressions of ileum and cecum mucosal epithelial goblet cells obviously decreased (P < 0.05); the number and expressions of ileum and cecum mucosal epithelial Paneth cells increased (P < 0.01). Expressions of ilium endocrine cells increased, while those of cecum and colon endocrine cells decreased in the CPT-11 group (P < 0.01). Compared with the CPT-11 group, scores for diarrhea were obviously lowered (P < 0.05, P < 0.01), grading of ileum, and cecum mucosal tissues decreased (P < 0.05, P < 0.01); expressions of ileum, cecum, and colon mucosal epithelial goblet cells obviously increased (P < 0.05, P < 0.01); the number and expressions of ileum cecum mucosal epithelial Paneth cells increased (P < 0.05); expressions of cecum and colon endocrine cells increased (P < 0.05, P < 0.01) in the SXD combined CPT-11 group. CONCLUSION: SXD played roles in preventing and treating CPT-11 induced delayed diarrhea by improving CPT-11 chemotherapy induced apoptosis and necrosis of intestinal mucosal and functional cells.

[Application of Ocular Trauma Score in Mechanical Ocular Injury in Forensic Medicine].

OBJECTIVE: To evaluate the application value for the prognosis of mechanical ocular injury cases using ocular trauma score (OTS). METHODS: Four hundred and eleven cases of mechanical ocular trauma were retrospectively reviewed. Of the 449 eyes, there were 317 closed globe injury and 132 open globe injury. OTS variables included numerical values as initial visual acuity, rupture, endophthalmitis, perforat- ing or penetrating injury, retinal detachment and relative afferent pupillary block. The differences be- tween the distribution of the final visual acuity and the probability of standard final visual acuity were compared to analyze the correlation between OTS category and final visual acuity. The different types of ocular trauma were compared. RESULTS: Compared with the distribution of final visual acuity in standard OTS score, the ratio in OTS-3 category was statistically different in present study, and no differences were found in other categories. Final visual acuity showed a great linear correlation with OTS category (r = 0.71) and total score (r = 0.73). Compared with closed globe injury, open globe injury was generally associated with lower total score and poorer prognosis. Rupture injury had poorer prognosis compared with penetrating injury. CONCLUSION: The use of OTS for the patients with ocular trauma can provide re- liable information for the evaluation of prognosis in forensic medicine.

The function of P2X3 receptor and NK1 receptor antagonists on cyclophosphamide-induced cystitis in rats.

PURPOSE: The purpose of the study is to explore the function of P2X3 and NK1 receptors antagonists on cyclophosphamide (CYP)-induced cystitis in rats. METHODS: Sixty female Sprague-Dawley (SD) rats were randomly divided into three groups. The rats in the control group were intraperitoneally (i.p.) injected with 0.9% saline (4 ml/kg); the rats in the model group were i.p. injected with CYP (150 mg/kg); and the rats in the intervention group were i.p. injected with CYP with subsequently perfusion of bladder with P2X3 and NK1 receptors' antagonists, Suramin and GR 82334. Spontaneous pain behaviors following the administration of CYP were observed. Urodynamic parameters, bladder pressure-volume curve, maximum voiding pressure (MVP), and maximum cystometric capacity (MCC), were recorded. Pathological changes in bladder tissue were observed. Immunofluorescence was used to detect the expression of P2X3 and NK1 receptors in bladder. RESULTS: Cyclophosphamide treatment increased the spontaneous pain behaviors scores. The incidence of bladder instability during urine storage period of model group was significantly higher than intervention group (χ(2) = 7.619, P = 0.007) and control group (χ(2) = 13.755, P = 0.000). MCC in the model group was lower than the control and intervention groups (P < 0.01). Histological changes evident in model and intervention groups rats' bladder included edema, vasodilation, and infiltration of inflammatory cells. In model group, the expression of P2X3 receptor increased in urothelium and suburothelium, and NK1 receptor increased in suburothelium, while the expression of them in intervention group was lower. CONCLUSIONS: In CYP-induced cystitis, the expression of P2X3 and NK1 receptors increased in urothelium and/or suburothelium. Perfusion of bladder with P2X3 and NK1 receptors antagonists ameliorated the bladder function.

Detection of congenital uterine malformation by using transvaginal three-dimensional ultrasound.

This study assessed the clinical application of transvaginal three-dimensional ultrasound (3D TVUS) in the diagnosis of congenital uterine malformation. A retrospective study was performed on 62 patients with congenital uterine malformation confirmed hysteroscopically and/or laparoscopically. The patients were subjected to transvaginal two-dimensional ultrasound (2D TVUS) and 3D TVUS. The accuracy rate was compared between the two methods. The accuracy rate of 3D TVUS was (98.38%, 61/62), higher than that of 2D TVUS (80.65%, 50/62). 3D TVUS coronal plane imaging could demonstrate the internal shape of the endometrial cavity and the external contour of the uterine fundus. It allowed accurate measurement on the coronary plane, and could three-dimensionally show the image of cervical tube, thereby providing information for the diagnosis of some complex uterine malformation. 3D TVUS imaging can obtain comprehensive information of the uterus malformation, and it is superior to 2D TVUS for the diagnosis of congenital uterine malformations, especially complex uterine anomaly.

Effect of cholic acid on fetal cardiac myocytes in intrahepatic choliestasis of pregnancy.

This study examined the effect of cholic acid (CA) on cultured cardiac myocytes (CMs) from neonatal rats with an attempt to explore the possible mechanism of sudden fetal death in intrahepatic cholestasis of pregnancy (ICP). Inverted microscopy was performed to detect the impact of CA on the beating rates of rat CMs. MTT method was used to study the effect of CA on the viability of CMs. CMs cultured in vitro were incubated with 10 µmol/L Ca(2+)-sensitive fluorescence indicator fluo-3/AM. The fluorescence signals of free calcium induced by CA were measured under a laser scanning confocal microscope. The results showed that CA decreased the beating rates of the CMs in a dose-dependent manner. CA could suppress the activities of CMs in a time- and dose-dependent manner. CA increased the concentration of intracellular free calcium in a dose-dependent manner. Our study suggested that CA could inhibit the activity of CMs by causing calcium overload, thereby leading to the sudden fetal death in ICP.

[Correlation between visual acuity and fixation characteristics].

OBJECTIVE: To explore the feasibility of fixation characteristics to evaluate visual acuity. METHODS: The fixation characteristics were examined in 75 subjects by MP-1 microperimeter. These subjects were divided into 3 groups: central fixation group, uncertain group and eccentric fixation group, and the differences of visual acuity among them were analyzed. Pearson correlation and regression analysis were performed on visual acuity and average retinal light sensitivity. RESULTS: (1) The visual acuity was 4.80±0.16 for central fixation group; 4.20±0.45 for uncertain group; and 3.40±0.57 for eccentric fixation group, respectively. Based on the one-way ANOVA, the visual acuities in the three groups had statistically significant differences (P<0.05). (2) There was linear relationship between visual acuity (y) and average retinal light sensitivity (x). And the linear regression equations was y=-18.76+6.21x. The Pearson correlation coefficient was 0.707 (P<0.05). CONCLUSION: There is significant positive correlation between visual acuity and fixation characteristics. Testing of fixation characteristics could be used to assess visual acuity objectively, which has a practical value in forensic clinical medicine.

Managing immune checkpoint inhibitor-associated gastritis: Insights and strategies.

Immune checkpoint inhibitors (ICIs) are widely used due to their effectiveness in treating various tumors. Immune-related adverse events (irAEs) are defined as adverse effects resulting from ICI treatment. Gastrointestinal irAEs are a common type of irAEs characterized by intestinal side effects, such as diarrhea and colitis, which may lead to the discontinuation of ICIs.

Clinical Efficacy of Percutaneous Osteoplasty Under Fluoroscopy and Cone-Beam CT Guidance for Painful Sternal Metastases: A Case Series.

Background: Although percutaneous osteoplasty (POP) has been widely accepted and is now being performed for the treatment of painful bone metastases outside the spine. It is emerging as one of the most promising procedures for patients with painful bone metastasis who are unsuitable for surgery or who show resistance to radiotherapy and/or analgesic therapies. However, there are only scarce reports regarding osteoplasty in painful sternal metastases. Subjects and Method: We report four patients with sternal metastases suffered with severe pain of anterior chest wall. The original tumors included lung cancer and thyroid cancer. For the initially pain medication failing, all the four patients received POP procedure under fluoroscopic and cone-beam CT (CBCT) guidance, and obtained satisfying resolution of painful symptoms at 6-month postop follow-up. Conclusion: POP is a safe and effective treatment for pain caused by metastatic bone tumors in the sternum. In practice, however, percutaneous puncture of pathologic sternal fractures can be a challenge because of the long flat contour and the defacement by lytic tumor of bony landmarks. We find that the use of fluoroscopic and CBCT can facilitate POP for flat bone fractures with displacing the trajectory planning, needle advancement, and cement delivery in time.

Dihydroartemisinin-driven selective anti-lung cancer proliferation by binding to EGFR and inhibition of NRAS signaling pathway-induced DNA damage.

Chemotherapeutic agents can inhibit the proliferation of malignant cells due to their cytotoxicity, which is limited by collateral damage. Dihydroartemisinin (DHA), has a selective anti-cancer effect, whose target and mechanism remain uncovered. The present work aims to examine the selective inhibitory effect of DHA as well as the mechanisms involved. The findings revealed that the Lewis cell line (LLC) and A549 cell line (A549) had an extremely rapid proliferation rate compared with the 16HBE cell line (16HBE). LLC and A549 showed an increased expression of NRAS compared with 16HBE. Interestingly, DHA was found to inhibit the proliferation and facilitate the apoptosis of LLC and A549 with significant anti-cancer efficacy and down-regulation of NRAS. Results from molecular docking and cellular thermal shift assay revealed that DHA could bind to epidermal growth factor receptor (EGFR) molecules, attenuating the EGF binding and thus driving the suppressive effect. LLC and A549 also exhibited obvious DNA damage in response to DHA. Further results demonstrated that over-expression of NRAS abated DHA-induced blockage of NRAS. Moreover, not only the DNA damage was impaired, but the proliferation of lung cancer cells was also revitalized while NRAS was over-expression. Taken together, DHA could induce selective anti-lung cancer efficacy through binding to EGFR and thereby abolishing the NRAS signaling pathway, thus leading to DNA damage, which provides a novel theoretical basis for phytomedicine molecular therapy of malignant tumors.