Hepatic encephalopathy （HE） is a common complication of severe liver disease in the end stage， and it is urgently needed to improve the rate of effective treatment and clarify the pathogenesis of HE. The liver is a crucial hub for immune regulation， and disruption of immune homeostasis is a key factor in the pathological mechanisms of HE. As the main metabolites of intestinal flora， short-chain fatty acids （SCFAs） play a vital role in the biological processes of both innate and adaptive immunity and can regulate the proliferation and differentiation of immune cells maintain the homeostasis of intestinal microenvironment and the integrity of barrier function. Studies have shown that SCFAs participate in bidirectional and dynamic interactions with the liver-gut-brain axis through immunomodulatory pathways， thereby playing an important role in the diagnosis， treatment， and prognostic evaluation of HE. Starting from the immunoregulatory effect of SCFAs， this article summarizes and analyzes the crosstalk relationship between SCFAs and the liver-gut-brain axis and the significance of SCFAs in the diagnosis and treatment of HE， in order to provide new ideas for optimizing clinical prevention and treatment strategies.

AIM: To investigate the effect of the relationship between scotopic pupil and optical zone diameters on short-term subjective and objective visual quality after small incision lenticule extraction(SMILE).METHODS:In this prospective cohort study, 98 patients(196 eyes)who underwent SMILE from September 2021 to June 2023 were included. Participants were divided into two groups based on the ratio of scotopic pupil diameter to optical zone diameter: group A(ratio >1, 70 eyes)and group B(ratio ≤1, 126 eyes). The preoperative and postoperative uncorrected visual acuity(UCVA), spherical equivalent(SE), total corneal high-order aberrations at 4, 6, and 8 mm of pupil diameters, objective scatter index(OSI), pre- and post-operative QoV subjective visual quality questionnaire were observed and recorded. The refractive status of different groups of patients at different time points before and after surgery, and differences in subjective and objective visual quality indices were analyzed. Furthermore, the changes in subjective and objective visual quality(postoperative-preoperative)at different postoperative time points were analyzed between the two groups.RESULTS:No significant differences in visual acuity or refractive state were observed between the two groups at 3 mo postoperatively. In both the group A and the group B, there was a difference in the changes of corneal total higher-order aberration centered on 8 mm cornea at 1 mo postoperatively(P<0.05), and there was a difference in the changes of total higher-order aberration and corneal spherical aberration centered on 8 mm cornea at 3 mo postoperatively(all P<0.05). At 3 mo after surgery, the most commonly reported symptoms in the group A were glare, starburst, hazy vision, and halo. In the group B, the most common symptoms were hazy vision, halo, starburst, and glare. Statistically significant differences were observed in the severity of glare and visual fluctuation between groups before surgery and at 3 mo postoperatively(all P<0.05). However, no significant differences were found in the severity of halo, starburst, blurred vision, double vision, or focusing difficulty at 3 mo postoperatively(all P>0.05).CONCLUSION:When the scotopic pupil diameter exceeds the optical zone, SMILE may increase postoperative corneal aberrations, as evidenced by an increase in high-order corneal aberrations within an 8-mm central corneal range, a higher incidence of postoperative glare, and more severe glare and visual fluctuation symptoms. Nevertheless, these symptoms are mild and remain within a safe range.

Nuclear factor-kappa B （NF-κB） is an important intracellular transcription factor widely involved in the processes such as immune response， inflammatory response， cell proliferation， and apoptosis. The abnormal activation of the NF-κB signaling pathway plays a pivotal role in various liver diseases including chronic hepatitis， liver fibrosis， liver cirrhosis， and hepatocellular carcinoma. Extensive studies have shown that inhibiting NF-κB activity may effectively reduce inflammation and fibrosis and improve metabolic disorders. Several natural compounds， such as matrine and salvianolic acid B， have shown the potential in suppressing NF-κB activity， thereby exerting anti-inflammatory， anti-fibrotic， and anti-tumor effects. This article systematically reviews the critical role of the NF-κB signaling pathway in liver diseases and its potential as a therapeutic target， in order to highlight its potential as a therapeutic target for liver diseases and provide new directions for the treatment of liver diseases.

BACKGROUND:In recent years,the treatment of anterior cruciate ligament injury has become more and more mature.However,there are still disputes about the timing of surgery,the choice of surgical methods,the choice of grafts,and the methods to promote graft healing after anterior cruciate ligament injury. OBJECTIVE:To summarize the latest research progress of surgical timing,surgical methods,graft selection and methods to promote graft healing after anterior cruciate ligament injury,and to find new treatment directions for anterior cruciate ligament injury. METHODS:Relevant articles concerning anterior cruciate ligament injury were retrieved from PubMed,CNKI,WanFang Date,VIP,SinoMed,ScienceDirect,Springer and Cochrane Library.After the screening,72 related articles were finally included. RESULTS AND CONCLUSION:(1)Surgical timing:Compared with delayed anterior cruciate ligament reconstruction,early reconstruction can reduce meniscus injury,elevate quality of life,and improve functional recovery.However,it is still uncertain whether the different operation timing will accelerate cartilage injury.(2)Surgical methods:Arthroscopic anterior cruciate ligament reconstruction is a common surgical method for anterior cruciate ligament injury.Dynamic internal stabilization repair of anterior cruciate ligament can bring similar results to traditional anterior cruciate ligament reconstruction in short-term and long-term effects.(3)Graft selection:Autogenous hamstring tendon is the first choice of anterior cruciate ligament graft,while bone-patellar tendon-bone grafts and allografts are the secondary choices.(4)Among the methods to promote graft healing,suture band strengthening can increase knee joint stability and ensure graft healing.Stem cells promote the tendon-bone healing of grafts through anti-inflammatory action,angiogenesis,inhibition of osteolysis and promotion of chondrocyte differentiation.Preserving the residual end of the anterior cruciate ligament can maintain the stability of the knee joint,promote the recovery of proprioception,and provide a prerequisite for the healing of the graft.The effectiveness of platelet-rich plasma in promoting graft healing remains to be discussed.However,biomaterials,gene therapy,stem cell application and other methods to promote tendon healing remain in the stage of molecular and animal researches.Clinical transformation is also needed in the future.

In vivo confocal microscopy of the cornea is a non-invasive, rapid, and comprehensive technique for real-time, dynamic observation of all layers of the cornea. Confocal microscopy allows the examination of the morphology and cell density in the different layers of the cornea through direct visualization. With the increasing prevalence of diabetes, ocular complications have become common and have garnered more interest and in-depth research from clinical and scientific communities. This paper provides a comprehensive review of research progress made using in vivo confocal microscopy to observe various layers of cornea tissue in diabetic patients.

Objective To study the relationship between serum neuron-specific enolase(NSE)and clinical features of pheochromocytoma/paraganglioma(PPGL).Methods Totally 501 PPGL patients diagnosed from January 2019 to December 2022 were divided into normal NSE group(NSE≤16.3 ng/mL)and elevated NSE group(NSE＞16.3 ng/mL).The clinical characteristics were compared between the two groups.Results Compared with normal NSE group,patients in the elevated NSE group had larger diameter in primary tumor(5.00 cm vs.4.60 cm),higher 24-hour urinary norepinephrine(NE)and 24-hour urinary dopamine(DA)levels,and a higher rate of metasta-sis(31.6%vs.13.7%)(P＜0.05).NSE level was positively correlated with the primary tumor size(r=0.131,P＜0.05),24-hour urinary NE level(r=0.195,P＜0.05)and 24-hour urinary DA level(r=0.119,P＜0.05).Conclusions The level of NSE is related to tumor size,secretion function and metastasis in PPGL patients.

Objective:To investigate the effects and mechanism of exosome (EXO)-loaded kringle V11 (KV11) delivery on corneal neovascularization (CNV).Methods:KV11 was bound to the surface of endothelial cell-derived exosomes by using CP05, an EXO-targeting anchoring peptide, to produce EXO-KV11.The binding efficiency and optimal concentration ratio were determined using the Apogee flow system.A total of 100 8-week-old healthy male SPF grade SD rats were selected, 10 of which were randomly selected as a normal control group without any treatment.The CNV model was established by alkali burn in the other 90 rats, which were randomly divided into three groups, EXO-KV11 group, KV11 group, and normal saline group by the random number table method, with 30 rats in each group.Each group was injected subconjunctivally with 100 μl of EXO-KV11 (25 μg), KV11 (25 μg), or normal saline every other day from the first day after the alkali burn, respectively.The CNV of rats was observed on days 1, 4, 7, and 14 after alkali burn.The CNV area was calculated by ventricular perfusion with fluorescein isothiocyanate-dextran (FITC-dextran) and corneal angiography.The amount of CNV lumen was observed by hematoxylin and eosin staining.The distribution of CD31 in rat corneas was determined by immunohistochemical method.The expression levels of voltage-dependent anion channel 1(VDAC1), endoplasmic reticulum stress, autophagy and apoptosis-associated proteins were detected by Western blot.This study was approved by the Animal Ethics Committee of Peking University People's Hospital (No.20210019). All animal procedures complied with the regulations of the Vision and Ophthalmology Association and the Animal Protection and Use Committee of Peking University.Results:The optimal concentration ratio of KV11 to EXO was 4∶1 and the binding affinity reached up to 87.5% by Apogee flow cytometers.On days 7 and 14 after alkali burn, there were significant differences in CNV area among the four groups ( F=4.613, 15.590; both at P<0.05). On day 7 after alkali burn, the CNV area was smaller in EXO-KV11 group than in KV11 and normal saline groups, with statistically significant differences (both at P<0.05). On day 14 after alkali burn, the CNV area was smaller in EXO-KV11 and KV11 groups than in normal saline group, and smaller in EXO-KV11 group than in KV11 group, showing statistically significant differences (all at P<0.05). The results of quantitative analysis of corneal fluorescence mounts showed that the relative CNV fluorescence area of the normal saline group, KV11 group and EXO-KV11 group were (8.3±1.7)%, (5.2±1.6)%and (3.4±0.7)%, respectively, showing a statistically significant overall comparison difference ( F=11.735, P<0.01). The relative CNV fluorescence area was larger in KV11 and normal saline groups than in EXO-KV11 group, and larger in normal saline group than in KV11 group, showing statistically significant differences (all at P<0.05). On day 14 after alkali burn, massive neovascular lumens were observed in the matrix of the normal saline group.The number of neovascular lumens in KV11 group was smaller than that in normal saline group.The corneal structure appeared normal in EXO-KV11 group, and neovascular lumens were rare.Numerous CD31-positive cells were observed in the corneal stroma of the normal saline group, which formed into lumen structures.The number of lumens surrounded by CD31-positive cells in the corneal stroma was smaller in KV11 group than in normal saline group, and smaller in EXO-KV11 group than in KV11 group.There were significant differences in the relative expression levels of VDAC1, protein kinase R-like endoplasmic reticulum kinase (PERK), p62, cleaved caspase 3 among the four groups ( F=35.960, 8.947, 17.791, 101.168; all at P<0.01). The relative expression levels of VDAC1, PERK, p62, cleaved caspase 3 were higher in EXO-KV11 group than in KV11 and normal saline groups, showing statistically significant differences (all at P<0.001). There was no significant difference in the relative expression of microtubule-associated proteins 1A/1B light chain 3B (LC3B)Ⅱ/LC3BⅠ protein among all four groups ( F=0.445, P=0.727). Conclusions:EXO-KV11 can inhibit CNV more remarkably than KV11.EXO-KV11 inhibits CNV by promoting the expression of VDAC1 and PERK and suppressing the autophagic flux.

Objective To study the mechanism of Sanhuang Decotion in the treatment of ulcerative colitis(UC)under Candida albicans colonization in mice based on Dectin-1-Syk-CARD9 signaling pathway.Methods Mice model of UC with fungal colonization were established with dextran sodium sulfate free drinking and C.albicans intragastric administration.Mice were divided into normal control group,model group,sulfasalazine group,fluconazole group,and Sanhuang Decotion low-and high-dosage groups,and receive corresponding drug interventions.General state of mice were observed,and the disease activity index(DAI)score of mice were calculated.The load of C.albicans in intestine was detected,the length of the colon was measured,and pathological scoring of the colon tissue was performed.The ultrastructural changes of colon epithelium were observed under transmission electron microscopy.The contents of TNF-α,IL-6 and IL-12 in serum and colon tissues were detected by ELISA.The mRNA and protein expression of Dectin-1,Syk,CARD9,NF-κBp65 and inflammation factors in intestinal epithelial cells and colon tissues were detected by qPCR,Western blot and immunohistochemistry.Results Compared with the normal control group,the model group mice showed reduced activity,decreased food intake,accompanied by loose stools,significantly increased DAI score,increased load of C.albicans in the intestine,shortened colon length,and increased histopathological score,with widening of gap between colon epithelial cells,cytoplasmic dissolution,mitochondrial swelling;TNF-α,IL-6 and IL-12 in serum and colon tissue increased,the expressions of Dectin-1 and CARD9 mRNA and protein in colon epithelial cells increased,p-Syk,p-NF-κBp65,CARD9,TNF-α,IL-1β,IL-6 protein expression in colon tissue increased(P<0.01,P<0.05).Compared with the model group,the Sanhuang Decotion high-dosage group mice showed a significant decrease in DAI score,decreased intestinal C.albicans load,increased colon length,decreased histopathological score,more complete and orderly arrangement of microvilli in colon epithelial cells,mild mitochondrial swelling,TNF-α,IL-6 and IL-12 in serum and colon tissue decreased,and the mRNA and protein expression of Dectin-1 and CARD9 in colon tissue increased,the expression of p-Syk,p-NF-κBp65,CARD9,TNF-α,IL-1β,IL-6 protein in colon tissue decreased(P<0.01,P<0.05).Conclusion Sanhuang Decotion may exert an anti C.albicans colonization UC effect by inhibiting the Dectin-1-Syk-CARD9 signaling pathway and reducing the release of inflammatory factors.

Small cell lung cancer (SCLC) is a highly malignant tumor with a very poor prognosis; therefore, more effective treatments are urgently needed for patients afflicted with the disease. In recent years, emerging molecular classifications based on key transcription factors of SCLC have provided more information on the tumor pathophysiology, metastasis, immune microenvironment, and acquired therapeutic resistance and reflected the intertumoral heterogeneity of the various SCLC phenotypes. Additionally, advances in genomics and single-cell sequencing analysis have further revealed the high intratumoral heterogeneity and plasticity of the disease. Herein, we review and summarize these recent lines of evidence and discuss the possible pathogenesis of SCLC.

Objective The aim of this study was to investigate the prospective association between physical activity (PA),independently or in conjunction with other contributing factors,and osteoporosis (OP) outcomes. Methods The Physical Activity in Osteoporosis Outcomes (PAOPO) study was a community-based cohort investigation. A structured questionnaire was used to gather the participants' sociodemographic characteristics. Bone mineral density (BMD) measurements were performed to assess OP outcomes,and the relationship between BMD and OP was evaluated within this cohort. Results From 2013 to 2014,8,471 participants aged 18 years and older were recruited from Tangshan,China's Jidong community. Based on their PA level,participants were categorized as inactive,moderately active,or very active. Men showed higher physical exercise levels than women across the activity groups. BMD was significantly higher in the very active group than in the moderately active and inactive groups. Individuals aged>50 years are at a higher risk of developing OP and osteopenia. Conclusion The PAOPO study offers promising insights into the relationship between PA and OP outcomes,encouraging the implementation of PA in preventing and managing OP.