ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress （CRS） and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank， model， positive drug （diazepam， 1 mg·kg^-1）， and low-， medium-， and high-dose （0.75， 1.5， 3 g·kg^-1， respectively） Fufang Kangjiaolv capsules groups. After 14 days of administration， the elevated plus maze test， open field test， light and dark box test， and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats， and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of zonula occludens-1 （ZO-1） and occludin in the colon of rats. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the colon， serum， and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1， occludin， nuclear factor-κB p65 （NF-κB p65） in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. ResultsCompared with the blank group， the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze， the time and frequency of rats entering the central area of the open field， the time of entering the open box， the times of passing through the light and dark box， and the number of unburied beads （P<0.05， P<0.01）. Compared with the model group， Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees， and the high-dose group had the best effect， with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze （P<0.05）， the number of rats entering the central area in the open field （P<0.05）， the time of entering the open box， the times of passing through the light and dark boxes， and the number of unburied beads （P<0.01）. Moreover， the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes， Deferribacterota， Romboutsia， and Phascolarctobacterium， while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota， Bacteroides， norank f norank o Clostridia UCG-014， and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group， the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon （P<0.01）， elevated levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated protein level of NF-κB p65 in the colon and hippocampus （P<0.01）， and down-regulated protein level of BDNF in the hippocampus （P<0.05）. Compared with the model group， high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon （P<0.01）， lowered the levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated the protein levels of ZO-1 （P<0.01） and occludin （P<0.05） in the colon， down-regulated the protein level of NF-κB p65 in the colon and hippocampus （P<0.05）， and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance， up-regulating the expression of tight junction proteins in the colon， repairing intestinal mucosal mechanical barrier， and down-regulating NF-κB/BDNF signaling pathway， thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis， providing a new idea for further research.

In the field of oral medicine, 3D-printed individualized titanium mesh technology is gradually becoming an important means for the treatment of severe alveolar bone defect augmentation. This article provides a comprehensive analysis of the advantages of this technology, the evaluation of osteogenic effects, and the progress of research in clinical applications. In response to the current issue of variability in bone augmentation outcomes, this paper delves into multiple factors affecting bone augmentation effects, including individualized titanium mesh design (involving the thickness, pore size, pore shape, porosity, contour shape, selection of titanium alloy materials, and 3D printing technology), intraoperative procedures (the accuracy of placement during 3D-printed individualized titanium mesh surgery), and postoperative care (including the prevention of complications, formation of pseudoperiosteum, and stability of the titanium mesh). By integrating the clinical experience and research findings of our team, we propose a series of targeted optimization strategies, including designing, manufacturing, and clinically applying self-positioning individualized titanium meshs (positioning wings + individualized titanium meshs) to improve the positioning accuracy of the titanium mesh; propose individualized treatment processes and titanium mesh design schemes based on specific conditions of alveolar bone defects and soft tissue status; and emphasize the importance of long-term stable fixation of the titanium mesh to reduce the risk of postoperative mesh loosening and displacement. In addition, we appropriately summarize the evaluation methods for the bone augmentation effects of 3D-printed individualized titanium meshes, covering the following key indicators: (1) vertical bone augmentation and horizontal bone augmentation; (2) changes in bone contour morphology; (3) bone volume increase; (4) clinical indicators (surgical success rate, titanium mesh exposure, infection rate, and postoperative recovery); (5) aesthetic effect evaluation; (6) long-term stability; (7) radiological assessment; (8) patient satisfaction; and (9) precision of surgical operation, aiming to assist doctors in comprehensively assessing and in-depth analyzing the surgical outcomes to achieve the best therapeutic effects. The purpose of this article is to provide a reference for the optimization and clinical application of 3D-printed individualized titanium mesh technology and to lay a theoretical foundation for achieving the best osteogenic effects.

OBJECTIVE To compare the measures taken by China， the U.S. and Japan to adapt drug instructions to aging， and provide reference for the reform of elderly-friendly drug instructions in China. METHODS The relevant documents published by the official websites of National Medical Products Administration of China， the U.S. FDA， and Pharmaceuticals and Medical Devices Agency of Japan， were consulted. Additionally， relevant literature from comprehensive databases such as CNKI， Wanfang data， and Web of Science， as well as search engines， was reviewed to understand the measures taken by the above countries in elderly-friendly management process of drug instructions. The comparative analysis was conducted for elderly-friendly adaptations of drug instructions in China， the U.S. and Japan， and the suggestions were put forward for the reform of elderly-friendly drug instructions in China. RESULTS & CONCLUSIONS The measures taken by China， the U. S.， and Japan in the process of elderly- friendly management of drug labels had different emphases： China adopted large fonts and simplified drug instructions to alleviate the problem of the elderly being unable to read and understand drug instructions； the U.S. had set up a special section for the elderly in the drug instructions for special populations and issued the principles for writing information on medications for the elderly. The U. S. and Japan had established a classification management system for patient instructions and professional instructions， promoted structured electronic instructions， and built a unified electronic instructions platform. It is recommended that China incorporate elderly-specific medication information into the writing requirements of drug instructions， improve specific measures to encourage the reform of drug instructions suitable for the elderly， improve the accessibility and readability of electronic drug instructions， and build a drug instruction information disclosure platform to better ensure the safety of medication for the elderly.

Gastrointestinal motility disorder is an important cause of digestive system diseases. Patients often suffer from nausea， vomiting， gastric retention， gastroparesis， constipation， and many other symptoms， and their quality of life is seriously reduced. Prokinetic agents are routinely used in clinical practice， but their long-term use is prone to problems such as reduced efficacy and increased adverse reactions. Since the incidence of gastrointestinal diseases has continued to rise globally in recent years， there is an urgent need for clinical development of safe and effective treatment strategies. Aurantii Fructus， a traditional Chinese medicine， has the effect of smoothing Qi and eliminating distention， and it has been used to treat gastrointestinal diseases for thousands of years. In modern clinical practice， it is mainly used for the treatment and auxiliary treatment of various gastrointestinal diseases such as functional dyspepsia， functional constipation， and irritable bowel syndrome. The efficacy is remarkable， and no adverse reactions have been reported at conventional doses. Therefore， it can greatly improve the symptoms of patients with gastrointestinal diseases and improve their quality of life. Modern research has revealed that there are many active components in Aurantii Fructus， among which flavonoids have the highest content and the most types. Flavonoids are the main active components in Aurantii Fructus to regulate gastrointestinal motility. Aurantii Fructus and its active components can affect gastrointestinal hormones， neural pathways， Cajal mesenchymal cells， and other multiple mechanisms. They can adjust gastrointestinal motility and correct gastrointestinal motility disorders， showing potential application value in the treatment of gastrointestinal motility disorders. However， a comprehensive analysis of Aurantii Fructus in this aspect is still lacking. This study summarized the pharmacological activities of active components of Aurantii Fructus extract and its flavonoids， volatile oils， alkaloids， and coumarin on the regulation of gastrointestinal motility and explored the latest research progress on its mechanism. Finally， the adverse reactions of Aurantii Fructus were summarized. It aims to provide a scientific basis for the research and clinical application of Aurantii Fructus and its active components in the regulation of gastrointestinal motility.

Regulated cell death (RCD) is a critical physiological process essential in maintaining skin homeostasis. Among the various forms of RCD, ferroptosis stands out due to its distinct features of iron accumulation, lipid peroxidation, and involvement of various inhibitory antioxidant systems. In recent years, an expanding body of research has solidly linked ferroptosis to the emergence of skin disorders. Therefore, understanding the mechanisms underlying ferroptosis in skin diseases is crucial for advancing therapy and prevention strategies. This review commences with a succinct elucidation of the mechanisms that underpin ferroptosis, embarks on a thorough exploration of ferroptosis’s role across a spectrum of skin conditions, encompassing melanoma, psoriasis, systemic lupus erythematosus (SLE), vitiligo, and dermatological ailments precipitated by ultraviolet (UV) exposure, and scrutinizes the potential therapeutic benefits of pharmacological interventions aimed at modulating ferroptosis for the amelioration of skin diseases.

Objective:To analyze the association between the peripheral blood lymphocyte subsets and the occurrence of carotid atherosclerosis(CAS)and discuss the risk factors of CAS,and to provide the basis for risk prediction and early intervention of CAS.Methods:A total of 419 subjects were selected according to the inclusion and exclusion criteria.All the subjects underwent carotid ultrasonography,and the detection of T lymphocyte,B lymphocyte,and natural killer(NK)cell subsets were performed.According to the carotid artery intima-media thickness(IMT),the subjects were divided into normal carotid artery group(n=166)and CAS group(n=253).The basic data and laboratory inspection indexes of the subjects in two groups were collected,including age,gender,blood pressure,medical history,smoking history,medication history,blood lipids,and percentages of T lymphocyte,B lymphocyte,and NK cell subsets.The risk factors for the occurrence of CAS of the subjects were analyzed using Logistic regression analysis.Results:The univariate analysis results showed that compared with normal carotid artery group,the age,morbidity rate of hypertension,morbidity rate of diabetes,and smoking rate of the subjects in CAS group were increased(P＜0.05),and the percentages of CD4+T lymphocytes,CD4+T lymphocyte count,CD4+/CD8+ratio,CD16+CD56+NK cell count,and low-density lipoprotein cholesterol(LDL-c)level in peripheral blood were increased(P＜0.05),while the percentage of CD8+T lymphocyte was decreased(P＜0.05).The multivariable Logistic regression analysis results showed that age(OR=1.112,95％CI:1.083-1.142,P＜0.001),smoking(OR=1.997,95％CI:1.192-3.346,P=0.009),LDL-c(OR=1.427,95％CI:1.017-2.001,P=0.039),and percentage of CD4+T lymphocyte(OR=1.044,95％CI:1.002-1.087,P=0.039)were the independent risk factors for the occurrence of CAS.Conclusion:The percentage of CD4+T lymphocyte is associated with the occurrence of CAS and it is a predictive risk factor for CAS.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Objective To investigate the pathological damage to and inflammation of different intestinal segments in a rat model of severe hemorrhage,and to explore the effect of polarization of intestinal macrophage on the pathophysiology of intestinal inflammation.Methods Male Wistar rats were randomly divided into two groups:the sham operation group and hemorrhage group.In the hemorrhage group,40％of the total blood volume was lost in 25-30 minutes,while in the sham operation group,only the femoral artery and vein were intubated without bleeding.The rats were killed at 0,3,6,12 and 24 hours.The entire intestine was isolated quickly,and sections of the intestine were cut at the duodenum,jejunum,ileocecal junction,colon and rectum for histopathological evaluation.ELISA was adopted to determine related inflammation factors while multi-color immunohistochemistry was used to calculate macrophage surface markers.The data was statistically analyzed.Results(1)Compared with the sham group,there was no significant difference in colon histology at 3 h and 6 h,but significant difference was detected in rectum scores only at 24 h.The scores of other intestinal segments were significantly different at each time point.The severity of ileocecal and colonic lesions after bleeding increased with time.The duodenum,jejunum and ileocecum were more critically injured at 3 h than the rectum at 6 h.The injury to the duodenum,jejunum,ileum and colon was much more pronounced than to the rectum at 12 h.(2)The expressions of TNF-α and IL-1β in the rectum were increased significantly at 12 h post operation.The expressions of IL-1β,TNF-α in the jejunum increased obviously at 3 h and 6 h,respectively.(3)Three hours after severe bleeding,the level of macrophages in the jejunum and ileocececal area increased significantly,and the percentage of M1 macrophages was higher.After 6 hours,the proportion of M2 macrophages in the jejunum and M1 macrophages decreased significantly.After 3 hours,the percentage of M1 macrophages in the colon decreased,but that of M2 macrophages increased.The proportion of M2 polarized macrophages in the duodenum and rectum increased at 3 h after severe bleeding but decreased at 6 h.Conclusion Pathological damage to intestinal sections after bleeding varies depending on the time,and is correlated with the inflammatory level of macrophages.

Ischemic stroke,due to its high prevalence and mortality,has become one of the most important public health concerns globally.Nerve cell damage is the main biological event in its patho-logical process and there is still a lack of effective neuroprotective drugs for clinical use.Numerous studies have shown that inhibitions of histone deacetylases(HDACs)can exert neuroprotective effects in ischemic stroke.Due to the multiple types of HDACs and the relatively poor specificity of HDAC inhib-itors,it has been difficult to identify any HDAC that plays a key role in ischemic stroke.ClassⅠHDACs include four members:HDAC1,HDAC2,HDAC3,and HDAC8,and have been more in-depth in isch-emic stroke.The complex mechanisms of classⅠHDAC inhibitors that have been discovered so far involve neural cell function,neuroinflammation and blood-brain barriers.This article is intended to study the regulatory role of classⅠHDACs in ischemic stroke in the hopes of providing reference for the developments of effective drugs targeting HDACs.

OBJECTIVE To investigate the distribution and regulation of G-quadruplex(G4)in enzymes related to glycolysis.METHODS The sequences of the transcription start site(TSS)region upstream of 1500 bp to the 5'-Untranslated region in 200 enzymes and their subtypes in glycolysis were selected for bioinformatics analysis.Related enzymes in glycolysis containing putative G-quadru-plex-forming sequences(PQSs)were identified.Circular Dichroism and Native polyacrylamide gel elec-trophoresis were used to verify the formation of G4.The ExonucleaseⅠhydrolysis assay was used to validate the stability of the formed G4 under 0,0.5,2,8,16,and 32 min.A reporter gene plasmid was constructed by inserting specific fragments of the related enzymes before the luciferase expression sequence.The dual-luciferase reporter assay system validate the expression level of luciferase to assess the impact of G4 on promoter activity.Real-time quantitative PCR was performed to validate the transcriptional regulatory role of G4 by detecting the mRNA levels of luciferase.RESULTS ①Bioin-formatics analysis showed that out of the 200 glycolysis-related enzymes,12 contained PQSs.Based on the analysis of the length and structure of PQSs,aldolase A(ALDOA)and phosphoglycerate mutase 2(PGAM2)proved to be able to form stable G4.② ALDOA and PGAM2 had the maximum positive absorption peak at 260 nm and maximum negative absorption peak at 240 nm.Both of them could form a G4 at the same time.③After digestion with ExonucleaseⅠ,ALDOA and PGAM2 showed no significant hydrolysis and demonstrated the stability of G4 structures.However,both of them could be gradually hydrolyzed after mutations in their PQSs.④ After PQS mutation of ALDOA and PGAM2,the mRNA levels and expression of downstream luciferase of ALDOA were significantly increased(P<0.05,P<0.01),while PGAM2 was significantly decreased(P<0.05,P<0.01).CONCLUSION The gene sequences of glycolysis-related enzymes and their subtypes contain a large number of PQSs.ALDOA and PGAM2 can form stable G4 and perform transcriptional regulatory functions.