Assembly of CpcL-phycobilisomes.

CpcL-phycobilisomes (CpcL-PBSs) are a reduced type of phycobilisome (PBS) found in several cyanobacteria. They lack the traditional PBS terminal energy emitters, but still show the characteristic red-shifted fluorescence at ~670 nm. We established a method of assembling in vitro a rod-membrane linker protein, CpcL, with phycocyanin, generating complexes with the red-shifted spectral features of CpcL-PBSs. The red-shift arises from the interaction of a conserved key glutamine, Q57 of CpcL in Synechocystis sp. PCC 6803, with a single phycocyanobilin chromophore of trimeric phycocyanin at one of the three ß82-sites. This chromophore is the terminal energy acceptor of CpcL-PBSs and donor to the photosystem(s). This mechanism also operates in PBSs from Acaryochloris marina MBIC11017. We then generated multichromic complexes harvesting light over nearly the complete visible range via the replacement of phycocyanobilin chromophores at sites α84 and ß153 of phycocyanins by phycoerythrobilin and/or phycourobilin. The results demonstrate the rational design of biliprotein-based light-harvesting elements by engineering CpcL and phycocyanins, which broadens the light-harvesting range and accordingly improves the light-harvesting capacity and may be potentially applied in solar energy harvesting.

Insights into the differential molecular response of non-germinated and germinated spores of Ameson portunus in vitro by comparative transcriptome analysis.

Ameson portunus, the recently discovered causative agent of "toothpaste disease" of pond-cultured swimming crabs in China has caused enormous economic losses in aquaculture. Understanding the process of spore germination is helpful to elucidate the molecular mechanism of its invasion of host cells. Here, we obtained mature and germinating spores by isolation and purification and in vitro stimulation, respectively. Then, non-germinated and germinated spores were subjected to the comparative transcriptomic analysis to disclose differential molecular responses of these two stages. The highest germination rate, i.e., 71.45 %, was achieved in 0.01 mol/L KOH germination solution. There were 9,609 significantly differentially expressed genes (DEGs), with 685 up-regulated and 8,924 down-regulated DEGs. The up-regulated genes were significantly enriched in ribosome pathway, and the down-regulated genes were significantly enriched in various metabolic pathways, including carbohydrate metabolism, amino acid metabolism and other metabolism. The results suggested that spores require various carbohydrates and amino acids as energy to support their life activities during germination and synthesize large amounts of ribosomal proteins to provide sites for DNA replication, transcription, translation and protein synthesis of the spores of A. portunus within the host cells. Functional genes related to spore germination, such as protein phosphatase CheZ and aquaporin, were also analyzed. The analysis of transcriptome data and identification of functional genes will help to understand the process of spore germination and invasion.

Dichromic Allophycocyanin Trimer Covering a Broad Spectral Range (550-660†nm).

Phycobilisomes, the light-harvesting complexes of cyanobacteria and red algae, are a resource for photosynthetic, photonic and fluorescence labeling elements. They cover an exceptionally broad spectral range, but the complex superstructure and assembly have been an obstacle. By replacing in Synechocystis sp. PCC 6803 the biliverdin reductases, we studied the role of chromophores in the assembly of the phycobilisome core. Introduction of the green-absorbing phycoerythrobilin instead of the red-absorbing phycocyanobilin inhibited aggregation. A novel, trimeric allophycocyanin (Dic-APC) was obtained. In the small (110 kDa) unit, the two chromophores, phycoerythrobilin and phytochromobilin, cover a wide spectral range (550 to 660 nm). Due to efficient energy transfer, it provides an efficient artificial light-harvesting element. Dic-APC was generated in vitro by using the contained core-linker, LC , for template-assisted purification and assembly. Labeling the linker provides a method for targeting Dic-APC.

[Research progress on structure, function and disease correlation of solute carrier family 4].

The solute carrier family 4 (SLC4) includes 10 members (SLC4A1-5, SLC4A7-11), which are expressed in multiple tissues in the human body. The SLC4 family members differ in their substrate dependence, charge transport stoichiometry and tissue expression. Their common function is responsible for the transmembrane exchange of multiple ions, which is involved in many important physiological processes, such as erythrocyte CO2 transport and the regulation of cell volume and intracellular pH. In recent years, many studies have focused on the role of SLC4 family members in the occurrence of human diseases. When SLC4 family members have gene mutations, a series of functional disorders will occur in the body, leading to the occurrence of some diseases. This review summarizes the recent progress about the structures, functions and disease correlation of SLC4 members, in order to provide clues for the prevention and treatment of related human diseases.

The role of lyases, NblA and NblB proteins and bilin chromophore transfer in restructuring the cyanobacterial light-harvesting complex‡.

Phycobilisomes are large light-harvesting complexes attached to the stromal side of thylakoids in cyanobacteria and red algae. They can be remodeled or degraded in response to changing light and nutritional status. Both the core and the peripheral rods of phycobilisomes contain biliproteins. During biliprotein biosynthesis, open-chain tetrapyrrole chromophores are attached covalently to the apoproteins by dedicated lyases. Another set of non-bleaching (Nb) proteins has been implicated in phycobilisome degradation, among them NblA and NblB. We report in vitro experiments with lyases, biliproteins and NblA/B which imply that the situation is more complex than currently discussed: lyases can also detach the chromophores and NblA and NblB can modulate lyase-catalyzed binding and detachment of chromophores in a complex fashion. We show: (i) NblA and NblB can interfere with chromophorylation as well as chromophore detachment of phycobiliprotein, they are generally inhibitors but in some cases enhance the reaction; (ii) NblA and NblB promote dissociation of whole phycobilisomes, cores and, in particular, allophycocyanin trimers; (iii) while NblA and NblB do not interact with each other, both interact with lyases, apo- and holo-biliproteins; (iv) they promote synergistically the lyase-catalyzed chromophorylation of the ß-subunit of the major rod component, CPC; and (v) they modulate lyase-catalyzed and lyase-independent chromophore transfers among biliproteins, with the core protein, ApcF, the rod protein, CpcA, and sensory biliproteins (phytochromes, cyanobacteriochromes) acting as potential traps. The results indicate that NblA/B can cooperate with lyases in remodeling the phycobilisomes to balance the metabolic requirements of acclimating their light-harvesting capacity without straining the overall metabolic economy of the cell.

[Textual research on history of Glycyrrhizae Radix et Rhizome processing].

The historical preparation methods of Glycyrrhizae Radix et Rhizoma were summarized and analyzed by consulting relevant literatures of herbal medicines and medical classics. This study also reviewed the records of Glycyrrhizae Radix et Rhizoma processing methods in previous editions of the Chinese Pharmacopoeia and the regulations on processing technology of Glycyrrhizae Radix et Rhizoma decoction pieces in China. This paper summarized the processing history of Glycyrrhizae Radix et Rhizoma and defined the development process of Glycyrrhizae Radix et Rhizoma processing. According to textual research from ancient times to today, there are many ways to process Glycyrrhizae Radix et Rhizoma. The processing methods without auxiliary materials include braising, frying, cooking, simmering and adding such auxiliary materials as wine, vinegar, salt, oil, ginger, honey, water and bile. There are 9 editions of the published Chinese Pharmacopoeia that document the processing of Glycyrrhizae Radix et Rhizoma, and 24 provinces and cities nationwide record the processing of Glycyrrhizae Radix et Rhizoma. At present, the 2015 edition of the Chinese Pharmacopoeia only records the processing technology of Glycyrrhizae Radix et Rhizoma honey, and the honey processing method is still widely usedtoday. Whether or not Zhigancao should be used uniformly for honey-processed Zhigancao today should be based on the processing methods of Chinese herbal medicine and its clinical use in previous ancient medical books. This paper provides a reference and historical basis for subsequent studies on other processing techniques of Glycyrrhizae Radix et Rhizoma, the rational selection of Glycyrrhizae Radix et Rhizoma varieties and the further development and utilization of corresponding medicinal materials.

Neurotrophin receptor p75 mediates amyloid ß-induced tau pathology.

Neurofibrillary tangles of hyperphosphorylated tau protein (p-tau) are a key pathological feature of Alzheimer's disease (AD). Tau phosphorylation is suggested to be secondary to amyloid-beta (Aß) accumulation. However, the mechanism by which Aß induces tau phosphorylation in neurons remains unclear. Neurotrophin receptor p75 (p75NTR) is a receptor for Aß and mediates Aß neurotoxicity, implying that p75NTR may mediate Aß-induced tau phosphorylation in AD. Here, we showed that Aß-induced tau hyperphosphorylation and neurodegeneration, including tau phosphorylation, synaptic disorder and neuronal loss, in the brains of both male wild-type (Wt) mice and male P301L transgenic mice (a mouse model of human tauopathy) were alleviated by genetic knockout of p75NTR in the both mouse models. We further confirmed that the activation or inhibition of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase-3ß (GSK3ß) significantly changed Aß/p75NTR-mediated p-tau levels in neurons. Treatment of male P301L mice with soluble p75NTR extracellular domain (p75ECD-Fc), which antagonizes the binding of Aß to p75NTR, suppressed tau hyperphosphorylation. Taken together, our findings suggest that p75NTR meditates Aß-induced tau pathology and is a potential druggable target for AD and other tauopathies.

[Modified Snodgrass technique for hypospadias].

OBJECTIVE: To investigate the clinical effect of modified Snodgrass surgical technique in the treatment of hypospadias. METHODS: We retrospectively analyzed the clinical data about 212 cases of hypospadias treated by urethroplasty from January 2008 to October 2016, 94 with the modified Snodgrass technique, namely with a silk line in addition to the urethral suture to make easier postoperative removal of the suture (group A), and the other 118 with the conventional Snodgrass technique (group B). The urethral suture was removed at 10 days after surgery for the patients in group A. We compared the success rate of surgery and incidence of postoperative complications between the two groups. RESULTS: Compared with group B, group A showed a significantly higher success rate of surgery (81.36% vs 91.49%, P <0.05) but lower incidence rates of postoperative incisional infection (12.71% vs 4.26%, P <0.05) and urinary fistula (16.10% vs 6.38%, P <0.05). No statistically significant difference was found in the incidence of urethral stenosis between the two groups (2.54% vs 2.13%, P >0.05). CONCLUSIONS: The modified Snodgrass technique can improve the success rate of surgery and reduce the incidence rates of incisional infection and urinary fistula, which deserves wide clinical application.

Red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain through stimulating the expressions of TNF-α and IL-1ß.

Our previous study has identified that glutamate in the red nucleus (RN) facilitates the development of neuropathic pain through metabotropic glutamate receptors (mGluR). Here, we further explored the actions and possible molecular mechanisms of red nucleus mGluR Ⅰ (mGluR1 and mGluR5) in the development of neuropathic pain induced by spared nerve injury (SNI). Our data indicated that both mGluR1 and mGluR5 were constitutively expressed in the RN of normal rats. Two weeks after SNI, the expressions of mGluR1 and mGluR5 were significantly boosted in the RN contralateral to the nerve injury. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN contralateral to the nerve injury at 2 weeks post-SNI significantly ameliorated SNI-induced neuropathic pain. However, unilateral administration of mGluRⅠ agonist DHPG to the RN of normal rats provoked a significant mechanical allodynia, this effect could be blocked by LY367385 or MTEP. Further studies indicated that the expressions of TNF-α and IL-1ß in the RN were also elevated at 2 weeks post-SNI. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN at 2 weeks post-SNI significantly inhibited the elevations of TNF-α and IL-1ß. However, administration of mGluR Ⅰ agonist DHPG to the RN of normal rats significantly enhanced the expressions of TNF-α and IL-1ß, these effects were blocked by LY367385 or MTEP. These results suggest that activation of red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain by stimulating the expressions of TNF-α and IL-1ß. mGluR Ⅰ maybe potential targets for drug development and clinical treatment of neuropathic pain.

Genome sequence of Paenibacillus sp. strain Aloe-11, an endophytic bacterium with broad antimicrobial activity and intestinal colonization ability.

Paenibacillus sp. strain Aloe-11, a Gram-positive, spore-forming, facultatively anaerobic bacterium isolated from the root of Aloe chinensis in the southwest region of China, has excellent antibiotic activity and intestine colonization ability. Here, we present the 5.8-Mb draft genome sequence of Paenibacillus sp. strain Aloe-11.

[Comparative analysis of early diagnostic tools for breast cancer].

OBJECTIVE: Mammography is the principle imaging modality used for early diagnosis of breast cancer in Western countries. It has not been well-established whether this Western diagnostic modality is adoptable for Chinese women. The aim of this study was to evaluate the respective accuracy of the common diagnostic tools for breast cancer including history-taking, physical examination, ultrasound and mammography. METHODS: Clinical presentation and investigations for consecutive patients undergoing history-taking, physical examination, ultrasound, mammography and pathological assessment at Peking Union Medical College Hospital were prospectively recorded between April 2010 and September 2011. Breast cancer high-risk factors acquired by history-taking were input into the risk assessment model established previously by Eleventh Five Year Key Programs for Science and Technology Development of China (Grant No. 2006BAI02A09) and classified into low-, medium-, high- and extremely high-risk groups. The low- and medium-risk groups were defined as test negative, while the high- and extremely high-risk groups were defined as test positive. Each mammogram and ultrasound was reported prospectively using a five-point reporting scale of the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS). Clinical data were compared with pathological findings. Sensitivity, specificity, positive predictive value (PRV), negative predictive value (NPV) and accuracy of respective diagnostic methods were calculated and compared. The patients were divided into two groups, above and below 50 years of age for subgroup analysis. RESULTS: A total of 1468 patients (1475 breast lesions) constituted the study population. The median age was 44 (range 13 - 92) years. Five hundred and fifty-one patients were diagnosed as breast cancer. The median age at diagnosis was 51 years and breast cancer peaked in the age group of 40 - 60 years. The sensitivity of risk assessment model, physical examination, ultrasound and mammogram was 47.5%, 86.2%, 89.8% and 79.3%, respectively; specificity was 68.8%, 83.3%, 81.0% and 88.7%, respectively; PRV was 47.6%, 75.5%, 73.8% and 80.8%, respectively; NPV was 68.8%, 91.0%, 93.0% and 87.8%, respectively; and accuracy was 60.9%, 84.4%, 84.3% and 85.2%, respectively. Further subgroup analysis demonstrated that age is an important factor influencing the sensitivity and specificity of physical examination, ultrasound and mammography. CONCLUSIONS: Ultrasound is more sensitive than mammography for early diagnosis of breast cancer in Chinese women and should be routinely used as a first-line diagnostic tool. Only a single diagnostic method is not enough sometimes and combined examination is needed for some high-risk populations.

Ultrasound-triggered microbubble destruction enhances the radiosensitivity of glioblastoma by inhibiting PGRMC1-mediated autophagy in vitro and in vivo.

BACKGROUND: Ultrasound-triggered microbubble destruction (UTMD) is a widely used noninvasive technology in both military and civilian medicine, which could enhance radiosensitivity of various tumors. However, little information is available regarding the effects of UTMD on radiotherapy for glioblastoma or the underlying mechanism. This study aimed to delineate the effect of UTMD on the radiosensitivity of glioblastoma and the potential involvement of autophagy. METHODS: GL261, U251 cells and orthotopic glioblastoma-bearing mice were treated with ionizing radiation (IR) or IR plus UTMD. Autophagy was observed by confocal microscopy and transmission electron microscopy. Western blotting and immunofluorescence analysis were used to detect progesterone receptor membrane component 1 (PGRMC1), light chain 3 beta 2 (LC3B2) and sequestosome 1 (SQSTM1/p62) levels. Lentiviral vectors or siRNAs transfection, and fluorescent probes staining were used to explore the underlying mechanism. RESULTS: UTMD enhanced the radiosensitivity of glioblastoma in vitro and in vivo (P < 0.01). UTMD inhibited autophagic flux by disrupting autophagosome-lysosome fusion without impairing lysosomal function or autophagosome synthesis in IR-treated glioblastoma cells. Suppression of autophagy by 3-methyladenine, bafilomycin A1 or ATG5 siRNA had no significant effect on UTMD-induced radiosensitization in glioblastoma cells (P < 0.05). Similar results were found when autophagy was induced by rapamycin or ATG5 overexpression (P > 0.05). Furthermore, UTMD inhibited PGRMC1 expression and binding with LC3B2 in IR-exposed glioblastoma cells (P < 0.01). PGRMC1 inhibitor AG-205 or PGRMC1 siRNA pretreatment enhanced UTMD-induced LC3B2 and p62 accumulation in IR-exposed glioblastoma cells, thereby promoting UTMD-mediated radiosensitization (P < 0.05). Moreover, PGRMC1 overexpression abolished UTMD-caused blockade of autophagic degradation, subsequently inhibiting UTMD-induced radiosensitization of glioblastoma cells. Finally, compared with IR plus UTMD group, PGRMC1 overexpression significantly increased tumor size [(3.8 ± 1.1) mm2 vs. (8.0 ± 1.9) mm2, P < 0.05] and decreased survival time [(67.2 ± 2.6) d vs. (40.0 ± 1.2) d, P = 0.0026] in glioblastoma-bearing mice. CONCLUSION: UTMD enhanced the radiosensitivity of glioblastoma partially by disrupting PGRMC1-mediated autophagy.

Red Nucleus Interleukin-6 Evokes Tactile Allodynia in Male Rats Through Modulating Spinal Pro-inflammatory and Anti-inflammatory Cytokines.

Our previous studies have clarified that red nucleus (RN) interleukin (IL)-6 is involved in the maintenance of neuropathic pain and produces a facilitatory effect by activating JAK2/STAT3 and ERK pathways. In this study, we further explored the immune molecular mechanisms of rubral IL-6-mediated descending facilitation at the spinal cord level. IL-6-evoked tactile allodynia was established by injecting recombinant IL-6 into the unilateral RN of naive male rats. Following intrarubral administration of IL-6, obvious tactile allodynia was evoked in the contralateral hindpaw of rats. Meanwhile, the expressions of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), IL-1ß, and IL-6 were elevated in the contralateral spinal dorsal horn (L4-L6), blocking spinal TNF-α, IL-1ß, or IL-6 with neutralizing antibodies relieved IL-6-evoked tactile allodynia. Conversely, the levels of anti-inflammatory cytokines transforming growth factor-ß (TGF-ß) and IL-10 were reduced in the contralateral spinal dorsal horn (L4-L6), an intrathecal supplement of exogenous TGF-ß, or IL-10 attenuated IL-6-evoked tactile allodynia. Further studies demonstrated that intrarubral pretreatment with JAK2/STAT3 inhibitor AG490 suppressed the elevations of spinal TNF-α, IL-1ß, and IL-6 and promoted the expressions of TGF-ß and IL-10 in IL-6-evoked tactile allodynia rats. However, intrarubral pretreatment with ERK inhibitor PD98059 only restrained the increase in spinal TNF-α and enhanced the expression of spinal IL-10. These findings imply that rubral IL-6 plays descending facilitation and produces algesic effect through upregulating the expressions of spinal pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 and downregulating the expressions of spinal anti-inflammatory cytokines TGF-ß and IL-10 by activating JAK2/STAT3 and/or ERK pathways, which provides potential therapeutic targets for the treatment of pathological pain.

[Retinoic acid protects neonatal rats from hyperoxia-induced lung injury through down-regulating connective tissue growth factor].

OBJECTIVE: To explore the mechanism of retinoic acid (RA)　protection　against hyperoxia-induced lung injury. METHODS: Ninety Sprague-Dawley rats were randomly assigned into three groups (n=30 each): air control group (exposed to air) and hyperoxia groups (exposed to 85% oxygen) with and without RA treatment. The RA-treated hyperoxia group received an intraperitoneal injection of RA (500 µg/kg) daily. Lungs were removed by tnoracotomy 4, 7 and 14 days after exposure. Radical alveolar counts (RAC) were observed by hematoxylin and eosin staining under a light microscope. The mRNA level of CTGF in lungs was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The expression of CTGF protein in lungs was detected by immunohistochemistry. RESULTS: With the prolonged hyperoxia exposure, the lungs developed inflammatory cell infiltration, alveolar structure disorders, a decrease in the number of alveoli, and alveolar interstitial thickening in the hyperoxia groups with and without RA treatment. Pathological changes in the RA-treated hyperoxia group were less severe than the untreated hyperoxia group. The CTGF mRNA and protein expression were up-regulated in the hyperoxia groups with and without RA treatment 7 and 14 days after exposure compared with the air control group. Significantly decreased CTGF mRNA and protein expression were noted in the RA-treated hyperoxia group compared with the untreated hyperoxia group 14 days after exposure. CONCLUSIONS: The expression of CTGF mRNA and protein increases in neonatal rats with hyperoxia-induced lung injury. RA may provide protections against the lung injury possibly through down-regulating CTGF expression.

Resveratrol inhibits right ventricular hypertrophy induced by monocrotaline in rats.

1. Resveratrol (RSV), a polyphenol in red wine, exhibits cardioprotective effects in vitro, such as inhibition of angiotensin II- or phenylephrine-induced cardiomyocyte hypertrophy in rat neonatal myocyte cultures and suppression of cardiac fibroblast proliferation. The aim of the present study was to investigate the protective effects of RSV against monocrotaline (MCT)-induced right ventricular (RV) hypertrophy in rats. 2. Male Sprague-Dawley rats were given a single injection of MCT (50 mg/kg, s.c.) and were then treated with either vehicle (normal saline) or RSV (10 and 30 mg/kg, i.g., twice daily) for 21 days. A separate group of control rats were not injected with MCT and were treated with normal saline for 21 days. At the end of the treatment period, all rats were subjected to echocardiography and haemodynamic measurements. In addition, after rats had been killed, the hearts were subjected to histopathological, untrastructural and immunohistochemical analyses. 3. In vehicle-treated rats, MCT injection resulted in 33% mortality, whereas mortality in RSV-treated MCT-injected rats was 0%. In vehicle-treated rats, MCT increased RV free wall thickness and RV systolic pressure and decreased pulmonary arterial acceleration time at the end of the experimental period. These dynamic changes were ameliorated by RSV in a dose-dependent manner. Histologically, MCT injection resulted in RV hypertrophy, swollen mitochrondria and cardiomyocyte apoptosis; all these morphological changes were dose-dependently improved in rats treated with RSV. 4. In conclusion, RSV inhibits the RV hypertrophy induced by MCT in rats and this effect is mediated by both a direct effect of RSV on cardiomyocytes and an indirect effect mediated via a reduction in pulmonary hypertension.

[Diagnosis and treatment of occult breast cancer: report of 23 cases].

OBJECTIVE: To explore the presenting clinical features, management approach and treatment outcomes for occult breast cancer. METHODS: Twenty-three patients with occult breast cancer presenting with axillary nodal metastases treated in our department between 1986 and 2007 were included in this study. The clinicopathological, imaging and follow-up data of the 23 cases were retrospectively analyzed. RESULTS: All patients were female. The mean age of diagnosis was 57.7 years with a range of 27 - 73 years. The mean follow-up was 15.70 months (range 1 - 62 months). Eight cases in 17 patients were positive by breast ultrasound, three cases in 9 patients were positive by mammography, one case in 2 patients was positive by breast MRI. 20 patients underwent modified radical mastectomy and three patients did not receive the mastectomy treatment. 16 patients had chemotherapy, four patients had radiotherapy, two patients had both chemotherapy and radiotherapy. Two patients had pulmonary metastasis, one patient had recurrence of axillary nodes, pulmonary metastasis and bone metastasis during follow-up. CONCLUSIONS: A normal check before operation to exclude a cancer of other origin can help to diagnose occult breast cancer. The breast must be treated. Axillary nodal dissection and mastectomy, or breast conservation with radiation therapy alone can be considered as a management option.

Fractures due to Aromatase Inhibitor Therapy for Breast Cancer: A Real-World Analysis of FAERS Data in the Past 15 Years.

INTRODUCTION: The adverse effect of fractures by different aromatase inhibitor (AI) drugs has not been thoroughly assessed in real-world studies. OBJECTIVE: To assess the adverse events of fractures of real-world breast cancer patients caused by AI therapy through the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: The FAERS data from January 2004 to December 2018 were sorted out and analyzed for correlations between fractures and AI use. Disproportionate analysis and Bayesian analysis were adopted to quantify the signal, the association between the AIs and fractures. The onset time and outcome of fractures after different AI regimens were also compared. RESULTS: Out of 23,064 adverse reports, 657 fracture reports (2.85%) were analyzed. Anastrozole showed a positive association with 4 detection methods, while letrozole and exemestane did so with 2. More exemestane-related reports (44.62%) resulted in initial or prolonged hospitalization than anastrozole (30.12%, p = 0.013) and letrozole (29.43%, p = 0.006). The fracture onset time showed no significant difference among anastrozole, letrozole, and exemestane (median onset time: 46.95, 34.25, and 40.58 months, respectively; p = 0.236). CONCLUSIONS: Anastrozole should be prescribed with more medical care. Analysis of FAERS data identified fracture risk tendencies with AI regimens, which supported continuous monitoring, risk evaluations, and further comparative studies.

A novel use for Levey-Jennings charts in prenatal molecular diagnosis.

BACKGROUND: The goal of this study was to determine whether Levey-Jennings charts, which are widely used in clinical laboratories, can be used to create standardized internal quality controls (IQCs) for prenatal molecular diagnosis. METHODS: Aneuploid amniocyte lines with trisomy 13, 21, and 18, and 47,XXY were established by transfection with SV40LTag-pcDNA3.1(-)and combined at different ratios to generate aneuploidy chimeric quality-control cell mixtures A to H. These quality-control cells were then used to calculate the [Formula: see text], [Formula: see text] ±1 standard deviation (SD), [Formula: see text] ±2 SD, and [Formula: see text] ±3 SD values to develop standardized IQCs for methods used for the prenatal diagnosis of aneuploidies such as FISH. RESULTS: Methods for constructing aneuploid amniocyte lines were developed and a set of quality-control cells (A-H) were prepared. The [Formula: see text] ±1 SD, [Formula: see text] ±2 SD, and [Formula: see text] ±3 SD values of these quality-control cells for trisomy 13 and 21 were 10.2 ± 1.7, 10.2 ± 3.4, and 10.2 ± 5.1, and 90.3 ± 2.3, 90.3 ± 4.6, and 90.3 ± 6.9, respectively. Based on the values and Levey-Jennings charts, a set of standardized IQCs for prenatal diagnosis such as FISH were established. CONCLUSIONS: This method resolves the problems of a shortage of quality-control materials and a lack of quality-control charts in prenatal molecular diagnosis such as NIPT, NGS, aCGH/SNP, PCR, and FISH. Levey-Jennings chart-based IQCs for prenatal diagnosis such as FISH can be used to easily monitor whether IQC results are within acceptable limits, and then infer whether the diagnostic results for clinical samples are reliable. We expect that this standardized IQC will be useful for a wide range of molecular diagnostic laboratories.

MicroRNA-27b-3p Promotes Tumor Progression and Metastasis by Inhibiting Peroxisome Proliferator-Activated Receptor Gamma in Triple-Negative Breast Cancer.

Introduction: The role and underlying mechanisms of miR-27b-3p in triple-negative breast cancer (TNBC) remains unclear. Methods: miR-27b-3p expression level was evaluated in 99 TNBC patients with a median follow-up time of 133 months. The biological functions of miR-27b-3p by targeting PPARG were assessed by luciferase reporter assay, CCK-8 assay, Transwell assay, wound healing assay, western blot analysis and xenograft models. Results: High level of miR-27b-3p expression was found to confer poor prognosis in TNBC patients. MiR-27b-3p overexpression increased TNBC cell proliferation, migration, invasion, and metastasis. Our data suggested peroxisome proliferator-activated receptor gamma (PPARG) was a target of miR-27b-3p. The capacity of miR-27b-3p to induce TNBC progression and metastasis depended on its inhibition of the PPARG expression. Furthermore, restoring PPARG expression reversed the effect of miR-27b-3p overexpression. Mechanistically, miR-27b-3p regulated metastasis-related pathways through PPARG by promoting epithelial-mesenchymal transition. By suppressing PPARG, miR-27b-3p could also activate transcription factors Snail and NF-κB, thereby promoting metastasis. Conclusions: miR-27b-3p promotes TNBC progression and metastasis by inhibiting PPARG. MiR-27b-3p may be a potential prognostic marker of TNBC, and PPARG may be a potential molecular therapeutic target of TNBC.

A Novel External Quality Assessment of Chromosomal Karyotype Analysis Based on Chimera Image Assembly.

OBJECTIVE: This study aimed to establish a new external quality assessment (EQA) of chromosomal karyotype analysis. METHODS: Chimeric assembly A1 was established by collecting chimeric chromosome images prepared artificially from chromosomally abnormal amniocytes remaining after prenatal diagnosis. Chimeric assembly B1 and nonchimeric assembly C1 were constructed through the collection of chimeric and nonchimeric chromosome images from prenatal diagnosis, respectively. Then, chromosome images were selected randomly from assemblies A1, B1, or C1 to send to 20 technicians via email to verify the validity of a new EQA of chromosomal karyotype analysis. RESULTS: According to the EQA of 20 technicians, 47,XX,+mar from assembly A was easily misdiagnosed as 47,XX,+19 or 47,XXY, and 45,XX,t(13;22) (q10;q10) was misdiagnosed as 45,XX,13S+,-22. The total misdiagnosis rate was 3.8%. For assembly B, 46,X,+mar and 46,X,idic(Y) were easily misdiagnosed as 46,XY and 46,X,+mar, respectively. In addition, some testers missed 47,XXX in 47,XXX[2]/46,XX[48], as well as 47,XX,+18 in 46,XX [47]/47,XX,+18[3], and 45,X and 47,XXX in 46,XX[47]/45,X[2]/47,XXX[1]. The total misdiagnosis rate was 4.2%. All karyo-types from assembly C were correctly diagnosed, although incorrect descriptions used for 4% of cases. CONCLUSION: The quality of chromosome karyotype analysis can be comprehensively evaluated by a new EQA based on assembly A1 or B1.