Objective To analyze the proportion and clinicopathological characteristics of HER2-positive breast cancer patients with BRCA1/2 pathogenic variants, and their response to neoadjuvant anti-HER2 targeted therapy. Methods The clinicopathological data of 531 breast cancer patients with germline BRCA1/2 pathogenic variants (201 with BRCA1 variants and 330 with BRCA2 variants) were analyzed. Results Among the 201 BRCA1 and 330 BRCA2 variants, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared with BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients did not present any significant differences in clinicopathological features; however, compared with triple-negative breast cancer patients, HER2-positive patients had a later onset age and lower tumor grade. Among the 17 patients who received neoadjuvant anti-HER2 targeted therapy, 10 cases achieved pCR (58.8%), whereas 7 cases did not (41.2%). Conclusion HER2-positive breast cancer accounts for more than 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy. This phenomenon highlights the possibility of combining anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.

Objective:To assess the predictive value of acute liver failure (ALF) for sepsis-free survival (SFS) in burn patients and to identify associated risk factors.Methods:A retrospective cohort study was conducted on burn patients meeting inclusion criteria from the 2014 Kunshan aluminum dust explosion disaster (August 2, 2014 - April 13, 2015). Eligible patients were stratified into ALF and non-ALF groups based on the development of ALF. Demographic characteristics, total burn surface area, organ dysfunction, time to sepsis onset, and clinical outcomes were collected and compared between groups. Kaplan-Meier survival analysis and multivariate Cox regression were performed to assess the impact of ALF on SFS. A nomogram model was constructed for individualized risk prediction.Results:Among 185 enrolled patients (ALF group:21, non-ALF group:164), ALF incidence was 11.35%. The ALF group demonstrated higher mortality (85.71% vs. 34.15%, P<0.001) and SFS failure rates (100.00% vs. 61.59%, P<0.001) compared to non-ALF patients. Multivariate Cox analysis identified ALF as an independent sepsis predictor ( HR=1.68, 95% CI: 1.00-2.80, P<0.05). Time-dependent ROC analysis showed AUCs of 0.626, 0.714, 0.703, and 0.706 for SFS prediction at 2, 4, 8, and 12 weeks respectively. The nomogram model demonstrated that ALF combined with other parameters effectively predicted sepsis risk within 2-12 weeks post-injury. ALF development showed significant associations with concurrent organ dysfunction including acute kidney injury, acute heart failure, and acute respiratory distress syndrome (all P<0.001). A higher proportion of ALF patients received hemodialysis ( P<0.001) and pre-hospital central venous catheterization ( P=0.017). Conclusions:ALF independently predicts SFS failure and correlates strongly with poor prognosis in burn patients. Early ALF recognition and targeted interventions may facilitate sepsis risk stratification and precision prevention strategies.

Myocardial fibrosis （MF） is a common pathological manifestation of various heart diseases. Due to the non-renewable nature of myocardial cells， the occurrence of MF represents irreversible damage to the myocardium. Previous studies have suggested that fibroblast-mediated collagen deposition is the main mechanism of MF. Recent studies have found that there is an immune regulation mechanism in the heart itself， and macrophage activation/polarization plays an important role in MF. With the deepening of traditional Chinese medicine research， scholars have found that traditional Chinese medicine can interfere with MF by regulating the renin-angiotensin-aldosterone system （RAAS） system and the inflammatory process， repairing the extracellular matrix， managing oxidative stress， and maintaining the balance of autophagy. This process is closely related to the activation and M1/M2 polarization of macrophages. Throughout the MF process， macrophage activation is beneficial， but excessive activation will be harmful. In the early stage of MF， appropriate M1 macrophage polarization is conducive to activating immunity and removing harmful substances. In the middle and late stages of MF， appropriate M2 macrophage polarization is conducive to remodeling the damaged myocardium. If macrophage activation is excessive/insufficient， or the balance of M1/M2 macrophage polarization is broken， the effect changes from improvement to destruction. Traditional Chinese medicines that regulate the activation/polarization of macrophages have the effects of replenishing Qi and nourishing Yin， as well as regulating Qi and activating blood， but there are also some heat-clearing， dampness-drying， and detoxification products. Therefore， the occurrence of MF may be caused by Qi and Yin deficiency， damp heat accumulation， and Qi stagnation and blood stasis. By summarizing the biological processes involved in macrophage activation/polarization in MF， this paper expounded on the research progress of traditional Chinese medicine in regulating macrophage activation and M1/M2 polarization from different angles to improve MF， so as to provide a reference for the treatment of MF with traditional Chinese medicine.

Objective To investigate the potential significance of FOXP3 expression in BRCA1/2-mutant breast cancer.Methods A total of 48 BRCA mutation carriers(16 with BRCA1 and 32 with BRCA2)and 78 age-matched non-carriers were included in this study.Immunohistochemistry was used to detect the expression of FOXP3 in breast cancer tissues.The FOXP3 RNA expression in 39 BRCA1,36 BRCA2,and 948 non-carrier breast cancer patients from TCGA-BRCA and the correlation with homologous recombin-ation deficiency scores were evaluated to validate the immunohistochemistry results.Results The FOXP3 positive rate was 43.8%(7/16)in BRCA1 mutation carriers,59.4%(19/32)in BRCA2 mutation carriers,and 9.0%(7/78)in non-carriers.The FOXP3 positive rates in patients with BRCA1/2 mutant breast cancer were significantly higher than those in non-carriers(P=0.002;P<0.001).TCGA-BRCA results showed that the FOXP3 RNA level in BRCA1/2 mutant breast cancer was significantly higher than that in non-carriers(P=0.02,P=0.004).The FOXP3 RNA level was positively correlated with the homologous recombination deficiency score(Spearman R=0.30,P<2.2e-16).Conclusion Patients with BRCA1/2 mutant breast cancers have higher FOXP3expression than non-carriers,and may be more sensitive to immunotherapy.

Objective To compare the clinicopathological characteristics between primary and contralateral cancers in patients with metachronous bilateral breast cancer (MBBC) who carried a BRCA1/2 germline pathogenic variant. Methods A total of 496 BRCA1/2 carriers with primary unilateral breast cancer were included (196 with BRCA1 and 300 with BRCA2). Clinicopathological information of patients was collected, and the median follow-up for the entire cohort was 10.4 years (0.4-20.8 years). Results Among all patients, 31 (15.8%) of the 196 BRCA1 carriers and 49 (16.3%) of the 300 BRCA2 carriers had MBBC, respectively. Among the 31 BRCA1 carriers who developed MBBC, the proportion of triple-negative breast cancer (TNBC) in primary cancer and contralateral cancer was 61.3% and 67.7%, respectively. If the primary cancer of BRCA1-mutated MBBC was TNBC, the probability of the contralateral breast cancer with TNBC was 89.5% (17/19), which was significantly higher than that if the primary cancer was non-TNBC (33.3%, 4/12) (P=0.004). Among the 49 BRCA2 carriers who developed MBBC, the predominant molecular phenotype of the primary and contralateral cancers was HR+ & HER2- (77.6% and 67.3%, respectively; P=0.53). Conclusion Approximately 60% of BRCA1 carriers exhibit TNBC. If a BRCA1 carrier with a TNBC primary breast cancer had an MBBC, the probability of the contralateral breast cancer being TNBC phenotype is almost 89.5%.

Confronted with the Coronavirus disease 2019 (COVID-19) pandemic, China has become an asset in tackling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and mutation, with several innovative platforms, which provides various technical means in this persisting combat. Derived from collaborated researches, vaccines based on the spike protein of SARS-CoV-2 or inactivated whole virus are a cornerstone of the public health response to COVID-19. Herein, we outline representative vaccines in multiple routes, while the merits and plights of the existing vaccine strategies are also summarized. Likewise, new technologies may provide more potent or broader immunity and will contribute to fight against hypermutated SARS-CoV-2 variants. All in all, with the ultimate aim of delivering robust and durable protection that is resilient to emerging infectious disease, alongside the traditional routes, the discovery of innovative approach to developing effective vaccines based on virus properties remains our top priority.
Humans ; COVID-19 Vaccines ; COVID-19/prevention & control* ; SARS-CoV-2 ; China/epidemiology* ; Vaccine Development

SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes (ISGs), that collectively foster an antiviral state. We report here the identification of a group of type I interferon suppressed genes, including fatty acid synthase (FASN), which are involved in lipid metabolism. Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection. More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern. Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type I interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.

Objective: To analyze long-term therapeutic effect and safety of warfarin anticoagulant therapy of different intensity on aged patients with nonvalvular atrial fibrillation (NVAF). Methods: According to age, a total of 197 NVAF patients followed up for five years were divided into advanced aged group [n=65，≥80(85±2.09)years], aged group [n=75, 65-79(76.5±2.27) years] and middle-aged group [n=57, ＜65(57.4±2.18)]. All enrolled patients received long-term warfarin anticoagulant therapy, advanced aged group and aged group received low intensity anticoagulation, international normalized ratio (INR) was 1.6~2.5, while middle-aged group received standard intensity anticoagulation and the INR was 2.0~3.0. Thrombus events and incidence rates of hemorrhage etc. over five years were compared among three groups, and the safe dose range of warfarin was explored. Results: During five-year follow-up, no acute cerebral infarction occurred in three groups. The bleeding and other adverse reaction among three groups were no significant difference（P＞0.05). Compared with middle-aged group, there were significant reductions in warfarin dose [(3.29±0.49) mg/d vs. (2.95±0.38) mg/d, (2.85±0.49) mg/d],INR [(2.54±0.43) vs. (2.20±0.29), (2.16±0.32)] and CHA2DS2-VASc [(3.02±0.89) score vs.( 2.64±0.77) score vs.( 2.33±0.48) score]in aged group and advanced aged group, P＜0.01 all; but there were no significant difference between aged group and advanced aged group (P>0.05). There were no significant difference in incidence rates of mild hemorrhage (21.1% vs. 14.7% vs. 24.6%) and severe hemorrhage (1.8% vs. 1.3% vs. 1.5%) among middle-aged group, aged group and advanced aged group, P>0.05 all. Conclusion: When INR is closely monitored, INR controlled within 1.6~2.5, warfarin anticoagulation is safe and effective in aged patients with nonvalvular atrial fibrillation.

Objective:To analyze long-term therapeutic effect and safety of warfarin anticoagulant therapy of differ- ent intensity on aged patients with nonvalvular atrial fibrillation (NVAF). Methods:According to age,a total of 197 NVAF patients followed up for five years were divided into advanced aged group [n=65,≥80 (85.00±2.09) years],aged group [n=75,65-79 (76.50±2.27)years]and middle-aged group [n=57,<65 (57.40±2.18) years].All enrolled patients received long-term warfarin anticoagulant therapy,advanced aged group and aged group received low intensity anticoagulation,international normalized ratio (INR)was 1.6~2.5,while middle-aged group received standard intensity anticoagulation and the INR was 2.0~3.0. Thrombus events and incidence rates of hemorrhage etc.over five years were compared among three groups,and the safe dose range of warfarin was ex- plored.Results:During five-year follow-up,no acute cerebral infarction occurred in three groups.The bleeding and other adverse reaction among three groups were no significant difference (P>0.05).Compared with middle- aged group,there were significant reductions in warfarin dose [(3.29±0.49)mg/d vs.(2.95±0.38)mg/d,(2.85 ±0.49)mg/d],INR [(2.54±0.43)vs.(2.20±0.29),(2.16±0.32)]and CHA2DS2-VASc [(3.02±0.89) scores vs.(2.64±0.77)scores vs.(2.33±0.48)scores]in aged group and advanced aged group,P<0.01 all;but there were no significant difference between aged group and advanced aged group (P>0.05).There were no signif- icant difference in incidence rates of mild hemorrhage (21.1% vs.14.7% vs.24.6%)and severe hemorrhage (1.8% vs.1.3% vs.1.5%)among middle-aged group,aged group and advanced aged group,P>0.05 all.Conclu-sion:When INR is closely monitored,INR controlled within 1.6-2.5 warfarin anticoagulation is safe and effective for in aged patients with nonvalvular atrial fibrillation.

OBJECTIVE:To systematically review the efficacy of agomelatine in the treatment of depression in acute phase, and provide evidence-based reference for the clinical treatment. METHODS:Retrieved from Cochrane Library,Medline,EMBase, CJFD,VIP,CBM,Wanfang Database,WHO Clinical Trials Registry Platform and American Clinical Trials Registry Platform, the randomized controlled trials (RCT) about agomelatine versus placebo in the depression patients in acute phase. After quality evaluation and data extraction,Meta-analysis was conducted by using Rev Man 5.2 statistics software. RESULTS:A total of 7 RCT were included,involving 2 378 patients. Results of Meta-analysis showed the effective rate in agomelatine group was obviously bet-ter than placebo group [RR=1.43 ,95%CI(1.29 ,1.59),P<0.001] ,remission rate was obviously better than placebo group [RR=1.27 ,95%CI(1.03 ,1.57),P=0.02] ,and the endpoint score of depression scales was obviously lower than placebo group [MD=-2.92,95%CI(-3.65,-2.20),P<0.001],there was statistically significance. CONCLUSIONS:Agomelatine is effective in the treatment of depression patients in acute phase. However,due to the limit of methodological quality and sample size,it remains to be further verified with more rigorously designed and long-term follow-up of large-scale RCT.