AIM: To investigate and analyze serum nitric oxide synthase 4(NOX4)and matrix metalloproteinase(MMP)-2 expressions in patients with diabetes mellitus(DM)complicated with neovascular glaucoma(NVG)and their clinical significance.METHODS: A prospective study was conducted on 161 patients with DM complicated with NVG admitted to Handan City Eye Hospital(The Third Hospital of Handan)from June 2020 to June 2023. Based on whether complications occurred 1 a after trabeculectomy in the study group patients, they were divided into a group with good prognosis(n=90)and a group with poor prognosis(n=71). During the same period, 161 patients with chronic angle-closure glaucoma without iris neovascularization were selected as the control group. ELISA method was applied to detect the expression levels of serum NOX4 and MMP-2. ROC curve was plotted to evaluate the diagnostic value and postoperative complication prediction value of NOX4 and MMP-2 in patients with DM complicated with NVG. Pearson method was applied to analyze the correlation of NOX4 and MMP-2 with vascular endothelial growth factor(VEGF)and interleukin-6(IL-6). Multivariate Logistic regression was applied to analyze the influencing factors of postoperative complications in the study group.RESULTS:The general information of the study group and control group of patients is comparable. Compared with the control group, the expression levels of serum NOX4, MMP-2, VEGF, and IL-6 in the study group were significantly increased(P<0.001). According to Pearson analysis, serum NOX4 and MMP-2 levels significantly positively correlated with VEGF and IL-6 levels, respectively(P<0.001). According to ROC curve, the AUC of NOX4 combined with MMP-2 in the diagnosis of DM complicated with NVG was better than that of individual diagnosis of NOX4(Z=3.341, P<0.05)and MMP-2(Z=2.788, P<0.05). The duration of DM, the proportion of people with intraocular pressure >21 mmHg, and the expression levels of NOX4, MMP-2, VEGF, and IL-6 in the poor prognosis group were all higher than those in the good prognosis group(P<0.001). The duration of DM, intraocular pressure >21 mmHg, the levels of NOX4, MMP-2, VEGF, and IL-6 were all risk factors for poor prognosis in DM patients with NVG(P<0.001). According to ROC curve, the combined prediction of NOX4 and MMP-2 for postoperative complications in patients with DM complicated by NVG was superior to the AUC predicted by NOX4(Z=3.727, P<0.05)and MMP-2(Z=2.219, P<0.05), respectively.CONCLUSION:NOX4 and MMP-2 are upregulated in the serum of patients with DM complicated by NVG. Combined detection of these two markers holds significant clinical value for the early diagnosis and prognosis of patients with DM complicated by NVG.

Objective To develop and validate a deep learning model based on chest CT images to accurately distinguish between drug-resistant(DR-TB)and-sensitive tuberculosis(DS-TB).Methods A retrospective study was conducted on 722 cases of confirmed secondary tuberculosis admitted in our center from January 2019 to December 2022.According to the results of antimicrobial susceptibility test,they were divided into 357 DS-TB cases and 365 DR-TB cases.Pre-existing U-Net segmentation model was employed to segment the lung parenchyma regions in CT images.The dataset was randomly partitioned into a training set and a testing set in an 8:2 ratio.Six 3D deep learning architectures(3D Swin Transformer,3D ShuffleNet v2,3D ViT,3D MobileNet v2,3D DenseNet,and 3D ResNet18)were employed to evaluate the discriminative efficiency between DS-TB and DR-TB.Hyperparameters were optimized by five-fold cross-validation on the training set to construct the optimal model.The performance of the constructed model was assessed using area under the curve(AUC),sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),and F1-score.Six radiologists independently evaluated DR-TB identification on the test set,and their performance was compared with the best-performing deep learning model.Results The AUC value in DR-TB prediction was 0.583,0.704,0.698,0.758,0.736,and 0.841,respectively,for 3D Swin Transformer,3D ShuffleNet v2,3D ViT,3D MobileNet v2,3D DenseNet,and 3D ResNet18.The 3D ResNet18 model demonstrated optimal performance,achieving a sensitivity of 0.935(95%CI:0.880～0.987),a specificity of 0.642(95%CI:0.492～0.757),a PPV of 0.750(95%CI:0.663～0.835),an NPV of 0.896(95%CI:0.809～0.976),an AUC value of 0.841,and a F1-score of 0.832.The radiologists got a F1-score of 0.571,0.450,0.675,0.623,0.617 and 0.635,respectively,and the F1-score of the 3D ResNet18 model is all higher than that of the radiologists.The highest-performing radiologist achieved sensitivity,specificity,PPV and NPV of 0.701(95%CI:0.605～0.802),0.567(95%CI:0.447～0.684),0.651(95%CI:0.549～0.757),and 0.623(95%CI:0.500～0.754),with all these values lower than those of the 3D ResNet18 model(P<0.05).Class activation mapping showed that the 3D ResNet18 model could focus on key lesion areas.The class activation mapping demonstrated that the 3D ResNet18 model could effectively focus on critical lesion regions.Conclusion Our 3D ResNet18 model shows the best predictive performance in identifying DR-TB,and is expected to assist clinical diagnosis for DR-TB.

Objective To explore the research hotspots and development trends of microbiota-gut-brain axis(MGBA)related literature both domestically and internationally.Methods Relevant MGBA literature from 2000 to 2023 was retrieved from the Web of Science Core Collection,and bib-liometric and visualization analyses were conducted using CiteSpace 6.3.R1 software.Results A total of 857 MGBA-related articles were analyzed.China and the United States are representative countries in this field,with CRYAN J F and University College Cork being the most influential author and the most productive institution,respectively.In recent years,high-frequency research had fo-cused on neurodegenerative diseases,intra-and extra-axis interactions with the body,and interventions involving short-chain fatty acids(SCFAs),tryptophan metabolism and serotonin.Conclusion The research in MGBA continues to be hotspot,and the research focus gradually transit from the verifica-tion of the relationship with diseases to the intra-axis interaction mechanism.The research hotspot of nervous system related diseases has been enduring in this field,and the therapeutic measures targeting the metabolites of intestinal flora and metabolomics are expected to become the future research trend in this field.

Anticipatory anxiety is a negative emotion that arises when individuals encounter potential threats or uncertainties in the future. It is the core symptom of a variety of anxiety disorders, and is closely associated with the occurrence, severity, treatment outcome, and prognosis of anxiety disorders, which has garnered a growing amount of focus in clinical practice. Nevertheless, scientific research on anticipatory anxiety continues to face obstacles such as unclear pathological mechanisms, the absence of simple and consistent self-assessment tools, and effective interventions. To improve understanding of the role of anticipatory anxiety in the diagnosis and treatment of anxiety disorders, this study reviews pertinent domestic and international literature, and briefly introduces the concept, assessment and measurement, activation paradigm, pathological mechanisms, and interventions of anticipatory anxiety.

Objective Explore the correlation among difference of skin temperature(ΔT)between proximal and distal ends,peripheral serum indicators and cardiac function,to screen the influencing factors of the main syndrome of"reverse coldness of limbs"in Sini decoction.Methods The clinical data of 134 critically ill patients who visited the emergency department of the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from January 2022 to September 2023 were collected,including echocardiographic indicators[ejection fraction(EF),anterior-posterior diameter of the aortic sinus,left atrial anterior-posterior diameter,right ventricle left-right diameter,right atrial left-right diameter,left ventricular diastolic end anterior-posterior diameter,interventricular septum thickness,left ventricular posterior wall thickness,left ventricular posterior wall movement amplitude,main pulmonary artery inner diameter,pulmonary artery valve flow velocity,aortic valve flow velocity,mitral valve flow velocity,pulmonary artery systolic pressure],blood routine[white blood cell count(WBC),red blood cell count(RBC),platelet count(PLT),hemoglobin(Hb)],myocardial markers[troponin(cTnI,cTnT),MB isoenzyme of creatine kinase(CK-MB),myoglobin(MYO),N-terminal pro-brain natriuretic peptide(NT-proBNP)],D-dimer,blood gas analysis[pH value,arterial oxygen partial pressure(PaO2),arterial partial pressure of carbon dioxide(PaCO2),lactic acid(Lac),arterial oxygen saturation(SaO2)],coagulation function indicators[prothrombin time(PT),activated partial thromboplastin time(APTT),thrombin time(TT),international normalized ratio(INR),fibrinogen(Fib)],infection indicators[C-reactive protein(CRP),procalcitonin(PCT)],biochemical indicators[K+,Na+,Cl-,Ca2+,P3+,total protein(TP),albumin(Alb),aspartate aminotransferase(AST),creatine kinase(CK),α-hydroxybutyrate dehydrogenase(α-HBDH),lactate dehydrogenase(LDH),urea,creatinine(Cr),uric acid(UA)],mean arterial pressure(MAP),and the top 10 disease types.These data were used as independent variables,and the ΔT value was used as the dependent variable for univariate linear regression analysis.Variables with statistically significant differences in the univariate analysis were subjected to multivariate linear regression analysis to identify the influencing factors causing an increase in the ΔT value.Results The univariate analysis analysis showed that variables such as shock,MAP,WBC,MYO,Lac,PT,APTT,TT,CRP,K+,P3+,Alb,urea,Cr,right ventricular left-right diameter,left ventricular posterior wall motion amplitude,main pulmonary artery diameter,pulmonary artery valve velocity,and aortic valve velocity were all risk factors influencing the increase of ΔT between the left axilla and the left hand in critically ill patients(all P<0.05);shock,respiratory failure,MAP,WBC,cTNI,MYO,Lac,PT,APTT,TT,CRP,Ca2+,P3+,Alb,urea,Cr,right ventricular left-right diameter,interventricular septum motion amplitude,left ventricular posterior wall motion amplitude,and main pulmonary artery inner diameter were all risk factors influencing the increase of ΔT between the left axilla and the left foot in critically ill patients(all P<0.05).Multivariate linear regression analysis showed that APTT,Lac,right ventricular left and right diameters,and urea were independent risk factors for the increase of ΔT in the left axilla and left hand[95%confidence interval(95%CI)was 0.016-0.036,0.024-0.095,-0.031 to-0.003,0.002-0.029,respectively;P values were 0.000,0.001,0.015,0.028,respectively],while PT,right ventricular left and right diameters,interventricular septal motion amplitude,and MYO were independent risk factors for the increase of ΔT left axilla and left foot(95%CI was 0.023-0.178,-0.103 to-0.019,0.031-0.245,0.000-0.002,respectively;P values were 0.012,0.006,0.013,0.015,respectively).Conclusion APTT,PT,Lac,MYO,urea,the right ventricular diameter and interventricular septal motion amplitude are key factors affecting the ΔT value of critically ill patients,which can cause reverse coldness of limbs.

The drugs used to improve brain metabolism mainly include ergotamine derivatives,GABA derivatives,vitamin B6 derivatives,neuropeptides,morpholines,hormones and other.However,these drugs may have adverse reactions during clinical application.This article focuses on the adverse effects of commonly used drugs for brain metabolism,and reviews the studies on the new state of pharmaceutical substances,such as drug combination,chiral resolution of isomers,crystal form of dominant drugs,co-crystal drugs and nanodrugs,with the aim of reducing adverse reactions.By summarizing the research on modifying the solid state of drugs to mitigate adverse reactions,this article provides new research insights for obtaining new drug with less adverse reaction and greater clinical value.

Currently,the first-generation of proton pump inhibitors(PPIs)commonly utilized in clinical practice for the treatment of peptic ulcer include omeprazole,lansoprazole,and pantoprazole,and the second generation include rabeprazole and esomeprazole.The predominant mode of PPI administration is oral,which poses numerous challenges in clinical settings owing to their poor solubility,susceptibility to gastric acid degradation,short half-life,and limited stability.This article presents a comprehensive review of studies exploring the novel states of these five PPIs,include polymorphism,co-crystal drugs,and nanodrugs.Furthermore,it summarizes the advancements in research aimed at modifying the physicochemical properties of these drugs through innovative solid states,thereby enhancing their bioavailability and stability.This work offers a new perspective for researchers endeavoring to develop new states of pharmaceutical substances that incorporate PPIs.

The drugs used to improve brain metabolism mainly include ergotamine derivatives,GABA derivatives,vitamin B6 derivatives,neuropeptides,morpholines,hormones and other.However,these drugs may have adverse reactions during clinical application.This article focuses on the adverse effects of commonly used drugs for brain metabolism,and reviews the studies on the new state of pharmaceutical substances,such as drug combination,chiral resolution of isomers,crystal form of dominant drugs,co-crystal drugs and nanodrugs,with the aim of reducing adverse reactions.By summarizing the research on modifying the solid state of drugs to mitigate adverse reactions,this article provides new research insights for obtaining new drug with less adverse reaction and greater clinical value.

Currently,the first-generation of proton pump inhibitors(PPIs)commonly utilized in clinical practice for the treatment of peptic ulcer include omeprazole,lansoprazole,and pantoprazole,and the second generation include rabeprazole and esomeprazole.The predominant mode of PPI administration is oral,which poses numerous challenges in clinical settings owing to their poor solubility,susceptibility to gastric acid degradation,short half-life,and limited stability.This article presents a comprehensive review of studies exploring the novel states of these five PPIs,include polymorphism,co-crystal drugs,and nanodrugs.Furthermore,it summarizes the advancements in research aimed at modifying the physicochemical properties of these drugs through innovative solid states,thereby enhancing their bioavailability and stability.This work offers a new perspective for researchers endeavoring to develop new states of pharmaceutical substances that incorporate PPIs.

Objective Explore the correlation among difference of skin temperature(ΔT)between proximal and distal ends,peripheral serum indicators and cardiac function,to screen the influencing factors of the main syndrome of"reverse coldness of limbs"in Sini decoction.Methods The clinical data of 134 critically ill patients who visited the emergency department of the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from January 2022 to September 2023 were collected,including echocardiographic indicators[ejection fraction(EF),anterior-posterior diameter of the aortic sinus,left atrial anterior-posterior diameter,right ventricle left-right diameter,right atrial left-right diameter,left ventricular diastolic end anterior-posterior diameter,interventricular septum thickness,left ventricular posterior wall thickness,left ventricular posterior wall movement amplitude,main pulmonary artery inner diameter,pulmonary artery valve flow velocity,aortic valve flow velocity,mitral valve flow velocity,pulmonary artery systolic pressure],blood routine[white blood cell count(WBC),red blood cell count(RBC),platelet count(PLT),hemoglobin(Hb)],myocardial markers[troponin(cTnI,cTnT),MB isoenzyme of creatine kinase(CK-MB),myoglobin(MYO),N-terminal pro-brain natriuretic peptide(NT-proBNP)],D-dimer,blood gas analysis[pH value,arterial oxygen partial pressure(PaO2),arterial partial pressure of carbon dioxide(PaCO2),lactic acid(Lac),arterial oxygen saturation(SaO2)],coagulation function indicators[prothrombin time(PT),activated partial thromboplastin time(APTT),thrombin time(TT),international normalized ratio(INR),fibrinogen(Fib)],infection indicators[C-reactive protein(CRP),procalcitonin(PCT)],biochemical indicators[K+,Na+,Cl-,Ca2+,P3+,total protein(TP),albumin(Alb),aspartate aminotransferase(AST),creatine kinase(CK),α-hydroxybutyrate dehydrogenase(α-HBDH),lactate dehydrogenase(LDH),urea,creatinine(Cr),uric acid(UA)],mean arterial pressure(MAP),and the top 10 disease types.These data were used as independent variables,and the ΔT value was used as the dependent variable for univariate linear regression analysis.Variables with statistically significant differences in the univariate analysis were subjected to multivariate linear regression analysis to identify the influencing factors causing an increase in the ΔT value.Results The univariate analysis analysis showed that variables such as shock,MAP,WBC,MYO,Lac,PT,APTT,TT,CRP,K+,P3+,Alb,urea,Cr,right ventricular left-right diameter,left ventricular posterior wall motion amplitude,main pulmonary artery diameter,pulmonary artery valve velocity,and aortic valve velocity were all risk factors influencing the increase of ΔT between the left axilla and the left hand in critically ill patients(all P<0.05);shock,respiratory failure,MAP,WBC,cTNI,MYO,Lac,PT,APTT,TT,CRP,Ca2+,P3+,Alb,urea,Cr,right ventricular left-right diameter,interventricular septum motion amplitude,left ventricular posterior wall motion amplitude,and main pulmonary artery inner diameter were all risk factors influencing the increase of ΔT between the left axilla and the left foot in critically ill patients(all P<0.05).Multivariate linear regression analysis showed that APTT,Lac,right ventricular left and right diameters,and urea were independent risk factors for the increase of ΔT in the left axilla and left hand[95%confidence interval(95%CI)was 0.016-0.036,0.024-0.095,-0.031 to-0.003,0.002-0.029,respectively;P values were 0.000,0.001,0.015,0.028,respectively],while PT,right ventricular left and right diameters,interventricular septal motion amplitude,and MYO were independent risk factors for the increase of ΔT left axilla and left foot(95%CI was 0.023-0.178,-0.103 to-0.019,0.031-0.245,0.000-0.002,respectively;P values were 0.012,0.006,0.013,0.015,respectively).Conclusion APTT,PT,Lac,MYO,urea,the right ventricular diameter and interventricular septal motion amplitude are key factors affecting the ΔT value of critically ill patients,which can cause reverse coldness of limbs.