ObjectiveTo explore the effect of Polygonati Odorati Rhizoma polysaccharides on hyperlipidemia in mice by modulating the gut microbiota. MethodsNinety male C57BL/6J mice were randomized into the following groups （n=15）： control， model， simvastatin， low- （100 mg·kg^-1）， medium- （200 mg·kg^-1）， and high-dose （400 mg·kg^-1） Polygonati Odorati Rhizoma polysaccharides groups. Other groups except the control group were fed with a high-fat diet for the modeling of hyperlipidemia， and drug interventions lasted for 12 weeks. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured by an automatic biochemical analyzer. The pathological changes in the liver and epididymal fat were observed by hematoxylin-eosin staining， and lipid accumulation in the liver was assessed by oil red O staining. The gut microbiota was analyzed by 16S rRNA gene sequencing. ResultsCompared with the control group， the model group exhibited an increase in body weight （P<0.01）， along with marked elevations in serum levels of TC， TG， and LDL-C （P<0.05，P<0.01）. Furthermore， the model group showcased increase in the liver index and epididymal fat coefficient （P<0.05）， increased liver fat accumulation， enlargement of adipocytes in the epididymal fat， decreases in both alpha and beta diversity of the gut microbiota， and an increase in the relative abundance of Allobaculum （P<0.01）. Compared with the model group， Polygonati Odorati Rhizoma polysaccharides suppressed the increase in body weight （P<0.01）， lowered the serum levels of TC， TG， and LDL-C （P<0.05，P<0.01）， reduced the liver index and epididymal fat coefficient （P<0.05）， alleviated liver fat accumulation， and decreased the size of adipocytes in the epididymal fat. Furthermore， it enhanced the alpha and beta diversity of the gut microbiota in mice， reduced the relative abundance of Allobaculum， Erysipelotrichaceae， and Clostridium （P<0.01）， and increased the relative abundance of Akkermansia and Blautia （P<0.01）. ConclusionPolygonati Odorati Rhizoma polysaccharides can ameliorate hyperlipidemia induced by a high-fat diet in mice by regulating the diversity and composition of the gut microbiota.

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

Flowering and bolting are important agronomic traits in cruciferous crops such as Brassica juncea. Timely flowering can ensure the crop organ yield and quality, as well as seed propagation. The WRKY family plays an important role in regulating plant bolting and flowering, while the function and mechanism of WRKY12 in B. juncea remain unknown. To explore its function and mechanism in bolting and flowering of B. juncea, we cloned and characterized the BjuWRKY12 gene in B. juncea and found that its expression levels were significantly higher in flowers and inflorescences than in leaves. BjuWRKY12 belonged to the Ⅱc subfamily of the WRKY family, and subcellular localization indicated that the protein was located in the nucleus. Ectopic overexpression of BjuWRKY12 in transgenic lines promoted bolting and flowering, leading to significant increases in the expression levels of flowering integrators SOC1 and FUL. Furthermore, yeast one-hybrid and dual luciferase reporter system assays confirmed that BjuWRKY12 directly bound to the promoters of BjuSOC1 and BjuFUL, undergoing protein-DNA interactions. This discovery gives new insights into the regulation network and molecular mechanisms of BjuWRKY12, laying a theoretical foundation for the breeding of high-yield and high-quality varieties of B. juncea.
Mustard Plant/metabolism* ; Flowers/growth & development* ; Plant Proteins/physiology* ; Promoter Regions, Genetic/genetics* ; Gene Expression Regulation, Plant ; Plants, Genetically Modified/genetics* ; Transcription Factors/metabolism* ; MADS Domain Proteins/metabolism*

ObjectiveTo explore the mechanism of Buzhong Yiqitang in ameliorating inflammatory injury in autoimmune thyroiditis (AIT) mice based on the Toll-like receptor 4（TLR4）/nuclear transcription factor-kappa B（NF-κB）/absent in melanoma 2（AIM2）inflammasome signaling pathway. MethodThe 120 genetically susceptible 8-week-old NOD.H-2^h4 mice were selected and randomly divided into control group， model group， low， medium and high dose groups of Buzhong Yiqitang （4.78， 9.56， 19.12 g·kg^-1）， and western medicine group （selenium yeast tablets， 3.033×10^-5 g·kg^-1）. The AIT model mice in each group drank ad libitum 0.05% sodium iodide aqueous solution for 8 weeks to establish the AIT model， and the control group drank ad libitum distilled water. Eight weeks later， the mice in each dosing group were divided into groups and gavage. The swelling of thyroid tissue was observed with the naked eye， and the weight of spleen was weighed. The content of serum inflammatory factors interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， and Real-time PCR was used to detect the expression of HMGB1， TLR4， AIM2， NF-κB p65，apoptosis-associated speck-like protein（ASC），cysteinyl aspartate-specific protease-1（Caspase-1）， IL-1β mRNA. Western blot was used to detect the expression of high motility group protein 1 （HMGB1）， TLR4， AIM2， NF-κB p65， phosphorylation（p）-NF-κB p65， ASC， Caspase-1， and IL-1β proteins in thyroid tissue， and immunofluorescence staining was used to observe the protein expression of HMGB1， AIM2， and NF-κB p65 in thyroid tissue of mice. ResultCompared with the control group， the thyroid tissue of mice in the model group was significantly swollen， the spleen quality was significantly increased， and the expression of HMGB1， TLR4， NF-κB p65， AIM2， ASC， Caspase-1， IL-1β in thyroid tissue was significantly increased （P<0.01）. Compared with the model group， the swelling of thyroid tissue in mice in each dose group of Buzhong Yiqitang was improved， the quality of spleen was significantly reduced， and the expression of HMGB1， TLR4， AIM2， NF-κB p65， p-NF-κB p65， ASC， Caspase-1， IL-1β in thyroid tissue was significantly reduced （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT， and regulating the abnormal activation of the TLR4/NF-κB/AIM2 inflammasome signal pathway may be one of its intervention mechanisms.

ObjectiveTo investigate the mechanism of Buzhong Yiqitang in ameliorating ferroptosis in autoimmune thyroiditis （AIT） mice based on the nuclear factor erythroid 2-related factor 2 （Nrf2）/peroxisome proliferator-activated receptor γ （PPARγ）/glutathione peroxidase 4 （GPX4） pathway. Method120 SPF-grade 7-8-week-old NOD.H-2^h4 mice were randomly divided into control group， model group， low-， medium-， and high-dose Buzhong Yiqitang groups， and western medicine group， with 20 mice in each group. Except for the control group， all mice were fed with classic high-iodine water （0.05% NaI） to induce AIT models after 8 weeks. The low-， medium-， and high-dose Buzhong Yiqitang groups were administered 4.78， 9.56， 19.12 g·kg^-1 of Buzhong Yiqitang， respectively， via gavage. The western medicine group was given 3.033×10^-5 g·kg^-1 selenium yeast tablet suspension via gavage， while the control and model groups were given an equal volume of distilled water via gavage. After 8 weeks of continuous treatment， samples were collected. The pathological morphology of mouse thyroid tissue was observed through hematoxylin-eosin （HE） staining，the content of serumantithyroid peroxidase autoantibody（TPOAb）and anti-thyroglobulin antibodies（TGAb）was measured by enzyme-linked immunosorbent assay （ELISA），the kit was used to detect the levels of superoxide dismutase （SOD）， and malondialdehyde （MDA） in mouse serum. Immunofluorescence was used to detect the localized expression of GPX4 in thyroid tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression of Nrf2， PPARγ， solute carrier family 7 member 11 （SLC7A11）， solute carrier family 3 member 2 （SLC3A2）， lysolipid lecithin acyltransferase 3 （LPCAT3）， and GPX4 mRNA in thyroid tissue. Western blot was used to detect the expression of Nrf2， PPARγ， SLC7A11， SLC3A2， LPCAT3， and GPX4 proteins in thyroid tissue. ResultCompared with control group， model group under light microscopy showed significant lymphocyte infiltration in the thyroid tissue， significantly increased levels of TGAb and TPOAb in serum （P<0.01）， significantly increased MDA levels and decreased SOD levels in serum （P<0.01）， significantly decreased expression of Nrf2， PPARγ， SLC7A11， SLC3A2， and GPX4 （P<0.01） in thyroid tissue， while the expression of LPCAT3 was significantly increased （P<0.01）. Compared with model group， the Buzhong Yiqitang groups and the western medication group under light microscopy showed lymphocyte infiltration in the thyroid tissue of was decreased， significantly decreased levels of TPOAb and TGAb in serum （P<0.05，P<0.01）， decreased MDA levels and increased SOD levels in serum（P<0.05，P<0.01），significantly increased expression of Nrf2， PPARγ， SLC7A11， SLC3A2， and GPX4， while the expression of LPCAT3 was significantly decreased （P<0.05，P<0.01） in the thyroid tissue. Compared with western medication group， Buzhong Yiqitang groups showed significant overall trends in the expression of Nrf2， PPARγ， SLC7A11， SLC3A2， GPX4， and LPCAT3 （P<0.05，P<0.01）. ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT， and its mechanism of action may be related to the regulation of Nrf2/PPARγ/GPX4 to inhibit ferroptosis.

ObjectiveTo explore the mechanism of Buzhong Yiqitang in improving autoimmune thyroiditis （AIT） by regulating helper T cell 17（Th17） cells through microRNA-155 （miR-155）/Nedd4 family interaction protein 1 （Ndfip1）/phosphatase and tensin homology （Pten） axis. MethodThe 100 SPF grade 8 week-old NOD.H-2^h4 mice were fed with high iodine water （0.05% NaI） for 8 weeks， and AIT model was made. They were divided into model group， Buzhong Yiqitang low-，medium-，and high-dose groups （4.78，9.56，19.12 g·kg^-1·d^-1） and selenium yeast tablet group （3.033×10^-5 g·kg^-1） according to random number table method. There were 20 mice in each group and 20 mice in the control group. The control group and the model group were given the same amount of distilled water. After 8 weeks of continuous administration， Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression of miR-155-5p， Ndfip1， Pten， protein tyrosine kinase 1 （Jak1）， signaling and transcriptional activator 3 （Stat3） retinoic acid-associated orphan receptor γt （RORγt）， and interleukin-17 （IL-17） mRNA in mouse thyroid tissue. Western blot was used to detect the expression of Ndfip1， Pten， Jak1， Stat3， RORγt， and IL-17 proteins in mouse thyroid tissue， immunohistochemical method was used to detect the expression of Ndfip1 and Pten proteins in mouse thyroid tissue； flow cytometry was used to detect the proportion of Th17 cells in mouse spleen. ResultCompared with the control group， the proportion of Th17 cells was increased （P<0.01）. The expressions of miR-155-5p， Jak1， Stat3， RORγt and IL-17 were increased （P<0.01）， while the expressions of Ndfip1 and Pten were decreased （P<0.01）. Compared with model group， the proportion of Th17 cells was decreased （P<0.05，P<0.01）. The expressions of miR-155-5p， Jak1， Stat3， RORγt and IL-17 were decreased （P<0.05，P<0.01）， while the expressions of Ndfip1 and Pten were increased （P<0.05，P<0.01）. ConclusionThe application of Buzhong Yiqitang can improve the autoimmune disorder of AIT mice， the mechanism of which may be related to the regulation of Ndfip1/Pten axis by miR-155 and then the regulation of Th17 cell differentiation.

ObjectiveTo investigate the effects of Buzhong Yiqitang on the tumor necrosis factor receptor superfamily member 6 （Fas）/Fas related death domain protein （FADD）/Caspase-8 cell apoptotic signaling pathway in mice model with autoimmune thyroiditis （AIT）. MethodThere were 120 SPF grade NOD.H-2^h4 mice aged 8 weeks， 100 of which were fed with high iodine water （0.05% NaI）， and the AIT model was made after 8 weeks. According to random number table method， they were divided into model group， Buzhong Yiqitang low-dose， medium-dose and high-dose groups （4.78， 9.56， 19.12 g·kg^-1）， selenium yeast tablet group （3.033×10^-5 g·kg^-1）， with 20 mice in each group and 20 control group. The apoptosis of thyroid cells was detected by in situ end labeling （TUNEL） after 8 weeks of administration. The real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of Fas， FADD， Caspase-8， and Caspase-3 in thyroid tissue. Western blot was used to detect the protein expression of Fas， FADD， Caspase-8， Caspase-3， cleaved Caspase-8， and cleaved Caspase-3 in thyroid tissue， and the immunohistochemical method was used to detect the protein expression of Fas and Caspase-3 in thyroid tissue. ResultCompared with control group， there were more positive expressions of apoptotic cells in model group under fluorescence microscope， and the expressions of Fas， FADD， Caspase-8， Caspase-3， cleaved Caspase-8 and cleaved Caspase-3 were significantly increased （P<0.05， P<0.01）. Compared with model group， the positive expression of thyroid apoptotic cells in each administration group was decreased under fluorescence microscope， and the expressions of Fas， FADD， Caspase-8， Caspase-3， cleaved Caspase-8， cleaved Caspase-3 were significantly decreased （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can effectively improve thyroid cell apoptosis and inflammatory injury in AIT mice. The mechanism may be related to the inhibition of Fas/FADD/Caspase-8 signaling pathway.

AIM: To evaluate the effect of capsular tension ring(CTR)on the stability and accuracy of Barrett universal Ⅱ intraocular lens(IOL)calculation formula in patients with high myopia and cataract.METHODS:Prospective study. A total of 40 cases(80 eyes)of high myopia and cataract that visited our hospital from January to June 2022 were selected. The patients were divided into CTR group and blank group by random number table method, with 40 eyes in each group. All patients were measured by IOL Master, and the actual implanted IOL power and predicted postoperative power were calculated according to Barrett universal Ⅱ formula. The uncorrected visual acuity(UCVA)and best corrected visual acuity(BCVA)at 6 mo after surgery were recorded, and the mean absolute error(MAE)was compared at 6 mo after surgery. Furthermore, the stability of postoperative refractive status and the relationship between the predicted postoperative diopter and CTR were evaluated.RESULTS:The UCVA and BCVA of the two groups were improved at 6 mo after operation(P>0.05), and there was no significant difference in UCVA and BCVA between the two groups at each time point(all P>0.05). After the implantation of IOL in 80 eyes based on the Barrett universal Ⅱ formula, the predicted postoperative diopter was -2.01±0.71 D, the actual postoperative diopter was -1.64±0.88 D, and the MAE was 0.37±0.98 D in the CTR group; in the blank group, the predicted diopter was -2.12±0.64 D, the actual diopter was -1.54±0.88 D, and the MAE was 0.58±0.31 D. The difference between the two groups was statistically significant(P<0.05). According to the axial length, CTR implantation can effectively reduce refractive error for any axial length(P>0.05). With the grouth of axial length, the MAE value increased. The postoperative MAE value of patients with axial length ≥30 mm was statistically different between the two groups(P<0.05).The proportion of hyperopic drift was 18%(7/40)in the CTR group and 30%(12/40)in the blank group, respectively, with a significant difference between the two groups(P<0.05).CONCLUSION: For patients with high myopia and cataract, the Barrett universal Ⅱ formula has high accuracy in predicting postoperative diopter. Intraoperative implantation of CTR can not only maintain the shape of the capsule bag, effectively prevent the intraoperative rupture of the suspensory ligament of the lens and make the IOL more neutral, but also is conducive to the early stability of postoperative diopter of cataract patients. It also provides more stable refractive results and reduces refractive drift. For myopic patients considering CTR implantation, it is recommended to increase the preoperative reserve diopter of -0.50 D to achieve the ideal refractive state.

OBJECTIVE To provide a reference for the adjustment of antibacterial drug regimens， identification of adverse reactions， and personalized pharmaceutical care for patients with bullous pemphigoid and pulmonary aspergillosis combined with disseminated Nocardia farcinica infection. METHODS Clinical pharmacists participated in the entire treatment process of a patient with bullous pemphigoid and pulmonary aspergillosis combined with disseminated N. farcinica infection. Evidence-based medicine was used to assist in the selection of an initial combined drug regimen against nocardiosis， and timely communication with the microbiology laboratory to provide early antimicrobial susceptibility data. When the patient exhibited epilepsy， the suspected drugs were identified， and it was reminded that imipenem-cilastatin sodium could affect the efficacy of valproic acid. It was suggested to replace valproic acid with levetiracetam for anti-epileptic treatment and to discontinue imipenem-cilastatin sodium. During treatment， it was recommended to monitor the blood concentrations of voriconazole and linezolid， and assist in adjusting the dosage promptly based on the monitoring results. RESULTS The physicians accepted the recommendations of the clinical pharmacists. The patient’s condition improved， and they were discharged with medication. CONCLUSIONS Based on evidence-based medical evidence， antimicrobial susceptibility test results， and blood concentration monitoring data， clinical pharmacists assist clinicians in selecting a sensitive anti-infective regimen for the patient， identifying adverse reactions， adjusting the treatment regimen and providing full-course medication monitoring to ensure the safety and efficacy of clinical drug therapy.