Anaplastic lymphoma kinase (ALK) fusions represent the second most common oncogenic driver mutation in non-small cell lung cancer (NSCLC). As the new class of 3rd generation of ALK tyrosine kinase inhibitor (TKI), lorlatinib has shown robust potency and brain-penetrant clinical activity against a wide spectrum of multiple resistance mutations within the ALK domain detected during crizotinib and 2nd generation ALK TKI treatment. Lorlatinib is generally well-tolerated with unique adverse drug reaction/adverse event, including hyperlipidemia and central nervous system effects, which are mostly mild to moderate severity and manageable through dosage modifications and/or standard medical intervention. For advanced NSCLC with ALK positivity, patients should be evaluated for baseline characteristics and pre-existing medication, informed of the potential toxicities, and periodically monitored to balance benefits and risks. Moreover, a multidisciplinary group of experts is essential to establish a comprehensive diagnostic and therapeutic strategy.
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Aminopyridines ; Carcinoma, Non-Small-Cell Lung/pathology* ; China ; Consensus ; Drug Resistance, Neoplasm/genetics* ; Drug-Related Side Effects and Adverse Reactions/drug therapy* ; Humans ; Lactams ; Lactams, Macrocyclic/adverse effects* ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/adverse effects* ; Protein-Tyrosine Kinases/genetics* ; Pyrazoles

Objective:To improve recognition of the clinical phenotype and genotype of achondroplasia(ACH).Methods:The clinical data and genetic test results of 2 children with ACH were analyzed retrospectively, and the related literature was reviewed.Results:Case 1 was a 1-year-old girl whose mother was short in stature.She was admitted to the hospital due to knee reflexes of both lower limbs for more than 9 months.Physical examination showed that her head circumference was 45 cm and she had short stature, short limbs, low muscle tension of both lower limbs, the developmental quotient was 65 scores.Bilateral ilium and hip joint lesions by X-ray were considered as ACH.According to the submitted gene results, FGFR3 gene c. 1138G >A (p.Gly380Arg) of the girl showed the heterozygous variation, and that gene of her mother showed the heterozygous variation.Case 2 was a 10-month-old girl, who was admitted to the hospital due to limb weakness for over 5 months.Physical examination showed head circumference of 46 cm, short stature, short limbs, reduced muscle tension of limbs, grade 4 muscle strength of limbs, and the developmental quotient was 41 scores.X-ray showed that both lower limbs were in accordance with ACH.The gene results suggested the heterozygous variation of FGFR3 gene c. 1138G >A (p.Gly380Arg) in the girl(a novel mutation), and a wild-type gene in her parents. Conclusions:The clinical features of achondroplasia are diverse.The bone changes and nerve development also need to be recognized and discriminated.

Objective To evaluate the efficacy of MoodGYM Internet-delivered Cognitive Behavior-al Therapy in the treatment of anxiety and depression among nurses. Methods A total of 180 nurses with anxiety or depression were randomly divided into three groups,60 in each group,and 2 months of intervention with MoodGYM and health education ( once a week,30-45 minutes each time) in MoodGYM group and health education group,respectively. Another group was as a control group. Before and after intervention,De-pression Anxiety Stress Scale 21 ( DASS-21),Minnesota Satisfaction Questionnaire ( MSQ) and Subjective Happiness Scale (SHS) were used to evaluate psychological status. Results Compared with pre-interven-tion,the scores of anxiety in DASS-21 ((16. 76±7. 61) vs (9. 67±5. 78),t=21. 339,P<0. 01) and depres-sion in DASS-21 ((13. 86±7. 60) vs (10. 91±7. 12),t=16. 716,P<0. 01) decreased,meanwhile job satis-faction in MSQ((65. 11±11. 12) vs (67. 97±11. 10),t=-16. 400,P<0. 01) and subjective well-being in SHS((17. 67 ± 4. 59) vs (21. 83 ± 3. 53),t=-20. 221, P<0. 01) increased in post-intervention in the MoodGYM group. The scores of anxiety((15. 81±8. 24) vs (12. 45± 7. 68),t=17. 566,P<0. 01) and de-pression((12. 44± 8. 23) vs ( 12. 09 ± 7. 95), t=3. 934,P<0. 01) decreased, meanwhile job satisfaction ((67. 37±9. 76) vs (68. 91± 9. 67),t=-4. 474,P<0. 01) and subjective well-being(( 17. 93± 3. 80) vs (19. 85±3. 96),t=-14. 897,P<0. 01) increased in post-intervention in the health education group. After in-tervention,the effect of improving anxiety, depression, job satisfaction and subjective well-being in the MoodGYM group was more obvious than that in the health education group (P<0. 01). Conclusion -MoodGYM intervention can relieve anxiety and depression of nurses,improve their job satisfaction and sub-jective well-being.

Objective To investigate the prevalence and characters of residual physical symptoms in Chinese depressive patients after acute treatment and the influence on the quality of life and social function.Methods In the multi-centers cross-sectional study,1 503 adult depressive outpatients,from 11 hospitals,who had been treated by antidepressants for 8-12 weeks with significant improvement of at least 50％ by Self-rating Visual Analog Scale were involved.The group with residual physical symptoms could be differentiated by Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) ＞5,while the QIDS-SR16 of remission group was ≤5.The QIDS-SR16,Patient Health Questionnaire-15 (PHQ-15),Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the depressive symptoms,physical symptoms and social function.Results 49.8％ (748/1 503) patients had residual physical symptoms (PHQ-15＞4).The most common physical symptoms (PHQ-15≥1) were feeling tired or having low energy (56.3％,846/1 503),trouble sleeping (50.6％,760/1 503),headache(43.6％,655 / 1 503),constipation,loose stools or diarrhea(41.3％,620/1 503),feeling heart pound or race (37.6％,565/1 503),dizziness (34.0％,511/ 1 503),nausea,gas or indigestion (33.6％,505/1 503),etc.The 75.7％ (555/733) of the physical symptoms (PHQ-15＞4) in residual group was significantly higher than the 25.1％ (193/770;x2=385.38,P＜0.01) in remission group.The differences on social function (t=2.77-10.47) and life quality (t=3.04-11.41) between two groups were significant (P＜0.01).Generalized linear regression analysis showed that gender (female),present history of first episode were related to better social function,and the factors related to both social function and quality of life included residual depressive symptoms,residual physical symptoms of different severity,comorbid medical conditions,age,duration of antidepressant treatment for this episode.Conclusion The rate of residual physical symptoms is higher in patients with major depression who responded to acute phase treatment.The more severe the residual physical symptoms,the worse the quality of life and social function.It suggests that physical symptoms be focused in order to achieve clinical recovery.

Objective To investigate the prevalence and correlates of depression in residents aged 15 and older in Hainan province.Methods Stratified multistage random sampling methods were utilized to identify 12 117 individuals (≥15 years old) from 59 villages (neighborhoods) in 24 towns (streets) within 6 counties (cities) in Hainan Province from September 2010 to November 2011.The subjects were screened with an expanded version of the General Health Questionnaire (GHQ-12) and the respondents were divided into three groups by high risk,moderate risk and low risk of mental disorder,followed by formal diagnosis according to the Structured Clinical Interview for DSM-IV-TR (SCID-I/P) by psychiatrists among 100％ subjects in group with high risk,40％ subjects in group with moderate risk and 10％ subjects in group with low risk.The adjusted rate,standardized rate,and 95％ confidence interval (95％CI) of the one-month and lifetime prevalence were also calculated among the 3 groups of individuals who were diagnosed with depressive disorder.The difference in whether they suffered depression was determined by the chi-squared test.Correlations to depressive disorder and the odds ratio (OR) were explored with multiple regression analysis.Results There were 97 cases of depressive disorders (1-month) and 166 cases of lifetime depressive disorders finally confirmed.The adjusted rate of 1-month prevalence was 1.38％ (95％CI:1.12-1.59) and the life-time adjusted prevalence rate was 2.80％ (95％CI:2.51-3.09).Female (OR=1.55,95％CI:1.12-2.14),mid-age(50-64 y,OR=1.84,95％CI:1.13-2.99),being divorced or living separated (OR=4.87,95％CI:1.86-12.73),suffering chronic diseases (OR=2.19,95％CI:1.56-3.07),and low family income were significantly associated with suffering depressive disorder.Conclusions The prevalence of the depressive disorder among residents aged 15 and older in Hainan province is lower than the nationwide prevalence.People who are female,mid-age,being divorced or not living with the partner,earning a low income,and suffering chronic diseases have more predisposition to develop the depressive disorder in Hainan province.

Objective To investigate the prevalence and characters of residual physical symptoms in Chinese depressive patients after acute treatment and the influence on the quality of life and social function.Methods In the multi-centers cross-sectional study,1 503 adult depressive outpatients,from 11 hospitals,who had been treated by antidepressants for 8-12 weeks with significant improvement of at least 50％ by Self-rating Visual Analog Scale were involved.The group with residual physical symptoms could be differentiated by Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) ＞5,while the QIDS-SR16 of remission group was ≤5.The QIDS-SR16,Patient Health Questionnaire-15 (PHQ-15),Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the depressive symptoms,physical symptoms and social function.Results 49.8％ (748/1 503) patients had residual physical symptoms (PHQ-15＞4).The most common physical symptoms (PHQ-15≥1) were feeling tired or having low energy (56.3％,846/1 503),trouble sleeping (50.6％,760/1 503),headache(43.6％,655 / 1 503),constipation,loose stools or diarrhea(41.3％,620/1 503),feeling heart pound or race (37.6％,565/1 503),dizziness (34.0％,511/ 1 503),nausea,gas or indigestion (33.6％,505/1 503),etc.The 75.7％ (555/733) of the physical symptoms (PHQ-15＞4) in residual group was significantly higher than the 25.1％ (193/770;x2=385.38,P＜0.01) in remission group.The differences on social function (t=2.77-10.47) and life quality (t=3.04-11.41) between two groups were significant (P＜0.01).Generalized linear regression analysis showed that gender (female),present history of first episode were related to better social function,and the factors related to both social function and quality of life included residual depressive symptoms,residual physical symptoms of different severity,comorbid medical conditions,age,duration of antidepressant treatment for this episode.Conclusion The rate of residual physical symptoms is higher in patients with major depression who responded to acute phase treatment.The more severe the residual physical symptoms,the worse the quality of life and social function.It suggests that physical symptoms be focused in order to achieve clinical recovery.

Objective To investigate the prevalence and correlates of depression in residents aged 15 and older in Hainan province.Methods Stratified multistage random sampling methods were utilized to identify 12 117 individuals (≥15 years old) from 59 villages (neighborhoods) in 24 towns (streets) within 6 counties (cities) in Hainan Province from September 2010 to November 2011.The subjects were screened with an expanded version of the General Health Questionnaire (GHQ-12) and the respondents were divided into three groups by high risk,moderate risk and low risk of mental disorder,followed by formal diagnosis according to the Structured Clinical Interview for DSM-IV-TR (SCID-I/P) by psychiatrists among 100％ subjects in group with high risk,40％ subjects in group with moderate risk and 10％ subjects in group with low risk.The adjusted rate,standardized rate,and 95％ confidence interval (95％CI) of the one-month and lifetime prevalence were also calculated among the 3 groups of individuals who were diagnosed with depressive disorder.The difference in whether they suffered depression was determined by the chi-squared test.Correlations to depressive disorder and the odds ratio (OR) were explored with multiple regression analysis.Results There were 97 cases of depressive disorders (1-month) and 166 cases of lifetime depressive disorders finally confirmed.The adjusted rate of 1-month prevalence was 1.38％ (95％CI:1.12-1.59) and the life-time adjusted prevalence rate was 2.80％ (95％CI:2.51-3.09).Female (OR=1.55,95％CI:1.12-2.14),mid-age(50-64 y,OR=1.84,95％CI:1.13-2.99),being divorced or living separated (OR=4.87,95％CI:1.86-12.73),suffering chronic diseases (OR=2.19,95％CI:1.56-3.07),and low family income were significantly associated with suffering depressive disorder.Conclusions The prevalence of the depressive disorder among residents aged 15 and older in Hainan province is lower than the nationwide prevalence.People who are female,mid-age,being divorced or not living with the partner,earning a low income,and suffering chronic diseases have more predisposition to develop the depressive disorder in Hainan province.

To observe the clinical efficacy of dopamine modulator methylphenidate (MPH) of extended-release formulations (MPH-ER) augmentation of ongoing fluvoxamine treatment in refractory obsessive-compulsive disorder (OCD) and its effects on patient's anxiety and sleep quality.
 Methods: A pilot randomized, placebo-controlled, and double-blind trial was conducted at an outpatient, single-center academic setting. Participants included 44 adults with serotonin reuptake inhibitor treatment-refractory OCD and they received a stable fluvoxamine pharmacotherapy with Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores higher than 20. The 44 patients were randomly assigned into a study group and a control group, with 22 patiencs in each group. Fluvoxamine and MPH-ER were given to the study group, while fluvoxamine and placebo were given to the control group, with 8 weeks of the treatment course. Y-BOCS, Hamilton Anxiety Scale (HAMA) were used to assess the efficacy, Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality, and Treatment Emergent Symptom Scale (TESS) was used to evaluate the side effects. Data were analyzed in the intention-to-treat sample.
 Results: The improvement in the Y-BOCS total score, Y-BOCS obsession subscale score and HAMA score were more prominent in the study group than those in the control group (P<0.001). There was no significant difference in PSQI score and TESS score between the two groups. MPH-ER was well tolerated.
 Conclusion: Fluvoxamine combined with MPH-ER is effective in the treatment of refractory obsessive-compulsive disorder. It can improve anxiety and has no adverse effect on sleep quality.
Adult ; Double-Blind Method ; Drug Therapy, Combination ; Fluvoxamine ; therapeutic use ; Humans ; Methylphenidate ; therapeutic use ; Obsessive-Compulsive Disorder ; drug therapy ; Psychiatric Status Rating Scales ; Treatment Outcome

Objective To assess the type and prevalence of residual symptoms in Chinese depressive patients after acute phase treatment and the impact on the quality of life and social function. Method It was a nationwide, multi-center survey. A total of 11 sites participated and 1503 outpatients with major depressive disorder who subjectively self-reported a least 50%improvement after 8-12 weeks of antidepressants treatment were included in this study. Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16), Patient Health Questionnaire-15 (PHQ-15), Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the symptoms and function. Results Altogether 48.8%(733/1503) of patients who self-reported an improvement after acute-phase treatment still presented with residual symptoms (QIDS-SR16>5). The most common residual symptoms (QIDS-SR16≥1) were poor concentration/decision making (82.4%, 604/733), low energy (79.7%, 584/733), loss of interest (75.2%, 551/733), sad mood (72.4%, 531/733) and mid-nocturnal insomnia (72.3%, 530/733). The patients with severe residual symptoms had higher PHQ-15 total score (t=-10.55,P<0.01), lower Q-LES-Q-SF score (t=10.20,P=0.010) and higher SDS score (t=-13.22,P<0.01). Conclusion The great majority of patients who self-report an improvement after acute phase antidepressant treatment may still have residual symptoms. The severity of residual symptoms is associated with significant function impairment and poor life satisfaction.

Objective To assess the type and prevalence of residual symptoms in Chinese depressive patients after acute phase treatment and the impact on the quality of life and social function. Method It was a nationwide, multi-center survey. A total of 11 sites participated and 1503 outpatients with major depressive disorder who subjectively self-reported a least 50%improvement after 8-12 weeks of antidepressants treatment were included in this study. Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16), Patient Health Questionnaire-15 (PHQ-15), Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the symptoms and function. Results Altogether 48.8%(733/1503) of patients who self-reported an improvement after acute-phase treatment still presented with residual symptoms (QIDS-SR16>5). The most common residual symptoms (QIDS-SR16≥1) were poor concentration/decision making (82.4%, 604/733), low energy (79.7%, 584/733), loss of interest (75.2%, 551/733), sad mood (72.4%, 531/733) and mid-nocturnal insomnia (72.3%, 530/733). The patients with severe residual symptoms had higher PHQ-15 total score (t=-10.55,P<0.01), lower Q-LES-Q-SF score (t=10.20,P=0.010) and higher SDS score (t=-13.22,P<0.01). Conclusion The great majority of patients who self-report an improvement after acute phase antidepressant treatment may still have residual symptoms. The severity of residual symptoms is associated with significant function impairment and poor life satisfaction.