The interleukin-10 （IL-10） family is expressed in various types of cells and has a wide range of biological functions， and it plays an important role in the development and progression of hepatic fibrosis. Hepatic fibrosis is a chronic liver disease characterized by abnormal repair of hepatic tissues after injury， activation of hepatic stellate cells， and excessive accumulation of extracellular matrix. The IL-10 family members include IL-10， IL-19， IL-20， IL-22， IL-24， IL-26， IL-28， IL-29， and IL-35， with similarities in structure and function， and changes in their expression levels are closely associated with the progression of hepatic fibrosis. Moderate upregulation of the expression of IL-10 family members can help maintain the quiescent state of hepatic stellate cells， promote the transformation of macrophages to anti-inflammatory phenotype， and regulate the activity of natural killer cells， thereby inhibiting inflammatory response， regulating cell apoptosis and autophagy， and finally reversing the progression of hepatic fibrosis. This article discusses the mechanism of action of IL-10 family members and their application in traditional Chinese medicine and Western medicine therapies， in order to provide new thoughts for the treatment of hepatic fibrosis.

Liver failure （LF） is a severe clinical syndrome characterized by severe impairment or decompensation of liver function. At present， the key role of immune molecules in the pathogenesis of LF has been well established. These molecules not only directly participate in the pathological process of LF， but also influence the course of LF by modulating the behavior of immune cells. In addition， immune molecules can be used as potential biomarkers for evaluating the prognosis of LF. This article summarizes the role of immune molecules in LF and explores the therapeutic strategies based on these immune molecules， in order to provide new directions for the diagnosis and treatment of LF.

Objective: To investigate the therapeutic effect of patchouli alcohol on mice with lung-heat syndrome based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/nuclear factor-kappa B(NF-κB) signaling pathway. Methods: First, network pharmacology was used to predict the potential targets of patchouli alcohol in the treatment of lung-heat syndrome, and a "component-disease-key target" network was constructed for pathway analysis. Then, 40 BALB/c mice were assigned to the normal, lung-heat model, honeysuckle, and low-dose and high-dose patchouli alcohol groups. All groups, except the blank group, were intranasally infected with 50 μL (103 TCID50) of influenza virus solution. After two hours of infection, mice were treated once a day for seven consecutive days. The therapeutic mechanism of patchouli alcohol was explored by measuring pulmonary inflammatory factors, the PI3K/Akt/NF-κB pathway, hypothalamic fever markers (PGE2, cAMP, cGMP levels), rectal temperature, and tissue energy metabolism. Results: Network pharmacology identified 135 target genes related to patchouli alcohol and lung-heat syndrome, with the key targets being STAT3, H1F1A, and NF-κB1. In animal experiments, patchouli alcohol significantly alleviated influenza virus-induced lung inflammatory damage in mice with lung-heat syndrome, inhibited the expression of TNF-α and IL-6 in lung tissues(P<0.01), and suppressed the activation of the PI3K/Akt/NF-κB pathway. It also reduced hypothalamic levels of PGE2 and cAMP(P<0.01), suppressed the increase in rectal temperature, significantly decreased liver glycogen and pyruvate levels(P<0.01), and increased the activities of SDH, LDH, and Na+ -K+ -ATPase in the liver(P<0.01) Conclusion Patchouli alcohol improves the symptoms of lung-heat syndrome in mice by inhibiting the activation of the PI3K/Akt/NF-κB pathway, reducing proinflammatory cytokines and inflammatory damage, and regulating hypothalamic fever markers and energy metabolism.

Objective: To investigate the biological effects of carvacrol on rats with stomach-heat and stomach-cold and its regulation on transient receptor potential(TRP) channels in rats with stomach-heat, and to study the cold and heat properties of carvacrol and its possible mechanism. Methods: According to the random number method, 100 SD rats were divided into stomach-heat blank group, stomach-heat model group, Coptidis Rhizoma group, stomach-heat low-dose and high-dose carvacrol group, stomach-cold blank group, stomach-cold model group, Baked ginger group, stomach-cold low-dose group and high-dose carvacrol group, 10 rats in each group. The rat model of stomach-heat was established by intragastric administration of pepper aqueous solution (0.80 g/kg) and anhydrous ethanol, and the rat model of stomach-cold was established by intragastric administration of water extract of Anemarrhena asphodeloides and sodium hydroxide (10.40 g/kg). On the day of modeling, the rats in the Baked ginger group were given Baked ginger decoction (0.78 g/kg), and the rats in the Coptidis Rhizoma group were given Coptidis Rhizoma decoction (0.43 g/kg).The stomach-cold and stomach-heat low-dose group of carvacrol was given carvacrol emulsion (40 mg/kg), high-dose group was given carvacrol emulsion (80 mg/kg).All rats of the blank and model groups were given the equal volume of emulsion prepared by 5% dimethyl sulfoxide, 1% Tween 80, 1% polyethylene glycol 400, and 93% normal saline, once a day, for 7 days. The general condition of rats was observed and the body mass was recorded. The pathological morphology of gastric tissue was observed by hematoxylin-eosin staining. The changes of material and energy metabolism, cyclic nucleotide (cAMP), thyroid hormone and gastrointestinal hormone in each group were determined by enzyme-linked immunosorbent assay. The expression levels of transient receptor potential vanilloid subtype 1 (TRPV1), transient receptor potential channel M8 (TRPM8) and uncoupling protein-1 (UCP1) in rats with gastric fever were detected by Western blotting. Results: Compared with the stomach-heat blank group, the body mass of rats in the stomach-heat model group decreased at the fifth and seventh day (P<0.05). The contents (or ratio) of hepatic glycogen (HGlyc), total cholesterol (TC), triglyceride (TG), and vasoactive intestinal peptide (VIP) were decreased (P<0.05), and Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, cytochrome C oxidase (COX), NADH dehydrogenase (ND), cyclic adenosine phosphate (cAMP), cAMP/cyclic guanosine phosphate (cGMP), triiodothyronine (T3), thyroxine (T4), gastrin (GAS), motilin (MTL), and α-amylase (α-AMS) all increased (P<0.05). Compared with the stomach-heat model group, the body mass of rats in the Coptidis Rhizoma group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, VIP and α-AMS were increased, and Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and GAS all decreased (P<0.05). The body mass of rats in the stomach-heat low-dose carvacrol group decreased at the seventh day. The contents (or ratio) of HGlyc, TC, and VIP were increased, Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and MTL all decreased, the expression of TRPV1 and UCP1 in gastric tissue decreased, while TRPM8 increased (P<0.05) in rats of the stomach-heat low-dose and high-dose carvacrol groups. Compared with the stomach-cold blank group, the body mass of rats in the stomach-cold model group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, α-AMS, and VIP all increased, while Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, GAS, and MTL all decreased (P<0.05). Compared with the stomach-cold model group, the body mass of rats in the Baked ginger group was increased at the seventh day, and the contents (or ratio) of HGlyc, VIP, and α-AMS all decreased, while Na+ -K+ -ATPase, COX, ND, cAMP/cGMP, T3, T4, GAS, and MTL all increased (P<0.05). The contents of HGlyc, cAMP, α-AMS, and VIP of rats in the stomach-cold low and high-dose carvacrol group all decreased (P<0.05). TG in the stomach-cold low-dose carvacrol group was increased. TC, Ca2+ -Mg2+ -ATPase, and cGMP all increased, while cAMP/cGMP decreased (P<0.05) in the high-dose carvacrol group. Conclusion In this study, the rat model of stomach-cold and stomach-heat were successfully established by using cold and heat factors. The result showed that carvacrol had a certain inhibitory effect on body mass, material energy metabolism, cyclic nucleotide level, thyroid hormone and gastrointestinal function in rats with stomach-heat, indicating that the drug was cold. Carvacrol′s cold medicinal property could be biologically explained by TRPV1 activation, UCP1 induction, and TRPM8 suppression.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Aim To explore the effect of CXCL7/CX-CR2 axis on obesity-related cognitive dysfunction at both animal and cellular levels.Methods The novel object recognition test was performed to assess the cog-nition.After the preparation of the frozen sections,the activation of microglia and astrocytes in hippocampi and the level of PSD95 were determined by immunoflu-orescence staining.The content of CXCL7 in hipp-ocampi was determined by enzymelinked immunosor-bent assay.The dendritic spine density of hippocampal neurons was observed by Golgi staining.Furthermore,HT22 cells were treated with the recombinant mouse CXCL7 and/or si-RNA targeting CXCR2.After the treatment,the levels of CXCL7 and PSD95 were ob-served by immunocytochemistry staining.Results Compared with animals in the control group,there was significantly decreased discrimination index,increased activation of microglia and astrocytes,decreased con-tent of PSD95,decreased density of dendritic spine,and increased content of CXCL7 in hippocampi in the DIO group.Compared with animals in the DIO group,there were significantly increased discrimination index in the AWL group.In HT22 cells,the level of PSD95 significantly decreased in the Ctrl+CXCL7 group com-pared with the control group.This decrease was attenu-ated in the si-CXCR2+CXCL7 group compared with the Ctrl+CXCL7 group.Conclusion Chronic high-fat diet induces neuroinflammation and subsequently induces cognitive dysfunction,which may be related to the synaptic plasticity mediated by the CXCL7/CXCR2 axis.

Growth differentiation factor 15(GDF15)is a mem-ber of transforming growth factor β superfamily.Previous studies have shown that GDF15 binds to receptors expressed on the neu-rons of the aera postrema and the nucleus tractus solitarius,acti-vates multiple downstream brain regions related to feeding,and reduces food intake and body weight,showing the potential for treating obesity.However,GDF15 also causes visceral malaise such as nausea and vomiting,which may limit its further appli-cation.This article will summarize the neural circuits of these effects and the possible ways to block its effect of visceral ma-laise.

Aim To investigate the mechanism of py-roptosis mediated by the NLRP3/caspase-1/GSDMD signaling pathway and the intervention effect of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA)in radiation-induced pulmonary fi-brosis.Methods Fifty Wistar rats were randomly di-vided into five groups,with ten rats in each group.Ex-cept for the blank control group,all other groups of rats were anesthetized and received a single dose of 40 Gy X-ray local chest radiation to establish a radiation-in-duced pulmonary fibrosis rat model.After radiation,the rats in the RAS-RA intervention groups were orally administered doses of 0.12,0.24 and 0.48 g·kg-1 once a day for 30 days.The average weight and lung index of the rats were observed after 30 days of contin-uous administration.Hydroxyproline(HYP)content in lung tissue was determined by hydrolysis method.The levels of IL-18 and IL-1 β in serum were detected by ELISA.Lung tissue pathological changes were ob-served by HE and Masson staining.Ultrastructural changes in lung tissue were observed by transmission e-lectron microscopy.The expression levels of NLRP3/caspase-1/GSDMD pyroptosis pathway-related proteins and fibrosis-related proteins in lung tissue were detec-ted by Western blot.Results Compared with the blank group,the HYP content in lung tissue and the levels of IL-18 and IL-1 β in serum significantly in-creased in the model group(P＜0.01).HE and Mas-son staining showed inflammatory cell infiltration and collagen fiber deposition.Transmission electron mi-croscopy revealed increased damaged mitochondria,disordered arrangement,irregular morphology,shallow matrix,outer membrane rupture,mostly fractured and shortened cristae,mild expansion,increased electron density of individual mitochondrial matrix,mild sparse structure of lamellar bodies,partial disorder,unclear organelles,and characteristic changes of pyroptosis.Western blot analysis showed increased expression of caspase-1,GSDMD,NLRP3,CoL-Ⅰ,α-SMA,and CoL-Ⅲ proteins(P＜0.01).Compared with the model group,the RAS-RA intervention group showed signifi-cant improvement in body mass index and lung index of rats,decreased levels of IL-18 and IL-1 β inflammatory factors(P＜0.01),improved mitochondrial structure,reduced degree of fibrosis,and decreased expression of caspase-1,GSDMD,NLRP3,COL-Ⅰ,COL-Ⅲ,and α-SMA proteins in lung tissue(P＜0.01).Conclusion RAS-RA has an inhibitory effect on radiation-in-duced pulmonary fibrosis,and its mechanism may be related to the inhibition of pyroptosis through the regu-lation of the NLRP3/caspase-1/GSDMD signaling pathway.

Opioid receptors μOR,δOR,κOR and NOPR are all G protein-coupled receptors(GPCRs),which mainly function through G protein and β-ar-restin.Recent studies have found that G protein mediates analgesia,while β-arrestin reduces anal-gesia and is related to the side effects of opioids.Oliceridine is the first biased μOR agonist approved for commerce.It mainly exerts analgesic effect by activating G protein.It has rapid onset of action and reliable analgesic effect.Due to its low activity on β-arrestin,the incidence of side effects is low,comparing to the classic opioid morphine.Oliceri-dine can be safely used in patients with liver or kid-ney insufficiency and its metabolite is inactive.This article summarizes the current progress of pharma-cological research and clinical application of oliceri-dine,aiming to provide reference for the clinical practice of oliceridine.

Tamoxifen(TAM)has been widely used for the treatment of ER+breast cancer.However,the inevitable emergence of resistance to tamoxifen obstructs the successful treatment of this cancer.The tumor suppressor gene N-myc downstream-regulated gene 2(NDRG2)plays a significant role in the de-velopment of ER+breast cancer.However,it is unclear whether NDRG2 participates in mediating TAM resistance in ER+breast cancer.Here,we investigate the expression of NDRG2 mRNA and protein in TAM-sensitive and TAM-resistant ER+breast cancer cells.The results of immunoblotting experiments re-vealed a negative correlation between NDRG2 expression and TAM resistance ability in ER+breast cancer cells(P＜0.001).CCK-8 cell viability assays and soft agar colony formation assays showed that NDRG2 overexpression in TAM resistant cells significantly reduced the TAM IC50 value and the soft agar colony formation rate(P＜0.001).For the mechanism,the ERAD reporter protein assays showed that NDRG2 overexpression upregulated the expression of the ERAD reporter protein CD3ε-YFP and increased the lev-els of spliced XBP1s mRNA,leading to severe endoplasmic reticulum stress in TAM resistant cells(P＜0.001).Immunoblot analysis confirmed that overexpression of NDRG2 significantly increased the level of phosphorylation of the endoplasmic reticulum stress sensor IRE 1α and the expression levels of its down-stream protein factors,including ERdj4,P58IPK,EDEM and PDIA5(P＜0.001).The in vivo xenograft tumor experiments in mice further verified that NDRG2 overexpression significantly inhibited the growth of resistant tumors,which enhanced the therapeutic effect of TAM(P＜0.001).These findings indicate that increasing NDRG2 expression and triggering severe endoplasmic reticulum stress upon TAM treatment can reverse the resistance of ER+breast cancer cells to TAM and inhibits the growth of ER+breast canc-er tumors.Our results provide valuable new insights and potential targets for improving the clinical man-agement of TAM-resistance and prognosis in ER+breast cancer.