Objective To investigate the role and potential mechanism of secreted phosphoprotein 1 (SPP1)⁺ macrophages in the formation of chronic renal allograft fibrosis. Methods The expression features of SPP1⁺ macrophages in renal allografts of chronic allograft dysfunction (CAD) patients were analyzed based on single-cell transcriptome data of renal tissues from patients with CAD. Transcription factor VIPER analysis and DoRothEA transcription factor activity analysis were performed on the single-cell transcriptome data. Renal tissue samples were collected from kidney transplant recipients, including the CAD group (n=5) and the non-renal allograft fibrosis group (CTL group, n=5). A mouse model of chronic allograft rejection was established and divided into the allogeneic kidney transplantation group (CAD group, n=3) and the syngeneic kidney transplantation group (SYN group, n=3). Hematoxylin-eosin staining was used to detect renal tissue injury in mice, and Masson staining was used to detect renal tissue fibrosis. Immunofluorescence staining was performed to detect SPP1 expression in renal tissues of transplant recipients and mouse renal allografts. Bone marrow-derived macrophages (BMDMs) were extracted from mice and subjected to hypoxia stimulation. The expression of hypoxia-inducible factor (HIF)-1α and SPP1 was detected by Western blot, and SPP1 expression was detected by flow cytometry. BMDMs were transfected with HIF-1α overexpression plasmid and HIF-1α small interfering RNA (siRNA) followed by hypoxia intervention, and the expression of HIF-1α and SPP1 was detected by Western blot. Mouse aortic endothelial cells (MAECs) were co-cultured with the supernatant of BMDMs, and the expression of endothelial-mesenchymal transition (EndMT)-related markers was detected by Western blot and immunofluorescence. Results Single-cell transcriptome analysis showed that the proportion of SPP1⁺ macrophages in renal allograft tissues was significantly higher in the CAD group than in the CTL group (P<0.05). The renal injury score and the percentage of interstitial fibrotic area in the CAD group were significantly higher than those in the SYN group (both P<0.05). Immunofluorescence staining showed that the proportion of SPP1⁺ macrophages was increased in the CAD group compared with the CTL group, and also increased in the CAD group compared with the SYN group (both P<0.05). VIPER analysis and DoRothEA transcription factor activity analysis revealed activation of the hypoxia pathway and upregulated expression of transcription factors such as HIF-1α in SPP1⁺ macrophages. SPP1 expression was elevated in BMDMs under hypoxic conditions. Knockdown of HIF-1α inhibited hypoxia-induced SPP1 protein expression, whereas overexpression of HIF-1α upregulated SPP1 protein levels. After co-culture of hypoxia-induced BMDMs with MAECs, the expression levels of EndMT-related markers were increased. Conclusions SPP1⁺ macrophages differentiated under hypoxia are significantly infiltrated in the formation of chronic renal allograft fibrosis, and may promote renal allograft fibrosis by inducing EndMT in renal vascular endothelial cells.

OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Simultaneous management of intestinal mucosal barrier dysfunction and gut microbiota dysregulation represents a significant challenge in the treatment of inflammatory bowel disease (IBD). Herein, we report a novel system that integrates multi-enzyme mimicking cerium single-atom nanocatalysts (CeSACs) with Lactobacillus reuteri probiotics (LR@CeSACs) for multipronged management of IBD. In this system, CeSACs demonstrate robust multi-enzyme activities across a broad pH range, effectively scavenging elevated reactive oxygen species, downregulating pro-inflammatory cytokines, and suppressing the expression of fibrosis-related genes. Moreover, probiotics promote the targeting and retention of the CeSACs for sustained catalytic antioxidant therapy. In turn, the inflammation relief enabled by CeSACs promotes bacterial viability, allowing for the rapid reshaping of intestinal barrier function and the restoration of gut microbiota. Therefore, LR@CeSACs exhibit excellent catalytic anti-inflammatory and anti-fibrotic therapeutic effects, as well as a certain prophylactic effect, as demonstrated in several murine models.

OBJECTIVE: To investigate the association between ABO blood types and gestational diabetes mellitus (GDM) risk. METHODS: A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) between ABO blood types and GDM risk. RESULTS: A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A ( OR = 1.05) or B ( OR = 1.04). However, women with type AB had a 19% increased risk of GDM ( OR = 1.19, 95% CI = 1.05-1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses. CONCLUSION The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it-either as a single risk factor or in combination with other known factors-could help identify individuals at risk for GDM before or during early pregnancy.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/etiology* ; ABO Blood-Group System ; Adult ; Prospective Studies ; Risk Factors ; Young Adult

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

[Purpose]To analyze the prevalence and disease burden of malignant tumors in cancer registration areas of Hubei Province in 2020.[Methods]The incidence and mortality data of ma-lignant tumors in cancer registration areas in Hubei Province in 2020 were collected,and the data were quality controlled according to the quality evaluation standards and methods formulated by the National Cancer Center.The data from 24 registries met the inclusion criteria.Using descrip-tive epidemiological methods to calculate incidence/mortality rate,age-specific incidence/mortality rate,standardized incidence/mortality rate by Chinese standard population(ASRC),standardized incidence/mortality rate by world standard population(ASRW).Disability-adjusted life years(DALY)and DALY rates were calculated using formulas provided by the World Health Organization to as-sess the disease burden of malignant tumors.[Results]In 2020,the crude incidence of malignant tumors in cancer registration areas of Hubei Province was 311.36/105,the ASRC was 184.14/105,the ASRW was 197.37/105,and the cumulative rate of 0～74 years old was 20.52％.The age-spe-cific incidence of malignant tumors in the province and rural areas reached its peak in the age group of 75～79 years old,while in urban areas it reached its peak in the age group of 80～84 years old.In 2020,the crude mortality rate of malignant tumors in cancer registration areas of Hubei Province was 184.58/105,the ASRC was 96.91/105,the ASRW was 110.92/105,and the cumulative rate of 0～74 years old was 11.01％.The age-specific mortality rate of malignant tumors in the province and urban areas reached its peak in the age group of above 85 years old,while in rural areas it reached its peak in the age group of 80～84 years old.Lung cancer ranked first in the incidence and mortality of malignant tumors in the province.In the cancer registration area of Hubei Province,the DALY of malignant tumors in 2020 was 641 497 person-years,and the DALY rate was 28.6‰.[Conclusion]Common cancers such as lung cancer,female breast cancer and upper digestive tract cancer have a great impact on the incidence,mortality and disease burden of malignant tumors in Hubei Province.Targeted cancer screening and early diagnosis and treatment are the most effective means to improve social and economic benefits.

[Purpose]To analyze the epidemiological characteristics of lung cancer in 2020 and the trend from 2012 to 2020 in Hubei Province.[Methods]Qualified lung cancer registry data reported by 24 cancer registries in Hubei Province was utilized to estimate the number of new lung cancer cases and deaths.Incidence/mortality rate,age-specific incidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC and ASMRC)and by world stan-dard population(ASIRW and ASMRW),cumulative rate of 0～74 years old and other indicators of lung cancer in urban and rural areas,different sex,age groups in 2020 were calculated.Annual percentage change(APC),average annual percentage change(AAPC)and 95％confidence interval(CI)were calculated to analyze the trends of incidence and mortality of lung cancer in cancer regi-stration areas of Hubei Province from 2012 to 2020.[Results]In 2020,the estimated number of new lung cancer cases in Hubei Province was 41 531,accounting for 23.17％of all new cancer cases.The incidence rate was 72.13/105,with the ASIRC of 38.19/105 and ASIRW of 42.75/105 respectively.The cumulative incidence rate of 0～74 years old was 4.82％.The estimated number of lung cancer deaths in Hubei Province in 2020 was 31 374,accounting for 29.52％of all cancer deaths.The mortality rate was 54.49/105,with the ASMRC of 27.66/105 and ASMRW of 31.95/105,respectively.The cumulative mortality(0～74 years old)was 3.36％.The incidence of lung cancer was higher in urban areas than that in rural areas,and higher in men than that in women.The in-cidence and mortality of lung cancer increased with age,and reaching the peak in the age groups of 75～79 and 80～85 years old respectively.From 2012 to 2020,the overall trend of crude inci-dence and mortality of lung cancer in Hubei Province was stable.The ASIRC and ASMRC showed a slow decline during 2012-2020,with the AAPCs of-0.51％(95％CI:-1.06％～-0.02％)and-1.84％(95％CI:-2.65％～-0.53％),respectively.The ASIRC showed a slow decline(APC=-1.76％,95％CI:-3.30％～-1.03％)during 2012-2018 and increase trend(APC=3.33％,95％CI:0.61％～5.02％)during 2018-2020,respectively,while ASMRC showed a significant decrease trend(APC=-3.00％,95％CI:-6.58％～-1.13％)during 2016-2020.[Conclusion]The incidence and mortality levels of lung cancer in Hubei Province were relatively high,resulted in a heavy disease burden and no significant downward trend.In the future,we should continue to strengthen the compre-hensive prevention and treatment of lung cancer,and promote lung cancer screening and early diagno-sis and treatment for target populations vigorously,especially in rural areas.

[Purpose]To analyze the opportunistic screening results of upper gastrointestinal can-cer in Hubei Province from 2022 to 2023.[Methods]The data of upper gastrointestinal cancer opportunistic screening program in Hubei Province from January 1,2022 to December 31,2023 were summarized.The biopsy rate,positive lesion detection rate and early diagnosis rate were ana-lyzed.The differences in rates between/among different sexes,age groups and regions were com-pared by x2 test,trend x2 test.[Results]A total of 372 507 people were included in the oppor-tunistic screening of upper gastrointestinal cancer from 2022 to 2023.Among them,100 379 in-dividuals underwent biopsy histopathological examination,with a biopsy rate of 26.95％.A total of 4 678 positive cases(high-grade intraepithelial neoplasia,early-stage cancer and advanced can-cer)were detected in the opportunistic screening,with a positive lesion detection rate of 1.26％.The detection rates of positive lesion in the esophagus,cardia and stomach were 0.61％,0.07％and 0.58％,respectively.There were 721 cases of early upper gastrointestinal cancer(high-grade intraepithelial neoplasia,early-stage cancer),representing an early diagnosis rate of 15.41％.The early diagnosis rates for the esophagus,cardia and stomach were 14.53％,11.96％and 16.89％,respectively.[Conclusions]The implementation of opportunistic screening for upper gastrointesti-nal cancer is conducive to expanding the coverage of screening.It is necessary to strengthen stan-dardized and homogeneous training and complete high-quality endoscopic examination to improve the detection rate and early diagnosis rate of opportunistic screening program for upper gastroin-testinal cancer.

Malignant tumors,as chronic diseases that seriously affect human life and health,are one of the most serious public health problems worldwide in the 21st century.Hubei Province at-taches great importance to the prevention and control of chronic diseases such as cancer,and launched the"323"campaign in 2021.This paper reviews the progress of cancer prevention and control in the"323"campaign from 2021 to 2024 from the aspects of science popularization,tu-mor registration,cancer screening,standardized diagnosis and treatment,and grassroots capacity improvement,and explores the key points of cancer prevention and control work in Hubei Province in the next step.