BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases,and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival;however,there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE:To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS:Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed.A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at+2 days were categorized into the recombinant human thrombopoietin group;a total of 27 patients who started to orally take Herombopag Olamine at+2 days were categorized into the Herombopag Olamine group;and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group.The implantation status,incidence of acute graft-versus-host disease of degree II-IV within 100 days,1-year survival rate,1-year recurrence rate,and safety were analyzed in the three groups. RESULTS AND CONCLUSION:(1)The average follow-up time was 52(12-87)months.The implantation time of neutrophils in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group was(12.95±3.88)days,(14.04±3.71)days,and(13.89±2.74)days,respectively,with no statistically significant difference(P=0.352);the implantation time of platelets was(15.16±6.27)days,(17.67±6.52)days,and(17.00±4.75)days,with no statistically significant difference(P=0.287).(2)The complete platelet implantation rate on day 60 was 64.06%,90.28%,and 92.59%,respectively,and the difference was statistically significant(P<0.001).The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant(P<0.001),and the difference between the blank control group and the Herombopag Olamine group was statistically significant(P=0.004).The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group(P=0.535).(3)100-day II-IV degree acute graft-versus-host disease incidence in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group were 25.00%,30.56%,and 25.93%,respectively,and the difference was not statistically significant(P=0.752).(4)The incidence of cytomegalovirus anemia,cytomegalovirus pneumonia,and hepatic function injury had no statistical difference among the three groups(P>0.05).(5)During the follow-up period,there was no thrombotic event in any of the three groups of patients.(6)The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation,with comparable efficacy and good safety.

BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*

BACKGROUND: Lung adenocarcinoma (LUAD) is the predominant subtype of non-small cell lung cancer (NSCLC). Damage-specific DNA binding protein 1 (DDB1), as a core protein of the CUL4-DDB1 ubiquitin ligase complex, is involved in the regulation of DNA damage repair, epigenetic modification, and cell cycle checkpoint activation. While the involvement of DDB1 in tumour progression through DNA repair and RNA transcriptional regulation has been reported, its expression and role in LUAD remain to be elucidated. This study aims to investigate the expression and role of DDB1 in LUAD. METHODS: The expression, clinicopathological features and prognosis of DDB1 in LUAD were analysed using databases such as UALCAN, Kaplan-Meier Plotter and GEPIA; The interaction network and enriched functional pathways were constructed by GeneMANIA and Metascape; the correlation between DDB1 and immune cells by combining with TISIDB infiltration was evaluated, and the clustering results of cell subtypes and the expression of DDB1 in different immune cell subpopulations were analysed by single-cell sequencing; finally, tissue microarrays were used to further verify the expression and prognostic value of DDB1 in LUAD. RESULTS: The mRNA and protein expression of DDB1 in LUAD tissues were significantly higher than those in normal tissues (P<0.01), and the high expression correlated with later clinical stage (P<0.001), lymph node metastasis (P<0.001) and poor prognosis (P<0.001). Functional enrichment showed that DDB1 was involved in DNA repair and RNA transcriptional regulation, and TISIDB evaluation revealed that DDB1 was negatively correlated with the expression level of immune cells, suggesting the potential regulation of the immune microenvironment. Single cell analysis showed that DDB1 was mainly expressed in T cells, alveolar macrophages and dendritic cells. Tissue microarrays confirmed that overall survival was shorter in the DDB1 high expression group (P<0.001), and Cox multifactorial analysis showed that DDB1 was an independent predictor of LUAD prognosis. CONCLUSIONS DDB1 is highly expressed in LUAD, which is associated with poor prognosis, and is closely related to tumor immune cell infiltration, and is involved in tumourigenesis and development through DNA repair and RNA transcriptional regulation. DDB1 can be used as a potential prognostic marker and therapeutic target for LUAD.
Humans ; Adenocarcinoma of Lung/immunology* ; DNA-Binding Proteins/metabolism* ; Lung Neoplasms/diagnosis* ; Gene Expression Regulation, Neoplastic ; Prognosis ; Male ; Female ; Middle Aged

【Objective】 To analyze the clinical characteristics of serum vitamin K2 in children and its correlation with bone mineral density, so as to provide reference for the prevention of insufficient bone strength in children. 【Methods】 A total of 4 145 children who underwent serum vitamin K2 testing and physical examination at pediatric outpatient clinics of several municipal and county hospitals in Chongqing from January 2020 to March 2023 were retrospectively selected into this study for serum vitamin K2-related analysis.Further 844 school-age children who completed serum 25-(OH)D and lumbar bone densitometry measurements were screened to analyze the correlation between vitamin K2level and bone mineral density 【Results】 The overall serum vitamin K2 deficiency rate was 61.6% (2 553/4 145), and the difference in serum vitamin K2 deficiency rate between different age groups was statistically significant (χ²=39.364, P<0.05).The vitamin K2 level of children was significantly influenced by season and maternal education level (χ²=45.310,9.990, P<0.05).There were significant differences in age (Z=3.416), gender (χ²=9.218) and serum vitamin K2 deficiency rate (χ²=5.826) between normal bone mass development group and insufficient bone mass development group (P<0.05).Multivariate Logistic regression analysis suggested that vitamin K2 deficiency was an independent risk factor for insufficient bone mass development in school-age children (OR=1.37,95%CI:1.03 - 1.83, P=0.030). 【Conclusions】 There is a higher serum vitamin K2 deficiency rate among children, especially infants and school-age children.Decreased bone mineral density in school-age children may be associated with serum vitamin K2 deficiency.

Disseminated intravascular coagulation (DIC) triggered by sepsis is a major challenge in the emergency and critical care of severely ill patients. The inflammasome is an essential component of the human immune system, and its activation can mediate pyroptosis and then release interleukin (IL)-1β and IL-18, which further activates platelets and the coagulation system and exacerbates inflammatory responses and coagulation processes, thus creating great uncertainty for the treatment and prognosis of sepsis. This article aims to review the correlation between the inflammasome and pyroptosis, as well as their impact on coagulation function, in hope of providing new insights for the clinical treatment of DIC.

In fixed prosthodontics, clear exposure of the preparation margin is the prerequisite for obtaining accurate digital impressions and improving the marginal fit of restorations. To resolve the issues associated with the cord retraction technique, such as pain, acute injury, and prolonged procedural time, this study proposes a new technology for intraoral digital impression taking with pneumatic gingival retraction. The new scanning head blows a high-speed airflow that instantaneously separates the free gingiva, locally exposing the subgingival preparation margin. Combined with the farthest point preservation stitching algorithm based on the distance from the normal vector and high-speed laser scanning photography, it achieves global preparation edge data and gingival reconstruction, realizing painless, non-invasive, and efficient precise acquisition of the preparation margin. Using this new technique, a patient with a full porcelain crown restoration on a posterior tooth was treated. The digital impression revealed a clear margin of the preparation, and the crown made from this data has a good marginal fit.

Disseminated intravascular coagulation (DIC) triggered by sepsis is a major challenge in the emergency and critical care of severely ill patients. The inflammasome is an essential component of the human immune system, and its activation can mediate pyroptosis and then release interleukin (IL)-1β and IL-18, which further activates platelets and the coagulation system and exacerbates inflammatory responses and coagulation processes, thus creating great uncertainty for the treatment and prognosis of sepsis. This article aims to review the correlation between the inflammasome and pyroptosis, as well as their impact on coagulation function, in hope of providing new insights for the clinical treatment of DIC.

Objective To develop an effective method for delivering VEGF and CD47 double-modified exosomes to treat renal damage induced by heat stroke so as to reduce and repair renal damage.Methods A plasmid fusion-expressing VEGF and CD47 targeting renal injury was constructed,transfected into rat bone marrow derived mesenchymal stem cells (BMMSCs),and then fusion-exosomes were isolated and extracted.Transmission electron microscopy,nanoparticle tracking analysis,and Western blotting were used to identify the obtained exosomes.Rats were intravenously injected with 200 μg of DiD-labeled unmodified exosomes,VEGF-modified exosomes and VEGF-CD47 double-modified exosomes,respectively,through the tail vein,and the effects of exosomes on the kidneys were detected and analyzed using a small animal in vivo imaging instrument.A total of 60 SD rats were randomly divided into 6 groups,with 10 rats in each group,that is,blank control group (group A),heat stroke-induced renal injury model receiving PBS in 12,24 and 36 h after modelling (group B),empty plasmid group (group C),Exos group (group D),ExosVEGF group (group E) and ExosVEGF-CD47.Kidney tissue and blood samples were collected in 72 h after 3 times of treatment.Pathological changes in kidney tissue were observed at the tissue level and the damage were scored.Changes in serum blood urea nitrogen (BUN)and serum creatinine (Scr)levels were detected to evaluate the therapeutic effect.Western blotting and qRT-PCR were used to analyze the expression of the pro-inflammatory factors TNF-α and NF-κB,the proliferation regulatory signaling molecules Ki67,FGF2,pAMPK and pERK,and the fibrosis regulatory molecule FGF23,in order to comprehensively analyze the effects on proliferation and inhibition of fibrosis.Results BMMSCs and ExosVEGF-CD47 were successfully isolated and characterized,and a rat model of acute kidney injury was effectively constructed.Higher fluorescence intensity was found in the kidney tissue of the Exos VEGF-CD47group than the Exos-Ctrl group and Exos VEGF group (P<0.05).In 72 h after treatment,the ExosVEGF-CD47 group had significantly lower serum BUN and Scr levels (P<0.0001),and notably lower Tubular casts score (P<0.0001),decreased levels of pro-inflammatory factors TNF-α and NF-κB (P<0.0001),up-regulated Ki67 and FGF2 expression (P<0.05),and down-regulated FGF23 expression (P<0.0001)when compared with the AKI+Exos group and AKI+ExosVEGF group.Conclusion VEGF and CD47 show promise in targeting acute kidney injury induced by heat stroke,effectively mitigate damage and facilitate repair,which may be due to exosome-mediated inhibition of renal tissue inflammation,promotion of proliferation,and inhibition of fibrosis.

Objective:Based on the construction of benign organizational climate of tertiary public hospitals, this paper tries to understand the practical demands of hospital staff for the internal organizational climate.Methods:A seven-dimension organizational climate questionnaire for public hospitals was designed by literature review and Delphi expert survey method. On the basis of satisfying the reliability and validity test, Kano questionnaire analysis and Better-Worse coefficient analysis were combined to identify the key climate factors to improve the satisfaction of hospital staff.Results:28 climate indicators were divided into: 9 (32.1%) attractive requirements, 7 (25.0%) one-dimensional requirements, 4 (14.3%) hybrid requirements, 6 (21.4%) must-be requirements, and 2 (7.2%) indifference requirements.Conclusions:According to Kano model classification results and satisfaction influence matrix distribution results, Some suggestions are put forward for constructing benign organizational climate in hospitals from the aspects of constructing equitable system, popularizing democratic leadership, attaching importance to cultivating scientific research and improving humanistic care.

Objective: To evaluate the clinical and radiological outcomes,and the complications of staged minimally invasive surgery for adult degenerative scoliosis, comparing with that of the conventional open surgery. Methods: From Jun 2013 to Jun 2017, a total of 42 cases of degenerative scoliosis underwent surgical treatment. Among which, 23 cases underwent staged minimally invasive surgery(MIS group) and 19 cases underwent posterior open surgery(open group). The intra-operative bleeding, and operation time were recorded.The clinical outcomes were assessed using the Oswestry Disability Index (ODI), Visual Analogue Scale (VAS) for low back pain and leg pain.The radiological outcome was evaluated with Cobb angles and sagittal balance parameters (Sagittal Vertical Axis (SVA), Pelvic Incidence (PI)-Lumbar Lordosis (LL), Pelvic Tilt (PT)). The occurrence of complications was recorded. Results: The baseline demographic features of both groups (gender, age, medical comorbidity, etc.) were similar.The mean follow-up period for both groups was more than 2 years.The intraoperative bleeding in the MIS group 405.7±144.8 ml was significantly lower than that in the open group (2 005.3±728.4 ml, t=10.31, P<0.001); The total operation time 414.3±63.0 min of MIS group was significantly longer than that of the open group (304.2±51.8 min, t=6.10, P<0.001), but the operating time of each stage was shorter than the open group. The VAS score for back pain and leg pain,the ODI scores were significantly improved after surgery for both group, there was no significant difference between the two groups, but the low back pain and function in MIS group were better than the open group. The parameters of the coronal and sagittal deformity were significantly improved in both groups, correction of coronal deformity in MIS groupwassignificantly superior to the open group (F=12.02, P=0.001), there was no significant difference in sagittal balance correction between the two groups. The overall complication rate (63.2%) was slightly higher in the open group than in the MIS group (34.8%) without significant difference(χ²=3.36, P=0.07). The incidence of major complications in the open group was significantly higher than that in the MIS group (P=0.014). Conclusion Staged minimally invasive surgery can significantly relieve the patient's pain, improve functionand the coronal and sagittal balance of the patient, the early clinical and radiological outcomes were comparable to the open surgery; Minimally invasive surgery may significantly reduce the amount of bleeding and major complications. Minimally invasive surgery is safe and effective for carefully selected patients with degenerative scoliosis.However, the long-term outcomes of minimally invasive surgery remains to be followed up.