[Clinical features and influencing factors of long-term prognosis in patients with tuberculous meningitis].

Objective: To investigate the clinical features and influencing factors of long-term prognosis of tuberculous meningitis(TBM), and to provide a recommendation for treatment and early intervention of TBM. Methods: Clinical data of TBM patients were retrospectively collected at Peking Union Medical College Hospital from January 2014 to December 2021. Patients who were followed-up more than one year were divided into two groups according to modified Rankin Scale (mRS). Risk factors associated with long-term prognosis were analyze by conditional logistic stepwise regression. Results: A total of 60 subjects were enrolled including 33 (55%) males and 27 (45%) females with age 15-79 (44.5±19.8) years. There were 30 cases (50%) complicated with encephalitis, 21 cases (35%) with miliary tuberculosis. The diagnosis was microbiologically confirmed in 22 patients (36.7%), including 5 cases (22.7%, 5/22) by acid-fast staining, 8 cases (36.4%, 8/22) by Mycobacterium tuberculosis (MTB) culture, and 20 cases (90.9%, 20/22) by molecular biology. The median follow-up period was 52(43, 66 ) months in 55 cases surviving more than one year. Among them, 40 cases (72.7%) were in favorable group (mRS 0-2) and 15 cases (27.3%) were in unfavorable group (mRS 3-6) with poor prognosis. The mortality rate was 20% (11/55). Elderly (OR=1.06, P=0.048 ) , hyponatremia(OR=0.81,P=0.020), high protein level in cerebrospinal fluid (CSF) (OR=3.32,P=0.033), cerebral infarction(OR=10.50,P=0.040) and hydrocephalus(OR=8.51,P=0.049) were associated with poor prognosis in TBM patients. Conclusions: The mortality rate is high in patients with TBM. Molecular biology tests improves the sensitivity and shorten the diagnosis time of TBM. Elderly, hyponatremia, high protein level in CSF, cerebral infarction and hydrocephalus are independent risk factors of long-term survival in TBM patients.

A long non-coding RNA, ELFN1-AS1, sponges miR-1250 to upregulate MTA1 to promote cell proliferation, migration and invasion, and induce apoptosis in colorectal cancer.

OBJECTIVE: Long non-coding RNA (lncRNA), is essential for the development and progression of cancers. LncRNA regulates target gene expression by sponging the corresponding microRNA (miRNA) during tumorigenesis. This work aimed to explore the role of one lncRNA, ELFN1-AS1, in colorectal cancer (CRC) development and elucidate the pertinent signaling pathway. PATIENTS AND METHODS: First, we found that ELFN1-AS1 was highly abundant in the human CRC tissues and cell lines. Silence of ELFN1-AS1 expression reduced cell proliferation, colony formation, migration and invasion, while inducing apoptosis in vitro; moreover, knockdown of ELFN1-AS1 decreased the size and weight of tumor in vivo. RESULTS: Luciferase reporter assay revealed that ELFN1-AS1 interacted with miR-1205 and suppressed its expression. In addition, miR-1205 could bind to the 3' untranslated region (3'-UTR) of Metastasis Associated Protein1 (MTA1) and inhibited ELFN1-AS1 expression. More importantly, overexpression of MTA1 completely rescued the phenotype of ELFN1-AS1 knockdown. CONCLUSIONS: In sum, our study demonstrated that ELFN1-AS1 sponges miR-1205 to upregulate MTA1, which is essential for CRC cell proliferation, migration, and invasion as well as apoptosis induction.

LncRNA AOC4P affects biological behavior of gastric cancer cells through MAPK signaling pathway.

OBJECTIVE: Long non-coding RNA (lncRNA) is closely related to the occurrence and development of gastric cancer, but the mechanism and clinical significance of lncRNA AOC4P are still unclear. This study aimed to investigate the expression and function of lncRNA AOC4P in gastric cancer. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of lncRNA AOC4P in 80 gastric cancer tissues and adjacent normal tissues. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), flow cytometry and transwell assays were used to study the effects of lncRNA AOC4P on the proliferation, apoptosis, migration and invasion of gastric cancer cells. Western blot was used to detect the related protein level of the mitogen-activated protein kinase (MAPK) signal pathway. RESULTS: The expression of lncRNA AOC4P in gastric cancer tissues was higher than that in adjacent tissues. OS or DFS time were significantly shortened in patients with gastric cancer with high expression of lncRNA AOC4P. Inhibition of lncRNA AOC4P expression can inhibit cell proliferation, migration and invasion, promoting cell apoptosis to some extent. Inhibition of lncRNA AOC4P expression also can result in the decreased expression levels of extracellular-signal-regulated kinase 1 (ERK1), c-Jun N-terminal kinases (JNK) and p38 proteins. CONCLUSIONS: High expression of lncRNA AOC4P in gastric cancer may be related to the occurrence, development and prognosis of gastric cancer. LncRNA AOC4P is expected to become a new diagnostic marker and therapeutic target for gastric cancer.

LncRNA CASC19 promotes the proliferation, migration and invasion of non-small cell lung carcinoma via regulating miRNA-130b-3p.

OBJECTIVE: To uncover the biological role of long non-coding RNA (lncRNA) CASC19 in the pathogenesis of non-small cell lung carcinoma (NSCLC) and the potential mechanism. PATIENTS AND METHODS: Expression pattern of lncRNA CASC19 in NSCLC tissues and cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Survival analysis on the correlation between CASC19 level and prognosis of NSCLC patients was conducted by introducing for the Kaplan-Meier estimator. After the transfection of si-CASC19 in A549 and PC9 cells, changes in viability, migratory, and invasive capacities were evaluated. Dual-luciferase reporter gene assay was performed to explore the interaction between microRNA-130b-3p (miRNA-130b-3p) and CASC19/ZEB2. Their interactive effects on the progression of NSCLC were finally investigated through rescue experiments. RESULTS: LncRNA CASC19 was upregulated in NSCLC tissues and cell lines. NSCLC patients with high expression of CASC19 presented a worse survival. Knockdown of CASC19 attenuated proliferative, migratory, and invasive capacities of A549 and PC9 cells. CASC19 sponged miRNA-130b-3p and negatively regulated its level. ZEB2 was the direct target of miRNA-130b-3p. The knockdown of miRNA-130b-3p reversed the regulatory effects of CASC19 on A549 and PC9 cells. CONCLUSIONS: CASC19 sponges miRNA-130b-3p to regulate ZBR2 as a ceRNA, thus accelerating the progression of NSCLC by regulating proliferative, migratory, and invasive capacities of tumor cells.

[Clinicopathologic features of gastric plexiform fibromyxoma].

Objective: To analyse the clinicopathologic features of gastric plexiform fibromyxoma (PF) including diagnosis, differential diagnosis, immunohistochemistry and molecular pathology. Methods: Eight cases of PF were collected from June 2006 to June 2017 at the Second Affiliated Hospital of Zhengzhou University and the First Affiliated Hospital of Zhengzhou University. The clinicopathologic findings of eight cases of PF were retrospectively analyzed, and immunohistochemistry (EnVision method) and molecular detection of glioma-associated oncogene homologue 1 (GLI1) gene translocation were performed. All cases were histologically reviewed with immunohistochemical staining for smooth muscle actin (SMA), CD10, CD117, DOG1, CD34, ER, PR, ALK and S-100. Fluorescence in situ hybridization (FISH) was used to detect the GLI1 gene translocation, and mutation of CKIT exons 9, 11, 13 and 17; and PDGFRA exons 12, 14 and 18 were identified by Sanger sequencing in four cases. Relevant literature was reviewed. Results: The study included four men and four women, age ranged from 26 to 72 years (mean 51 years). Histologically, the tumors were rich in small thin-walled blood vessels and myxoid matrix, and exhibited multiple nodular growth pattern in the gastric wall. The tumor cells were bland, spindled or oval. Immunohistochemically, all cases strongly expressed vimentin and SMA, and some expressed CD10 (4/8), desmin (3/8), H-caldesmon (5/8) and PR (5/8), but were negative for CD34, S-100, ER, ALK, CD117 and DOG1. The GLI1 gene translocation detection was performed in eight cases by FISH with three positive cases and five negative cases. Mutation analyses for exons 9, 11, 13, and 17 of CKIT genes and exons 12, 14, and 18 of the PDGFRA genes were performed and the tumors all of four tested cases were wild-type. Seven patients were followed up (ranged from 24 to 95 months, mean 50 months) after diagnosis and none of the patients had recurrence or metastasis. Conclusions: PF is a rare novel mesenchymal tumor of the stomach. Its distinct clinicopathologic features and immunohistochemical positivity for SMA, CD10 and PR can help differentiating this entity from other gastrointestinal mesenchymal tumors. FISH detection of GLI1 gene translocation offers an additional molecular diagnostic marker for the diagnosis.

Mutagenicity of biodiesel or diesel exhaust particles and the effect of engine operating conditions.

BACKGROUND: Changing the fuel supply from petroleum based ultra-low sulfur diesel (ULSD) to biodiesel and its blends is considered by many to be a viable option for controlling exposures to particulate material (PM). This is critical in the mining industry where approximately 28,000 underground miners are potentially exposed to relatively high concentrations of diesel particulate matter (DPM). This study was conducted to investigate the mutagenic potential of diesel engine emissions (DEE) from neat (B100) and blended (B50) soy-based fatty acid methyl ester (FAME) biodiesel in comparison with ULSD PM using different engine operating conditions and exhaust aftertreatment configurations. METHODS: The DPM samples were collected for engine equipped with either a standard muffler or a combination of the muffler and diesel oxidation catalytic converter (DOC) that was operated at four different steady-state modes. Bacterial gene mutation activity of DPM was tested on the organic solvent extracts using the Ames Salmonella assay. RESULTS: The results indicate that mutagenic activity of DPM was strongly affected by fuels, engine operating conditions, and exhaust aftertreatment systems. The mutagenicity was increased with the fraction of biodiesel in the fuel. While the mutagenic activity was observed in B50 and B100 samples collected from both light-and heavy-load operating conditions, the ULSD samples were mutagenic only at light-load conditions. The presence of DOC in the exhaust system resulted in the decreased mutagenicity when engine was fueled with B100 and B50 and operated at light-load conditions. This was not the case when engine was fueled with ULSD. Heavy-load operating condition in the presence of DOC resulted in a decrease of mutagenicity only when engine was fueled with B50, but not B100 or ULSD. CONCLUSIONS: Therefore, the results indicate that DPM from neat or blended biodiesel has a higher mutagenic potency than that one of ULSD. Further research is needed to investigate the health effect of biodiesel as well as efficiency of DOC or other exhaust aftertreatment systems.

Mutagenicity of diesel exhaust particles from an engine with differing exhaust after treatments.

This study was conducted to investigate the effects of engine operating conditions and exhaust aftertreatments on the mutagenicity of diesel particulate matter (DPM) collected directly in an underground mine environment. A number of after-treatment devices are currently used on diesel engines in mines, but it is critical to determine whether reductions in DPM concentrations result in a corresponding decrease in adverse health effects. An eddy-current dynamometer was used to operate naturally aspirated mechanically controlled engine at several steady-state conditions. The samples were collected when the engine was equipped with a standard muffler, a diesel oxidation catalytic converter, two types of uncatalyzed diesel particulate filter systems, and three types of disposable diesel particulate filter elements. Bacterial gene mutation activity of DPM was tested on acetone extracts using the Ames Salmonella assay. The results indicated strong correlation between engine operating conditions and mutagenic activity of DPM. When the engine was fitted with muffler, the mutagenic activity was observed for the samples collected from light-load, but not heavy-load operating conditions. When the engine was equipped with a diesel oxidation catalyst, the samples did not exhibit mutagenic activity for any of four engine operating conditions. Mutagenic activity was observed for the samples collected when the engine was retrofitted with three types of disposable filters and sintered metal diesel particulate filter and operated at light load conditions. However, those filtration systems substantially reduced the concentration-normalized mutagenic activity from the levels observed for the muffler.

A laser-Compton scattering prototype experiment at 100 MeV linac of Shanghai Institute of Applied Physics.

As a prototype of the Shanghai Laser Electron Gamma Source in the Shanghai Synchrotron Radiation Facility, an x-ray source based on laser-Compton scattering (LCS) has been installed at the terminal of the 100 MeV linac of the Shanghai Institute of Applied Physics. LCS x-rays are generated by interactions between Q-switched Nd:yttrium aluminum garnet laser pulses [with wavelength of 1064 nm and pulse width of 21 ns (full width at half maximum)] and electron bunches [with energy of 108 MeV and pulse width of 0.95 ns (rms)] at an angle of 42 degrees between laser and electron beam. In order to measure the energy spectrum of LCS x-rays, a Si(Li) detector along the electron beam line axis is positioned at 9.8 m away from a LCS chamber. After background subtraction, the LCS x-ray spectrum with the peak energy of 29.1+/-4.4|(stat)+/-2.1|(syst) keV and the peak width (rms) of 7.8+/-2.8|(stat)+/-0.4|(syst) keV is observed. Normally the 100 MeV linac operates with the electron macropulse charge of 1.0 nC/pulse, and the electron and laser collision repetition rate of 20 Hz. Therefore, the total LCS x-ray flux of (5.2+/-2.0) x 10(2) Hz can be achieved.

Induction of micronuclei in rat bone marrow by four model compounds.

Studies have been performed to determine the dose and sampling time responses of micronuclei after Sprague-Dawley rats were treated with triethylenemelamine, mitomycin C. dimethylbenzanthracene, and vincristine by a single intraperitoneal injection. Three doses were tested for each compound. Animals were sacrificed 24, 48, and 72 h after chemical treatment. Slides prepared from the bone marrow were stained with May-Gruenwald and Giemsa stains. The number of micronucleated polychromatic erythrocytes among 2,000 polychromatic erythrocytes (PCEs) and the ratio of PCEs to normochromatic erythrocytes were determined for each animal. The results show that all four compounds cause micronucleus formation in rat bone marrow. The peak response sampling time, either 24 or 48 h posttreatment, is dependent on the chemical as well as the dose. In all cases, however, an increase in the micronucleated PCEs was detected 24 h after chemical treatment. These results seem to indicate that two sampling times, 24 and 48 h, may be adequate for the micronucleus assay using rat bone marrow cells.

Effect of tetrandrine on micronucleus formation and sister-chromatid exchange in both in vitro and in vivo assays.

The genotoxicity of tetrandrine, a drug potentially useful for the treatment of silicosis, was studied using the micronucleus and the sister-chromatid exchange (SCE) assay systems. Cultured Chinese hamster lung (V79) cells were used for the in vitro micronucleus and sister-chromatid exchange studies. Mouse bone marrow was used for the in vivo micronucleus assay and mouse spleen cells for the in vivo/in vitro sister-chromatid exchange analysis. The results show that SCE levels in V79 and in spleen cells were significantly elevated by treatment with tetrandrine at doses above 0.08 mg/ml and 100 mg/kg bw, respectively. Increased tetradrine-induced SCE in vitro was metabolic activation dependent. Tetrandrine failed to induce micronuclei at any of the doses tested. A decrease of replicative index with an increase in the concentration of tetrandrine was found both in vitro and in vivo. These results indicate that tetrandrine is a weak indirect-acting genotoxicant.

Effects of artemether on peripheral T, B, T mu and T gamma lymphocytes in beagle dog.

The effects of intramuscular injection of Artemether on peripheral T, B, T mu and T gamma lymphocytes in beagle dogs was investigated cytochemically. Doses used were 6, 19, and 32 MKD, respectively. Results showed that after injection of Artemether for 15 successive days, the T, B, and T mu lymphocytes of the 19 and 32 MKD groups were markedly reduced and the T gamma lymphocytes of all 3 dosage groups were decreased to zero. 28 days after cessation of the drug, T, T mu and T gamma lymphocytes had recovered to control levels, while the B lymphocytes of the 19 and 32 MKD groups remained markedly lower than those of the control groups. The differences and similarities of the effects on the peripheral T, B, T mu and T gamma lymphocytes produced by the 3 dosages of Artemether and the relationship between the changes of T, B lymphocytes and immunological function of beagle dogs are discussed.

[Studies on the surveillance and purifying measures for filariasis in controlled areas].

This paper reports the results of longitudinal surveillance of filariasis for 4 years in Jining City, Shandong, where the disease has been controlled. It showed that the microfilaremia rate dropped from 0.48% to 0.03% and no new case was found and the natural infective rate of the main vector mosquito Culex pipiens fell from 0.45% to 0.03% and no larva III was detected. The purifying measures should put emphasis on the management of migrating persons repeatedly examining and treating old microfilaremia cases, the border areas with high microfilaremia rate, as well as working out a plan to cure the advanced patients and mosquito control measures with special reference to construction of new village settlements.

Pharmacology of radioiodinated hexadecenoic acid--a myocardial imaging agent.

123I- and 131I-labeled hexadecenoic acid (IHDA, radiochemical purity over 92%, dissolved in 6% bovine serum albumin solution) was investigated in vivo. ICR mice were administered IHDA via the tail vein. Maximum myocardial uptake (27.3 +/- 5.1%) was reached about 0.5 min after the injection. The ratio of uptake in the heart to that in the lungs was 2.3, to that in liver 1.5 and to that in other organs 2.4 to 6.4. The dog myocardium was visualized distinctly within 3-5 min with a gamma camera after i.v. 131I-IHDA, and not interfered with by activities in the lungs, liver and other organs. The low blood levels at 20 min had little effect on the quality of the heart images.

A study of 11C-benzoate as a radiopharmaceutical for renal imaging.

11C-benzoic acid prepared in a radiochemical purity over 90% was studied radiopharmacologically in mice and rabbits. The uptake of 11C-benzoate in ICR mice increased quickly. The ratio of kidney uptake rate to that in other organs reached values between 9 and 55 with a maximum at 10 min after i.v. injection. Gamma camera imaging of rabbits showed that uptake in the kidneys began at 2 min after injection and that activity began to appear in the bladder 4 min later. Rabbits with left renal artery ligature showed no uptake in the left kidney but the right kidney was imaged to the same extent as that of a rabbit without artery ligature. The kidney imaging of 11C-benzoic acid may be a useful method for renal diagnosis.