[Porphyromonas gingivalis promotes the occurrence of esophageal squamous cell carcinoma via an inflammatory microenvironment].

Objective: To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis (P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods: A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 µg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results: At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P＜0.05) and mild/moderate dysplasia (median 2.00, P＜0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1ß [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm2), the thickness of the esophageal wall (median 172.52 µm), the foci of hyperproliferation (median 1.00, P＜0.05), and mild/moderate dysplasia (median 1.00, P＜0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1ß [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions: P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.

MRI parameters for predicting the effect of ultrasound-guided high-intensity focused ultrasound in the ablation of uterine fibroids.

AIM: To study the value of magnetic resonance imaging (MRI) parameters in predicting the efficacy of ultrasonic ablation of fibroids. MATERIALS AND METHODS: A total of 91 patients were divided into groups based on non-perfused volume (NPV) ratio and blood supply type. The preoperative MRI parameters were measured and analysed. A correlation analysis between the MRI parameters and the NPV ratio was performed. Receiver operating characteristic (ROC) curves were used to analyse and determine the cut-off value of MRI parameters to predict the ablation rate of fibroids. RESULTS: The uterine fibroids group with an NPV ratio <80% and the group with an NPV ratio of ≥80% had significant differences in signal intensity (SI) at MRI T2-weighted imaging (WI), fibroid-to-rectus abdominis SI ratio (SIR) at T2WI, and blood supply type (p<0.05). There were no significant differences in fibroid volume, T2WI signal uniformity, and apparent diffusion coefficient (ADC) values. The ADC value and SI and SIR at MRI T2WI in the group with poor blood supply were lower than those in the group with a rich blood supply (p<0.05). SI at MRI T2WI correlated negatively with the NPV ratio. The cut-off values for SI and SIR at MRI T2WI of fibroids whose NPV ratio exceeds 80% were 220.58 and 1.315, respectively. CONCLUSION: SI at MRI T2WI and blood supply type could be predictors of the efficacy of ablation. Ultrasonic ablation of fibroids with MRI T2WI hyperintensity and a rich blood supply had poor efficacy.

[Analysis of the difference in MGMT promoter status in gliomas and its significance in prognosis assessment].

The data of 1 268 newly diagnosed gliomas from the Fourth Ward of Neurosurgery Department of Beijing Tiantan Hospital between April 2013 and March 2022 were retrospectively analyzed. Based on postoperative pathology, the gliomas were divided into groups: oligodendrogliomas (n=308), astrocytomas (n=337) and glioblastomas (n=623). According to the O6-methylguanine-DNA methyl transferase (MGMT) promoter status defined by the 12% of best cut-off value in previous research results, patients were divided into methylation group (n=763) and non-methylation group (n=505). Methylation level [M (Q1, Q3)] in patients with glioblastoma, astrocytoma and oligodendroglioma was 6% (2%, 24%), 17% (10%, 28%) and 29% (19%, 40%), respectively (P<0.001). Compared with non-methylation patients, the progression-free survival (PFS) and overall survival (OS) of glioblastomas patients with methylation of MGMT promoter demonstrated more favorable prognosis [M (Q1, Q3)]) of PFS: 14.0 (6.0, 36.0) months vs 8.0 (4.0, 15.0) months, P<0.001; M (Q1, Q3) of OS: 29.0 (17.0, 60.5) months vs 16.0 (11.0, 26.5) months, P<0.001]. In astrocytomas patients, the PFS was much longer for those with methylation [the median PFS of patients with methylation was not observed at the end of follow-up, but those without methylation showed a median PFS of 46.0 (29.0, 52.0) months] (P=0.001). However, no statistically significant difference was observed in OS [the median OS of patients with methylation was not observed at the end of follow-up, but those without methylation had a median OS of 62.0 (46.0, 98.0) months] (P=0.085). In oligodendrogliomas patients, no statistically significant differences of PFS and OS were observed between patients with methylation and those without methylation. MGMT promoter status was a related factor affecting PFS and OS in glioblastomas (PFS: HR=0.534,95%CI: 0.426-0.668, P<0.001; OS: HR=0.451, 95%CI: 0.353-0.576, P<0.001). Moreover, MGMT promoter status was also a related factor affecting PFS in astrocytomas (HR=0.462, 95%CI: 0.221-0.966, P=0.040), but not for OS (HR=0.664, 95%CI: 0.259-1.690, P=0.389). The methylation level of MGMT promoter differed substantially in different types of gliomas, and the status of MGMT promoter profoundly affected the prognosis of glioblastomas.

[Clinical characteristics of 13 cases with entrapped temporal horn syndrome and efficacy of refined temporal-to-frontal horn shunt].

Thirteen consecutive patients with entrapped temporal horn syndrome in the Department of Neurosurgery of Beijing Tiantan Hospital from February 2018 to September 2022 were retrospectively analyzed, and there were 5 males and 8 females, with a mean age of (43±21) years. Increased intracranial pressure caused by hydrocephalus was the main clinical symptom. All the patients underwent refined temporal-to-frontal horn shunt, and all the symptoms were improved after surgery. Postoperative Karnofsky performance score (KPS) [90 (90, 100)] was higher than preoperative KPS [57 (40, 70)] (P=0.001). However, postoperative entrapped temporal horn volume [13.85 (8.90, 15.25) cm3] decreased, compared with preoperative volume [66.52 (38.65, 88.65) cm3] (P=0.001). Likewise, postoperative midline shift [0.77 (0, 1.50) mm] was longer than preoperative midline shift [6.69 (2.50, 10.00) mm] (P=0.002). No surgery-related complications were observed after the operation. Therefore, the refined temporal-to-frontal horn shunt is safe and effective treatment for entrapped temporal horn syndrome, with favorable outcomes.

[Research progress of ocular organoids].

The development of ocular organoids, which closely mimic the tissue structure and functionality of the human eye, has emerged as a prominent area of research in the field of ophthalmology. These organoids serve as valuable models for investigating the mechanisms and interventions of eye-related diseases. However, the establishment of in vitro models that accurately represent the tissue structure and functionality of the human eye has long been a challenge in ophthalmic research. Numerous efforts have been made to enhance the fidelity of ocular organoid models, aiming to improve their suitability for studying disease pathogenesis and drug efficacy. With advancements in technology, it has become possible to construct individual components of the eye, such as the cornea and retina, in vitro. This review summarizes the recent advancements in ocular organoid research, with a focus on corneal and retinal organoids.

[Predictive value of serum lactate dehydrogenase on prognosis of patients with paraquat poisoning].

Objective: To investigate the predictive value of serum lactate dehydrogenase (LDH) in the prognosis of patients with paraquat (PQ) poisoning, and to provide evidence for early prognosis assessment. Methods: In February 2022, 50 patients with PQ poisoning who completed serum LDH detection admitted to the Department of Emergency Medicine, the First Affiliated Hospital of Wenzhou Medical University from January 2012 to December 2021 were selected as the observation group, and 50 healthy physical examination personnel were randomly selected as the control group. Patients with PQ poisoning were divided into survival group and death group according to the prognosis, and the differences of blood routine routine, liver and kidney function and other indicators in the first admission between the two groups were compared. Multivariate logisitic regression model was established, ROC curve was drawn, and the influencing factors of prognosis of patients with PQ poisoning were analyzed. Results: Compared with the control group, the white blood cell count (WBC), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), LDH, glucose (GLU) and creatinine (Cr) in observation group were significantly increased, while albumin (ALB) and total cholesterol (TC) were significantly decreased (P<0.05). Univariate analysis showed that WBC, elevated LDH (>247 U/L), TBil, ALT, AST and Cr were significantly different between PQ poisoning survival group and death group (P<0.05). Multivariate logisitic regression analysis showed that elevated serum LDH was an independent risk factor for the prognosis of PQ poisoning patients (OR=9.95, 95%CI: 1.34-73.82, P=0.025). The area under the ROC curve of LDH was 0.811 (95%CI: 0.692-0.930). When the cut-off value was 340 U/L, the sensitivity was 0.889 and the specificity was 0.719. Log-rank test showed that there was a statistically significant difference in survival rate between the normal LDH group and the elevated LDH group (P=0.001) . Conclusion: Serum LDH has a good predictive value in evaluating the prognosis of patients with PQ poisoning. Elevated LDH is a risk factor for poor prognosis of patients with PQ poisoning.

[Artificial intelligence aided measurement of cervical squamous epithelial thickness and its correlation with cervical precancerous lesions].

Objective: To study the thickness of cervical squamous epithelia and its correlation with cervical precancerous lesions. Methods: We selected 495 HE slides of 209 cervical biopsies from January 2020 to June 2020 in the Department of Pathology, the First and Seventh Medical Center of the PLA General Hospital, including 173 slides with low grade squamous intraepithelial lesion (LSIL) and 214 slides with high grade squamous intraepithelial lesion (HSIL). Artificial intelligence labeling software was used to assist in measuring the epithelial thickness of normal cervical squamous epithelium, LSIL and HSIL of each slide. The thickest, thinnest, and middle widths of epithelial thickness were measured, respectively. Average epithelial thickness was defined as the sum of the above three widths divided by 3. The correlation statistical analysis was performed by combining the data of age and pathological diagnosis. Results: The average thickness of normal cervical squamous mucosa was (245.83±91.40) µm, which was (222.42±81.22) µm and was (195.95±66.59) µm in LSIL and HISL epithelial respectively (F=27.09, P<0.01). The average cell layers of normal cervical squamous epithelium was (15.5±4.2) layers, which of LSIL was (14.8±4.8) layers, and that of HSIL was (15.8±4.8) layers. The differences among normal, LSIL and HSIL were not statistically significant (P>0.05). Further statistical analysis was stratified by age (≤30 years, 31-40 years, 41-50 years, 51-60 years, and >60 years), the results of Pearson correlation analysis showed that the thickness of normal cervical squamous epithelial gradually thinned with age (correlation coefficient r=-0.141 9, P<0.05), while LSIL and HSIL epithelial thickness had significant correlation with age (P>0.05). In the subgroup of ≤50 years old, the epithelial thickness of normal squamous epithelium was the thickest, followed by LSIL, and HSIL epithelial thickness was the thinnest. The differences were statistically significant (P<0.05). While in the subgroup of >50 years, the differences were not statistically significant (P>0.05). Conclusions: The cervical squamous epithelium gradually becomes thinner with the degree of precancerous lesions increasing among patients of ≤50 years old. However, after age of 50 years, with the onset of menopause, the normal mucosal epithelium is becoming atrophy, so that mucosal thickness is no longer correlated with the extent of the lesion. In addition, it is suggested that the cervical vinegar white test performance during colposcopy is related to the protein changes in the mucosal epithelial cells, but not directly related to the thickness of the epithelial layer.

[Different treatment regimens for primary central nervous system lymphoma:based on SEER database].

Objectives: To explore the prognostic factors of primary central nervous system lymphoma(PCNSL) and to analyze the efficacy of different treatment methods. Methods: Clinical data of 4 812 patients with PCNSL in SEER database from January 1975 to December 2016 were retrospectively analyzed.Among them, 2 831 were male and 1 981 were female, the ratio of male to female was 1.4∶1.0.There were 2 236 cases(46.47%) under 60 years old, 1 718 cases(35.70%) aged 60 to 74 years old, and 858 cases(17.83%) aged 75 years old or above. Two thousand four hundred and seventeen cases(50.23%) had supratentorial tumors, 299 cases (6.21%) had infratentorial tumors, and 554 cases(11.51%) had multiple brain tumors, 1 542 cases (32.04%) were other or unspecified location.Three thousand five hundred and thirteen cases(73.00%) had diffuse large B-cell lymphoma (DLBCL), 234 cases(4.86%) had non DLBCL, 1 065 cases (22.13%) had other or unspecified types of tumor.The treatment included 2 011 cases (41.77%) of biopsy, 61 cases (1.27%) of subtotal resection(STR), 54 cases (1.12%) of gross total resection(GTR), 2 384 cases (49.54%) of biopsy and chemotherapy, 159 cases (3.30%) of STR and chemotherapy, 144 cases (3.00%) of GTR and chemotherapy.Univariate and multivariate Cox regression models were used to analyze the prognostic factors affecting the overall survival of the patients.Fine-Gray test and competitive risk model were used to analyze the prognostic factors affecting cancer-specific survival.Kaplan-Meier method and Log-rank test was used for survival analysis. Results: Univariate and multivariate Cox regression analyses showed that age, race, marital status, tumor site, pathological subtype, surgery, chemotherapy, combined with other malignant tumors, and HIV infection were the independent prognostic factors affecting the overall survival of PCNSL patients.The results of Fine-Gray test and competitive risk model analyses showed that age, race, marital status, tumor location, pathological subtype, surgical method, chemotherapy, combined with other malignant tumors, and HIV infection were independent prognostic factors affecting cancer-specific survival, while gender and radiotherapy had no significant correlation with cancer-specific survival.Compared with biopsy, PCNSL patients may benefit from surgical resection (STR:HR=0.805, 95%CI:0.656‒0.989, P=0.04; GTR:HR=0.521, 95%CI:0.414‒0.656, P<0.01).Kaplan-Meier survival analysis showed that the median survival time of biopsy+chemotherapy group was 28 months (95%CI:24.497‒31.503), 2 months (95%CI:1.756‒2.244) in the biopsy group, 2 months (95%CI:1.410-2.590) in the STR group, 19 months (95%CI:0‒39.311) in the biopsy+chemotherapy group, 67 months (95%CI:46.187-87.813) in the STR+chemotherapy group, 84 months (95%CI:57.448‒110.552) in the GTR+chemotherapy group.The median survival time of patients with different treatment methods was statistically significant (P<0.01). Conclusions: Surgical resection may improve the prognosis of some PCNSL patients.Patients who have access to receive GTR or STR combined with chemotherapy may have prolonged Cancer-specific survival.

Direct Detection Constraints on Dark Photons with the CDEX-10 Experiment at the China Jinping Underground Laboratory.

We report constraints on the dark photon effective kinetic mixing parameter (κ) with data taken from two p-type point-contact germanium detectors of the CDEX-10 experiment at the China Jinping Underground Laboratory. The 90% confidence level upper limits on κ of solar dark photon from 205.4 kg-day exposure are derived, probing new parameter space with masses (m_{V}) from 10 to 300 eV/c^{2} in direct detection experiments. Considering dark photon as the cosmological dark matter, limits at 90% confidence level with m_{V} from 0.1 to 4.0 keV/c^{2} are set from 449.6 kg-day data, with a minimum of κ=1.3×10^{-15} at m_{V}=200 eV/c^{2}.

[The 475th case: renal tubular acidosis, renal failure, anemia, and lactic acidosis].

A 47-year-old female patient presented nausea and vomiting for half a year and elevated serum creatinine for 3 days. Proximal renal tubular acidosis (RTA) complicated with anemiawas confirmed after admission. Secondary factors, such as autoimmune disease, drugs, poison, monoclonal gammopathy, were excluded. Renal biopsy revealed acute interstitial nephritis. The patient was administrated with daily prednisone 50 mg, sodium bicarbonate 4 g, 3 times per day, erythropoietin 3 000 U, 2 times per week, combined with potassium, calcium, and calcitriol tablets. Serum creatinine reduced to 90 µmol/L. However nausea and vomiting deteriorated with lactic acidosis. Bone marrow biopsy indicated the diagnosis of non-Hodgkin lymphoma, therefore the patient was treated with chemotherapy. Although metabolic acidosis improved gradually after chemotherapy, severe pneumocystis carinii pneumonia developed two weeks later. The patient refused further treatment and was discharged.

[Research and application of assessment tools for Residents' Nutrition Literacy].

Nutrition literacy is an important part of health literacy, as well as an significant factor to enhance the quality of population, improving the nutritional status of residents and preventing nutrition-related diseases. In 2010, China developed an evaluation tool for health literacy and began to monitor residents' health literacy. So far, eight national surveys on health literacy have been completed, providing an important basis for health promotion intervention strategies and related policies. However, in health literacy evaluation system, there is neither evaluation content of nutrition literacy, nor evaluation tools. In order to achieve the goals of "national nutrition plan (2017-2030)"and evaluate the implementation effect, it is urgent to carry out the assessment and monitoring of nutrition literacy. According to the nutritional characteristics of different populaitons, this research organizes national experts in related fields, following the principles of scientificity, conciseness and generality and through the scientific formulation procedures to construct the nutrition literacy assessment tools for different populations. This assessment tool can enhance the pertinence and scientificity of nutrition education and improve nutrition development strategy. The establishment of the nutrition literacy assessment tool is the premise of gradually establishing the nutrition literacy assessment system of the residents, and also lays a solid foundation for further conducting the national nutrition literacy evaluation work.

[Factor analysis of cerebrospinal fluid spread in glioblastoma].

Objective: To analyze the prognosis factors of cerebrospinal fluid (CSF) spread after surgery in glioblastoma (GBM) patients when tumors progressed and the effect factors on prognosis. Methods: A retrospective study was conducted on 124 patients who were pathologically diagnosed as glioblastoma after surgery, and found tumor progressed during regularly follow-up at Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University between January 2009 and August 2017.There were 82 males and 42 females, aged 47.9 years(range: 19 to 75 years) .Patients were divided into local recurrence group(96 cases) and CSF spread group (28 cases) .Clinical data were recorded in detail and compared by independent sample t test or χ(2) test.Kaplan-Meier survival curves was used to demonstrated the distribution of progression free survival (PFS) overall survival (OS) and post progression survival (PPS), and differences between local recurrence and CSF spread groups were assessed by Log-rank test.Cox proportion hazard regression analysis was used to identify independent prognostic factors. Results: Logistics regression analysis showed ventricle entry was the only prognosis factor of CSF spread (OR=2.667, 95% CI: 1.128 to 6.304, P=0.025).No significant distinction was observed in PFS between CSF spread group and local recurrence group(7.0 months vs.9.3 months, P=0.066).However, OS and PPS were substantially shortened in CSF spread group (13.0 months vs.23.0 months, P=0.011; 6.0 months vs.11.0 months, P=0.022, respectively).Mutations of isocitrate dehydrogenase gene, distant spread, gross-total resection, Ki-67 index>30% were independent prognostic factors of GBM patients. Conclusions: Ventricle entry is a prognosis factor for CSF spread, after which the median OS and PPS are markedly diminished.However, ventricle entry is not independent prognosis factor shortening survival.

Gene deficiency and pharmacological inhibition of caspase-1 confers resilience to chronic social defeat stress via regulating the stability of surface AMPARs.

Both inflammatory processes and glutamatergic systems have been implicated in the pathophysiology of mood-related disorders. However, the role of caspase-1, a classic inflammatory caspase, in behavioral responses to chronic stress remains largely unknown. To address this issue, we examined the effects and underlying mechanisms of caspase-1 on preclinical murine models of depression. We found that loss of caspase-1 expression in Caspase-1-/- knockout mice alleviated chronic stress-induced depression-like behaviors, whereas overexpression of caspase-1 in the hippocampus of wild-type (WT) mice was sufficient to induce depression- and anxiety-like behaviors. Furthermore, chronic stress reduced glutamatergic neurotransmission and decreased surface expression of glutamate receptors in hippocampal pyramidal neurons of WT mice, but not Caspase-1-/- mice. Importantly, pharmacological inhibition of caspase-1-interleukin-1ß (IL-1ß) signaling pathway prevented the depression-like behaviors and the decrease in surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in stressed WT mice. Finally, the effects of chronic stress on both depression- and anxiety-like behaviors can be mimicked by exogenous intracerebroventricular (i.c.v.) administration of IL-1ß in both WT and Caspase-1-/- mice. Taken together, our findings demonstrate that an increase in the caspase-1/IL-1ß axis facilitates AMPAR internalization in the hippocampus, which dysregulates glutamatergic synaptic transmission, eventually resulting in depression-like behaviors. These results may represent an endophenotype for chronic stress-induced depression.

Epidemiologic characteristics of outbreaks of three norovirus genotypes (GII.2, GII.17 and GII.4 Sydney) in Guangzhou, China, from 2012 to 2018.

To compare the epidemiologic features (e.g. settings and transmission mode) and patient clinical characteristics associated with outbreaks of different norovirus (Nov) strains, we retrospectively analysed data of Nov outbreaks occurring in Guangzhou, China from 2012 to 2018. The results suggested that outbreaks of Nov GII.2, GII.17 and GII.4 Sydney exhibited different outbreak settings, transmission modes and symptoms. GII.2 outbreaks mainly occurred in kindergartens, elementary and high schools and were transmitted mainly through person-to-person contact. By contrast, GII.4 Sydney outbreaks frequently occurred in colleges and were primarily associated with foodborne transmission. Cases from GII.2 and GII.17 outbreaks reported vomiting more frequently than those from outbreaks associated with GII.4 Sydney.

Hexarelin protects cardiac H9C2 cells from angiotensin II-induced hypertrophy via the regulation of autophagy.

Hexarelin is a synthetic growth hormone-releasing peptide that exerts cardioprotective effects. Regulation of autophagy is known to be cardioprotective so this study examined the role of autophagy and potential regulatory mechanisms in hexarelin-elicited anti-cardiac hypertrophic action in cardiomyocytes subjected to hypertrophy. H9C2 cardiomyocytes were subjected to hypertrophy by angiotensin-II (Ang-II). Autophagic light chain-3 (LC3) and cytoskeletal proteins were determined by immunofluorescence assay. Autophagy was also detected using monodansylcadaverine (MDC) for autophagic vacuole visualization and Cyto-ID staining for autophagic flux measurement. Molecular changes were analysed by Western blotting and qRT-PCR. Apoptosis was evaluated using flow cytometry and TUNEL assay. ATP content and CCK-8 assay were used in assessing enhanced cell survival whilst oxidative stress was analysed by measuring malondialdehyde(MDA) and superoxide dismutase(SOD) levels. Ang-II induced cardiomyocyte hypertrophy, oxidative stress, apoptosis and decreased cell survival, all of which were significantly suppressed by hexarelin treatment which also enhanced autophagy in hypertrophic H9C2 cells. Furthermore, inhibition of hexarelin induced autophagy by 3-methyladenine (3MA) abolished the anti-hypertrophic function of hexarelin and also abrogated the protection of hexarelin against cell survival inhibition and apoptosis. Conversely, the application of autophagy stimulator rapamycin in H9C2 hypertrophic cells inhibited apoptosis, cell survival and reduced cell size as well. Additionally, hexarelin regulated the upstream signalling of autophagy by inhibiting the phosphorylation of mammalian target of rapamycin(mTOR). We propose that hexarelin plays a novel role of attenuating cardiomyocyte hypertrophy and apoptosis via an autophagy-dependent mechanism associated with the suppression of the mTOR signalling pathway.

[The 467th case: proteinuria, periungual fibromas, and facial steatadenomas].

A 22-year-old manpresented as a refractory nephrotic syndrome with edema and proteinuria for more than one year. Physical examination revealed facial steatadenomas and periungual fibromas. Images were characterized by hamartomatous lesions in multiple organs, including the central nervous system, heart, lungs, liver, and kidneys. Gene tests verified TSC2 mutation and confirmed the diagnosis of tuberous sclerosis complex. The APOL1 mutation was positive in this patient, which indicated the possibility of steroid-resistant focal segmental glomerulonephritis. Thus, he was treated with sirolimus. Renal angiomyolipoma was shrunk, but proteinuria was not relieved (24h unine protein>10 g) and eventually led into renal insufficiency. Nondialytic therapy was initiated consequently. Losartan 50 mg/d was used to control proteinuria under the close watch of serum creatinine. A recent phone call on October 2018 failed to reachthe patient. Therefore, the follow-up information was not updated.

[Identification of circulating tumor cells in peripheral blood for gliomas by detection of aneuploid cells].

Objective: To investigate the feasibility of detecting circulating tumor cells based on capture of heteroploid chromosome cells in peripheral blood of glioma patients. Methods: A total of 88 patients who were considered to suffer from gliomas and 10 healthy volunteers were enrolled in this study during January 2016 to December 2016 at Beijing Tiantan Hospital, from whom 6 ml preoperative blood was collected. Subtraction enrichment (SE)-immunostaining FISH (iFISH) was applied to capture the heteroploid chromosome 8 cells in those samples. Meanwhile, centromere probe 8(CEP-8)-FISH was used to identify aneuploid cells in 10 tumors and 10 brain tissues. Results: Numerous heteroploid chromosome 8 cells were observed in tumors whereas negative result was present in brain tissues (P<0.01). CTC was successfully detected in 90.9% glioma patients, in contrast, only one healthy volunteer was shown with a heteroploid chromosome 8 cell (P<0.01). Glial fibrillary acidic protein was not exhibited in the overwhelming majority of CTC (96.1%). High grade glioma (HGG) without IDH mutation possessed much more CTC than low grade (12.0 vs 2.2), P<0.01. Furthermore, multiploidy (≥5 copies) CTC accounted for a much significant percentage in HGG, either in tumors originating from oligodendrocyte or astrocyte (75.9% vs 56.0%), P<0.01; 62.7% vs 51.7%, P=0.016, respectively). Conclusion: CTC could be identified and enumerated in glioma by detecting aneuploidy cells in blood. The number and multiploidy proportion of CTC may be correlative with tumor grade and molecular characteristics.

[Clinical prognostic factors of adult supratentorial glioblastoma].

Objective: To analyze the treatment effect of patients with glioblastoma (GBM) and explore prognostic factors. Methods: The clinical data of 635 patients diagnosed as GBM at Neurosurgical Oncology Department Ⅳ of Beijing Tiantan Hospital, Capital Medical University from January 2007 to March 2018 were retrospectively reviewed. There were 386 males and 249 females with an age of (48.7±11.8) years (range: 18-75 years). Patients were divided into three groups according to the time of admission: 2007-2010 group(n=174), 2011-2014 group (n=237) and 2015-2018 group (n=224). Kaplan-Meier plot was used to analyze the effects of different treatment periods, treatment schemes and clinical factors on the survival of patients with GBM. Cox proportion hazard regression analysis was used to identify independent prognostic factors. Results: The median progression-free survival (PFS) and overall survival (OS) of patients in 2007-2010 group, 2011-2014 group, 2015-2018 group was 9.0 months (95% CI: 7.5-10.5), 10.0 months (95% CI: 8.8-11.2), 12.0 months (95% CI: 10.7-13.3) and 17.0 months (95% CI: 13.2-20.8), 20.0 months (95% CI: 16.9-23.1), 23.0 months(95% CI: 17.5-28.5), respectively. The PFS and OS of patients improved significantly over the years (χ(2)=9.693, P=0.008 and χ(2)=8.616, P=0.013). Multivariate survival analysis showed that age, extent of resection, radiotherapy and tumor distant dissemination were independent prognostic factors (all P<0.05). Conclusions: With the continuous development of clinical treatment regimen, the therapeutic effect of Chinese GBM patients has improved remarkably. Age, extent of resection, radiotherapy and tumor distant dissemination are independent prognostic factors associated with survival time.

[ERK on apoptosis of gastric cancer cells induced by microRNA-433].

Objective: To investigate the role of ERK in the apoptosis of gastric cancer cells induced by miR-433. Methods: Lentivirus was used to transfect BGC-823 gastric cancer cell line to over-express miR-433. The blank control group (BGC-823), negative control group (BGC-823+ miR-433 negative control) and experimental group (miR-433+ miR-433, BGC-823-pMD18-T- miR-433)were set up. After treatment, the gastric cancer cell line BGC-823 was detected at 24 h, 48 h, and 72 h after culture, in vitro cell activity, cell apoptosis assays were performed by CCK-8 and Annexinv-FITC, respectively, to elucidate biological effects of miRNA-433, and After 72 h of culture, the ERK1/2 detected their protein expression were quantified by BCA method. Result: The growth activity of BGC-823+ miR-433 cells cultured in vitro was significantly lower than that of BGC-823 cells and BGC-823+ miR-433 negative control cells at 48 h and 72 h; BGC-823+ miR-433 cell apoptosis index was significantly increased at 24 h, 48 h, and 72 h; the expression of ERK1/2 was significantly lower than BGC-823 cells and BGC-823+ miR-433 negative contral after 72 h culture. There were no significant differences between BGC-823+ miR-433 negative control cells and BGC-823 cells. Conclusion: ERK plays an important role in the apoptosis of gastric cancer cells induced by miR-433.

Direct uterine sampling using the SAP-l sampler device to detect endometrial lesions during histopathological examination.

AIMS: To evaluate the sampling adequacy and diagnostic accuracy of the endometrial SAP-l sampling device in detecting endometrial lesions based on histopathological examination. MATERIALS AND METHODS: In total, 182 patients who required an endometrial biopsy were enrolled in this study. All of the patients underwent endometrial biopsies with the SAP-l sampler prior to hysteroscopy (169/182) or dilatation and curettage (D&C) (13/182). Endometrial tissues were obtained at biopsy for histopathological examination. RESULTS: Ad- equate endometrial specimens were obtained in 148 of 182 patients (81.32%). Menopause (p = 0.000), endometrial thickness (p = 0.004), and the types of endometrial diseases (p = 0.009) differed significantly between the two groups. Among the 169 patients who underwent hysteroscopy, sampling scratches were observed in the uterine cavity in 147 cases (86.98%). Compared to traditional methods, such as hysteroscopy and D&C, the sampling diagnostic sensitivity, specificity, and positive and negative predictive values were 82.35%, 100%, 100% , and 97.76% for endometrial carcinoma (n=17) and 37.5%, 100%, 100% and 97.76% for endometrial atypical hyperplasia (n=8), respectively. Those that were misdiagnosed occurred because the lesions were focal or localized in a small part of the uterine cavity. The sampling diagnostic sensitivity for polyps (n=32) was 12.5%. Two patients with submucosal leiomyoma went undiagnosed based on the sample specimens. CONCLUSION: Endometrial sampling using the SAP-l sampler is a minimally invasive altemative technique for obtaining adequate endometrial specimens for histopathological examination. The SAP-l sampler was useful in detecting endometrial carcinoma and atypical hyperplasia cases that were not highly suspected to be localized; however, this method was not useful in detecting endometrial polyps and submucosal leiomyomas.