ObjectiveTo analyze the distribution characteristics of traditional Chinese medicine （TCM） syndrome elements in different risk populations of heart failure complicated with type 2 diabetes. MethodsClinical data of 675 type 2 diabetes patients were retrospectively collected. Lasso-multivariate Logistic regression was used to construct a clinical prediction nomogram model. Based on this， 441 non-heart failure patients were divided into a low-risk group （325 cases） and a high-risk group （116 cases） according to the median risk score of heart failure complicated with type 2 diabetes. TCM diagnostic information （four diagnostic methods） was collected for both groups， and factor analysis was applied to summarize the distribution of TCM syndrome elements in different risk populations. ResultsLasso-multivariate Logistic regression analysis identified age， disease duration， coronary heart disease， old myocardial infarction， arrhythmia， absolute neutrophil count， activated partial thromboplastin time， and α-hydroxybutyrate dehydrogenase as independent risk factors for heart failure complicated with type 2 diabetes. These were used as final predictive factors to construct the nomogram model. Model validation results showed that the area under the curve （AUC） of the receiver operating characteristic （ROC） curve for the modeling group and validation group were 0.934 and 0.935， respectively. The Hosmer-Lemeshow test （modeling group P = 0.996， validation group P = 0.121） indicated good model discrimination. Decision curve analysis showed that the curves for All and None crossed in the upper right corner， indicating high clinical utility. The low-risk and high-risk groups each obtained 14 common factors. Preliminary analysis revealed that the main disease elements in the low-risk group were qi deficiency （175 cases， 53.85%）， dampness （118 cases， 36.31%）， and heat （118 cases， 36.31%）， with the primary locations in the spleen （125 cases， 38.46%） and lungs （99 cases， 30.46%）. In the high-risk group， the main disease elements were yang deficiency （73 cases， 62.93%）， blood stasis （68 cases， 58.62%）， and heat （49 cases， 42.24%）， with the primary locations in the kidney （84 cases， 72.41%） and heart （70 cases， 60.34%）. ConclusionThe overall disease characteristics in different risk populations of type 2 diabetes patients with heart failure are a combination of deficiency and excess， with deficiency being predominant. Deficiency and heat are present throughout. The low-risk population mainly shows qi deficiency with dampness and heat， related to the spleen and lungs. The high-risk population shows yang deficiency with blood stasis and heat， related to the kidneys and heart.

Bacillus coagulans can utilize the hydrolyzed carbon source of agricultural waste to produce lactic acid via a homofermentative pathway. However, a significant carbon source metabolic repression effect was observed when the strain metabolized mixed sugars (glucose and xylose), reducing the productivity of lactic acid. In this study, we obtained the fermentation conditions for the simultaneous utilization of the mixed sugars by B. coagulans by changing the ratio of glucose to xylose in the medium. Through transcriptome sequencing, several key genes responsible for xylose utilization were identified. The critical role of xylose isomerase (XylA, EC 5.3.1.5) in the synchronous utilization of glucose/xylose in B. coagulans was investigated via qRT-PCR (quantitative real-time polymerase chain reaction). Subsequently, the heterologous expression and characterization of the XylA-encoding gene (XylA) were conducted. It was determined that the gene encoded a protein composed of 440 amino acid residues. The secondary structure of the encoded protein was predominantly composed of α-helixes and random coils, while the higher structure of the protein was identified as a homotetramer. Then, XylA was cloned and expressed in Escherichia coli BL21(DE3), and the recombinant protein Bc-XlyA was obtained with a molecular weight of approximately 50 kDa. The optimal pH and temperature of Bc-XylA were 8.0 and 60 ℃, respectively, and Mn²⁺, Mg²⁺, and Co²⁺ had positive effects on the activity of Bc-XlyA. The present study provides scientific data on the molecular modification of B. coagulans, offering theoretical support for the efficient utilization of xylose in the strain.
Xylose/metabolism* ; Cloning, Molecular ; Bacillus coagulans/enzymology* ; Aldose-Ketose Isomerases/metabolism* ; Fermentation ; Bacterial Proteins/metabolism* ; Glucose/metabolism*

Objective:To explore the interplay between tumor microenvironment (TME)-associated genes, cuproptosis, and the prognosis of liver cancer through transcriptome sequencing and functional genomics analysis.Methods:Employing a hybrid approach that integrates bioinformatics with fundamental experimental research, we utilized the TCGA database to acquireexpression profiles and clinical-pathological information from 424 liver hepatocellular carcinoma patients. We evaluated ImmuneScore and StromalScore to categorize patients into high and low groups, subsequently identifying differentially expressed genes (DEG) at the intersection of these groups. Core DEG were identified through univariate Cox regression analysis and protein-protein interaction (PPI) network analysis. The association between the expression levels of core genes and the survival time of liver cancer patients was analyzed using the R language and Kaplan-Meier analysis, and verified using the Kaplan-Meier Plotter online database. We established a cuproptosis cell model and performed RNA-seq to examine gene expression alterations during copper-induced cell death, followed by in vitro cell experiments for verification.Results:A total of 1 701 and 2 041 DEG were llinked t ImmuneScore and StromalScore, respectively, encompassing 1 134 commonly upregulated genes and 60 commonly downregulated genes. The top 30 core genes from the PPI network's dominant nodes were cross-referenced with univariate Cox regression results, leading to the identification of the pivotal immune gene CCR7. CCR7 mRNA expression levels were higher in hepatocellular carcinoma tissues than in normal tissues ( P<0.05). Patients with high expression of CCR7 in liver cancer had a longer overall survival compared to those with low expression ( P=0.003). Treatment with elesclomol-CuCl2significantly curtailed the survival of hepatocellular carcinoma cel ( P<0.001). RNA-seq data from the cuproptosis model indicated a downregulation of CCR7 expression during the onset of cuproptosis [|log 2(FC)|=2.27, P<0.001], and downregulation of CCR7 expression enhanced the sensitivity of hepatocellular carcinoma cells to cuproptosis inducers. Conclusion:The TME-related gene CCR7 is implicated in cuproptosis, and its downregulation might facilitate the process in liver cancer.CCR7 holds potential as a biomarker for liver cancer prognosis.

Objective To analyze and discuss the medication rule of professor Ruan Yan in the treatment of children with allergic rhinitis by using data mining method,and to provide reference for the clinical research and patented drugs development for the treatment of children with allergic rhinitis.Methods The outpatient medical records of professor Ruan Yan for the treatment of children with allergic rhinitis were collected.Microsoft Excel 2010 software was used for frequency statistics.SPSS Clementine 12.0 software was used for association rule analysis,cluster analysis and factor analysis to obtain the data.The frequency of use of various drugs and the association rules between drugs were obtained.Then the medication rules in professor Ruan Yan's prescription were analyzed.Results A total of 308 Chinese medicine compounds were included,involving 80 kinds of Chinese medicines,among which relieving drugs and qi-invigorating herbs were high-frequently used.The distribution of traditional Chinese medicine syndrome types was mainly characterized by lung-qi deficiency-cold syndrome and lung-spleen qi deficiency syndrome.The medicinal properties were mainly spicy,warm and sweet,and most of them belonged to the lung,spleen and stomach meridians.Five core prescriptions were extracted by factor analysis.Four drug combinations were obtained by systematic cluster analysis.Conclusion Ventilating lung and opening the orifices,expelling wind and removing cold,strengthening the spleen and replenishing qi are basic therapeutic principles for professor Ruan Yan in the treatment of children with allergic rhinitis.The treatment mainly focused on dispelling evil,ventilating lung and opening the orifices,expelling wind and removing cold during the acute stage of allergic rhinitis.In the remission period,according to the principle of"treating disease must be based on its origin",the treatment should enhance children's physical fitness,tonify lung and strengthen spleen,thereby reducing recurrence.

AIM:This study aimed to investigate the expression and localization of ALOX12P2 in oral squa-mous cell carcinoma(OSCC),as well as its effects on cell viability,migration,and invasion.METHODS:The expres-sion of ALOX12P2 in head and neck squamous cell carcinoma(HNSCC)tissues and its correlation with clinicopathologi-cal features were analyzed using the UALCAN database(University of Alabama at Birmingham Cancer Data Analysis Por-tal).Additionally,the expression of ALOX12P2 in OSCC and its impact on survival prognosis were evaluated through the GDC and UCSC Xena databases.The expression levels of ALOX12P2 in OSCC cell lines were assessed via quantitative re-al-time PCR(RT-qPCR).The subcellular localization of ALOX12P2 was determined using nucleoplasmic RNA isola-tion.CAL-27 cells were used to establish an ALOX12P2 knockdown group(SS-ALOX12P2)and a control group(SS-NC).HN30 cells were employed to form an ALOX12P2 overexpression group(ALOX12P2)and a control group(vector).The effects of altered ALOX12P2 expression on the epithelial-mesenchymal transition(EMT)-related gene E-cadherin and the PI3K/AKT signaling pathway were assessed through Western blot analysis.RESULTS:ALOX12P2 expression was significantly higher in HNSCC and OSCC tissues compared to normal tissues,with its expression correlating with poor prog-nosis.RT-qPCR analysis indicated that the relative expression of ALOX12P2 in OSCC cells was comparable to that in nor-mal cells(P<0.05).RNA nucleoplasmic isolation confirmed that ALOX12P2 localized in the nucleus.In comparison to the SS-NC group,the SS-ALOX12P2 group exhibited a marked reduction in ALOX12P2 expression(P<0.01),alongside significant decreases in cell viability,migration,and invasion(P<0.01).Conversely,the ALOX12P2 group showed sub-stantially higher relative expression compared to the vector group(P<0.01),with enhanced cell viability,migration,and invasion abilities(P<0.01).Western blot analysis demonstrated that ALOX12P2 knockdown resulted in upregulation of E-cadherin and downregulation of N-cadherin and Vimentin(P<0.01),while overexpression of ALOX12P2 yielded the opposite effects(P<0.01).Knockdown of ALOX12P2 led to decreased protein expression of p-PI3K and p-AKT(P<0.01),whereas overexpression increased these protein levels(P<0.01).CONCLUSION:ALOX12P2 is highly ex-pressed in OSCC and promotes cell viability,migration,and invasion.This effect may be linked to the activation of the PI3K/AKT signaling pathway,which facilitates the epithelial-mesenchymal transition(EMT)process.

Objective:To evaluate the effect of ultrasound-guided adductor canal combined with knee joint posterior capsule space block on the recovery period delirium in elderly patients undergoing total knee arthroplasty (TKA).Methods:A total of 68 elderly patients who underwent unilateral TKA at the Nanjing First Hospital from December 2021 to December 2022 were selected. They were randomly divided into a control group ( n=34) and an observation group ( n=34) using a random number table method. Both groups received general anesthesia, and the observation group received ultrasound-guided myofascial tube combined with knee joint posterior capsule space block before the surgery began. The incidence of delirium within 24 hours after surgery was mainly observed in two groups of patients. The surgical time, recovery time, intraoperative blood loss, infusion volume, total use of propofol and remifentanil were recorded; The resting and motor Visual Analogue Scale (VAS) scores of the patient were recorded at 4, 8, and 24 hours postoperatively. The patient′s serum tumor necrosis factor-α (TNF-α) and melatonin levels were measured on the day before surgery, the evening after surgery, and the first day after surgery. The subjective sleep quality score was recorded on the first day after surgery; The total dosage of sufentanil for patient-controlled intravenous analgesia (PCIA) within 24 hours after surgery, the effective number of compressions (P1) and actual number of compressions (P2) of PCIA, and the number of cases of additional oxycodone analgesia were recorded; The occurrence of respiratory depression, excessive sedation, nausea, and vomiting within 24 hours after surgery was recorded; The occurrence of complications of nerve block in the observation group was recorded. Results:The incidence of delirium during the recovery period in the observation group was lower than that in the control group ( P<0.05). The dosage of propofol and remifentanil in the observation group was lower than that in the control group (all P<0.05), and the awakening time was shorter than that in the control group ( P<0.05). The VAS scores at rest and exercise at 4, 8, and 24 hours after surgery in the observation group were lower than those in the control group (all P<0.05). Compared with the day before surgery, the observation group showed an increase in melatonin levels on the night after surgery ( P<0.05) and an increase in TNF-α levels on the first day after surgery ( P<0.05); The control group had a decrease in melatonin levels on the first day after surgery ( P<0.05), and an increase in TNF-α levels on the night and day after surgery (all P<0.05). The serum melatonin levels in the observation group were higher than those in the control group on the evening and first day after surgery (all P<0.05), and TNF-α levels were lower than those in the control group (all P<0.05). The subjective sleep quality score of the observation group showed that the total dosage of PCIA sufentanil, P1, P2, and the number of cases of additional oxycodone analgesia within 24 hours after surgery were lower than those of the control group (all P<0.05). The incidence of nausea in the control group (13 cases, 38.2%) was higher than that in the observation group (3 cases, 8.8%) ( P<0.05). Conclusions:In elderly patients undergoing unilateral TKA under general anesthesia, preoperative use of ultrasound-guided adductor tube combined with knee joint posterior capsule space block can effectively reduce the occurrence of postoperative delirium.

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.

ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan， and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups， including Wujiwan group（A group， 62.96 g·L^-1）， Coptidis Rhizoma group（B group， 38.4 g·L^-1）， processed Euodiae Fructus group（C group， 5.88 g·L^-1） and fried Paeoniae Radix Alba group（D group， 18.68 g·L^-1）， with 65 rats in each group， and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma， liver， small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components［berberine（Ber）， palmatine（Pal）， evodiamine（Evo）， rutecarpine（Rut） and paeoniflorin（Pae）］ in Wujiwan， their concentrations in plasma， liver， small intestine and brain were detected at different time， plasma samples were processed by protein precipitation， and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component， and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve（AUC_0-t） of the five representative components were ranked as follows：Ber and Pal were small intestine>liver>blood， Evo and Rut were liver>small intestine>plasma， Pae was small intestine>plasma， which was not detected in the liver， no other components were detected in brain except for Ber. In comparison with plasma and other tissues， peak concentration（C_max） of Ber， Pal， Evo， and Rut were the highest and time to peak（t_max） were the lowest in the liver of A group. In plasma， the AUC_0-t and C_max of Evo and Rut were increased in A group compared with C group， t_max of Pea was elevated and its C_max was decreased in A group compared with D group. In the liver， compared with B-D groups， C_max values of 5 representative components except Pae were elevated， AUC_0-t of Pae was decreased and AUC_0-t of Evo and Rut were increased in the A group. In the small intestine， half-life（t_1/2） of each representative components in A group was elevated and t_max was decreased， and C_max of each representative ingredient except Pal was decreased， AUC_0-t values of Ber and Pal were increased， whereas the AUC_0-t values of Evo and Rut were decreased. ConclusionThe small intestine， as the effector organ， is the most distributed， followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility， which is more favorable to the exertion of its pharmacodynamic effects.

Objective To evaluate the cost-utility of tiotropium/olodaterol in treating Chinese patients with moderate to very severe chronic obstructive pulmonary disease(COPD)and to provide references for selecting more economical inhaled preparations in clinical practice.Methods A four-state lifetime Markov model was established with a 3-month cycle.The health outcomes included life years and quality-adjusted life years.Costs,including direct medical costs,were calculated from the perspective of the Chinese health system.Discontinuation rates were derived from the discontinuation curve using GetData Graph Digitizer.The main output indicator of the model was the incremental cost-utility ratio,which was calculated from the queue simulation results to judge the economy of tiotropium bromide/odataterol.The scenario analysis and sensitivity analyses were carried out to detect the robustness of the base case result.Results Compared with tiotropium bromide,the patient treated with tiotropium bromide/odataterol gained an additional 0.0846 life years,an additional cost of ￥3 201.50,and additional 0.029 6 QALY.The incremental cost-utility ratio was 108 140.11 yuan/QALY,lower than the willingness-to-pay threshold of three times China's per capita GDP in 2021.The costs of tiotropium bromide and tiotropium bromide/odataterol had the greatest impact on the result in the one-way sensitivity analysis.93.8%of the Chinese COPD population was willing to pay for tiotropium bromide/odataterol under the threshold in the probability sensitivity analysis.Conclusion Tiotropium/olodaterol is a cost-effective alternative compared to tiotropium for patients with moderate to very severe COPD in China and the results were robust in the sensitivity analyses.

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.