This study primarily investigates the effect of Liuwei Dihuang Pills on the activation and proliferation of female germline stem cells(FGSCs) in the ovaries and cortex of mice with premature ovarian failure(POF), and how it improves ovarian function. ICR mice were randomly divided into the control group, model group, Liuwei Dihuang Pills group, Liuwei Dihuang Pills double-dose group, and estradiol valerate group. A mouse model of POF was established by intraperitoneal injection of cyclophosphamide. After successful modeling, the mice were treated with Liuwei Dihuang Pills or estradiol valerate for 28 days. Vaginal smears were prepared to observe the estrous cycle and body weight. After the last administration, mice were sacrificed and sampled. Serum levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-Müllerian hormone(AMH) were measured by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe ovarian morphology and to count follicles at all stages to evaluate ovarian function. Immunohistochemistry was used to detect the expression of mouse vasa homolog(MVH), a marker of ovarian FGSCs. Immunofluorescence staining, using co-labeling of MVH and proliferating cell nuclear antigen(PCNA), was used to detect the expression and localization of specific markers of FGSCs. Western blot was employed to assess the protein expression of MVH, octamer-binding transcription factor 4(Oct4), and PCNA in the ovaries. The results showed that compared with the control group, the model group exhibited disordered estrous cycles, decreased ovarian index, increased atretic follicles, and a reduced number of follicles at all stages. FSH and LH levels were significantly elevated, while AMH and E_2 levels were significantly reduced, indicating the success of the model. After treatment with Liuwei Dihuang Pills or estradiol valerate, hormone levels improved, the number of atretic follicles decreased, and the number of follicles at all stages increased. MVH marker protein and PCNA proliferative protein expression in ovarian tissue also increased. These results suggest that Liuwei Dihuang Pills regulate estrous cycles and hormone disorders in POF mice, promote the proliferation of FGSCs, improve follicular development in POF mice, and enhance ovarian function.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Cell Proliferation/drug effects* ; Mice, Inbred ICR ; Ovary/cytology* ; Primary Ovarian Insufficiency/genetics* ; Follicle Stimulating Hormone/metabolism* ; Humans ; Anti-Mullerian Hormone/blood* ; Antineoplastic Agents/adverse effects* ; Luteinizing Hormone/metabolism* ; Cyclophosphamide/adverse effects*

OBJECTIVE: To detect and analyze the expression and clinical significance of long non-coding RNA tyrosine kinase non-catalytic region adaptor protein 1-antisense RNA1 (NCK1-AS1) in patients with acute myeloid leukemia (AML). METHODS: 89 AML patients and 23 healthy controls were included from the People's Hospital Affiliated to Jiangsu University. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of NCK1-AS1 and NCK1 in bone marrow samples. The relationship between the expression of NCK1-AS1 and the clinical characteristics of patients were analyzed, as well as the correlation between NCK1-AS1 and NCK1. RESULTS: The expression level of NCK1-AS1 in all AML, non-M3 AML and cytogenetically normal AML (CN-AML) patients was significantly higher than that in the control group (P < 0.01, P < 0.05, P < 0.01, respectively). In non-M3 AML, patients with high NCK1-AS1 expression had a significantly lower hemoglobin level than those with low NCK1-AS1 expression (P =0.036), furthermore, NCK1-AS1 ^high patients had shorter overall survival than NCK1-AS1^low patients (P =0.0378). Multivariate analysis showed that NCK1-AS1 expression was an independent adverse factor in patients with non-M3 AML ( HR =2.392, 95% CI :1.089-5.255, P =0.030). In addition, NCK1 expression was also significantly upregulated in all AML, non-M3 AML and CN-AML patients compared with controls (P < 0.01, P < 0.01, P < 0.001, respectively). There was a certain correlation between NCK1-AS1 and NCK1 expression (r =0.37, P =0.0058). CONCLUSION High expression of NCK1-AS1 in AML indicates poor prognosis of AML patients.
Humans ; Leukemia, Myeloid, Acute/genetics* ; RNA, Long Noncoding/genetics* ; Oncogene Proteins/genetics* ; Adaptor Proteins, Signal Transducing/genetics* ; Prognosis ; Male ; Female ; Middle Aged ; Adult ; Case-Control Studies ; Clinical Relevance

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 To analyze the research status of in situ simulation in the medical field and explore its hotspots and trends. Methods Relevant literature was searched in China National Knowledge Infrastructure and Web of Science core collection from the inception to February 2024.CiteSpace 6.3.R1 was used to analyze the authors,institutions,and keywords and draw visual knowledge maps. Results A total of 25 Chinese articles and 438 English articles were included.Only 14 English articles were from China.In Chinese articles,the authors with the largest number of articles were Dai Hengmao and Liu Shangkun,and the institution with the largest number of articles was Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology.There was little cooperation between the authors and institutions.In English articles,the author and institution with the largest number of articles was Auerbach Marc and Yale University,respectively,and the cooperation between authors and institutions was close.Emergency medicine,emergency event handling,and on-the-job training were the keywords with high frequency in Chinese articles.Patient safety,medical education,and cardiac arrest were the keywords with high frequency in English articles.A total of 4 clusters were generated for Chinese keywords and 13 clusters for English keywords. Conclusions The application of in situ simulation in the medical field is still in the initial stage,and the development is not balanced at home and abroad.The number of articles published and the cooperation between authors and institutions in China obviously lags behind those abroad.Treatment and care of emergency critical patients,emergency event handling and skill training,identification of latent safety threats,improvement of readiness,and promotion of medical quality improvement are the future research hotspots and research trends in this field.
Bibliometrics ; Humans ; China ; Simulation Training ; Education, Medical ; Emergency Medicine/education*

italic>Platycodon grandiflorum (Jacq.) A. DC is one of the most commonly used bulk medicinal herbs. It has important value in the fields of medicine, food and cosmetics, and its market demand is increasing year by year, and it has a good development prospect. In this study, based on 403 distribution records and 8 environmental variables, we used Maxent model to predict the potential distribution of P. grandiflorum under climate change. The results showed that the model simulation effect was the best when the Maxent parameter was FC (feature combination) = LQPH (L: linear features; Q: quadratic features; P: product features; H: hinge features) and RM (regularization multiplier) = 2.1, AUC (area under curve) = 0.901, and the model prediction showed that P. grandiflorum was widely distributed in 28 provinces of China under the current climate conditions, with a suitable area of 2 337 419.98 km². Under the influence of climate change in the future, the area of suitable habitat of P. grandiflorum showed a decreasing trend, and the distribution center as a whole showed a trend of northward and eastward shift. The distribution area of P. grandiflorum in the three main producing areas is affected by climate change, and the overall trend is that the future suitable distribution area of Chifeng in Inner Mongolia increases, while the future suitable distribution area of Zibo in Shandong and Taihe, Bozhou in Anhui decreases or even disappears under the SSP5-8.5 scenario (shared socioeconomic pathways). It is suggested to maintain and protect the ecological environment and germplasm resources of the reserved area suitable for the growth of P. grandiflorum, and increase the cultivation research in the expansion area of P. grandiflorum, so as to lay a foundation for the subsequent expansion of P. grandiflorum planting and to promote the protection and sustainable development of P. grandiflorum resources.

To promote the conservation and utilization of the germplasm resources and provide a basis for the breeding of new varieties of Murraya paniculata, this study analyzed the genetic diversity of the germplasm resources and developed the molecular identity(ID) card of M. paniculata. Multiple fluorescence PCR-capillary electrophoresis was performed for 65 germplasm accessions of M. paniculata based on 9 SSR markers identified from the M. paniculata genome, and the molecular weights and alleles of the amplified bands were analyzed. According to the banding patterns of the 9 SSR primers, this study analyzed the genetic diversity of each germplasm accession of M. paniculata and developed molecular ID cards for the test samples. The results showed that 9 pairs of SSR primers detected 78 alleles, with an average of 8.67 alleles. The observed and expected heterozygosity was 0.338-0.831(average of 0.601) and 0.413-0.853(average of 0.721), respectively. The Shannon's information index varied within the range of 0.880-1.994, with an average of 1.41. The polymorphic information content was within the range of 0.391-0.835, with an average of 0.696, which indicated rich genetic diversity. When the genetic identity was 0.347, the 65 germplasm accessions were classified into 5 groups. Based on the results, this study employed the 5 SSR primers with higher polymorphisms to develop the molecular ID cards for the germplasm resources of M. paniculata and created QR code ID cards for the 49 core germplasm accessions preserved in the Yunfu germplasm nursery, laying a foundation for the new variety breeding, production, utilization, and traceability of M. paniculata.
Microsatellite Repeats ; DNA, Plant/genetics* ; Murraya/classification* ; Genetic Variation ; Alleles ; Polymerase Chain Reaction ; Polymorphism, Genetic

Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%-50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.

Objective: To compare digital polymerase chain reaction (dPCR) and real-time quantitative PCR (qPCR) measurements of BCR::ABL (P210) mRNA expression in patients with chronic myeloid leukemia (CML) . Methods: In this non-interventional, cross-sectional study, BCR::ABL (P210) mRNA was simultaneously measured by dPCR and qPCR in peripheral blood samples collected from patients with CML who underwent tyrosine kinase inhibitor therapy and who achieved at least a complete cytogenetic response from September 2021 to February 2023 at Peking University People's Hospital. The difference, correlation, and agreement between the two methods were evaluated using the Wilcoxon signed-rank test, Spearman's correlation, and Bland-Altman analysis, respectively. Results: In total, 459 data pairs for BCR::ABL mRNA expression measured by dPCR and qPCR from 356 patients with CML were analyzed. There was a significant difference in BCR::ABL mRNA expression between the two methods (P<0.001). When analyzed by the depth of the molecular response (MR), a significant difference only existed for patients with ≥MR4.5 (P<0.001). No significant difference was observed for those who did not achieve a major MR (no MMR; P=0.922) or for those who achieved a major MR (MMR; P=0.723) or MR4 (P=0.099). There was a moderate correlation between the BCR::ABL mRNA expression between the two methods (r=0.761, P<0.001). However, the correlation gradually weakened or disappeared as the depth of the MR increased (no MMR: r=0.929, P<0.001; MMR: r=0.815, P<0.001; MR4: r=0.408, P<0.001; MR4.5: r=0.176, P=0.176). In addition, the agreement in BCR::ABL mRNA expression between the two methods in those with MR4.5 was weaker than other groups (no MMR: ▉= 0.042, P=0.846; MMR:▉=0.054, P=0.229; MR4:▉=-0.020, P=0.399; MR4.5:▉=-0.219, P<0.001) . Conclusions: dPCR is more accurate than qPCR for measuring BCR::ABL (P210) mRNA expression in patients with CML who achieve a stable deep MR.
Humans ; Cross-Sectional Studies ; Cytogenetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics* ; Real-Time Polymerase Chain Reaction ; RNA, Messenger/genetics*

Objective To enhance the triage efficiency of patients with acute heart failure(AHF)by improving emergency severity index(ESI)score,and to achieve stratified care for patients with AHF.Additionally,the aim is to improve the combination of stratified scores and nursing care in emergency departments to address the limitations of current studies.Methods A retrospective nested cohort study was conducted on 120 patients with AHF admitted to the Affiliated Hospital of Guizhou Medical University from January 1,2019 to December 30,2021.According to the clinical outcomes of the patients,the patients were divided into subgroup A(71 cases,recovered after treatment,no serious complications during treatment),subgroup B[35 cases,discharged after treatment,multiple organ dysfunction syndrome(MODS),acute respiratory distress syndrome(ARDS),shock and other serious complications occurred during treatment],and subgroup C(14 cases,cardiac death during treatment).A prospective randomized controlled study involving 106 patients with AHF admitted to our hospital from January 1 to December 30,2022,was conducted,and the patients were divided into control group(53 cases)and stratified care group(53 cases)according to the random number table method.The control group received routine nursing care,while patients in the stratified care group received stratified care based on the ESI scoring clinical care pathway.The early warning score model of elderly patients with AHF was constructed with risk threshold as warning signal.The improved ESI scoring criteria were used to score AHF patients,with a total score of 25 points.The higher the score,the higher the risk.0-10 is divided into Ⅰ level risk,>10-20 is divided into Ⅱ level risk,>20 is divided into Ⅲ level risk.Implement nuring at grades Ⅲ,Ⅱ,and Ⅰ,respectively.The changes of modified ESI scores in subgroup A,subgroup B and subgroup C were observed,and Spearman correlation coefficient was used to evaluate the correlation between modified ESI scores and clinical outcomes of different severity of disease.Receiver operator characteristic curve(ROC curve)was drawn to evaluate the effectiveness of the risk threshold classification method of different nursing plan designs in the stratified nursing group and the control group,and to compare the efficiency differences of emergency nursing rescue time,rescue success rate,and stay time in the emergency department,and the incidence of complications such as MODS,ARDS,shock and nursing satisfaction during treatment between the stratified nursing group and the control group.Results The modified ESI score in subgroup C was the highest,significantly higher than that in subgroup B and A(19.6±1.7 vs.17.8±1.5,15.3±1.3,all P<0.05).Spearman correlation analysis showed that the modified ESI score was significantly positively correlated with the occurrence of complications,the occurrence of cardiac death,and the recovery after treatment(r values were 0.623,0.635,0.322,P values were 0.004,0.003,0.012,respectively).Therefore,an improved ESI score has a certain early warning effect on complications and cardiac death of patients.ROC curve analysis showed that the area under the ROC curve(AUC)of routine care for stratified care was 0.710 and 0.620,and the 95％ confidence interval(95％ CI)was 0.620-0.750 and 0.580-0.690,respectively,with Pvalues of 0.023 and 0.034.It shows that the difference between the two nursing methods is significant,and further indicates that the risk threshold classification method designed in this study is effective.With the increase of risk,the rescue time and emergency stay time of the two groups were gradually extended,and the success rate of rescue was gradually decreased,the rescue time and emergency stay time of grade Ⅲ risk were the longest and the success rate of rescue was the lowest,and the rescue time and emergency stay time of the stratified nursing group were significantly shorter than those of the control group(minutes:59.6±6.3 vs.76.5±7.2 and 57.6±5.4 vs.68.2±7.1,both P<0.05),the success rate of rescue was significantly increased[(68.7±6.1)％ vs.(54.6±5.2)％,P<0.05],and the difference of rescue time between grade Ⅰ risk and grade Ⅲ risk was the largest.There were significant differences in the success rate of rescue and the duration of emergency stay in grade Ⅲ risk.The incidence of complications such as MODS,ARDS and shock in stratified care group was significantly lower than that in control group[incidence of MODS:13.2％(7/53)vs.18.9％(10/53),incidence of ARDS:15.1％(8/53)vs.22.6％(12/53),incidence of shock:13.2％(7/53)vs.20.8％(11/53),all P<0.05],satisfaction of patients with service attitude,operation technique,comfort and timeliness were significantly improved compared with the control group[service attitude:28.3％(15/53)vs.18.9％(10/53),operation technology:30.2％(16/53)vs.20.8％(11/53),comfort:32.1％(17/53)vs.24.5％(13/53),timeliness:32.1％(17/53)vs.24.5％(13/53),all P<0.05].Conclusion Based on the modified ESI score,early risk warning thresholds are divided and stratified nursing is conducted,which is beneficial for timely intervention in AHF,effectively ensuring the clinical nursing value of patients during the implementation of medical measures,and has broad application prospects.

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*