ObjectiveTo explore effect of Xianlian Jiedu prescription on the recurrence of colorectal cancer （CRC） and investigate the related mechanisms. MethodsA postoperative recurrence model was established in 25 Balb/c mice by injecting CT26 cells subcutaneously into the armpit， followed by surgical removal of 99% of the subcutaneous tumor. The mice were randomly divided into model group， low-dose Xianlian Jiedu prescription （XLJDP-L） group （6.45 g·kg^-1·d^-1）， medium-dose Xianlian Jiedu prescription （XLJDP-M） group （12.9 g·kg^-1·d^-1）， high-dose Xianlian Jiedu prescription （XLJDP-H） group （25.8 g·kg^-1·d^-1）， and 5-fluorouracil （5-FU） group （1×10^-3 g·kg^-1·d^-1）. The mice were euthanized after 14 days of continuous intervention， and recurrent tumor tissue was harvested. Hematoxylin and eosin （HE） staining was used to observe pathological and morphological changes in the recurrent tumor tissue. Immunohistochemistry （IHC） was employed to assess the expression of proliferating cell nuclear antigen （Ki67）， vascular endothelial growth factor （VEGF）， and platelet-endothelial cell adhesion molecule （CD31） in recurrent tumor tissue. The Western blot was used to detect the protein expression levels of angiopoietin-2 （ANG-2）， VEGF， phosphorylated-protein kinase B （p-Akt）， protein kinase B （Akt）， phosphorylated-phosphatidylinositol 3-kinase （p-PI3K）， and phosphatidylinositol 3-kinase （PI3K） in recurrent tumor tissue. ResultsBefore treatment， there were no statistical differences in tumor volume， tumor weight， and body mass among the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group compared to the model group， indicating model stability. After treatment， compared with those in the model group， the tumor volume and tumor weight in the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly reduced （P<0.01）， showing dose dependency. Meanwhile， there were no significant differences in body weight among the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group compared to the model group. HE staining showed that compared with that in the model group， tumor tissue in the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group had loosely arranged cells， increased intercellular spaces， small and shriveled nuclei， light staining， fewer mitotic figures and atypical nuclei， and increased necrotic areas. IHC showed that compared with those of the model group， the positive rates of Ki67， VEGF， and CD31 in the recurrent tumor tissue of the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly reduced （P<0.01） in a dose-dependent manner. Western blot results showed that compared with those of the model group， the protein expression levels of ANG-2 and VEGF in the recurrent tumor tissue of the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly downregulated （P<0.05， P<0.01）， and the p-Akt/Akt and p-PI3K/PI3K ratios were significantly decreased in a dose-dependent manner （P<0.05， P<0.01）. ConclusionXianlian Jiedu prescription significantly inhibits the recurrence of CRC in mice after subcutaneous tumor surgery. The mechanism may involve regulating the PI3K/Akt pathway and downregulating key angiogenic proteins such as ANG-2， VEGF， and CD31.

Booster vaccinations are highly recommended in combating the SARS-CoV-2 Omicron variant and its subvariants. However, the optimal booster vaccination strategies and related immune mechanisms with different prior vaccinations are under-revealed. In this study, we systematically evaluated the immune responses in mice and hamsters with different prime-boost regimens before their protective efficacies against Omicron were detected. We found that boosting with Ad5-nCoV, S_WT-2P or S_Omicron-6P induced significantly higher levels of neutralization activities against Omicron variants than CoronaVac and ZF2001 by eliciting stronger germinal center (GC) responses. Specifically, S_Omicron-6P induced even stronger antibody responses against Omicron variants in CoronaVac and Ad5-nCoV-primed animals than non-Omicron-specific vaccines but with limited differences as compared to Ad5-nCoV and S_WT-2P. In addition, boosting with a specific vaccine has the potential to remodel the existing immune profiles. These findings indicated that adenovirus-vectored vaccines and mRNA vaccines would be more effective than other types of vaccines as booster shots in combating Omicron infections. Moreover, the protective efficacies of the vaccines in booster vaccinations are highly related to GC reactions in secondary lymphatic organs. In summary, these findings provide timely important information on prime-boost regimens and future vaccine design.

ObjectiveTo explore the biological foundation of colorectal adenoma in damp-heat accumulation syndrome and the possible anti-tumor mechanism of Shenbai Jiedu prescription. MethodEight patients with colorectal adenoma in damp-heat accumulation syndrome， 11 patients with non-damp-heat accumulation syndrome， and 10 patients with colorectal cancer recruited by Jiangsu Provincial Hospital of Traditional Chinese Medicine from February 2019 to December 2020 meeting the inclusion criteria were clinically obtained， and the tissue of the three groups of patients was subjected to transcriptome sequencing to screen for the differentially expressed genes between the syndrome and the diseases. The intersection of the differentially expressed genes between the syndrome and the disease was taken for further screening of the differentially expressed genes sequentially increasing or sequentially decreasing in patients with non-damp-heat accumulation syndrome， damp-heat accumulation syndrome， and colorectal cancer， and functional enrichment analysis and signaling pathway enrichment analysis were carried out. Real-time polymerase chain reaction （Real-time PCR） was used to detect the effect of Shenbai Jiedu prescription on the expression of the above key differential genes. ResultBy comparing the damp-heat accumulation syndrome and non-damp-heat accumulation syndrome， a total of 384 differentially expressed genes were screened， of which 203 were up-regulated genes， and 181 were down-regulated genes. By comparing the colorectal adenoma of colorectal cancer and damp-heat accumulation syndrome， a total of 2 965 differentially expressed genes were screened， of which 2 460 were up-regulated genes， and 505 were down-regulated genes. The intersection of differentially expressed genes of the two groups was taken， and a total of 58 differentially expressed genes with the same changes were screened. The gene ontology functions were mainly enriched in UDP-galactose： β-N-acetylglucosamine beta-1，3-galactosyltransferase activity， N-acetyllactosaminide beta-1，3-N-acetylglucosaminyltransferase activity， and poly-N-acetyllactosamine biosynthetic process. Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathways were mainly enriched in glycosphingolipid biosynthesis-globo and isoglobo series， glycosphingolipid biosynthesis-lacto and neolacto series， and IL-17 signaling pathway. Shenbai Jiedu prescription significantly inhibited the expression of key genes involved in the enrichment， such as FOSB and B3GALT5， in a dose-dependent manner （P<0.05）. ConclusionGlycolipid metabolism may be the biological foundation of colorectal adenoma in damp-heat accumulation syndrome， and Shenbai Jiedu prescription may inhibit colorectal adenoma carcinogenesis by down-regulating the expression of FOSB and B3GALT5.

ObjectiveTo observe the effects of Shenbai Jiedu prescription on fecal metabolomics and intestinal flora diversity distribution in patients with colorectal adenoma and explore its potential targets. MethodA total of 21 patients diagnosed with colorectal adenoma were enrolled in this study. Following a four-week administration of Shenbai Jiedu prescription， their clinical symptoms were observed， and fecal samples of patients before and after treatment were collected. Untargeted metabolomics and metagenomic analysis based on liquid chromatography-mass spectrometry （LC-MS） were employed to investigate the possible metabolic pathway of Shenbai Jiedu prescription and its influence on the distribution of intestinal flora in patients. ResultThe total scores of traditional Chinese medicine （TCM） syndromes of patients after drug administration decreased significantly （P<0.01）. The results of untargeted metabolomics showed that the distribution of metabolites exhibited aggregation before and after drug administration， and a total of 106 differential metabolites were screened out （P<0.05）. The Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis revealed that arginine-proline metabolism， ferroptosis， glycine， and serine and threonine metabolism were significantly enriched metabolic pathways （P<0.05）. Notably， L-4-hydroxyglutamate semialdehyde， glutathione， isopentenyl pyrophosphate， creatinine， 4-acetamido-2-aminobutanoic acid， and guanidoacetic acid were found to be involved in these aforementioned metabolic pathways. Furthermore， the association between these metabolites and different intestinal flora was analyzed， and the results showed that Shenbai Jiedu prescription could interfere with metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma by regulating intestinal flora such as Lachnoclostridium， Eggerthella， and Dialister （P<0.05）. ConclusionShenbai Jiedu prescription may improve the clinical symptoms of patients by increasing the abundance of intestinal beneficial bacteria， reducing the abundance of harmful bacteria， and regulating metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma. This study may provide some research ideas and directions for Shenbai Jiedu prescription to interfere with colorectal adenoma recurrence and carcinogenesis.

Colorectal adenoma is a benign tumor originating from the mucosal glandular epithelium of the colorectum and belongs to the category of intraepithelial neoplasia. Its etiology and pathogenesis are not completely clear， and some patients have genetic factors. In recent years， with the improvement in living standards， the incidence of colorectal adenoma has gradually increased due to high-fat diets， intestinal flora disorder， and emotional disturbance. As one of the precancerous lesions of colorectal cancer， colorectal adenoma is increasingly threatening human health. Surgical resection is the most direct and effective method for the treatment of colorectal adenoma， but some patients with colorectal adenoma have the possibility of recurrence after resection. At present， there is still a lack of effective prevention and treatment measures for the recurrence of colorectal adenoma. Traditional Chinese medicine （TCM） plays a unique advantage in improving the clinical symptoms of patients with colorectal adenoma and preventing postoperative recurrence and carcinogenesis. Therefore， this review summarized the clinical research and mechanism of TCM compounds in the prevention and treatment of colorectal adenoma in recent years. The clinical study on the prevention and treatment of colorectal adenoma by TCM compounds can be divided into internal treatment， external treatment， and internal and external combined treatment. The internal treatment mainly focuses on strengthening the spleen， and the external treatment includes retention enema， acupoint application， and other methods. The internal and external combined treatment is mainly based on the internal administration of TCM compounds combined with acupuncture， retention enema， and acupoint stimulation. The study on the mechanism of TCM compounds in preventing and treating colorectal adenoma was mainly explored from the aspects of regulating intestinal flora， regulating cell proliferation immune function， and achieving anti-inflammation. This review summarized the research progress of TCM compounds in the prevention and treatment of colorectal adenoma in recent years and provided a reference for future treatment with TCM.

Objective:This study aimed to explore the clinical value of myostatin(MST) and follistatin(FST) as biological biomarkers in evaluating sarcopenia in elderly women.Methods:This was a retrospective cross-sectional study that enrolled 350 females aged 20-89 years who underwent physical examinations in Shanghai Huadong Hospital in 2021. Demographic characteristics, muscle mass, fat mass, bone mineral density, hand grip strength, gait speed, and serum indices of MST and FST were collected.Results:The serum levels of MST did not change significantly with age. However, the serum levels of FST increased with age. In women aged≥60 years, MST was positively correlated with total lean mass and appendicular skeletal muscle index(ASMI; r=0.236, P=0.041; r=0.289, P=0.014), while FST was negatively correlated with ASMI( r=-0.265, P=0.030). In multivariate stepwise regression analysis, after adjusting for age, body mass index, hip bone mineral density, and total fat mass, only FST was independently correlated with ASMI( β=-0.238, P=0.006), while MST was not correlated with ASMI. The receiver operating characteristic curve was plotted using muscle mass reduction as the state variable and serum FST level as the test variable. The area under the curve was 0.753. And when the FST cutoff value was 17.49 ng/mL, the maximum Jordan index was 0.46, with a sensitivity of 77.3% and a specificity of 68.7%. Women aged ≥60 years were divided into three groups based on serum FST levels. Compared to the upper third of the serum FST level group, the low third of the FST level group had a significantly reduced risk of suffering from sarcopenia( OR=0.098, P =0.036). Conclusions:Serum FST lever has a better correlation with muscle mass among elderly women, making it a promising biomarker for evaluating muscle mass.

Objective:To observe any effects of contralateral repeated transcranial magnetic stimulation (rTMS) of the swallowing motor cortex on the swallowing and brainstem auditory evoked potentials (BAEPs) of stroke survivors with dysphagia.Methods:A total of 83 stroke survivors with dysphagia were randomly divided into an ipsilesional stimulation group ( n=22), a contralesional stimulation group ( n=21), a bilateral stimulation group ( n=20), and a control group ( n=20). In addition to their conventional dysphagia training, those in the three stimulation groups received 3Hz rTMS while the control group was given fake stimulation. The treatment was administered daily for 20 minutes, 6 days a week, for 5 consecutive weeks. Before and after the treatment, swallowing function was assessed videofluoroscopically and using the Dysphagia Outcome and Severity Scale (DOSS). The oral and pharyngeal stages of swallowing were evaluated using the videofluoroscopic dysphagia scale (VDS). Brain stem conduction was assessed using BAEPs. Results:After treatment the average DOSS scores of all 4 groups were significantly better than before the treatment. The average DOSS scores of the contralesional and bilateral sti-mulation groups were then significantly better than those of the other two groups. The sub-item and total VDS scores of all 4 groups had decreased significantly, but the average score of the bilateral stimulation group was significantly lower than the control group′s average. Ipsilesional stimulation significantly improved the VDS sub-item scores for the triggering of pharyngeal swallowing, laryngeal elevation, and pharyngeal transit time compared with the control group. In the contralesional stimulation group the average total score and the VDS sub-item scores for apraxia, premature bolus loss, oral transit times, the triggering of pharyngeal swallowing, vallecular residue, laryngeal elevation, coating on the pharyngeal wall, and pharyngeal transit time were significantly lower than those of the control group, on average. After the treatment the latencies of BAEP waves I, III and V and the I-III, III-V and I-V interpeak intervals had decreased significantly in all four groups, but the average latencies and intervals of the bilateral and contralesional groups were significantly shorter than those of the control group. The latencies and intervals of the bilateral stimulation group were then significantly shorter than those in the ipsilesional stimulation group on average. The average latency of wave V in the bilateral stimulation group (6.53±0.73ms) was significantly shorter than that in the contralesional stimulation group after the treatment.Conclusion:Bilateral rTMS over the swallowing motor cortex combined with conventional dysphagia training can significantly improve the swallowing of dysphagic stroke survivors.

Licking behavior is important for water intake. The deep mesencephalic nucleus (DpMe) has been implicated in instinctive behaviors. However, whether the DpMe is involved in licking behavior and the precise neural circuit behind this behavior remains unknown. Here, we found that the activity of the DpMe decreased during water intake. Inhibition of vesicular glutamate transporter 2-positive (VGLUT2⁺) neurons in the DpMe resulted in increased water intake. Somatostatin-expressing (SST⁺), but not protein kinase C-δ-expressing (PKC-δ⁺), GABAergic neurons in the central amygdala (CeA) preferentially innervated DpMe VGLUT2⁺ neurons. The SST⁺ neurons in the CeA projecting to the DpMe were activated at the onset of licking behavior. Activation of these CeA SST⁺ GABAergic neurons, but not PKC-δ⁺ GABAergic neurons, projecting to the DpMe was sufficient to induce licking behavior and promote water intake. These findings redefine the roles of the DpMe and reveal a novel CeA^SST-DpMe^VGLUT2 circuit that regulates licking behavior and promotes water intake.

ObjectiveTo investigate the mechanism by which Shenbai Jiedu prescription （SBJDF） inhibits the proliferation of colorectal cancer （CRC） HCT116 cells. MethodAfter 48 h treatment of HCT116 cells with SBJDF （0， 0.25， 0.5， 1， 2， 4 g·L^-1）， the viability of HCT116 cells were determined by methyl thiazolyl tetrazolium （MTT） colorimetry. Following the classification of cells into blank control group and SBJDF （1， 2， 4 g·L^-1） groups， the effect of SBJDF on HCT116 cell morphology was observed under an inverted microscope. The effects of SBJDF on the proliferation of HCT116 cells and mitochondrial membrane potential （Δψm） were detected by colony formation assay and JC-1 probe， respectively. The flow cytometry was then performed for determining cell cycle distribution and apoptosis. The effects of SBJDF on cell cycle-， apoptosis-， and nuclear factor kappa-B （NF-κB） signaling pathway-related proteins were determined by Western blot. ResultSBJDF effectively inhibited the vitality of HCT116 cells and changed their morphology in a concentration-dependent manner. Compared with the blank control group， SBJDF at 1， 2， 4 g·L^-1 significantly reduced cell colony formation （P<0.05， P<0.01），and SBJDF at 2 and 4 g·L^-1 arrested the HCT116 cell cycle at G₀/G₁ phase （P<0.05， P<0.01）. Compared with the blank control group， SBJDF at 1， 2， 4 g·L^-1 remarkably down-regulated the protein expression of CyclinD₁ （P<0.05， P<0.01）. SBJDF at 2 and 4 g·L^-1 lowered the CyclinA₂ and cyclin-dependent kinase 4 （CDK4） （P<0.05， P<0.01）. SBJDF at 4 g·L^-1 reduced the cyclin-dependent kinase 1 （CDK1） （P<0.01）. Compared with the blank control group， SBJDF at 2 and 4 g·L^-1 induced HCT116 cell apoptosis， down-regulated the protein expression of anti-apoptosis-related proteins Bcl-2 and Bcl-xl as well as the NF-κB signaling pathway-related proteins IκB kinase α （IKKα），inhibitor α of NF-κB （IκBα），and phospho-NF-κB p65 （p-p65） （P<0.05， P<0.01）， and diminished the mitochondrial membrane potential of HCT116 cells. ConclusionSBJDF inhibits the proliferation of HCT116 cells， which may be related to its inhibition of the activation of NF-κB signaling pathway and the induction of cell cycle arrest and apoptosis.

ObjectiveTo study the mechanism of Shenbai Jiedu prescription inhibiting the proliferation of HCT116 colorectal cancer （CRC） cells by regulating the phosphatase and tensin homolog deleted on chromosome ten （PTEN）/phosphatidylinositol 3-kinase （PI3K）/ protein kinase B （Akt） signaling pathway. MethodShenbai Jiedu prescription was extracted by water extraction and alcohol precipitation to prepare freeze-dried powder. HCT116 cells were cultured in vitro， and treated with different concentrations of Shenbai Jiedu prescription （2， 4， 8， 16 g·L^-1）. The inhibitory effect of Shenbai Jiedu prescription on the proliferation of HCT116 cells was tested by methyl thiazolyl tetrazolium （MTT）. Real-time quantitative PCR was used to detect the mRNA expression levels of PTEN， PI3K， Akt， glycogen synthase kinase-3β （GSK-3β）， c-Myc， survivin and Cyclin D₁. Western blot was employed to measure the protein expression levels of PTEN， phosphorylated PTEN （p-PTEN）， PI3K， Akt， phosphorylated Akt （p-Akt）， GSK-3β， phosphorylated GSK-3β （p-GSK-3β）， c-Myc， survivin and Cyclin D₁， β-catenin nuclear import was explored by immunofluorescence assay. ResultCompared with the control group， Shenbai Jiedu prescription inhibited the proliferation of HCT116 cells in a dose-dependent manner （P<0.01）. Compared with the control group， the mRNA expression levels of PTEN and GSK-3β were up-regulated whereas those of PI3K， Akt， c-Myc， survivin and CyclinD₁ were down-regulated after treatment with Shenbai Jiedu prescription （P<0.01）. The protein expression levels of PTEN， p-PTEN and GSK-3β were up-regulated whereas those of PI3K， Akt， p-Akt， GSK-3β， p-GSK-3β， c-Myc， survivin and CyclinD₁ were down-regulated （P<0.05， P<0.01）. Immunofluorescence assay showed that Shenbai Jiedu prescription suppressed β-catenin nuclear import in HCT116 cells. ConclusionShenbai Jiedu prescription inhibited the proliferation of HCT116 cells via the mechanism of regulating the PTEN/PI3K/Akt signaling pathway.