Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer.

BACKGROUND: Invasive lobular breast cancer (ILC) is the second most common type of breast cancer after invasive breast cancer of no special type (NST), representing up to 15% of all breast cancers. DESIGN: Latest data on ILC are presented, focusing on diagnosis, molecular make-up according to the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT) guidelines, treatment in the early and metastatic setting and ILC-focused clinical trials. RESULTS: At the imaging level, magnetic resonance imaging-based and novel positron emission tomography/computed tomography-based techniques can overcome the limitations of currently used imaging techniques for diagnosing ILC. At the pathology level, E-cadherin immunohistochemistry could help improving inter-pathologist agreement. The majority of patients with ILC do not seem to benefit as much from (neo-)adjuvant chemotherapy as patients with NST, although chemotherapy might be required in a subset of high-risk patients. No differences in treatment efficacy are seen for anti-human epidermal growth factor receptor 2 (HER2) therapies in the adjuvant setting and cyclin-dependent kinases 4 and 6 inhibitors in the metastatic setting. The clinical utility of the commercially available prognostic gene expression-based tests is unclear for patients with ILC. Several ESCAT alterations differ in frequency between ILC and NST. Germline BRCA1 and PALB2 alterations are less frequent in patients with ILC, while germline CDH1 (gene coding for E-cadherin) alterations are more frequent in patients with ILC. Somatic HER2 mutations are more frequent in ILC, especially in metastases (15% ILC versus 5% NST). A high tumour mutational burden, relevant for immune checkpoint inhibition, is more frequent in ILC metastases (16%) than in NST metastases (5%). Tumours with somatic inactivating CDH1 mutations may be vulnerable for treatment with ROS1 inhibitors, a concept currently investigated in early and metastatic ILC. CONCLUSION: ILC is a unique malignancy based on its pathological and biological features leading to differences in diagnosis as well as in treatment response, resistance and targets as compared to NST.

Regulation of miR-33b on endometriosis and expression of related factors.

The article "Regulation of miR-33b on endometriosis and expression of related factors, by W.-W. Yang, L. Hong, X.-X. Xu, Q. Wang, J.-L. Huang, L. Jiang, published in Eur Rev Med Pharmacol Sci 2017; 21 (9): 2027-2033-PMID: 28537685" has been retracted by the authors. They state that the reproducibility of protocell experiments was not high, and the research results were significantly different from those in the earlier stage. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/12676.

Probiotic Lactobacillus rhamnosus GG (LGG) restores intestinal dysbacteriosis to alleviate upregulated inflammatory cytokines triggered by femoral diaphyseal fracture in adolescent rodent model.

OBJECTIVE: The aim of the study was to examine the influence of femoral shaft fracture on systemic inflammation and gut microbiome in adolescent rats and evaluate the anti-inflammatory effect of Lactobacillus rhamnosus GG (LGG) and its regulation of intestinal flora, as well as illustrate the mechanism by which LGG ameliorates the inflammatory response and restores intestinal dysbacteriosis. MATERIALS AND METHODS: Twenty-four male Sprague Dawley rats of 5 to 6 weeks of age were subjected to a standard femoral shaft fracture and internally fixed with LGG supplementation in advance or on the same day of injury or with saline solution for 1 week. The levels of TNF-α, IL-6, IL-10, and CRP were assessed using standard protocols. Furthermore, gut microbiota composition was analyzed in the fecal samples using 16S rDNA gene sequencing, and the relationship between gut microbiota variation and inflammatory response was tested. RESULTS: The serum indices of the above-mentioned inflammatory cytokines were significantly increased, and the gut microbial balance was significantly disturbed in adolescent rats by diaphyseal fractures of the femur and surgery. Moreover, L. rhamnosus strains manipulated the gut microbiota by decreasing the relative abundance of Proteobacteria and increasing that of Firmicutes, Actinobacteria and Bacteroidetes, which in turn increased the levels of IL-10 and alleviated the levels of IL-6, CRP, and TNF-α. CONCLUSIONS: LGG exhibited anti-inflammatory effects by alleviating the inflammatory response and regulating the gut microbiota in adolescent rats who underwent skeletal fracture and surgery. Our results suggested that the L. rhamnosus strains could be considered as an alternative dietary supplement for the prevention or treatment of skeletal injury and its associated complications.

[Surveillance data on notifiable infectious diseases among students aged 6-22 years in China, 2011-2016].

Objective: To analyze the epidemiological characteristics of notifiable infectious diseases among Chinese students from 2011 to 2016 and to provide reference for the effective prevention and control programs on infectious disease among students. Methods: Both morbidity and mortality of notifiable infectious diseases among Chinese students aged 6-22 years from 2011 to 2016 were analyzed, with main characteristics of the disease described. Results: During 2011 to 2016, morbidities of Categories A, B and C infectious diseases among the Chinese students aged 6-22 years showed a decreasing trend, from 248.24/100 000 in 2012 to 158.57/100 000 in 2016. Mortality rates of Category A, B and C infectious diseases had also decreased from 0.12/100 000 in 2011 to 0.07/100 000 in 2016. The average morbidity of the top four diseases from Category A and B infectious diseases appeared as: tuberculosis (16.24/100 000), scarlet fever (9.39/100 000), hepatitis B (7.69/100 000) and bacillary and amebic dysentery (7.15/100 000). The average rates of mortality on the top four diseases appeared as: rabies (0.044 8/100 000), HIV/AIDS (0.027 7/100 000), tuberculosis (0.008 0/100 000) and Japanese encephalitis (0.005 9/100 000). The average rates of morbidity on the top four diseases appeared as: mumps (75.81/100 000), hand-foot-mouth disease (28.55/100 000), other infectious diarrhea (22.41/100 000) and influenza (15.67/100 000) in the Category C. Reported death cases were from hand-foot-mouth disease (11 cases), influenza (9 cases), mumps (1 case) and rubella (1 case). The prevalence rates varied among different student populations, with higher HIV/AIDS, hepatitis B and tuberculosis rates among college and senior high school students, while higher mumps, influenza and hand-foot-mouth disease rates among primary school and junior high school students. Conclusions: Both morbidity and mortality of notifiable infectious diseases among Chinese students aged 6-22 years had decreased significantly in 2011-2016. However, the major infectious diseases had become new challenges among students. HIV/AIDS had become a key infectious disease among college students and the relatively high prevalence of tuberculosis was seen in college and high school students.

[Investigation of human brucellosis diagnosis and report quality in medical institutions in key areas of Shanxi province].

Objective: To evaluate the accuracy of human brucellosis diagnosis and reporting in medical institutions in Shanxi province, and understand the performance of clinical doctors to diagnose human brucellosis according to diagnostic criteria. Methods: Field investigation was conducted in 6 medical institutions in the key areas of human brucellosis in Shanxi province. The diagnosis data of the reported brucellosis cases in 2015 were collected and reviewed retrospectively for the evaluation of the diagnosis accuracy with systematic sampling method. The database was established with Excel 2010 and the descriptive analysis and statistical test were conducted with software R 3.3.2. Results: The diagnosis consistent rate of the 377 brucellosis cases reviewed was 70.8% (267/377), the diagnosis consistent rates in medical institutions at city-level and country-level were 77.0% (127/165) and 66.0% (140/212) respectively, the differences had significance (χ(2)=5.4, P=0.02). Among the reviewed cases, the diagnosis consistent rate of laboratory diagnosis and clinical diagnosis were 87.1% (256/294) and 13.3% (11/83) respectively, and the differences had significance (χ(2)=170.7, P<0.001). Among the 21 investigated clinical doctors, the numbers of the doctors who correctly diagnosed the suspected cases, probable cases and lab-confirmed cases were only 3, 0 and 8 respectively. All of the clinical doctors knew that it is necessary to report the brucellosis cases within 24 hours after diagnosis. Conclusion: The accuracy of human brucellosis diagnosis in key areas of human brucellosis in Shanxi was low, and the performance of the clinical doctors to diagnose human brucellosis according to diagnostic and case classification criteria was unsatisfied.

Autologous blood salvage in the era of patient blood management.

Almost 150 years after the first autologous blood transfusion was reported, intraoperative blood salvage has become an important method of blood conservation. The primary goal of autologous transfusion is to reduce or avoid allogeneic red blood cell transfusion and the associated risks and costs. Autologous salvaged blood does not result in immunological challenge and its consequences, provides a higher quality red blood cell that has not been subjected to the adverse effects of blood storage, and can be more cost-effective than allogeneic blood when used for carefully selected surgical patients. Cardiac, orthopaedic and vascular surgery procedures with large anticipated blood loss can clearly benefit from the use of cell salvage. There are safety concerns in cases with gross bacterial contamination. There are theoretical safety concerns in obstetrical and cancer surgery; however, careful cell washing as well as leucoreduction filters makes for a safer autologous transfusion in these circumstances. Further studies are needed to determine whether oncologic outcomes are impacted by transfusing salvaged blood during cancer surgery. In this new era of patient blood management, where multimodal methods of reducing dependence on allogeneic blood are becoming commonplace, autologous blood salvage remains a valuable tool for perioperative blood conservation. Future studies will be needed to best determine how and when cell salvage should be utilized along with newer blood conservation measures.

Peripherally inserted central catheters for calcium requirements after successful parathyroidectomy: a comparison with centrally inserted catheters.

BACKGROUND Intravenous calcium supplements are often required following parathyroidectomy to avoid postoperative hypocalcaemia. The aim of this study was to compare application effect of a femoral central venous catheter (CVC) and peripherally inserted central catheter (PICC) on intravenous calcium supplements after parathyroidectomy. METHODS We retrospectively reviewed the hospital records of 73 patients with secondary hyperparathyroidism who underwent a successful parathyroidectomy at the Huashan Hospital attached to Fudan University between 1 April 2011 and 1 February 2016. RESULTS Of the 73 study participants, 39 (53.4%) had a PICC and 34 (46.6%) had a CVC, respectively. Patients in the CVC group needed 6-7 days of intravenous calcium supplements, while patients in PICC group needed only 2-3 days to achieve normal serum calcium concentration (2.2-2.6 mmol/L). Furthermore, the duration of calcium supplementation was 71.62 ± 4.48 hours in PICC group and 100.4 ± 5.43 hours in CVC group (P < 0.05). Of the patients in PICC group, the incidence of catheter occlusion, operation failure and hypocalcaemia was 0%, which was significantly lower than those in CVC group (2.56%, 7.69% and 7.69%, respectively). CONCLUSIONS PICC is a safe and efficient alternative in contrast to CVC for providing venous access for calcium supplementation in surgical patients after parathyroidectomy.

Regulation of miR-33b on endometriosis and expression of related factors.

OBJECTIVE: Endometriosis is a common benign disease in gynecology, and can cause chronic pelvic pain, dysmenorrhea and even infertility. Its pathogenesis mechanism has not been fully illustrated. miRNA (miR) participates in various biological activities including cell growth, proliferation, apoptosis, organ formation, inflammation and tumor. Its role in endometriosis has not been reported. MiR-33b is involved in cell metabolism, proliferation and invasion, but with its function and mechanism in endometriosis unknown. PATIENTS AND METHODS: Real-time PCR was used to test miR-33b expression in ectopic endometrial and normal tissues. In vitro cultured endometrial cells were transfected with miR-33b mimic or inhibitor, followed by Real-time PCR for miR-33b expression. MTT method detected endometrial cell proliferation. Caspase 3 activity was quantified by test kit. Real-time PCR and Western blot measured effect of miR-33b on vascular endothelial growth factor (VEGF) and matrix metalloprotein 9 (MMP-9). RESULTS: MiR-33b was down-regulated in ectopic endometrial tissues (p < 0.05 compared to normal tissues). Transfection of miR-33b inhibitor facilitated endometrial proliferation, decreased Caspase 3 activity, increased VEGF and MMP-9 mRNA or protein expression (p < 0.05 compared to control group). MiR-33b mimic suppressed endometrial proliferation, elevated Caspase 3 activity, and decreased VEGF or MMP-9 expression (p < 0.05 compared to control group). CONCLUSIONS: MiR-33b can mediate cell apoptosis, alter VEGF and MMP-9 expression and affect proliferation and apoptosis of uterus endometrial cells, thus participating endometriosis formation.

Relationship between deficiencies in vitamin A and E and occurrence of infectious diseases among children.

OBJECTIVE: To investigate the relationship between vitamin A deficiency (VAD), vitamin E deficiency (VED) and infectious diseases. PATIENTS AND METHODS: We chose 684 cases of healthy children age 5 months-12 years from our hospital, measured their VA, VE from vein under the light proof condition with high-pressure liquid chromatography. Thereafter, the children who get the acute respiratory tract infection (ARI) or diarrhea two weeks later were registered. RESULTS: After the two weeks trial (N=684 cases), the VA level of children with ARI was lower than that of children without ARI (0.23±0.02 mg/ml/0.33±0.01 mg/ml), p<0.05. Moreover, the VE level of children with ARI was significantly lower than that of children without ARI (p<0.05). Most interestingly, the proportion of children with diarrhea accompanied with decreased VA level in serum was higher than that of children without diarrhea, indicating that VA level <0.2 mg/L more easily affected acute respiratory tract infection. CONCLUSIONS: We were able to demonstrate that Children who presented vitamin A deficiency were easier to get the acute respiratory tract infection (ARI) and diarrhea. Children who presented vitamin E deficiency were easier to get the acute respiratory tract infection (ARI). Vitamin A and vitamin E deficiencies are one of the important factors related to occurrences of acute infectious diseases in children.

Enhanced salt tolerance in tomato plants constitutively expressing heat-shock protein in the endoplasmic reticulum.

The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and activates the unfolded protein response (UPR) signaling pathway. The UPR signaling pathway is associated with plant responses to adverse environmental conditions. Thus, changes in the UPR signaling pathway might affect plant abiotic tolerance. Here, the role of ER small heat-shock protein (ER-sHSP) in improving plant resistance to salt stress was explored. Under salt stress conditions, ER-sHSP transgenic plants were found to have more vigorous roots, maintain a higher relative water content, absorb less Na(+), accumulate more osmolytes and Ca(2+), and sustain less damage to the photosystem, compared to wild-type non-transgenic plants. Furthermore, we found that the constitutive expression of ER-sHSP under salt stress depressed the expression of other ER molecular chaperones. These results indicate that the constitutive expression of ER-sHSP enhanced salinity tolerance of tomato plants significantly, and alleviated the ER stress caused by the salt stress in plant cells.

Association of BCSC-1 with human esophageal squamous cell carcinoma.

Breast cancer suppressor candidate-1 (BCSC-1) is a newly identified candidate tumor suppressor gene. BCSC-1 shows decreased levels in a variety of cancer types. In this study, we investigated the association between BCSC-1 and human esophageal squamous cell carcinoma (ESCC). BCSC-1 expression was detected in ESCC and normal tissues adjacent to tumor tissues by Western blot analysis and real-time PCR  as well as immunohistochemistry of paraffin sections. The relationships between BCSC-1 expression and various clinicopathological characteristics were analyzed. Western blot analysis and real-time PCR showed that levels of BCSC-1 protein and mRNA expression in ESCC significantly decreased compared with those in adjacent normal tissues.  Immunohistochemistry exhibited marked reduction of BCSC-1 in 38 of 105 ESCC specimens. Moreover, downregulation of BCSC-1 was associated with the grade of tumor cellular differentiation (P<0.05). These findings indicate that BCSC-1 downregulation in ESCC is associated with carcinogenesis and may play important roles during the process of ESCC cancer development.

The effect of calcium channel blockers on prevention of preeclampsia in pregnant women with chronic hypertension.

BACKGROUND: Pregnant women with chronic hypertension are at increased risk for complications. This study aims to investigate whether calcium channel blockers plus low dosage aspirin therapy can reduce the incidence of complications during pregnancy with chronic hypertension and improve the prognosis of neonates. MATERIALS AND METHODS: From March 2011 to June 2013, 33 patients were selected to join this trial according to the chronic hypertension criteria set by the Preface Bulletin of American College of Obstetricians and Gynecologists, (ACOG). Patients were administrated calcium channel blockers plus low-dosage aspirin and vitamin C. The statistic data of baseline and prognosis from the patients were retrospectively reviewed and compared. RESULTS: Blood pressure of patients was controlled by these medicines with average systolic pressure from 146.3 to 148.7 mmHg and average diastolic pressure from 93.8 to 97.9 mmHg; 39.4% patients complicated mild preeclampsia; however, none of them developed severe preeclampsia or eclampsia, or complicate placental abruption. 30.3% patients delivered at preterm labour; 84.8% patients underwent cesarean section. The neonatal average weight was 3,008 ± 629.6 g, in which seven neonatal weights were less than 2,500 g. All of the neonatal Apgar scores were 9 to 10 at one to five minutes. Small for gestational age (SGA) occurred in five (15%). CONCLUSIONS: Calcium channel blockers can improve the outcome of pregnancy women with chronic hypertension to avoid the occurrence of severe pregnancy complication or neonatal morbidity.

Stability of daphnoretin in vitro.

The stability of daphnoretin in sodium phosphate buffers at different pH and temperature, and in different biological samples at 37 degrees C was investigated using HPLC with UV detector set at 345 nm. Daphnoretin degraded rapidly in alkaline environment and was stable in acidic environment. Daphnoretin was stable in simulated gastrointestinal liquid, stomach contents, gastric mucosa and colon contents; it was unstable in plasma, liver homogenates, small intestine contents, small intestinal mucosa and blind gut contents. The stability of daphnoretin in plasma and other biomaterials could have a significant impact on its absorption.

Hollow fiber liquid-phase microextraction for the determination of nimesulide in human plasma and its application to a pharmacokinetic study.

A hollow fiber liquid-phase microextraction (HF-LPME) method in combination with HPLC-UV for the determination of nimesulide in human plasma was developed and validated. A small volume of dihexyl ether contained within a polypropylene hollow fiber was used for the extraction of nimesulide from acidified plasma solutions. Factors affecting the extraction efficiency were optimized and discussed. With HPLC-UV as the end analysis technique, the procedure was validated for nimesulide in the concentration range of 50-5000 ng/mL. The intra- and inter-assay precisions were less than 9.1%, and accuracy was within 3.2%. The lower limit of quantification (LLOQ) was 50 ng/mL. Enrichment factor from 144-fold to 156-fold was achieved at three quality control (QC) concentrations. The mean extraction recovery was greater than 41.2%. This method was successfully applied for the evaluation of pharmacokinetics of nimesulide after single oral doses of 100 mg nimesulide to six healthy Chinese volunteers.

A mutation in the Kit gene leads to novel gonadal phenotypes in both heterozygous and homozygous mice.

The direct sequencing of the Kit cDNA obtained from mutant mice was used to reveal the molecular nature of the W(-3Bao) ENU-induced mutation. There was a T to A transversion at the 441st nucleotide in the W(-3Bao) open reading frame (ORF), which introduced a pre-mature termination codon at residue 147. The gross embryonic development, hematopoiesis and spermatogenesis were examined in the mutant mice. There was no visible difference among the W(-3Bao/+), W(-3Bao/3Bao) and wild type embryos before embryonic day 12.5. W(-3Bao/3Bao) embryos appeared pale after E14.5 and dwarf after E16.5. An extremely low level of hematochrome and large red blood cells were found in W(-3Bao/3Bao) 18.5 days old embryos, leading to the stillbirth of the homozygotes. In 18.5 days old embryos the spermatogonia of W(-3Bao/3Bao) embryos did not migrate to the contorted seminiferous tubules properly, but instead were found in the interstitial tissue. The spermatogonia of W(-3Bao/+) or W(+/+) mice were present in both the interstitial tissue and contorted seminiferous tubules. In the adult male hetereozygotes, there are contorted seminiferous tubules with no spermatogonia, suggesting that the migration defect was dominant. In female W(-3Bao/3Bao) ovaries, primordial follicles were absent while primordial follicles appeared clearly in the ovaries of W(-3Bao/+) or W(+/+) mice. With a nonsense mutation in the Kit gene, W(-3Bao/+) mice show white spotting and an abnormal development of the contorted seminiferous tubules and W(-3Bao/3Bao) mice are stillborn due to severe macrocytic anemia, and have abnormal genital glands in both the male and female.

Production and characterization of pure Clostridium spore suspensions.

AIMS: A general protocol was derived for optimizing the production of pure, high concentration Clostridium endospore suspensions. METHODS AND RESULTS: Two sporulation methods were developed that yielded high concentrations of notably pure Clostridium sporogenes, C. hungatei and C. GSA-1 (Greenland ice core isolate) spore suspensions (10 ml of 10(9) spores ml(-1) with >99% purity each). Each method was derived by evaluating combinations of three sporulation conditions, including freeze drying of inocula, heat shock treatment of cultures, and subsequent incubation at suboptimal temperatures that yielded the highest percentage of sporulation. Pure spore suspensions were characterized in terms of dipicolinic acid content, culturability, decimal reduction time (D) value for heat inactivation (100 degrees C) and hydrophobicity. CONCLUSIONS: While some Clostridium species produce a high percentage of spores with heat shock treatment and suboptimal temperature incubation, other species require the additional step of freeze drying the inocula to achieve a high percentage of sporulation. SIGNIFICANCE AND IMPACT OF THE STUDY: Pure Clostridium spore suspensions are required for investigating species of medical and environmental importance. Defining the conditions for optimal spore production also provides insight into the underlying mechanisms of Clostridium sporulation.

E2F6 negatively regulates ultraviolet-induced apoptosis via modulation of BRCA1.

E2F6 is believed to repress E2F-responsive genes and therefore plays an important role in cell-cycle regulation. However, the role of E2F6 in the control of apoptosis remains unknown. We show here that the expression of E2F6 was downregulated with a concurrent increase in BRCA1 mRNA and cleaved protein during ultraviolet (UV)-induced apoptosis in human embryonic kidney 293 cells. Moreover, E2F6 overexpression distinctly inhibited UV-induced apoptosis as well as UV-induced increases in BRCA1 expression and cleavage, accompanied with increases of the full-length BRCA1 and BRCA1 nuclear foci. In contrast, knockdown of E2F6 by small interfering RNA had opposite effects. Furthermore, these effects of E2F6 on BRCA1 depended upon the association of E2F6 with BRCA1 via its C-terminus in a UV-triggered manner and upon the transcriptional repression by E2F6 on the BRCA1 promoter. These findings provide the first demonstration of the important role for E2F6 in the control of apoptosis via targeting of BRCA1.

Nitric oxide regulates body temperature, neuronal activation and interleukin-1 beta gene expression in the hypothalamic paraventricular nucleus in response to immune stress.

An immune challenge initiates a complex cascade of events in the body including important responses from the central nervous system. As nitric oxide (NO) has been implicated in the central regulation of neuroendocrine and autonomic responses, this study was performed to determine if NO regulates physiological responses, neuronal activation, and/or interleukin-1 beta (IL-1 beta) gene expression in the paraventricular nucleus of the rat hypothalamus (PVN) in response to intravenous endotoxin, lipopolysaccharide (LPS, 100 microg/kg). Intracerebroventricular injections of NO synthase (NOS) inhibitors (7-nitroindazole sodium salt for neuronal NOS, N(G)-nitro-L-arginine for neuronal NOS and endothelial NOS, and aminoguanidine for inducible NOS) in LPS-treated rats showed that inhibition of NOS eliminated the drop in body temperature and led to increased neuronal activation in the PVN as assessed by immunohistochemistry for Fos-like immunoreactivity. Activation of NO-producing PVN neurons was also increased in these rats suggesting that NO influences neuronal NOS activity in PVN neurons. Finally, increased IL-1 beta gene expression in the PVN of LPS-treated rats receiving N(G)-nitro-L-arginine showed that NO regulates brain IL-1 beta gene expression. The results obtained with the NOS inhibitors support the hypothesis that NO produced from eNOS in the brain participates in temperature regulation, and inhibits PVN neuronal activity and IL-1 beta gene expression during immune stress.