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.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Guided by Zhang Zhongjing's axiom that"blood stasis induces water",this study develops stage-specific treatment strategies for edema in Kidney Consumption Disorder by examining its four-stage pathogenic progression:Sluggish Flow → Stagnant Obstruction → Depressed Accumulation → Stasis Congelation.We propose an integrated approach that reinforces the root by warming the kidney and replenishing essence,while addressing the branch by activating blood circulation and promoting diuresis.Stage-specific interventions include:for the Sluggish Flow Phase,warming and tonifying kidney Yang combined with unblocking Yang to promote uri-nation;for the Stagnant Obstruction Phase,warming the kidney and replenishing essence supported by activating blood circulation and freeing the collateral channels;for the Depressed Accumulation Phase,quickening blood and resolving stasis,regulating Qi and trans-forming turbidity,along with warming the kidney and strengthening essence;and for the Stasis Congelation Phase,expelling stagnant accumulations while simultaneously regulating essence and blood.This framework advances novel pattern-determined strategies for Kid-ney Consumption edema management.

Objective To explore the influencing factors of acute kidney injury in severe burn patients,and to construct a visual risk nomogram model.Methods A total of 390 patients with severe burn admitted to the Institute of Burn Frostbite and Tissue Function Reconstruction of Chinese People's Armed Police Force Specialty Medical Center from January 2018 to January 2022 were collected as an internal training data set,and 50 patients with severe burn admitted from February to December 2022 were collected as an external validation data set.The 390 patients of the internal training data set were divided into the acute kidney injury group and the non-acute kidney injury group according to the occurrence of acute kidney injury,and the baseline data of patients in the two groups were compared.Univariate and multivariate Logistic regression were used to analyze the risk factors of acute kidney injury in severe burn patients of the internal training data set,and a nomogram model was drawn.Subsequently,the model was verified both internally and externally.Kaplan-Meier analysis and Log-rank test were used to compare the 90-day survival rate of patients between the acute kidney injury group and the non-acute kidney injury group.Results The burn area(OR=1.18,95%CI:1.06 to 2.36,P=0.004),sequential organ failure assessment(SOFA)score(OR=1.81,95%CI:1.21 to 5.92,P<0.001),inhalation injury(OR=3.21,95%CI:1.23 to 6.35,P<0.001),neutrophil to lymphocyte ratio(NLR)(OR=1.22,95%CI:1.05 to 3.65,P<0.001)and albumin(ALB)(OR=0.78,95%CI:0.57 to 0.92,P=0.011)were the independent risk factors for the development of acute kidney injury in severe burn patients.The nomogram model was established by the above factors.The area under the receiver operating characteristic curve(AUC)of the internal training data set was 0.833(95%CI:0.752 to 0.935),the sensitivity was 81.2%,and the specificity was 83.2%.The AUC of the external validation data set was 0.842(95%CI:0.762 to 0.912),the sensitivity 87.2%,and the specificity was 78.7%.The 90-day survival rate of patients in the acute kidney injury group after burns was significantly lower than that in the non-acute kidney injury group(P<0.001).Conclusion Larger burn area,higher SOFA score,combined inhalation injury,increased NLR,and decreased ALB level are the risk factors for the occurrence of acute kidney injury in severe burn patients,which are related to the 90-day survival rate of patients after burns.The nomogram model based on the risk factors can provide certain reference for clinical individualized prevention and treatment of acute kidney injury in severe burn patients.

Diaphragmatic dysfunction often occurs in ICU patients with prolonged mechanical ventilation, which seriously affects patients′prognosis. This article reviewed the progress of rehabilitation treatment of diaphragmatic dysfunction in ICU patients with mechanical ventilation, focused on the concept and assessment of diaphragm rehabilitation, the current status, evaluation indexes, emphasized the importance of nurses, analyzed the dilemmas and countermeasures in the application, which aimed to provide a reference for the promotion of diaphragm rehabilitation in clinical practice.

Objective To assess the impact of long working hours on sleep disorders among manufacturing workers and explore the roles of alcohol consumption and mental health factors(anxiety and depressive symptoms)in this association.Methods A cross-sectional study design was used to survey 1 336 manufacturing workers in Shenzhen.We collected the data of their demographic characteristics,work-related factors,personal behaviors,sleep disorders,and mental health status.Multivariate Logistic regression analysis was used to assess the association between long working hours and sleep disorders.Stratified analysis and mediation effect models were applied to examine the effect modification by alcohol consumption and the mediating role of mental health factors,respectively.Results Among the study samples,31.8％reported long working hours and 45.6％had sleep disorders.Multivariate Logistic regression analysis showed that long working hours significantly increased the risk of sleep disorders(adjusted OR=2.073,95％ CI:1.478-2.907,P＜0.001).Stratified analysis revealed that the association between long working hours and sleep disorders was more pronounced among alcohol consumers(adjusted OR=2.556,95％ CI:1.432-4.562,P=0.001).Mediation effect analysis showed that anxiety and depressive symptoms partially mediated the relationship between long working hours and sleep disorders,with indirect effects accounting for 25.71％ and 27.14％,respectively.Conclusion Long working hours increase the risk of sleep disorders among manufacturing workers,particularly among those who consume alcohol.Anxiety and depressive symptoms partially explain the association between long working hours and sleep disorders.

Guided by Zhang Zhongjing's axiom that"blood stasis induces water",this study develops stage-specific treatment strategies for edema in Kidney Consumption Disorder by examining its four-stage pathogenic progression:Sluggish Flow → Stagnant Obstruction → Depressed Accumulation → Stasis Congelation.We propose an integrated approach that reinforces the root by warming the kidney and replenishing essence,while addressing the branch by activating blood circulation and promoting diuresis.Stage-specific interventions include:for the Sluggish Flow Phase,warming and tonifying kidney Yang combined with unblocking Yang to promote uri-nation;for the Stagnant Obstruction Phase,warming the kidney and replenishing essence supported by activating blood circulation and freeing the collateral channels;for the Depressed Accumulation Phase,quickening blood and resolving stasis,regulating Qi and trans-forming turbidity,along with warming the kidney and strengthening essence;and for the Stasis Congelation Phase,expelling stagnant accumulations while simultaneously regulating essence and blood.This framework advances novel pattern-determined strategies for Kid-ney Consumption edema management.

ObjectiveThis paper aims to use the digital muscle function assessment system Myoton PRO to assess the correlation between muscle tension，clinical characteristics， and traditional Chinese medicine（TCM） syndromes in patients with hepatolenticular degeneration ［also known as Wilson disease（WD）］. MethodsA total of 104 patients with WD accompanied by abnormal muscle tension（increased or decreased，hereinafter the same） who were hospitalized in the Brain Disease Centre of the First Affiliated Hospital of Anhui University of Chinese Medicine from April 2021 to November 2023 were selected，all of whom were subjected to TCM syndrome diagnosis and Myoton PRO for the measurement of F value of muscle tension，Goldstein， and UWDRS-N scales. The age of onset of the disease and disease duration were analyzed，and the differences and correlations of the above indexes in different TCM syndromes of WD were analyzed ResultsAmong the 104 patients with WD ，the phlegm and stasis syndrome was the most common（60 patients），followed by the damp-heat syndrome（33 patients），and the least common was the liver-kidney Yin deficiency syndrome（11 patients）. The F value of the phlegm and stasis syndrome group was higher than that of the liver-kidney Yin deficiency syndrome group and the damp-heat syndrome group（P<0.01）. The F value of the damp-heat syndrome group was higher than that of the liver-kidney Yin deficiency syndrome group（P<0.05），and the F value of the lower limbs of each group was higher than that of the upper limbs（P<0.01）. Goldstein and UWDRS-N scores of the patients in the phlegm and stasis syndrome group were higher than those in the damp-heat syndrome group and the liver-kidney Yin deficiency syndrome group（P<0.05）. There was no significant difference between the Goldstein and UWDRS-N scores of patients in the liver-kidney Yin deficiency syndrome group and the damp-heat syndrome group. Correlation analysis revealed that the age of onset and duration of the disease were positively correlated with the F values of the lower limbs（r=0.20，P<0.05，r=0.38，P<0.01）and had no significant correlation with those of the upper limbs. The F value levels of muscle tension of all limbs in the three groups of patients were positively correlated with the Goldstein and UWDRS-N scores（muscle tension of the upper limbs in the phlegm and stasis syndrome group，r=0.36，P<0.01，r=0.42，P<0.01. muscle tension of the lower limbs in the phlegm and stasis syndrome group，r=0.70，P<0.01，r=0.60，P<0.01. muscle tension of the upper limbs in the damp-heat syndrome group，r=0.64，P<0.01，r=0.53，P<0.01. muscle tension of the lower limbs in the damp-heat syndrome group，r=0.59，P<0.01，r=0.70，P<0.01. muscle tension of the upper limbs in the liver-kidney Yin deficiency syndrome group，r=0.70，P<0.01，r=0.74，P<0.01. muscle tension of the lower limbs in the liver-kidney Yin deficiency syndrome group，r=0.85，P<0.01，r=0.62，P<0.01）. Conlusion： The digital muscle function assessment system Myoton PRO can objectively evaluate the muscle tension level of patients with WD accompanied by abnormal muscle tension. This level has significant differences among different TCM syndromes and can evaluate the patient's condition to some extent.

Background Long working hours are a risk factor for occupational health, particularly in labor-intensive sectors such as manufacturing. Prolonged working hours may have adverse effects on the sleep and mental health of employees. Objective To investigate the impact of long working hours on insomnia, anxiety, and depression symptoms among manufacturing industry employees and provide scientific evidence for relevant occupational health interventions. Methods A cross-sectional study was conducted involving 1524 employees from eight manufacturing enterprises in Shenzhen. Data were collected using a structured questionnaire, which included demographic characteristics, work conditions (e.g., years of employment, job type, shift work, night shifts, weekly working hours), personal behaviors (e.g., smoking and drinking habits), and the occurrence of insomnia (by the Athens Insomnia Scale), anxiety (by the Generalized Anxiety Disorder Scale), and depression (by the Patient Health Questionnaire). Participants were classified into two groups based on working hours: long working hours (≥55 h per week) and normal working hours (35-40 h per week). Binary logistic regression was used to analyze the association between long working hours and the occurrences of insomnia, anxiety, and depression symptoms. Results A total of 1491 manufacturing industry employees were included in the study (response rate: 97.8%). The sample consisted of 54.19% males and 45.81% females, with the largest proportion was those aged 40-49 years (45.48%). The proportion of workers with long working hours in the total population was 31.52%, with the highest proportion among production and technical employees (36.49%). The prevalence of insomnia, anxiety, and depression symptoms was 56.2%, 26.6%, and 23.8%, respectively in the long working hours group, significantly higher than those in the normal working hours group (P<0.05). After adjusting for potential confounders, the logistic regression analysis showed that long working hours were significantly associated with increased risks of insomnia (OR=2.16, 95%CI: 1.60, 2.91), anxiety (OR=1.94, 95%CI: 1.34, 2.81), and depression symptoms (OR=1.62, 95%CI: 1.11, 2.38) compared to normal working hours. Conclusion Long working hours significantly increase the risks of insomnia, anxiety, and depression symptoms among manufacturing industry employees. It is recommended that measures should be implemented to limit working hours, increase rest periods, and provide occupational health education and psychological support to improve the sleep and mental health of employees.