Objective:To explore the role of arginine metabolism in the inflammatory response to influenza A virus (FluA) infection.Methods:Eighteen-month-old mice were infected with FluA via nasal drip, with samples collected on the 6th day post-infection. The concentration of cytokines was determined by the Luminex multifactor assay, while the metabolites in bronchoalveolar lavage fluid (BALF) were analyzed using targeted metabolomic method. Correlation analysis was employed to examine the correlation between cytokines and metabolites. Macrophages were infected with FluA at a multiplicity of infection (MOI) of 1 and cultured with different concentrations of arginine for 24 h. The mRNA and protein expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α) and IL-10 were detected by real time fluorescence quantitative RT-PCR (qRT-PCR) and Cytometric Bead Array (CBA).Results:In comparison to the control group, the levels of surfactant protein D (SP-D), TNF-α, monocyte chemotactic protein-1 (MCP-1), IL-1α, IL-6, IL-10, recombinant S100 calcium binding protein (S100) A9, interferon inducible protein 10 (IP-10), macrophage inflammatory protein-1α (MIP-1α), matrix metalloprotein-9 (MMP-9), and Complement Factor D in BALF of FluA infection exhibited a significant elevation. The concentrations of arginine, aspartate, citrulline, glutamic acid, ornithine, proline, creatine, and sarcosine in arginine metabolism were up-regulated, which was correlated with most of elevated cytokine levels. The supplementation of arginine after FluA infection significantly decreased the levels of IL-1β, IL-6, and TNF-α, but increased the level of IL-10 in macrophages.Conclusions:Arginine reduces the inflammatory response induced by FluA infection in macrophages, suggesting that it may be a potential intervention target for severe pulmonary inflammation following FluA infection.

Objective To investigate the application value of extracellular volume fraction(ECV)obtained from enhanced CT in diagnosis and classification of acute pancreatitis.Methods The clinical data from patients with acute pancreatitis(acute pancreatitis group)and normal controls(control group)underwent enhanced CT were analyzed retrospectively.The CT values of pancreas and abdominal aorta in the same sclice on precontrast and equilibrium-phase images were measured,and then pancreatic ECV was calcu-lated.The measured parameters were compared between the groups of control and acute pancreatitis,and subgroups of non-severe and severe pancreatitis.The logistic regression analysis was used to identify the risk factors for acute pancreatitis and severe pancrea-titis,and the receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficiency in diagnosis and classifica-tion of acute pancreatitis.Results The pancreatic CT value and ECV were independent risk factors for acute pancreatitis(P＜0.05),and the ECV was an independent risk factor for severe pancreatitis(P＜0.05).The area under the curve(AUC)of ECV was higher in acute pancreatitis group(0.81)and severe pancreatitis subgroup(0.68).Conclusion As a quantitative parameter,the ECV obtained from enhanced CT has higher clinical application value and higher popularity in the diagnosis and classification of acute pancreatitis.

Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85％of all cancer cases in the country.Several guidelines have been used to diagnose and treat liver cancer.However,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual patients.Therefore,it is necessary to establish a comprehensive and practical expert consensus,specifically for China,to enhance the diagnosis and treatment of HCC using the Delphi method.The classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were developed.These recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment prognosis.The findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

AIM:To explore the effect and mechanism of hydrogen sulfide(H2S)on autophagy and angiogene-sis in skin wound of diabetic rats.METHODS:Among 36 healthy 8-week-old male Sprague-Dawley rats,12 rats were se-lected as control group,and the remaining rats were intraperitoneally injected with streptozotocin(STZ)to induce diabetic model and were randomly divided into diabetes mellitus(DM)group and NaHS(H2S donor)intervention(DM+NaHS)group,with 12 rats in each group.A skin trauma model was established by excising the skin of the back of rats in each group.The rats in DM+NaHS group were intraperitoneally injected with NaHS(56 μmol/kg),and the rats in control and DM groups were daily received the same volume of normal saline for 21 consecutive days.The healing of skin wound was measured on days 0,7,14 and 21 after operation.On the 21st day after surgery,the content of H2S in skin tissues was de-tected by C-7Az fluorescent probe,and the morphological changes and angiogenesis of wound tissues were observed by HE staining.The expression of CD31 was detected by immunofluorescence staining,and endothelial autophagy was detected by double staining of CD31 and beclin-1.The protein levels of cystathionine γ-lyase(CSE),CD31,microtubule-associated protein 1 light chain 3(LC3),beclin-1,P62,Bcl-2,Bax,phosphatidylinositol 3-kinase(PI3K),protein kinase B(PKB/Akt)and mammalian target of rapamycin(mTOR)in wound tissues were determined by Western blot.Caspase-3 and propidium iodide(PI)staining was used to detect cell apoptosis,and apoptosis of vascular endothelial cells was deter-mined with CD31 and TUNEL double immunofluorescence staining.RESULTS:Compared with DM group,the wound healing rate,H2S content and CSE protein expression were significantly increased in DM+NaHS group(P＜0.01),but still lower than those in control group(P＜0.01).HE staining showed that the wound surface in DM group was thin and wide,with few capillary,while that in DM+NaHS group was thicker with lots of capillary and wound width was reduced.Com-pared with DM group,CD31 expression was markedly increased(P＜0.01),the fluorescence intensity of caspase-3 and PI was significantly decreased(P＜0.01),and CD31+/beclin-1+ as well as CD31+/TUNEL+ cells were decreased(P＜0.01)in DM+NaHS group.Western blot analysis showed that compared with DM group,the levels of beclin-1,Bax and LC3-Ⅱ/LC3-Ⅰ were significantly decreased(P＜0.01),while the levels of P62 and Bcl-2,as well as ratios of p-PI3K/PI3K,p-Akt/Akt and p-mTOR/mTOR were significantly increased(P＜0.01)in DM+NaHS group.CONCLUSION:H2S can promote skin wound healing,which may be related to activation of PI3K/Akt/mTOR signaling pathway,inhibition of endothelial au-tophagy and apoptosis,and promotion of angiogenesis in diabetic rats.

Objective:To investigate the status of corneal epithelial remodeling and changes in corneal aberration after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and FS-LASIK combined with corneal collagen cross-linking (FS-LASIK Xtra), and to analyze the relationship between corneal epithelial thickness (CET) and corneal aberration.Methods:A cohort study was conducted.A total of 172 patients (172 eyes) who underwent FS-LASIK at Yinhai Eye Hospital of Chengdu University of Traditional Chinese Medicine were enrolled from June 2021 to February 2022.The 172 eyes were divided into FS-LASIK group (94 eyes) and FS-LASIK Xtra group (78 eyes) according to the surgical procedure, with a total follow-up of 6 months.The cornea was divided into a central 2-mm ring and a ring of 2-5 mm centered on the central cornea.CET at 9 regions in the central 0-5 mm area was measured by OCT before and at 1, 3 and 6 months after surgery, and the corneal higher-order aberration (HOA) was measured by the iTrace visual function analyzer.The main outcomes were the increase in CET (ΔCET), and corneal HOA at 6 months after surgery.The relationship between central corneal ΔCET and corneal aberration was analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Yinhai Eye Hospital of Chengdu University of Traditional Chinese Medicine (No.2021yh-009). Written informed consent was obtained from each subject.Results:At 1, 3 and 6 months after surgery, the central, superior, superior nasal, nasal, inferior nasal, inferior, inferior temporal, temporal and superior temporal ΔCET were significantly smaller in FS-LASIK Xtra group than in FS-LASIK group (all at P<0.05). In FS-LASIK Xtra group, 6-month postoperative central, superior, superior nasal, inferior and inferior temporal ΔCET were significantly larger than those at 1 month after surgery, and 3- and 6-month postoperative temporal ΔCET were significantly larger than that at 1 month after surgery, and 6-month postoperative superior temporal ΔCET was significantly larger than those at 1 and 3 months after surgery (all at P<0.05). In FS-LASIK group, 3- and 6-month postoperative central, superior, inferior and inferior temporal ΔCET were significantly larger than those at 1 month after surgery, and 6-month postoperative superior nasal ΔCET was significantly larger than that at 3 months after surgery, and 6-month postoperative nasal, inferior nasal, temporal, superior temporal ΔCET were significantly larger than those at 1 and 3 months after surgery (all at P<0.05). There was no significant difference in vertical trefoil, vertical and horizontal coma changes at different time points after surgery between both groups (vertical trefoil: χ2group=4.27, P=0.118; χ2time=0.01, P>0.05.vertical coma: χ2group=5.74, P=0.057; χ2time=0.08, P=0.957.horizontal coma: χ2group=3.97, P=0.137; χ2time=0.51, P=0.773). The tilted trefoil changes at 1, 3 and 6 months after surgery of FS-LASIK Xtra group were significantly larger than those of FS-LASIK group (all at P<0.05). The 6-month spherical aberration change in FS-LASIK Xtra group was significantly higher than that at 1 month after surgery, and the 6-month spherical aberration change in FS-LASIK group was significantly higher than that at 1 and 3 months after surgery (all at P<0.05). The 6-month total HOA change in FS-LASIK group was significantly lower than that at 1 and 3 months after surgery (all at P<0.05). In FS-LASIK group, central corneal ΔCET was weakly positively correlated with spherical aberration at 1 and 6 months after surgery ( rs=0.257, P=0.008; rs=0.244, P=0.012), and was weakly positively correlated with total HOA ( rs=0.253, P=0.009; rs=0.279, P=0.004). Conclusions:The postoperative ΔCET after FS-LASIK Xtra is smaller than that after FS-LASIK, but the homogeneity of ΔCET in each region is similar between the two groups.The changes in corneal HOA after surgery are similar in both groups, and there is a certain association between the overall epithelial distribution and corneal aberration.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective To investigate the value of transient elastography (TE) in the staging of hepatic fibrosis in patients with autoimmune liver disease (ALD). Methods PubMed, Embase, the Cochrane Library, CNKI, Wanfang Data, and VIP databases were searched for English and Chinese articles on TE in the staging of hepatic fibrosis in ALD published from January 2000 to January 2021. Two reviewers independently performed data extraction for the articles included, and QUADAS2 was used for quality assessment. The bivariate mixed effects model in Stata 15.0 software was used to perform the Meta-analysis. Results A total of 11 articles were included, with 1041 patients in total. In the diagnosis of significant hepatic fibrosis (F≥2), TE had a pooled sensitivity of 0.81 (95% CI : 0.75-0.86), a specificity of 0.87(95% CI 0.79-0.92), and an area under the receiver operating characteristic curve (AUC) of 0.91(95% CI 0.88-0.93); in the diagnosis of advanced hepatic fibrosis (F≥3), TE had a pooled sensitivity of 0.81(95% CI 0.74-0.87), a sensitivity of 0.90(95% CI 0.85-0.93), and an AUC of 0.92(95% CI 0.90-0.94); in the diagnosis of early-stage liver cirrhosis (F4), TE had a pooled sensitivity of 0.87(95% CI 0.74-0.93), a specificity of 0.93(95% CI 0.87-0.97), and an AUC of 0.96(95% CI 0.94-0.97). Conclusion TE has a good diagnostic value in evaluating significant liver fibrosis, advanced liver fibrosis, and early-stage liver cirrhosis in patients with ALD, especially with a relatively high diagnostic accuracy for early-stage liver cirrhosis.

Aim To study the antiviral anrl antipyretic mechanism of Phillvrin in vitro and in vivo.Methods By respiratory virus infection cell model, SI index and antiviral activity of forsythia glycosides virus activity in vitro were detected.A mouse model of influenza virus infection was established, and hemagglutination titer, lung index, lung histopathology pathology were detec¬ted.Hemagglutination titer, lung index, lung histopa¬thology pathology were observed and in vivo anti-influ¬enza virus and pneumonia effects were investigated.Dry yeast induced rat fever model was established, temperature and plasma and hypothalamus thermoregu¬lation and inflammation of the related factors were test¬ed , and its antipyretic mechanism was investigated.By AutoDock Vina software for molecular docking, the docking results were plotted with PyMol software.Re¬sults Phillyrin had certain inhibitory effects on H3N2, RSV, E71 , ADV-3, HSV-1 and HSV-2 (SI >2).Phillyrin could reduce hemagglutination titer of infected lung tissue, decrease lung index, and alleviate lung lesions, especially interstitial pneumonia.Phill- vrin could also significantly reduce the body tempera¬ture of rats with fever, and its antipyretic mechanism might he related to the decrease of PGE2 and IL-ip levels in plasma and hypothalamus of rats.Molecular docking results showed that the binding energies of Phillyrin with a-MSH, IL-lp, PEG2, A VP, cAMP and other proteins were all less than - 5 kcal • mol 1.Conclusions Phillyrin has obvious antiviral, antipy-retic and improvement of pulmonary inflammatory le¬sions, and it is speculated that it can play an anti-in¬fluenza effect through "treating both symptoms and root causes".

Porcine epidemic diarrhea (PED) is a major disease of pigs that inflicts heavy losses on the global pig industry. The etiologic agent is the porcine epidemic diarrhea virus (PEDV), which is assigned to the genus Alphacoronavirus in the family Coronaviridae. This review consists of five parts, the first of which provides a brief introduction to PEDV and its epidemiology. Part two outlines the passive immunity in new born piglets and the important role of colostrum, while the third part summarizes the characteristics of the immune systems of pregnant sows, discusses the concept of the "gut-mammary gland-secretory IgA(sIgA) axis" and the possible underpinning mechanisms, and proposes issues to be addressed when designing a PEDV live vaccine. The final two parts summarizes the advances in the R&D of PEDV vaccines and prospects future perspectives on prevention and control of PEDV, respectively.
Animals ; Antibodies, Viral ; Coronavirus Infections/veterinary* ; Female ; Immunization ; Porcine epidemic diarrhea virus ; Pregnancy ; Swine ; Swine Diseases/prevention & control* ; Viral Vaccines