Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

Objective To evaluate the regulatory effects of psilocybin on social behavior of male C57BL/6J mice.Methods Adult male C57BL/6J mice were intraperitoneally injected with psilocybin(0.2,1 and 5 mg/kg,i.p.),and the effects of psilocybin on prosocial behavior were evaluated by the three-chamber test.Stressed mice undergoing chronic social defeat stress(CSDS)were given acute intraperitoneal injection of psilocybin(1 mg/kg)to evaluate the moderation of social novelty preference behavior using the modified two-chamber test.Results Intraperitoneal injection of psilocybin(1 mg/kg)promoted prosocial behavior and prolonged social time(P＜0.01),while intraperitoneal injection of psilocybin(0.2 mg/kg)had no apparent effect on the prosocial behavior of mice,and intraperitoneal injection of psilocybin(5 mg/kg)inhibited prosocial behavior before promoting it.Further studies showed that intraperitoneal injection of psilocybin(1 mg/kg)increased the social novelty exploration time in stressed mice undergoing CSDS.Conclusion This study shows that 1 mg/kg dose of psilocybin can promote the prosocial behavior in mice,and potentially ameliorate the deficit of social novelty preference behavior in CSDS mice.

Objective To investigate the role of JAK1/STAT3/KHSRP axis in mediating the regulatory effect of LINC00626 on progression of esophagogastric junction adenocarcinoma.Methods We collected surgical tumor and adjacent tissue specimens from 64 patients with esophagogastric junction adenocarcinoma and examined the expression levels of LINC00626 and KHSRP.qRT-PCR was used to detect the expressions of LINC00626 and KHSRP in 6 esophageal adenocarcinoma cell lines(OE-19,TE-7,Bic-1,Flo-1,SK-GT-4,and BE-3)and a normal esophageal epithelial cell line(HET-1A).OE-19 and TE-7 cell lines with stable LINC00626 knockdown and FLO-1 and SK-GT-4 cells stably overexpressing LINC00626 were constructed by lentiviral transfection,and the changes in proliferation,migration and invasion of the cells were evaluated using Cell Counting Kit-8(CCK-8)assay and Transwell migration/invasion assay.The expressions of KHSRP and JAK/STAT pathway proteins in the transfected cells were detected with Western blotting.The effects of LINC006266 knockdown and overexpression on subcutaneous tumor formation and lung metastasis of OE-19 and FLO-1 cell xenografts were tested in nude mice.Results The expression levels of LINC00626 and KHSRP were significantly increased in esophagogastric junction adenocarcinoma tissues and in esophageal adenocarcinoma cells.LINC00626 knockdown obviously inhibited the proliferation,migration and invasion of esophageal adenocarcinoma cells in vitro and decreased their tumor formation and lung metastasis abilities in nude mice,while overexpression of LINC00626 produced the opposite effects.In esophageal adenocarcinoma cells,LINC0626 knockdown significantly decreased and LINC00626 overexpression strongly enhanced the phosphorylation of JAK1 and STAT3.Conclusion High LINC00626 expression promotes esophageal-gastric junction adenocarcinoma metastasis by activating the JAK1/STAT3/KHSRP signal axis.

Objective To investigate the role of JAK1/STAT3/KHSRP axis in mediating the regulatory effect of LINC00626 on progression of esophagogastric junction adenocarcinoma.Methods We collected surgical tumor and adjacent tissue specimens from 64 patients with esophagogastric junction adenocarcinoma and examined the expression levels of LINC00626 and KHSRP.qRT-PCR was used to detect the expressions of LINC00626 and KHSRP in 6 esophageal adenocarcinoma cell lines(OE-19,TE-7,Bic-1,Flo-1,SK-GT-4,and BE-3)and a normal esophageal epithelial cell line(HET-1A).OE-19 and TE-7 cell lines with stable LINC00626 knockdown and FLO-1 and SK-GT-4 cells stably overexpressing LINC00626 were constructed by lentiviral transfection,and the changes in proliferation,migration and invasion of the cells were evaluated using Cell Counting Kit-8(CCK-8)assay and Transwell migration/invasion assay.The expressions of KHSRP and JAK/STAT pathway proteins in the transfected cells were detected with Western blotting.The effects of LINC006266 knockdown and overexpression on subcutaneous tumor formation and lung metastasis of OE-19 and FLO-1 cell xenografts were tested in nude mice.Results The expression levels of LINC00626 and KHSRP were significantly increased in esophagogastric junction adenocarcinoma tissues and in esophageal adenocarcinoma cells.LINC00626 knockdown obviously inhibited the proliferation,migration and invasion of esophageal adenocarcinoma cells in vitro and decreased their tumor formation and lung metastasis abilities in nude mice,while overexpression of LINC00626 produced the opposite effects.In esophageal adenocarcinoma cells,LINC0626 knockdown significantly decreased and LINC00626 overexpression strongly enhanced the phosphorylation of JAK1 and STAT3.Conclusion High LINC00626 expression promotes esophageal-gastric junction adenocarcinoma metastasis by activating the JAK1/STAT3/KHSRP signal axis.

Objective:To evaluate the efficacy and safety of oliceridine for treatment of moderate to severe pain after surgery with general anesthesia in patients.Methods:The patients with moderate to severe pain (numeric pain rating scale ≥4) after abdominal surgery with general anesthesia from 14 hospitals between July 6, 2021 and November 9, 2021 were included in this study. The patients were assigned to either experiment group or control group using a random number table method. Experiment group received oliceridine, while control group received morphine, and both groups were treated with a loading dose plus patient-controlled analgesia and supplemental doses for 24 h. The primary efficacy endpoint was the drug response rate within 24 h after giving the loading dose. Secondary efficacy endpoints included early (within 1 h after giving the loading dose) drug response rates and use of rescue medication. Safety endpoints encompassed the development of respiratory depression and other adverse reactions during treatment.Results:After randomization, both the full analysis set and safety analysis set comprised 180 cases, with 92 in experiment group and 88 in control group. The per-protocol set included 170 cases, with 86 in experiment group and 84 in control group. There were no statistically significant differences between the two groups in 24-h drug response rates, rescue analgesia rates, respiratory depression, and incidence of other adverse reactions ( P>0.05). The analysis of full analysis set showed that the experiment group had a higher drug response rate at 5-30 min after giving the loading dose compared to control group ( P<0.05). The per-protocol set analysis indicated that experiment group had a higher drug response rate at 5-15 min after giving the loading dose than control group ( P<0.05). Conclusions:When used for treatment of moderate to severe pain after surgery with general anesthesia in patients, oliceridine provides comparable analgesic efficacy to morphine, with a faster onset.

The recording and analysis of activities of calcium signals in neurons is of critical importance in the field of neuroscience.Over the past three decades,various fluorescent calcium imaging techniques not only have been used in the imaging study of functional activities of neuronal communities,but also can be combined with specific markers to record the functional activities of specific types of neuronal communities.To analyze neural activities at the cellular level,a series of preprocessing such as motion correction,cell body recognition,calcium signal extraction and peak deconvolution is required for the collected video.However,current methods for manual preprocessing are time-consuming and laborious,so computer automatic analysis technology is urgently needed to quickly repair the jitter in the video,identify the position and outline of a single cell,extract its activity trajectory and infer the action potential peak.In this paper,the methods of calcium imaging data processing used in recent years are summarized,and the future developments are predicted.

Objective To build a neural network based on the Unet infrastructure for recognition and segmentation of two-dimensional calcium imaging fluorescence images.Methods The in vivo miniaturized two-photon microscope(mTPM)was used for brain calcium imaging in freely moving mice.The imaging data was motion corrected using the NoRMCorre algorithm and processed using ImageJ software to obtain the original images after correction,and the labels were produced using the Labelme software.The neural network HDCGUnet was built using the original images and labels for training,and optimized to improve the model structure according to the training effect.Finally,the evaluation indexes were selected and compared with those of other models to verify the utility of this model.Results The HDCGUnet model,which was collected and made on our own,performed best in the two-photon calcium imaging dataset compared to other models,and performed well on the BBBC dataset either.Conclusion The HDCGUnet model provides a novel alternative for the recognition and segmentation of two-photon calcium imaging images.

Objective: To explore the effects of protein powder on the bioavailability of perfluoroalkyl substances (PFASs) in blood and kidneys of rats and renal function change. Methods: Twenty-four rats of the SD strain were randomly divided into the negative control group, PFASs group and protein powder group, with 8 rats (half males and half females) in each group. PFASs included 13 perfluorocarboxylic acids (PFCAs) and 8 perfluorosulfonic acids (PFSAs), and the mixture was used as a test subject for intervention. The rats in the negative control group were given deionized water at doses of 20 mL/kg·bw, in the PFASs group were given 5 mL/kg·bw of PFASs mixtures and 15 mL/kg·bw of deionized water, and in the protein powder group were given 5 mL/kg·bw of PFASs mixtures and 15 mL/kg·bw of protein powder (0.258 g/mL). After intervention for 28 successive days, body weight and kidney mass were weighed, and the kidney volume index was calculated. Serum creatinine and blood urea nitrogen were detected by an automatic biochemical analyzer. The PFCAs, PFSAs and PFASs contents were quantified in blood and kidney using ultra-high performance liquid chromatography-electrospray tandem mass spectrometry, and the bioavailability was estimated. Results: There was no significant differences in kidney mass, kidney volume index, serum creatinine and blood urea nitrogen among the negative control group, PFASs group and protein powder group (all P>0.05). The bioavailability of blood PFCAs, PFSAs and PFASs in the protein powder group was not significantly different from the PFASs group (all P>0.05). Compared with the PFASs group, the bioavailability of PFCAs, PFSAs and PFASs were significantly increased in kidneys of male rats in the protein powder group (all P<0.05), while were not significant different in those of female rats (all P>0.05). Conclusion Protein powder at the dose of this study can significantly improve the bioavailability of PFASs in kidneys of male rats, while there no obvious effects on the bioavailability of blood PFASs and renal function.

Objective To investigate the clinical effect of Mudan Granules combined with pentoxifylline in the treatment of type 2 diabetes mellitus (T2DM) with early renal disease and analyze its impact on the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway. Methods A total of 164 patients with T2DM and early renal disease admitted to the Second People's Hospital of Hunan Province between May 2022 and October 2023 were enrolled and randomly divided into observation group(n=82) and control group (n=82) using a random number table in a 1-to-1 ratio. The control group received pentoxifylline treatment, while the observation group received Mudan granules combined with pentoxifylline. The clinical effects and changes in renal function indicators[serum creatinine (SCr), urea nitrogen, urinary albumin-to-creatinine ratio (UACR)], TLR4/NF-κB signaling pathway indicators (TLR4, MyD88, NF-κB mRNA), and inflammation and oxidative stress indicators [C-reactive protein (CRP), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), total antioxidant capacity (TAC), and transforming growth factor β1 (TGF-β1)] before and after treatment were compared between the two groups. Results The total effective rate in the observation group was 97.56%, which was higher than 89.02% in the control group (P<0.05). At 6 and 12 weeks after treatment, the levels of SCr, urea nitrogen, and UACR in both groups decreased compared with those before treatment, and the levels of these indicators in the observation group were lower than those in the control group (P<0.05). At 6 and 12 weeks after treatment, the levels of TLR4, MyD88, and NF-κB mRNA in both groups decreased compared with those before treatment, and the levels of these indicators in the observation group were lower than those in the control group (P<0.05). At 6 and 12 weeks after treatment, the levels of GSH-PX and TAC in both groups increased, while the levels of CRP, MDA, and TGF-β1 decreased compared with those before treatment. The levels of GSH-PX and TAC in the observation group were higher than those in the control group, while the levels of CRP and MDA were lower (P<0.05). Conclusion Mudan Granules combined with pentoxifylline in the treatment of T2DM with early renal disease can improve renal function to a certain extent, regulate the TLR4/NF-κB signaling pathway, and reduce inflammation and oxidative stress responses, which is beneficial for disease control.

Objective To observe the role of dried tangerine peel in Yigong Powder improves iron metabolism and promotes red blood cell generation in anemia of chronic disease (ACD).Methods With a two-by-two factorial design,the Yigong Powder was divided into dried tangerine peel and Chenpi absent Decoction. According to the random number table method,32 zymosan-induced generalized inflammation (ZIGI) mice were randomly divided into the model group,the dried tangerine peel group,the Chenpi absent Decoction group,and the Yigong Powder group. The dried tangerine peel group,Chenpi absent Decoction group and the Yigong Powder group were given dried tangerine peel(3.083 g/kg),Chenpi absent Decoction(12.33g/kg),and Yigong Powder(15.413g/kg)by gavage to the corresponding group of mice. The model group was given an equal amount of physiological saline by gavage,and treated continuously for 7 days. After the completion of administration,the body weight of each group of mice was recorded. The hemoglobin content of each group of mice was detected using a fully automatic cell counter,the serum iron content was detected using colorimetry,the serum ferritin content was detected using enzyme-linked immunosorbent assay (ELISA),and the spleen index was calculated. The liver tissue inflammatory factors interleukin-1β (IL-1β),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),interferon-γ (IFN-γ),interleukin-4 (IL-4),and interleukin-10 (IL-10) levels were detected using Luminex method. The mRNA expressions of liver tissue hepcidin gene (HAMP) and membrane iron transporter ( Fpn) were detected using real-time fluorescence PCR method. Results Dried tangerine peel and Chenpi absent Decoction both showed interactive effects in regulating hemoglobin,serum iron,serum ferritin content,improving spleen index,and regulating the mRNA expressions of HAMP,Fpn,as well as IL-1β and IFN-γ (P<0.05). Compared with the model group,dried tangerine peel significantly increased hemoglobin,serum iron content,and Fpn mRNA expression in ZIGI model mice,while decreasing ferritin content,spleen index,HAMP mRNA expression,and the levels of IL-1β,IL-6,TNF-α,and IFN-γ (P<0.05). Chenpi absent Decoction significantly increased serum iron content and Fpn mRNA expression in ZIGI model mice,while reducing spleen index,ferritin content,HAMP mRNA expression,and the levels of IL-1β and IFN-γ、IL-4 (P<0.05). Conclusion The effects of dried tangerine peel on inflammatory factors (IL-6 and TNF-α) and Fpn may play a key role in the improvement effects of Yigong Powder on ACD and iron metabolism.