Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Objective To study the role of ubiquitin-conjugating enzyme 9(UBC9)in the pyroptosis of homocysteine-induced macrophages mediated by small ubiquitin-like modifier(SUMO)modification.Methods First,the effects of homocysteine at different concentrations(0 μmol/L,50 μ.mol/L,100 μmol/L,150 μmol/L and 200 μmol/L)on the viability and pyrodeath of mouse macrophages(RAW264.7)were detected by CCK-8 and Western blot.Western blot was used to detect the expression levels of UBC9,SUMO-1,and the inflammatory cytokine IL-1β in different groups of cells.qRT-PCR was used to detect the mRNA expression of UBC9 before and after RNA interference and the expression of UBC9,pyrogen-related protein,and SUMO-1 after RNA interference.Results After stimulation with 100 μmol/L homocysteine,the effect of macrophage activity was minimal,and NLRP3 and Caspase-1 were the proteins with the most obvious increase in expression(P＜0.05).Compared with the Control group,the Hcy group's expression of IL-1β and SUMO-1 was increased(P＜0.01).Compared with the Control group,the Hcy group's UBC9 protein and mRNA levels were increased(P＜0.05).The expression of NLRP3,Caspase-1,IL-1β,UBC9,and SUMO-1 was decreased in the si-UBC9+Hcy group compared with the si-NC+Hcy group(P＜0.01).Conclusions Homocysteine induces pyroptosis in macrophages,and its mechanism of action is related to the up-regulation of UBC9 to induce SUMO modification.

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 analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.

Objective:To explore the expression of GATA3 in breast cancer tissues and its correlation with pathological types of tumors and prognosis.Methods:The paraffin samples of breast cancer tissues and paraffin samples of normal para-cancerous tissues from 100 breast cancer patients who underwent surgical excision in Luanzhou People′s Hospital of Hebei Province from June 2014 to June 2017 were retrospectively analyzed. The expression of GATA3 in breast cancer tissues and normal para-cancerous tissues was detected by immunohistochemistry. And its significance in prognosis evaluation was analyzed. The survival rates of patients with different GATA3 expression were analyzed by Kaplan-Meier survival curves.Results:The positive expression rate of GATA3 in breast cancer tissues was significantly lower than that in normal para-cancerous tissues: 61.00% (61/100) vs. 86.00% (86/100), and there was statistical difference ( χ2 = 16.044, P<0.01). The positive expression rate of GATA3 was related with histological grading, lymph node metastasis, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2), P<0.05, and not related with age, TNM staging or tumor long diameter ( P>0.05). Multivariate Logistic regression analysis result showed that histological grading at gradeⅢ, positive HER-2 and lymph node metastasis were independent risk factors of GATA3 positive expression of breast cancer tissues in patients with breast cancer ( OR = 1.747, 2.699 and 1.730; 95% CI 1.107 to 2.758, 1.035 to 7.039 and 1.139 to 2.626; P<0.05). The 3-year survival rate in GATA3 positive patients was significantly higher than that in GATA3 negative patients: 86.89% (53/61) vs. 66.67% (26/39), and there was statistical difference ( P<0.05). Conclusions:The positive expression rate of GATA3 in breast cancer tissues is significantly lower than that in normal para-cancerous tissues. The expression level of GATA3 is related to pathological types of breast cancer, histological grading, lymph node metastasis, ER, PR and HER-2. The expression level of GATA3 is of certain significance in evaluating prognosis of patients.

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.