Pembrolizumab for the better treatment of EGFR-mutant T790M-negative advanced lung adenocarcinoma patients than dual treatment of pemetrexed plus platinum after tyrosine kinase inhibitor treatment failure.

BACKGROUND: The treatment of lung cancer patients, especially those with epidermal growth factor receptor (EGFR)-mutant T790M-negative adenocarcinoma, after first- or second-line tyrosine kinase inhibitor (TKI) treatment failure is challenging due to the poor prognosis and limited effectiveness of platinum two-drug chemotherapy or chemotherapy plus anti-angiogenesis therapy. It is well-known that pembrolizumab monotherapy exhibits low toxicity and long-term survival, but it is unknown in these patients. METHODS: From September 2018 to March 2021, 460 patients in Jiangmen Central Hospital were included and 82 patients with disease progression in lung adenocarcinoma who remained T790M-negative on the second biopsy were screened. Two groups were divided according to treatment status, and simple random sampling was performed to obtain 32 cases respectively. The safety of the patients was subsequently evaluated by telephone follow-up. RESULTS: The objective response rate (ORR) and disease control rate (DCR) in the pembrolizumab group were 15.63% and 53.13%. In the chemotherapy group, the ORR was 8.33% and the DCR was 25% (P<0.05). In the pembrolizumab group, the progression-free survival (PFS) [14.65 months, 95% confidence interval (CI): 13.03 to 16.28] was significantly higher than that of the control group (9.54 months, 95% CI: 8.43 to 10.65) (P<0.05). In the univariate analysis, programmed cell death protein 1 ligand (PD-L1) expression, smoking status, gender, and whether first-line chemotherapy was associated with survival. In the multivariate analysis, gender [P=0.001; hazard ratio (HR) 10.98, 95% CI: 2.49-46.67], first-line chemotherapy (P=0.037; HR 4.5, 95% CI: 1.1-4.81), and PD-L1 expression (P=0.039; HR 0.16, 95% CI: 0.04-0.68) were correlated with patient survival. Grade 3 or grade 4 treatment-related adverse events were not found in the pembrolizumab group, while 2 cases of grade 3 or 4 treatment-related adverse events occurred in the control group. CONCLUSIONS: In advanced lung adenocarcinoma patients with EGFR-mutant T790M-negative after TKI treatment, pembrolizumab had a higher ORR and PFS. Pembrolizumab in women with first-line chemotherapy and PD-L1 ≥25% of those patients may have a good response and a low rate of adverse reactions. A multicenter, prospective, evidence-based study of pembrolizumab salvage therapy in those patients is warranted for posterior line treatment.

Comparing Behavioral and Psychological Symptoms of Dementia and Caregiver Distress Caused Between Older Adults With Dementia Living in the Community and in Nursing Homes.

Objectives: To investigate differences in behavioral and psychological symptoms of dementia (BPSD) and caregiver distress caused between older adults with dementia living in the community and in nursing homes. Design: A comparative cross-sectional study. Setting and Participants: Participants were recruited from outpatient clinics of a tertiary psychiatric hospital and dementia units of a nursing home in Guangzhou, China. Methods: Neuropsychiatric Inventory was used to assess symptoms and caregiver distress. Dementia severity was determined using the Clinical Dementia Rating. Results: This study included 157 community and 112 nursing home residents with dementia. Clinically significant symptoms (item score ≥ 4) were found in 88.5% of the former and 75% of the latter. Caregivers of 79.6% of the former and 26.8% of the latter reported that at least one of these caused them moderate-to-severe distress (distress score ≥ 3). Among the community patients, anxiety was the most frequent "very severe" symptom, while sleep disorders and agitation caused the most frequent "very severe" caregiver distress. After controlling for dementia severity and medication use, family caregiving remained an independent risk predictor for clinically significant symptoms and moderate-to-severe caregiver distress. The prediction of caregiver distress based on symptom scores varied across caregiver types and individual symptoms (R2 0.36-0.82). Group differences in clinically significant symptoms and moderate-to-severe caregiver distress showed at the stage of moderate-to-severe dementia. Conclusions and Implications: Tailored management strategies to relieve family caregivers' BPSD-induced distress are needed, especially at the stage of moderate-to-severe dementia. An effective service system should be established for supporting family caregivers to cope with BPSD.

Construction of boric acid-functionalized metal-organic frameworks for glycopeptide recognition in the serum of cervical cancer patients.

RATIONALE: Cervical cancer is one of the most common malignant tumors in women, and it is essential to explore potential biomarkers such as glycopeptides closely related to cancer in physiological samples of cervical cancer patients. Sample pretreatment is required before direct detection using mass spectrometry because there are certain limitations. Meanwhile, it is still highly desired to promote the functionalization and application of metal-organic framework (MOF)-derived materials. METHODS: Using a post-synthesis modification method, a novel type of boric acid-functionalized MOF probe (designated as UiO-66@PEI@Au@B(OH)2 ) is prepared for recognition of glycopeptides. The results are obtained using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and nano-liquid chromarography-tandem mass spectrometry. RESULTS: The UiO-66@PEI@Au@B(OH)2 probe exhibits a low detection limit (0.6 fmol µL-1 ), an excellent recovery rate, comparatively good reusability and selectivity (HRP digests:BSA digests = 1:500). When UiO-66@PEI@Au@B(OH)2 is used to selectively capture glycopeptides from the serum of a healthy person and a cervical cancer patient, 101 glycopeptides corresponding to 54 glycoproteins and 108 glycopeptides corresponding to 57 glycoproteins are detected, respectively. CONCLUSIONS: The successful preparation of UiO-66@PEI@Au@B(OH)2 provides a path for the investigation of the functionalization of MOF-derived materials. The excellent performance of UiO-66@PEI@Au@B(OH)2 not only demonstrates the huge potential of functionalized MOFs in the glycoproteome, but also opens up new phases of the application of MOF-based materials.

Structural and Functional Abnormalities of Olfactory-Related Regions in Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Disease.

BACKGROUND: Odor identification (OI) dysfunction is an early marker of Alzheimer's disease (AD), but it remains unclear how olfactory-related regions change from stages of subjective cognitive decline (SCD) and mild cognitive impairment (MCI) to AD dementia. METHODS: Two hundred and sixty-nine individuals were recruited in the present study. The olfactory-related regions were defined as the regions of interest, and the grey matter volume (GMV), low-frequency fluctuation, regional homogeneity (ReHo), and functional connectivity (FC) were compared for exploring the changing pattern of structural and functional abnormalities across AD, MCI, SCD, and normal controls. RESULTS: From the SCD, MCI to AD groups, the reduced GMV, increased low-frequency fluctuation, increased ReHo, and reduced FC of olfactory-related regions became increasingly severe, and only the degree of reduced GMV of hippocampus and caudate nucleus clearly distinguished the 3 groups. SCD participants exhibited reduced GMV (hippocampus, etc.), increased ReHo (caudate nucleus), and reduced FC (hippocampus-hippocampus and hippocampus-parahippocampus) in olfactory-related regions compared with normal controls. Additionally, reduced GMV of the bilateral hippocampus and increased ReHo of the right caudate nucleus were associated with OI dysfunction and global cognitive impairment, and they exhibited partially mediated effects on the relationships between OI and global cognition across all participants. CONCLUSION: Structural and functional abnormalities of olfactory-related regions present early with SCD and deepen with disease severity in the AD spectrum. The hippocampus and caudate nucleus may be the hub joining OI and cognitive function in the AD spectrum.

A combination of two ELISA tests for nasopharyngeal carcinoma screening in endemic areas based on a case-control study.

For populations with a high risk of nasopharyngeal carcinoma (NPC) in Guangdong province in southern China, mass screening is the first choice to prevent death from NPC. To improve the performance of NPC screening, we used a combination based on the IgA antibody against the Epstein-Barr virus (EBV) capsid antigen (VCA-IgA) and the IgA antibody against Epstein-Barr virus nuclear antigen 1 (EBNA1-IgA) to NPC screening by enzyme-linked immunosorbent assay (ELISA). A multiplication model was applied to measure the level of the combination. We evaluated the NPC screening effect of the markers.A case-control study was performed to assess the NPC screening effect of the markers. A total of 10,894 serum specimens were collected, including 554 samples from NPC patients and 10,340 samples from healthy controls. In the training stage, 640 subjects were randomly selected, including 320 NPC cases and 320 healthy controls. In the verification stage, 10,254 subjects were used to verify the NPC screening effect of the combination. Receiver operating characteristic (ROC) analysis was performed. In the verification stage, the combination achieved an sensitivity of 91.45%, a specificity of 93.45%, and an area under the ROC curve (AUC) of 0.978 (95% CI [0.968-0.987]). Compared with VCA-IgA and EBNA1-IgA individually, the combination had an improved screening performance. A probability (PROB) calculated by logistic regression model based on VCA-IgA and EBNA1-IgA was applied to NPC screening by ELISA in China. The AUC of the combination was a little bit larger than the PROB. There was a slight increase (3.13%) in the sensitivity of the combination compared to the sensitivity of the PROB, while the specificity was lower for the combination (92.50%) than for the PROB (95.94%). We successfully applied a combination of two ELISA tests based on VCA-IgA and EBNA1-IgA for NPC screening by using a multiplication model. The results suggested that the combination was effective and can be an option for NPC screening.

Comparative Study of Cognitive Function Between Treatment-Resistant Depressive Patients and First-Episode Depressive Patients.

OBJECTIVE: Despite reports of cognitive dysfunction during the acute phase of depression, there is a lack of studies in patients with treatment-resistant depression (TRD). The aim of this study was to investigate the cognitive function profile of TRD and compare cognitive dysfunction between subjects with TRD and first-episode depression. PATIENTS AND METHODS: The study included 31 patients with TRD and 53 with first-episode depression. Cognitive function was assessed by a series of neuropsychological tools such as the verbal fluency test, Modified Wisconsin Card Sorting Test (M-WCST), Tower of Hanoi test, Chinese-revision of the Wechsler Adult Intelligence Scale (WAIS-RC), and Trail Making Test A and B. RESULTS: There were no significant demographic differences between the TRD, first-episode depression, and normal control groups (gender, age, years of education). The full-scale, verbal, and performance intelligence quotients measured with the WAIS-RC were also not significantly different (p>0.05). The normal group scores were all significantly better than TRD and first-episode depression, and the TRD group performed significantly worse than subjects with first-episode depression on Trail Making Test B, two WCST subscales, and the profile score of the Tower of Hanoi test (all p<0.05). CONCLUSION: Patients with depression exhibited global impairments in cognitive function, and these were more common in TRD. Poor executive function may play an important role in TRD.

Prevalence of mild cognitive impairment and its subtypes in community-dwelling residents aged 65 years or older in Guangzhou, China.

BACKGROUND: Prevalence of mild cognitive impairment (MCI) has been reported substantial variations, and mostly in Western countries. Less is known about MCI in the south of China. The study is to estimate the prevalence of MCI and its subtypes in residents aged 65year or older in community-dwelling residents of Guangzhou, China. METHODS: The study was a community-based, cross-sectional study conducted in rural and urban areas of Guangzhou between April and October 2009. Eight communities were randomly selected using a cluster sampling method. Each elderly was interviewed with Montreal Cognitive Assessment, the Mini-Mental state examination, Auditory Verbal Learning Test, the Clinical Dementia Rating scale et al. MCI was classified as amnestic MCI (a-MCI) or nonamnestic MCI (na-MCI). RESULTS: 2427 individuals were contacted, but in-person interviews were conducted with 2111 participants. 299 participants with MCI were identified. The prevalence of MCI, a-MCI and na-MCI was 14.2%, 12.2%, 2.0% respectively. The prevalence of MCI and a-MCI increased with age, decreased with education level, and was higher in rural areas than in urban areas. The difference of prevalence of MCI and a-MCI between women with men wasn't statistically significant(MCIχ2=1.0, OR 0.9, 95%CI=0.6-1.2; a-MCIχ2=1.0, OR 0.9, 95%CI=0.6-1.2), when controlling for education by logistic regression analysis. CONCLUSIONS: The results suggest that 14.2% of elderly individuals are affected by MCI in Guangzhou, China. And MCI was dominated by a-MCI. The prevalence of MCI and a-MCI increased with age, decreased with education level, and was higher in the rural population compared to the urban population.

Comparison of three data mining models for predicting diabetes or prediabetes by risk factors.

The purpose of this study was to compare the performance of logistic regression, artificial neural networks (ANNs) and decision tree models for predicting diabetes or prediabetes using common risk factors. Participants came from two communities in Guangzhou, China; 735 patients confirmed to have diabetes or prediabetes and 752 normal controls were recruited. A standard questionnaire was administered to obtain information on demographic characteristics, family diabetes history, anthropometric measurements and lifestyle risk factors. Then we developed three predictive models using 12 input variables and one output variable from the questionnaire information; we evaluated the three models in terms of their accuracy, sensitivity and specificity. The logistic regression model achieved a classification accuracy of 76.13% with a sensitivity of 79.59% and a specificity of 72.74%. The ANN model reached a classification accuracy of 73.23% with a sensitivity of 82.18% and a specificity of 64.49%; and the decision tree (C5.0) achieved a classification accuracy of 77.87% with a sensitivity of 80.68% and specificity of 75.13%. The decision tree model (C5.0) had the best classification accuracy, followed by the logistic regression model, and the ANN gave the lowest accuracy.

[Cost-effectiveness evaluation of seven screening strategies for nasopharyngeal carcinoma].

OBJECTIVE: To evaluate the cost-effectiveness of different screening strategies for nasopharyngeal carcinoma (NPC) and recommend a preferable NPC screening strategy. METHODS: A Markov simulation model was constructed based on the natural history of NPC. Seven strategies (A. Annual screening; B. Annual screening for (Epstein-Barr virus, EBV) EBV-seropositive subjects, triennial screening for seronegative subjects; C. Biennial screening; D. Triennial screening; E. 4-year screening; F. 5-year screening; G. 6-year screening) were evaluated. The NPC-pickup rate, cost, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. RESULTS: The ICERs of the 7 strategies were 83 111.6, 47 768.9, 50 164.7, 40 016.2, 34 272.8, 32 215.6, and 32 248.0 Yuan/QALY, respectively. The discounted QALYs of the strategies were 23 079.9, 22 955.6, 22 810.4, 22 636.5, 22 522.7, 22 445.0, and 22 361.9 years, respectively. The ICERs of the strategies were less than three times of the average per capita gross domestic product (89 976 Yuan) in China in 2010. The strategy A achieved a highest NPC pick-up rate (81.7%), a highest discounted QALY and a smallest number of NPC death (681), but a highest discounted cost and a greatest ICER. Compared with the strategy A, the strategy B achieved a little smaller NPC pick-up rate (73.1%), a little smaller number of NPC death (707), however, the ICER of the strategy B decreased by 38.2%. CONCLUSION: The strategy B (annual screening for EB virus seropositive subjects and triennial screening for seronegative subjects) is a preferable option for NPC screening.

Which factors are associated with actual 5-year survival of oesophageal squamous cell carcinoma?

UNLABELLED: OBJECTIVES; The demographic and clinicopathologic factors associated with 5-year survivors have not been well documented in oesophageal squamous cell carcinoma (OSCC). We evaluated factors predictive of actual 5-year survival in the present research. METHODS: We analysed 1241 patients underwent oesophagectomy for invasive OSCC retrospectively. The demographic and clinicopathologic characteristics were compared between patients who were alive >5 years after oesophagectomy and patients who died within 5 years of oesophagectomy. RESULTS: Univariate analysis showed significant differences between the two groups regarding 11 different factors. Further analysis by logistic regression showed that eight factors were identified as independent predictors of actual 5-year survival. CONCLUSIONS: The independent positive predictors for actual 5-year survival are younger patients, female gender, absence of weight loss, R0 resection, lower pathological T stage, lower pathological N stage, higher histologic grade and more resected lymph nodes.

Neuropsychological performance in bipolar I, bipolar II and unipolar depression patients: a longitudinal, naturalistic study.

BACKGROUND: It has been suggested that cognitive deficits existed in mood disorders. Nevertheless, whether neuropsychological profiles differ three main subtypes of mood disorder (Bipolar I, Bipolar II and UP) remain understudied because most current studies include either mixed samples of bipolar I and bipolar II patients or mixed samples of different states of the illness. The main aim of the present study is to determine whether, or to some extent, specific cognitive domains could differentiate the main subtypes of mood disorders in the depressed and clinically remitted status. METHOD: Three groups of bipolar I (n=92), bipolar II (n=131) and unipolar depression (UP) patients (n=293) were tested with a battery of neuropsychological tests both at baseline (during a depressive episode) and after 6 weeks of treatment, contrasting with 202 healthy controls on cognitive performance. The cognitive domains include processing speed, attention, memory, verbal fluency and executive function. RESULTS: At the acute depressive state, the three patient groups (bipolar I, bipolar II and UP) showed cognitive dysfunction in processing speed, memory, verbal fluency and executive function but not in attention compared with controls. Post comparisons revealed that bipolar I depressed patients performed significantly worse in verbal fluency and executive function than bipolar II and UP depressed patients. No difference was found between bipolar II and UP depressed patients except for the visual memory. After 6 weeks of treatment, clinically remitted bipolar I and bipolar II patients only displayed cognitive impairment in processing speed and visual memory. Remitted UP patients showed cognitive impairment in executive function in addition to processing speed and visual memory. The three remitted patient groups scored similarly in processing speed and visual memory. LIMITATION: Clinically remitted patients were just recovered from a major depressive episode after 6 weeks of treatment and in relatively unstable state. CONCLUSION: Bipolar I, bipolar II and UP patients have a similar pattern of cognitive impairment during the state of acute depressive episode, but bipolar I patients experience greater impairment than bipolar II and UP patients. In clinical remission, both bipolar and UP patients show cognitive deficits in processing speed and visual memory, and executive dysfunction might be a status-maker for bipolar disorder, but a trait-marker for UP.

Establishment of VCA and EBNA1 IgA-based combination by enzyme-linked immunosorbent assay as preferred screening method for nasopharyngeal carcinoma: a two-stage design with a preliminary performance study and a mass screening in southern China.

A two-stage study was conducted in southern China to determine and validate an optimal combination of Epstein-Barr virus (EBV)-related seromarkers for nasopharyngeal carcinoma (NPC) screening. In the first stage, six seromarkers [VCA-IgA, EA-IgA, Epstein-Barr virus nuclear antigen 1 (EBNA1-IgA), EBNA1-IgG, Zta-IgA and Rta-IgG] were detected by enzyme-linked immunosorbent assay (ELISA) and two traditional NPC screening seromarkers (VCA-IgA and EA-IgA) were detected by immunofluorescence assay (IFA) in serum samples from 191 NPC patients and 337 controls. An optimal combination of seromarkers for NPC diagnosis was selected using logistic regression models. Results showed that the diagnostic performances of VCA-IgA and EA-IgA tested by ELISA were superior to the performances of the same seromarkers by IFA. VCA-IgA combined with EBNA1-IgA by ELISA was identified as the optimal combination, with an area under the receiver operating characteristic (ROC) curve (AUC) up to 0.97, a sensitivity of 95.3% and a specificity of 94.1% for classification of NPCs vs. controls. In the second stage, 5,481 participants aged 30-59 years and without clinical evidence of NPC were recruited into a population-based NPC screening program from May 2008 to February 2009 in Sihui City, China. Their sera were tested simultaneously by both the new and the traditional screening schemes and eight early stage NPC patients were subsequently histopathologically confirmed. The traditional and the new screening schemes had comparable specificity (estimated as 98.5%), but the sensitivity of the new scheme (75.0%) was significantly higher than that of the traditional one (25.0%). The combination of VCA-IgA and EBNA1-IgA by ELISA outperforms the traditional NPC screening scheme and could become the preferred serodiagnostic strategy for NPC screening in high-incidence areas.

Evaluation of choline acetyltransferase gene polymorphism (2384 G/A) in Alzheimer's disease and mild cognitive impairment.

BACKGROUND/AIMS: It has been hypothesized that choline acetyltransferase (ChAT) activity might be associated with cognitive impairment in Alzheimer's disease (AD). A functional single nucleotide polymorphism (2384 G/A) of ChAT was proposed to be associated with AD risk and age of onset. The aim of this study was to evaluate this polymorphism in a cohort of Chinese AD patients and patients with mild cognitive impairment (MCI). METHODS: We conducted a case-control study in 273 cases of sporadic AD, 97 MCI patients and 271 nondemented controls from the Chinese Han population. RESULTS: In AD, ChAT 2384 A carriers had a significantly earlier age of onset and worse individual cognitive function in Fuld Object-Memory Evaluation; in MCI, the carriers of both 2384 A and ApoE epsilon4 had a significantly earlier age of onset. CONCLUSION: ChAT 2384 A allele is a risk factor for AD and MCI.