Enteral lorlatinib after immune hyperprogression as a treatment option for anaplastic lymphoma kinase­positive non­small cell lung cancer: A case report.

Fusion of the anaplastic lymphoma kinase (ALK) gene is a rare driver in non-small cell lung cancer (NSCLC). Lorlatinib is a third-generation ALK inhibitor approved for the treatment of locally advanced or metastatic ALK+ NSCLC. The traditional administration method of lorlatinib is whole tablet ingestion, while the efficacy effect of gastric tube injection after water dissolution remains unclear. In the present report, a marked response to lorlatinib in a 49-year-old patient with ALK+ NSCLC who was administered lorlatinib through a gastric tube, was described. The patient had received chemotherapy combined with immune checkpoint inhibitors prior to targeted drug therapy and developed hyperprogression, which was mainly manifested as rapid enlargement of the primary lesion with multiple new systemic metastases, accompanied by poor performance status score, esophageal compression and difficulty eating. The patient was injected with pre-dissolved lorlatinib through the nasogastric tube. After 6 days, related symptoms, such as dyspnea and dysphagia, were relieved. After 18 days, the esophageal stenosis was significantly alleviated, and the gastric tube was removed. In conclusion, gastric tube injection be used as a means of lorlatinib administration in patients with ALK+ NSCLC with dysphagia, regardless of previous immunotherapy-associated hyperprogression.

Combining inhibitory and facilitatory repetitive transcranial magnetic stimulation (rTMS) treatment improves motor function by modulating GABA in acute ischemic stroke patients.

BACKGROUND: The combination of inhibitory and facilitatory repetitive transcranial magnetic stimulation (rTMS) can improve motor function of stroke patients with undefined mechanism. It has been demonstrated that rTMS exhibits a neuro-modulatory effect by regulating the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) in other diseases. OBJECTIVES: To evaluate the effect of combined inhibitory and facilitatory rTMS on GABA in the primary motor cortex (M1) for treating motor dysfunction after acute ischemic stroke. METHODS: 44 ischemic stroke patients with motor dysfunction were randomly divided into two groups. The treatment group was stimulated with 10 Hz rTMS at the ipsilesional M1 and 1 Hz rTMS at the contralesional M1. The sham group received bilateral sham stimulation at the motor cortices. The GABA level in the bilateral M1 was measured by proton magnetic resonance spectroscopy (1H-MRS) at 24 hours before and after rTMS stimulation. Motor function was measured using the Fugl-Meyer Assessment (FMA). The clinical assessments were performed before and after rTMS and after 3 months. RESULTS: The treatment group exhibited a greater improvement in motor function 24 hours after rTMS compared to the sham group. The increased improvement in motor function lasted for at least 3 months after treatment. Following 4 weeks of rTMS, the GABA level in the ipsilesional M1 of the treatment group was significantly decreased compared to the sham group. Furthermore, the change of FMA score for motor function was negatively correlated to the change of the GABA:Cr ratio. Finally, the effect of rTMS on motor function outcome was partially mediated by GABA level change in response to the treatment (27.7%). CONCLUSIONS: Combining inhibitory and facilitatory rTMS can decrease the GABA level in M1, which is correlated to the improvement of motor function. Thus, the GABA level in M1 may be a potential biomarker for treatment strategy decisions regarding rTMS neuromodulatory interventions.

Size effect on the spontaneous coalescence of nanowires.

This paper investigates the size effect on the coalescence process of contacting nanoparticles. It is revealed by molecular dynamics that the nanometer-sized surface curvature coupled with the effective melting temperature exhibits a strong influence on the atom diffusion at the interface, and is therefore critical to the coalescence time. This effect is particularly pronouncing for surface curvatures below 20 nm. A phenomenological model is derived from the melting point reduction approach to describe the kinetic process of nanowire coalescence and is validated against a variety of simulation datasets. The quantitative correlation between the sample size, the sintering temperature and the contact morphology evolution is demonstrated.

Multi-medium distributions of HCHs, DDTs, and PCBs in typical petrochemical industrial area and surrounding regions of Jilin Province, Northeast China.

The levels of DDTs, HCHs and PCBs in topsoil, cereal and irrigation water from typical industrial and agricultural areas of Jilin Province in Northeastern China were evaluated by using gas chromatography coupled with an electron capture detector. The amount of ∑OCPs and ∑(7)PCBs found in topsoils ranged from 24.7 to 98.0 and 17.2 to 98.7 ng g(-1), respectively. The geometric means of ∑HCHs, ∑DDTs and ∑(7)PCBs in rice stem samples were 28.9, 32.4 and 49.0 ng g(-1), respectively. The average level of total OCPs concentration in rice field water in Meihekou area (0.849 ng g(-1)) is higher than that in Jilin area (0.178 ng g(-1)) and all OCPs concentrations in rice field water met the water quality standards for Grade I regulated by China's national environmental quality standard of surface water.

[Dynamics of polycyclic aromatic hydrocarbons (PAHs) in the paddy-soil system during the crop rotation process].

The concentrations of polycyclic aromatic hydrocarbons (PAHs) in the paddy root-soil system were determined to study the dynamic and the influencing factors during crop rotation period. It showed that the dynamic of PAHs in paddy roots was most correlative with the factor of root surface area, but less correlated with PAHs in air and particles, which indicates that the physiological characters rather than the environment media are the main factors influencing the PAHs accumulation in paddy roots. According to the EPA risk standard about BaP and sigma PAHs, the PAHs accumulation in the paddy seeds won't decrease the food security to human being. The PAHs concentrations in paddy soil showed a declined trend during the period of paddy growth, which was affected not only by the processes of water elution and microbe degradation, but also depended on the absorption rate of paddy roots. When the crop rotation begins and paddy planting rolls into the next growing period, the PAHs in the paddy soil will again increase into a higher level which is correlated with the TOC content in the soil.

Hypermethylation of Syk gene in promoter region associated with oncogenesis and metastasis of gastric carcinoma.

AIM: To investigate the relationship between methylation of Syk (spleen tyrosine kinase) gene in promoter region and oncogenesis, metastasis of gastric carcinoma. The relation between silencing of the Syk gene and methylation of Syk promoter region was also studied. METHODS: By using methylation-specific PCR (MSP) technique, the methylation of Syk promoter region in specimens from 61 gastric cancer patients (tumor tissues and adjacent normal tissues) was detected. Meanwhile, RT-PCR was used to analyse syk expression exclusively. RESULTS: The expression of the Syk gene was detected in all normal gastric tissues. Syk expression in gastric carcinoma was lower in 14 out of 61 gastric cancer samples than in adjacent normal tissues (chi(2)=72.3, P<0.05). No methylation of Syk promoter was found in adjacent normal tissues. hypermethylation of Syk gene in promoter was detected 21 cases in 61 gastric carcinoma patients. The rate of methylation of Syk promoter in gastric carcinoma was higher than that in adjacent normal tissues (chi(2)=25.1, P<0.05). In 31 patients with lymph node metastasis, 17 were found with Syk promoter methylation. A significant difference was noted between two groups (chi(2)=11.4,P<0.05). CONCLUSION: Hypermethylation leads to silencing of the Syk gene in human gastric carcinoma. Methylation of Syk promoter is correlated to oncogenesis and metastasis of gastric carcinoma. Syk is considered to be a potential tumor suppressor and anti-metastasis gene in human gastric cancer.