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.

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 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 study the correlation between patients with type 2 diabetes mellitus combined with nonalcoholic steatohepatitis in order to provide theoretical support for the treatment of NAFLD through aerobic exercise performance.Methods:253 cases with T2DM combined with NAFLD were selected. 93 cases consented to undergo a liver biopsy. Among them, 74 cases with liver biopsy successfully passed the symptom-limited cardiopulmonary exercise test (CPET) and respiratory quotient (RQ)≥1.05. Patients were divided into two groups according to the NAFLD activity score (NAS) of the pathological biopsy: the non-NASH group (NAS < 4) and the NASH group (NAS≥4). The differences in general clinical and biochemical indicators and exercise parameters were compared between the two groups. The relevant factors that affect aerobic exercise performance in NAFLD patients were explored by correlation and regression analysis.Results:The peak oxygen uptake [VO2 @ peak, (17.82 ± 5.61) ml·kg -1·min -1 and (23.14 ± 5.86) ml·kg -1·min -1] and anaerobic threshold [VO2 @ AT, (11.47 ± 3.12) ml·kg -1·min -1 and (13.81 ± 3.53) ml·kg -1·min -1] were lower in the NASH group than those in the non-NASH group in T2DM patients, with P < 0.01, indicating a significant decrease in aerobic exercise performance in NASH patients compared to non-NASH patients. Correlation analysis showed that patients with T2DM combined with NAFLD VO2@peak was positively correlated with RQ, carbohydrate oxidation rate (%CHO), daily carbohydrate energy supply (CHO Kcal/d), high-density lipoprotein cholesterol (HDL-C), and maximal voluntary ventilation (MVV) ( r 0.360, 0.334, 0.341, 0.255, 0.294, P < 0.05 or P < 0.01, respectively) and negatively correlated with NAS score, fat attenuation, liver stiffness, fat oxidation rate (%FAT), daily fat energy supply (FAT Kcal/d), aspartate aminotransferase (AST), alanine aminotransferase (ALT), body mass, and body mass index (BMI) ( r -0.558, -0.411, -0.437, -0.340, -0.270, -0.288, -0.331, -0.295, -0.469, P < 0.05 or P < 0.01, respectively). VO2@AT were positively correlated with RQ, %CHO, total cholesterol (TC), and HDL-C ( r 0.351, 0.247, 0.303, 0.380, P < 0.05 or P < 0.01, respectively), while it was negatively correlated with NAS score, fat attenuation, liver stiffness, %FAT, FAT (Kcal/d), ferritin (Fer), ALT, AST, body weight, and BMI ( r -0.330, -0.384, -0.428, -0.270, -0.318, 0.320, -0.404, -0.416, -0.389, -0.520, P < 0.05 or P < 0.01, respectively). Stepwise multiple regression analyses revealed that BMI, RQ, and NAS scores were independent correlated factors of aerobic exercise performance. Conclusion:Hepatic inflammation and fibrosis affect the aerobic exercise performance of patients with T2DM combined with NAFLD.

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.

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".

Objective:To examine the feasibility and safety of endoscopic subcutaneous mastectomy and immediate reconstruction via a small skin incision approach without gas and mesh for early breast carcinomas.Methods:We analyzed 7 patients diagnosed with breast cancer who underwent an endoscopic subcutaneous mastectomy and immediate reconstruction from Jun. to Nov. 2021 using a gasless and meshless small skin incision approach at the Department of Thyroid and Breast Surgery, the First Affiliated Hospital of USTC. Mean age was 44.9 (29-63) years. Clinical stage, postoperative complications and other data of patients were collected. Patients were required to fill in BREAST-Q scale anonymously before and during postoperative follow-up. The difference was considered significant for P < 0.05. Results:The tumors were all unilateral and solitary lesions, with a mean diameter of 1.74 (0-5) cm. The average distance of mass from the nipple on imaging was 2.11cm (range 0 to 4) . Postoperative pathological clinical stage,1 patient was in Tis, 3 patients were in stage I, 2 patients were in stage II and a pathological complete response was achieved in one patient (ypT0pN0cM0 CR) . The mean operative time was 245.3 (195-316) min, the mean intraoperative bleeding volume was 37.1ml, the mean postoperative hospital stay was 5.1 d, and the median follow-up time was 8.8 (6-11.2) months. All the 7 patients had incision healing at the first stage, and no complications such as infection, incision complications, capsular contracture, nipple-areola complex or skin flap necrosis, removal or displacement of breast implant occurred. No local recurrence or metastasis was detected during the follow-up period. Compared with preoperative, the scores of postoperative psychosocial status, chest wall status were lower ( P<0.05) , but still ideal, while breast satisfaction and sexual satisfaction scores were not significantly different from preoperative baseline ( P>0.05) . Conclusion:This study indicates that endoscope-assisted breast reconstruction with gasless and meshless is a safe and feasible surgical intervention method for early breast cancer, with good cosmetic effects, and can be promoted as a new type of breast reconstruction.

With the increasing incidence of breast cancer, the relationship between tumor and immune function has attracted more and more attention. This article reviews the relationship between breast cancer and T lymphocyte subsets, in order to explore the changes of immune function before and after operation in breast cancer patients, so as to select appropriate surgical methods, radiotherapy, chemotherapy and immunotherapy for the patients.

Objective:To evaluate the safety of two inactivated COVID-19 vaccines in a large-scale emergency use.Methods:Based on the "Vaccination Information Collection System", the incidence data of adverse reactions in the population vaccinated with the inactivated COVID-19 vaccines developed by Beijing Institute of Biological Products Co., Ltd and Wuhan Institute of Biological Products Co., Ltd, respectively, in emergency use were collected, and the relevant information were analyzed with descriptive epidemiological and statistical methods.Results:By December 1, 2020, the vaccination information of 519 543 individuals had been collected. The overall incidence rate of adverse reactions was 1.06%, the incidence rate of systemic adverse reactions was 0.69% and the incidence rate of local adverse reactions was 0.37%. The main systemic adverse reactions included fatigue, headache, fever, cough and loss of appetite with the incidence rates of 0.21%, 0.14%, 0.06%, 0.05% and 0.05%, respectively; the main local adverse reactions were injection site pain and injection site swelling with the incidence rates of 0.24% and 0.05%, respectively.Conclusion:The two inactivated COVID-19 vaccines by Beijing Institute of Biological Products Co., Ltd and Wuhan Institute of Biological Products Co., Ltd showed that in the large-scale emergency use, the incidence rate of general reactions was low and no serious adverse reactions were observed after the vaccinations, demonstrating that the vaccines have good safety.