The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.

This study aims to investigate the effects of Pulsatilla powder(PP)on colonic intestinal flora and tryptophan metabolism in piglets with diarrhea.Twenty-four weaned piglets were ran-domly divided into the normal control group,model group,self-healing group,and PP group.The model of piglet diarrhea was established by the compound factor of external evil+internal injury+epi-demic virus,and treated with PP.During the modeling period,the body weight,mental status and fecal patterns of piglets were monitored daily.After the experiment,the colon tissues were collect-ed for histopathological observation,and the inflammatory factors IL-1β and IL-6 in the colon tis-sue was detected by ELISA,16S rRNA was used to analyze colonic intestinal flora and RT-qPCR was used to determine the expression of genes related to tryptophan metabolism in the colon.The results showed that,compared with the model group,PP significantly improved the pathological status of the colon in piglets with diarrhea,with elevated body mass and a significant increase in goblet cells(P＜0.05);and significantly reduced the levels of IL-1β and IL-6 in the colon of diar-rhea piglets(P＜0.05).The results of intestinal flora showed that PP increased the abundance of Firmicutes(P＜0.01),Spirochaeota(P＜0.01)and Lactobacillus(P＜0.05),reduced the abun-dance of Bacteroidota(P＜0.05)、Prevotella_NK3B31_group(P＜0.05)and Clostridium_sensu_stricto 1(P＜0.01).Meanwhile,PP significantly reduced the expression level of TPH1 mRNA(P＜0.05),increased the expression levels of AhR(P＜0.05)and IL-22 mRNA in the co-lon of diarrhea piglets.These results indicates that PP may alleviate diarrhea in piglets by regula-ting colonic intestinal flora and genes related to intestinal tryptophan metabolism.This study pro-vides data support for the subsequent investigation of piglet diarrhea prevention and treatment.

Objective To investigate the effects of human milk on serum bilirubin levels and gut microbiota in neonatal rats with hyperbilirubinemia.Methods A total of 24 7-day-old specific-pathogen-free Sprague-Dawley rats were injected with bilirubin or normal saline,respectively,and human milk or formula milk was administered 24 hours later for intervention.The rats were divided randomly into four groups:human milk-normal saline group(HN),human milk-bilirubin group(HB),formula milk-normal saline group(FN),and formula milk-bilirubin group(FB).Samples were taken 72 hours later,and serum bilirubin values were detected by enzyme-linked immunosorbent assay.The intestinal microbiota were analyzed using 16S rDNA high-throughput sequencing.Results There was no significant difference in bilirubin values among the groups.Pseudomonas was negatively correlated with indirect bilirubin value(P＜0.05).The composition of the intestinal microbiota differed significantly between human milk and formula milk after gastric administration,with Firmicutes(P＜0.01),Enterococci(P＜0.05),being the main microbiota in the HN and HB groups,and Proteobacteria(P＜0.001),Escherichia Shigella(P＜0.01)and Acinetobacter(P＜0.01)being the main in the FN and FB groups.Conclusions Pseudomonas may be negatively associated with bilirubin,and the structure of the intestinal microbiota may differ in relation to human milk and formula feeding.

Objective To investigate the effects of human milk on serum bilirubin levels and gut microbiota in neonatal rats with hyperbilirubinemia.Methods A total of 24 7-day-old specific-pathogen-free Sprague-Dawley rats were injected with bilirubin or normal saline,respectively,and human milk or formula milk was administered 24 hours later for intervention.The rats were divided randomly into four groups:human milk-normal saline group(HN),human milk-bilirubin group(HB),formula milk-normal saline group(FN),and formula milk-bilirubin group(FB).Samples were taken 72 hours later,and serum bilirubin values were detected by enzyme-linked immunosorbent assay.The intestinal microbiota were analyzed using 16S rDNA high-throughput sequencing.Results There was no significant difference in bilirubin values among the groups.Pseudomonas was negatively correlated with indirect bilirubin value(P＜0.05).The composition of the intestinal microbiota differed significantly between human milk and formula milk after gastric administration,with Firmicutes(P＜0.01),Enterococci(P＜0.05),being the main microbiota in the HN and HB groups,and Proteobacteria(P＜0.001),Escherichia Shigella(P＜0.01)and Acinetobacter(P＜0.01)being the main in the FN and FB groups.Conclusions Pseudomonas may be negatively associated with bilirubin,and the structure of the intestinal microbiota may differ in relation to human milk and formula feeding.

This study aims to investigate the effects of Pulsatilla powder(PP)on colonic intestinal flora and tryptophan metabolism in piglets with diarrhea.Twenty-four weaned piglets were ran-domly divided into the normal control group,model group,self-healing group,and PP group.The model of piglet diarrhea was established by the compound factor of external evil+internal injury+epi-demic virus,and treated with PP.During the modeling period,the body weight,mental status and fecal patterns of piglets were monitored daily.After the experiment,the colon tissues were collect-ed for histopathological observation,and the inflammatory factors IL-1β and IL-6 in the colon tis-sue was detected by ELISA,16S rRNA was used to analyze colonic intestinal flora and RT-qPCR was used to determine the expression of genes related to tryptophan metabolism in the colon.The results showed that,compared with the model group,PP significantly improved the pathological status of the colon in piglets with diarrhea,with elevated body mass and a significant increase in goblet cells(P＜0.05);and significantly reduced the levels of IL-1β and IL-6 in the colon of diar-rhea piglets(P＜0.05).The results of intestinal flora showed that PP increased the abundance of Firmicutes(P＜0.01),Spirochaeota(P＜0.01)and Lactobacillus(P＜0.05),reduced the abun-dance of Bacteroidota(P＜0.05)、Prevotella_NK3B31_group(P＜0.05)and Clostridium_sensu_stricto 1(P＜0.01).Meanwhile,PP significantly reduced the expression level of TPH1 mRNA(P＜0.05),increased the expression levels of AhR(P＜0.05)and IL-22 mRNA in the co-lon of diarrhea piglets.These results indicates that PP may alleviate diarrhea in piglets by regula-ting colonic intestinal flora and genes related to intestinal tryptophan metabolism.This study pro-vides data support for the subsequent investigation of piglet diarrhea prevention and treatment.

Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.

The proteolysis targeting chimeras (PROTACs) technology has been rapidly developed since its birth in 2001, attracting rapidly growing attention of scientific institutes and pharmaceutical companies. At present, a variety of small molecule PROTACs have entered the clinical trial. However, as small molecule PROTACs flourish, non-small molecule PROTACs (NSM-PROTACs) such as peptide PROTACs, nucleic acid PROTACs and antibody PROTACs have also advanced considerably over recent years, exhibiting the unique characters beyond the small molecule PROTACs. Here, we briefly introduce the types of NSM-PROTACs, describe the advantages of NSM-PROTACs, and summarize the development of NSM-PROTACs so far in detail. We hope this article could not only provide useful insights into NSM-PROTACs, but also expand the research interest of NSM-PROTACs.

Objective To investigate the expression levels of basic leucine zipper and W2 domain 2 (BZW2) and isovaleryl-CoA dehydrogenase (IVD) in hepatocellular carcinoma (HCC) and evaluate their effect on clinical prognosis of liver transplant recipients with HCC. Methods Pathological specimens and clinical data of 87 liver transplant recipients with HCC were collected and retrospectively analyzed. The recurrence and metastasis of HCC after liver transplantation were assessed. Immunohistochemical staining was used to detect the expression levels of BZW2 and IVD. The relationship between BZW2, IVD and clinicopathological parameters of HCC and their effect on postoperative recurrence and clinical prognosis of the recipients was analyzed. Results Among 87 recipients, 31 cases recurred with a recurrence rate of 36%. HCC recurred at postoperative 2-49 months and the median recurrence time was postoperative 7 months. Immunohistochemical staining demonstrated that the positive expression rate of BZW2 in the HCC tissues was significantly higher than that in normal liver tissues (76% vs. 30%), and the positive expression rate of IVD was significantly lower compared with that in normal liver tissues (51% vs. 69%) (both P < 0.01). BZW2 expression was significantly correlated with tumor diameter and tumor capsule (both P < 0.05), whereas IVD expression was significantly associated with tumor diameter, alpha-fetoprotein (AFP) level, tumor, node and metastasis (TNM) staging and whether vascular invasion was found or not (all P < 0.05). In the high BZW2 expression group, the cumulative recurrence rate of HCC was significantly higher and the cumulative survival rate was significantly lower than those in the low BZW2 expression group. In the low IVD expression group, the cumulative recurrence rate of HCC was significantly higher and the cumulative survival rate was significantly lower compared with those in the high IVD expression group (all P < 0.05). Conclusions The expression level of BZW2 protein is up-regulated, whereas that of IVD protein is down-regulated in the HCC tissues. Moreover, the cumulative recurrence rate of HCC is relatively high and the cumulative survival rate is relatively low in liver transplant recipients with high BZW2 expression and low IVD expression.

Objective:To analyze the incidence and epidemiological characteristics of traumatic spinal cord injury in China in 2018.Methods:Multi-stage stratified cluster sampling was used to randomly select hospitals capable of treating patients with spinal cord injury from 3 regions，9 provinces and 27 cities in China to retrospectively investigate eligible patients with traumatic spinal cord injury admitted in 2018. National and regional incidence rates were calculated. The data of cause of injury，injury level，severity of injury，segment and type of fracture，complications，death and other data were collected by medical record questionnaire，and analyzed according to geographical region，age and gender.Results:Medical records of 4，134 patients were included in this study，with a male-to-female ratio of 2.99∶1. The incidence of traumatic spinal cord injury in China in 2018 was 50.484 / 1 million （95% CI 50.122-50.846）. The highest incidence in the Eastern region was 53.791 / 1 million （95% CI 53.217-54.365）. In the whole country，the main causes of injury were high falls （29.58%），as well as in the Western region （40.68%），while the main causes of injury in the Eastern and Central regions were traffic injuries （31.22%，30.10%）. The main injury level was cervical spinal cord in the whole country （64.49%），and the proportion of cervical spinal cord injury in the Central region was the highest （74.68%），and the proportion of lumbosacral spinal cord injury in the Western region was the highest （32.30%）. The highest proportion of degree of injury was incomplete quadriplegia （55.20%），and the distribution pattern was the same in each region. A total of 65.87% of the patients were complicated with fracture or dislocation，77.95% in the Western region and only 54.77% in the Central region. In the whole country，the head was the main combined injury （37.87%），as well as in the Eastern and Central regions，while the proportion of chest combined injury in the Western region was the highest （38.57%）. A total of 32.90% of the patients were complicated with respiratory complications. There were 23 patients （0.56%） died in hospital，of which 17（73.91%） died of respiratory dysfunction. Conclusions:The Eastern region of China has a high incidence of traumatic spinal cord injury. Other epidemiological features include high fall as the main cause of injury cervical spinal cord injury as the main injury level，incomplete quadriplegia as the main degree of injury，head as the main combined injury，and respiratory complications as the main complication.

The constitutive androstane receptor (CAR, NR3I1) belongs to nuclear receptor superfamily. It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein (YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration. TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice. Hepatocytes enlargement around central vein (CV) area was observed, meanwhile hepatocytes proliferation was promoted as evidenced by the increased number of KI67