Age-related macular degeneration (AMD) is a disease that affects the vision of elderly individuals worldwide. Although current therapeutics have shown effectiveness against AMD, some patients may remain unresponsive and continue to experience disease progression. Therefore, in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment. Recently, studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species (ROS) and activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) innate immunity pathways, ultimately resulting in sterile inflammation and cell death in various cells, such as cardiomyocytes and macrophages. Therefore, combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management. Notably, emerging evidence indicates that natural products targeting mitochondrial quality control (MQC) and the cGAS/STING innate immunity pathways exhibit promise in treating AMD. Here, we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways, as well as their interconnected mediators, which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses, thereby hoping to offer new insights into therapeutic interventions for AMD treatment.

CD8⁺ T cell-based immune-therapeutics, including immune checkpoint inhibitors and adoptive cell therapies (tumor-infiltrating lymphocytes (TILs), T cell receptor-engineered T cells (TCR-T), chimeric antigen receptor T cells (CAR-T)), have achieved significant successes and prolonged patient survival to varying extents and even achieved cure in some cases. However, immunotherapy resistance and tumor insusceptibility frequently occur, leading to treatment failure. Recent evidences have highlighted the ponderance of tumor cells metabolic reprogramming in establishing an immunosuppressive milieu through the secretion of harmful metabolites, immune-inhibitory cytokines, and alteration of gene expression, which suppress the activity of immune cells, particularly CD8⁺ T cells to evade immune surveillance. Therefore, targeting tumor cell metabolic adaptations to reshape the immune microenvironment holds promise as an immunomodulatory strategy to facilitate immunotherapy. Here, we summarize recent advances in the crosstalk between immunotherapy and tumor reprogramming, focusing on the regulatory mechanisms underlying tumor cell glucose metabolism, amino acid metabolism, and lipid metabolism in influencing CD8⁺ T cells to provide promising metabolic targets or combinational strategies for immunotherapy.

ObjectiveTo investigate the situation and development trend of the disease burden of acute hepatitis B in China in 1990 — 2019. MethodsThe Global Burden of Disease 2019 was used to analyze the incidence rate， mortality rate， and disability-adjusted life year （DALY） rate of acute hepatitis B in different sex and age groups and predict the trend of the incidence rate of acute hepatitis B. ResultsIn 2019， the incidence rate， mortality rate， and DALY rate of acute hepatitis B in China were 1 623.71/100 000， 0.20/100 000， and 10.04/100 000 respectively， which were reduced by 42.03%， 79.38%， and 80.21%， respectively， compared with the data in 1990， and women showed lower incidence rate， mortality rate， and DALY rate of acute hepatitis B than men. In 2019， the 20～<54 years group had the highest incidence rate （2 285.85/100 000） and DALY rate （10.53/100 000）， and the ≥55 years group had the highest mortality rate of 0.52/100 000. The Joinpoint regression model analysis showed that the incidence rate， mortality rate， and DALY rate of acute hepatitis B in China tended to decrease from 1990 to 2019， with an average annual percent change of -1.9%， -5.2%， and -5.5%， respectively （P<0.05）. The grey prediction model GM （1，1） showed that the incidence rate of acute hepatitis B will decrease from 2020 to 2030 in China. ConclusionThe disease burden of acute hepatitis B tended to decrease from 1990 to 2019 in China， indicating that the prevention and treatment measures for acute hepatitis B have achieved a marked effect in China； however， due to the large population base of China， active preventive measures should be further adopted to reduce the disease burden of acute hepatitis B.

Objective:To study the relationship of pathogenic bacteria in midstream urine culture and stone composition of patients characteristics with infection stones.Methods:Between January 2016 and December 2020, 989 patients with infectious stones who attended Tsinghua Chang Gung Hospital, affiliated with Tsinghua University, for surgical treatment were enrolled in the study. There were 545 male and 444 female patients, with the mean age (48±14) years. The left and right side stones were 396 and 333, respectively. There were 260 bilateral stones, 264 single stones, 334 multiple stones, and 391 deer-stalker-shaped stones. The maximum diameter of stones was (33.4±26.5)mm, combined with diabetes in 109 cases and hypertension in 235 cases. Clean middle-urine was collected for bacterial culture, and intraoperative stone specimens were collected by percutaneous nephrolithotomy (PCNL). Personal characteristics of the patient such as gender, age, body mass index, clinical information such as stone size, location, comorbidities, results of urine culture and stone composition were recorded. The differences of infectious stone composition was analyzed between urease-producing, non-urease-producing bacteria.Results:Among the 989 patients with infectious stones, 259 were pure infectious stones, 131 were mixed infectious stones, and 599 were combined with infectious stone components. Urine cultures were positive in 627(63.4%) patients with infectious stones. The predominant urease-producing bacteria included Ureaplasma urealyticum(94 case), Proteus mirabilis(58 case), and Staphylococcus spp.(36 case). Pure infectious stones were common in Proteus mirabilis, while combined with infectious stone components were common in Ureaplasma urealyticum and Staphylococcus spp. The predominant non-urease-producing bacteria included Escherichia coli(175 case), Enterococcus spp.(76 case) and Streptococcus spp.(35 case). Escherichia coli commonly contained in infectious stone components and pure infectious stones, whereas Enterococcus spp. and Streptococcus spp. commonly contained in infectious stone components. Escherichia coli (61 case), Proteus mirabilis (44 case) and Enterococcus spp.(20 case) were the most common bacteria in 259 cases of pure infectious stones. Escherichia coli (36 case), Enterococcus spp. (14 case) and Ureaplasma urealyticum (10 case) were the most common bacteria in 131 cases of mixed infectious stones. The most common bacteria in 599 cases of combined infectious stones were Escherichia coli (78 case), Ureaplasma urealyticum (68 case) and Enterococcus spp. (42 case).Conclusions:Urease producing bacteria were not common in infectious stones. It was common for the Ureaplasma urealyticum in combined infectious stone components, while Escherichia coli was common in pure and combined infectious stone components.

Objective:To evaluate the long-term prognosis and recurrence of young liver transplant recipients with hepatocellular carcinoma(HCC).Methods:Based upon the database of liver transplantation center, clinical data were retrospectively reviewed for 39 young recipients(18~40 years)and 158 middle-aged and elderly recipients(over 40 years)from 2013 to 2017. The parameters of overall survival(OS), recurrence-free survival(RFS)and disease-specific survival(DSS)were compared between two groups.Cox's proportional hazard model was utilized for evaluating the prognostic factors.Results:Significant inter-group difference existed in recurrence rate of HCC. Kaplan-Meier analysis revealed no significant difference in OS rate(1/3-year OS, 82.1%, 66.7% and 86.1%, 74.7%, P>0.05)and DSS rate(1/3-year DSS, 94.9%, 82.1% and 99.4%, 91.1%, P=0.053); RFS rate(1/3-year RFS, 51.3%, 41.0% and 73.0%, 62.7%, P=0.008)showed significant differences; Cox multivariate analysis revealed that AFP>400 μg/L was an independent risk factor for OS, DSS and RFS; poorly differentiated tumors and positive micro-vascular invasion(MVI)were independent risk factor for DSS; poorly differentiated tumors and total tumor size >5 cm were independent risk factors for RFS. Conclusions:Although RFS of young adult group is worse than that in middle-aged and elderly group after LT, no significant inter-group difference exists in OS or DSS. And LT is still a quite effective treatment for young HCC patients.

BACKGROUND: Hepatectomy for hepatocellular carcinoma (HCC) beyond the Milan criteria is shown to be beneficial. However, a high rate of post-operative HCC recurrence hinders the long-term survival of the patients. This study aimed to investigate and compare the impacts of tenofovir (TDF) and entecavir (ETV) on the recurrence of hepatitis B viral (HBV)-related HCC beyond the Milan criteria. METHODS: Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers. Recurrence-free survival (RFS) analysis was performed using the Kaplan-Meier method. Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence. RESULTS: The analysis incorporates 595 HBV-related HCC patients. The overall 5-year RFS was 21.3%. Among them, 533 and 62 patients received ETV and TDF treatment, respectively. The 1-, 3-, and 5-year RFS rates were 46.3%, 27.4%, and 19.6%, respectively, in the ETV group compared with 65.1%, 41.8%, and 37.2%, respectively, in the TDF group (P < 0.001). Multivariate analysis showed that TDF treatment (hazard ratio [HR]: 0.604, P = 0.005), cirrhosis (HR: 1.557, P = 0.004), tumor size (HR: 1.037, P = 0.008), microvascular invasion (MVI) (HR: 1.403, P = 0.002), portal vein tumor thrombus (PVTT) (HR: 1.358, P = 0.012), capsular invasion (HR: 1.228, P = 0.040), and creatinine levels (CREA) (HR: 0.993, P = 0.031) were statistically significant prognostic factors associated with RFS. CONCLUSIONS Patients with HCC beyond the Milan criteria exhibited a high rate of HCC recurrence after hepatectomy. Compared to the ETV therapy, TDF administration significantly lowered the risk of HCC recurrence.
Antiviral Agents/therapeutic use* ; Carcinoma, Hepatocellular/surgery* ; Guanine/analogs & derivatives* ; Hepatectomy ; Hepatitis B virus ; Hepatitis B, Chronic/drug therapy* ; Humans ; Liver Neoplasms/surgery* ; Retrospective Studies ; Tenofovir/therapeutic use*

【Objective】 To guide the scientific and rational platelet transfusion in clinical and reduce refractory platelet transfusion by constructing a nomogram prediction model for the efficacy of platelet transfusion. 【Methods】 The basic information of 298 patients underwent prophylactic transfusion of apheresis platelet in our hospital from 2019 to 2020 was collected, including gender, age, blood group, number of blood transfusions, hours before expiration, platelet count before and after transfusion, body temperature after transfusion, and splenomegaly. Potential risk factors causing refractory platelet transfusion were screened out by univariate logistic regression analysis, and the independent risk factors were further evaluated by multivariate binary logistic regression. The independent risk factors were then imported into Rstudio software to fit the effect prediction nomogram mode, which was verified by bootstrap repeated sampling,, evaluated by ROC, and calibrated by Calibration. 【Results】 212 out of 298 apheresis platelet transfusions were effective, with the effective rate at 71.14%. The binary logistic regression analysis showed that the non-immune factors causing refractory platelet transfusion were gender, blood transfusions≤ 4 occasions, blood transfusion more than 4 occasions, body temperature, splenomegaly, and platelet count before transfusion; the OR value and 95% CI were: 3.773 (1.796~7.924), 29.081 (8.668~97.568), 10.416 (1.525~71.134), 7.376 (3.145~17.301), 17.385 (6.428~47.018), and 0.947 (0.904~0.992), respectively. Regression model Hosmer-Lemeshaw test P value was 0.805. The AUC of fitted nomogram prediction model was 0.895, 95% CI (0.855~0.936). 【Conclusion】 The independent risk factors causing refractory platelet transfusion are gender, body temperature, number of blood transfusions, splenomegaly and platelet count before transfusion. The area under the curve of the fitted nomogram prediction model is 0.899, which has a good predictive ability and presents the probability of ineffective transfusion visually and quantitatively, so as to guide scientific and rational use of platelets, and reduce refractory platelet transfusion.

Objective To establish a clinical scoring system for the prognosis of patients with single large hepatocellular carcinoma (HCC) after hepatectomy.Methods 268 patients with single large HCC who underwent hepatectomy in West China Hospital of Sichuan University from January 2009 to December 2013 were included in this prospective study. There were 227 males and 41 females, of which 198 cases aged≤60 years old, 70 aged>60 years old. The informed consents of all patients were obtained and the local ethical committee approval was received. The patients' survival were observed. The independent risk factors for postoperative prognosis of patients with single large HCC were selected by Cox proportional risk regression mode. Based on the risk factors, the prognostic scoring system for single large HCC wasestablished. The scoring system was tested through survival analysis by Kaplan-Meier and Log-rank test. Results The median overall postoperative survival was 45 months, and the tumor-free survival was 31 months. Platelet-to-lymphocyte ratio (PLR)≥107, tumor diameter≥6.8 cm and positive microvascular invasion (MVI) were the independent risk factors for postoperative overall survival and tumor-free survival in patients with single large HCC (HR=1.004, 1.092, 2.233 and 1.003, 1.062, 1.534; P<0.05). Every independent risk factor was assigned 1 point. All patients were divided into low risk group (0 point), moderate risk group (1-2 points) and high risk group (3 points). The 5-year survival rate of high risk group was 25.4％, and that of moderate and low risk group was 33.2％ and 52.1％ respectively, where significant difference was observed (χ2=23.1, P<0.05). Similar Results were observed when the scoring system was used in patients with or without cirrhosis.Conclusions PLR≥107, tumor diameter≥6.8 cm and positive MVI are the independent risk factors for the prognosis of patients with single large HCC after resection. The prognostic scoring system established in this study can be used to predict the postoperative long-term survival of patients.

Child and adolescent mental disorders are common disorders with various symptoms,and attracting more attention due to the increasing prevalence.Mental disorders,especially the attention-deficit hyperactivity disorder (ADHD) and the autism spectrum disorder (ASD),have great influence on the development of children and adolescents.Nowadays,the biomarkers from neuroimaging such as magnetic resonance imaging (MRI) have a great importance on the diagnosis of mental disorders,and machine learning has been proved to be very powerful in the processing for neuroimages.Nowadays,many researchers are focusing on the studies of computer-aided diagnosis (CAD) based on machine learning and neuroimaging.In this review,the technical details of machine learning based CAD of child and adolescent mental disorders are briefly introduced,and the research progress in CAD of ADHD and ASD based on machine learning and structural MRI are summarized.These studies showed that many machine learning methods have been used in the diagnosis of child and adolescent mental disorders,but the relevant methods cannot be applied to clinical diagnosis.Further studies should be conducted to improve the diagnostic ability of machine learning methods from multiple perspectives,and provide an objective and reliable tool for the clinical diagnosis of child and adolescent mental disorders.