Bladder cancer （BCa） is the most common malignant tumor of the urinary system， and its incidence is increasing year by year. At present， for all patients with resectable non-metastatic muscle-invasive BCa， radical cystectomy + bilateral pelvic lymph node dissection is strongly recommended， but they still face the risk of recurrence， metastasis and death. In recent years， the proportion of patients with advanced and metastatic BCa is increasing among patients with newly diagnosed BCa. Although current treatment models are diverse， they often struggle to achieve significant efficacy due to their low effectiveness and adverse effects， resulting in low survival rates for patients with advanced and metastatic BCa. Therefore， the treatment of BCa still faces great challenges， and there is an urgent need to discover an effective new antitumor drug. With the improvement of medical standards， traditional Chinese medicine has shown great advantages in the treatment of BCa. Traditional Chinese medicine is mild and easy to accept， and can inhibit tumor progression through a multi-pathway， multi-way and multi-target manner， so as to exert its anticancer effect. Taraxaci Herba is a medicinal and food homologous plant， which has many biological activities， such as antibacterial， anti-inflammatory， anti-oxidation， anti-tumor， protecting liver and gallbladder， reducing blood sugar and enhancing immunity， and it has shown a clear anticancer effect in breast cancer， liver cancer， gastric cancer， tongue cancer and lung cancer. By reviewing previous studies worldwide， this article summarizes the mechanism of Taraxaci Herba extract in inducing autophagy and apoptosis， inhibiting cell migration and invasion， regulating cell cycle and proliferation， regulating cell metabolism， inhibiting tumor angiogenesis， combining the effects of chemotherapeutic drugs， and regulating the transduction of related signal pathways. On this basis， this study systematically elaborates on the potential mechanism of Taraxaci Herba against BCa， in order to provide a theoretical basis for the research and treatment of BCa.

ObjectiveThis study aims to explore the potential mechanism of Danggui Niantongtang in treating knee osteoarthritis （KOA） by regulating the intestinal flora through 16S rDNA analysis. MethodThirty-six C57BL/6J mice were subjected to anterior cruciate ligament transection （ACLT） to establish a KOA model and were randomly divided into the sham surgery group， model group， low-dose Danggui Niantongtang group （0.819 g·kg^-1）， medium-dose Danggui Niantongtang group （1.638 g·kg^-1）， high-dose Danggui Niantongtang group （3.276 g·kg^-1）， and Meloxicam group （0.975 mg·kg^-1）， with 6 mice in each group. Except for the treatment groups， the sham surgery group and model group were given normal saline by gavage. After 4 weeks of continuous intervention， feces and intact knee joints of the mice were collected. Hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining were performed to observe the pathological changes in knee joint tissue morphology. The 16S rDNA sequencing was used to analyze changes in the abundance and diversity of intestinal microorganisms before and after treatment， along with corresponding functional predictions. ResultHigh-dose Danggui Niantongtang and Meloxicam significantly relieved pain symptoms in KOA mice， improved the disorder of joint structure， maintained the integrity of knee articular cartilage， increased the expression of type Ⅱ collagen alpha 1 （Col2a1） in articular cartilage， and decreased the expression of matrix metalloproteinase-13 （MMP-13）. The results of 16S rDNA sequencing showed that high-dose Danggui Niantongtang could adjust the abundance and structure of intestinal microbial species. Compared with the sham surgery group， the abundance of Proteobacteria， Actinobacteria， Ruminococcus， and Bacteroides was significantly increased in the model group （P<0.05）， while in the Danggui Niantongtang group， the abundance of these four flora was significantly reduced compared with the model group. Compared with the sham surgery group， the abundance of Verrucomicrobia， Oscillospira， and Akkermansia was significantly decreased in the model group （P<0.05）， while in the Danggui Niantongtang groups， the abundance of these three flora was significantly increased compared with the model group （P<0.05）. Functional pathway prediction of differential genera revealed that species differences among groups mainly involved metabolic pathways with high abundance associated with biosynthesis and precursors， as well as energy production， including amino acid biosynthesis， nucleotide and nucleoside biosynthesis， cofactors， prosthetic groups， electron carriers， and vitamin biosynthesis. ConclusionDanggui Niantongtang can effectively protect articular cartilage and delay the progression of KOA， possibly by regulating the structure of the intestinal flora， promoting probiotics， and inhibiting the growth of harmful pathogenic bacteria.

Objective:To understand the epidemiology of rubella and the genetic characteristics of the virus circulating during the period 2021-2022, providing basic scientific data for rubella prevention and control in China.Methods:National rubella incidence data for the period 2021-2022 were obtained from the Infectious Disease Surveillance System module and the Surveillance Report Management module of the China′s Disease Prevention and Control Information System. Positive rubella virus(RuV)isolates were obtained from the National Measles/Rubella Laboratory Network. Two nucleotide (nt) fragments [F1-480 (8 633-9 112 nt) and F2-633 (8 945-9 577 nt)] located in the E1 gene were amplified and determined by reverse transcription polymerase chain reaction (RT-PCR), and the target gene (E1-739) was obtained after collating and splicing. The sequences obtained in this study were used to construct a phylogenetic tree with the reported reference strains for genotype and lineage identification. Additionally, the phylogenetic analysis was performed to assess their genetic relatedness of RuV strains prevalent in China during 2018-2020 from GenBank database.Results:In 2021-2022, the rubella incidence in China was 0.06/100, 000 (2021: 840 cases; 2022: 784 cases), with cases primarily concentrated in the western and southern provinces. Age distribution analysis showed that rubella cases in 2021-2022 was mainly in children under 5 years of age (2021: 34.17%, 287/840; 2022: 42.09%, 330/784), with the highest proportion in children aged 0-2 years. Further analysis of the immunization history of cases revealed that in the 8-23 months age group, a significant proportion of cases had received only one dose of rubella containing vaccine (RCV); cases in the 2-14 years age group were mainly among children who had received two or more doses of RCV; however, cases over 15 years of age were primarily found in individuals who had not received RCV or had unknown immunization history. National virological surveillance data showed that totally 22 RuV virus isolates were obtained, from 6 provinces in China during 2021-2022, which belonged to lineage 1E-L2 (11 strains) and 2B-L2c (11 strains). And these viruses displayed high genetic homology with RuV prevalent from 2018 to 2020.Conclusions:The incidence of rubella in China was maintained at a low level during 2021-2022, and the prevalent RuV strains were lineage 1E-L2 and 2B-L2c.

Objective:To explore any effect of transcranial direct current stimulation (tDCS) on neurons, behavior, cerebral blood flow (CBF), vascular regeneration, and the expression of vascular endothelial growth factor (VEGF) and CD34 protein in rats modeling cerebral infarction.Methods:Thirty-two adult male Sprague-Dawley rats were randomly divided into a sham surgery group (Sham group), a model group (modeled with middle cerebral artery occlusion, MCAO group), an anode transcranial direct current stimulation group (A-tDCS group), and a cathode transcranial direct current stimulation group (C-tDCS group), each of 8. MCAO models were established in the rats of the MCAO, A-tDCS and C-tDCS groups using thread fixation. Twenty-four hours after successful modeling, both the Sham and MCAO groups were connected with electrodes without current stimulation, while the A-tDCS and C-tDCS groups were given 20 minutes of 200μA anodic or cathodic electrical stimulation daily, 5 days a week for 12 days. Before and 24 hours after the modeling, and then after the 12 days of treatment, the four groups received Longa neurobehavioral scoring. Moreover, three days after the modeling as well as after the 12 days of treatment, changes in CBF were observed using MRI. Any blood vessel regeneration was observed using immunofluorescence methods, and the expression of VEGF and CD34 proteins were detected using western blotting.Results:The rats in the MCAO, A-tDCS and C-tDCS groups exhibited various degrees of neurological deficit after the modeling. After the 12 days of treatment the average neurobehavioral scores of the A-tDCS and C-tDCS groups were significantly lower than that of the MCAO group, with the A-tDCS group′s average significantly lower than that of the C-tDCS group. Three days after the modeling, 3D-arterial spin labeling scanning showed a significant decrease in CBF around the ischemic lesion in the MCAO, A-tDCS and C-tDCS groups, but that had increased to varying degrees after 12 days of treatment. The changes in the A-tDCS and C-tDCS groups were significantly larger than in the MCAO group on average, with the former group improving significantly more than the latter. After the 12 days of treatment, new vascularization and the expression of VEGF and CD34 proteins were significantly higher in the A-tDCS and C-tDCS groups than in the MCAO group, with the change in the former group again significantly greater than in the latter.Conclusions:tDCS can relieve the symptoms of neurological deficits in rats with cerebral infarction, promote vascular regeneration, CBF, and expression of VEGF and CD34 proteins. Anodic is superior to cathodic stimulation.

ObjectiveTo explore the mechanism of Danggui Niantongtang （DGNTT） against adjuvant-induced arthritis （AA） in rats with wind-dampness-heat arthralgia （FSR） based on the variation of intestinal flora. MethodA total of 60 SD rats were randomized into normal （control） group， FSR group， low-， medium-， and high-dose DGNTT （5.67， 11.34， 22.68 g·kg^-1） groups， and methotrexate （MTX） group （1.35 mg·kg^-1）， with 10 rats in each group. The rats， except the control group， were injected with Mtb adjuvant and then exposed to artificial climatic chamber （hot and humid with wind） for 64 h for modeling. The rats were treated with water， DGNTT or MTX for 28 days from the day of injection. Arthritis index （AI） of rats was measured and paw volume was determined with a volume meter. The morphology of synovial tissues of the knees was observed based on hematoxylin-eosin （HE） staining and the changes of intestinal flora were analyzed based on 16S rRNA sequencing. ResultDGNTT can alleviate the hyperplasia of synovial tissue and inflammation of AA rats with FSR and inhibit the formation of pannus. The results of 16S rRNA sequencing showed that the relative abundance of Firmicutes， Lactobacillus， Prevotella 9， and Alloprevotella decreased （P<0.05， P<0.01） and the relative abundance of Bacteroidetes and Bacteroides increased （P<0.01） in FSR group compared those in the control group. Compared with the FSR group， all DGNTT groups and MTX group had high relative abundance of Lactobacillus （P<0.05， P<0.01） and low relative abundance of Bacteroidetes （P<0.01） and medium-dose and high-dose DGNTT groups and MTX group showed high abundance of Firmicutes， Prevotella 9， and Alloprevotella and low abundance of Bacteroides （P<0.05， P<0.01）. Spearman's correlation analysis suggested that the abundance of Bacteroides and Helicobacter was in positive correlation with AI （P<0.05）， while the abundance of Prevotella 9 and Candidatus Saccharimonas was in negative correlation with AI （P<0.01， P<0.05）. There was a negative correlation between the abundance of Prevotella 9 and paw volume （P<0.01）， and the abundance of Ruminococcaceae NK4A214 group， Christensenellaceae R-7 group， and Bacteroides was in negative correlation with spleen index （P<0.05）. The abundance of Prevotella 9 was in negative correlation with spleen index （P<0.01）. ConclusionDGNTT is effective for arthritis with FSR， as it can regulate the composition of intestinal flora in AA rats by increasing the abundance of probiotics and inhibiting the growth of pathogenic bacteria. The mechanism is the likelihood that it improves intestinal immune metabolism to ensure intestinal homeostasis.

The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases, such as depression and anxiety. Meanwhile, the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor (CB₁R), which is strongly expressed in the amygdala of non-human primates (NHPs). However, it remains largely unknown how the CB₁Rs in the amygdala of NHPs regulate mental diseases. Here, we investigated the role of CB₁R by knocking down the cannabinoid receptor 1 (CNR1) gene encoding CB₁R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA. We found that CB₁R knockdown in the amygdala induced anxiety-like behaviors, including disrupted night sleep, agitated psychomotor activity in new environments, and reduced social desire. Moreover, marmosets with CB₁R-knockdown had up-regulated plasma cortisol levels. These results indicate that the knockdown of CB₁Rs in the amygdala induces anxiety-like behaviors in marmosets, and this may be the mechanism underlying the regulation of anxiety by CB₁Rs in the amygdala of NHPs.
Animals ; Callithrix ; Receptors, Cannabinoid ; Anxiety ; Amygdala ; Cannabinoids ; Phenotype

Objective:To study the diagnostic value of ultrasonic elastography (UE) CEUS in differentiated thyroid cancer (DTC) and its correlation with invasive gene and proliferative gene expression in DTC tissue.Methods:100 DTC patients who were treated in the Ultrasound Department of Zhuji People’s Hospital of Zhejiang Province from Jan. 2019 to Jan. 2022 were retrospectively selected and included in the TC group, and 100 thyroid adenoma patients who were treated during the same period were included in the thyroid adenoma group. UE and CEUS tests were performed on all patients, and the expression levels of proliferative and invasive genes in tumor tissues were measured. Time to peak (TTP) , average time of contrast medium passage (MTT) and peak intensity (PI) were recorded. DTC patients were divided into groups according to the blue area ratio, elastic ratio of lesions, optimal ROC truncation value of TTP, MTT and PI, that is, elastic value > 1.66, blue area ratio > 51.21%, PI≤17.11dB, MTT≤36.39s, TTP≤18.90s were group A, and vice president was Group B. SPSS 19.0 was used for data analysis, and P < 0.05 was considered to be statistically significant. Results:The blue area ratio and elastic ratio of lesions in TC group were higher than those in thyroid adenoma group ( P < 0.05) , while TTP, MTT and PI in TC group were lower than those in thyroid adenoma group ( P < 0.05) . There were statistically significant differences in blue area ratio, elastic ratio of lesions, TTP, MTT and PI among TC groups with different clinical stages, capsule invasion and lymph node metastasis ( P<0.05) . ROC curve was drawn. The AUC of DTC combined with blue area ratio, elastic ratio of lesions, TTP, MTT and PI was the highest, the specificity of combined detection was 86.37%, and the detection sensitivity was 80.16%. Compared with thyroid adenoma group, Xklp2 target protein (TPX2) , chemokine receptor 4, CXCR4) and polymetalloproteinase-9 (ADAM9) gene expression levels were higher, but TDCD4 gene expression levels were lower ( P<0.05) . The expression levels of TPX2, CXCR4 and ADAM9 genes in group A were higher than those in group B ( P<0.05) , and the programmed death factor 4 (PDCD4) gene in group A was lower than that in group B ( P<0.05) . According to Pearson linear analysis, the blue area ratio and elastic ratio of lesions were positively correlated with the expression levels of TPX2, ADAM9 and CXCR4 genes in DTC tissues, and inversely correlated with the expression levels of PDCD4 genes in DTC tissues ( P<0.05) . The expression levels of TPX2, ADAM9 and CXCR4 genes in TTP, MTT and PI were inversely proportional to the expression levels of PDCD4 genes in DTC patients ( P<0.05) . Conclusion:The combination of blue area ratio, elastic ratio of lesions, TTP, MTT and PI has good diagnostic value for DTC, and the blue area ratio, elastic ratio of lesions, TTP, MTT and PI are correlated with the expression levels of invasive genes and proliferating genes in tumor tissues.

Pathological insulin resistance (IR) is closely related to gestational diabetes mellitus (GDM) and adverse pregnancy outcomes in women with GDM. Increasing studies have investigated the efficacy of IR indices, such as quantitative insulin sensitivity index, homeostasis model assessment of insulin resistance, triglyceride-glucose index and sex hormone-binding globulin, in predicting GDM and related complications in recent years. This article reviews the research progress in the above topics.

ObjectiveTo explore the mechanism of Danggui Niantongtang （DGNT） against adjuvant arthritis （AA） rats with wind-dampness-heat arthralgia by quantitative proteomics. MethodSixty SD rats were randomly divided into normal group， model group， angelica came pain soup low， medium and high dose group and methotrexate （MTX） group， each group of 10， only the rat tail root subcutaneously inactivated mycobacterium tuberculosis （Mtb） of adjuvant to build model of AA， artificial climate box intervention 16 d rheumatic fever bi syndrome model is set up， building the day began to drug intervention， The intervention lasted for 28 days. The proteins of synovial tissues in experimental rats were extracted. The differential proteins in the medium-dose DGNT group and the model group were detected and analyzed by 4D label-free quantification （4D-LFQ） proteomics. The differentially expressed proteins associated with mitochondrial pathway apoptosis were verified by immunohistochemistry and Western blot. ResultA total of 4 756 proteins were identified from rat synovial tissues， of which 4 234 proteins contained quantitative information. There were 814 differential proteins between the model group and the DGNT group. As revealed by Gene Ontology （GO） and Kyoto Encyclopedia of Gene and Genome （KEGG） enrichment analyses， DGNT had an effect on the synovial proteome of AA rats with wind-dampness-heat arthralgia， and the differential proteins were enriched in the regulation of the immune system， response to acute inflammation， and apoptosis regulation. As demonstrated by the results of immunohistochemistry and Western blot， compared with the model group， the DGNT groups and the MTX group showed increased protein expression of B-cell lymphoma 2 （Bcl-2）-associated X protein （Bax） and cytochrome C （Cyt C）（P<0.05， P<0.01）， reduced Bcl-2 level （P<0.05， P<0.01）， elevated level of cleaved cysteinyl aspartate-specific protease 9 （Caspase-9）/Caspase-9 （P<0.01）， and decreased level of phosphorylated protein kinase B （p-Akt）/Akt（P<0.05， P<0.01）. ConclusionDGNT involved multiple targets in the treatment of AA with wind-dampness-heat arthralgia and it may exert its effect in the prevention and treatment by regulating the Akt/Bax/Bcl-2 pathway and promoting the cell apoptosis in the mitochondrial pathway.

Objective:To investigate the effects of nebulization with high-dose budesonide (BUD) combined with ipratropium bromide (IB) on airway remodeling and mucus secretion in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).Methods:Ninety patients with AECOPD who received treatment in Wenling Hospital of Traditional Chinese Medicine between January 2020 and June 2021 were included in this study. They were assigned to the conventional-dose group ( n = 45, odd number) and high-dose group ( n = 45, even number) according to the number of admission. In the conventional-dose group, nebulization with IB (0.5 mg administered within 20 minutes, three times daily) and BUD (2 mg administered within 20 minutes, twice daily) was performed. In the high-dose group, nebulization with IB (0.5 mg administered within 20 minutes, three times daily) and BUD (4 mg administered within 20 minutes, twice daily) was performed. After nebulization, a mouthwash was required in each group. After 7 days of treatment, clinical efficacy was compared between the two groups. Before and 7 days after treatment, airway remodeling level (matrix metalloproteinase-9 and interleukin-8), airway mucus secretion (mucin-5ac and neutrophil elastase) and the incidence of adverse reactions were compared between the two groups. Results:Total response rate in the high-dose group was significantly higher than that in the conventional-dose group [95.56% (43/45) vs. 82.22% (37/45), χ2 = 4.05, P < 0.05]. After 7 days of treatment, serum matrix metalloproteinase-9 and interleukin-8 levels in the high-dose group were (416.96 ± 30.96) μg/L and (6.33 ± 1.03) μg/L, respectively, which were significantly lower than those in the conventional-dose group [(452.25 ± 32.16) μg/L, (7.85 ± 1.24) μg/L, t = 5.30, 6.32, both P < 0.001)]. After 7 days of treatment, serum mucin-5ac and neutrophil elastase levels in the high-dose group were (1.33 ± 0.21) μg/L and (4.06 ± 1.03) μg/L, respectively, which were significantly lower than those in the conventional-dose group [(1.58 ± 0.23) μg/L, (5.11 ± 1.14) μg/L, t = 5.38, 4.58, both P < 0.001]. There was no significant difference in incidence of adverse reactions between high-dose and conventional-dose groups [8.89% (4/45) vs. 4.44% (2/45), χ2 = 0.71, P > 0.05). Conclusion:Nebulization with high-dose BUD combined with IB for treatment of AECOPD can improve airway remodeling, reduce airway mucus hypersecretion and has definite therapeutic effects. Findings from this study are of great innovation and science.