Objective:To analyze the prevalence, disease burden of type 2 diabetes mellitus (T2DM) and risk factors in China from 1990 to 2021 predict future trends and provide evidence for the development of precise prevention and control policies.Methods:Based on the Global Burden of Disease Study 2021 database, the data on disease burden and risk factors of T2DM in China and in the world from 1990 to 2021 were extracted. Age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized disability adjusted life year rate (ASDR) were used to evaluate the prevalence and disease burden of T2DM. Joinpoint regression models were used to calculate the average annual percentage change (AAPC) to evaluate change trends. Bayesian age-period-cohort analysis models were constructed to predict the prevalence and disease burden of T2DM from 2022 to 2046.Results:In 2021, the ASIR, ASPR, and ASDR of T2DM in China were 308.37/100 000, 10 626.04/100 000, and 1 050.47/100 000, which increased by 12.92% (AAPC=0.388%, P=0.009), 61.60% (AAPC=1.546%, P<0.001), and 25.26% (AAPC=0.756%, P<0.001) compared with 1990, respectively. However, the ASMR dropped to 15.84/100 000, a decrease of 4.75% (AAPC=0.122%, P=0.154). The prediction results showed that the ASPR and ASDR of T2DM in China would continue to increase steadily from 2022 to 2046 , which would increase to 19 732.71/100 000 and 1 941.25/100 000 in 2046, while the ASIR and ASMR would decrease to 258.35/100 000 and 11.49/100 000 in 2046. It is predicted that the annual ASIR, ASPR, ASMR, and ASDR of T2DM in China would remain lower than the global levels from 2022 to 2046. The disease burden level of T2DM was higher in men and the elderly in China. Based on data from China and the world, metabolic factors (high FPG glucose and high BMI) are consistently the main risk factors leading to the disease burden of T2DM, and ambient particulate matter pollution is the main environmental factor. While the global disease burden of T2DM attributed to smoking has become stabilized, China still maintains a relatively high level and the level is predicted to keep rising in the future. Conclusions:The disease burden of T2DM continues to increase in China, posing significant challenges for prevention and treatment. The prevention and intervention strategies should focus on the key modifiable risk factors.

Objective:To analyze the prevalence, disease burden of type 2 diabetes mellitus (T2DM) and risk factors in China from 1990 to 2021 predict future trends and provide evidence for the development of precise prevention and control policies.Methods:Based on the Global Burden of Disease Study 2021 database, the data on disease burden and risk factors of T2DM in China and in the world from 1990 to 2021 were extracted. Age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized disability adjusted life year rate (ASDR) were used to evaluate the prevalence and disease burden of T2DM. Joinpoint regression models were used to calculate the average annual percentage change (AAPC) to evaluate change trends. Bayesian age-period-cohort analysis models were constructed to predict the prevalence and disease burden of T2DM from 2022 to 2046.Results:In 2021, the ASIR, ASPR, and ASDR of T2DM in China were 308.37/100 000, 10 626.04/100 000, and 1 050.47/100 000, which increased by 12.92% (AAPC=0.388%, P=0.009), 61.60% (AAPC=1.546%, P<0.001), and 25.26% (AAPC=0.756%, P<0.001) compared with 1990, respectively. However, the ASMR dropped to 15.84/100 000, a decrease of 4.75% (AAPC=0.122%, P=0.154). The prediction results showed that the ASPR and ASDR of T2DM in China would continue to increase steadily from 2022 to 2046 , which would increase to 19 732.71/100 000 and 1 941.25/100 000 in 2046, while the ASIR and ASMR would decrease to 258.35/100 000 and 11.49/100 000 in 2046. It is predicted that the annual ASIR, ASPR, ASMR, and ASDR of T2DM in China would remain lower than the global levels from 2022 to 2046. The disease burden level of T2DM was higher in men and the elderly in China. Based on data from China and the world, metabolic factors (high FPG glucose and high BMI) are consistently the main risk factors leading to the disease burden of T2DM, and ambient particulate matter pollution is the main environmental factor. While the global disease burden of T2DM attributed to smoking has become stabilized, China still maintains a relatively high level and the level is predicted to keep rising in the future. Conclusions:The disease burden of T2DM continues to increase in China, posing significant challenges for prevention and treatment. The prevention and intervention strategies should focus on the key modifiable risk factors.

Remarkable improvement relative to traditional approaches in the treatment of hematological malignancies by chimeric antigen receptor (CAR) T-cell therapy has promoted sequential approvals of eight commercial CAR T products within last 5 years. Although CAR T cells' productization is now rapidly boosting their extensive clinical application in real-world patients, the limitation of their clinical efficacy and related toxicities inspire further optimization of CAR structure and substantial development of innovative trials in various scenarios. Herein, we first summarized the current status and major progress in CAR T therapy for hematological malignancies, then described crucial factors which possibly compromise the clinical efficacies of CAR T cells, such as CAR T cell exhaustion and loss of antigen, and finally, we discussed the potential optimization strategies to tackle the challenges in the field of CAR T therapy.
Humans ; Receptors, Chimeric Antigen/therapeutic use* ; Immunotherapy, Adoptive ; Hematologic Neoplasms/therapy* ; Treatment Outcome

Objective Drug resistance is the main cause of chemotherapy failure in hepatocellular carcinoma (HCC), and thioredoxin reductase 1 (TXNRD1), as a major influencing factor for reactive oxygen species (ROS) metabolism, has been proven to be associated with the poor prognosis of patients with HCC. This study aims to explore the role of TXNRD1 in the mechanism of multidrug resistance in HCC. Methods BEL/FU cells in BEL-7402 cell line were selected as the multidrug-resistant cell line. The siRNA was used for the intervention of TXNRD1 expression; quantitative real-time PCR and Western blotting were used to measure the expression of TXNRD1; CCK-8 assay and flow cytometry were used to evaluate the effect of TXNRD1 on hepatocyte ROS accumulation, resistance to 5-fluorouracil (5-Fu) and doxorubicin (DOX), and apoptosis in vitro; a xenograft tumor model was established to investigate the effect of auranofin (AUR) on drug resistance in vivo. The two-independent-samples t test was used for comparison of continuous data between two groups. Results As a multidrug-resistant HCC cell line, BEL/Fu showed high mRNA and protein expression levels of TXNRD1 (both P < 0.05). Compared with 5-Fu or DOX treatment alone, the TXNRD1 inhibitor AUR combined with 5-Fu or DOX had had a significant reduction in the number of colony formation ( P < 0.01) and a significant increase in apoptosis ratio ( P < 0.001). The ROS scavenger N-acetylcysteine (NAC) significantly weakened the effect of TXNRD1 knockdown by siRNA on the drug resistance of BEL/Fu cells, and the application of NAC effectively reduced the apoptosis ratio of cells after siRNA interference ( P < 0.001). Animal experiments also confirmed that compared with the nude mice treated with 5-Fu alone, the nude mice treated with 5-Fu and AUR had a significantly lower tumor mass ( P < 0.001) and a significantly smaller tumor volume ( P < 0.001). Conclusion TXNRD1 plays an important role in the drug resistance of HCC, and inhibition of its level in cells can effectively improve drug resistance. As a TXNRD1 inhibitor, AUR has great application prospects in the multimodality therapy for HCC.

The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to detachment of lamina-associated domains (LADs) from the nuclear periphery accompanied with global chromatin redistribution and decompaction. Consequently, the inter-chromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, chromatin compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.
Chromatin ; Chromosomes ; Genome ; Humans ; Lamin Type B/genetics*

Hepatocellular carcinoma is one of the common causes of tumor-related death, and it has high morbidity and mortality rates in China. Recent studies have shown that platelets are closely associated with the development of hepatocellular carcinoma. Literature review shows that platelets not only participate in hemostasis, but also act on liver cells and tumor microenvironment, promote the formation of new blood vessels, and participate in the development and progression of hepatocellular carcinoma as a cell mediator through immune response and other pathways. In addition, platelets and their derivatives can be used as potential therapeutic targets for hepatocellular carcinoma. Therefore, antiplatelet therapy is expected to become a new adjuvant strategy for the treatment of hepatocellular carcinoma, which has important clinical significance.

Objective:To explore the occurrence and influencing factors of serum uric acid elevation in patients with coronavirus disease 2019 (COVID-19) treated with favipiravir.Methods:Medical records of patients with COVID-19 who were hospitalized in Beijing Ditan Hospital between June 1, 2020 and June 30, 2021 and treated with the 5- or 10-day regimen of favipiravir were collected and retrospectively analyzed. After favipiravir withdrawal, if the elevation in serum uric acid was ≥30% of baseline level, it was defined as serum uric acid elevation. Then patients were divided into serum uric acid elevation group and non-serum uric acid elevation group. The clinical characteristics such as gender, age, body mass index, comorbidities, smoking and drinking behavior, COVID-19 grade, favipiravir regimen, and serum uric acid level and renal function before treatment in patients between the 2 groups were compared. Influencing factors of favipiravir-associated serum uric acid elevation was analyzed using multivariate logistic regression method.Results:A total of 179 patients were included in the analysis, including 104 (58.1%) males and 75 (41.9%) females, aged from 19 to 70 years with a median age of 43 years. The level of serum uric acid in 179 patients after favipiravir treatment was significantly higher than before [(451±119) μmol/L vs. (332±94) μmol/L, P<0.001]. The change rate of serum uric acid from baseline level ranged from -57.1% to 157.8% with the median of 38.6%. The elevation in serum uric acid of ≥ 30% of baseline level occurred in 108 (60.3%) patients. The incidences of serum uric acid elevation in patients treated with 5-day and 10-day regimens of favipiravir were 46.8% (36/77) and 70.6% (72/102), respectively, and the difference between them was significant ( P=0.001). Multivariate logistic regression analysis showed that body mass index 24.0 to <28.0 kg/m 2 ( OR=3.109, 95 %CI: 1.209-7.994, P=0.019) and 10-day regimen of favipiravir ( OR=3.017, 95 %CI: 1.526-5.964, P=0.001) were independent risk factors for favipiravir-associated serum uric acid elevation. Conclusions:More than half of COVID-19 patients treated with favipiravir can develop serum uric acid elevation. Overweight and 10-day regimen of favipiravir are independent risk factors for serum uric acid elevation in patients.

Objective:To explore the occurrence and influencing factors of serum uric acid elevation in patients with coronavirus disease 2019 (COVID-19) treated with favipiravir.Methods:Medical records of patients with COVID-19 who were hospitalized in Beijing Ditan Hospital between June 1, 2020 and June 30, 2021 and treated with the 5- or 10-day regimen of favipiravir were collected and retrospectively analyzed. After favipiravir withdrawal, if the elevation in serum uric acid was ≥30% of baseline level, it was defined as serum uric acid elevation. Then patients were divided into serum uric acid elevation group and non-serum uric acid elevation group. The clinical characteristics such as gender, age, body mass index, comorbidities, smoking and drinking behavior, COVID-19 grade, favipiravir regimen, and serum uric acid level and renal function before treatment in patients between the 2 groups were compared. Influencing factors of favipiravir-associated serum uric acid elevation was analyzed using multivariate logistic regression method.Results:A total of 179 patients were included in the analysis, including 104 (58.1%) males and 75 (41.9%) females, aged from 19 to 70 years with a median age of 43 years. The level of serum uric acid in 179 patients after favipiravir treatment was significantly higher than before [(451±119) μmol/L vs. (332±94) μmol/L, P<0.001]. The change rate of serum uric acid from baseline level ranged from -57.1% to 157.8% with the median of 38.6%. The elevation in serum uric acid of ≥ 30% of baseline level occurred in 108 (60.3%) patients. The incidences of serum uric acid elevation in patients treated with 5-day and 10-day regimens of favipiravir were 46.8% (36/77) and 70.6% (72/102), respectively, and the difference between them was significant ( P=0.001). Multivariate logistic regression analysis showed that body mass index 24.0 to <28.0 kg/m 2 ( OR=3.109, 95 %CI: 1.209-7.994, P=0.019) and 10-day regimen of favipiravir ( OR=3.017, 95 %CI: 1.526-5.964, P=0.001) were independent risk factors for favipiravir-associated serum uric acid elevation. Conclusions:More than half of COVID-19 patients treated with favipiravir can develop serum uric acid elevation. Overweight and 10-day regimen of favipiravir are independent risk factors for serum uric acid elevation in patients.