KDM6A-SND1 interaction maintains genomic stability by protecting the nascent DNA and contributes to cancer chemoresistance.

Genomic instability is one of the hallmarks of cancer. While loss of histone demethylase KDM6A increases the risk of tumorigenesis, its specific role in maintaining genomic stability remains poorly understood. Here, we propose a mechanism in which KDM6A maintains genomic stability independently on its demethylase activity. This occurs through its interaction with SND1, resulting in the establishment of a protective chromatin state that prevents replication fork collapse by recruiting of RPA and Ku70 to nascent DNA strand. Notably, KDM6A-SND1 interaction is up-regulated by KDM6A SUMOylation, while KDM6AK90A mutation almost abolish the interaction. Loss of KDM6A or SND1 leads to increased enrichment of H3K9ac and H4K8ac but attenuates the enrichment of Ku70 and H3K4me3 at nascent DNA strand. This subsequently results in enhanced cellular sensitivity to genotoxins and genomic instability. Consistent with these findings, knockdown of KDM6A and SND1 in esophageal squamous cell carcinoma (ESCC) cells increases genotoxin sensitivity. Intriguingly, KDM6A H101D & P110S, N1156T and D1216N mutations identified in ESCC patients promote genotoxin resistance via increased SND1 association. Our finding provides novel insights into the pivotal role of KDM6A-SND1 in genomic stability and chemoresistance, implying that targeting KDM6A and/or its interaction with SND1 may be a promising strategy to overcome the chemoresistance.

HIF-1α in cartilage homeostasis, apoptosis, and glycolysis in mice with steroid-induced osteonecrosis of the femoral head.

With the prevalence of coronavirus disease 2019, the administration of glucocorticoids (GCs) has become more widespread. Treatment with high-dose GCs leads to a variety of problems, of which steroid-induced osteonecrosis of the femoral head (SONFH) is the most concerning. Since hypoxia-inducible factor 1α (HIF-1α) is a key factor in cartilage development and homeostasis, it may play an important role in the development of SONFH. In this study, SONFH models were established using methylprednisolone (MPS) in mouse and its proliferating chondrocytes to investigate the role of HIF-1α in cartilage differentiation, extracellular matrix (ECM) homeostasis, apoptosis and glycolysis in SONFH mice. The results showed that MPS successfully induced SONFH in vivo and vitro, and MPS-treated cartilage and chondrocytes demonstrated disturbed ECM homeostasis, significantly increased chondrocyte apoptosis rate and glycolysis level. However, compared with normal mice, not only the expression of genes related to collagens and glycolysis, but also chondrocyte apoptosis did not demonstrate significant differences in mice co-treated with MPS and HIF-1α inhibitor. And the effects observed in HIF-1α activator-treated chondrocytes were similar to those induced by MPS. And HIF-1α degraded collagens in cartilage by upregulating its downstream target genes matrix metalloproteinases. The results of activator/inhibitor of endoplasmic reticulum stress (ERS) pathway revealed that the high apoptosis rate induced by MPS was related to the ERS pathway, which was also affected by HIF-1α. Furthermore, HIF-1α affected glucose metabolism in cartilage by increasing the expression of glycolysis-related genes. In conclusion, HIF-1α plays a vital role in the pathogenesis of SONFH by regulating ECM homeostasis, chondrocyte apoptosis, and glycolysis.

Image Guided Energy Ablation for Palliation of Painful Bony Metastases - A Systematic Review.

PURPOSE: To analyze the effectiveness of image-guided energy ablation techniques with and without concurrent therapies in providing palliative pain relief in patients with bone metastases. MATERIALS AND METHODS: OVID Embase, OVID Medline, and Pubmed were searched from inception to April 14th, 2023 using search terms relating to bone lesions and MeSH terms regarding ablation therapy. English peer-reviewed primary articles were included that reported pain scores following image-guided energy-based ablation of bone metastases. Exclusion criteria included 1) non-palliative treatment, 2) pain scores associated with specific treatment modalities not reported, and 3) non-metastatic bone lesions. Mean percentage reduction in pain score was calculated. RESULTS: 1396 studies were screened and 54 were included. All but one study demonstrated decreased pain scores at final follow-up. Mean reduction in pain scores at final follow-up were 49% for radiofrequency ablation (RFA), 58% for radiofrequency ablation and adjunct (RFA-A), 54% for cryoablation (CA), 72% for cryoablation and adjunct (CA-A), 48% for microwave ablation (MWA), 81% for microwave ablation and adjunct (MWA-A), and 64% for high-intensity focused ultrasound (HIFU). Post-procedural adverse event rates were 4.9% for RFA, 34.8% for RFA-A, 9.6% for CA, 12.0% for CA-A, 48.9% for MWA, 33.5% for MWA-A and 17.0% for HIFU. CONCLUSION: Image-guided energy ablation demonstrated consistently strong reduction in pain across all modalities, with variable post-procedural adverse event rates. Due to heterogeneity of included studies, quantitative analysis was not appropriate. Future primary research should focus on creating consistent prospective studies with established statistical power, explicit documentation and comparison to other techniques.

Targeting metabolism to enhance immunotherapy within tumor microenvironment.

Cancer metabolic reprogramming has been considered an emerging hallmark in tumorigenesis and the antitumor immune response. Like cancer cells, immune cells within the tumor microenvironment or premetastatic niche also undergo extensive metabolic reprogramming, which profoundly impacts anti-tumor immune responses. Numerous evidence has illuminated that immunosuppressive TME and the metabolites released by tumor cells, including lactic acid, Prostaglandin E2 (PGE2), fatty acids (FAs), cholesterol, D-2-Hydroxyglutaric acid (2-HG), adenosine (ADO), and kynurenine (KYN) can contribute to CD8+ T cell dysfunction. Dynamic alterations of these metabolites between tumor cells and immune cells can similarly initiate metabolic competition in the TME, leading to nutrient deprivation and subsequent microenvironmental acidosis, which impedes immune response. This review summarizes the new landscape beyond the classical metabolic pathways in tumor cells, highlighting the pivotal role of metabolic disturbance in the immunosuppressive microenvironment, especially how nutrient deprivation in TME leads to metabolic reprogramming of CD8+ T cells. Likewise, it emphasizes the current therapeutic targets or strategies related to tumor metabolism and immune response, providing therapeutic benefits for tumor immunotherapy and drug development in the future. Cancer metabolic reprogramming has been considered an emerging hallmark in tumorigenesis and the antitumor immune response. Dynamic alterations of metabolites between tumor cells and immune cells initiate metabolic competition in the TME, leading to nutrient deprivation and subsequent microenvironmental acidosis, which impedes immune response.

Research on Data Poisoning Attack against Smart Grid Cyber-Physical System Based on Edge Computing.

Data poisoning attack is a well-known attack against machine learning models, where malicious attackers contaminate the training data to manipulate critical models and predictive outcomes by masquerading as terminal devices. As this type of attack can be fatal to the operation of a smart grid, addressing data poisoning is of utmost importance. However, this attack requires solving an expensive two-level optimization problem, which can be challenging to implement in resource-constrained edge environments of the smart grid. To mitigate this issue, it is crucial to enhance efficiency and reduce the costs of the attack. This paper proposes an online data poisoning attack framework based on the online regression task model. The framework achieves the goal of manipulating the model by polluting the sample data stream that arrives at the cache incrementally. Furthermore, a point selection strategy based on sample loss is proposed in this framework. Compared to the traditional random point selection strategy, this strategy makes the attack more targeted, thereby enhancing the attack's efficiency. Additionally, a batch-polluting strategy is proposed in this paper, which synchronously updates the poisoning points based on the direction of gradient ascent. This strategy reduces the number of iterations required for inner optimization and thus reduces the time overhead. Finally, multiple experiments are conducted to compare the proposed method with the baseline method, and the evaluation index of loss over time is proposed to demonstrate the effectiveness of the method. The results show that the proposed method outperforms the existing baseline method in both attack effectiveness and overhead.

Notch-RBPJ Pathway for the Differentiation of Bone Marrow Mesenchymal Stem Cells in Femoral Head Necrosis.

Femoral head necrosis (FHN) is a common leg disease in broilers, resulting in economic losses in the poultry industry. The occurrence of FHN is closely related to the decrease in the number of bone marrow mesenchymal stem cells (BMSCs) and the change in differentiation direction. This study aimed to investigate the function of differentiation of BMSCs in the development of FHN. We isolated and cultured BMSCs from spontaneous FHN-affected broilers and normal broilers, assessed the ability of BMSCs into three lineages by multiple staining methods, and found that BMSCs isolated from FHN-affected broilers demonstrated enhanced lipogenic differentiation, activated Notch-RBPJ signaling pathway, and diminished osteogenic and chondrogenic differentiation. The treatment of BMSCs with methylprednisolone (MP) revealed a significant decrease in the expressions of Runx2, BMP2, Col2a1 and Aggrecan, while the expressions of p-Notch1/Notch1, Notch2 and RBPJ were increased significantly. Jagged-1 (JAG-1, Notch activator)/DAPT (γ-secretase inhibitor) could promote/inhibit the osteogenic or chondrogenic ability of MP-treated BMSCs, respectively, whereas the differentiation ability of BMSCs was restored after transfection with si-RBPJ. The above results suggest that the Notch-RBPJ pathway plays important role in FHN progression by modulating the osteogenic and chondrogenic differentiation of BMSCs.

Psychrophilic phage VSW-3 RNA polymerase reduces both terminal and full-length dsRNA byproducts in in vitro transcription.

RNA research and applications are underpinned by in vitro transcription (IVT), but RNA impurities resulting from the enzymatic reagents severely impede downstream applications. To improve the stability and purity of synthesized RNA, we have characterized a novel single-subunit RNA polymerase (RNAP) encoded by the psychrophilic phage VSW-3 from a plateau lake. The VSW-3 RNAP is capable of carrying out in vitro RNA synthesis at low temperatures (4-25°C). Compared to routinely used T7 RNAP, VSW-3 RNAP provides a similar yield of transcripts but is insensitive to class II transcription terminators and synthesizes RNA without redundant 3'-cis extensions. More importantly, through dot-blot detection with the J2 monoclonal antibody, we found that the RNA products synthesized by VSW-3 RNAP contained a much lower amount of double-stranded RNA byproducts (dsRNA), which are produced by transcription from both directions and are significant in T7 RNAP IVT products. Taken together, the VSW-3 RNAP almost eliminates both terminal loop-back dsRNA and full-length dsRNA in IVT and thus is especially advantageous for producing RNA for in vivo use.

Downregulation of miR-30b-5p Facilitates Chondrocyte Hypertrophy and Apoptosis via Targeting Runx2 in Steroid-Induced Osteonecrosis of the Femoral Head.

As a widely used steroid hormone medicine, glucocorticoids have the potential to cause steroid-induced osteonecrosis of the femoral head (SONFH) due to mass or long-term use. The non-coding RNA hypothesis posits that they may contribute to the destruction and dysfunction of cartilages as a possible etiology of SONFH. MiR-30b-5p was identified as a regulatory factor in cartilage degeneration caused by methylprednisolone (MPS) exposure in our study through cell transfection. The luciferase reporter assay confirmed that miR-30b-5p was downregulated and runt-related transcription factor 2 (Runx2) was mediated by miR-30b-5p. The nobly increased expression of matrix metallopeptidase 13 (MMP13) and type X collagen (Col10a1) as Runx2 downstream genes contributed to the hypertrophic differentiation of chondrocytes, and the efficiently upregulated level of matrix metallopeptidase 9 (MMP9) may trigger chondrocyte apoptosis with MPS treatments. The cell transfection experiment revealed that miR-30b-5p inhibited chondrocyte hypertrophy and suppressed MPS-induced apoptosis. As a result, our findings showed that miR-30b-5p modulated Runx2, MMP9, MMP13, and Col10a1 expression, thereby mediating chondrocyte hypertrophic differentiation and apoptosis during the SONFH process. These findings revealed the mechanistic relationship between non-coding RNA and SONFH, providing a comprehensive understanding of SONFH and other bone diseases.

Bisphosphonate-Conjugated Photo-Crosslinking Polyanionic Hyaluronic Acid Microbeads for Controlled BMP2 Delivery and Enhanced Bone Formation Efficacy.

In this study, we designed bisphosphonate-conjugated polyanionic hyaluronic acid (HA) microbeads (MBs) for the controlled delivery of bone morphogenetic protein 2 (BMP2). MBs were prepared via the photo-crosslinking of bisphosphonate (alendronate)-conjugated methacrylated HA (Alen-MHA). The polyanionic Alen-MHA MBs actively absorbed cationic BMP2 up to 91.0% of the loading efficacy and displayed a sustained release of BMP2 for 10 days. BMP2/Alen-MHA MBs induced osteogenic-related genes in cellular experiments and showed the highly increased bone formation efficacy in thigh muscle injection and rat spinal fusion animal models. Thus, BMP2/Alen-MHA MBs provide a promising opportunity to improve the delivery efficiency of BMP2.

Radio Frequency Fingerprint-Based Intelligent Mobile Edge Computing for Internet of Things Authentication.

In this paper, a light-weight radio frequency fingerprinting identification (RFFID) scheme that combines with a two-layer model is proposed to realize authentications for a large number of resource-constrained terminals under the mobile edge computing (MEC) scenario without relying on encryption-based methods. In the first layer, signal collection, extraction of RF fingerprint features, dynamic feature database storage, and access authentication decision are carried out by the MEC devices. In the second layer, learning features, generating decision models, and implementing machine learning algorithms for recognition are performed by the remote cloud. By this means, the authentication rate can be improved by taking advantage of the machine-learning training methods and computing resource support of the cloud. Extensive simulations are performed under the IoT application scenario. The results show that the novel method can achieve higher recognition rate than that of traditional RFFID method by using wavelet feature effectively, which demonstrates the efficiency of our proposed method.

Deep-Learning-Based Physical Layer Authentication for Industrial Wireless Sensor Networks.

In this paper, a deep learning (DL)-based physical (PHY) layer authentication framework is proposed to enhance the security of industrial wireless sensor networks (IWSNs). Three algorithms, the deep neural network (DNN)-based sensor nodes' authentication method, the convolutional neural network (CNN)-based sensor nodes' authentication method, and the convolution preprocessing neural network (CPNN)-based sensor nodes' authentication method, have been adopted to implement the PHY-layer authentication in IWSNs. Among them, the improved CPNN-based algorithm requires few computing resources and has extremely low latency, which enable a lightweight multi-node PHY-layer authentication. The adaptive moment estimation (Adam) accelerated gradient algorithm and minibatch skill are used to accelerate the training of the neural networks. Simulations are performed to evaluate the performance of each algorithm and a brief analysis of the application scenarios for each algorithm is discussed. Moreover, the experiments have been performed with universal software radio peripherals (USRPs) to evaluate the authentication performance of the proposed algorithms. Due to the trainings being performed on the edge sides, the proposed method can implement a lightweight authentication for the sensor nodes under the edge computing (EC) system in IWSNs.

Clustering Based Physical-Layer Authentication in Edge Computing Systems with Asymmetric Resources.

In this paper, we propose a clustering based physical-layer authentication scheme (CPAS) to overcome the drawback of traditional cipher-based authentication schemes that suffer from heavy costs and are limited by energy-constrained intelligent devices. CPAS is a novel cross-layer secure authentication approach for edge computing system with asymmetric resources. The CPAS scheme combines clustering and lightweight symmetric cipher with physical-layer channel state information to provide two-way authentication between terminals and edge devices. By taking advantage of temporal and spatial uniqueness in physical layer channel responses, the non-cryptographic physical layer authentication techniques can achieve fast authentication. The lightweight symmetric cipher initiates user authentication at the start of a session to establish the trust connection. Based on theoretical analysis, the CPAS scheme is secure and simple, but there is no trusted party, while it can also resist small integer attacks, replay attacks, and spoofing attacks. Besides, experimental results show that the proposed scheme can boost the total success rate of access authentication and decrease the data frame loss rate, without notable increase in authentication latencies.

[Regulatory effect and relevant mechanisms of fraction from heat-clearing and detoxifying herb couplet on macrophage M1/M2 phenotypes].

To explore the regulatory effect and relevant mechanisms of the fraction of Hedyotis diffusa and Scutellaria barbata herb couple(YDW11) on polarization of macrophage between M1/M2 phenotypes.RAW264.7 cells were induced with LPS/IFN-γ or IL-4/IL-13 to establish M1 or M2 macrophage cell model. MTT assay was used to measure the cell cytotoxicity of YDW11. Griess reaction was used to detect the changes of nitrite accumulation in the cell supernatant. Trans-well assay was used to measure the migration capability. QRT-PCR was used to assay mRNA expressions of iNOS, IL-1ß, Arg-1 and MR. Western blot was used to detect the effect of YDW11 on iNOS and Arg-1 protein expressions. Taqman MicroRNA RT-PCR was used to detect the effect of YDW11 on miR155 expression under M1 and M2 phenotype conditions. In addition, MS-UPLC assay was carried out to identify the constituents in YDW11. The results showed that the ethyl acetate of H. diffusa and S. barbata extracted in 1:1 ratio with water (YDW11) showed the activity in suppressing the nitrite content in M1 macrophages without cytotoxicity. YDW11 also inhibited the migration of breast cancer cells with the help of M2 macrophages by blocking their polarization towards M2. YDW11 decreased iNOS, IL-1ß, Arg-1and MR mRNA expressions and iNOS and Arg-1 protein expressions. YDW11 down-regulated miR155 expression in M1 phenotype, and up-regulated miR155 expression in M2 phenotype. Based on MS-UPLC,four compounds were identified in YDW11, including 4'-hydroxyacetophenone, scutellarin, luteolin and apigenin. YDW11 inhibited M1/M2 phenotypes of macrophages by regulating the expression of miR155.

Influence of an aniline supplement on the stability of aerobic granular sludge.

In order to evaluate the stability of aerobic granules in a toxic environment, this study discussed the influence of an aniline supplement on the properties and microbial community of aerobic granules. In the early stages of sequencing batch reactor (SBR) operation, an aniline supplement slightly affected the properties of the aerobic granules (strength, growth rate, SVI and so on). This effect was thereafter removed because of a change in the microbial community and the structure of aerobic granules: with the present of aniline, microbes with biodegradation ability appeared and gathered in the aerobic granules and the aerobic granules densified and settled faster as their SVI decreased to 35 mL/g and settling velocity increased to 41.56 m/h. When a synthetic waste water containing acetate as carbon source was used as influent, aniline (10-500 mg/L) could be degraded in 6 h, at a rate as high as 37.5 mg aniline/(L·h), with a removal rate in excess of 90%, while the effluent COD fell below 100 mg/L from the initial about 2000 mg/L. The aerobic granules cultured by acetate were compact, stable and resistant to aniline.

Dielectric engineered graphene transistors for high-performance near-infrared photodetection.

Graphene, known for its ultrahigh carrier mobility and broadband optical absorption, holds significant potential in optoelectronics. However, the carrier mobility of graphene on silicon substrates experienced a marked decrease due to surface roughness, phonon scattering affects. Here we report carrier mobility enhancement of graphene dielectric engineering. Through the fabrication of devices utilizing Si/SiO2/Al2O3/graphene layers and subsequent electrical characterization, our findings illustrate the navigable nature of the Al2O3 dielectric layer is navigable for reducing the SiO2 phonon scattering and increasing graphene's carrier mobility by up to ∼8000 cm2V-1s-1. Furthermore, the improvement in carrier mobility of graphene has been utilized in the hybrid near-infrared photodetector, resulting in outstanding responsivity of ∼400 AW-1, detectivity of ∼2.2 ✕ 1011 Jones in the graphene/Ag2Te detector. Our study establishes pathways for the seamless integration of graphene or other 2D materials within the standard CMOS processes, thereby facilitating the fabrication of advanced optoelectronic devices.

Dbl family RhoGEFs in cancer: different roles and targeting strategies.

Small Ras homologous guanosine triphosphatase (Rho GTPase) family proteins are highly associated with tumorigenesis and development. As intrinsic exchange activity regulators of Rho GTPases, Rho guanine nucleotide exchange factors (RhoGEFs) have been demonstrated to be closely involved in tumor development and received increasing attention. They mainly contain two families: the diffuse B-cell lymphoma (Dbl) family and the dedicator of cytokinesis (Dock) family. More and more emphasis has been paid to the Dbl family members for their abnormally high expression in various cancers and their correlation to poor prognosis. In this review, the common and distinctive structures of Dbl family members are discussed, and their roles in cancer are summarized with a focus on Ect2, Tiam1/2, P-Rex1/2, Vav1/2/3, Trio, KALRN, and LARG. Significantly, the strategies targeting Dbl family RhoGEFs are highlighted as novel therapeutic opportunities for cancer.

Ferroptosis regulation by methylation in cancer.

Epigenetic regulation plays a critical role in cancer development and progression. Methylation is an important epigenetic modification that influences gene expression by adding a methyl group to nucleic acids and proteins. Ferroptosis is a new form of regulated cell death triggered by the accumulation of iron and lipid peroxidation. Emerging evidence have shown that methylation regulation plays a significant role in the regulation of ferroptosis in cancer. This review aims to explore the methylation regulation of ferroptosis in cancer, including reactive oxygen species and iron bio-logical activity, amino acid and lipid metabolism, and drugs interaction. The findings of this review may provide new insights and strategies for the prevention and treatment of cancer.

FXR agonist GW4064 enhances anti-PD-L1 immunotherapy in colorectal cancer.

Colorectal cancer (CRC) is one of the top three malignant tumors in terms of morbidity, and the limited efficacy of existing therapies urges the discovery of potential treatment strategies. Immunotherapy gradually becomes a promising cancer treatment method in recent decades; however, less than 10% of CRC patients could really benefit from immunotherapy. It is pressing to explore the potential combination therapy to improve the immunotherapy efficacy in CRC patients. It is reported that Farnesoid X receptor (FXR) is deficiency in CRC and associated with immunity. Herein, we found that GW4064, a FXR agonist, could induce apoptosis, block cell cycle, and mediate immunogenic cell death (ICD) of CRC cells in vitro. Disappointingly, GW4064 could not suppress the growth of CRC tumors in vivo. Further studies revealed that GW4064 upregulated PD-L1 expression in CRC cells via activating FXR and MAPK signaling pathways. Gratifyingly, the combination of PD-L1 antibody with GW4064 exhibited excellent anti-tumor effects in CT26 xenograft models and increased CD8+ T cells infiltration, with 33% tumor bearing mice cured. This paper illustrates the potential mechanisms of GW4064 to upregulate PD-L1 expression in CRC cells and provides important data to support the combination therapy of PD-L1 immune checkpoint blockade with FXR agonist for CRC patients.

Assessment of Hepatic Lesions After non-Thermal Tumor Ablation by Irreversible Electroporation in a Pig Model.

Irreversible electroporation (IRE) is a non-thermal and minimal invasive modality to ablate pathologic lesions such as hepatic tumors. Histological analysis of the initial lesions after IRE can help predict ablation efficacy. We aimed to investigate the histological characteristics of early hepatic lesions after IRE application using animal models. IRE (1500 V/cm, a pulse length of 100 µs, 60 or 90 pulses) was applied to the liver of miniature pigs. H&E and TUNEL staining were performed and analyzed. Ablated zones of pig liver were discolored and separated from the normal zone after IRE. Histologic characteristics of ablation zones included preserved hepatic lobular architecture with a unique hexagonal-like structure. Apoptotic cells were detected, and sinusoidal dilatation and blood congestion were observed, but hepatic arteries and bile ducts were intact around the ablation zones. The early lesions obtained by delivering monophasic square wave pulses through needle electrodes reflected typical histological changes induced by IRE. Therefore, it was found that the histological assessment of the early hepatic lesion after IRE can be utilized to predict the IRE ablation effect.

Epidemiological features and trends in the mortality rates of 10 notifiable respiratory infectious diseases in China from 2004 to 2020: Based on national surveillance.

Objectives: The aim of this study is to describe, visualize, and compare the trends and epidemiological features of the mortality rates of 10 notifiable respiratory infectious diseases in China from 2004 to 2020. Setting: Data were obtained from the database of the National Infectious Disease Surveillance System (NIDSS) and reports released by the National and local Health Commissions from 2004 to 2020. Spearman correlations and Joinpoint regression models were used to quantify the temporal trends of RIDs by calculating annual percentage changes (APCs) in the rates of mortality. Results: The overall mortality rate of RIDs was stable across China from 2004 to 2020 (R = -0.38, P = 0.13), with an APC per year of -2.2% (95% CI: -4.6 to 0.3; P = 0.1000). However, the overall mortality rate of 10 RIDs in 2020 decreased by 31.80% (P = 0.006) compared to the previous 5 years before the COVID-19 pandemic. The highest mortality occurred in northwestern, western, and northern China. Tuberculosis was the leading cause of RID mortality, and mortality from tuberculosis was relatively stable throughout the 17 years (R = -0.36, P = 0.16), with an APC of -1.9% (95% CI -4.1 to 0.4, P = 0.1000). Seasonal influenza was the only disease for which mortality significantly increased (R = 0.73, P = 0.00089), with an APC of 29.70% (95% CI 16.60-44.40%; P = 0.0000). The highest yearly case fatality ratios (CFR) belong to avian influenza A H5N1 [687.5 per 1,000 (33/48)] and epidemic cerebrospinal meningitis [90.5748 per 1,000 (1,010/11,151)]. The age-specific CFR of 10 RIDs was highest among people over 85 years old [13.6551 per 1,000 (2,353/172,316)] and was lowest among children younger than 10 years, particularly in 5-year-old children [0.0552 per 1,000 (58/1,051,178)]. Conclusions: The mortality rates of 10 RIDs were relatively stable from 2004 to 2020 with significant differences among Chinese provinces and age groups. There was an increased mortality trend for seasonal influenza and concerted efforts are needed to reduce the mortality rate of seasonal influenza in the future.