Objective To explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). Methods The Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. Gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients’ 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. Results Differentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. The scRNA-seq analysis showed that RORA and KLF10 were mainly expressed in natural killer cells. Conclusion The prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.

Objective To apply network Meta-analysis to evaluate the clinical efficacy of 3 classical prescriptions Xuebijing,Xijiao Dihuang decoction,and Qingyuan Shenghua decoction in treating sepsis complicated with coagulation dysfunction.Methods Computer-based searches were conducted in the following databases:China National Knowledge Infrastructure(CNKI),VIP Database,Wanfang Database,PubMed Database,and the Cochrane Library,to retrieve randomized controlled trial(RCT)on the treatment of sepsis complicated with coagulation dysfunction and disseminated intravascular coagulation(DIC)using 3 classical prescriptions-Xuebijing,Xijiao Dihuang decoction,and Qingyuan Shenghua decoction.The search period was from database inception to May 1,2023.The control group received conventional Western medicine treatment alone,while the treatment group received additional therapy with Xuebijing,Xijiao Dihuang decoction,or Qingyuan Shenghua decoction.Primary outcome measures included the sequential organ failure assessment(SOFA)score,acute physiology and chronic health evaluationⅡ(APACHEⅡ)score,activated partial thromboplastin time(APTT),D-dimer,fibrinogen(Fib),prothrombin time(PT)and platelet count(PLT).Two researchers evaluated and screened the included studies,performed data extraction,and assessed literature quality.The network Meta-analysis was conducted using Stata 17.0 software.Results A total of 27 RCTs were finally included,with 2268 cases enrolled.The network Meta-analysis results showed that the surface under the cumulative ranking curve(SUCRA):①In terms of improving APACHEⅡscores:Qingyuan Shenghua decoction combination group(93.2%)>Xuebijing combination group(67.9%)>Xijiao Dihuang decoction combination group(37.5%)>conventional Western medicine treatment alone group(1.4%);②In terms of improving SOFA scores:Qingyuan Shenghua decoction combination group(93.7%)>Xuebijing combination group(63.0%)>Xijiao Dihuang decoction combination group(41.8%)>conventional Western medicine treatment alone group(1.5%);③In terms of improving APTT:Qingyuan Shenghua decoction combination group(95.6%)>Xijiao Dihuang decoction combination group(57.1%)>Xuebijing combination group(46.6%)>conventional Western medicine treatment alone group(0.7%);④In terms of improving D-dimer:Xijiao Dihuang decoction combination group(86.1%)>Qingyuan Shenghua decoction combination group(80.5%)>Xuebijing combination group(33.3%)>conventional Western medicine treatment alone group(0.0%);⑤In terms of improving Fib:Xijiao Dihuang decoction combination group(97.5%)>Qingyuan Shenghua decoction combination group(63.5%)>conventional Western medicine treatment alone group(37.8%)>Xuebijing combination group(1.2%);⑥In terms of shortening PT:Qingyuan Shenghua decoction combination group(67.5%)>Xuebijing combination group(67.4%)>Xijiao Dihuang decoction combination group(63.0%)>conventional Western medicine treatment alone group(2.2%);⑦In terms of improving PLT:Xuebijing combination group(83.6%)>Qingyuan Shenghua decoction combination group(54.9%)>Xijiao Dihuang decoction combination group(49.4%)>conventional Western medicine treatment alone group(12.1%).Conclusion The 3 classical Chinese herbal prescriptions combined with conventional Western medicine all demonstrated significant improvement effects on sepsis complicated with coagulation dysfunction.Among them,Xuebijing showed the most stable clinical efficacy,improving both disease severity scores and multiple coagulation indicators.Qingyuan Shenghua decoction was more effective in improving overall prognosis compared to the other two prescriptions.As for Xijiao Dihuang decoction,its clinical efficacy in ameliorating sepsis-related thrombosis warrants further exploration.

Objective To apply network Meta-analysis to evaluate the clinical efficacy of 3 classical prescriptions Xuebijing,Xijiao Dihuang decoction,and Qingyuan Shenghua decoction in treating sepsis complicated with coagulation dysfunction.Methods Computer-based searches were conducted in the following databases:China National Knowledge Infrastructure(CNKI),VIP Database,Wanfang Database,PubMed Database,and the Cochrane Library,to retrieve randomized controlled trial(RCT)on the treatment of sepsis complicated with coagulation dysfunction and disseminated intravascular coagulation(DIC)using 3 classical prescriptions-Xuebijing,Xijiao Dihuang decoction,and Qingyuan Shenghua decoction.The search period was from database inception to May 1,2023.The control group received conventional Western medicine treatment alone,while the treatment group received additional therapy with Xuebijing,Xijiao Dihuang decoction,or Qingyuan Shenghua decoction.Primary outcome measures included the sequential organ failure assessment(SOFA)score,acute physiology and chronic health evaluationⅡ(APACHEⅡ)score,activated partial thromboplastin time(APTT),D-dimer,fibrinogen(Fib),prothrombin time(PT)and platelet count(PLT).Two researchers evaluated and screened the included studies,performed data extraction,and assessed literature quality.The network Meta-analysis was conducted using Stata 17.0 software.Results A total of 27 RCTs were finally included,with 2268 cases enrolled.The network Meta-analysis results showed that the surface under the cumulative ranking curve(SUCRA):①In terms of improving APACHEⅡscores:Qingyuan Shenghua decoction combination group(93.2%)>Xuebijing combination group(67.9%)>Xijiao Dihuang decoction combination group(37.5%)>conventional Western medicine treatment alone group(1.4%);②In terms of improving SOFA scores:Qingyuan Shenghua decoction combination group(93.7%)>Xuebijing combination group(63.0%)>Xijiao Dihuang decoction combination group(41.8%)>conventional Western medicine treatment alone group(1.5%);③In terms of improving APTT:Qingyuan Shenghua decoction combination group(95.6%)>Xijiao Dihuang decoction combination group(57.1%)>Xuebijing combination group(46.6%)>conventional Western medicine treatment alone group(0.7%);④In terms of improving D-dimer:Xijiao Dihuang decoction combination group(86.1%)>Qingyuan Shenghua decoction combination group(80.5%)>Xuebijing combination group(33.3%)>conventional Western medicine treatment alone group(0.0%);⑤In terms of improving Fib:Xijiao Dihuang decoction combination group(97.5%)>Qingyuan Shenghua decoction combination group(63.5%)>conventional Western medicine treatment alone group(37.8%)>Xuebijing combination group(1.2%);⑥In terms of shortening PT:Qingyuan Shenghua decoction combination group(67.5%)>Xuebijing combination group(67.4%)>Xijiao Dihuang decoction combination group(63.0%)>conventional Western medicine treatment alone group(2.2%);⑦In terms of improving PLT:Xuebijing combination group(83.6%)>Qingyuan Shenghua decoction combination group(54.9%)>Xijiao Dihuang decoction combination group(49.4%)>conventional Western medicine treatment alone group(12.1%).Conclusion The 3 classical Chinese herbal prescriptions combined with conventional Western medicine all demonstrated significant improvement effects on sepsis complicated with coagulation dysfunction.Among them,Xuebijing showed the most stable clinical efficacy,improving both disease severity scores and multiple coagulation indicators.Qingyuan Shenghua decoction was more effective in improving overall prognosis compared to the other two prescriptions.As for Xijiao Dihuang decoction,its clinical efficacy in ameliorating sepsis-related thrombosis warrants further exploration.

Objective To explore the feasibility of harmonic waves analysis for observing morphological brain network changes in patients with depressive disorder(DD).Methods Whole brain 3D high resolution T1WI of 55 DD patients(DD group)and 46 normal controls(NC group)were acquired.Six kinds of morphological features brain network were constructed with FreeSurfer tool,including the number of brain region vertices,surface area,gray matter volume,average cortical thickness,Gaussian curvature and fold index.Laplace operator was applied to obtain common harmonic wave.The harmonic power of different morphological features and the gray matter volume in different brain regions were compared between groups.Results No significant difference of total harmonic energy was found between groups.The specific harmonic wave energies were significantly different between groups,including the number of brain region vertices corresponding to the 2nd,6th,15th,44th and 57th harmonic waves,surface area corresponding to the 2nd,6th,16th and 57th harmonic waves,gray matter volume corresponding to the 2nd,12th,13th,15th and 57th harmonic waves,average cortical thickness corresponding to the 2nd,19th,35th,36th and 44th harmonic waves,Gaussian curvature corresponding to the 34th,40th,54th and 57th harmonic waves,as well as fold index corresponding to the 5th,16th,21st and 57th harmonic waves.Gray matter volumes of transverse temporal gyrus in left hemisphere in DD group were significantly larger than that in NC group(t=2.900,P=0.004).Conclusion Harmonic waves analysis was feasible for observing morphological brain network changes in DD patients.

Objective:To investigate the association between C-reactive protein (CRP)/albumin (ALB) ratio (CAR) and mortality in peritoneal dialysis (PD) patients.Methods:Clinical data of 791 PD patients in the Second Affiliated Hospital of Soochow University from January 1, 2004 to December 31, 2019 were retrospectively collected. According to the baseline quartiles of CAR, patients were divided into three groups: low-level CAR group (CAR≤0.161 mg/g, n=264), medium-level CAR group (CAR 0.162-0.214 mg/g, n=263) and high-level CAR group (CAR≥0.215 mg/g, n=264). The clinical data among the three groups were compared. Follow-up was ended on March 31, 2020, or when the patients stopped PD due to death, shift to hemodialysis, renal transplantation or recovery of renal function. Kaplan-Meier survival curve, multivariate Cox proportional hazard model and Fine-Gray competing risk model were used to assess the relationship between CAR and all-cause mortality and cardiovascular and cerebrovascular mortality. The association between CAR, CRP, ALB, neutrophil to lymphocyte ratio (NLR), or platelet to lymphocyte ratio (PLR) and mortality in PD patients was compared by receiver-operating characteristic curve (ROC curve) analysis. Results:The age of the patients was (59.8±15.7) years old, and 447(56.5%) patients were males. 714(90.3%) patients had hypertension. 233(29.5%) patients had diabetes. 182(23.0%) patients had cardiovascular diseases. The median follow-up time was 55(31, 88) months. By the end of the follow-up, 236 deaths (29.8%) happened, and 95 patients (12.0%) died from cardiovascular and cerebrovascular diseases. Kaplan-Meier survival analysis results showed that the overall survival rate of the high-level CAR group was lower than those of the low-level CAR group and medium-level CAR group (Log-rank test χ2=109.50, P<0.001). Multivariate Cox regression analysis and Fine-Gray competing risk model revealed that CAR was independently correlated with all-cause mortality and cardiovascular and cerebrovascular mortality after adjusting for confounding factors ( HR=2.891, 95% CI 1.921-4.351, P<0.001; SHR=1.297, 95% CI 1.128-1.490, P<0.001). ROC curve analysis results showed that the area under the curve ( AUC) of CAR for predicting the risk of all-cause mortality in PD patients was 0.737(95% CI 0.700-0.774), which was superior to those of CRP ( AUC=0.643, 95% CI 0.599-0.687), NLR( AUC=0.608, 95% CI 0.563-0.653) and PLR ( AUC=0.554, 95% CI 0.508-0.601), and slightly lower than ALB ( AUC=0.752, 95% CI 0.716-0.788). The optimal cutoff value of CAR for death was 0.19 mg/g, with the sensitivity and specificity of 70.8% and 68.3%, respectively. Conclusions:Increasing CAR level is an independent risk factor of all-cause mortality and cardiovascular and cerebrovascular mortality in PD patients, and its correlation with mortality is higher than those of inflammatory parameters such as CRP, NLR and PLR.

Objective:To understand and analyze the occurrence of medication error (ME) on insulin preparations and its influencing factors and provide reference for the standard use of insulin preparations.Methods:The ME reports on insulin preparation-related MEs in the National Monitoring Network for Clinical Safe Medication (monitoring network) from May 6, 2015 to June 30, 2022, were collected and information of MEs including drugs involved, grading, error content, the persons who caused and found the errors, and the factors that triggered the errors were analyzed.Results:During the set period, a total of 2 215 ME reports from 193 hospitals in 26 provinces and municipalities in China were collected in the monitoring network. A total of 2 215 patients were involved, including 1 345 males (60.72%) and 870 females (39.28%), aged from 1 to 95 years, with an average age of (52±4) years. Two thousand one hundred and eighty-two MEs (98.51%) were mild and 33 (1.49%) were severe. The 2 215 ME reports involved 8 classes and 29 kinds of insulin, and a total of 2 263 times of ME content. The top 3 ME contents of insulin preparations were variety errors (40.70%, 921), interaction/compatibility errors (18.29%, 414), and dosage errors (9.06%, 205). Among the 2 215 MEs, 58.24% (1 290 MEs) were triggered by physicians, 28.26% (626 MEs) by pharmacists, 6.5% (144 MEs) by patients and their families, 5.6% (124 MEs) by nurses, and 1.40% (31 MEs) by others; 1 741 MEs (78.60%) were detected and intercepted in time, of which 75.70% (1 318) were found by pharmacists, 14.01% (244) by patients/family members, 7.76% (135) by nurses, and 2.53% (44) by physicians. The main factors that caused MEs were lack of knowledge (23.28%, 701), similar drug names (19.36%, 583), fatigue (14.51%, 437), etc.Conclusions:The contents of insulin preparations-related MEs mainly include variety error, interaction/compatibility error, and dosage error. MEs are mainly caused by physicians and mostly discovered and intercepted by pharmacists. Lack of knowledge, similar drug names, and fatigue are the major factors causing MEs.

Objective:To investigate resting-state regional homogeneity in patients with bipolar disorder in different mood states and the potential trait imaging markers of bipolar disorder.Methods:This is a cross-sectional study involving 169 patients who met the diagnosis criteria of bipolar disorder in DSM-Ⅳ-TR (including 68 patients with bipolar depression, 29 patients with bipolar (hypo)mania, 72 patients with bipolar euthymia) and 113 controls matched by age and gender. The severity of depression, mania, and the positive and negative affects were assessed by the Hamilton Depression Scale (HAMD 17), Young Mania Rating Scale (YMRS), and Positive and Negative Affect Schedule (PANAS). Resting-state fMRI data were obtained. After fMRI data processing, 64 patients with bipolar depression, 28 patients with bipolar (hypo)mania, 66 patients with bipolar euthymia, and 112 controls were included in the final analysis. The regional homogeneity (ReHo) values were computed, and analysis of covariance was performed on ReHo values among the four groups. Post hoc analysis was conducted based on the ReHo values extracted from the brain regions with significant differences. The relationship between the ReHo values and clinical scores was examined. Results:Significant ReHo differences were observed in the bilateral posterior cerebellum ( F=11.41 for left, F=10.45 for right), bilateral calcarine cortex ( F=10.60 for left, F=9.59 for right), and right superior temporal gyrus ( F=10.58). Compared to controls, bipolar patients in all mood states demonstrated decreased ReHo in the left posterior cerebellum ( P<0.01 for all) and increased ReHo in the right posterior cerebellum ( P<0.05 for all), bilateral calcarine cortex and right superior temporal gyrus ( P<0.01 for all). The clinical score of negative affects was negatively correlated with the ReHo values in the right calcarine cortex ( r=-0.17, P=0.04, uncorrected). Conclusions:Bipolar disorder is characterized by regional homogeneity changes in the bilateral posterior cerebellum, bilateral calcarine cortex and right superior temporal gyrus across different mood states. The functional abnormalities in the cerebellum, visual network and sensorimotor network could comprise a trait biomarker for bipolar disorder.

Objective:To understand and analyze the occurrence of medication error (ME) on insulin preparations and its influencing factors and provide reference for the standard use of insulin preparations.Methods:The ME reports on insulin preparation-related MEs in the National Monitoring Network for Clinical Safe Medication (monitoring network) from May 6, 2015 to June 30, 2022, were collected and information of MEs including drugs involved, grading, error content, the persons who caused and found the errors, and the factors that triggered the errors were analyzed.Results:During the set period, a total of 2 215 ME reports from 193 hospitals in 26 provinces and municipalities in China were collected in the monitoring network. A total of 2 215 patients were involved, including 1 345 males (60.72%) and 870 females (39.28%), aged from 1 to 95 years, with an average age of (52±4) years. Two thousand one hundred and eighty-two MEs (98.51%) were mild and 33 (1.49%) were severe. The 2 215 ME reports involved 8 classes and 29 kinds of insulin, and a total of 2 263 times of ME content. The top 3 ME contents of insulin preparations were variety errors (40.70%, 921), interaction/compatibility errors (18.29%, 414), and dosage errors (9.06%, 205). Among the 2 215 MEs, 58.24% (1 290 MEs) were triggered by physicians, 28.26% (626 MEs) by pharmacists, 6.5% (144 MEs) by patients and their families, 5.6% (124 MEs) by nurses, and 1.40% (31 MEs) by others; 1 741 MEs (78.60%) were detected and intercepted in time, of which 75.70% (1 318) were found by pharmacists, 14.01% (244) by patients/family members, 7.76% (135) by nurses, and 2.53% (44) by physicians. The main factors that caused MEs were lack of knowledge (23.28%, 701), similar drug names (19.36%, 583), fatigue (14.51%, 437), etc.Conclusions:The contents of insulin preparations-related MEs mainly include variety error, interaction/compatibility error, and dosage error. MEs are mainly caused by physicians and mostly discovered and intercepted by pharmacists. Lack of knowledge, similar drug names, and fatigue are the major factors causing MEs.

Objective:To investigate resting-state regional homogeneity in patients with bipolar disorder in different mood states and the potential trait imaging markers of bipolar disorder.Methods:This is a cross-sectional study involving 169 patients who met the diagnosis criteria of bipolar disorder in DSM-Ⅳ-TR (including 68 patients with bipolar depression, 29 patients with bipolar (hypo)mania, 72 patients with bipolar euthymia) and 113 controls matched by age and gender. The severity of depression, mania, and the positive and negative affects were assessed by the Hamilton Depression Scale (HAMD 17), Young Mania Rating Scale (YMRS), and Positive and Negative Affect Schedule (PANAS). Resting-state fMRI data were obtained. After fMRI data processing, 64 patients with bipolar depression, 28 patients with bipolar (hypo)mania, 66 patients with bipolar euthymia, and 112 controls were included in the final analysis. The regional homogeneity (ReHo) values were computed, and analysis of covariance was performed on ReHo values among the four groups. Post hoc analysis was conducted based on the ReHo values extracted from the brain regions with significant differences. The relationship between the ReHo values and clinical scores was examined. Results:Significant ReHo differences were observed in the bilateral posterior cerebellum ( F=11.41 for left, F=10.45 for right), bilateral calcarine cortex ( F=10.60 for left, F=9.59 for right), and right superior temporal gyrus ( F=10.58). Compared to controls, bipolar patients in all mood states demonstrated decreased ReHo in the left posterior cerebellum ( P<0.01 for all) and increased ReHo in the right posterior cerebellum ( P<0.05 for all), bilateral calcarine cortex and right superior temporal gyrus ( P<0.01 for all). The clinical score of negative affects was negatively correlated with the ReHo values in the right calcarine cortex ( r=-0.17, P=0.04, uncorrected). Conclusions:Bipolar disorder is characterized by regional homogeneity changes in the bilateral posterior cerebellum, bilateral calcarine cortex and right superior temporal gyrus across different mood states. The functional abnormalities in the cerebellum, visual network and sensorimotor network could comprise a trait biomarker for bipolar disorder.

Coagulation disorder or disseminated intravascular coagulation (DIC) is a clinicopathological syndrome, in which the imbalance between coagulation and fibrinolysis is the main pathogenesis, and systemic microthrombosis and systemic bleeding tendency are the main clinical manifestations. The clinical outcome is often the induction of systemic multiple organ dysfunction. As a common complication of sepsis, DIC significantly increases the mortality of septic patients. The coagulation disorder in sepsis is closely related to the inflammatory response of the body. Studying the mechanism of sepsis-related coagulation disorder will provide new possibilities for its early diagnosis and prognosis evaluation. This article reviews the latest research progress on the molecular mechanism of sepsis-related coagulation disorders in immunity and inflammation, in order to provide new possibilities for potential therapeutic targets.