Objective To analyze the epidemiological characteristics and disease burden of liver cancer in Guangdong Province in 2020, and to provide a scientific foundation for the development of regionalized prevention and control strategies for liver cancer. Methods According to the cancer registry data of Guangdong Province, the incidence, mortality and age-standardized rate by Chinese standard population in 2020 were calculated to analyze the epidemiological characteristics of liver cancer. The disability adjusted life years (DALYs), year of life loss (YLL), year of lived with disability (YLD), and cause-eliminated life expectancy were used to assess the disease burden of liver cancer. Results In 2020, the crude incidence rate and the age-standardized incidence rate of liver cancer in Guangdong Province were 27.79/100 000 and 20.84/100 000，respectively, and the crude mortality rate and the age-standardized mortality rate of liver cancer were 25.49/100,000 and 17.64/100 000, respectively. The total DALY and DALY rate of liver cancer in Guangdong Province were 515 311 person-years and 513.83/100 000, respectively. After eliminating the causes of death from liver cancer, the life expectancy in Guangdong Province increased from 84.60 years to 84.99 years. All indicators consistently demonstrated that the burden of liver cancer was higher in males than that in females, and the burden of liver cancer was higher in rural areas than that in urban areas. Conclusion Liver cancer in Guangdong Province exhibits a high incidence, mortality and disease burden level in 2020. There are obvious differences of gender, age and region in cancer burden. It is necessary to strengthen liver cancer screening and diagnosis and treatment in men, the elderly and those in rural areas to reduce the burden of liver cancer gradually in Guangdong Province.

BACKGROUND:Some studies have confirmed the changes in the function of immune cell subsets such as monocytes,T cells,B cells,and natural killer cells(NK cells)in patients with osteoarthritis,but the specific regulatory mechanisms are unclear.OBJECTIVE:To explore the causal relationship between plasma metabolite-mediated immune cells and hip osteoarthritis.METHODS:The Genome-Wide Association Studies(GWAS)data of 731 immune cells were used as the exposure,the GWAS data of hip osteoarthritis were used as the outcome,and 1 400 plasma metabolites were selected as mediating factors.The GWAS database is an important database for genetic association studies,maintained by international organizations with no country-specific affiliation.The inverse variance weighting method in the two-sample Mendelian randomization method was the main method,and the Bayesian weighted Mendelian randomization method was used to analyze the prior distribution,sample data and weights,which were then used to calculate the posterior distribution.The accuracy and reliability of the inverse variance weighting results were evaluated according to the posterior distribution,supplemented by MR-Egger,weighted median,simple model,and weighted mode methods.The pliotropy test and heterogeneity test were used to ensure the robustness of the process.The results of the inverse variance weighting method were used for subsequent mediating effect analysis.RESULTS AND CONCLUSION:(1)The inverse variance weighting method identified 4 immune cells strongly correlated with hip osteoarthritis,and 20 metabolites strongly associated with hip osteoarthritis,all of which had no reverse causal relationship.At the same time,the validation results of Bayesian weighted Mendelian randomization method showed that the posterior mean value was similar to the estimated value of the inverse variance weighting,and the posterior variance was relatively lower.One monocyte subtype(PDL-1 on CD14-CD16+)was finally screened out to have a causal relationship with hip osteoarthritis,with a total effect of-0.047(odds ratio=0.954,95％confidence interval:0.926-0.983),and a mediating effect of-0.004(odds ratio=0.939,95％confidence interval:0.902-0.978)mediated by alliin levels,accounting for 8.5％of the total effect.It was concluded that alliin is a protective factor in the progression of hip osteoarthritis,in which this metabolite plays a mediating role.(2)The large amount of data from international databases and European population analysis is of great significance to Chinese biomedicine,which can provide clues for research on the genetic susceptibility to similar diseases in the Chinese population,aiding in discovering the unique associations.The pharmacogenomic approaches used can be adapted to screen for drug response genes in the Chinese population,enhancing the precision of personalized medicine.Additionally,the advanced high-throughput technologies and statistical methods employed can be learned and applied to disease prevention and treatment research.

ObjectiveMitochondria are not only the central organelles responsible for cellular energy metabolism but also play essential roles in regulating cell cycle progression and cytoskeletal dynamics. In recent years, accumulating evidence has demonstrated that mitochondrial homeostasis is closely associated with mitotic progression and cytokinesis. Schizosaccharomyces pombe serves as a classical and well-established model organism. Because its cell cycle regulatory mechanisms are highly conserved throughout evolution, its genetic background is clearly defined, and experimental manipulation is efficient and convenient, it has been extensively applied in studies of cell growth, division, and reproductive mechanisms. The SPBC1604.04 gene encodes a previously uncharacterized mitochondrial carrier protein in Schizosaccharomyces pombe. This gene is located on chromosome II and spans 1 018 base pairs in length. It encodes a protein consisting of 238 amino acids with a predicted molecular mass of approximately 31.03 ku. Bioinformatic analysis predicts that this protein is responsible for the transport of thiamine pyrophosphate (TPP) into mitochondria. However, the effects of SPBC1604.04 gene deletion on mitotic cell dynamics under different temperature conditions have not been fully elucidated. MethodsThe SPBC1604.04 deletion strain of Schizosaccharomyces pombe was used as the experimental model. Fluorescent protein markers were constructed in the deletion background to label mitochondria, microtubules, actin, myosin, the nuclear envelope, and chromosomes. Live-cell imaging was performed using a TCS-SP8 laser scanning confocal microscope under normal temperature conditions (25℃) and heat stress conditions (37℃). Time-lapse microscopy was applied to dynamically monitor mitochondrial morphology and distribution, spindle assembly and elongation, chromosome segregation, as well as the formation and constriction of the actomyosin ring during cytokinesis. ImageJ software was used for quantitative measurements, including microtubule length during mitosis, spindle length at different mitotic stages, mitochondrial fluorescence intensity as an indicator of mitochondrial content, actomyosin ring length, nuclear envelope area, and chromosome segregation timing. Statistical analyses were conducted to compare phenotypic differences between the wild-type and SPBC1604.04 deletion strains at both temperature conditions. Through these analyses, we systematically investigated the impact of SPBC1604.04 deletion on mitotic cell dynamics in fission yeast under both normal physiological conditions and temperature stress. ResultsAt 25℃, compared with wild-type cells, the SPBC1604.04Δ strain exhibited a pronounced tendency toward mitochondrial fragmentation, accompanied by abnormal mitochondrial content and a significant reduction in mitochondrial fluorescence intensity. These observations suggest impaired mitochondrial homeostasis under normal growth conditions. In addition, the constriction time of actomyosin ring during cytokinesis was markedly prolonged, indicating that deletion of SPBC1604.04 affects the dynamics of the contractile machinery. However, no obvious defects were observed in spindle assembly, spindle elongation, or chromosome segregation. Under heat stress at 37℃, mitochondrial morphology in the SPBC1604.04Δ strain showed a tendency to recover toward a continuous tubular network structure. Mitochondrial content was restored, fluorescence intensity increased, and the constriction time of the actomyosin ring returned to levels comparable to those of wild-type cells. These results indicate that the mitotic defects observed at normal temperature are partially or fully alleviated under heat stress conditions. ConclusionThis study demonstrates that deletion of the SPBC1604.04 gene leads to abnormal mitochondrial content in Schizosaccharomyces pombe. The mitochondrial carrier protein SPBC1604.04 participates in regulating actomyosin ring constriction during mitosis but does not appear to be directly involved in the regulation of spindle dynamics or chromosome segregation. Our findings provide key experimental evidence for understanding the functional link between the SPBC1604.04 gene, mitochondrial homeostasis, and mitotic regulation.

ObjectiveMitochondria are not only the central organelles responsible for cellular energy metabolism but also play essential roles in regulating cell cycle progression and cytoskeletal dynamics. In recent years, accumulating evidence has demonstrated that mitochondrial homeostasis is closely associated with mitotic progression and cytokinesis. Schizosaccharomyces pombe serves as a classical and well-established model organism. Because its cell cycle regulatory mechanisms are highly conserved throughout evolution, its genetic background is clearly defined, and experimental manipulation is efficient and convenient, it has been extensively applied in studies of cell growth, division, and reproductive mechanisms. The SPBC1604.04 gene encodes a previously uncharacterized mitochondrial carrier protein in Schizosaccharomyces pombe. This gene is located on chromosome II and spans 1 018 base pairs in length. It encodes a protein consisting of 238 amino acids with a predicted molecular mass of approximately 31.03 ku. Bioinformatic analysis predicts that this protein is responsible for the transport of thiamine pyrophosphate (TPP) into mitochondria. However, the effects of SPBC1604.04 gene deletion on mitotic cell dynamics under different temperature conditions have not been fully elucidated. MethodsThe SPBC1604.04 deletion strain of Schizosaccharomyces pombe was used as the experimental model. Fluorescent protein markers were constructed in the deletion background to label mitochondria, microtubules, actin, myosin, the nuclear envelope, and chromosomes. Live-cell imaging was performed using a TCS-SP8 laser scanning confocal microscope under normal temperature conditions (25℃) and heat stress conditions (37℃). Time-lapse microscopy was applied to dynamically monitor mitochondrial morphology and distribution, spindle assembly and elongation, chromosome segregation, as well as the formation and constriction of the actomyosin ring during cytokinesis. ImageJ software was used for quantitative measurements, including microtubule length during mitosis, spindle length at different mitotic stages, mitochondrial fluorescence intensity as an indicator of mitochondrial content, actomyosin ring length, nuclear envelope area, and chromosome segregation timing. Statistical analyses were conducted to compare phenotypic differences between the wild-type and SPBC1604.04 deletion strains at both temperature conditions. Through these analyses, we systematically investigated the impact of SPBC1604.04 deletion on mitotic cell dynamics in fission yeast under both normal physiological conditions and temperature stress. ResultsAt 25℃, compared with wild-type cells, the SPBC1604.04Δ strain exhibited a pronounced tendency toward mitochondrial fragmentation, accompanied by abnormal mitochondrial content and a significant reduction in mitochondrial fluorescence intensity. These observations suggest impaired mitochondrial homeostasis under normal growth conditions. In addition, the constriction time of actomyosin ring during cytokinesis was markedly prolonged, indicating that deletion of SPBC1604.04 affects the dynamics of the contractile machinery. However, no obvious defects were observed in spindle assembly, spindle elongation, or chromosome segregation. Under heat stress at 37℃, mitochondrial morphology in the SPBC1604.04Δ strain showed a tendency to recover toward a continuous tubular network structure. Mitochondrial content was restored, fluorescence intensity increased, and the constriction time of the actomyosin ring returned to levels comparable to those of wild-type cells. These results indicate that the mitotic defects observed at normal temperature are partially or fully alleviated under heat stress conditions. ConclusionThis study demonstrates that deletion of the SPBC1604.04 gene leads to abnormal mitochondrial content in Schizosaccharomyces pombe. The mitochondrial carrier protein SPBC1604.04 participates in regulating actomyosin ring constriction during mitosis but does not appear to be directly involved in the regulation of spindle dynamics or chromosome segregation. Our findings provide key experimental evidence for understanding the functional link between the SPBC1604.04 gene, mitochondrial homeostasis, and mitotic regulation.

BACKGROUND:Some studies have confirmed the changes in the function of immune cell subsets such as monocytes,T cells,B cells,and natural killer cells(NK cells)in patients with osteoarthritis,but the specific regulatory mechanisms are unclear.OBJECTIVE:To explore the causal relationship between plasma metabolite-mediated immune cells and hip osteoarthritis.METHODS:The Genome-Wide Association Studies(GWAS)data of 731 immune cells were used as the exposure,the GWAS data of hip osteoarthritis were used as the outcome,and 1 400 plasma metabolites were selected as mediating factors.The GWAS database is an important database for genetic association studies,maintained by international organizations with no country-specific affiliation.The inverse variance weighting method in the two-sample Mendelian randomization method was the main method,and the Bayesian weighted Mendelian randomization method was used to analyze the prior distribution,sample data and weights,which were then used to calculate the posterior distribution.The accuracy and reliability of the inverse variance weighting results were evaluated according to the posterior distribution,supplemented by MR-Egger,weighted median,simple model,and weighted mode methods.The pliotropy test and heterogeneity test were used to ensure the robustness of the process.The results of the inverse variance weighting method were used for subsequent mediating effect analysis.RESULTS AND CONCLUSION:(1)The inverse variance weighting method identified 4 immune cells strongly correlated with hip osteoarthritis,and 20 metabolites strongly associated with hip osteoarthritis,all of which had no reverse causal relationship.At the same time,the validation results of Bayesian weighted Mendelian randomization method showed that the posterior mean value was similar to the estimated value of the inverse variance weighting,and the posterior variance was relatively lower.One monocyte subtype(PDL-1 on CD14-CD16+)was finally screened out to have a causal relationship with hip osteoarthritis,with a total effect of-0.047(odds ratio=0.954,95％confidence interval:0.926-0.983),and a mediating effect of-0.004(odds ratio=0.939,95％confidence interval:0.902-0.978)mediated by alliin levels,accounting for 8.5％of the total effect.It was concluded that alliin is a protective factor in the progression of hip osteoarthritis,in which this metabolite plays a mediating role.(2)The large amount of data from international databases and European population analysis is of great significance to Chinese biomedicine,which can provide clues for research on the genetic susceptibility to similar diseases in the Chinese population,aiding in discovering the unique associations.The pharmacogenomic approaches used can be adapted to screen for drug response genes in the Chinese population,enhancing the precision of personalized medicine.Additionally,the advanced high-throughput technologies and statistical methods employed can be learned and applied to disease prevention and treatment research.

Purpose: Dual anti–human epidermal growth factor receptor 2 (HER2) drugs have become the standard regimen for neoadjuvant systemic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels. Materials and Methods: A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 immunohistochemistry classes (HER2 2+/in situ hybridization [ISH] + or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro. Results: Compared to HER2 3+ subgroup, the HER2 2+/ISH+ group had a higher proportion of hormone receptor–positive status (48.7% vs. 76.1%, p < 0.001), more HER2 protein loss after NST, lower pathological complete response (pCR) rate (46.07% vs. 16.24%, p < 0.001), and tended to have worse disease-free survival (DFS). In HER2 2+/ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%, p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+/ISH+ cell lines; however, fam-trastuzumab deruxtecan drugs had a satisfactory effect. Conclusion Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+/ISH+ group to be a distinct subtype and defined it as the HER2-moderate–positive subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with antibody-drug conjugate drugs as potential options.

[Objective] To investigate the factors associated with alanine aminotransferase (ALT) abnormalities in multi-ethnic blood donors across five Zang autonomous prefectures in the plateau regions of Qinghai Province, and to provide evidence for ensuring blood safety and formulating screening strategies. [Methods] A retrospective analysis was performed on the ALT abnormal test results of blood donors in the Zang autonomous prefectures of Qinghai from 2022 to 2024. The correlations between ALT levels and factors including gender, age, altitude, and infectious markers were investigated. [Results] The overall ALT unqualified rate among blood donors in this region was 9.01%. Significant differences in ALT levels were observed across genders and age groups (P<0.05). Variations in ALT abnormality rates were also noted among different plateau regions (P<0.05). Overall, ALT values exhibited an increasing trend with rising altitude. The average ALT unqualified rates were 11.19% in Zang donors, 7.96% in Han donors, and 4.79% in donors from other ethnic groups (P<0.05). No statistically significant association was observed between ALT abnormality and the presence of HBV/HCV infectious markers (P>0.05). [Conclusion] In the plateau areas of Qinghai, multi-ethnic blood donors have a relatively high ALT levels and ALT unqualified rates, showing distinct regional characteristics. ALT elevation in voluntary blood donors is related to non-pathological factors such as gender, age, and dietary habits, but not to infectious indicators.

Objective To evaluate the efficacy and safety of systemic thrombolysis(ST)and standard anticoagulation(SA)in the treatment of lower extremity fracture complicated with distal deep vein thrombosis(DDVT).Methods We retrospectively analyzed the clinical data of 60 patients with lower extremity fracture complicated with DDVT treated from January 2021 to December 2023.When the lower limb venography indicated a calf thrombus burden score ≥3 points,a retrievable inferior vena cava filter(IVCF)was successfully placed in the healthy femoral vein before orthopedic surgery.The patients who received further anticoagulant or thrombolytic therapy after surgery were allocated into a ST group(n=30,urokinase ST and SA)and a SA group(n=30,only SA).The two groups were compared in terms of calf thrombus burden score,thrombus dissolution rate,IVCF placement time,IVCF retrieval rate,intercepted thrombi,hemoglobin level,platelet count,D-dimer level,and complications.Results There was no statistically significant difference in the calf thrombus burden score between the two groups before treatment(P=0.431).However,after treatment,the scores in both groups decreased(both P<0.001),with the ST group showing lower score than the SA group(P=0.002).The thrombus dissolution rate in the ST group was higher than that in the SA group(P<0.001).There was no statistically significant difference in the IVCF placement time between the two groups(P=0.359),and the IVCF retrieval rate was 100% in both groups.The ST group had fewer intercepted thrombi than the SA group(P=0.002).There was no statistically significant difference in hemoglobin level(P=0.238),platelet count(P=0.914),or D-dimer level(P=0.756)between the two groups before treatment.However,after treatment,both groups showed an increase in platelet count(both P<0.001)and a decrease in D-dimer level(both P<0.001).There was no statistically significant difference in the occurrence of complications between the two groups(P=0.704).Conclusions Both SA and ST demonstrate safety and efficacy in the treatment of lower extremity fractures complicated with DDVT,serving as valuable options for clinical application.Compared with SA,ST not only enhances the thrombus dissolution in the calf but also mitigates the risk of thrombosis associated with IVCF.
Humans ; Venous Thrombosis/therapy* ; Retrospective Studies ; Thrombolytic Therapy/methods* ; Male ; Female ; Middle Aged ; Fractures, Bone/complications* ; Lower Extremity/injuries* ; Anticoagulants/therapeutic use* ; Aged ; Treatment Outcome ; Adult

IgA nephropathy（IgAN）is the most common primary glomerular disease，characterized by the deposition of IgA in the glomerular mesangial area. IgAN is a progressive disease with a protracted and relapsing course. Approximately 50%~75% of adult IgAN patients experience renal function deterioration and eventually progress to end-stage kidney disease（ESKD）within 20 years after diagnosis. Among patients with onset in childhood，about 30% ultimately progress to ESKD after 20 years of long-term follow-up. In recent years，numerous studies have continuously explored important signaling pathways and key molecules in its pathogenesis. This review introduces the therapeutic advances in IgAN，aiming to provide better treatment options for clinicians.

Objective:To investigate the impact of Wenyang Ligong Decoction on pregnancy outcomes after transcervical resection of adhesions (TCRA) in patients with intrauterine adhesions (IUA).Methods:A retrospective cohort study was conducted to collect clinical data from 151 patients with IUA who underwent TCRA in the Reproductive Medicine Department of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine between January 2020 and January 2023. Patients were divided into a Traditional Chinese medicine (TCM) group (79 patients) and a control group (72 patients) based on whether they received Wenyang Ligong Decoction after TCRA. The TCM group received estrogen and progesterone sequential therapy post-surgery, combined with Wenyang Ligong Decoction for 2-3 menstrual cycles. The control only received sequential treatment with estrogen and progesterone.Pregnancy outcomes one year after surgery were compared between the two groups. After adjusting for confounding factors using multivariate Cox regression analysis, the effect of Wenyang Ligong Decoction on pregnancy outcomes after TCRA in patients with IUA was observed.Results:The live birth rate [54.43%　(43/79)], the ongoing pregnancy rate [56.96% (45/79)], and the clinical pregnancy rate [52.03% (49/79)] were higher in the TCM group than in the control [26.39% (19/72), P<0.001; 30.56% (22/72), P=0.001;37.50% (27/72), P=0.003], with statistically significant differences. There were no statistically significant differences in early abortion rate and late abortion rate between the TCM group and the control (all P>0.05). According to the stratified analysis by preparation methods, in the natural conception group, the live birth rate [60.78% (31/51)], the ongoing pregnancy rate [62.75% (32/51)], and the clinical pregnancy rate [68.63% (35/51)] in the TCM group were significantly higher than those in control group [21.43% (12/56), P<0.001; 26.79% (15/56), P<0.001; 33.93% (19/56), P<0.001]; there were no statistically significant differences in early miscarriage rate and late miscarriage rate between the two groups (both P>0.05). In the assisted reproductive technology group, there were no statistically significant differences in live birth rate, ongoing pregnancy rate, clinical pregnancy rate, early miscarriage rate, and late miscarriage rate between the two groups (all P>0.05). According to the stratified analysis by age, in the <35-year-old patients, the live birth rate [66.00% (33/50)], the ongoing pregnancy rate [70.00% (35/50)], and the clinical pregnancy rate [74.00% (37/50)] in the TCM group were significantly higher than those in control group [41.30% (19/46), P=0.015; 47.83% (22/46), P=0.027; 54.35% (25/46), P=0.044]; there were no statistically significant differences in early miscarriage rate and late miscarriage rate between the two groups (both P>0.05). In the ≥35-year-old patients, the live birth rate [34.48% (10/29)], the ongoing pregnancy rate [34.48% (10/29)], and the clinical pregnancy rate [41.38% (12/29)] in the TCM group were significantly higher than those in control group [0%, P=0.001; 0%, P=0.001; 7.69% (2/26), P=0.004]; there were no statistically significant differences in early miscarriage rate and late miscarriage rate between the two groups (both P>0.05).Univariate Cox regression analysis showed that age, number of previous uterine cavity interventions, IUA score, degree of IUA, and endometrial thickness after TCRA were independent risk factors for live births, and age, IUA score, degree of IUA, intima thickness after TCRA, and treatment group were the influencing factors of persistent pregnancy (all P<0.05). After adjusting for confounding factors, multivariate Cox regression analysis showed that Wenyang Ligong Decoction significantly improved the live birth rate ( HR=3.19, 95% CI: 1.77-8.11, P=0.001) and the rate of continuous pregnancy ( HR=3.66, 95% CI: 1.80-7.48, P<0.001) in patients with IUA. Conclusion:Wenyang Ligong Decoction can significantly improve pregnancy outcomes after TCRA in patients with IUA.