BACKGROUND:Type 2 diabetes mellitus is a secondary causative factor for osteoporosis.As highly heterogeneous innate immune cells,macrophages may be polarized in a hyperglycemic environment,which affects osteogenesis-angiogenesis coupling.This may be a research target for improving bone quality in patients with type 2 diabetic osteoporosis.OBJECTIVE:To explore the role of modulating macrophage M1/M2 polarization to influence osteogenesis-angiogenesis coupling in type 2 diabetic osteoporosis and to summarize the effects of commonly used anti-glucose and anti-osteoporosis drugs and bone biorepair materials on bone osteogenesis-angiogenesis coupling by regulating macrophage M1/M2 polarization.METHODS:The keywords of"macrophage polarization,type 2 diabetes,osteoporosis,osteogenesis-angiogenesis coupling"in Chinese and"macrophages,macrophage polarization,osteogenesis-angiogenesis coupling"in English were used to search for relevant literature in CNKI and PubMed,respectively.Seventy-nine pieces of literature were screened and analyzed.RESULTS AND CONCLUSION:(1)Type 2 diabetes mellitus causes the body to be in a hyperglycemic environment and increases the secretion of inflammatory-related factors in the body,which promotes macrophage polarization towards M1 and decreases the number of M2 macrophages.(2)In type 2 diabetes,promoting M2 macrophage polarization is beneficial for osteogenesis-angiogenesis coupling.(3)Some anti-glycemic drugs,active ingredients in traditional Chinese medicine and bone biorepair materials can improve type 2 diabetic osteoporosis by regulating macrophage M1/M2 polarization,reducing M1/M2 ratio,and promoting osteogenesis-angiogenesis coupling.

ObjectiveThis paper aims to systematically reveal the effect difference and mechanisms of Zishenwan against chronic prostatitis （CP） before and after salt-processing of Anemarrhenae rhizoma and Phellodendri chinensis cortex based on an integrated strategy of ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry （UPLC-Q-Orbitrap-MS/MS）， network pharmacology， and serum metabolomics. MethodsZishenwan samples before and after salt-processing of Anemarrhenae rhizoma and Phellodendri chinensis cortex were extracted by alcohol-water dual extraction. The chemical components of each sample were detected by UPLC-Q-Orbitrap-MS/MS， and differential components were screened by multivariate statistical analysis. Network pharmacology analysis was performed based on the identified chemical components of Zishenwan to construct a protein-protein interaction （PPI） network of "component， target， and pathway"， and the core components， targets， and pathways of Zishenwan against CP were screened. Forty-two male Sprague-Dawley （SD） rats were randomly divided into a blank group， a model group， a Qianliekang group （1.54 g·kg^-1）， low- and high-dose raw Zishenwan groups （1.8， 5.4 g·kg^-1）， and low- and high-dose salt-processed Zishenwan groups （1.8， 5.4 g·kg^-1）. The CP rat model was established by intraprostatic injection of carrageenan. After one week of recovery， the rats were administered the corresponding drugs for 21 days， while those in the blank group and model group received the same volume of normal saline. After the experiment， serum and tissue samples were collected to evaluate pharmacodynamic indicators including organ indices， histopathology， and inflammatory factors in serum. Subsequently， untargeted serum metabolomics technology was used to analyze metabolite changes and perform pathway enrichment analysis. The network pharmacology was used to construct a network of "differential metabolite， reaction， enzyme， and gene". ResultsA total of 76 components were identified in raw and salt-processed Zishenwan， and 34 differential components were screened by multivariate statistical analysis. Among them， the contents of 14 components， including berberine， berberrubine， and phellodendrine， increased after salt-processing， while the contents of 20 components， such as neomangiferin， decreased. The 28 active components and 185 potential targets were screened out by network pharmacology. The core components included berberine， phellodendrine， magnoflorine， and jatrorrhizine， and the core targets included signal transducer and activator of transcription 3 （STAT3）， protein kinase B1 （Akt1）， and transcription factor AP-1 （JUN）. These targets were significantly enriched in pro-inflammatory signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） and mitogen-activated protein kinase （MAPK）. Compared with the model group， all Zishenwan administration groups showed decreased prostate index， reduced levels of interleukin （IL）-1β， IL-18， and B-cell lymphoma-2 （Bcl-2） in serum （P<0.05， P<0.01）， as well as varying degrees of alleviation in histopathological damage. At the same dose， compared with the raw Zishenwan groups， the salt-processed Zishenwan groups showed lower prostate index， pathological scores， and IL-1β， IL-18， and Bcl-2 levels in serum， but the differences were not statistically significant. Metabolomics reveals that 38 differential metabolites were reversed after salt-processed Zishenwan administration. Both raw and salt-processed Zishenwan regulated pathways such as β-alanine metabolism and tryptophan metabolism. In addition to the common regulated pathways， the salt-processed group specifically regulated pantothenate and coenzyme A biosynthesis， pyrimidine metabolism， and arginine and proline metabolism. The intersecting pathways between network pharmacology and metabolomics were tryptophan metabolism and arginine and proline metabolism， with overlapping targets including monoamine oxidase A （MAOA） and arginase 1 （ARG1）. ConclusionThe increased contents of components such as berberine and phellodendrine in salt-processed Zishenwan may enhance its therapeutic effect on CP by inhibiting the PI3K/Akt and MAPK signaling pathways， along with multi-target regulation of tryptophan， arginine， and pantothenate metabolism pathways to comprehensively regulate inflammatory and immune responses.

BACKGROUND:Type 2 diabetes mellitus is a secondary causative factor for osteoporosis.As highly heterogeneous innate immune cells,macrophages may be polarized in a hyperglycemic environment,which affects osteogenesis-angiogenesis coupling.This may be a research target for improving bone quality in patients with type 2 diabetic osteoporosis.OBJECTIVE:To explore the role of modulating macrophage M1/M2 polarization to influence osteogenesis-angiogenesis coupling in type 2 diabetic osteoporosis and to summarize the effects of commonly used anti-glucose and anti-osteoporosis drugs and bone biorepair materials on bone osteogenesis-angiogenesis coupling by regulating macrophage M1/M2 polarization.METHODS:The keywords of"macrophage polarization,type 2 diabetes,osteoporosis,osteogenesis-angiogenesis coupling"in Chinese and"macrophages,macrophage polarization,osteogenesis-angiogenesis coupling"in English were used to search for relevant literature in CNKI and PubMed,respectively.Seventy-nine pieces of literature were screened and analyzed.RESULTS AND CONCLUSION:(1)Type 2 diabetes mellitus causes the body to be in a hyperglycemic environment and increases the secretion of inflammatory-related factors in the body,which promotes macrophage polarization towards M1 and decreases the number of M2 macrophages.(2)In type 2 diabetes,promoting M2 macrophage polarization is beneficial for osteogenesis-angiogenesis coupling.(3)Some anti-glycemic drugs,active ingredients in traditional Chinese medicine and bone biorepair materials can improve type 2 diabetic osteoporosis by regulating macrophage M1/M2 polarization,reducing M1/M2 ratio,and promoting osteogenesis-angiogenesis coupling.

Allergen immunotherapy（AIT）can alter the natural course of allergic diseases through immunomodulatory mechanisms and maintain the efficacy after completion. The induction of immune tolerance by AIT is considered to be effective treatment and the mechanism involves the participation of a variety of immune cells，including effector T cells，B cells，dendritic cells，innate lymphoid cells，mast cells and basophils. Studies have found that a variety of immune cells in peripheral blood changed during AIT treatment and the changes of some immune cells were related to the efficacy of AIT，which may provide some theoretical reference for practical clinical activities and may become potential biomarkers for predicting and evaluating the efficacy of AIT. This article reviews the changes of peripheral blood immune cells in the treatment of AIT.

Diabetic retinopathy(DR),as one of the most common microvascular complications in patients with diabe-tes mellitus(DM),has a complex and multifaceted etiology that involves multiple factors.The unique characterization of DR in genomics,epigenomics,transcriptomics,proteomics,and metabolomics has opened new avenues for the exploration and development of novel therapeutic strategies for this disease.However,the inherent limitation of single-omics approa-ches is that they can only analyze the biological and molecular mechanisms underlying the disease from a single dimension,which makes it difficult to comprehensively capture the complex nature of DR.With the rapid advancement of high-throughput sequencing technology,multi-omics joint analysis combines the advantages of different histological techniques and can explore the pathogenesis of DR from multiple dimensions and levels.This paper aims to comprehensively review the latest progress of multi-omics technologies in revealing the pathogenesis of DR and its complex molecular mechanisms and thoroughly explore the new opportunities,current challenges,and future development prospects of multi-omics tech-nologies for DR research.

Background and Aims:Laparoscopic cholecystectomy(LC)is a common surgical method for the treatment of gallbladder diseases.However,some patients experience symptoms such as dyspepsia after surgery,which can affect their quality of life.Compound azinomide enteric-coated tablets,a novel drug,may improve dyspeptic symptoms after LC.This study was conducted to explore the clinical efficacy of compound azinomide enteric-coated tablets in treating post-LC dyspepsia symptoms through a multicenter clinical trial.Methods:A multicenter,superior efficacy,open-label,parallel-controlled design was used.Patients with postoperative dyspepsia were enrolled in 7 centers between January 2023 and May 2024.Patients were randomly assigned to either the observation or control groups using a random number table.The observation group received compound azinomide enteric-coated tablets,while the control group was treated with a combination of oryzae pancreatin tablets and ursodeoxycholic acid tablets.Both groups were treated for 4 weeks.The primary endpoints included gastrointestinal symptom scores and quality of life scores assessed before and at 14 and 28 d after treatment.Additionally,the incidence of adverse reactions and cost-effectiveness ratio(CER)were compared between the groups.Results:A total of 303 patients were included,with 150 in the observation group and 153 in the control group.Baseline characteristics were balanced between the groups before treatment(all P>0.05).After treatment,the observation group showed significantly higher effective rates at 14 d and 28 d than the control group(44.7%vs.29.4%;98.0%vs.73.9%,both P<0.05).The observation group also had significantly lower symptom scores and quality of life scores at both 14 and 28 d,with a significantly higher improvement rate in symptom scores compared to the control group(all P<0.05).Further analysis of the improvement rate and treatment efficacy for individual symptoms revealed that,except for the 14-d improvement in abdominal pain/discomfort,the observation group showed better improvement in all other symptoms at 14 d and in all symptoms at 28 d compared to the control group(all P<0.05).No adverse reactions were observed in either group.The CER for the observation group was 283.78 yuan/efficacy rate at 14 d and 128.57 yuan/efficacy rate at 28 d,while the control group's CER was 729.93 yuan/efficacy rate at 14 d and 290.22 yuan/efficacy rate at 28 d.Conclusion:Compound azinomide enteric-coated tablets demonstrated good clinical efficacy in treating dyspepsia symptoms after LC with excellent safety and high cost-effectiveness.Despite some limitations,the results provide a new treatment option for dyspepsia after LC.Larger-scale randomized controlled trials are needed to validate this study's conclusions further.

Objective To explore the syndrome differentiation rules of the Yin Dan and Yang Dan method,and summarize Professor Yang Zhimin's valuable experience in the treatment of insomnia.Methods The case data of 11390 insomnia patients treated by Professor Yang Zhimin was retrospectively analyzed,and the distribution of symptoms,signs,pathogenesis and syndrome differentiation rules of insomnia patients was examined based on latent structure analysis.Result A total of 44 symptoms and signs can explain the overall situation of insomnia patients,showing the characteristics of both excess and deficiency,cold and heat.A total of 36 hidden categories(symptom clusters and pathogenesis)was composed.Symptoms and signs such as fear of wind and cold can explain the overall situation of insomnia patients with cold syndrome due to weakness of Wei Qi,symptoms and signs such as pale eyelid can explain the overall situation of insomnia patients with heat syndrome due to weakness of Ying Xve,and established diagnostic criteria for insomnia patients with cold syndrome due to weakness of Wei Qi and heat syndrome due to weakness of Ying Xve.Conclusion Based on the Yang Dan and Yin Dan method to distinguish and treat insomnia from the perspective of disharmony between Ying and Wei,it is in line with the basic understanding of the pathogenesis of insomnia in the classics of traditional Chinese medicine.The pattern differentiation rules obtained through the latent structure analysis method are helpful to summarize valuable clinical experience and provide a certain reference and basis for clinical practice.

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

In recent years, prone mechanical ventilation has been widely used to improve oxygenation dysfunction in critically ill patients. During prone mechanical ventilation, the patient's face is compressed for a long time, and due to the difficulty in changing, facial pressure injuries and ocular complications are common and severe. These complications increase patient discomfort, reduce their tolerance and compliance with prone ventilation, and even cause tracheal tube displacement or dislodgement, leading to significant clinical challenges. In order to change this situation, the medical staff of the department of critical care medicine of the Second People's Hospital of Hengshui and the department of critical care medicine of Harrison International Peace Hospital had developed an adjustable facial support pad for prone ventilation, and obtained a National Utility Model Patent of China (ZL 2022 2 3295294.4). The device is composed of a facial support platform, a supporting telescopic foot frame and so on. There are front, back, left and right adjustable tracks below the support cushion platform, which can be adjusted to the best state suitable for the patient's face shape, which can alleviate the facial pressure injuries and ocular complications caused by the different sizes of each patient's face, improve the patient's comfort, and reduce the incidence of facial pressure injury and the occurrence of ocular complications of the patient. The height of the platform is adjusted by the telescopic feet, and there is a hook assembly below, which can be fixed by the clamp of the ventilator tubing, so as to prevent the ventilator tubing from pulling the endotracheal intubation due to the gravity of condensation, resulting in the displacement or even prolapse of the tracheal intubation, and reducing the occurrence of adverse events of tracheal intubation. It is worth promoting in the clinic.
Humans ; Respiration, Artificial/methods* ; Prone Position ; Equipment Design ; Face