Clinical predictive factors of the efficacy of immune checkpoint inhibitors and kinase inhibitors in advanced hepatocellular cancer.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly aggressive tumor associated with significant morbidity and mortality rates. Combination therapy with immune checkpoint inhibitors (ICIs) and kinase inhibitors has emerged as a promising strategy for liver cancer treatment in recent years. However, the clinical factors predicting the outcomes of combination therapy in patients with advanced liver cancer remain uncertain. Therefore, this study investigated the relationships between clinical predictors and the efficacy of ICI plus kinase inhibitor therapy to personalize treatment plans. METHODS: We retrospectively enrolled 98 patients who received combination treatment with ICIs and kinase inhibitors for advanced HCC. Based on blood lipid levels and other clinical factors prior to treatment, we investigated potential biomarkers that could predict treatment responses in this patient population. RESULTS: Mean progression-free survival (PFS) and overall survival (OS) in this cohort were 10.1 and 17.2 months, respectively. Via multivariate analysis, the absence of extrahepatic metastasis, the absence of portal vein thrombosis (PVT), neutrophil-to-lymphocyte ratio (NLR) < 3.225, platelet-to-lymphocyte ratio (PLR) < 140.75, and prognostic nutritional index (PNI) ≥ 37.25 were identified as independent predictors of improved PFS. Factors associated with better OS included PLR < 140.75 and total cholesterol (TC) < 3.46 mmol/L. Univariate analysis identified significant associations of Eastern Cooperative Oncology Group performance status (ECOG PS), hepatitis B virus (HBV) DNA levels, Child-Pugh classification, alpha-fetoprotein (AFP), TC, and the receipt of regorafenib with PFS. Additionally, ECOG PS, Child-Pugh classification, AFP, PVT, NLR, PNI, and the receipt of regorafenib were significantly associated with OS. CONCLUSIONS: PLR and TC were potential clinical predictive factors for survival outcomes in patients with advanced HCC who received ICI/kinase inhibitor combination therapy. It is important to know the clinical characteristics of patients prior to treatment initiation to optimize outcomes.

Novel insights into hotspots of insect vectors of GLRaV-3: Dynamics and global distribution.

Grapevine leafroll-associated virus 3 (GLRaV-3) is the most prevalent and economically damaging virus in grapevines and is found on nearly all continents, except Antarctica. Ten mealybugs act as vector insects transmitting the GLRaV-3. Understanding the potential distribution range of vector insects under climate change is crucial for preventing and managing vector insects and controlling and delaying the spread of GLRaV-3. This study investigated the potential geographical range of insect vectors of GLRaV-3 worldwide using MaxEnt (maximum entropy) based on occurrence data under environmental variables. The potential distributions of these insects were projected for the 2030s, 2050s, 2070s, and 2090s under the three climate change scenarios. The results showed that the potential distribution range of most vector insects is concentrated in Southeastern North America, Europe, Asia, and Southeast Australia. Most vector insects contract their potential distribution ranges under climate-change conditions. The stacked model suggested that potential distribution hotspots of vector insects were present in Southeastern North America, Europe, Southeast Asia, and Southeast Australia. The potential distribution range of hotspots would shrink with climate change. These results provide important information for governmental decision-makers and farmers in developing control and management strategies against vector insects of GLRaV-3. They can also serve as references for studies on other insect vectors.

PD-1 inhibition combined with intensity-modulated radiotherapy, to better serve patients with retroperitoneal lymph node metastases from gastrointestinal cancer.

Background: Gastrointestinal (GI) cancer is the most frequent kind of cancer to involve the retroperitoneal lymph nodes (RPLNs). Radiotherapy (RT) is common treatment of RPLN metastases in patients with GI cancer, while RT is local. Meanwhile, most patients have extra-retroperitoneal metastases. Immunotherapy plus RT have showed effective in advanced non-small cell lung cancer. However, whether the combination therapy is effective on GI cancer with RPLN metastases. In our study, we would estimate the effect of programmed death-1 (PD-1) inhibition in association with intensity modulated radiation therapy (IMRT). Methods: Metastatic GI cancer patients with RPLN who were treated at a single institution were retrospectively evaluated from October 2016 to April 2023, who all had measurable lesion and received any therapy of PD-1 inhibitors alone, IMRT alone or PD-1 inhibitors plus IMRT. The follow-ups were assessed by abdominal computed tomography (CT) every 2 or 3 months to progression, dose-limiting toxicity or death. Results: Among the 98 patients, 46 were treated by PD-1 inhibitors combined with IMRT, 26 were by PD-1 inhibitors only and 26 were by IMRT only. Of those, the median age 62 years (range, 25-84 years). Median progression-free survival (PFS) was 7.5 months and median overall survival (OS) was 10.8 months across the 3 therapy groups. Univariate analysis (UVA) indicated that therapy method (P=0.032) and tumor response (P=0.035) were significantly related to PFS. In the PD-1 inhibitors plus IMRT group, 1 patient (2.2%) achieved complete response (CR), 30 (65.2%) had partial remission, and 14 (30.4%) had stable disease. There was no case with CR by IMRT or PD-1 inhibitors alone. Objective response rate (67.4%) and disease control rate (97.8%) were higher in the PD-1 inhibitors combined with IMRT group. In the PD-1 inhibitors plus IMRT and PD-1 inhibitors alone groups, hepatitis B virus (HBV)-positive patients had better OS (P=0.041) on UVA. Meanwhile, in the PD-1 inhibitors plus IMRT group, we observed superior PFS (P=0.041) and OS (P=0.049) in HBV-positive patients on UVA. Conclusions: PD-1 inhibitors plus IMRT may be a better method for advanced GI cancer patients with RPLN metastases. HBV-positive patients can benefit from either PD-1 inhibitors alone or in combination with IMRT.

Two Species Delimitation of Pseudaulacaspis (Hemiptera: Diaspididae) Based on Morphology, Molecular Clustering, and Niche Differentiation.

Pseudaucalaspis pentagona and P. prunicola are notorious pests and commonly feed on various ornamental plants and fruit trees worldwide. The two species share many host-plant species, and are similar in morphological characteristics and life cycle, making it difficult to distinguish to distinguish between them. In this study, morphological characteristics, molecular evidence, and ecological niches were used to define these species. We performed PCA analysis on 22 morphological characteristics that allowed the delineation of the species. We then sequenced the COI gene of both species revealing five populations of P. pentagona and one population of P. prunicola, and the higher support rate could distinguish the two species. We also identified the potential distribution area of the two species based on the MaxEnt niche model, which showed that the degree of niche overlap was high, but that they occupied different niches. Ultimately, we combined three lines of evidence to show that the two species are distinctly different. This study supports species definition using combined morphology, genetics, and ecology and provides a theoretical basis for the effective control of these two pests in the future.

Risk factors of temperature increase after cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy.

Background: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the standard treatment for patients with peritoneal cancer (PC). Following CRS-HIPEC, patients may also face risks caused by whole body hyperthermia. This study analyzed the incidence of temperature increases following CRS-HIPEC and identified the attendant risk factors. Methods: A retrospective analysis was carried out among 458 patients who received CRS-HIPEC at the Fourth Hospital of Hebei Medical University between August 2018 and January 2021. The patients were divided into two groups according to post-HIPEC axillary temperature (≥38°C), with the demographics and the laboratory test results subsequently analyzed and compared, and the risk factors pertaining to temperature increases analyzed using univariate and multivariate logistic regression. Results: During CRS-HIPEC, 32.5% (149/458) of the patients with a temperature increase had an axillary temperature of not lower than 38°C, and 8.5% (39/458) of the patients with hyperpyrexia had an axillary temperature of not lower than 39°C. Female gender, gynecological malignancies, type of chemotherapy drug, increased postoperative neutrophil percentage, and a sharp drop in postoperative prealbumin were associated with the incidence of a temperature increase and axillary temperatures of >38°C. Among these factors, the type of chemotherapy drug was identified as an independent risk factor for a temperature increase during CRS-HIPEC. Conclusion: By determining the risk factors pertaining to temperature increases during CRS-HIPEC, medical staff can identify the attendant risks among the patients and thus take preventive measures in a timely manner to maintain the patient's body temperature at a stable level. This suggests that further clinical research should be conducted to build a risk-prediction model for temperature increases following CRS-HIPEC.

ß2-Microglobulin exacerbates neuroinflammation, brain damage, and cognitive impairment after stroke in rats.

ß2-Microglobulin (ß2M), a component of the major histocompatibility complex class I molecule, is associated with aging-related cognitive impairment and Alzheimer's disease. Although upregulation of ß2M is considered to be highly related to ischemic stroke, the specific role and underlying mechanistic action of ß2M are poorly understood. In this study, we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery. We found that ß2M levels in the cerebral spinal fluid, serum, and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period. RNA interference was used to inhibit ß2M expression in the acute period of cerebral stroke. Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreased ß2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits, respectively. Notably, glial cell, caspase-1 (p20), and Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation as well as production of the inflammatory cytokines interleukin-1ß, interleukin-6, and tumor necrosis factor-α were also effectively inhibited by ß2M silencing. These findings suggest that ß2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.

Is flexible bronchoscopy necessary in the preoperative workup of patients with peripheral cT1N0 subsolid lung cancer? -a prospective multi-center cohort study.

BACKGROUND: Necessity of flexible bronchoscopy (FB) examination as a routine preoperative work-up for peripheral clinical T1N0 subsolid lung cancer was unknown. METHODS: This was a prospective, multi-center clinical trial (NCT03591445). Patients with peripheral GGO nodules (GGNs) who were candidates for surgical resection were enrolled. FB examination was performed preoperatively. Surgical plan could be changed if any aberrant histologic and anatomic findings were detected by FB examination. Primary endpoint was the rate that surgical plan was changed by positive FB findings. Secondary endpoints were rate of positive FB findings and rate of procedural complications. RESULTS: Six hundred and fifteen patients with peripheral subsolid nodules detected by thoracic CT were enrolled. There were 187 (30.4%) male and 428 (69.6%) female patients, mean age was 54.85±10.41 y (range, 26-78). 262 (42.6%) patients had pure GGNs and 353 (57.4%) patients had part-solid nodules. Mean size of nodules was 13.87±6.37 mm (range, 5-30). FB examinations confirmed one (0.16%) adenocarcinoma, seven (1.14%) bronchial variations, one (0.16%) segmental bronchostenosis, one (0.16%) segmental bronchial occlusion and one (0.16%) bronchial inflammation. No complications of FB examinations occurred. 568 (92.35%) thoracoscopic and 47 (7.65%) open surgeries were performed. No established surgical plan was changed by positive FB findings. Final pathologies revealed 26 (4.2%) adenocarcinoma in situ (AIS), 240 (39%) minimal invasive adenocarcinomas (MIAs), 343 (55.8%) invasive adenocarcinomas (IADs), one (0.2%) adenosquamous cell carcinoma, one (0.2%) squamous cell carcinoma, two (0.3%) atypical adenoid hyperplasia and two (0.3%) inflammations. CONCLUSIONS: FB examination was unnecessary in the preoperative assessment of peripheral clinical T1N0 subsolid lung cancer.

Pretreatment Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Factors and Reference Markers of Treatment Options for Locally Advanced Squamous Cell Carcinoma Located in the Middle and Upper Esophagus.

BACKGROUND: Various inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been well authenticated to predict clinical outcomes in numerous types of cancer. The optimal treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC) located in the middle or upper region is still inconclusive. The aim of the study was to examine pretreatment NLR and PLR to select from radical surgery or definitive chemoradiotherapy (dCRT) for these patients. The linkage between pretreatment NLR/PLR and prognosis was also analyzed. METHODS: NLR and PLR were calculated in 113 locally advanced ESCC located in the middle or upper esophagus of patients who underwent radical surgery or dCRT between January 2014 and December 2019. A receiver operating characteristic curve was plotted to select the best cut-off value of NLR and PLR for predicting survival. A survival curve was plotted using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were applied to assess predictors for survival. RESULTS: NLR and PLR were associated with the extent of lymph node metastasis (NLR: P = 0.045; PLR: P = 0.002). Additionally, high PLR and recurrence with distant organ metastasis were closely related (P = 0.014), and NLR was related to the tumor stage (P = 0.043). The results of the multivariate analysis revealed that NLR (>2.07) and PLR (>183.06) were independently associated with poor prognosis. It is noteworthy that surgery was associated with a superior OS compared with dCRT in the low NLR population (P = 0.045). CONCLUSION: Low pretreatment NLR patients are fit to undergo radical surgery with a substantial therapeutic benefit. Pretreatment NLR and PLR are independent predictors for patients with locally advanced ESCC located in the middle and upper esophagus who underwent radical surgery or dCRT.

Hyperbranch-Crosslinked S-SEBS Block Copolymer Membranes for Desalination by Pervaporation.

Sulfonated aromatic polymer (SAP) featuring hydrophilic nanochannels for water transport is a promising membrane material for desalination. SAPs with a high sulfonation degree favor water transport but suffer from reduced mechanical strength and membrane swelling. In this work, a hyperbranched polyester, H302, was introduced to crosslink a sulfonated styrene-ethylene/butylene-styrene (S-SEBS) copolymer membrane. The effects of crosslinking temperature and amount of H302 on the microstructure, and the pervaporation desalination performance of the membrane, were investigated. H302/S-SEBS copolymer membranes with different crosslinking conditions were characterized by various techniques including FTIR, DSC, EA, SEM, TEM and SAXS, and tensile strength, water sorption and contact angle measurements. The results indicate that the introduction of hyperbranched polyester enlarged the hydrophilic microdomain of the S-SEBS membrane. Crosslinking with hyperbranched polyester with heat treatment effectively enhanced the mechanical strength of the S-SEBS membrane, with the tensile strength being increased by 140-200% and the swelling ratio reduced by 45-70%, while reasonable water flux was maintained. When treating 5 wt% hypersaline water at 65 °C, the optimized crosslinked membrane containing 15 wt% H302 and heated at 100 °C reached a water flux of 9.3 kg·m-2·h-1 and a salt rejection of 99.9%. The results indicate that the hyperbranched-S-SEBS membrane is promising for use in PV desalination.

Potential distribution of two invasive pineapple pests under climate change.

BACKGROUND: The number of global invasive species has significantly increased during the past two centuries due to globalization. The understanding of species invasion under climate change is crucial for sustainable biodiversity conservation, community dynamics, ecosystem function, and resource distribution. Two invasive species, Dysmicoccus brevipes (Cockerell) and D. neobrevipes (Beardsley) have greatly expanded their ranges during recent years. These insects are now considered as extremely serious pests for various plants, especially pineapple. In addition, they are the primary vectors for pineapple wilt associated virus. However, the potential distribution range and management strategies for these pests are unclear. RESULTS: In this study, potential risk maps were developed for these pests with MaxEnt (maximum entropy) based on occurrence data under different environmental variables. The potential distributions of these pests were projected for 2050s and 2070s under three climate change scenarios as described in the Special Report on Emissions Scenarios of the Intergovernmental Panel on Climate Change. Results showed that both pests have similar potential distributions, with high environmental suitability in South America, Africa and South Asia. In addition, potential range expansions or reductions were predicted under different climate change scenarios. The annual mean temperature was the most important factor, accounting for 43.4% of D. brevipes distribution. The minimum temperature of coldest month and mean temperature of coldest quarter was found to be responsible for 90.3% of D. neobrevipes distribution. CONCLUSION: This research provided a theoretical reference framework to develop policies in the management and control of these invasive pests. © 2019 Society of Chemical Industry.

Turn-on detection of MicroRNA155 based on simple UCNPs-DNA-AuNPs luminescence energy transfer probe and duplex-specific nuclease signal amplification.

A novel luminescence energy transfer (LET) probe for detection of tumor related microRNAs using NaGdF4:Yb,Er@NaYF4 upconversion nanoparticles (UCNPs) as energy donors and gold nanoparticles (AuNPs) as energy acceptors was developed. Using the double modified complementary DNA sequences of microRNA155 (miRNA155) as a bridge, NaGdF4:Yb,Er@NaYF4 UCNPs and AuNPs were conjugated to form NaGdF4:Yb,Er@NaYF4 UCNPs-DNA-AuNPs nanocomplexes (UCNPs-DNA-AuNPs) probe. The energy transfer would occur when the distance between donor and acceptor gets closer. In the presence of target miRNA155, DNA-RNA heteroduplexes appeared as product, but the luminescence intensity was not changed obviously. In the existence of duplex-specific nuclease (DSN), DSN could hydrolyze the DNA strand of DNA-RNA heteroduplexes, the bridge linked NaGdF4:Yb,Er@NaYF4 UCNPs and AuNPs was destroyed, which induced that the quenched luminescence intensity was recovered and RNA was released. The released miRNA155 could react with another UCNPs-DNA-AuNPs probe to form DNA-RNA heteroduplexes again. This cyclic reaction generates an amplification of luminescence signal for quantitative detection of miRNA155. Under the illumination of 980 nm laser, the concentration ranges from 0.1 nM to 15 nM and the detection of limits was 0.045 nM for detection of miRNA155. Moreover, the UCNPs-DNA-AuNPs probe was used in quantify miRNA155 in cell lysates with satisfactory results.

Detection of tyramine and tyrosinase activity using red region emission NaGdF4:Yb,Er@NaYF4 upconversion nanoparticles.

A selective, simple and environment-friendly type fluorescence sensing platform between upconversion nanoparticles (UCNPs) and melanin-like polymer utilizing the photoinduced electron-transfer (PET) mechanism was developed. The effective fluorescence quenching of UCNPs by melanin-like polymers could detect tyramine and tyrosinase (TYR) activity through the bio-catalysed oxidation of tyramine to the melanin-like polymer products. At optimal conditions, the range of linearity in detection was 0.167-33.3 µΜ for tyramine, and the limit of detection of tyramine was 0.026 µΜ. The linear range of TYR was 0.0033-1 U·mL-1, and the limit of detection of TYR was 0.003 U·mL-1. Furthermore, the strategy could be applied to real sample analysis with satisfactory results.

[Pathogen distribution and bacterial resistance in children with severe community-acquired pneumonia].

OBJECTIVE: To investigate the distribution of pathogens and bacterial resistance in children with severe community-acquired pneumonia (CAP). METHODS: A total of 522 children with severe CAP who were hospitalized in 2016 were enrolled as study subjects. According to their age, they were divided into infant group (402 infants aged 28 days to 1 year), young children group (73 children aged 1 to 3 years), preschool children group (35 children aged 3 to 6 years), and school-aged children group (12 children aged ≥6 years). According to the onset season, all children were divided into spring group (March to May, 120 children), summer group (June to August, 93 children), autumn group (September to November, 105 children), and winter group (December to February, 204 children). Sputum specimens from the deep airway were collected from all patients. The phoenix-100 automatic bacterial identification system was used for bacterial identification and drug sensitivity test. The direct immunofluorescence assay was used to detect seven common respiratory viruses. The quantitative real-time PCR was used to detect Mycoplasma pneumoniae (MP) and Chlamydia trachomatis (CT). RESULTS: Of all the 522 children with severe CAP, 419 (80.3%) were found to have pathogens, among whom 190 (45.3%) had mixed infection. A total of 681 strains of pathogens were identified, including 371 bacterial strains (54.5%), 259 viral strains (38.0%), 12 fungal strains (1.8%), 15 MP strains (2.2%), and 24 CT strains (3.5%). There were significant differences in the distribution of bacterial, viral, MP, and fungal infections between different age groups (P<0.05). There were significant differences in the incidence rate of viral infection between different season groups (P<0.05), with the highest incidence rate in winter. The drug-resistance rates of Streptococcus pneumoniae to erythromycin, tetracycline, and clindamycin reached above 85%, and the drug-resistance rates of Staphylococcus aureus to penicillin, erythromycin, and clindamycin were above 50%; they were all sensitive to vancomycin and linezolid. The drug-resistance rates of Haemophilus influenzae to cefaclor and cefuroxime were above 60%, but it was sensitive to cefotaxime. The drug-resistance rates of Escherichia coli and Klebsiella pneumoniae to ampicillin, cefotaxime, and ceftriaxone were above 60%, but they were sensitive to carbapenems and compound preparation of enzyme inhibitors. CONCLUSIONS: Bacteria are the main pathogens in children with severe CAP and mixed infection is prevalent. The drug-resistance rates of these pathogenic bacteria are high.

PD-L1 and c-MET expression and survival in patients with small cell lung cancer.

BACKGROUND: Blocking the binding between the PD-1 and PD-L1 has been reported to produce antitumor responses. The MET/HGF axis appears to be another signaling pathway frequently altered in small cell lung cancer (SCLC). Our study was aimed to investigate the expression and prognostic roles of PD-L1 and c-MET in SCLC. METHODS: The expression levels of PD-L1 and c-MET were evaluated by immunohistochemical analysis in 83 SCLC specimens. Survival analysis was performed using the Kaplan-Meier method. RESULTS: Of the SCLC specimens, 51.8% and 25.3% exhibited positivity for PD-L1 and c-MET, respectively. Higher PD-L1 expression in tumor specimens was significantly correlated with a limited disease (LD) stage, normal levels of serum lactate dehydrogenase (LDH) and neuron-specific enolase (NSE). No association was found between the levels of c-MET and PD-L1 expression or between c-MET expression and other clinical characteristics. SCLC patients with PD-L1-positive tumors showed significantly longer overall survival (OS) than patients with PD-L1-negative tumors (17.0 vs 9.0, p=0.018). Conversely, those with positive c-MET expression exhibited a shorter OS trend (12.0 vs 15.0, p=0.186). However, sub-analysis of LD-stage patients revealed longer OS among the c-MET-negative group (25.0 vs 14.0; p=0.011). The OS of patients with positivity for both PD-L1 and c-MET showed no significant difference compared with other patients (p=0.17). According to multivariate analyses, neither PD-L1 nor c-MET immunoreactivity was a prognostic factor. CONCLUSION: Expression of PD-L1 was correlated with LD stage and might serve as a prognostic for better OS in SCLC patients. In LD-stage patients, high c-MET expression might be predictive of a poor outcome.

A recurrent headache circumscribed in a coronal line-shaped area around the head: a coronal linear headache.

BACKGROUND: Linear headache (LH) has recently been described as a paroxysmal or continuous head pain restricted in a linear trajectory of 5-10 mm in width, linking one endpoint in occipital or occipitocervical region with another endpoint in ipsilateral nasion or forehead region. The sagittal line-shaped pain area of LH is close and parallel to a sagittal venous sinus, the superior sagittal sinus (SSS). For some patients, the LH had some features resembling the pattern of migraine without aura. CASE DESCRIPTION: A 45 year-old woman complained with a distinct headache for more than half years. The pain trajectory of the headache is confined to a coronal line-shaped area of 5-10 mm in width linking the two points in the bilateral temporal regions with the occipital protuberance. This coronal line-shaped pain area is close and parallel to a coronal cambered venous sinus complex, the combination of the confluences of sinus and the bilateral cavernous sinus (CS), superior petrosal sinus (SPS) linking the CS with transverse sinus (TS) and TS into which the SPS feeds. The patient had a past history of migraine without aura for 10 years and her son had a benign paroxysmal vertigo (BPV) for 12 years. Both of her coronal line-shaped headache and her son's vertigo had well response to sodium valproate. DISCUSSION AND EVALUATION: Its clinical characteristics were distinctly different from those of other two headache entities defined with topographical criteria, nummular headache and epicrania fugax, and different from other existing headache entities except for migraine without aura. CONCLUSION: The distinct coronal line-shaped headache is suggestive of a variant of LH, a coronal LH, and probably belongs to a subtype of migraine without aura as proposed for LH. This coronal LH reinforces the proposal of LH as a new headache syndrome or a subtype of a previously known headache syndrome, probably of migraine.

Linear headache: clinical characteristics of eight new cases.

BACKGROUND: Linear headache (LH) has recently been described as a paroxysmal or continuous fixed head pain restricted in a linear trajectory of 5-10 mm in width, linking one endpoint in occipital or occipitocervical region with another endpoint in ipsilateral nasion or forehead region. For some patients, this headache had some features resembling migraine without aura. METHODS: We made a prospective search of patients presenting with a clinical picture comprised under the heading of LH and we have accessed eight new cases. A detailed clinical feature of the headache was obtained in all cases to differentiate with cranial neuralgia, paroxysmal hemicrania, cervicogenic headache, nummular headache and migraine. RESULTS: The eight LH patients complained of a recurrent moderate to severe, distending, pulsating, or pressure-like pain within a strictly unilateral line-shaped area. The headache duration would be ranged from 1 h to 2 days or persistent for 1-6 months with recurrent worsening of headaches. For some patients, this headache had couple of features similar to that of migraine pattern, such as accompaniments of nausea, vomiting, and phonophobia, diziness, triggering factors of noise, bright night, resting after physical activity, fatigue, menstruation, and response to anti-migraine therapy. CONCLUSIONS: This description reinforces the proposal of LH as a new headache syndrome or a new variant of a previously known headache syndrome, probably of migraine.

Combined action of EGFR tyrosine kinase inhibitors and whole-brain radiotherapy on EGFR-mutated non-small-cell lung cancer patients with brain metastasis.

BACKGROUND: Lung cancer is the most common type of cancer to spread to the brain (brain metastasis [BM]). This study assessed the effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in combination with whole-brain radiotherapy (WBRT) on EGFR-mutant non-small-cell lung cancer (NSCLC) patients with BM. PATIENTS AND METHODS: Thirty-nine patients, who had receieved different EGFR TKIs plus 30 Gy WBRT until disease progression, were retrospectively analyzed between 2010 and 2014. Treatment response was evaluated and survival data were collected and analyzed. RESULTS: Among the 39 patients, 18 had an EGFR exon 19 deletion and 21 had an EGFR exon 21 point mutation. After therapy, 19 (48.7%) patients had complete remission, 12 (30.8%) had partial remission, and eight (20.5%) had stable disease in the intracranial lesions. Besides, there was no single case of complete remission, 21 (53.8%) had partial remission, and 18 (46.2%) had stable disease of the extracranial lesions. The median progression-free survival (PFS) of intracranial lesions and extracranial lesions was 18 and 12 months, respectively. The median overall survival (OS) was 26 months. The univariate analysis showed that graded prognostic assessment (P=0.006) and Karnofsky Performance Scale (P=0.045) were associated with intracranial progression-free survival (iPFS), while recursive partitioning analysis (P=0.049) was associated with OS of patients. CONCLUSION: EGFR TKIs plus concomitant WBRT controlled intracranial lesions of lung cancer metastasis and significantly improved OS of patients. Further studies will be needed to confirm whether this combination treatment could be used as a standard therapy for EGFR-mutated NSCLC patients with BM.

[Research Progression of Maintenance Therapy in Small Cell Lung Cancer].

Lung cancer is one of the common malignant tumors in the world, the incidence of small cell lung cancer is about 15% among them. Small cell lung cancer is highly sensitive to first-line chemotherapy, but most of the patients relapse after the first-line therapy quickly. Despitemany clinical researchof chemotherapy, biological agents and molecular targeting agents since the 1980s, there still remains a substantial lack of consensus regarding the appropriate therapeutic management on maintenance therapy of small cell lung cancer. The review focuses on maintenance therapy of small cell lung cancer.

The SP-AP compound wave in patients with auditory neuropathy.

CONCLUSIONS: This study suggests that the asynchronization of the cochlear afferent pathway may be one mechanism of the etiopathogenesis of auditory neuropathy. OBJECTIVE: To investigate the characteristics of the SP-AP compound wave and its generating mechanism in patients with auditory neuropathy. SUBJECTS AND METHODS: The electrocochleogram (ECochG) was recorded with external ear canal electrode in patients with auditory neuropathy and normal subjects. The peak-latency, amplitude, and time course of the SP-AP compound wave were measured by using an 'assessor-blind' study. The discrepancy between the two groups was evaluated by statistical analysis. RESULTS: The SP-AP compound waveform in the auditory neuropathy patient group was unrepresentative. The transient character of the SP-AP compound wave was more atypical than that for the normal cases. SP dominance (-SP/AP>0.4) appeared. The amplitude of both AP and SP was lower than that of the control group. The width of the SP-AP compound wave at one-third of its peak was greater than that of the control group.