The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

Objective    To predict the probability of lymph node metastasis after thoracoscopic surgery in patients with lung adenocarcinoma based on nomogram. Methods    We analyzed the clinical data of the patients with lung adenocarcinoma treated in the department of thoracic surgery of our hospital from June 2018 to May 2021. The patients were randomly divided into a training group and a validation group. The variables that may affect the lymph node metastasis of lung adenocarcinoma were screened out by univariate logistic regression, and then the clinical prediction model was constructed by multivariate logistic regression. The nomogram was used to show the model visually, the receiver operating characteristic (ROC) curve, calibration curve and clinical decision curve to evaluate the calibration degree and practicability of the model. Results    Finally 249 patients were collected, including 117 males aged 53.15±13.95 years and 132 females aged 47.36±13.10 years. There were 180 patients in the training group, and 69 patients in the validation group. There was a significant correlation between the 6 clinicopathological characteristics and lymph node metastasis of lung adenocarcinoma in the univariate logistic regression. The area under the ROC curve in the training group was 0.863, suggesting the ability to distinguish lymph node metastasis, which was confirmed in the validation group (area under the ROC curve was 0.847). The nomogram and clinical decision curve also performed well in the follow-up analysis, which proved its potential clinical value. Conclusion    This study provides a nomogram combined with clinicopathological characteristics, which can be used to predict the risk of lymph node metastasis in patients with lung adenocarcinoma with a diameter≤3 cm.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant solid tumor of the digestive system, characterized by rapid progression and difficulties of early diagnosis. Five-year survival rate of the patients is less than 9%. With the acceleration of global population aging and lifestyle change, the incidence of PDAC has been increasing annually. Currently, surgical treatment and chemotherapy remain the standard treatment options for PDAC patients. Early symptoms of PDAC are so undetectable that most patients miss the optimal opportunity for radical surgical resection. Even among those who undergo surgery, the high recurrence rate remains a major problem. PDAC is known for its unique tumor microenvironment. The cellular and non-cellular components in the tumor microenvironment account for as much as 90% of the tumor stroma, presenting many potential targets for PDAC therapy. Activated pancreatic stellate cells within PDAC tissue express specific proteins and secrete various cytokines and metabolites, which directly contribute to the proliferation, invasion, and metastasis of PDAC cells. These elements are critical in extracellular matrix production, connective tissue hyperplasia, immune tolerance, and drug resistance. Immune cells, such as macrophages and neutrophils, exert immunosuppressive and tumor-promoting roles in PDAC progression. The extracellular matrix, which serve as a natural physical barrier, induces interstitial hypertension and reduces blood supply, thereby hindering the delivery of drugs to the tumor. Additionally, it helps the metastasis and differentiation of PDAC cells, reducing the efficacy of clinical chemotherapy and immunotherapy. Although chemotherapeutic agents like gemcitabine have been used in the clinical treatment of PDAC for more than 20 years, the curative effect is obstructed by their poor stability in the bloodstream, low cellular uptake, and poor targeting. While small-molecule inhibitors targeting mutations such as KRAS^G12C, BRCA, and NTRK fusion have shown great potential for molecular targeted treatments and gene therapies of PDAC, their broader application is limited by side effects and restricted scope of patients. The advancement of nanotechnology brings new strategies for PDAC treatment. By virtue of unique size characteristics and actual versatility, different drug-delivery nanosystems contribute to overcome the dense stromal barrier, prolong the circulation time of therapeutics and realize precise PDAC treatment by targeted drug delivery. Clinical nanodrugs such as albumin-bound paclitaxel (nab-paclitaxel) and irinotecan liposome greatly improve the pharmacokinetics of conventional chemotherapeutics and promote drug accumulation inside the tumor, thereby are applying to the first-line treatment of PDAC. It is noteworthy that none nanodrugs with active targeting design have been approved for clinical treatment yet, though many are in clinical trials. In this review, we discuss promising targeting strategies based on different nanodrug delivery systems for treatment of PDAC. One major nanostrategy focuses on the tumor cell targeting and its applications in chemotherapy, molecular targeting therapy, gene therapy, and immunotherapy of PDAC. Another nanostrategy targets the tumor microenvironment, which highlights the nanosystems specifically regulating pancreatic stellate cells, immune cells and the extracellular matrix. Recent progress of developing new nanotheraputics for breakthrough in the fight of PDAC are elaborated in this review. We also provide our perspectives on the challenges and opportunities in the field.

DNA genetic markers have always played important roles in individual identification, kinship analysis, ancestry inference and phenotype characterization in the field of forensic medicine. DNA methylation has unique advantages in biological age inference, body fluid identification and prediction of phenotypes. The majority of current studies independently examine DNA and DNA methylation markers using various workflows, and they use various analytical procedures to interpret the biological information these two markers present. Integrated methods detect DNA and DNA methylation markers simultaneously through a single experimental workflow using the same preparation of sample. Therefore, they can effectively reduce consumption of time and cost, streamline experimental procedures, and preserve valuable DNA samples taken from crime scenes. In this paper, the integrated detection approaches of DNA and DNA methylation markers on different detection platforms were reviewed. In order to convert methylation modifications to detectable forms, several options were available for pretreatment of genomic DNA, including digestion with methylation-sensitive restriction enzyme, affinity enrichment of methylated fragments, conversion of methylated or unmethylated cytosine. Multiplexed primers can be designed for DNA markers and converted DNA methylation markers for co-amplification. The schemes of using capillary electrophoresis platform for integrated detection add the pretreatment of genomic DNA on the basis of detecting DNA genetic markers. DNA and DNA methylation markers are then integrated by co-amplification. But the limited number of fluorescent options available and the length of amplicons restrict the type and quantity of markers that can be integrated into a panel. Pyrophosphate sequencing also supports integrated detection of DNA and DNA methylation markers. On this platform, due to the conversion of unmethylated cytosine to thymine after treatment with bisulfite, the methylation level of CpG site can be directly calculated using the peak height ratio of cytosine bases and thymine bases. Therefore, the methylation levels and SNP typing can be simultaneously obtained. However, due to the limited read length of sequencing, the detection of markers with longer amplicons is restricted. It is not conducive to fully interpret the complete information of the target sequence. Next-generation sequencing also supports integrated detection of DNA and DNA methylation markers. A preliminary experimental process including DNA extraction, pretreatment of genomic DNA, co-preparation of DNA and DNA methylation library and co-sequencing, has been formed based on the next-generation sequencing platform. It confirmed the feasibility of next-generation sequencing technology for integrated detection of DNA and DNA methylation markers. In field of biomedicine, various integrated detection schemes and corresponding data analysis approaches of DNA and DNA genetic markers developed based on the above detection process.Co-analysis can simultaneously obtain the genomic genetic and epigenetic information through a single analytic process. These schemes suggest that next-generation sequencing may be an effective method for achieving more accurate and highly integrated detection, helping to explore the potential for application in forensic biological samples. We finally explore the impact of interactions between sites and different pretreatment methods on the integrated detection of DNA and DNA methylation markers, and also propose the challenge of applying third-generation sequencing for integrated detection in forensic samples.

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

ObjectiveTo observe the clinical efficacy and safety of Chaihu Shugansan combined with Xuanfu Daizhetang （CHSG-XFDZ） in the management of Barrett's esophagus （BE） with liver-stomach disharmony. MethodA randomized， parallel， controlled， double-blind clinical trial was conducted. BE patients who met the inclusion criteria were randomized into an observation group and a control group， with 34 patients in each group. The observation group was treated with CHSG-XFDZ combined with omeprazole capsules， and the control group was treated with CHSG-XFDZ mimetic combined with omeprazole capsules. Both groups were treated for 12 weeks. The traditional Chinese medicine （TCM） symptom scores， response rate， BE lesion area， BE pathological changes， and bile acid profile were taken as the indicators to jointly evaluate the clinical efficacy and safety of the two groups. ResultA total of 62 patients who completed the trial were included for statistical analysis， including 32 in the observation group and 30 in the control group. There were no statistically significant differences in baseline demographics or disease characteristics between two groups， which suggested that the two groups were comparable. The total response rate in the observation group was 93.7% （30/32）， which was higher than that （60.0%， 18/30） in the control group （χ²=24.766， P<0.05）. After treatment， the response rate regarding the pathological changes in the observation group was 62.5% （20/32）， which was higher than that （23.3%， 7/30） in the control group （χ²=10.270， P<0.05）. The response rate regarding the BE lesion area change in the observation group was 21.9% （7/32）， which had no statistically significant difference from that （6.7%， 2/30） in the control group， which indicated that the advantages of the two regimens were not obvious in terms of reducing the area of BE lesions. Compared with the control group after treatment， the observation group regulated the bile acid profile， which pointed out the direction for further exploring the mechanism of CHSG-XFDZ in treating BE. Neither group showcased adverse reactions with clinical significance during the treatment period. ConclusionCHSG-XFDZ outperformed the control group in terms of alleviating TCM symptoms， ameliorating pathological changes， and improving the bile acid profile in the BE patients with liver-stomach disharmony. It demonstrates certain potential in reducing the lesion area. This formula is safe and effective in treating BE patients with liver-stomach disharmony and deserves further clinical research and widespread application.

Objective:To explore the differences of microenviroment between peri-implant tissue and oral mucosal tissue.Methods:The gene chip data GSE43744 was downloaded from the GEO database,bioinformatics tools were used to analyze the differentially ex-pressed genes between the peri-implant tissue and normal oral mucosal tissue in rat.Results:1315 differentially expressed important genes,including 797 upregulated genes and 518 downregulated genes,were screened out.Gene enrichment analysis showed that com-pared with normal oral mucosal tissue,the gene expression of innate immune activity,cell activation,inflammatory response,and func-tional expression related to external and bacterial stimuli in peri-implant tissue were significantly upregulated,while that of extracellular matrix tissue,adhesion,extracellular matrix polysaccharides,response to mechanical stimuli and response to toxic substances was sig-nificantly downregulated.Meanwhile,multiple molecular functions and biological pathways related to T cells were highly expressed,which may play an important role in the peri-implant microenvironment.In addition,PPI network was constructed,and screened 7 core genes including FCER1G,TYROBP,PTPRC,ITGB2,AIF1,EMR1 and RAC2,which may be target genes for studying peri-implant microenvironment.Conclusion:There is a significant difference of microenvironment characteristics between peri-implant tissue and o-ral mucosa.The target genes screened using PPI network may be the key to future research on the peri-implant microenvironment.

Acute myocardial infarction (AMI) has become the leading cause of death in cardiovascular diseases. Myocardial ischemia and reperfusion (MI/R) occurs when myocardial blood circulation is reconstructed after blood supply is limited or lack, often after myocardial infarction, and is the main cause of acute myocardial injury. According to the length of ischemia time, arrhythmia, myocardial inhibition, and myocardial infarction may occur in sequence in MI/R. Mitochondria are the key organelles involved in MI/R injury. Mitochondrial ROS eruption, Ca²⁺ imbalance, mPTP opening, mitochondrial swelling, and release of pro-apoptotic proteins all lead to mitochondrial dysfunction and myocardial function impairment. Exercise is an effective intervention to prevent myocardial ischemia-reperfusion injury, and its protective effect is closely related to the intensity of exercise, the length of exercise time, the type of exercise and the internal exercise ability. The mitochondrial mechanism of exercise protection against myocardial ischemia-reperfusion injury is determined by many factors. During reperfusion, the heart after trained is better able to maintain energy homeostasis, maintain ΔΨ_m and limit mPTP activation, maintain ATP synthesis. Activation of the sarcoK_ATP and/or mitoK_ATP channels by exercise induces cellular and/or myocardial hyperpolarization, protecting the mitochondria and myocardium during MI/R. Exercise-trained hearts can regulate calcium homeostasis during MI/R and limit mitochondrial Ca²⁺ overload. Exercise training can improve the activity of mitochondrial antioxidant enzymes to clear ROS and regulate mitochondrial Ca²⁺ concentration during MI/R. Exercise can increase the bioavailability of NO near mitochondria and indirectly achieve exercise-induced myocardial protection through protein S-nitrosylation and the eNOS-NO pathway is related to mitochondrial biogenesis after exercise training. Exercise training can also affect mitochondrial dynamics during MI/R by preventing mitochondrial division and promoting mitochondrial fusion. Exercise training can promote autophagy of damaged mitochondria and reduces apoptosis through mitochondria too, thus helping to maintain the function of mitochondrial bank. Besides these, exercise training leads to the production of motor factors (mainly from the muscles, but also from the brain, red blood cells, and other tissues) that contribute to remote regulation of the heart. This paper reviews the mitochondrial mechanism of MI/R, the protective effect of exercise on MI/R and the role of mitochondria in it, in order to provide more theoretical basis and new therapeutic targets for the diagnosis and treatment of heart disease, and provide new targets for drug research and development. In future clinical treatment, it is expected that sports pills targeted mitochondria can treat MI/R injury for bedridden people who cannot exercise or people who do not want to exercise through new technological means such as nanoparticle packaging.

BACKGROUND:Mitochondrial reactive oxygen bursts have been shown to play a key role in skeletal muscle ischemia-reperfusion injury.3-Nitro-N-methylsalicylamide(3-NNMS)can effectively reduce the electron transport rate and has a potential protective effect on limb ischemia-reperfusion injury,but there is no clear research and clinical application. OBJECTIVE:To investigate the protective effect of 3-NNMS on the skeletal muscle after limb ischemia-reperfusion injury in rats and its mechanism. METHODS:Forty healthy 8-week-old Sprague-Dawley rats were randomly divided into control group,0,25 and 125 μg/mL 3-NNMS groups,with 10 rats in each group.Animal models of limb ischemia-reperfusion injury were prepared in the latter three groups.3-NNMS was injected into the injury site 30 minutes before reperfusion.The animals were sacrificed 2 hours after reperfusion.Blood from the apical part of the heart,and the tissue of the rectus femoris muscle of the right lower limb were taken for testing.The pathological morphology of the rectus femoris muscle was detected by hematoxylin-eosin staining.Serum levels of creatine kinase found in the skeletal muscle(CK-MM),lactate dehydrogenase,and myeloperoxidase were detected using ELISA;the levels of nuclear factor κB,tumor necrosis factor α,interleukin 1β,cyclooxygenase 2,malondialdehyde,reactive oxygen species,superoxide dismutase,catalase and glutathione peroxidase in the rectus femoris muscle were measured;and adenosine triphosphate(ATP)level,ATPase activity,and mitochondrial respiratory control rate were tested. RESULTS AND CONCLUSION:Compared with the control group,the model rats with ischemia-reperfusion injury had increased serum levels of CK-MM,lactate dehydrogenase,and myeloperoxidase,increased levels of nuclear factor κB,tumor necrosis factor α,interleukin 1β,cyclooxygenase 2,malondialdehyde and reactive oxygen species in the rectus femoris muscle,decreased levels of catalase and glutathione peroxidase in the rectus femoris muscle,and reduced ATPase activity and mitochondrial respiratory control rate.Moreover,cell morphology was irregular,inflammatory cell infiltration was obvious,and the cells were swollen in rats after ischemia-reperfusion injury.Compared with the 0 μg/mL group,the serum CK-MM and lactate dehydrogenase levels decreased,the levels of nuclear factor κB and cyclooxygenase 2 in the rectus femoris muscle decreased,reactive oxygen species level decreased,and superoxide dismutase activity increased in the 25 μg/mL group;cell morphology was more regular,inflammatory cell infiltration was lighter,and cell swelling was alleviated.Compared with the 0 μg/mL group,the 125 μg/mL group had a reduction in the serum levels of CK-MM,lactate dehydrogenase,and myeloperoxidase and the levels of nuclear factor κB,tumor necrosis factor α,cyclooxygenase 2,malondialdehyde and reactive oxygen species in the rectus femoris muscle,as well as an increase in the levels of superoxide dismutase and glutathione peroxidase in the rectus femoris muscle,and mitochondrial respiratory control rate.Moreover,the cells were arranged neatly,the outline was clear and complete,and the inflammatory cell infiltration was light.To conclude,3-NNMS can alleviate the functional impairment of the skeletal muscle caused by limb ischemia-reperfusion,and its mechanism of action may be through improving mitochondrial function,reducing reactive oxygen species production,decreasing oxidative stress and inflammatory response,and thus reducing tissue damage and repairing skeletal muscle function.