Association Between TP53 Mutation and Prognosis in Wilms Tumor: A Meta-Analysis.

BackgroundTP53 mutation has been suggested to have prognostic value for patients with Wilms tumor (WT), but the results are still controversial. Methods: Relevant studies published until August 1, 2019 were identified by searching PubMed, EMBASE and Cochrane Library. A random-effect model was performed to assess pooled data. Begg's and Egger's test were used to evaluate the potential publication bias. Sensitivity analysis was used to evaluate the stability of results. Results: A total of seven eligible articles were included. There was no significant difference in the risk of death among patients with WT with different TP53 mutation status (odds ratio [OR] = 3.09, 95% confidence interval[CI]: 0.81-11.84). Combined hazard ratio (HR) suggested that TP53 mutation had an unfavorable impact on overall survival (OS) (HR = 4.17, 95% CI: 1.97-6.36) and disease-free survival (DFS) (HR = 2.23, 95% CI: 1.29-3.17) in WT. Conclusions: This meta-analysis demonstrates that TP53 mutations are associated with poorer prognosis in WT.

Celastrol inhibits colorectal cancer cell proliferation and migration through suppression of MMP3 and MMP7 by the PI3K/AKT signaling pathway.

Colorectal cancer (CRC) is one of the most frequent malignant tumors. Signaling by the PI3K/AKT pathway is crucial for CRC development and progression, including proliferation and migration. Celastrol has an anticancer effect, but its mechanism needs to be determined. Here, we showed that celastrol suppressed CRC cell proliferation and migration. Celastrol treatment also decreased the PI3K/AKT pathway components, and MMP3 and MMP7 expression levels. In addition, knockdown of AKT, not mTOR, inhibited MMP3 and MMP7 expression levels and AKT silencing promoted the celastrol-induced effects on CRC cell proliferation and migration. Taken together, these findings indicated that the celastrol-induced antitumor effects were mediated through MMP3 and MMP7 by the PI3K/AKT signaling pathway.

Effects of azimuthal angles on laser interference lithography.

This paper discusses the effects of azimuthal angles on two-, three-, and four-beam laser interference. In two- or three-beam laser interference, periodic surface structures of lines or dots were obtained. In four-beam laser interference with the polarization mode of TE-TM-TE-TM, the modulation in a particular direction was formed and calculated. In the work, a He-Ne laser system was used to simulate two-, three-, and four-beam laser interference, and the interference pattern was detected by a CCD. A high-power Nd:YAG laser interference lithography system was set up to pattern silicon wafers. In the experiments, one azimuthal angle was changed every time to form interference patterns when polarization states were fixed and incident angles were equal. The experimental results have shown that the azimuthal angle affects the periods and feature sizes of the interference patterns and the fabricated surface structures, which are in accordance with the theoretical and computer simulation results.

Fano resonance of nanoparticles embedded in Fabry-Perot cavities.

We present an optical structure, which consists of metal nanoparticles embedded in Fabry-Perot (F-P) cavity, to investigate the Fano resonance, which originates from the interaction between F-P mode and the plasmon modes supported by the nanoparticles. The coupling system is modeled theoretically by coupled-mode theory in time domain and the transmission properties are demonstrated numerically by the finite-difference time-domain method. The charge distribution features of the nanoparticle plasmon modes are further characterized by using boundary integral equation technology. Results show that the F-P modes can be used to active the optical inactive surface plasmon modes by breaking the mode symmetry.

Quantum dot-based immunochromatography test strip for rapid detection of Campylobacter jejuni.

Campylobacter jejuni is a recognized human foodborne pathogen which is one of the leading causes of human gastrointestinal enteritis worldwide. In stress conditions, C. jejuni is able to enter into a viable but non-culturable state that is difficult to diagnose. Hence a rapid, sensitive, and specific method is required to monitor food and water for natural or intentional contamination by this pathogen. We report a quantum dot (QD)-based immunochromatography test strip (QDITS) for rapid detection of C. jejuni. The QDITS is based on a sandwich type immunoassay with QD fluorescence for sensitive detection. Under optimized conditions, this QD-based fluorescence biosensor exhibits detection of 10(4) CFU/ml in pure culture of C. jejuni which is 10 times more sensitive than colloidal-gold ITS. The improved sensitivity is attributed to the high quantum yield and brightness of the photostable QDs. When the QDITS were tested in 206 chicken samples and 120 beef samples, this exhibited a specificity of 98.5% and 99.1% respectively. On these real samples, the sensitivity of the QDITS was 100% in agreement with traditional culture method. The QDITS that took only 10 minutes to complete hold promise for rapid, sensitive detection of C. jejuni in real samples without the need for sample preparations steps.

Speciation of organic phosphorus in a sediment profile of Lake Taihu. II. Molecular species and their depth attenuation.

The understanding of organic phosphorus (P) dynamics in sediments requires information on their species at the molecular level, but such information in sediment profiles is scarce. A sediment profile was selected from a large eutrophic lake, Lake Taihu (China), and organic P species in the sediments were detected using solution phosphorus-31 nuclear magnetic resonance spectroscopy (31P NMR) following extraction of the sediments with a mixture of 0.25 mol/L NaOH and 50 mmol/L EDTA (NaOH-EDTA) solution. The results showed that P in the NaOH-EDTA extracts was mainly composed of orthophosphate, orthophosphate monoesters, phospholipids, DNA, and pyrophosphate. Concentrations of the major organic P compound groups and pyrophosphate showed a decreasing trend with the increase of depth. Their half-life times varied from 3 to 27 years, following the order of orthophosphate monoesters > phospholipids > or = DNA > pyrophosphate. Principal component analysis revealed that the detected organic P species had binding phases similar to those of humic acid-associated organic P (NaOH-NRP(HA)), a labile organic P pool that tends to transform to recalcitrant organic P pools as the early diagenetic processes proceed. This demonstrated that the depth attenuation of the organic P species could be partly attributed to their increasing immobilization by the sediment solids, while their degradation rates should be significantly lower than what were suggested in previous studies.

A Nomogram and Risk Classification System Predicting the Prognosis of Patients with De Novo Metastatic Breast Cancer Undergoing Immediate Breast Reconstruction: A Surveillance, Epidemiology, and End Results Population-Based Study.

Background The lifespan of patients diagnosed with de novo metastatic breast cancer (dnMBC) has been prolonged. Nonetheless, there remains substantial debate regarding immediate breast reconstruction (IBR) for this particular subgroup of patients. The aim of this study was to construct a nomogram predicting the breast cancer-specific survival (BCSS) of dnMBC patients who underwent IBR. Methods A total of 682 patients initially diagnosed with metastatic breast cancer (MBC) between 2010 and 2018 in the Surveillance, Epidemiology, and End Results (SEER) database were included in this study. All patients were randomly allocated into training and validation groups at a ratio of 7:3. Univariate Cox hazard regression, least absolute shrinkage and selection operator (LASSO), and best subset regression (BSR) were used for initial variable selection, followed by a backward stepwise multivariate Cox regression to identify prognostic factors and construct a nomogram. Following the validation of the nomogram with concordance indexes (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCAs), risk stratifications were established. Results Age, marital status, T stage, N stage, breast subtype, bone metastasis, brain metastasis, liver metastasis, lung metastasis, radiotherapy, and chemotherapy were independent prognostic factors for BCSS. The C-indexes were 0.707 [95% confidence interval (CI), 0.666-0.748] in the training group and 0.702 (95% CI, 0.639-0.765) in the validation group. In the training group, the AUCs for BCSS were 0.857 (95% CI, 0.770-0.943), 0.747 (95% CI, 0.689-0.804), and 0.700 (95% CI, 0.643-0.757) at 1 year, 3 years, and 5 years, respectively, while in the validation group, the AUCs were 0.840 (95% CI, 0.733-0.947), 0.763 (95% CI, 0.677-0.849), and 0.709 (95% CI, 0.623-0.795) for the same time points. The calibration curves for BCSS probability prediction demonstrated excellent consistency. The DCA curves exhibited strong discrimination power and yielded substantial net benefits. Conclusions The nomogram, constructed based on prognostic risk factors, has the ability to provide personalized predictions for BCSS in dnMBC patients undergoing IBR and serve as a valuable reference for clinical decision making.

The autophagy-senescence connection in chemotherapy: must tumor cells (self) eat before they sleep?

Exposure of MCF-7 breast tumor cells or HCT-116 colon carcinoma cells to clinically relevant concentrations of doxorubicin (Adriamycin; Farmitalia Research Laboratories, Milan, Italy) or camptothecin results in both autophagy and senescence. To determine whether autophagy is required for chemotherapy-induced senescence, reactive oxygen generation induced by Adriamycin was suppressed by N-acetyl cysteine and glutathione, and the induction of ataxia telangiectasia mutated, p53, and p21 was modulated pharmacologically and/or genetically. In all cases, autophagy and senescence were collaterally suppressed. The close association between autophagy and senescence indicated by these experiments reflects their collateral regulation via common signaling pathways. The potential relationship between autophagy and senescence was further examined through pharmacologic inhibition of autophagy with chloroquine and 3-methyl-adenine and genetic ablation of the autophagy-related genes ATG5 and ATG7. However, inhibition of autophagy by pharmacological and genetic approaches could not entirely abrogate the senescence response, which was only reduced and/or delayed. Taken together, our findings suggest that autophagy and senescence tend to occur in parallel, and furthermore that autophagy accelerates the development of the senescent phenotype. However, these responses are not inexorably linked or interdependent, as senescence can occur when autophagy is abrogated.

Coupled-resonator-induced transparency in photonic crystal waveguide resonator systems.

We present an optical coupling system, which consists of waveguide, cavity and waveguide resonator, to investigate coupled-resonator-induced transparency effect. The transmission properties are analyzed theoretically by using coupled-mode theory in time domain. We also numerically demonstrate the effect by simulating the propagation of electromagnetic waves in photonic crystals by finite-difference time-domain method.

Expression of P-450(c11beta) in adrenal aldosterone-producing adenomas and nodular hyperplasia tissues.

BACKGROUND: Our previous study suggests that decreased P-450(c17alpha) expression correlated with the overproduction of aldosterone in APA and nodular hyperplasia in patients with primary aldosteronism. This study was performed to further investigate if P-450(c11beta) contributes to the overproduction of aldosterone in APA and nodular hyperplasia tissues. METHODS: Total RNA and protein were extracted from 7 cases of APA tissue, 3 nodular hyperplasia tissues, 7 normal adrenal glands. P-450(c11beta) mRNA was examined by dot blot and confirmed by Northern blot analysis and by realtime PCR. Protein expression level of P-450(c11beta) was also investigated by immunohistochemical staining and confirmed by Western blot. RESULTS: The relative expression level of P-450(c11beta) mRNA to beta-actin in APA, nodular hyperplasia and the normal adrenal gland group are 47 +/- 22%, 55 +/- 13%, 64 +/- 16% respectively by dot blot and are 94 +/- 18%, 101 +/- 20%, 112 +/- 62% respectively by Northern blot. These results are further confirmed by realtime PCR. This result was also supported by the relative protein expression level of P-450(c11beta) to beta-actin which are 118 +/- 15%, 107 +/- 32%, 108 +/- 22% respectively evaluated by Western blot. There was no significant difference in protein expression level of P-450(c11beta) among the normal adrenal gland tissues, APA and adrenal nodular hyperplasia tissue, either (P > 0.05). CONCLUSIONS: These results suggest that P-450(c11beta) is not a key contributor to the overproduction of aldosterone in APA and nodular hyperplasia and can not be considered as a potential marker to differentiate between them in patients with primary aldosteronism.

Mst2 Overexpression Inhibits Thyroid Carcinoma Growth and Metastasis by Disrupting Mitochondrial Fitness and Endoplasmic Reticulum Homeostasis.

Although the incidence of thyroid carcinoma has increased over the past several decades, it has an excellent prognosis and overall 5-year survival, with a stable mortality rate, except in cases with advanced stages or rare malignant tumor types. Biomarkers have emerged as effective targets of molecular therapy against thyroid carcinoma due to their rapid and convenient detection; however, there has been little clinical application. Macrophage stimulating 2 (Mst2) is a proapoptotic protein with implications in carcinogenesis and metastasis. We found that Mst2 overexpression-induced endoplasmic reticulum (ER) stress in MDA-T32 thyroid carcinoma cells, accompanied by elevated caspase-12 activity, increased apoptotic rate, and reduced cell viability. In addition, Mst2 overexpression contributed to mitochondrial damage, as evidenced by increased mitochondrial oxidative stress and activated the mitochondrial apoptotic pathway. Inhibition of the JNK pathway abolished these effects. These results show Mst2 to be a novel tumor suppressor that induces mitochondrial dysfunction and ER stress via the JNK pathway. Thus, Mst2 could potentially serve as a biomarker for developing targeted therapy against thyroid carcinoma.

Influence of the phosphodiesterase-5 inhibitor, sildenafil, on sensitivity to chemotherapy in breast tumor cells.

Studies were performed to determine the influence of the phosphodiesterase-5 inhibitor, sildenafil, on sensitivity to adriamycin (doxorubicin) in four human breast tumor cell lines and one murine breast tumor line. Sildenafil did not interfere with the effectiveness of adriamycin in any of the cell lines tested. Sildenafil also failed to protect MDA-MB231 cells against the cytotoxicity of cisplatin, taxol or camptothecin. Sildenafil enhanced sensitivity to adriamycin markedly in the p53 mutant MDA-MB231 and p53 null MCF-7/E6 cells and moderately in the MCF-7/caspase 3 and 4T1 cell lines. In the MDA-MB231 cells, sildenafil increased the extent of DNA damage induced by adriamycin as well as the extent of apoptotic cell death. Sildenafil did not influence sensitivity to adriamycin in bone marrow cells or macrophages. In an immunocompetent model of breast cancer (4T1 mammary carcinoma in Balb/c mice), sildenafil did not attenuate the antitumor effects of adriamycin; furthermore, the combination of sildenafil with adriamycin was no more toxic to the animals than adriamycin alone. Given that sildenafil has been shown to have the potential to protect the heart against the toxicity of adriamycin, these studies suggest that the inclusion of sildenafil with conventional chemotherapeutic protocols involving adriamycin (and possibly cisplatin, camptothecin and/or paclitaxel) should not compromise the antitumor effectiveness of these drugs nor enhance their toxicity to the patient.

FDA Approval Summary: Calaspargase Pegol-mknl For Treatment of Acute Lymphoblastic Leukemia in Children and Young Adults.

On December 20, 2018, the Food and Drug Administration approved calaspargase pegol-mknl (CALASP), an asparagine-specific enzyme, as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) in pediatric and young adult patients age 1 month to 21 years. Efficacy was determined on the basis of achievement and maintenance of steady-state nadir serum asparaginase activity (NSAA) above 0.1 U/mL when using CALASP, 2,500 U/m2 intravenously, every 3 weeks. In a randomized comparison to pegaspargase (PEGASP) every 2 weeks, treatment with CALASP every 3 weeks had a similar safety profile and no substantial impairment in event-free survival. The pharmacokinetics of CALASP were studied when administered in combination with multiagent chemotherapy in 124 patients with B-cell ALL in Study AALL07P4 and Study DFCI 11-001. The results showed that 123 [99%, 95% confidence interval (CI), 96%-100%] of the 124 patients maintained NSAA >0.1 U/mL at weeks 6, 12, 18, 24, and 30 of post-induction phase. Maintaining adequate NSAA levels is critical to successful treatment of ALL. Herein, we describe the FDA review and approval of CALASP.See related commentary by Lew, p. 325.

Downregulation of Long Noncoding RNA HOTAIR and EZH2 Induces Apoptosis and Inhibits Proliferation, Invasion, and Migration of Human Breast Cancer Cells.

BACKGROUND: The long noncoding RNA HOTAIR (HOX transcript antisense intergenic RNA) has been reported to be a biomarker for various malignant tumors; however, its involvement in breast cancer is not fully understood. The aim of this study was to investigate the effects involved with long noncoding RNA HOTAIR and EZH2 (enhancer of zeste homologue 2) on the processes of proliferation, invasion, migration, and apoptosis of breast cancer cells. MATERIALS AND METHODS: The expressions of HOTAIR and EZH2 in both normal human mammary epithelial cell (HBL-100) and breast cancer cell lines (MCF-7, MDA-MB-231, and SKBR-3) were detected by means of reverse transcription-quantitative polymerase chain reaction. The MCF-7 cells that exhibited the highest HOTAIR expressions were selected for further studies and divided into the control, negative control, and small interfering RNA-HOTAIR groups. The proliferation, invasion, migration, and apoptosis of breast cancer cells were evaluated by MTT assay, Scratch test, Transwell assay, and flow cytometry, respectively. The combination of HOTAIR with EZH2 and PTEN was predicted by bioinformation, with a dual-luciferase reporter gene assay providing further verification. RESULTS: Initially, lower expressions of HOTAIR and EZH2 in the normal human mammary epithelial cells, while higher expressions in the breast cancer cells of MCF-7, MDA-MB-231, and SKBR-3 were detected. In addition, the downregulation of HOTAIR or silencing of EZH2 was revealed to repress the proliferation, invasion, and migration, while acting to promote the apoptosis of the breast cancer cells. Furthermore, HOTAIR could bind specifically to EZH2 and PTEN, highlighting the capability of HOTAIR to inhibit the expression of PTEN by recruiting EZH2 in breast cancer, while the TCGA database demonstrated the expressions of PTEN were lower in breast cancer cells. CONCLUSIONS: The study suggests the higher expressions of HOTAIR and EZH2 among three breast cancer cells. Furthermore, the downregulation of HOTAIR or silencing of EZH2 was noted to inhibit the proliferation, invasion, and migration of breast cancer cells, while promoting their apoptosis.

Jujubae Fructus alleviates intestinal injury caused by toxic medicinals in Shizao Decoction based on correlation between intestinal flora and host metabolism / 中国中药杂志

Genkwa Fols, Kansui Radix, and Euphorbiae Pekinensis Radix in Shizao Decoction(SZD) are toxic to intestinal tract. Jujubae Fructus in this prescription can alleviate the toxicity, but the mechanism is still unclear. Therefore, this study aims to explore the mechanism. To be specific, 40 normal Sprague-Dawley(SD) rats were classified into the normal group, high-dose and low-dose SZD groups, and high-dose and low-dose SZD without Jujubae Fructus(SZD-JF) groups. The SZD groups were given(ig) SZD, while SZD-JF groups received the decoction without Jujubae Fructus. The variation of body weight and spleen index were recorded. The patho-logical changes of intestinal tissue were observed based on hematoxylin and eosin(HE) staining. The content of malondialdehyde(MDA) and glutathione(GSH) and activity of superoxide dismutase(SOD) in intestinal tissue were measured to evaluate the intestinal injury. Fresh feces of rats were collected to detect intestinal flora structure by 16S ribosomal RNA gene(16S rDNA) sequencing technology. The content of fecal short chain fatty acids and fecal metabolites was determined by gas chromatography-mass spectrometer(GC-MS) and liquid chromatography-mass spectrometer ultra-fast liquid chromatography-quadrupole-time-of-flight mass spectrometer(UFLC-Q-TOF-MS), separately. Spearman's correlation analysis was employed to analyze the differential bacteria genera and differential metabolites. RESULTS:: showed that high-dose and low-dose SZD-JF groups had high content of MDA in intestinal tissue, low GSH content and SOD activity, short intestinal villi(P<0.05), low diversity and abundance of intestinal flora, variation in the intestinal flora structure, and low content of short chain fatty acids(P<0.05) compared with the normal group. Compared with high-dose and low-dose SZD-JF groups, high-dose and low-dose SZD groups displayed low content of MDA in intestinal tissue, high GSH content and SOD activity, recovery of the length of intestinal villi, increased abundance and diversity of intestinal flora, alleviation of dysbacteria, and recovery of the content of short chain fatty acids(P<0.05). According to the variation of intestinal flora and fecal metabolites after the addition of Jujubae Fructus, 6 differential bacterial genera(Lactobacillus, Butyricimonas, Clostridia＿UCG-014, Prevotella, Escherichia-Shigella, Alistipes),4 differential short chain fatty acids(such as acetic acid, propionic acid, butyric acid, valeric acid) and 18 differential metabolites(such as urolithin A, lithocholic acid, and creatinine) were screened out. Beneficial bacteria such as Lactobacillus were in positive correlation with butyric acid and urolithin A(P<0.05). The pathogenic bacteria such as Escherichia-Shigella were in negative correlation with propionic acid and urolithin A(P<0.05). In summary, SZD-JF caused obvious intestinal injury to normal rats, which could lead to intestinal flora disorder. The addition of Jujubae Fructus can alleviate the disorder and relieve the injury by regulating intestinal flora and the metabolites. This study discusses the effect of Jujubae Fructus in relieving the intestinal injury caused by SZD and the mechanism from the perspective of intestinal flora-host metabolism, which is expected to serve as a reference for clinical application of this prescription.

The research on the efficiency of single-port plus-one robot-assisted pyeloplasty for children with UPJO / 中华泌尿外科杂志

Objective:To investigate the effect of Da Vinci robot-assisted single-port plus-one laparoscopic pyeloplasty (RSPY) in children with ureteropelvic junction obstruction (UPJO).Methods:The clinical data of 13 children with UPJO diagnosed by robot-assisted single-port plus-one laparoscopic pyeloplasty in Fujian Provincial Hospital from September 2021 to August 2022 were retrospectively analyzed. The mean age of the children was 60.0 (1.3, 108.0) months. The lesions of 10 patients were on the left, and 3 were on the right. The clinical manifestations were abdominal pain in 3 cases, urinary tract infection in 2 cases, and no symptoms in 10 cases. Preoperative isotope renogram showed affected renal function (28.32±1.82)%, and bilateral renal function difference > 10% in 7 cases. Mechanical obstruction existed in 5 cases. Preoperative ultrasound showed the affected side's renal cortex thickness of (1.98 ± 0.23) cm. During the operation, a single-port multi-channel trocar was placed in the umbilicus with another single port in the epigastrium, and a robotic system was placed to explore the subperitoneal dilated renal pelvis. The renal pelvis was suspended and pulled through the abdominal wall. The visual field was exposed, and the dilated renal pelvis was incised. The dilated renal pelvis was cut, a ureteral stent was placed, and the ureteropelvic duct was anastomosed.Results:The operation of 13 cases was successfully completed, without conversion to open surgery. The operation time was 180.0(165.0, 190.2)min. The intraoperative blood loss was < 5 ml. The postoperative hospital stay was 7.0(7.0, 7.0)d, and hospitalization costs were 56.3(52.1, 56.5)thousand yuan. The ureteral stent was removed 2 months after the operation, and no obvious complications such as urinary tract infection or low back pain occurred. The median postoperative follow-up was 12 months, ranged from 6 to 18 months. Urinary color ultrasound showed that the renal cortex was (4.95±0.57) cm, which was thicker than before. Isotope renogram showed that the renal function was (38.02±1.76)%, which was higher than before. Mechanical obstruction was transformed into incomplete obstruction.Conclusions:Da Vinci robot-assisted single-port plus-one laparoscopic pyeloplasty is precise and could achieve good surgical results on the basis of the effective restoration of lesion kidney function.

Effect of acupuncture at neck-Jiaji (EX-B 2) and tuina on the cognitive function in the patients with subjective cognitive decline / 中国针灸

OBJECTIVES@#To observe the effects on cognitive function, sleep quality and hemodynamics in the patients with subjective cognitive decline (SCD) after treated with acupuncture at neck-Jiaji (EX-B 2) and tuina on the base of healthy lifestyle education and meta-memory training.@*METHODS@#Sixty SCD patients were randomly divided into an observation group (30 cases, 1 case dropped out) and a control group (30 cases, 3 cases dropped out). In the control group, the healthy lifestyle education and meta-memory training was performed, twice daily, 15 min each time; the 5-day intervention was delivered a week, lasting consecutively 4 weeks. On the base of the intervention as the control group, in the observation group, acupuncture at neck-Jiaji (EX-B 2) and tuina was conducted. First, one-finger pushing and plucking method of tuina was exerted on the neck region along the running courses of the bladder meridian of foot-taiyang and the governor vessel, for 10 min to 15 min; afterwards, acupuncture was delivered at bilateral neck-Jiaji (EX-B 2), from C1 to C7; and the needles were retained for 30 min. This intervention was given once daily, 5 times a week, for consecutive 4 weeks. Before and after treatment, the score of the mini-mental state examination (MMSE), the score of full scale memory quotient (FSMQ) were assessed by Wechsler memory scale-fourth edition (WMS-Ⅳ) and the score of the Pittsburgh sleep quality index (PSQI) was compared between the two groups. Using transcranial Doppler ultrasound, the hemodynamic indexes (the mean velocity [Vm] and pulsatility index [PI] of the left vertebral artery [LVA], the right vertebral artery [RVA] and the basilar artery [BA]) were determined in the two groups.@*RESULTS@#After treatment, the scores of MMSE and FSMQ increased compared with those before treatment in the two groups (P<0.05, P<0.001), PSQI score was lower (P<0.05) and Vm of BA was higher (P<0.001) in the observation group when compared with those before treatment. The scores of MMSE and FSMQ, as well as Vm of BA were higher (P<0.05, P<0.001), and PSQI score was decreased (P<0.05) in the observation group when compared with the control group.@*CONCLUSIONS@#The combined therapy of acupuncture at neck-Jiaji (EX-B 2) and tuina is more advantageous to improving cognitive function, relieving chronic emotional stress and ameliorating sleeping quality in the patients with subjective cognitive decline, which may be achieved by improving the blood supply of the basilar artery.

Clinicopathological features of gastric carcinomas with NTRK-rearrangement/amplification: report of four cases / 中华病理学杂志

Objective: To investigate the clinicopathological, immunohistochemical and molecular genetic characteristics of gastric carcinoma with NTRK-rearrangement/amplification. Methods: The clinicopathological data of gastric carcinoma cases with NTRK-rearrangement/amplification diagnosed from January 2011 to September 2020 at the Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, China, were collected. The clinicopathological, immunophenotypic and molecular pathological features were analyzed. The relevant literature was reviewed. Results: There were 4 cases of gastric carcinoma with NTRK-rearrangement/amplification. All 4 patients were male, aged 57-67 years (average, 63 years). Tumor sizes ranged from 3.5 to 5.2 cm (average, 4.8 cm). All tumors were in the antrum. All 4 patients underwent radical gastrectomy and were followed up after the surgery. Morphologically, all tumors showed histological features with enteroblastic-differentiated gastric carcinoma. Tumor cells showed predominantly tubular/papillary architecture, with conspicuous vesicular nuclei and pale staining or transparent cytoplasm. Immunohistochemistry showed pan-TRK expression in all cases, with various degrees of positivity in the cytoplasm. All cases were subject to NTRK1/2/3 detection using fluorescence in situ hybridization. There were NTRK translocations in 2 cases and NTRK amplifications in 2 cases. These cases were further verified by RNAseq next generation sequencing which confirmed that NTRK1 gene translocation (TPM3-NTRK1) and NTRK2 gene translocation (NTRK2-SMCHD1) occurred in two cases, respectively. Conclusions: NTRK mutation occurs less frequently in gastric cancer. In this study, the cases mainly occur in the antrum. The morphology has the characteristics of enteroblastic differentiation. The tumors have unique histological, immunophenotypic and molecular characteristics, which require much attention from pathologists to effectively guide clinicians to choose the best treatment.

Effect and mechanism investigation on improving kidney deficient in mice of Polygoni Multiflori Radix Praeparata based on plasma metabolomics / 药学学报

Plasma nontargeted metabolomics technology was developed for investigating the effect and mechanism of improving kidney deficient in mice of Polygoni Multiflori Radix Praeparata. Thirty-five ICR mice were randomly divided into the control group, the model group, the BB24 h (braising with black bean sauce for 24 hours) group, the BB32 h group, and the BB40 h group. Biochemical indices in blood plasma of mice were measured by collecting eye blood after modeling. Changes in plasma endogenous metabolites of mice from each group were determined by ultra-performance liquid chromatography-linear trap quadrupole-orbitrap XL (UPLC-LTQ-orbitrap XL), and differential metabolites were screened. The results of pharmacodynamic investigation showed that compared to the model group, the levels of estradiol increased obviously in the BB24 h (P < 0.05), and the levels of cortisol increased obviously in BB32 h (P < 0.05). The hormone level of mice with kidney deficiency was significantly improved after taking processed Polygonum multiflorum. A total of 70 differential endogenous metabolites in blood plasma of mice were identified from all treatment groups, which mainly involved glycerophospholipid meta-bolism, arachidonic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and linoleic acid metabolism. The study indicated that Polygoni Multiflori Radix Praeparata may play the role of tonifying liver and kidney by improving the disorder of hypothalamic-pituitary-adrenal axis and regulating lipid metabolism in mice. Correlation analysis on differential metabolites in blood plasma and the chemical constituents showed that stilbene glycosides and saccharides may be the key pharmacodynamic material basis. The present study provides a new reference and theoretical foundation for revealing the potential pharmacodynamic material basis and mechanism investigation on tonifying liver and kidney of Polygoni Multiflori Radix Praeparata. This study was carried out following the ethical guidelines and regulations for the use of laboratory animals of the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences and passed the animal experimental ethical review [No. SYXK (Jing) 2019-0003].

Erythropoietin fails to interfere with the antiproliferative and cytotoxic effects of antitumor drugs.

PURPOSE: Erythropoietin (EPO) therapy is widely used for the prevention and treatment of anemia resulting from cancer chemotherapy. Native EPO regulates erythropoiesis, at least in part, by protecting erythroid progenitor cells from apoptotic cell death. The recent discovery of the EPO receptor (EPOR) on cancer cells raises the concern that EPO therapy might stimulate tumor growth and/or protect cancer cells from drug-induced apoptosis. Therefore, the capacity of EPO to interfere with the effects of conventional chemotherapeutic drugs on proliferation, apoptosis, and the induction of senescence was investigated in MCF-7 and MDA-MB231 breast tumor cells, which express the EPOR as well as in F-MEL erythroleukemia cells. EXPERIMENTAL DESIGN: Breast cancer cells and F-MEL leukemic cells were cultured in the presence or absence of EPO and then exposed to antitumor drugs. Cell proliferation was assessed by a standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye reduction assay 72 hours after drug exposure. Cytotoxicity was monitored by clonogenic survival. Apoptosis was evaluated either by the terminal deoxyribonucleotide transferase-mediated nick-end labeling assay or fluorescence-activated cell sorting analysis, and senescence was monitored by beta-galactosidase staining. EPO signaling was assessed by monitoring the phosphorylation/activation of specific signaling proteins. RESULTS: EPO failed to stimulate the proliferation of MCF-7 or MDA-MB231 breast tumor cells or F-MEL leukemic cells. EPO treatment also failed to interfere with the antiproliferative and/or cytotoxic effects of Adriamycin, Taxol, and tamoxifen in breast tumor cells (or of cytarabine and daunorubicin in F-MEL cells). EPO failed to prevent apoptosis induced by Taxol or senescence induced by Adriamycin in MCF-7 cells. EPO stimulated the activation of extracellular signal-regulated kinase, p38, and c-Jun-NH(2)-kinase in MCF-7 cells but did not activate Akt or signal transducers and activators of transcription 5 (STAT5). EPO failed to activate any of these signaling pathways in MDA-MB231 cells. Cytarabine and daunorubicin interfered with EPO signaling in F-MEL cells. CONCLUSIONS: These findings suggest that EPO is unlikely to directly counteract the effectiveness of cancer chemotherapeutic drugs. This may be a consequence of either ineffective signaling through the EPOR or drug-mediated suppression of EPO signaling.