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1.
Heliyon ; 10(15): e35454, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39170111

ABSTRACT

Background: Conditional approvals, also known as accelerated approvals, have been introduced by many pharmaceutical regulators around the world, allowing innovative drugs to enter the market earlier on the basis of limited evidence. This research aims to systematically analyze and compare the post-marketing requirements for conditional approvals of oncology drugs in China and the United States. By collecting and categorizing different types of post-marketing requirements, this study seeks to elucidate how these requirements are proposed and discern the underlying logic and patterns. Methods: This study delved into oncology drug approvals, encompassing FDA accelerated approvals (up to December 31, 2022) and NMPA conditional approvals (from 2017 to December 31, 2022). Leveraging review documents from FDA and NMPA, comprehensive data on product characteristics, all post-marketing commitments and requirements, and especially those related to confirmatory requirements were extracted. The analysis incorporated descriptive statistics, visualizations such as Upset plots, and thorough examination of confirmatory requirement timeframes. Findings: This study examined 168 FDA accelerated approvals and 41 NMPA conditional approvals for oncology indications. Post-marketing requirements displayed diversity: FDA emphasized confirmatory studies, clinical pharmacology studies, and more, while NMPA predominantly focused on confirmatory studies. Confirmatory requirement timeframes indicated higher FDA-required completion times for new confirmatory trials compared to continued completion of original pivotal trials. In contrast, NMPA's requirement patterns were comparatively singular, with relatively fixed timeframes. FDA's evolving trend showed decreasing timeframes over time, suggesting an increasing demand for timely confirmatory data. Interpretation: Conditional approvals offer a unique approach to bring potentially life-saving drugs to the market faster, despite limited supporting evidence. Our analysis of oncology drug conditional approvals in the U.S. and China reveals diverse post-marketing requirement patterns. This study provides valuable insights for regulatory decision-making in a dynamic pharmaceutical landscape. Balancing the risks and rewards of conditional approvals is crucial in ensuring both patient safety and timely access to innovative treatments.

2.
Nucleic Acids Res ; 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39149894

ABSTRACT

The 3D chromatin organization plays a major role in the control of gene expression. However, our comprehension of the governing principles behind nuclear organization remains incomplete. Particularly, the spatial segregation of loci with similar repressive transcriptional states in plants poses a significant yet poorly understood puzzle. In this study, employing a combination of genetics and advanced 3D genomics approaches, we demonstrated that a redistribution of facultative heterochromatin marks in regions usually occupied by constitutive heterochromatin marks disrupts the 3D genome compartmentalisation. This disturbance, in turn, triggers novel chromatin interactions between genic and transposable element (TE) regions. Interestingly, our results imply that epigenetic features, constrained by genetic factors, intricately mold the landscape of 3D genome organisation. This study sheds light on the profound genetic-epigenetic interplay that underlies the regulation of gene expression within the intricate framework of the 3D genome. Our findings highlight the complexity of the relationships between genetic determinants and epigenetic features in shaping the dynamic configuration of the 3D genome.

3.
Hum Vaccin Immunother ; 20(1): 2383509, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-39132758

ABSTRACT

The investigation was conducted to describe the status of coverage of HBV vaccination among the health care workers in Gansu province and to explore the associated factors of HBV vaccination in this study. A cross-sectional study was conducted among 1544 health care workers from 64 hospitals in Gansu province. A self-designed questionnaire was used to interview the health care workers about HBV vaccination coverage. A multivariate logistic regression model explored the associated factors with HBV vaccination. The vaccination coverage was 89.17% for health care workers, nurses (90.40%) had the highest rate, followed by administration staff (89.38%) and medical technicians (89.30%). The full-dose HBV vaccination coverage was 64.25% for health care workers, and administration staff (65.04%) had the highest rate, followed by nurses (65.00%). This study found that the associated factors with HBV vaccination and full-dose vaccination were the history of training and the detection of serological indicators. The coverage of HBV vaccination among health care workers in Gansu province was high, but full-dose HBV vaccination coverage was low. It is necessary to strengthen the HBV knowledge and training in HBV prevention and treatment among health care workers in Gansu Province.


Subject(s)
Health Personnel , Hepatitis B Vaccines , Hepatitis B , Vaccination Coverage , Humans , Vaccination Coverage/statistics & numerical data , Cross-Sectional Studies , Health Personnel/statistics & numerical data , Female , Male , Hepatitis B/prevention & control , Adult , Hepatitis B Vaccines/administration & dosage , Middle Aged , Surveys and Questionnaires , China/epidemiology , Young Adult , Vaccination/statistics & numerical data
4.
J Cardiovasc Magn Reson ; : 101080, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39127261

ABSTRACT

BACKGROUND: Cardiovascular magnetic resonance (CMR) has demonstrated excellent performance in the diagnosis of cardiac amyloidosis (CA). However, misdiagnosis occasionally occurs because the morphological and functional features of CA are non-specific. This study was performed to determine the value of non-contrast CMR T1ρ in the diagnosis of CA. METHODS: This prospective study included 45 patients with CA, 30 patients with hypertrophic cardiomyopathy (HCM), and 10 healthy controls (HCs). All participants underwent cine (whole heart), T1ρ mapping, pre- and post-contrast T1 mapping imaging (three slices), and late gadolinium enhancement using a 3T whole-body MRI system. All participants underwent T1ρ at two spin-locking frequencies: 0Hz and 298Hz. ECV maps were obtained using pre- and post-contrast T1 maps. The myocardial T1ρ dispersion map, termed myocardial dispersion index (MDI), was also calculated. All parameters were measured in the left ventricular myocardial wall. Participants in the HC group were scanned twice on different days to assess the reproducibility of T1ρ measurements. RESULTS: Excellent reproducibility was observed upon evaluation of the coefficient of variation between two scans (T1ρ [298Hz]: 3.1%; T1ρ [0Hz], 2.5%). The ECV (HC: 27.4 ± 2.8% vs. HCM: 32.6 ± 5.8% vs. CA: 46 ± 8.9%; p < 0.0001), T1ρ [0Hz] (HC: 35.8 ± 1.7 ms vs. HCM: 40.0 ± 4.5 ms vs. CA: 51.4 ± 4.4 ms; p < 0.0001) and T1ρ [298Hz] (HC: 41.9 ± 1.6 ms vs. HCM: 48.8 ± 6.2 ms vs. CA: 54.4 ± 5.2 ms; p < 0.0001) progressively increased from the HC group to the HCM group, and then the CA group. The MDI progressively decreased from the HCM group to the HC group, and then the CA group (HCM: 8.8 ± 2.8 ms vs. HC: 6.1 ± 0.9 ms vs. CA: 3.4 ± 2.1 ms; p < 0.0001). For differential diagnosis, the combination of MDI and T1ρ [298Hz] showed the greatest sensitivity (98.3%) and specificity (95.5%) between CA and HCM, compared with the native T1 and ECV. CONCLUSIONS: The T1ρ and MDI approaches can be used as non-contrast CMR imaging biomarkers to improve the differential diagnosis of patients with CA.

5.
Am J Transl Res ; 16(7): 3385-3394, 2024.
Article in English | MEDLINE | ID: mdl-39114686

ABSTRACT

BACKGROUND: Surgery is an important treatment modality for patients with digestive system tumors, and perioperative management is crucial for the patients' recovery and quality of life. During the perioperative period, significant changes can occur in the oral environment of patients, such as dry mouth, mucosal ulceration, and oral infections. These issues not only cause discomfort to the patients but may also affect postoperative recovery and treatment outcomes. Therefore, it is essential to investigate and analyze the oral environment during the perioperative period in patients with digestive system tumors. AIM: This study aims to investigate the oral health status in patients with digestive system tumors during the perioperative period and analyze the influencing factors. METHODS: In this retrospective study, a total of 242 patients with digestive system tumors admitted to The Seventh Affiliated Hospital, Xinjiang Medical University from September 2021 to June 2023 were selected as the study population (patient group). During the same period, 245 healthy volunteers who received oral examinations were selected as the healthy group. The study compared the oral hygiene environment of the two groups, including the Dental Plaque Index (DI), Calculus Index (CI), and Periodontal Disease Index (PDI). Measurements were taken at admission (T0), 1 hour before surgery (T1), and 3 days after surgery (T2). Based on the PDI index, the patient group was divided into a periodontal disease group (PDI ≥ 3, n = 196) and a periodontal healthy group (PDI < 3, n = 46). The risk factors for the development of periodontal disease in digestive system tumor patients were analyzed, considering variables such as gender, age, BMI, smoking status, alcohol consumption frequency, monthly income, tumor type, oral self-care habits, low-grade inflammation, and nutritional status. RESULTS: The DI, CI and PDI indexes in patient group were higher than those in healthy group (3.23±0.64 vs 1.46±0.43, 1.92±0.46 vs 1.21±0.41, 3.83±0.79 vs 2.65±0.69, all P < 0.05). DI index, CI index and PDI index at T1 and T2 were significantly lower than those at T0 (P < 0.05), and these indices at T2 were slightly higher than T1, but the difference was not statistically significant (all P > 0.05). Multivariate analyses identified high levels of high-sensitivity C-Reactive Protein [OR: 15.070 (1.611-140.951)], low levels of hemoglobin [OR: 0.239 (0.058-0.981)], and presence of dental caries [OR: 246.737 (1.160-52464.597)] as risk factors associated with periodontal disease in patients with digestive system tumors. CONCLUSION: It is important to enhance the attention and management of the oral environment during the perioperative period for patients with digestive system tumors.

6.
Front Pharmacol ; 15: 1361561, 2024.
Article in English | MEDLINE | ID: mdl-38974041

ABSTRACT

Background: Osteoarthritis (OA) is a chronic degenerative disease mainly characterized by cartilage damage and synovial inflammation. Si Miao Powder, an herbal formula, was recorded in ancient Chinese medicine prescription with excellent anti-inflammatory properties. Based on the classical formula, the modified Si Miao Powder (MSMP) was developed with the addition of two commonly Chinese orthopedic herbs, which had the efficacy of strengthening the therapeutic effect for OA. Methods: In the in vivo experiments, thirty-six 8-week-old male C57BL/6 mice were randomly divided into six groups: sham group, OA group, celecoxib group, low-MSMP group, middle-MSMP group, and high-MSMP group. OA mice were constructed by destabilization of medial meniscus (DMM) and treated with MSMP granules or celecoxib by gavage. The effects of MSMP on cartilage, synovitis and inflammatory factor of serum were tested. For in vitro experiments, control serum and MSMP-containing serum were prepared from twenty-five C57BL/6 mice. Macrophages (RAW264.7 cells) were induced by lipopolysaccharide (LPS) and then treated with MSMP-containing serum. The expression of inflammatory factors and the change of the NF-κB pathway were tested. Results: In vivo, celecoxib and MSMP alleviated OA progression in the treated groups compared with OA group. The damage was partly recovered in cartilage, the synovial inflammatory were reduced in synovium, and the concentrations of IL-6 and TNF-α were reduced and the expression of IL-10 was increased in serum. The function of the middle MSMP was most effective for OA treatment. The results of in vitro experiments showed that compared with the LPS group, the MSMP-containing serum significantly reduced the expression levels of pro-inflammatory (M1-type) factors, such as CD86, iNOS, TNF-α and IL-6, and promoted the expression levels of anti-inflammatory (M2-type) factors, such as Arg1 and IL-10. The MSMP-containing serum further inhibited NF-κB signaling pathway after LPS induction. Conclusion: The study demonstrated that MSMP alleviated OA progression in mice and MSMP-containing serum modulated macrophage M1/M2 phenotype by inhibiting the NF-κB signaling pathway. Our study provided experimental evidence and therapeutic targets of MSMP for OA treatment.

7.
Curr Microbiol ; 81(8): 253, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954028

ABSTRACT

Two Gram-stain-negative, facultative anaerobic, rod-shaped, motile bacterial strains, designated F26243T and F60267T were isolated from coastal sediment in Weihai, China. Strains F26243T and F60267T were grown at 4-40 °C (optimum 33 °C), pH 7.0-9.5 and pH 6.5-9.5 (optimum at pH 7.0), in the presence of 1.0-7.0% (w/v) NaCl (optimum 2.5%) and 1.0-12.0% (w/v) NaCl (optimum 2.0%), respectively. The 16S rRNA gene sequences phylogenetic analysis showed that strains F26243T and F60267T are closely related to the genus Marinobacter and exhibited the highest sequence similarities to Marinobacter salexigens HJR7T (97.7% and 98.0%, respectively), the similarity between two isolates was 96.7%. Strains F26243T and F60267T displayed genomic DNA G + C content of 53.6% and 53.8%, respectively. When compared to the M. salexigens HJR7T, the average nucleotide identity (ANI) values were 83.7% and 84.1%, and the percentage of conserved proteins (POCP) values were 79.9% and 84.6%, respectively. Ubiquinone 9 (Q-9) was the only respiratory quinone detected in both isolates. The major cellular fatty acids (> 10.0%) were summed feature 3 (comprising C16:1ω7c and/or C16:1ω6c), C16:0 and C18:1ω9c. The polar lipid profiles of strains F26243T and F60267T contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidyldimethylethanolamine, phosphatidylglycerol, aminophospholipid and one unidentified phospholipid. Based on genomic characteristics, phenotypic and chemotaxonomic, strains F26243T and F60267T represent two novel species of the genus Marinobacter, for which the names Marinobacter sediminicola sp. nov. and Marinobacter xiaoshiensis sp. nov. are proposed, the type strains are F26243T (= KCTC 92640T = MCCC 1H01345T) and F60267T (= KCTC 92638T = MCCC 1H01346T).


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Geologic Sediments , Marinobacter , Phylogeny , RNA, Ribosomal, 16S , Marinobacter/genetics , Marinobacter/classification , Marinobacter/isolation & purification , Geologic Sediments/microbiology , RNA, Ribosomal, 16S/genetics , Fatty Acids/chemistry , Fatty Acids/analysis , DNA, Bacterial/genetics , China , Phospholipids/analysis , Sequence Analysis, DNA , Seawater/microbiology
8.
Proc Natl Acad Sci U S A ; 121(28): e2400737121, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38968127

ABSTRACT

In recent years, the exploration of genome three-dimensional (3D) conformation has yielded profound insights into the regulation of gene expression and cellular functions in both animals and plants. While animals exhibit a characteristic genome topology defined by topologically associating domains (TADs), plants display similar features with a more diverse conformation across species. Employing advanced high-throughput sequencing and microscopy techniques, we investigated the landscape of 26 histone modifications and RNA polymerase II distribution in tomato (Solanum lycopersicum). Our study unveiled a rich and nuanced epigenetic landscape, shedding light on distinct chromatin states associated with heterochromatin formation and gene silencing. Moreover, we elucidated the intricate interplay between these chromatin states and the overall topology of the genome. Employing a genetic approach, we delved into the role of the histone modification H3K9ac in genome topology. Notably, our investigation revealed that the ectopic deposition of this chromatin mark triggered a reorganization of the 3D chromatin structure, defining different TAD-like borders. Our work emphasizes the critical role of H3K9ac in shaping the topology of the tomato genome, providing valuable insights into the epigenetic landscape of this agriculturally significant crop species.


Subject(s)
Epigenome , Histones , Solanum lycopersicum , Solanum lycopersicum/genetics , Solanum lycopersicum/metabolism , Histones/metabolism , Histones/genetics , Epigenesis, Genetic , Genome, Plant , Chromatin/metabolism , Chromatin/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant , Heterochromatin/metabolism , Heterochromatin/genetics , Histone Code/genetics
10.
Article in English | MEDLINE | ID: mdl-38904664

ABSTRACT

Two Gram-stain-negative, rod-shaped, non-motile, strictly aerobic strains, forming yellow colonies and designated F6058T and S2608T, were isolated from marine sediment collected in Weihai, PR China. Both strains grow at 4-40 °C (optimum, 30-33 °C), pH 6.0-7.5 (optimum, pH 6.5) and in the presence of 0-7.0 % (w/v) NaCl. The optimum NaCl concentrations for strains F6058T and S2608T were 2.0 % and 2.5 %, respectively. Phylogenetic analysis of the 16S rRNA gene sequences indicated that strains F6058T and S2608T share an evolutionary lineage with members of the genus Aequorivita. The isolates exhibited a 16S rRNA gene sequence similarity of 96.7 % to each other. Strains F6058T exhibited the highest 16S rRNA gene sequence similarity to Aequorivita xiaoshiensis F64183T (98.8 %), and S2608T was most similar to Aequorivita capsosiphonis A71T (96.9 %). Iso-C15:0, anteiso-C15:0 and iso-C17:0 3-OH were the major fatty acids of strains F6058T and S2608T. The sole respiratory quinone of both isolates was menaquinone 6 (MK-6). The polar lipid profiles of the isolates both consisted of phosphatidylethanolamine and phosphoglycolipids; however, strain F6058T exhibited one glycolipid, one aminolipid and two unidentified polar lipids, and strain S2608T also had two glycolipids and one unidentified polar lipid. The DNA G+C contents of strains F6058T and S2608T were 34.6 % and 37.7 mol%, respectively. Based on their phenotypic, chemotaxonomic and genomic characteristics, strains F6058T and S2608T were considered to represent novel species of the genus Aequorivita, for which the names Aequorivita sediminis sp. nov. and Aequorivita marina sp. nov. were proposed. The type strains are F6058T (=KCTC 92653T=MCCC 1H01358T) and S2608T (KCTC 92652T=MCCC 1H01361T).


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Geologic Sediments , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Vitamin K 2 , RNA, Ribosomal, 16S/genetics , Geologic Sediments/microbiology , Fatty Acids/chemistry , China , Vitamin K 2/analogs & derivatives , Vitamin K 2/analysis , DNA, Bacterial/genetics , Seawater/microbiology , Molecular Sequence Data , Phospholipids/chemistry , Phosphatidylethanolamines
11.
Cancer Med ; 13(12): e7372, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38923216

ABSTRACT

BACKGROUND: Chimeric antigen receptor T (CAR-T) cell therapy has emerged as a potent treatment for relapsed or refractory multiple myeloma, demonstrating significant clinical efficacy. Despite these advances, treatment-related toxicities, particularly infections, pose a significant challenge to patient safety. METHODS: This review synthesizes current knowledge on the mechanisms underlying post-CAR-T therapy infections, focusing on the interplay between immune dysfunction, host factors, and treatment-induced toxicity. It provides a comprehensive analysis of the temporal and individual variability in infection characteristics and the confounding clinical presentation of cytokine release syndrome. RESULTS: The review identifies that patients receiving CAR-T cells are at increased risk of concurrent infections due to the heterogeneity in infection characteristics across different time periods, individuals, and patient groups. It highlights the diagnostic and therapeutic complexities introduced by the overlapping symptoms of infection and cytokine release syndrome. CONCLUSION: To enhance the infection control post-CAR-T therapy, this review proposes preventive strategies tailored to the early and long-term management of patients. It underscores the need for a nuanced understanding of infection mechanisms and the importance of personalized prevention plans to improve clinical outcomes in multiple myeloma treatment.


Subject(s)
Immunotherapy, Adoptive , Multiple Myeloma , Humans , Multiple Myeloma/therapy , Multiple Myeloma/immunology , Immunotherapy, Adoptive/adverse effects , Immunotherapy, Adoptive/methods , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/prevention & control , Receptors, Chimeric Antigen/immunology , Infections/etiology , Risk Factors
12.
J Med Virol ; 96(6): e29755, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38922896

ABSTRACT

Throughout the COVID-19 pandemic, rhinovirus (RV) remained notable persistence, maintaining its presence while other seasonal respiratory viruses were largely suppressed by pandemic restrictions during national lockdowns. This research explores the epidemiological dynamics of RV infections among pediatric populations on Hainan Island, China, specifically focusing on the impact before and after the zero-COVID policy was lifted. From January 2021 to December 2023, 19 680 samples were collected from pediatric patients hospitalized with acute lower respiratory tract infections (ARTIs) at the Hainan Maternal and Child Health Hospital. The infection of RV was detected by tNGS. RV species and subtypes were identified in 32 RV-positive samples representing diverse time points by analyzing the VP4/VP2 partial regions. Among the 19 680 pediatric inpatients with ARTIs analyzed, 21.55% were found to be positive for RV infection, with notable peaks observed in April 2021 and November 2022. A gradual annual decline in RV infections was observed, alongside a seasonal pattern of higher prevalence during the colder months. The highest proportion of RV infections was observed in the 0-1-year age group. Phylogenetic analysis on 32 samples indicated a trend from RV-A to RV-C in 2022. This observation suggests potential evolving dynamics within the RV species although further studies are needed due to the limited sample size. The research emphasizes the necessity for ongoing surveillance and targeted management, particularly for populations highly susceptible to severe illnesses caused by RV infections.


Subject(s)
COVID-19 , Genetic Variation , Phylogeny , Picornaviridae Infections , Respiratory Tract Infections , Rhinovirus , Humans , Rhinovirus/genetics , Rhinovirus/classification , Rhinovirus/isolation & purification , China/epidemiology , Infant , Child, Preschool , Picornaviridae Infections/epidemiology , Picornaviridae Infections/virology , Child , Female , Male , COVID-19/epidemiology , COVID-19/virology , Respiratory Tract Infections/virology , Respiratory Tract Infections/epidemiology , Infant, Newborn , Seasons , Adolescent , Prevalence , Child, Hospitalized/statistics & numerical data , SARS-CoV-2/genetics , Hospitalization/statistics & numerical data
13.
China CDC Wkly ; 6(19): 418-423, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38854752

ABSTRACT

What is already known on this topic?: In China, there is limited data available on the use and coverage of the non-program, combined diphtheria, tetanus toxoid, acellular pertussis adsorbed, inactivated poliovirus and haemophilus influenzae type b (DTaP-IPV/Hib) pentavalent vaccine, and its role as a substitute for the separately administered standalone program vaccines. What is added by this report?: We evaluated the use and coverage of the pentavalent vaccine in nine provincial-level administrative divisions (PLADs) spanning eastern, central, and western China from 2019 to 2021. Initial use and coverage were low, but demonstrated annual growth albeit with regional and urban-rural discrepancies. The pentavalent vaccine was increasingly substituted for standalone vaccines over the course of this period. What are the implications for public health practice?: Parents in China are increasingly opting to replace the standard program vaccines with voluntarily purchased combination vaccines, particularly the pentavalent vaccine. The development of combination vaccines should thus be promoted in China, as it could enhance utilization and coverage rates, and decrease the economic burden.

14.
Front Pharmacol ; 15: 1374669, 2024.
Article in English | MEDLINE | ID: mdl-38895626

ABSTRACT

Pulmonary fibrosis is a progressive, irreversible, chronic interstitial lung disease associated with high morbidity and mortality rates. Current clinical drugs, while effective, do not reverse or cure pulmonary fibrosis and have major side effects, there are urgent needs to develop new anti-pulmonary fibrosis medicine, and corresponding industrially scalable process as well. Salvia castanea Diels f. tomentosa Stib., a unique herb in Nyingchi, Xizang, China, is a variant of S. castanea. and its main active ingredient is rosmarinic acid (RA), which can be used to prepare methyl rosmarinate (MR) with greater drug potential. This study presented an industrially scalable process for the preparation of MR, which includes steps such as polyamide resin chromatography, crystallization and esterification, using S. castanea Diels f. tomentosa Stib. as the starting material and the structure of the product was verified by NMR technology. The anti-pulmonary fibrosis effects of MR were further investigated in vivo and in vitro. Results showed that this process can easily obtain high-purity RA and MR, and MR attenuated bleomycin-induced pulmonary fibrosis in mice. In vitro, MR could effectively inhibit TGF-ß1-induced proliferation and migration of mouse fibroblasts L929 cells, promote cell apoptosis, and decrease extracellular matrix accumulation thereby suppressing progressive pulmonary fibrosis. The anti-fibrosis effect of MR was stronger than that of the prodrug RA. Further study confirmed that MR could retard pulmonary fibrosis by down-regulating the phosphorylation of the TGF-ß1/Smad and MAPK signaling pathways. These results suggest that MR has potential therapeutic implications for pulmonary fibrosis, and the establishment of this scalable preparation technology ensures the development of MR as a new anti-pulmonary fibrosis medicine.

15.
Molecules ; 29(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38731434

ABSTRACT

Cannabidiol (CBD), a non-psychoactive ingredient extracted from the hemp plant, has shown therapeutic effects in a variety of diseases, including anxiety, nervous system disorders, inflammation, and tumors. CBD can exert its antitumor effect by regulating the cell cycle, inducing tumor cell apoptosis and autophagy, and inhibiting tumor cell invasion, migration, and angiogenesis. This article reviews the proposed antitumor mechanisms of CBD, aiming to provide references for the clinical treatment of tumor diseases and the rational use of CBD.


Subject(s)
Apoptosis , Cannabidiol , Neoplasms , Cannabidiol/pharmacology , Cannabidiol/therapeutic use , Cannabidiol/chemistry , Humans , Apoptosis/drug effects , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/metabolism , Animals , Autophagy/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Movement/drug effects , Cell Cycle/drug effects , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry
16.
Trials ; 25(1): 335, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773529

ABSTRACT

BACKGROUND: With suicide as a leading cause of death, the issue of children and adolescent suicide risks is in the spotlight today. To empower teachers in primary and secondary schools to serve as gatekeepers and to ensure the safety of children and adolescents, the systematically tailored and localized Life Gatekeeper suicide prevention program was designed for Chinese schools. OBJECTIVE: With the ultimate goal of preventing child and adolescent suicide, we aim to outline a research protocol for examining outcomes of the recently created standardized school-based Life Gatekeeper program in reducing teachers' stigma, increasing their knowledge, willingness to intervene, and perceived competence. METHODS: Participants will be recruited from eligible primary and secondary schools. Cluster sampling will be used to randomly assign each school to either the intervention group or the control group. The primary outcomes are stigma against suicide, suicide literacy, perceived competence, and willingness to intervene with suicidal individuals, which will be measured using the Stigma of Suicide Scale, the Literacy of Suicide Scale, and the Willingness to Intervene Against Suicide Questionnaire, respectively. Measurements will be taken at four time points, including pre-intervention, immediately after the intervention, 6-month follow-up, and 1-year follow-up. CONCLUSIONS: The current study features innovative implementation in the real world, by using a randomized controlled trial design to examine the effectiveness of a school-based gatekeeper program among primary and secondary school teachers, following a sequence of defined and refined steps. The research will also investigate the viability of a school-based gatekeeper program for primary and secondary school teachers that could be quickly and inexpensively implemented in a large number of schools.


Subject(s)
Health Knowledge, Attitudes, Practice , School Health Services , School Teachers , Social Stigma , Suicide Prevention , Teacher Training , Humans , China , Adolescent , Child , School Teachers/psychology , Teacher Training/methods , Randomized Controlled Trials as Topic , Suicide/psychology , Time Factors , Male , Female , Adolescent Behavior , School Mental Health Services , Program Evaluation , Child Behavior
17.
J Hazard Mater ; 472: 134578, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38743971

ABSTRACT

Microplastics (MPs) are widespread in agricultural soil, potentially threatening soil environmental quality and plant growth. However, toxicological research on MPs has mainly been limited to individual components (such as plants, microbes, and animals), without considering their interactions. Here, we examined earthworm-mediated effects on tomato growth and the rhizosphere micro-environment under MPs contamination. Earthworms (Eisenia fetida) mitigated the growth-inhibiting effect of MPs on tomato plant. Particularly, when exposed to environmentally relevant concentrations (ERC, 0.02% w/w) of MPs, the addition of earthworms significantly (p < 0.05) increased shoot and root dry weight by 12-13% and 13-14%, respectively. MPs significantly reduced (p < 0.05) soil ammonium (NH4+-N) (0.55-0.69 mg/kg), nitrate nitrogen (NO3--N) (7.02-8.65 mg/kg) contents, and N cycle related enzyme activities (33.47-42.39 µg/h/g) by 37.7-50.9%, 22.6-37.2%, and 34.2-48.0%, respectively, while earthworms significantly enhanced (p < 0.05) inorganic N mineralization and bioavailability. Furthermore, earthworms increased bacterial network complexity, thereby enhancing the robustness of the bacterial system to resist soil MPs stress. Meanwhile, partial least squares modelling showed that earthworms significantly influenced (p < 0.01) soil nutrients, which in turn significantly affected (p < 0.01) plant growth. Therefore, the comprehensive consideration of soil ecological composition is important for assessing MPs ecological risk.


Subject(s)
Microplastics , Oligochaeta , Rhizosphere , Soil Pollutants , Solanum lycopersicum , Solanum lycopersicum/drug effects , Solanum lycopersicum/growth & development , Oligochaeta/drug effects , Animals , Soil Pollutants/toxicity , Microplastics/toxicity , Plant Roots/drug effects , Plant Roots/growth & development , Nitrogen/metabolism , Soil Microbiology
18.
BMC Public Health ; 24(1): 940, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38566105

ABSTRACT

Family has a significant impact on individual mental health. Based on social support theory, family system theory and the Mental Health Continuum Short Form (MHC-SF), this research constructed a model of the pathway of perceived family support on psychological well-being and the results empirically clarified that perceived family support has a significant positive relationship with emotional well-being, social well-being, and psychological well-being (P < 0.001). Emotional well-being positively influences social well-being and psychological well-being (P < 0.001). Social well-being positively affects psychological well-being (P < 0.001). There were direct mediating effects of emotional well-being (13.45%), direct mediating effects of social well-being (32.82%) and a serial mediating effect (28.07%) between perceived family support and psychological well-being (P < 0.001).


Subject(s)
Family Support , Psychological Well-Being , Humans , Mental Health , Emotions , Social Support
19.
Heliyon ; 10(7): e28341, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38623204

ABSTRACT

Purpose: To explore global/regional myocardial deformation across various layers, vascular distributions, specific levels and distinct walls in healthy individuals using cardiovascular magnetic resonance feature tracking (CMR-FT). Methods: We selected a cohort of 55 healthy participants and CMR cine images were used to obtain the left ventricular (LV) peak longitudinal, circumferential, radial strains (LS, CS, RS). The characteristics of normal LV strain in various layers (endocardium, myocardium, epicardium), territories [left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA)], levels (basal, middle, apical) and walls (anterior, septum, inferior, lateral) were compared. Results: The absolute values of the LV global LS and CS gradually decreased from endocardium to epicardium. The absolute LV global RS (65.7 ± 47.7%) was maximum relative to LS (-22.0 ± 10.8%) and CS (-22.8 ± 7.7%). The absolute values of the LCX territorial strain were the largest compared with the LAD and RCA territorial strains. Regional RS, endo-CS and endo-LS gradually increased from the basal to the apical level. The LV lateral walls had the highest strain values (CS, LS, and RS). Conclusions: Variations in normal LV strain values across various layers, territories, levels, and walls were observed, suggesting the necessity for careful clinical interpretation of these strain values. These findings also partially revealed the complexity of normal cardiac mechanics.

20.
Sci Total Environ ; 927: 172268, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38583629

ABSTRACT

Due to the inappropriate disposal of waste materials containing lead (Pb) and irrigation with sewage containing Pb, the migration of Pb2+ within the soil profile has been extensively investigated. The conventional Pb2+ block method is challenging to implement due to its complex operational procedures and high construction costs. To address this issue, this study introduces the microbial-induced carbonate precipitation (MICP) technique as a novel approach to impede the migration of Pb2+ in the soil profile. Soil acclimatization with urea resulted in an increased proportion of urease-producing microorganisms, including Bacillus, Paenibacillus, and Planococcaceae, along with heightened expression of urea-hydrolyzing genes (UreA, UreB, UreC, and UreG). This indicates that urea-acclimatized soil (Soil-MICP) possesses the potential to induce carbonate precipitation. Batch Pb2+ fixation experiments confirmed that the fixation efficiency of Soil-MICP on Pb2+ exceeded that of soil without MICP, attributed to the MICP process within the Soil-MICP group. Dynamic migration experiments revealed that the MICP reaction transformed exchangeable lead into carbonate-bound Pb, effectively impeding Pb2+ migration in the soil profile. Additionally, the migration rate of Pb2+ in Soil-MICP was influenced by varying urea amounts, pH levels, and pore flow rates, leading to a slowdown in migration. The Two-site sorption model aptly described the Pb2+ migration process in the Soil-MICP column. This study aims to elucidate the MICP biomineralization process, uncover the in-situ blocking mechanism of MICP on lead in soil, investigate the impact of Pb on key genes involved in urease metabolism, enhance the comprehension of the chemical morphology of lead mineralization products, and provide a theoretical foundation for MICP technology in preventing the migration of Pb2+ in soil profiles.


Subject(s)
Carbonates , Lead , Soil Microbiology , Soil Pollutants , Soil , Soil/chemistry , Urease/metabolism , Chemical Precipitation
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