Objective:To investigate the efficacy and safety of tenofovir amibufenamide in patients over 65 years old with chronic hepatitis B and liver cirrhosis.Methods:We recruited 45 patients in Linyi People's Hospital with chronic hepatitis B and liver cirrhosis who were treated with TMF antiviral therapy for 48 weeks, compared the virologic response rate and HBV DNA decrease level at 12, 24 and 48 weeks, and the changes in hepatitis B surface antigen, alanine aminotransferase, glomerular filtration rate, creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum phosphorus and blood lipids, and the changes in ALT normalization rate at 48 weeks. P<0.05 was statistically significant. Results:The age of the enrolled patients was 69.0 (67.0, 72.5) years. At 12, 24, and 48 weeks of treatment, the complete virological response rates were 32.4% (12/37), 70.0% (28/40), and 84.6% (33/39) respectively, and the level of HBV DNA decreased from baseline ( P＜0.05). After 48 weeks of treatment, the level of HBsAg decreased ( P<0.05), and there was no negative HBsAg conversion and seroconversion. After 48 weeks of treatment, the level of ALT decreased ( P<0.05). At 48 weeks of treatment, the rates of ALT reverted to normality were 88.9% (16/18) and 70.4% (19/27), respectively. There was no significant difference in the levels of glomerular filtration rate, creatinine, phosphorus, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol estimated at baseline before and after treatment ( P＞0.05), and no serious adverse events were observed. Conclusions:For patients over 65 years old with chronic hepatitis B and liver cirrhosis, TMF can significantly inhibit HBV DNA replication, and the ALT normalization rate is high and well tolerated.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective:To describe the trend of mortality and death spectrum in Shandong Province from 1970 to 2021 and provide basis for the targeted disease prevention and control.Methods:The data were collected from the death registration reports of Shandong and 3 national retrospective surveys of death causes in Shandong. The change in levels of overall and specific deaths in Shandong in different years were analyzed based on mortality rate, age-standardized mortality rate and constituent ratio of cause of death, differential decomposition was used to quantify the contribution of demographic and non-demographic factors to changes of mortality.Results:The crude mortality rate in residents in Shandong was basically stable from 1970 to 2021, and the mortality rate during 2020-2021 (732.73/100 000) was slightly higher than that during 1970-1974 (671.98/100 000). While the standardized mortality rate decreased significantly, and the mortality during 2020-2021 (183.39/100 000) decreased by 67.71% compared with that during 1970-1974 (568.00/100 000). The negative increase of population factors and the positive decrease of non-population factors reacted each other, so the mortality was relatively stable. Cardiac-cerebrovascular disease was always the leading cause of death, but the constituent ratio of death increased rapidly from 19.70% during 1970-1974 to 54.72% during 2020-2021. The rank in the causes of death changed from the fourth (11.46%) to the second (25.70%) for malignant tumor, from the seventh (5.85%) to the third (5.59%) for injury, from the second (12.87%) to the fourth (4.99%) for chronic respiratory diseases, from the third (12.27%) to the tenth (0.42%) for infectious diseases. The standardized mortality rates of the main causes of death decreased at different degrees, the standardized mortality rates of obstetrical disease, infectious disease, gastrointestinal disease and chronic respiratory disease decreased by more than 50.00%. The age distribution of deaths and the death spectrum in different age groups and in urban-rural populations changed significantly. During 2020-2021, the proportion of deaths in young people aged 0-14 years was 0.54%, which was 97.05% lower than that during 1970-1974, while the proportion of deaths in the elderly aged ≥75 years was 55.14%, which was 55.75% higher than that during 1970-1974. The rank of infectious diseases in the causes of death descended significantly in all age groups, but the ranks of injury, neuropsychiatric disease and malignant tumor rose significantly in adolescents, and the ranks of endocrine nutrition and metabolic disease rose in middle-aged and elderly people. The difference of death spectrum between urban area and rural area became less obvious and the main death causes in urban and rural residents were basically the same during 2020-2021.Conclusions:The death spectrum of residents in Shandong changed significantly. Chronic and non-communicable diseases, especially cardiac-cerebrovascular disease and malignant tumor, should be the focus in disease control and prevention. The prevention and control of diseases in Shandong made remarkable achievement during 1970-2021. However, in the context of population ageing, it is suggested to strengthen the treatment, prevention of diseases and injuries related to the health of the elderly and elderly health care in the future.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.
Animals ; Mice ; Colitis, Ulcerative/drug therapy* ; Ursodeoxycholic Acid/adverse effects* ; Berberine/pharmacology* ; Interleukin-6 ; Tumor Necrosis Factor-alpha/pharmacology* ; Drugs, Chinese Herbal/pharmacology* ; Colon ; Nanoparticles ; Dextran Sulfate/adverse effects* ; Disease Models, Animal ; Colitis/chemically induced*

Objective: To compare the 5-year follow-up outcomes of radiofrequency catheter ablation (RFCA) combined with left atrial appendage closure (LAAC) and long-term oral anticoagulant (OAC) after RFCA in patients with atrial fibrillation. Methods: This retrospective cross-sectional study included patients with atrial fibrillation who underwent"one-stop"procedure in the First Affiliated Hospital of Ningbo University from September 2015 to December 2017 (RFCA+LAAC group). Baseline data of patients were collected. Propensity score matching at the ratio of 1∶1 was used to select patients with atrial fibrillation who took long-term OAC after RFCA (RFCA+OAC group). The maintenance rate of sinus rhythm and the incidence of adverse events during follow-up were compared between the two groups. Results: A total of 110 patients were enrolled in the RFCA+LAAC group and RFCA+OAC group, respectively. Age of patients was (67.4±8.8) years in RFCA+LAAC group, and there were 42 (38.2%) female patients. Age of patients was (67.3±7.9) years in RFCA+OAC group, and there were 47 (42.7%) female patients. The patients were followed up for mean of (5.3±1.1) years. There was no significant difference in the maintenance rate of sinus rhythm (log-rank: χ²=0.277, P=0.602) and incidence of ischemic stroke events (2.7% (3/110) vs. 4.5% (5/110), P=0.719) during follow-up between the two groups. The incidence of bleeding events (6.4% (7/110) vs. 18.2% (20/110), P=0.008) and major bleeding events (1.8% (2/110) vs. 8.2% (9/110), P=0.030) was significantly higher in the RFCA+OAC group than in the RFCA+LAAC group. Conclusion: There is no significant difference between RFCA+LAAC group and RFCA+OAC group in maintenance rate of sinus rhythm and incidence of ischemic stroke events. Patients in the RFCA+LAAC group have a lower risk of bleeding events compared to the RFCA+OAC group.
Humans ; Female ; Middle Aged ; Aged ; Male ; Atrial Fibrillation/surgery* ; Cross-Sectional Studies ; Follow-Up Studies ; Retrospective Studies ; Anticoagulants/therapeutic use* ; Catheter Ablation ; Ischemic Stroke

Objective: To compare the 5-year follow-up outcomes of radiofrequency catheter ablation (RFCA) combined with left atrial appendage closure (LAAC) and long-term oral anticoagulant (OAC) after RFCA in patients with atrial fibrillation. Methods: This retrospective cross-sectional study included patients with atrial fibrillation who underwent"one-stop"procedure in the First Affiliated Hospital of Ningbo University from September 2015 to December 2017 (RFCA+LAAC group). Baseline data of patients were collected. Propensity score matching at the ratio of 1∶1 was used to select patients with atrial fibrillation who took long-term OAC after RFCA (RFCA+OAC group). The maintenance rate of sinus rhythm and the incidence of adverse events during follow-up were compared between the two groups. Results: A total of 110 patients were enrolled in the RFCA+LAAC group and RFCA+OAC group, respectively. Age of patients was (67.4±8.8) years in RFCA+LAAC group, and there were 42 (38.2%) female patients. Age of patients was (67.3±7.9) years in RFCA+OAC group, and there were 47 (42.7%) female patients. The patients were followed up for mean of (5.3±1.1) years. There was no significant difference in the maintenance rate of sinus rhythm (log-rank: χ²=0.277, P=0.602) and incidence of ischemic stroke events (2.7% (3/110) vs. 4.5% (5/110), P=0.719) during follow-up between the two groups. The incidence of bleeding events (6.4% (7/110) vs. 18.2% (20/110), P=0.008) and major bleeding events (1.8% (2/110) vs. 8.2% (9/110), P=0.030) was significantly higher in the RFCA+OAC group than in the RFCA+LAAC group. Conclusion: There is no significant difference between RFCA+LAAC group and RFCA+OAC group in maintenance rate of sinus rhythm and incidence of ischemic stroke events. Patients in the RFCA+LAAC group have a lower risk of bleeding events compared to the RFCA+OAC group.
Humans ; Female ; Middle Aged ; Aged ; Male ; Atrial Fibrillation/surgery* ; Cross-Sectional Studies ; Follow-Up Studies ; Retrospective Studies ; Anticoagulants/therapeutic use* ; Catheter Ablation ; Ischemic Stroke

The mortality of female breast cancer in Shandong Province has increased since the 1970. The differential decomposition analysis found that the slight decline in the crude mortality of breast cancer among women was entirely due to non-demographic factors during the 1970-1990, and the significant increase in the crude mortality was due to a combination of demographic and non-demographic factors since the 1990. The contribution rate of demographic factor has gradually increased from 53.5% in 2004-2005 to 59.5% in 2011-2013, while that of non-demographic factor has decreased from 46.5% to 40.5%. The women aged 45-64 years old were the major population of female breast cancer deaths, accounting for 40%-60% of total breast cancer deaths in different times, and then the mortality in female aged 55-64 years old increased rapidly, with increases of 52.12%, 115.19% and 29.01% in 2011-2013 over the 1970-1974, 1990-1992 and 2004-2005, respectively (Z=-7.342,P<0.001). Compared with 1970-1974, the age-standardized mortality rate of rural women increased by 41.86% in 2011-2013 (Z=-17.933, P<0.001), and that of urban women increased by 18.62% in 2011-2013 (Z=-25.642, P<0.001). The age-standardized mortality rate of breast cancer in urban women was higher than that in rural women in different times (all P<0.05). The spatial scan analysis found that eastern Shandong Province was found to be a sustained high-risk area for death, and other high-risk areas were transferred from north to southwest of Shandong between 1970 and 2013.
Breast Neoplasms/epidemiology* ; Female ; Humans ; Middle Aged ; Rural Population ; Spatial Analysis