OBJECTIVE To provide technical support for improving recognition rate of adverse drug events （ADEs） related to traditional Chinese medicine （TCM） formula granules and decoction pieces among inpatient patients. METHODS By referencing the global trigger tool （GTT） whitepaper， literature on adverse reactions to TCM， and expert review opinions， ADE trigger items for TCM formula granules and decoction pieces used in the inpatients were established. GTT was applied to analyze ADEs in inpatients who had used TCM formula granules and decoction pieces in our hospital from August 2013 to August 2023， utilizing the Chinese Hospital Pharmacovigilance System. The effectiveness of GTT and the characteristics of these ADEs were analyzed. RESULTS A total of forty-eight triggers were established， including thirty-two laboratory test indexes， thirteen clinical symptoms， and three antidotes. Among the 1 682 patients included， GTT identified 652 potential ADEs， 284 true positive ADEs，with a trigger rate of 38.76% and a positive predictive value of 43.56%. After review by the auditor， 278 cases of ADEs were finally confirmed， with an incidence rate of 16.53%， significantly higher than the number of spontaneously reported ADEs during the same period （0）. The 278 cases of ADEs were mostly grade 1 （223 cases）， mainly involving hepatobiliary system， gastrointestinal system， blood- lymphatic system， etc；a total of 219 types of TCMs are involved，and the top five suspected TCMs used at a frequency higher than 1% were Poria cocos， Codonopsis pilosula， Atractylodes macrocephala， fried Glycyrrhiza uralensis， and Scutellaria baicalensis. CONCLUSIONS The established GTT can improve the recognition rate of ADEs for hospitalized patients using traditional Chinese medicine formula granules and decoction pieces.

A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals ; Humans ; Cardiomegaly/physiopathology* ; Ribosomes/physiology* ; Protein Biosynthesis/physiology* ; Mice ; Cardiomyopathy, Dilated/genetics* ; Ribosome Profiling

The mechanism of L-perilla alcohol(L-POH) in intervening hypoxic pulmonary hypertension(HPAH) was discussed based on network pharmacology, and experimental verification. The active components and potential targets of the volatile oil of Rhodiola tangutica(VORA) in the intervention of HPAH were screened by network pharmacology. The biological process of Gene Ontology(GO) and the signaling pathway enrichment of Kyoto Encyclopedia of Genes and Genomes(KEGG) were analyzed for the core targets, and a "component-common target-disease" network was constructed. Four active components were screened from VORA: L-POH, linalool, geraniol, and(-)-myrtenol. The core targets for treating HPAH were HSP90AA1, AKT1, ESR1, PIK3CA, EP300, EGFR, and JAK2. GO enrichment analysis mainly involved biological processes such as reaction to hypoxia, heme binding, and steroid binding. KEGG enrichment analysis mainly involved hypoxia-inducing factor 1(HIF-1) signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT) signaling pathway, and Janus kinase/activator of signal transduction and transcription(JAK/STAT) signaling pathway. The vasodilation effects of the four active components were screened by perfusion experiment of extracorporeal vascular rings, and the mechanism of the main active component L-POH was studied by channel blockers. The inhibitory effects of the four active components on the proliferation of pulmonary artery smooth muscle cells(PASMCs) induced by hypoxia were screened by cell proliferation experiment, and the mechanism of the main active component L-POH was studied by flow cytometry, cell cycle experiment, and Western blot. The results showed that L-POH could directly act on vascular smooth muscle to relax pulmonary arterioles, induce ATP-sensitive potassium channels to open, and inhibit extracellular Ca~(2+) influx through voltage-gated calcium channels to relax blood vessels. In addition, L-POH could inhibit the abnormal proliferation of PASMCs induced by hypoxia and promote its apoptosis, and its mechanism may be related to the increase in Bax protein expression and the decrease in p-JAK2, p-STAT3, Bcl-2, and cyclinA2 protein expression. In summary, L-POH can interfere with HPAH by relaxing pulmonary arterioles and inhibiting the proliferation of smooth muscle cells.
Network Pharmacology ; Animals ; Hypertension, Pulmonary/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Hypoxia/metabolism* ; Rhodiola/chemistry* ; Signal Transduction/drug effects* ; Humans ; Monoterpenes/chemistry* ; Male ; Cell Proliferation/drug effects* ; Rats, Sprague-Dawley

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVE: To assess the efficacy and safety of a new conditioning regimen with chidamide and BEAM for autologous hematopoietic stem cell transplantation (AHSCT) in patients with lymphoma. METHODS: Medical records and further follow-up data from 85 patients with lymphoma from May 2015 to September 2020 in our hospital were retrospectively collected and analyzed. RESULTS: Among 85 patients, 52 cases accepted BEAM regimen and 33 cases accepted CBEAM followed by AHSCT. In CBEAM group, 18 patients (54.5%) received AHSCT as salvage therapy, while only 26.9% (14 cases) for salvage in BEAM group ( P < 0.01). CBEAM conditioning resulted in shorter neutrophil engraftment of 2 days, while no significant difference was found in platelet engraftment. Although the incidence of liver impairment was higher in CBEAM group (12.1%), the grade of impairment was only Ⅰ to Ⅱ. The two conditioning regimens both achieved good complete remission rate of over 90%, and no transplant-related death occurred. The median follow-up time in the CBEAM group was 18(12, 22) months, and 39(20, 59) months in the BEAM group. There were no significantly differences in 2-year progression-free survival (PFS) and overall survival (OS) rate between the two groups (P >0.05). In patients with refractory or relapsed non-Hodgkin lymphoma, the 2-year PFS rate after transplantation in BEAM group and CBEAM group was 74.1% and 92.9%, respectively (P >0.05), indicating that chidamide may have certain advantages in prolonging PFS. CONCLUSION CBEAM conditioning regimen has a good efficacy and safety in lymphoma patients before AHSCT, especially in refractory and relapsed non-Hodgkin lymphoma patients, suggesting that it could serve as an alternative conditioning regimen prior to AHSCT for lymphoma.
Humans ; Hematopoietic Stem Cell Transplantation ; Transplantation Conditioning/methods* ; Transplantation, Autologous ; Retrospective Studies ; Aminopyridines/therapeutic use* ; Lymphoma/therapy* ; Benzamides/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Male ; Female ; Cytarabine/therapeutic use* ; Melphalan/therapeutic use* ; Adult ; Middle Aged ; Podophyllotoxin/therapeutic use* ; Carmustine ; Etoposide

OBJECTIVE: To explore and evaluate the efficacy and safety of a modified thiotepa-based conditioning regimen combined with autologous hematopoietic stem cell transplantation (ASCT) for the treatment of primary central nervous system lymphoma (PCNSL). METHODS: In a retrospective, single center, single arm study, we collected data of 28 patients with PCNSL who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) at our center from March 2021 to December 2024. The clinical characteristics of the patients, the conditioning regimen details, treatment-related toxicities and adverse reactions, post-transplant disease remission status, and survival outcomes were analyzed. RESULTS: A total of 28 patients were included. Among them, 19 patients received ASCT as first-line consolidation therapy in complete response (CR) or partial response (PR) status, and 9 patients with relapsed/refractory disease underwent salvage ASCT. The median time to neutrophil engraftment was 9 days (range: 5-11 days), and the median time to platelet engraftment was 10 days (range: 6-13 days). All patients achieved CR at the initial efficacy evaluation post-ASCT. The main complications during the transplantation period were febrile neutropenia (26 cases) and grade 3 diarrhea (9 cases). No transplantation-related mortality occurred. Post-ASCT, 19 patients received maintenance therapy, which was demonstrated to be safe and effective. Three patients relapse, and one patient died. The median progression-free survival (PFS) and overall survival (OS) of patients were not reached. The estimated 1-year and 2-year cumulative PFS rates were 88.4% and 66.3%, respectively, while the 1-year and 2-year OS rates were both 94.1%. CONCLUSION The modified thiotepa-based conditioning regimen combined with ASCT is safe and effective for the treatment of PCNSL.
Humans ; Thiotepa/therapeutic use* ; Retrospective Studies ; Transplantation, Autologous ; Transplantation Conditioning/methods* ; Central Nervous System Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Adult ; Lymphoma/therapy* ; Treatment Outcome ; Aged

OBJECTIVE: The aim of this study is to explore the influencing factors of fertility preservation decision-making in testicular cancer patient and provide a basis for clinical decision. METHODS: A descriptive qualitative study was conducted using purposive sampling in 18 testicular cancer patients. Semi-structured interviews were performed, and data were analyzed through content analysis. RESULTS: A total of 3 themes and 10 subthemes were extracted including individual factors (fertility circumstance, concerns about sperm cryopreservation efficacy/quality, the preferred choice between treatment and fertility preservation, confidence in future fertility), medical factors (physicians' recommendations on fertility preservation, fertility-related information, urgency of treatment), and socio-environmental factors (traditional beliefs of fertility, family/partner support, accessibility/cost of cryopreservation). CONCLUSION This study highlights many influencing factors of fertility preservation decision-making in testicular cancer patients, emphasizing the need for clinicians to enhance awareness of fertility preservation, provide timely and targeted information, and advocate for policy interventions to reduce financial barriers. Strengthening healthcare support and systemic safeguards may optimize patients' decision-making outcomes.
Humans ; Male ; Fertility Preservation ; Testicular Neoplasms/therapy* ; Decision Making ; Qualitative Research ; Cryopreservation ; Adult ; Infertility, Male/prevention & control*

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*