[A case of crizotinib-associated renal cysts].

Crizotinib-associated renal cysts (CARC) are the development of new renal cysts or pre-existing renal cysts after the treatment with crizotinib. Most CARC disappear after crizotinib is stopped. A few CARC showed aggressive behavior that could go beyond the invasion of the renal cortex into nearby structures, including perirenal space, psoas major muscle, intestine, and abdominal wall. A case of EML4-ALK fusion mutation in invasive lung adenocarcinoma has been reported. Multiple cystic changes occurred repeatedly in both kidneys, right rectus muscle, and psoas major muscle after treatment with crizotinib, and spontaneous absorption and resolution after discontinuation of the drug.

Retraction Note: METTL3 promotes the progression of nasopharyngeal carcinoma through mediating M6A modification of EZH2.

The article "METTL3 promotes the progression of nasopharyngeal carcinoma through mediating M6A modification of EZH2, by Q.-Z. Meng, C.-H. Cong, X.-J. Li, F. Zhu, X. Zhao, F.-W. Chen, published in Eur Rev Med Pharmacol Sci 2020; 24 (8): 4328-4336-DOI: 10.26355/eurrev_202004_21014-PMID: 32373970" has been retracted by the authors. After publication, several issues were raised on PubPeer about the reliability of the published results. The same authors stated that the study was not performed in accordance with the standard procedures required. In particular, Figure 1 also presents some concerns as it does not reflect the experimental data reported in the study. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21014.

Effect of polyethylene Glycol Loxenatide (long-acting GLP-1RA) on lipid, glucose levels and weight in type 2 diabetes mellitus patients with obesity.

OBJECTIVE: To explore the effect of polyethylene glycol loxenatide (long-acting GLP-1R agonist) on the lipid, glucose levels, and weight in type 2 diabetes mellitus patients with obesity. PATIENTS AND METHODS: A total of 40 obese patients with type 2 diabetes mellitus in our hospital from July 2019 to June 2020 were randomly divided into a control group and a study group. The study group was treated with metformin and polyethylene glycol loxenatide injection, while the control group was treated with metformin. RESULTS: Before treatment, there was no significant difference in FPG (Fasting Blood Glucose) and PPG (Post Prandial Glycaemia) levels between the study group and the control group (p>0.05). After a treatment period, the FPG and PPG levels in the study group were significantly lower than those in the control group (p<0.05). With the longer treatment time, the patient's weight and BMI were lower (p<0.05). The weight and BMI of patients changed the least after one month of treatment, and the weight and BMI changed the most after more than seven months of treatment. After a period of treatment, the levels of FPG and PPG in the blood of male patients in the study group were significantly lower than those of female patients (p<0.05). After treatment, the TG level of the study group was significantly lower than that of the control group (p<0.05). In comparison, the HDL-C level was significantly higher than that of the control group (p<0.05). CONCLUSIONS: Lipid and glucose levels of type 2 diabetes mellitus patients with obesity have decreased after 12 weeks of polyethylene glycol loxanatide use. The weight of type 2 diabetes mellitus patients with obesity has changed after using polyethylene glycol loxenatide for a period of treatment. Among them, there is a certain relationship between body weight and treatment time, gender, and original body weight, which is worthy of further research and promotion in clinical practice.

MiR-29c-3p reduces bone loss in rats with diabetic osteoporosis via targeted regulation of Dvl2 expression.

OBJECTIVE: The aim of this study was to investigate the influence of micro ribonucleic acid (miR)-29c-3p on rats with diabetic osteoporosis (DOP) and its underlying mechanism. MATERIALS AND METHODS: A total of 30 specific pathogen-free (SPF)-grade male Wistar rats aged 6-week-old were randomly selected and divided into three groups according to different intervention means, including: NC group (control rats only injected with normal saline), DOP group (rats with DOP induced by injection of streptozotocin), and ME group (DOP rats injected with miR-29c-3p agonist for 4 consecutive weeks). The changes in blood glucose and body weight were recorded in the rats of each group every week. Enzyme-linked immunosorbent assay (ELISA) was applied to detect the content of bone turnover markers (BTMs) in serum, such as alkaline phosphatase (ALP), osteocalcin (OC), and procollagen type I N-terminal propeptide (PINP). The variations in serum calcium (Ca) and phosphorus (P) levels in the abdominal aorta were determined using an atomic absorption spectrometer in the three groups. Meanwhile, bone mineral density (BMD) of femur and lumbar vertebra (L1-L4) were examined. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the changes in messenger RNA (mRNA) expressions of miR-29c-3p and Disheveled 2 (Dvl2) in the bone tissues of intervened rats. In addition, the staining and expression changes of Dvl2 protein in bone tissues were determined via immunohistochemistry. RESULTS: The rats in NC group had normal behavioral activities, normally increased body weight, sensitive responses, as well as normal and stable blood glucose. In DOP group, the rats manifested clinical symptoms of diabetes mellitus (DM) (i.e., polydipsia, polyphagia, polyuria, and weight loss), lackluster hairs, decreased behavioral activities, slow responses, and blood glucose at a concentration higher than 16.7 mmol/L. However, the blood glucose rose first, and then, declined and it was maintained at a level higher than normal concentration in ME group. Meanwhile, the rate of weight loss significantly decreased. The results of qRT-PCR indicated that the relative expression level of miR-29c-3p in bone tissues of DOP group was remarkably lower than that in NC group (p<0.01). However, it was significantly higher in ME group than that in DOP group (p<0.05). DOP group exhibited significantly upregulated serum BTMs (ALP, CTX-1, OC, TRACP-5b, and PIPN) when compared with NC group (p<0.05) and ME group (p<0.05). Furthermore, femoral BMD decreased in DOP group (p<0.05) while increased in ME group, showing statistically significant difference between the two groups (p<0.05). Immunohistochemistry results indicated that the bone tissues of DOP rats were deeply stained, and protein expression of Dvl2 protein was significantly higher in comparison with NC group. The bone tissues were lightly stained in ME group, and the protein expression of Dvl2 was lower than that in DOP group. Besides, qRT-PCR results demonstrated that the mRNA expression changes of Dvl2 were consistent with its protein expression trends. CONCLUSIONS: MiR-29c-3p reduces bone loss in rats with DOP via targeted regulation of Dvl2 expression.

Analysis of pharmacoeconomic value of sitagliptin in the treatment of diabetes mellitus.

OBJECTIVE: Diabetes mellitus is a chronic metabolic disease which has an adverse impact on the quality of patient's life, so patients often need to receive treatment for a long time. Selection of medications with high therapeutics effects and low cost is very important for patients to take medicine for a longer period of time. Sitagliptin is a drug which is widely used in clinics and can effectively control blood glucose level. This article explores the pharmacoeconomic value of Sitagliptin in the treatment of diabetes mellitus. PATIENTS AND METHODS: A total of 100 patients with diabetes mellitus treated were recruited in this study. The patients were randomly divided into 4 groups with 25 cases in each group. Patients in group A were treated with pioglitazone, group B with Sitagliptin, group C with metformin and group D with glimepiride. The cost of the drugs, the treatment results and adverse effects were compared. RESULTS: Compared with group A, C and D, the cost-effectiveness ratio of group B was low (p<0.05), and the therapeutic effect was high (p<0.05). In addition, the incidence of adverse reactions in group B was lower than that in group A, C and D (p<0.05). There was no significant difference in the levels of FPG, 2hPG and HbAlc in patients among the four groups before treatment (p>0.05). After treatment, the levels of FPG, 2hPG and HbAlc in group B were significantly lower than those in groups A, C and D (p<0.05). Finally, there was no significant difference in waist circumference and BMI among the four groups before treatment (p>0.05). After treatment, the waist circumference and BMI in group B were lower than those in groups A, C and D (p<0.05). CONCLUSIONS: The application of Sitagliptin in the treatment of diabetic patients can effectively enhance the therapeutic effect. The cost effectiveness is satisfactory, and the blood glucose level can be maintained at a stable state.

METTL3 promotes the progression of nasopharyngeal carcinoma through mediating M6A modification of EZH2.

OBJECTIVE: The aim of this study was to investigate whether METTL3 promoted the progression of nasopharyngeal carcinoma (NPC) by silencing CDKN1C through EZH2. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression level of METTL3 in 48 pairs of NPC tissues and adjacent normal tissues. METTL3 expression in patients with different tumor lymph node metastasis (TNM) stages was detected by qRT-PCR as well. The Kaplan-Meier method was used to analyze the interplay between METTL3 expression and the prognosis of patients with NPC. At the same time, METTL3 expression in normal epithelial cell line (BEAS-2B) and NPC cell lines (SUNE-1 and C666-1) was examined using qRT-PCR. After METTL3 was knocked down in SUNE-1 cells, cell viability and migration abilities were analyzed by cell counting kit-8 (CCK-8) test and wound healing assay, respectively. The mRNA and protein expressions of EZH2 were detected by qRT-PCR and Western blot, respectively. RNA immunoprecipitation (RIP) assay was applied to detect the binding of METTL3 to EZH2 mRNA and the m6A modification on EZH2 mRNA. After knockdown of EZH2 in SUNE-1 cells, qRT-PCR was used to detect the mRNA expression of CDKN1C. Meanwhile, chromatin immunoprecipitation (ChIP) assay was conducted to analyze the binding of EZH2 to the CDKN1C promoter region. After down-regulation of METTL3 in SUNE-1 cells, the protein expressions of EZH2 and CDKN1C were detected using Western blot. After simultaneous knockdown of METTL3 and CDKN1C in SUNE-1 cells, CCK8 assay and wound healing assay were applied to examine cell viability and migration abilities. RESULTS: METTL3 expression in NPC tissues was remarkably higher than that of adjacent normal tissues. Meanwhile, METTL3 expression in T3 and T4 tumors was significantly higher than that of T1 and T2 tumors. In patients with lymph node metastasis, the expression of METTL3 was remarkably higher than those without metastasis. Survival analysis demonstrated that patients with higher expression of METTL3 exhibited significantly longer overall survival time than those with lower METTL3 expression. QRT-PCR revealed that METTL3 was highly expressed in NPC cell lines, including SUNE-1 and C666-1. After knock-down of METTL3 in SUNE-1 cells, cell viability and migration abilities were both markedly weakened. Meanwhile, the protein expression of EZH2 was remarkably reduced. However, no significant changes were observed in EZH2 mRNA level. RIP assay revealed that METTL3 could bind to EZH2 mRNA, and a m6A modification was verified on EZH2 mRNA. After knockdown of EZH2, the mRNA level of CDKN1C in SUNE-1 cells was significantly up-regulated. CHIP assay indicated that EZH2 could bind to CDKN1C. Western blot showed that, after interfering with METTL3 in SUNE-1 cells, the protein expression of EZH2 decreased significantly, while CDKN1C was up-regulated. In addition, simultaneous downregulation of METTL3 and CDKN1C in SUNE-1 cells reversed the influence of METTL3 on cell viability and migration abilities. CONCLUSIONS: METTL3 was highly expressed in NPC tissues, which might inhibit EZH2 expression by mediating M6A modification of EZH2 mRNA. Furthermore, CDKN1C could increase the malignancy of NPC cells and promote the progression of NPC.

Eliminate coherence spike in reflection-type pump-probe measurements.

The coherence spike of femtosecond laser pulses in the reflection-type pump-probe measurements has been systematically studied in the semiconductor (100) InP. By varying the setup of the pump-probe measuring system, i.e. the polarizations of pump and probe pulses, the incident angles of pump and probe beams, and the interval of delay time between pump and probe pulses, the dramatic changes in the strength of coherence spike could be clear observed. Furthermore, the proposed methods to remove the coherence spike from the transient reflectivity curves have been demonstrated in the time-domain measurements.

Transmembrane molecular pump activity of Niemann-Pick C1 protein.

Niemann-Pick C1 (NPC1) disease is characterized by cholesterol accumulation in lysosomes and aberrant feedback regulation of cellular cholesterol homeostasis. We provide evidence that the NPC1 protein has homology with the resistance-nodulation-division (RND) family of prokaryotic permeases and may normally function as a transmembrane efflux pump. Studies of acriflavine loading in normal and NPC1 fibroblasts indicated that NPC1 uses a proton motive force to remove accumulated acriflavine from the endosomal/lysosomal system. Expression of NPC1 in Escherichia coli (i) facilitated the transport of acriflavine across the plasma membrane, causing cytosolic accumulation, and (ii) resulted in transport of oleic acid but not cholesterol or cholesterol-oleate across the plasma membrane. These studies establish NPC1 as a eukaryotic member of the RND permease family.

Clinical implications of gastrointestinal symptoms in systemic amyloidosis.

BACKGROUND: Gastrointestinal (GI) symptoms in systemic amyloidosis patients are poorly characterized. This purpose of this study is to define the epidemiology and clinical implications of such symptoms. METHODS: This was a retrospective cohort study of 583 amyloid patients seen at a tertiary referral center. Of 96 symptomatic patients, 82 received endoscopic biopsies, subsequently grouped into those with histologic evidence of GI amyloid (biopsy proven) vs without (biopsy absent). KEY RESULTS: 16.8% of patients had GI symptoms, and had more abnormal NT-proBNP, cardiac ejection fraction, serum albumin, and alkaline phosphatase (P < .01). Of those who received endoscopy, the sites of highest diagnostic yield were stomach, duodenum and colon. The most common symptom was abdominal pain, nausea, or vomiting (50.0%). Of the symptomatic patients, only 37 (45%) had biopsy proven GI amyloid. Biopsy proven patients more often had cardiac involvement (P < .005), and more often received hematologic therapy or transplant (P = .01). Biopsy absent patients had more frequent neurologic involvement (P = .17). Biopsy status had no significant correlation with other indicators of amyloid burden, GI symptoms or management. CONCLUSIONS & INFERENCES: Nearly one in six amyloid patients have GI symptoms, and half do not have GI amyloid. The type of symptom does not predict endoscopic findings. Most biopsy absent patients are not managed as a functional disorder despite no alternative etiology. Gastroenterologists may have an increased role to play in the care of systemic amyloidosis beyond performing endoscopies, such as evaluating cardiac amyloid patients for concurrent GI amyloid.

Ribosomal proteins in cell proliferation and apoptosis.

Ribosomal proteins have the complex task of coordinating protein biosynthesis to maintain cell homeostasis and survival. Recent evidence suggests that a number of ribosomal proteins have secondary functions independent of their involvement in protein biosynthesis. A number of these proteins function as cell proliferation regulators and in some instances as inducers of cell death. Specifically, expression of human ribosomal protein L13a has been shown to induce apoptosis, presumably by arresting cell growth in the G2/M phase of the cell cycle. In addition, inhibition of expression of L13a induces apoptosis in target cells, suggesting that this protein is necessary for cell survival. Similar results have been obtained in the yeast Saccharomyces cerevisiae, where inactivation of the yeast homologues of L13a, rp22 and rp23, by homologous recombination results in severe growth retardation and death. In addition, a closely related ribosomal protein, L7, arrests cells in G1 and also induces apoptosis. Thus, it appears that a group of ribosomal proteins may function as cell cycle checkpoints and compose a new family of cell proliferation regulators.

Plaque-associated immune reactivity as a tool for the diagnosis and treatment of atherosclerosis.

In summary, we have confirmed that a specific humoral immune reactivity involves human atherosclerotic plaque. By isolating some of the autoantigens and employing them in prototype immunoassays, we have been able to measure for the presence of plaque-specific antibodies. Extracted plaque antigens have also served as immunogens in monoclonal antibody generation. These have shown early promise as plaque-directed in vivo targeting agents. Further scientific evaluation and reagent development remains before the practical utility of employing such reagents or methods in the care of patients with atherosclerosis-related diseases can be ascertained.

Effect of cranial irradiation on hypothalamus-pituitary function: follow-up study one year after radiotherapy.

Hypothalamic pituitary functions were studied in 24 patients before, 6 months after and 1 year after cranial irradiation with or without radiosensitizing chemotherapy for nasopharyngeal carcinoma (NPC). The estimated average total dose was 5,000 cGy to the hypothalamus and pituitary gland. The radiosensitizing chemotherapy used was endoxan, 4,900 +/- 873 mg (mean +/- SD) and/or methotrexate, 113 +/- 30 mg. All patients had normal pituitary function before radiotherapy. There was a progressive increase in baseline serum thyrotropin (TSH) after radiotherapy. The basal serum follicle stimulating hormone (FSH) was significantly increased 6 months after radiotherapy and remained so at 1 year after radiotherapy. The TSH response to thyrotropin-releasing hormone (TRH) also progressively increased after radiotherapy, suggesting primary hypothyroidism due to neck irradiation. The peak serum TSH response to TRH became delayed after radiotherapy, suggesting a defect in TRH release. In male patients who did not receive chemotherapy, the LH response to luteinizing hormone-releasing hormone (LHRH) decreased after radiotherapy. After an initial rise in the FSH response to LHRH 6 months after radiotherapy, there was a reduction in the FSH response at 1 year. This suggests a defect in LHRH pulsatile release. However, in male patients who received radiosensitizing chemotherapy, both the FSH and LH responses to LHRH had declined at 1 year after radiotherapy, as compared with their responses at 6 months. However, these were still higher than those obtained before radiotherapy. This suggests further GnRH neuron damage, which was previously masked by chemotherapy-induced primary hypogonadism. The adrenocorticotropic hormone (ACTH) response to ovine corticotropin-releasing hormone (CRH) had not changed further at 1 year after radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Idiopathic hypothalamic hypogonadism with polyostotic fibrous dysplasia: report of a case.

A 48-year-old man with Albright's syndrome and hypogonadism is presented. Eunuchoid status, hypogenitalia and hypogonadotropinemia were associated with pathological fracture and deformity of bones. GnRH test revealed minimal LH response and delayed FSH peak. After pulsatile GnRH priming, the LH response to GnRH increased. Results of other provocative hypothalamic-pituitary tests were consistent with hypothalamic lesions. To the best of our knowledge, this is the first report of a male patient with Albright's syndrome and idiopathic hypothalamic hypogonadism. The hypothesis of endocrinopathy and its relation to other components of this syndrome were reviewed.

Sonographic presentation in autoimmune thyroiditis.

We used real-time ultrasonography to examine 60 patients with autoimmune thyroiditis, then correlated the ultrasonic pictures with thyroid function, thyroid autoantibodies and fine needle aspiration cytology. In these 60 patients, 45 (75%) showed diffuse goiter, 6 (10%) showed multinodular goiter, and 9 (15%) had a solitary thyroid nodule sonographically. One of the 9 patients with a solitary nodule was a case of autoimmune thyroiditis combined with papillary carcinoma. The echogenicity of the thyroid was more than, the same as, or less than that of the adjacent muscles in 17, 22, and 21 patients, respectively. The groups were classified as hyperechoic, isoechoic, and hypoechoic, respectively. The mean serum T4 level was significantly lower in the hypoechoic group than in the hyperechoic or isoechoic groups (p less than 0.01 and p less than 0.05, respectively), and the incidence of hypothyroidism was significantly higher in the hypoechoic group than in the hyperechoic or isoechoic groups (p less than 0.001 and p less than 0.005, respectively). In addition, high titers of the antithyroid microsomal antibody (greater than or equal to 1280) were present more frequently in the hypoechoic group than in the hyperechoic or isoechoic groups (p less than 0.01 and p less than 0.05, respectively). There was no significant correlation between the cytomorphology and echogenicity of the thyroid in these cases. We conclude that sonography has two major uses in evaluating autoimmune thyroiditis: First, it is useful in excluding the coexistence of thyroid nodules; and second, marked hypoechogenicity of the thyroid implies an active cytotoxic autoimmune process and possibly a hypothyroid state.

Albright's syndrome with acromegaly and Hashimoto's thyroiditis: report of a case.

The case of a 35-year-old woman with Albright's syndrome, acromegaly and Hashimoto's thyroiditis is presented. She had noted deformity of the left mandible and chest from childhood. She developed persistent galactorrhea and amenorrhea after the delivery of her second child. X ray of the skull, and a head CT, revealed a pituitary tumor and fibrous dysplasia of the left mandible, sphenoid, zygomatic bone and pteryoid plate. Serum GH and PRL levels were markedly elevated. She received recontouring surgery of the left mandible, and a pathological examination confirmed the diagnosis of fibrous dysplasia. Chest X ray also showed fibrous dysplastic change of the left 4th, 5th, 6th and 7th ribs and left clavicle. Because of poor response to bromocriptine, she received a craniotomy to remove the pituitary macroadenoma. Pathological examination of the tumor revealed an acidophilic tumor. Postoperative radiotherapy was given for residual active tumor. She developed adrenal crisis two months after radiotherapy when she discontinued replacement therapy. The diagnosis of Hashimoto's thyroiditis was arrived at by palpation of the goiter, elevated thyroid antibodies, ultrasound pictures of the thyroid, fine needle aspiration cytology and hypothyroidism. To our knowledge, this is the first report of Albright's syndrome with Hashimoto's thyroiditis. The hypothesis of autoimmune disease is proposed to explain the hypofunction of the endocrine glands associated with Albright's syndrome.

Clinical experience of octreotide in the treatment of acromegaly.

To evaluate the efficacy and safety of octreotide (a somatostatin analogue) in the treatment of acromegaly, 10 patients were injected subcutaneously with octreotide, 50 micrograms, thrice daily before each meal for two days, followed by 100 micrograms thrice daily for six months. One case dropped out at the initial stage because of diarrhea, and another quit due to a lack of improvement in headaches after treatment for three months. Eight patients completed the study. The results showed that the circumference of the fourth finger and hand volume significantly decreased after treatment. Laboratory data demonstrated that serum growth hormone (GH) and somatomedin-C levels also decreased significantly. However, in six patients without a history of trans-sphenoidal adenomectomy, the serum GH and somatomedin-C levels returned to normal in only one case who had a serum GH level < 20 mU/L before treatment. In the oral glucose tolerance test, paradoxic elevation of GH subsided after treatment. In the TRH test, paradoxic elevation of GH improved after treatment. In the bromocriptine test, octreotide had a synergistic effect on the suppression of GH. All cases had the side effect of injection pain, especially at the initial stage. An increase in intestinal peristalsis and bowel movement occurred in the first week, but symptoms later subsided. Two out of these eight patients had gallbladder sludge after six months of treatment. In conclusion, octreotide is effective in the treatment of acromegaly; however, it is better used in patients who have serum GH levels < 20 mU/L, or after a trans-sphenoidal adenomectomy, and may be combined with bromocriptine to treat the patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased bone mineral density in patients with prolonged thyrotoxicosis before and after treatment.

To investigate the effects of prolonged thyrotoxicosis, we measured the bone mineral densities (BMD) of 24 untreated patients who had suffered from symptoms of thyrotoxicosis for at least 1 year. We also recruited 116 healthy Chinese women residing in the Taipei area as normal controls. The BMDs of these 24 patients for the whole body skeleton, lumbar spine, femoral neck, greater trochanter and Ward's triangle were all significantly lower than those of normal controls (one sample t-test, two-tailed alternative). Older patients had lower absolute values and a trend towards more severe bone loss, which was most significant at the femoral trochanter and Ward's triangle (p less than or equal to 0.05). The decrease in BMD was more pronounced in the vertebral bodies than in the proximal femur for all patients, implying predominantly trabecular bone loss in this disease. The BMDs of 10 patients were reevaluated 1 year after successful medical treatment. These 10 patients had remained euthyroid for 1 year with antithyroid drugs and showed a small, but significant, improvement in their BMDs at the lumbar spine and the proximal femur on reevaluation. However, the recovery was far from complete. Our findings suggest that thyrotoxicosis causes a remarkable loss of bone mineral, which cannot be compensated for after 1 year of successful treatment. Thus, early diagnosis and therapeutic intervention are important for preventing osteoporotic fractures, especially in elderly patients.

Thyroid cancer after irradiation.

Nine patients with thyroid cancer who had received irradiation on the thyroid region (four for breast cancer with deep x-ray or Co60, one for a skin lesion with deep x-ray and four for hyperthyroidism with I131) have been discussed. These cases might be within the range of statistical coicidence, but the potential carcinogenic effect of irradiation could not be ruled out completely. The need for detailed examination of the thyroid gland before and for many years after irradiation and early removal of thyroid gland nodules which develop after I131 treatment are emphasized.