Genetic variations in DNA excision repair pathway contribute to the chemosensitivity and prognosis of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a hematologic malignancy with a high recurrence rate and poor long-term prognosis. DNA excision repair systems, such as base excision repair (BER) and nucleotide excision repair (NER), play a major role in maintaining genomic stability and integrity. Further intensive investigations are necessary to uncover additional AML prognosis loci. In this study, we analyzed 16 candidate SNPs within NER and BER pathways in AML patients. Our results showed the GT/GG genotype of the XPC rs2228001 polymorphism was significantly associated with WBC count in dominant models (OR = 0.41, 95 % CI = 0.18-0.96, p = 0.039). Additionally, the rs25487 and rs3213245 SNPs in the XRCC1 gene, in both co-dominant and dominant models, were significantly associated with PLT count in AML (p < 0.05). The GG genotype of rs1130409 in APEX1 was more prone to adverse cytogenetics in both the codominant and recessive models (p < 0.05). Furthermore, the GA genotypes of ERCC8 rs158572 in codominant model was significantly correlated with refractory group (p < 0.05). ERCC8 rs158572 and XRCC1 rs3213245 in both codominant and dominant models were significantly correlated with the MRD positivity (p < 0.05). Kaplan-Meier analysis revealed an link between overall survival (OS) and the co-dominant, dominant, and recessive models of rs2228001 in XPC. Additionally, patients with the GG and GT/GG genotype in the co-dominant, dominant model and recessive model in XPC rs2228001 exhibited significantly longer survival (p < 0.05). Multivariate Cox analyses indicated that rs2228001 in both co-dominant and dominant models were independent favorable factors impacting patient OS (OR < 1). Our findings suggest that genetic polymorphisms in DNA excision repair pathway genetic polymorphisms contribute to the chemosensitivity and prognosis of acute myeloid leukemia.

Dietary n-3 fatty acids intake and all-cause and cardiovascular mortality in patients with pre-diabetes and diabetes.

BACKGROUND: While the association between n-3 polyunsaturated fatty acids (PUFA) and cardiovascular events has been thoroughly examined, there is still a scarcity of research regarding their impact on the long-term prognosis in diabetic patients. METHOD: Herein, a total of 16,539 eligible individuals were enrolled from the National Health and Nutrition Examination Survey (NHANES) 2003-2018, and categorized into T1, T2, and T3 based on the tertiles of n-3 PUFA. The Cox proportional risk regression models, Kaplan-Meier curve, and subgroup analysis were conducted to evaluate the association between n-3 PUFA and mortality. Restricted cubic spline (RCS) curves graphically demonstrated the dose-response relationship. Additionally, weighted quantile sum (WQS) models were adopted to measure the mixed and individual effects of n-3 PUFA on mortality. RESULTS: Following a median follow-up period of 8.42 years, 3,010 individuals died, with 989 deaths attributed to cardiovascular diseases. Significantly lower risk of all-cause [T2: 0.81 (0.71, 0.92), T3: 0.77 (0.64, 0.94)] and cardiovascular [T2: 0.75 (0.61, 0.93)] mortality was observed after adjusting for multivariable compared to the reference (T1). Meanwhile, the RCS curve revealed a negative non-linear association between the n-3 PUFA and mortality. None of the interactions in any subgroup analysis were statistically significant except for BMI (p for interaction = 0.049). Finally, the WQS analysis demonstrated alpha-linolenic acid (ALA) and docosapentaenoic acid (DPA) as the main contributors to the n-3 PUFA benefits against mortality. CONCLUSIONS: Increased dietary intake of n-3 PUFA, particularly ALA and DPA, was associated with a reduced risk of all-cause and cardiovascular mortality among Americans with prediabetes and diabetes.

Quality of Life and Glucose Regulation in Pediatric Patients with Type 1 Diabetes: A Study in the Ningxia Hui Autonomous Region.

Objective: In this study, we aimed to evaluate the current status of the quality of life (QOL) of pediatric patients and plasma glucose concentration regulation in children with type 1 diabetes (T1DM) in the Ningxia Hui autonomous region. Methods: The study involved children with T1DM admitted to the General Hospital of Ningxia Medical University between October 2011 and October 2021. The children and their parents completed general information and quality of life (QOL) questionnaires. The regulation of plasma glucose concentration was assessed based on HbA1c levels, and plasma glucose and QOL-influencing components were investigated. Results: Among the 136 pediatric patients diagnosed with T1DM, the mean glycated hemoglobin (HbA1c) level was recorded at 8.7% (7.2%, 10.5%). A breakdown of the patient cohort revealed that 44 patients (32.4%) demonstrated good regulation of plasma glucose, 33 patients (24.3%) exhibited acceptable glycemic control, and 59 patients (43.3%) displayed poor regulation of plasma glucose. The control of plasma glucose in pediatric patients diagnosed with T1DM was affected by the duration of the disease, the patient's age, the frequency of daily plasma glucose measurements, the use of CGM, diabetic ketoacidosis (DKA), and the education level of the mother. The control of plasma glucose, dietary management, DKA, the ability to learn, and health education are interfering factors of quality of life in children diagnosed with T1DM. Effective control of plasma glucose may ensure the QOL in children with T1DM, and DKA was the risk factor for QOL. Conclusion: In Ningxia, the regulation of plasma glucose in pediatric and adolescent patients with T1DM remains suboptimal, leading to poor QOL. There is a pressing need to enhance glucose regulation and QOL through comprehensive strategies, which include reinforced dietary management, rigorous monitoring of plasma glucose levels, and heightened health education levels.

ZFHX3 variants cause childhood partial epilepsy and infantile spasms with favourable outcomes.

BACKGROUND: The ZFHX3 gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between ZFHX3 variants and epilepsy. METHODS: Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A Drosophila Zfh2 knockdown model was used to validate the association between ZFHX3 and epilepsy. RESULTS: Compound heterozygous ZFHX3 variants were identified in eight unrelated cases. The burden of ZFHX3 variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In Zfh2 knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The Zfh2 knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone/steroids. The analyses of temporal expression (genetic dependent stages) indicated that ZFHX3 orthologous were highly expressed in the embryonic stage and decreased dramatically after birth. CONCLUSION: ZFHX3 is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness.

Effects of innovative reinforced concrete slit shaft configuration on seismic performance of elevated water tanks.

Elevated water tanks are considered crucial infrastructure due to their significant role in supporting essential services. A strong ground motion may result in a failure or significant damage to a reinforced concrete shaft of an elevated water tank because hysteric energy dissipation is limited to the formation of plastic hinges at the base of the shaft, while the nonlinear properties of the rest of the shaft remain underutilised. The innovative system of assembling RC shafts for elevated water tanks using a slit wall technique was developed to enhance energy dissipation along with the shaft height by introducing slit zones. The comparative nonlinear dynamic analysis between three-dimensional models of elevated water tanks with different shaft diameters and heights was conducted using SAP2000 software. The results of elevated water tanks with slit and solid reinforced concrete shafts were compared. The research findings showed that during a seismic event, the slit zones increased the ductility of the shaft, reduced stress concentration in the lower part of the shaft, and provided uniform stress distribution throughout the shaft's height. The effect of the innovative system is especially noticeable in the elevated water tanks with tall and slender shafts.

Reprint of: Recessive APC2 missense variants associated with epilepsies without neurodevelopmental disorders.

OBJECTIVES: The APC2 gene, encoding adenomatous polyposis coli protein-2, is involved in cytoskeletal regulation in neurons responding to endogenous extracellular signals and plays an important role in brain development. Previously, the APC2 variants have been reported to be associated with cortical dysplasia and intellectual disability. This study aims to explore the association between APC2 variants and epilepsy. METHODS: Whole-exome sequencing (WES) was performed in cases (trios) with epilepsies of unknown causes. The damaging effects of variants were predicted by protein modeling and in silico tools. Previously reported APC2 variants were reviewed to analyze the genotype-phenotype correlations. RESULTS: Four pairs of compound heterozygous missense variants were identified in four unrelated patients with epilepsy without brain malformation/intellectual disability. All variants presented no or low allele frequencies in the controls. The missense variants were predicted to be damaging by silico tools, and affect hydrogen bonding with surrounding amino acids or decreased protein stability. Patients with variants that resulted in significant changes in protein stability exhibited more severe and intractable epilepsy, whereas patients with variants that had minor effect on protein stability exhibited relatively mild phenotypes. The previously reported APC2 variants in patients with complex cortical dysplasia with other brain malformations-10 (CDCBM10; MIM: 618677) were all truncating variants; in contrast, the variants identified in epilepsy in this study were all missense variants, suggesting a potential genotype-phenotype correlation. SIGNIFICANCE: This study suggests that APC2 is potentially associated with epilepsy without brain malformation/intellectual disability. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic heterogeneity.

NUS1 Variants Cause Lennox-Gastaut Syndrome Related to Unfolded Protein Reaction Activation.

NUS1 encodes the Nogo-B receptor, a critical regulator for unfolded protein reaction (UPR) signaling. Although several loss-of-function variants of NUS1 have been identified in patients with developmental and epileptic encephalopathy (DEE), the role of the NUS1 variant in Lennox-Gastaut syndrome (LGS), a severe child-onset DEE, remains unknown. In this study, we identified two de novo variants of NUS1, a missense variant (c.868 C > T/p.R290C) and a splice site variant (c.792-2 A > G), in two unrelated LGS patients using trio-based whole-exome sequencing performed in a cohort of 165 LGS patients. Both variants were absent in the gnomAD population and showed a significantly higher observed number of variants than expected genome-wide. The R290C variant was predicted to damage NUS1 and decrease its protein stability. The c.792-2 A > G variant caused premature termination of the protein. Knockdown of NUS1 activated the UPR pathway, resulting in apoptosis of HEK293T cells. Supplementing cells with expression of wild-type NUS1, but not the mutant (R290C), rescued UPR activation and apoptosis in NUS1 knockdown cells. Compared to wild-type Drosophila, seizure-like behaviors and excitability in projection neurons were significantly increased in Tango14 (homolog of human NUS1) knockdown and Tango14R290C/+ knock-in Drosophila. Additionally, abnormal development and a small body size were observed in both mutants. Activated UPR signaling was also detected in both mutants. Thus, NUS1 is a causative gene for LGS with dominant inheritance. The pathogenicity of these variants is related to the UPR signaling activation, which may be a common pathogenic mechanism of DEE.

Dairy products intake and prevalence, incidence, and recovery of non-alcoholic fatty liver disease in Chinese population.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a growing public health concern. Modifiable factors such as diet and lifestyle are of research interest in preventing or reversing the disease. The relationship between dairy products and NAFLD remains unclear. METHODS: In this cohort study, 36,122 participants aged 20-74 were enrolled by multi-stage, stratified, randomized cluster sampling from 2016 to 2017. A total of 25,085 participants finished at least one follow-up visit from 2019 to 2023. Dairy intake was collected by food frequency questionnaire at baseline. NAFLD was defined as fatty liver diagnosed by ultrasonography with excessive alcohol drink excluded. Logistic regression and Cox proportional hazard models were used to analyze the association between dairy intake and NAFLD. RESULTS: A total of 34,040 participants were included in the baseline analysis. The prevalence of NAFLD was inversely associated with dairy intake (OR>7vs 0 servings/week = 0.91, 95% CI 0.84-0.98; ORper serving/day increase = 0.95, 95% CI 0.92-0.99). 20,460 participants entered the follow-up analysis. Among 12,204 without NAFLD at baseline, 4,470 developed NAFLD after a median time of 4.3 years. The incidence of NAFLD was inversely associated with dairy intake (HR>7 vs 0 servings/week = 0.89, 95% CI 0.81-0.98; HRper serving/day increase = 0.94, 95% CI 0.89-0.99). Among 8256 with NAFLD at baseline, 3,885 recovered after 4.2-year follow-up. Total dairy intake did not show significant associations with recovery of NAFLD, and the HRs (95% CI) were 0.96 (0.87-1.06) for > 7 servings/week and 0.98 (0.93-1.03) for per serving/day increase. CONCLUSION: Dairy product intake of more than one serving per day was associated with a lower prevalence and incidence of NAFLD in Chinese population. However, total dairy intake did not show significant association in NAFLD reversal.

Association of SOX6 gene polymorphisms with Kashin-Beck disease risk in the Chinese Han population.

Kashin-Beck disease (KBD) is an endemic osteochondropathy. A specific gene called SRY-box transcription factor 6 (SOX6) is important for forming cartilage. This study aims to explore the potential correlation between SOX6 single nucleotide polymorphisms (SNPs) and KBD risk for the first time. In the case-control study, 735 unrelated Chinese Han individuals were enrolled. The four mutation sites of the SOX6 gene (rs4539287 G/A, rs3203295 C/A, rs7928675 C/A, and rs10832681 A/G) were screened and genotyped on the Agena MassARRAY platform. The correlation between SOX6 SNPs and KBD risk was explored based on logistic regression analysis. The interaction between SNP and SNP was analyzed based on the multi-factor dimensionality reduction (MDR) method. Overall analysis revealed a remarkable correlation between rs7928675 and rs10832681 and the reduction of KBD risk (p < 0.05). Subgroup analyses further indicated that these two SNPs have a significant protective effect on KBD risk among participants aged ≤65 years, males, and non-smokers (p < 0.05). MDR displayed a marked interaction between rs3203295 and rs10832681. Our study revealed that SOX6 rs7928675 and rs10832681 are markedly correlated with a reduced risk of KBD in the Chinese Han population, providing a new direction for the prevention, diagnosis, and treatment of KBD.

Global, regional, and national burden of HIV and other sexually transmitted infections in older adults aged 60-89 years from 1990 to 2019: results from the Global Burden of Disease Study 2019.

BACKGROUND: Sexually active older adults are often more susceptible to HIV and other sexually transmitted infections (STIs) due to various health conditions (especially a weakened immune system) and low use of condoms. We aimed to assess the global, regional, and national burdens and trends of HIV and other STIs in older adults from 1990 to 2019. METHODS: We retrieved data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 on the incidence and disability-adjusted life-years (DALYs) of HIV and other STIs (syphilis, chlamydia, gonorrhoea, trichomoniasis, and genital herpes) for older adults aged 60-89 years in 204 countries and territories from 1990 to 2019. Estimated annual percentage changes in the age-standardised incidence and DALY rates of HIV and other STIs, by age, sex, and Socio-demographic Index (SDI), were calculated to quantify the temporal trends. Spearman correlation analysis was used to examine the relationship between age-standardised rates and SDI. FINDINGS: In 2019, among older adults globally, there were an estimated 77 327 (95% uncertainty interval 59 443 to 97 648) new cases of HIV (age-standardised incidence rate 7·6 [5·9 to 9·6] per 100 000 population) and 26 414 267 (19 777 666 to 34 860 678) new cases of other STIs (2607·1 [1952·1 to 3440·8] per 100 000). The age-standardised incidence rate decreased by an average of 2·02% per year (95% CI -2·38 to -1·66) for HIV and remained stable for other STIs (-0·02% [-0·06 to 0·01]) from 1990 to 2019. The number of DALYs globally in 2019 was 1 905 099 (95% UI 1 670 056 to 2 242 807) for HIV and 132 033 (95% UI 83 512 to 225 630) for the other STIs. The age-standardised DALY rate remained stable from 1990 to 2019, with an average change of 0·97% (95% CI -0·54 to 2·50) per year globally for HIV but decreased by an annual average of 1·55% (95% CI -1·66 to -1·43) for other STIs. Despite the global decrease in the age-standardised incidence rate of HIV in older people from 1990 to 2019, many regions showed increases, with the largest increases seen in eastern Europe (average annual change 17·84% [14·16 to 21·63], central Asia (14·26% [11·35 to 17·25]), and high-income Asia Pacific (7·52% [6·54 to 8·51]). Regionally, the age-standardised incidence and DALY rates of HIV and other STIs decreased with increases in the SDI. INTERPRETATION: Although the incidence and DALY rates of HIV and STIs either declined or remained stable from 1990 to 2019, there were regional and demographic disparities. Health-care providers should be aware of the effects of ageing societies and other societal factors on the risk of HIV and other STIs in older adults, and develop age-appropriate interventions. The disparities in the allocation of health-care resources for older adults among regions of different SDIs should be addressed. FUNDING: Natural Science Foundation of China, Fujian Province's Third Batch of Flexible Introduction of High-Level Medical Talent Teams, Science and Technology Innovation Team (Tianshan Innovation Team) Project of Xinjiang Uighur Autonomous Region, Cure Alzheimer's Fund, Helse Sør-Øst, the Research Council of Norway, Molecule/VitaDAO, NordForsk Foundation, Akershus University Hospital, the Civitan Norges Forskningsfond for Alzheimers Sykdom, the Czech Republic-Norway KAPPA programme, and the Rosa Sløyfe/Norwegian Cancer Society & Norwegian Breast Cancer Society.

Association of frailty with activity levels and sedentary behaviours in patients with hepatitis B cirrhosis: A cross-sectional study.

BACKGROUND AND AIMS: Research on the association between activity levels and sedentary behaviour with frailty in patients affected by hepatitis B cirrhosis is sparse. This study aimed to explore the association of frailty with activity levels and sedentary behaviours in patients with hepatitis B cirrhosis. DESIGN: This cross-sectional study followed the STROBE checklist. METHODS: This study was conducted in Guangzhou, China, between August 2021 and October 2022. The frailty condition of patients with hepatitis B cirrhosis was assessed using the liver frailty index (LFI). Their physical activity levels and sedentary time were assessed using the International Questionnaire of Physical Activity. Pearson correlation and binary logistic regression were used to analyse the data. RESULTS: Among the 503 patients with hepatitis B cirrhosis in the final analysis, 107 (21.3%) were identified as frail. Frailty was negatively correlated with walking time (r = -0.174, p < 0.001), moderate-intensity activity time (r = -0.185, p < 0.001), high-intensity activity time (r = -0.243, p < 0.001) and total activity time (r = -0.256, p < 0.001). Patients with insufficient activity (<150 min/week) and sedentary behaviour (≥420 min/day) were found to have 2.829 times higher risk of frailty than those with sufficient activity (≥150 min/week) and no sedentary behaviour (<420 min/day) (95% CI: 1.380, 5.799). CONCLUSION: Patients with hepatitis B cirrhosis who exhibited frailty demonstrated limited physical activity and engaged in sedentary behaviours. NO PATIENT OR PUBLIC CONTRIBUTION: Patients with hepatitis B cirrhosis contributed their data to the study.

Risk assessment of SARS-CoV-2 replicating and evolving in animals.

The retransmissions of SARS-CoV-2 from several mammals - primarily mink and white-tailed deer - to humans have raised concerns for the emergence of a new animal-derived SARS-CoV-2 variant to worsen the pandemic. Here, we discuss animal species that are susceptible to natural or experimental infection with SARS-CoV-2 and can transmit the virus to mates or humans. We describe cutting-edge techniques to assess the impact of a mutation in the viral spike (S) protein on its receptor and on antibody binding. Our review of spike sequences of animal-derived viruses identified nine unique amino acid exchanges in the receptor-binding domain (RBD) that are not present in any variant of concern (VOC). These mutations are present in SARS-CoV-2 found in companion animals such as dogs and cats, and they exhibit a higher frequency in SARS-CoV-2 found in mink and white-tailed deer, suggesting that sustained transmissions may contribute to maintaining novel mutations. Four of these exchanges, such as Leu452Met, could undermine acquired immune protection in humans while maintaining high affinity for the human angiotensin-converting enzyme 2 (ACE2) receptor. Finally, we discuss important avenues of future research into animal-derived viruses with public health risks.

Seroprevalence and transmission of severe fever with thrombocytopenia syndrome virus in a coastal endemic area in Southeastern China.

Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerged tick-borne viral zoonosis and widely prevalent in China, Japan and South Korea. Most reported SFTS cases have been identified in mountainous and hilly areas, with a few in island areas. In this study, we conducted a systematic investigation about natural infection of SFTS virus (SFTSV) among humans, animals and ticks in a coastal endemic prefecture, containing island, plains and mountain settings, in Zhejiang Province, Southeastern China. From July 2020 to June 2021, 1117 participants completed a survey with questionnaire interview and serum testing. Meanwhile, 862 serum samples of domestic animals, 275 spleen tissue samples of wild animals and 829 ticks representing five species (predominantly Haemaphysalis longicornis and Rhipicephalus sanguineus sensu lato) were collected. The seroprevalence of anti-SFTSV total antibody and IgM antibody among the participants was 4.8 % (54/1117) and 0.6 % (7/1117), respectively. Multivariate logistic regression analysis indicated that living in the island area (OR=2.66; 95 %CI: 1.04-6.80; P = 0.041) was significantly associated with seropositivity of total antibody to SFTSV. Furthermore, a higher seroprevalence was observed in domestic animals (36.1 %), while the SFTSV-RNA infection rate was 0.4 % in wild animals and the minimum infection rate (MIR) was 0.8 % for all tick species combined. The only tick species infected with SFTSV was H. longicornis. The prevalence of SFTSV infection in the island area, manifested by anti-SFTSV total antibody (P = 0.012) and IgM antibody (P = 0.004) among humans, anti-SFTSV total antibody (P<0.001) among domestic animals, and SFTSV-RNA among ticks (P = 0.022), was significantly higher than that in the mountainous area and the plain area. Furthermore, phylogenetic analysis showed that SFTSV sequences obtained from ticks in the island area were clustered with reported strains in Japan and South Korea. These results suggest that islands in the study area might be an important natural focus of SFTSV.

Incidence, clearance, and factors associated with anal human papilloma virus infection among men with HIV.

OBJECTIVES: This study aims to estimate the incidence and persistence/clearance of anal human papilloma virus (HPV) infection and related factors among men with HIV in Taizhou, China. DESIGN: A prospective cohort study. METHODS: Men with HIV were recruited and followed up from 2016 to 2021. Questionnaire surveys were used to collect social-demographic and behavioral characteristics, and anal swabs were collected for HPV Genotyping. RESULTS: A total of 675 men with HIV were recruited and followed up. After an average follow-up time of 1.75 years, HPV39 (3.8/100 person-years), HPV52 (3.6/100 person-years), HPV51 (3.1/100 person-years), HPV58 (2.5/100 person-years) and HPV16 (2.4 cases/100 person-years) in the high-risk types showed the highest incidence rate. In marriage with woman [adjusted hazard ratio (aHR) = 0.44, 95% confidence interval (CI) 0.20-0.99] showed an inverse association with HPV incidence, while bisexuality or undetermined sexual orientation (aHR = 2.62, 95% CI 1.08-6.36) showed a positive association. For those infected at baseline, the top three high-risk HPV with the lowest clearance density were HPV52 (32.2/100 person-years), HPV58 (38.1/100 person-years), and HPV16 (43.5/100 person-years). Daily consumption of 1-28 g alcohol (aHR = 0.62, 95% CI 0.41-0.95) showed an inverse association with HPV clearance, while illicit drug use (aHR = 3.24, 95% CI 1.59-6.59) showed a positive association. CONCLUSION: Anal HPV infection and clearance were both active in men with HIV in China. Marriage status and sexuality were associated with the incidence of HPV infection, while substance use including alcohol and illicit drug were associated with HPV clearance. More studies are needed to explore the risk factors of HPV persistence.

Purification of fibrinolytic enzyme from Bacillus amyloliquefaciens GUTU06 and properties of the enzyme.

A producing-fibrinolytic enzyme strain was isolated with high yield. The strain was identified as Bacillus amyloliquefaciens. B. amyloliquefaciens GUTU06 fibrinolytic enzyme was purified by acetone precipitation and reverse micelle. Acetone precipitation condition and reverse micelle condition were examined. Results showed that the total reverse micelle extraction efficiency was 64.49 % ± 1.6 %. The purification fold of the entire process reached 13.38. The optimum pH of purified enzyme is 5, and the optimum temperature is 45 °C. Fe3+ and K+ can enhance the fibrinolytic activity of the enzyme. Compared to commercial fibrinolytic enzymes such as urokinase and lumbrukinase, GUTU06 fibrinolytic enzymes have a lower pH optimal range and higher temperature stability. The molecular weight of the enzyme was approximately 28 kDa. Reverse micelle extraction with cetyl trimethylammonium bromide as a surfactant combined with acetone precipitation is suitable for separating and purifying fibrinolytic enzymes and a promising technique for obtaining active proteins.

Semisynthesis and in Vitro Anti-cancer Effect of New Magnolol Derivatives on the Cell Proliferation, Apoptosis, Migration, and Invasion of Human Hepatocellular Carcinoma SMMC-7721 Cells.

Four new magnolol derivatives were synthesized and evaluated for their in vitro anti-cancer properties. Among these, compound 3 showed the most potent cytotoxic activity against the SMMC-7721, SUN-449, and HepG2 human hepatocellular carcinoma cell lines, with IC50 values of 3.39, 4.11, and 6.88 µM, respectively. Compound 3 also induced apoptosis of SMMC-7721 cells by down-regulating Bcl-2 and Akt protein levels, up-regulating of Bax protein level, and cleaving caspase-9 and -3. In addition, transwell assays showed that compound 3 significantly suppressed the migration and invasion of SMMC-7721 cells, which was confirmed based on the down-regulation of hypoxia inducible factor-1α (HIF-1α), matrix metalloproteinase-2 and -9 (MMP-2, and MMP-9) protein levels.

Nursing care of patients with relapsed and refractory multiple myeloma treated with B-cell mature antigen-targeted universal chimeric antigen receptor T cells.

To investigate the efficacy of a nursing approach using B-cell maturation antigen (BCMA)-targeted universal chimeric antigen receptor T-cell (BCMA-UCART) immunotherapy in the treatment of 8 patients with relapsed refractory multiple myeloma (MM). In this study, 16 patients with relapsed and refractory MM who were treated with BCMA-targeted UCART in our department from May 2020 to November 2022 were selected, and were divided into a control group and an experimental group of 8 cases each according to the difference in the nursing methods, and the control group adopted the conventional universal nursing program. The experimental group used the nursing protocol that cooperated with the immunotherapy of this study, and the main points of nursing care included timely assessment of organ functional status, safe and accurate infusion of BCMA-UCART, identification and management of hyperthermia, hypotension, arrhythmia and central nervous system adverse reactions caused by cytokine release after BCMA-UCART infusion, as well as management of fluid imbalance, maintenance of stable blood pressure, and cooperation with physicians to effectively control of inflammatory factors. In addition, patients were provided with psychological and dietary support. The duration of hospitalization was compared between the two groups after the intervention. The discharge time of the experimental group was significantly shorter than that of the control group (P he.05), and the experimental group effectively controlled cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome and acute graft-versus-host disease. The nursing program with BCMA-UCART immunotherapy is effective in intervening MM patients and promotes their early recovery and discharge from the hospital.

Association of Insomnia, Sleep Quality, and Sleep Duration With Risk of Physical Frailty in Middle-aged and Older People With HIV.

Background: Frailty is one of the major concerns among aging people with HIV (PWH). Evidence regarding the association between sleep disorders and physical frailty in PWH is limited. Methods: PWH and HIV-negative individuals aged ≥40 years were included and frequency-matched in a 1:2 ratio by sex and age. Logistic regression models were used to estimate the odds ratios (ORs) and 95% CIs of the association between sleep disorders and physical frailty, and restricted cubic splines were used to describe the dose-response association. The contribution of depression to the association was estimated by mediation analysis. Results: A total of 1526 PWH and 3052 HIV-negative individuals were included. Logistic regression indicated that insomnia (OR, 3.05; 95% CI, 1.63-5.72) and poor sleep quality (OR, 2.32; 95% CI, 1.21-4.45) were significantly associated with physical frailty in middle-aged and older PWH, especially in those with current CD4+ T-cell counts <350 cells/µL, but not in HIV-negative participants. A U-shaped and J-shaped dose-response relation between sleep duration and physical frailty was observed in PWH and HIV-negative participants, respectively. Shorter and longer sleep duration was associated with an increased risk of physical frailty in PWH. However, in HIV-negative participants, only longer sleep duration was associated with physical frailty. Mediation analysis revealed that depression mediated the relation between sleep disorders and frailty among PWH. Conclusions: Sleep disorders including insomnia, poor sleep quality, and short and long sleep duration were significantly associated with physical frailty among middle-aged and older PWH. Depression may play a mediating role in the sleep-frailty association.