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 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.

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.

ObjectiveTo preliminarily confirm the effective anti-lung cancer sites of Momordicae Semen and Epimedii Folium and study their mechanism of action. MethodOn the basis of preliminary research， the extraction method of Momordicae Semen and Epimedii Folium was optimized and the effective parts were screened under the guidance of pharmacological effects. Different ethanol elution and water elution sites of Momordicae Semen and Epimedii Folium were obtained through adsorption and elution with D101 macroporous resin. The methylthiazolyldiphenyl-tetrazolium bromide （MTT） colorimetric assay was used to detect the effects of total drug extracts and different elution sites on the proliferation of various tumor cell lines， and to screen for the optimal elution site and tumor sensitive strains. Flow cytometry was used to detect the effect of the elution sites of Momordicae Semen and Epimedii Folium on intracellular reactive oxygen species （ROS） and apoptosis in A549 cells. Western blot was used to compare the expressions of tumor protein 53 （p53）， Bcl-2-associated X protein （Bax）， cysteinyl aspartate specific proteinase-3 and 9 （Caspase-3 and Caspase-9） proteins in A549 cells. ResultThe inhibitory effect of Momordicae Semen on the proliferation of A549 cells was better than the kernel of Momordicae Semen， with 50% inhibitory concentration （IC₅₀） being （86.83±2.88） mg·L^-1 and （95.10±18.13） mg·L^-1， respectively. The effect of total extracts of Epimedii Folium on A549 anti proliferation IC₅₀ value was （4.71±0.81） mg·L^-1. The IC₅₀ values of the 40%， 60%， and 80% ethanol and anhydrous ethanol eluted macroporous resins of the total extracts of Momordicae Semen and Epimedii Folium inhibiting A549 proliferation were （45.32±4.38）、 （14.95±0.73）、 （17.07±1.76）、 （14.46±2.35）、 （51.7±2.26）、 （12.37±0.67）、 （20.29±0.93）、 and （3.43±0.91） mg·L^-1， respectively. Compared with the normal group， the 1∶1 combination of Momordicae Semen and Epimedii Folium inhibited A549 cell proliferation in a time-dependent and concentration-dependent manner. Compared with the normal group， 50 mg·L^-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased intracellular ROS expression （P<0.01）. Compared with the normal group， 12.5， 25， 50 mg·L^-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of A549 cell apoptosis （P<0.01）. Compared with the normal group， 25， 50 mg·L^-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of p53 in A549 cells （P<0.01）. Compared with the normal group， 12.5， 25， 50 mg·L^-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of Bax （P<0.01）. Compared with the normal group， 50 mg·L^-1 of the combination of Momordicae Semen and Epimedii Folium significantly reduced the expressions of Caspase-3 and Caspase-9 （P<0.01）. ConclusionThe anti-tumor effect of Momordicae Semen is better than that of the kernel of Momordicae Semen. The anti-tumor substances of Momordicae Semen and Epimedii Folium mainly concentrate in the 60% ethanol to anhydrous ethanol elution site. A549 cells are sensitive to the 1∶1 combination of Momordicae Semen and Epimedii Folium， which can effectively inhibit the cell proliferation. The mechanism may be related to increasing the generation of ROS in A549 cells， promoting their apoptosis， increasing the expressions of apoptotic proteins such as p53 and Bax， and reducing the expressions of Caspase-3 and Caspase-9.

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.

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.

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.

ObjectiveThis study explores the efficacy and pharmacological mechanism of Wujiwan in rats with inflammatory bowel disease （IBD） from the perspectives of the peroxisome proliferator-activated receptor γ （PPARγ） signaling pathway and T-cell immunity， providing reference for the treatment of IBD with traditional Chinese medicine. MethodThe study involved administering 2，4，6-trinitrobenzenesulfonic acid （TNBS） enemas to 35 rats to induce acute IBD. After 24 hours， the animals were divided into the following groups： normal group， model group， Wujiwan treatment group， and positive drug control group. Each group received gastric gavage for 8 consecutive days before the rats were dissected to compare the disease activity index （DAI） of the rat colon tissue， the colon mucosal damage index （CMDI）， and the spleen index. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β）， interleukin-10 （IL-10）， and tumor necrosis factor-α （TNF-α） in the serum. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of T-bet （T-box expressed in T cells） and Gata3 （Gata-binding protein-3） in the colon tissue. Western blot analysis was conducted to detect the protein expression levels of PPARγ， T-bet， and nuclear factor-κB p65 （NF-κB p65） in the rat colon. ResultThe rat model of IBD was successfully established. Compared with the model group， the Wujiwan treatment group showed reduced DAI， CMDI， and spleen index， decreased content of TNF-α in the serum（P<0.01）， significantly increased content of IL-10（P<0.01）， and elevated mRNA content of T-bet and Gata3（P<0.05） in the colon tissue. The expression of PPARγ protein was augmented（P<0.05）， and the expression of T-bet and NF-κB p65 protein was decreased（P<0.05，P<0.01）. ConclusionWujiwan activates or upregulates PPARγ expression in IBD rats to inhibit the generation of pro-inflammatory factors， participates in the inflammatory immune process， and alleviates inflammatory reactions. Its mechanism may involve regulating the NF-κB pathway through PPARγ， enhancing Th2 cell transcription expression， and reducing Th1 cell transcription.

Traditional Chinese medicine （TCM） has a long history of application in China and has consistently played a vital role in treating diseases and saving lives. TCM prescriptions （compounds） constitute the primary form of clinical TCM treatment and significantly differ from western medicine （chemicals） due to the diverse composition and chemical constituents of TCM （compounds）. Nevertheless， the potential multi-component， multi-target， and multi-pathway action characteristics of TCM prescriptions also demonstrate their possible （complementary） therapeutic advantages when compared with single-component chemical drugs. Therefore， driven by the development of modern science and technology and the demands of the modernization and internationalization of TCM， modern theories regarding the complexity of TCM prescription effects have been continuously proposed： Different from the abstract language of traditional prescription theory， the modern TCM prescription theory is more inclined to illustrate the connotation of prescription compatibility concretely and vividly from an experimental and scientific perspective. In this paper， new theories on the complexity of TCM prescriptions proposed in recent years are summarized to provide research references and ideas for the greater role of TCM prescriptions and a better scientific understanding.