Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences最新文献

Myelodysplastic syndromes (MDS) are clonal hematopoietic neoplasms characterized by chronic cytopenias and abnormal cell morphology, with a propensity to progress to bone marrow failure or acute myeloid leukemia. Behcet's syndrome is a systemic vasculitis distinguished by recurrent oral ulcers, skin lesions, and ocular inflammation. In recent years, an increasing number of clinical cases have reported the coexistence of MDS and Behcet's syndrome, suggesting a potential pathological relationship between these conditions. Abnormal immune cell activation, dysregulated cytokine secretion, and cytogenetic alterations are thought to play critical roles in the pathogenesis of MDS combined with Behcet's syndrome. Currently, treatment strategies for MDS combined with Behcet's syndrome are primarily individualized and include immunosuppressive therapy, cytotoxic drug therapy, and targeted therapy. However, due to the limited number of case reports and insufficient research on the underlying mechanisms, selecting appropriate treatment options remains challenging. This article reviews the pathogenesis and interrelationships of MDS combined with Behcet's syndrome and summarizes recent advancements in treatment strategies, providing a reference for clinical diagnosis and management.

Objectives: To investigate the medium- and long-term efficacy of Percutaneous mechanical thrombectomy (PMT) combined with stent implantation for treatment of iliac vein stenosis with lower limb deep vein thrombosis.

Methods: Clinical and follow-up data of 125 patients with iliac vein stenosis and lower limb deep vein thrombosis who underwent PMT and stent implantation at five hospitals in northern Zhejiang province from January 2017 to June 2021 were collected. The thrombus clearance rate, thrombus recurrence rate, post-thrombotic syndrome (PTS) occurrence rate and the patency rate of iliac vein stents were documented,and safety indicators such as bleeding, death, pulmonary embolism, stent fracture and displacement were assessed.

Results: Among 125 patients, for clearance rate of limb thrombosis, there were 8 cases of grade Ⅰ (6.4%), 10 cases of grade Ⅱ (8.0%), and 107 cases of grade Ⅲ (85.6%). Patients were followed up for a median period of 74 months. According to the Villalta score, the recurrence rate of limb thrombosis at 12, 24 and 36 months was 8.48%, 8.93% and 10.91%; the iliac vein patency rates were 91.52%, 91.07%, and 89.09%; and the incidence of PTS was 5.08%, 5.36% and 6.36%, respectively. There were no major safety events such as death, massive pulmonary embolism and severe hepatic and renal insufficiency, and no readmission intervention events due to stent fracture or other incidence were found.

Conclusions: Percutaneous mechanical thrombectomy combined with iliac vein stent implantation is effective for patients with iliac vein stenosis complicated by lower extremity deep vein thrombosis with good medium- and long-term efficacy and safety, which is worthy of clinical application.

The studies on specific transient receptor potential melastatin 2(TRPM2) channel inhibitors can deepen our understanding of the pathological mechanism of related diseases, and discover novel, effective targets for therapeutic drugs. The development of TRPM2 channel inhibitors can be broadly classified into four categories with distinct characteristics: reutilization and structural modification of homologous ion channel modulators to produce a diverse array of TRPM2 channel inhibitors with strong inhibitory effects; TRPM2 channel inhibitors developed on channel gating mechanism with high specificity; inhibitors developed through high-throughput screening with novel chemical structures; inhibitors developed from natural antioxidants with higher safety. In recent years, the application of computer-aided drug design has significantly accelerated the development of TRPM2 channel inhibitors. Several promising compounds such as ZA18, A1 and D9 have been discovered, and it is expected that more potent and selective TRPM2 channel inhibitor scaffolds will be discovered in the future. This article reviews the advances on the studies of TRPM2 channel inhibitors, aiming to provide insights for the further research and clinical application of TRPM2 channel inhibitors.

Virus-induced senescence (VIS) is a significant biological phenomenon, which is associated with declining immune function, accelerating aging process and causing aging-related diseases. Studies have shown that a variety of common viruses, such as SARS-CoV-2, herpesviruses and hepatitis B virus can cause VIS in host cells. The primary mechanisms include the abnormal activation of the cGAS-STING signaling pathway, DNA damage response, and potential correlations with the integrated stress response due to intracellular phase separation. Viral infection and cellular senescence interact with each other: cellular senescence serves as a defense to restrict viral replication and transmission, while some viruses exploit cellular senescence to enhance their infectivity and replication. Understanding the mechanisms of VIS is conducive to the development of therapeutic strategies for viral infections and promotion of healthy aging. However, there is lack of research on therapeutic targets and drug development in this field so far; although senolytics may be effective for anti senescent cells (SCs) therapy, its efficacy for VIS need evidence provided by further clinical trials. This article reviews the research progress on the connection between viral infection and cellular senescence, to provide insights for the prevention and treatment of aging related diseases.

A 39-year-old male patient was admitted to hospital with abdominal distension, unconsciousness, and anuria. Head computed tomography (CT) scan showed subarachnoid hemorrhage and diffuse cerebral edema. The high-density area of contrast accumulation region in the high-density CT plaque was 38 HU, and the preliminary diagnosis was SAH, incomplete intestinal obstruction, and sepsis caused by acute cerebrovascular disease. After admission, the patient had sudden upturned eyes, limb convulsions, serum procalcitonin level exceeding 100ng/mL, low blood pressure and septic shock. Imipenem was given for intensive anti-infection therapy. After treatment, the procalcitonin levels showed a slow decline, renal function returned to normal, intra-abdominal pressure dropped to normal, urine volume gradually increased, but platelets still showed a downward trend. The lumbar puncture showed colorless and clear cerebrospinal fluid, and the biochemical and routine results of cerebrospinal fluid were normal. SAH and intracranial infection were excluded, and it was considered that the head CT scan showed pseudo subarachnoid hemorrhage. On the 4th day of admission, laparoscopic exploratory laparotomy+appendectomy+abdominal drainage under general anesthesia were performed. During the operation, purulent gangrene was observed in the appendix, abscess and moss were observed on the surface of the intestine, and a large amount of pus was found in the abdominal cavity. Rhabdomyolysis syndrome appeared after surgery. After continuous renal replacement therapy, the indicators gradually returned to normal level. The patient was conscious, and the head CT examination was normal. The patient was discharged from the hospital on the 10th day after surgery, and no special discomfort and abdominal pain and distension occurred during the 3-month follow-up.

Inflammatory senescence is a process of cellular dysfunction associated with chronic inflammation, which plays a significant role in the onset and progression of liver diseases,and the research on its mechanisms becomes a hotspot currently. In viral hepatitis, the mechanisms of inflammatory senescence primarily involve oxidative stress, cell apoptosis and necrosis, as well as gut microbiota dysbiosis. In non-alcoholic fatty liver disease, the mechanisms of inflammatory senescence are more complex, involving insulin resistance, fat deposition, lipid metabolism disorders, gut microbiota dysbiosis, and NAD⁺ metabolism abnormalities. In liver tumors, inflammatory senescence is characterized by the weakening of tumor suppressive mechanisms, remodeling of the liver microenvironment, metabolic reprogramming, and enhanced immune evasion. Therapeutic strategies targeting inflammatory senescence have been developing recently, and antioxidant therapy, metabolic disorder improvement, and immunotherapy emerging are important interventions for liver diseases. This review focuses on the mechanisms of inflammatory secescence in liver diseases, aiming to provide novel insights for the prevention and treatment of liver diseases.

Objectives: To analyze sex and age distribution of global disease burden of non-rheumatic calcific aortic valve disease (CAVD) from 1990 to 2021.

Methods: CAVD data 1990-2021 were obtained from the IHME website for Global Burden of Disease (GBD). The prevalence, mortality, years lived with disability (YLDs), and disability-adjusted life years (DALYs) were analyzed by gender and age groups. Joinpoint regression was used to calculate annual percent change (APC) and average annual percent change (AAPC).

Results: In 2021, there were 13.32 million CAVD patients and 142 000 deaths caused by CAVD globally. Age-standardized prevalence was higher in males (193.2/10⁵) than that in females (128.9/10⁵). Patients in 65-85 age group accounted for 64.0% of total cases, while those ≥85 years old accounted for 16.1%. From 1990-2021, prevalence increased in both sexes with an AAPC of 0.72% for males and 0.57% for females, respectively. Prevalence grew fastest from 2000-2010, slowed thereafter, and declined from 2015-2021. In those <65 years old, the mortality of males was 2.4 times higher than that of females, while in those ≥85 years old, mortality of females (117.3/10⁵) exceeded that of males (99.1/10⁵). YLD rates increased with age, and were higher in males for all age groups. DALY rates decreased overall but increased in those ≥85 years old, with a greater increase in females.

Conclusions: There are significant gender and age disparities in global disease burden of CAVD, with particular concern for the elderly, especially super-elderly females, indicating the need for personalized intervention strategies.

Objectives: To analyze the global disease burden of cervical cancer and the association between screening coverage and the quality of disease management.

Methods: The data of global burden of cervical cancer 2021 and the data of cervical cancer screening 2019 were obtained from IHME Global Burden of Disease (GBD) and the WHO Global Health Observatory (GHO), respectively. The age-standardized disease burden index was calculated, the Quality of Disease Management Index (QCI) was determined with principal component analysis, the correlation between QCI and cervical cancer screening coverage was examined with linear regression analysis by regions and populations.

Results: The burden of cervical cancer and the quality of its management exhibited significant variability across countries with differing levels of social development. The indicators of cervical cancer burden in China were close to the average level of countries with higher socia-demographic index (SDI). The global QCI was 22.22 (10.50, 35.43), and that of China was 26.30. The global screening coverage rate for cervical cancer was 42% (12%, 86%) and that in China was 31%. After adjusting for the social development level of countries, the coverage level of cervical cancer screening was associated with QCI (β=0.27, P<0.01), no matter in countries with low or high SDI (P>0.05). The association was significantly stronger among younger women (β=1.48, P<0.05).

Conclusions: There are discrepancies in both the disease burden of cervical cancer and the quality of disease management among countries with different socioeconomic levels, and there is still considerable room for improvement in China. Expanding coverage of cervical cancer screening may be an effective strategy to enhance the management quality of cervical cancer, particularly among younger women where the screening benefits are most pronounced.

Objectives: To analyze the disease burden and inequalities of lower extremity peripheral artery disorders (LEPAD) among people aged 40 and above in the Belt and Road partner countries from 1990 to 2021.

Methods: Data were retrieved from the Global Burden of Disease 2021 database. The age-standardized prevalence rates, mortality rates, and the annual rate of years lived with disability (YLDs) of LEPAD were analyzed. Trends were measured using the estimated annual percentage change (EAPC), and the slope index of inequality (SII) and concentration index were used to quantify the absolute and relative inequalities.

Results: In 2021, the age-standardized prevalence and mortality rates of LEPAD were 3168.26/10⁵ and 3.09/10⁵, increasing by 4.30% and 19.31% compared to 1990, and YLDs rates decreased by 4.00%. Females had higher age-standardized prevalence and YLDs rates, while males had higher mortality rates. The EAPC for prevalence rates was slightly higher in males (0.22%) than in females (0.17%); while the EAPC of age-standardized mortality rate was 2.02% for females, compared to 1.45% for males. From 1990 to 2021, the age-standardized YLDs rates decreased from 16.23/10⁵ to 15.58/10⁵, with a faster decline in females (－0.12%) than in males (－0.06%). LEPAD prevalence varied across countries, with higher burdens in Europe and faster growth in Gulf states. Higher socio-demographic index countries had higher prevalence. Inequity improved, with the SII at 52.90/10⁵ and concentration index at 0.038 in 2021. Gender disparities persisted, with concentration index rising to 0.058 in females and falling to －0.026 in males.

Conclusions: LEPAD prevalence and mortality among people aged 40 and above in the Belt and Road partner countries were risen, while YLDs rates were decreased from 1990 to 2021. Significant differences exist among peoples with different gender and countries, highlighting the need for enhanced screening, health education, and shared public health strategies across the Belt and Road partner countries.