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.

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 investigate the differences of cognitive functions among ultra high-risk individuals(UHR),first-episode schizophrenia patients and healthy controls.Methods Twenty four participants meeting clinical inclusion criteria for initial prodromal states (IPS) selected from the first degree relatives of schizophrenia,23 first onset schizophrenia patients from the same family with UHR as well as 30 healthy controls were assessed with a comprehensive neuropsychological test battery including Trail Making Test (TMT),Stroop color word test and the Continuous Performance Test (CPT) to test the speed of information processing and sustained attention ability.Results ①The time of the Trail Making Test in UHR ((45.12±14.87) s) was shorter than first-episode schizophrenia patients((60.43± 19.30)s),but longer than healthy controls((27.13±7.74) s).The whole score of the Stroop color word test in UHR (28.46± 7.87) was higher than first-episode schizophrenia patients (18.78± 6.86),and lower than healthy controls (43.40±9.64).The score of the Continuous Performance Test in UHR (1.86 ± ± 1.05) was significanly higher than first-episode schizophrenia patients(1.17±0.67),but lower than healthy controls (2.63±0.67),and all these differences were significant (P＜0.01).②Taking age,years of education,occupation status,marital status and the Positive and Negative Syndrome Scale (PANSS) scores as the covariance,the analysis of covariance showed TMT and Stroop color word test were still statistically significant.Conclusion There are cognitive function changes in individuals at ultra high-risk for psychosis,lying between first-episode schizophrenia cases and healthy controls.

ObjectiveTo help physicians improve detection rate of depressive and anxiety disorders by exploring the complaints of gastrointestinal(GI) outpatients with these disorders in the general hospitals.Methods A multicenter cross-sectional study was conducted from May to June in 2007.A total of 1995 subjects from 13 general hospitals in China were screened with the hospital anxiety and depression scale ( HADS ) and patient health questionnaire 15-item (PHQ-15).Meanwhile patients'complaints were recorded.Psychiatrists interviewed subjects scored ≥8 on HADS and made diagnoses by using the mini international neuropsychiatric interview(MINI).There were 323 outpatients diagnosed as depressive or anxiety disorders and 1287 outpatients without diagnosis of depressive or anxiety disorders.The complaints and PHQ-15 sores were compared between these two groups.The logistic regression analysis was used to determine the risk of having depressive or anxiety disorders with the number of complaints as an independent variable.ResultsSome symptoms between two groups were statistically significant,including weakness(34.1％ vs 18.8％ ;χ2 =18.04; P=0.000),fatigue(9.6％ vs 5.7％ ;χ2 =6.58,P=0.010)and insomnia( 7.1％ vs 3.4％ ; χ2 =8.87 ; P =0.003 ).Logistic regression analysis showed that with each additional complaint,the odds for an interview-based diagnosis of depressive or anxiety disorders increased,the odds ratio(OR) was 1.12(95％ CI,1.08 ～ 1.17,P=0.000).In comparison to the outpatients without depressive or anxiety disorders,outpatients with these disorders signifycantly had higher PHQ-15 scores (( 11.12 ± 4.92 ) vs (6.68 ± 4.05 ) ; t =16.84,P =0.000).ConclusionThe GI outpatients with depressive and/or anxiety disorders have worse mental heath and more complaints,compared to patients without these disorders.These results may help physicians to better identify depressive disorders and anxiety disorders.

Objective To investigate the requirement and the attitude of the mental health knowledge and some psychological factors indifferent developed regions. Methods The mental patients, their caregivers and normal people in total of 534 were surveyed with the Zung'sSelf-rating Depression Scale, the Questionnaire of Experience and Attitude of the Psychosis (self-edited), the Questionnaire of Requirementand Attitude on Mental Health Knowledge (self-edited), the Social Support Rating Scale and the Simplified Coping Style Questionnaire. Theresults were compared between the developed and the developing regions. Results Compared with those from developing, the requirementwas more and the attitude was more positive on mental health knowledge in all the people from the developed regions; the patients obtainedand applied more support, and took more positive coping style, less depressive emotion; the caregivers took more positive and negative copingstyles, and more depressive emotion; the healthy people applied more support, and took more positive coping style; the caregivers feltmore un-safety and wished the patients stay in hospital longer. Conclusion Development of the region plays a role in the mental health. Thecaregivers need more support and care.

Objective To analyze the family burden of the caregivers of the psychosis patients in community, and the psychosocial factors which influence the family burden.Methods Conducted some questionnaires to survey the requirement and attitude on mental health knowledge,social support,family burden and coping style of the caregivers of the psychosis patients from the twelve communities which served as the stations for the psychosis of the twelve prefectures organized uniformly by Guangdong provincial disabled federation.Results 360 questionnaire was provided,and 308 replied to our questionnaire effectively.The mean score of each single item of the family burden questionnaire was beyond the moderate.The factor score of the economy burden was the highest among the factots of the economy burden(2.33±0.52),the daily activity of the family(2.17±0.53),the recreation activity of the family(2.00±0.58),the family relationship(2.10±0.54),the body health of the family members (2.03±0.65),and the mental health of the family members(2.09±0.68).The bad emotion and experience with the patients aggravated some factors of the family burden(P<0.05～0.01).According to correlation analysis and regression analysis,there were significant relation and impact between family burden with the requirement and attitude on mental health knowledge,subject support,coping style,age,economy,culture and so on(P<0.05～0.01). Conclusion Negative assumption to mental health will aggravate the family burden,transfering the positive message and changing passive coping style will help to reduce the family burden.

Objective To evaluate the effect of combination treatment by psychological intervention and a new atypical antipsychotic Paliperidone extended-release tablets(paliperidone ER)on first-episode schizophrenic out-patients.Methods All 62 patients diagnosed as first-episode schizophrenia by DSM-Ⅳ were randomly allocated into,combination treatment group and control group,for a 12-month treatment study.The combination treatment group was treated by paliperidone ER once a day and psychological counseling once a month,while the control group was treated only by paliperidone ER.The efficacy and social function were assessed by Positive and Negative Syndrome Scale(PANSS)and Personal and Social Performance Scale(PSP)individually at baseline,and following 1,3,6,9,12 months.The remission rate was calculated at the end of the 3rd,6th,9th month.The safety and tolerability were assessed using Barnes Akathisia Scale(BARS),extrapyramidal side effects scale(SAS)and involuntary movement scale(AIMS).Results Twenty-seven patients of combination treatment group and seventeen patients of the control group completed the trial with the discontinuation rate 12.9% and 45.2%,respectively.The difference between the above two groups was statistically significant(P＜0.05).The mean total score of PANSS and the PSP of the both groups were significantly improved(P＜0.05)after treatment.PANSS total score reduced more than 30% compared with baseline,and PSP total score increased more than 7.The remission rate of combination treatment group was 74.2%,51.6% and 67.7% at the end of 3rd,6th,and 9th month,which was better than the control group(45.2%,38.7% and 38.7%)(P＜0.05).Both incidence and types of adverse events were almost same between the two groups.The major adverse events were extrapyramidal symptoms,tachycardia,gastrointestinal discomfort and akathisia.Conclusion Paliperidone ER treatment combined with psychological intervention on first-episode schizophrenia out-patients can improve their treatment compliance by reducing the discontinuation rate.And this combination treatment can increase the remission rate and improve social functioning of the patients.

ObjectiveTo investigate the negative emoion and the relative factors in the caregivers of the schizophrenia patients in community. Methods212 caregivers from 12 communities psychotic service stations in 12 prefectures in Guangdong were investigated with the Zung Self-rate of Depression, the experience and attitude of the psychosis, the requirement and attitude on mental health knowledge, the social support scale, the family burden scale and the simply coping style questionaire. ResultsThere were 112 caregivers with no depression (52.8%), 57 with mild depression (26.9%), 30 with middle depression (14.2%), 13 with severe depression (6.1%). More than 50% caregivers worry about unsafty, getting into trouble, worse reputation, genetics, felt scare, strained relationship with the patients. There were significant differences in the hopelessness, the strained relaionship, treatment in other cities, superstition, hospitalization longer between the depression and no depression group, as well as in the economy burden, the interference in the family living, the amusement of family, the family relaionship, the body health and the mental health of the other family members, but no significant in the factors of the requirement and attitude on mental healh knowledge. The caregivers with depression reported less social support than the caregivers with no depression, but there was no difference between these groups in utilization of support. ConclusionThe caregivers of the schizophrenia patients experience negative emotion in community, who need mental and material assistance and the education of the knowledge about diseases.