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Objective The network pharmacological methods and molecular docking technology were used for investigating the possibility of Psoraleae Fructus in promoting precocious puberty in children and its potential mechanism.Methods The main active ingredients of Psoraleae Fructus and their therapeutic targets were obtained from BATMAN-TCM online platform.The disease targets related with precocious puberty were obtained from GeneCards database.A visualized network of active ingredients-disease targets was constructed by Cytoscape 3.7.1 software.Protein-protein interaction(PPI)network diagrams were constructed based on the STRING online database.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted using Metascape online tool.The structures of the main active ingredients were obtained from PubChem database,the structures of core targets were obtained from RCSB PDB database,and then the structures were imported into Autodock for molecular docking.Finally,the mimic diagrams of the molecular docking were drawn using PYMOL software.Results A total of 12 active ingredients of Psoraleae Fructus were obtained,involving 274 targets.And there were 11 active ingredients and 98 targets associated with precocious puberty.The main active compounds were stigmasterol,bakuchiol,angelicin,bavachalcone,isobavachalcone,and xanthotoxin.The main targets were estrogen receptor 1(ESR1),estrogen receptor 2(ESR2),insulin-like growth factor 1(IGF1),and progesterone receptor(PGR),which were mainly involved in the ovarian steroidogenic pathway and Hippo signaling pathway.The molecular docking results showed that the active compounds were well binded to the targets.Conclusion It is possible that Psoraleae Fructus can promote the sexual development in children and has its potential pharmacological mechanism.The results will provide theoretical references for the clinical prevention and treatment of precocious puberty and early pubertal development in children.
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Objective To analyze serum characteristics and determine the reference range for thyroid function among healthy 11~16 year-old teenagers in Xi'an in order to offer a theoretical basis for clinical diagnosis and therapy.Methods A sum of 1 378 healthy 11~16 year-old teenagers who met the inclusion criteria from the First Affiliated Hospital of the Air Force Medical University(Xijing Hospital)between January 2020 and December 2022 were selected as research subjects,including 628 males and 750 females.They were divided into three groups based on age:Group 1:11~<13 year-olds(433 cases),Group 2:13~<15 year-olds(425 cases),and Group 3:15~≤16 year-olds(520 cases).Differences in serum thyroid function indices among different genders and age groups were analyzed,the reference ranges for these indices were established,and 99 healthy 11-16 year-old teenagers who met the inclusion criteria were chosen for verification.Results There were no significant differences between different genders in thyroid stimulating hormone[TSH,2.56(1.80,3.63)μIU/ml vs 2.43(1.68,3.48)μIU/ml]and total thyroxine[TT4,97.84(85.34,111.00)nmol/L vs 98.20(87.16,111.23)nmol/L],the differences were statistically significant(Z=-1.881,-0.638,all P>0.05).Meanwhile,the differences in free thyroxine[FT4,16.93(15.49,18.60)pmol/L vs 16.26(14.80,17.83)pmol/L],free triiodothyronine[FT3,6.21(5.66,6.80)pmol/L vs 5.59(4.98,6.19)pmol/L],and total triiodothyronine[TT3,2.24(1.96,2.55)nmol/L vs 2.04(1.78,2.34)nmol/L]between different genders were significant(Z=-5.368,-11.994,-6.417 all P<0.01).The differences in thyroid function indices were significant among different age groups(Z=10.649~261.003,all P<0.05).The reference ranges for thyroid function indices across different age groups and genders were established,in which thyroid function indicators were verified to be within the established reference range by 99 samples.Conclusion Teenage hormone secretion varies greatly,and the secretion of thyroid hormones is influenced by various factors.Thus,the diagnosis and treatment of teenage thyroid diseases cannot fully rely on the reference ranges provided by adults or manufacturers.This study established the reference range of the thyroid function indices of 11~16 year-old teenagers in Xi'an,offering clinical doctors'diagnosis and treatment data support.
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Objective:To analyze the release and distribution characteristics of Chinese medical insurance payment policies,and to provide reference for future policy formulation in the field of medical insurance payment construction.Methods: Content analysis method was used to construct a two-dimensional framework of "policy goals-policy tools",and text analysis was carried out according to 63 policy documents.Results: A total of 493 policy codes were completed.From the perspective of policy goals,the policy objectives of Chinese medical insurance payment mainly focused on three aspects: improving the payment level,optimizing the medical insurance environment,and standardizing the supervision regulations.From the perspective of policy tools,environmental policy tools are the most used policy tools,followed by supply and demand tools.There is a shortage of financial input and talent training in all policy objectives,so more attention should be paid to demonstration and Category of payment.Conclusion: Our country puts forth effort to build a perfect medical insurance payment system,but should further strengthen policy content supplement,optimize the structure of policy tools,and give full play to the payment ability of medical insurance when pulling the demand of medical insurance payment and driving the supply of medical insurance payment.
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Background/Aims@#Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM. @*Methods@#We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis. @*Results@#Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR (P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp.and Veillonella dispar, and enriched Fusobacterium nucleatum. In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded. @*Conclusions@#In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.
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Objective To observe the value of ultrasonography for evaluating the anatomy and hemodynamic characteristics of vertebral artery course variation(VA-CV).Methods Totally 41 patients with VA-CV(VA-CV group)and 41 patients without VA-CV(control group)were enrolled.Lateral variation of vertebral artery(VA),the origin of V1 segment,the length of proximal subclavian artery(PSCA),the location of VA into the transverse foramen,the diameter of V2 segment,the peak systolic velocity(PSV)and the end-diastolic velocity(EDV)were evaluated with ultrasonography.The value of ultrasonography for evaluating VA-CV and relative hemodynamic changes were analyzed.Results Totally 49 variant VA were detected in VA-CV group,including 19 on the left and 30 on the right side,VA-CV on the right side was more often than on the left side.Seventeen(16 on the left and 1 on the right side)VA had abnormal origins,and abnormal VA origins on the left side were more than that on the right side(P<0.001).Meanwhile,VA origins of right VA-CV were mostly lower than that of the left side VA-CV(P<0.001).The length of right PSCA in VA-CA group was shorter than that in control group(P<0.05).More than half variant VA entered vertebral space from the transverse foramen of C5-6(33/49,67.35%),and the higher the entrance of transverse foramen,the shorter the PSCA(P<0.05).In VA-CV group,the diameter of V2 segment in left VA-CV patients was smaller than that in control group,while EDV in the former was lower than in the latter(both P<0.05).Conclusion Ultrasonography could be used to objectively evaluate VA-CV and relative hemodynamic changes.
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AIM To prepare the soluble microneedles of Aconitum brachypodum Diels alkaloids.METHODS Centrifugal molding method was adopted in the preparation of soluble microneedles.With chondroitin sulfate consumption,PVP K120 consumption and 40%ethanol consumption as influencing factors,piercing rate as an evaluation index,the formulation was optimized by Box-Behnken response surface method,after which the morphology,piercing performance,drug content and in vitro transdermal performance were investigated.RESULTS The optimal formulation was determined to be 123 mg for chondroitin sulfate consumption,298 mg for PVP K120 consumption,and 2.4 mL for 40%ethanol consumption,the piercing rate was 98.3%.The soluble microneedles were yellow and square patch with conoid needle,which could pierce aluminum foil and rat skin,along with the drug content of(0.94±0.025)mg.The soluble microneedle group demonstrated the accumulative permeability rate of 91.4%within 24 h,which was higher than that in the gel ointment group,and the permeability accorded with Higuchi equation.CONCLUSION The soluble microneedles of A.brachypodum alkaloids exhibit good mechanical strength,which can achieve effective transdermal delivery of drugs.
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Objective To investigate the prevalence of Anisakis infections in coastal marine fishes and awareness of anisakiasis control knowledge among local residents in Yantai City, Shandong Province in 2021, so as to provide insights into formulation of anisakiasis control interventions. Methods Marine fishes were purchased from Shunxin Port, Yantai City, Shandong Province in November 2021, and the presence of Anisakis was detected in different species of fishes and different fish sites. The correlations between body length and weight of marine fish and intensity of Anisakis infections were examined using Spearman’s rank correlation analysis, and the dietary habits and anisakiasis control knowledge were investigated using questionnaire surveys among local residents. Results A total of 201 marine fishes belonging to 20 species were dissected, and Anisakis was detected in 77 marine fishes (38.31%) belonging to 11 species (55.00%), with a mean infection intensity of 45.04 parasites per fish (3 468/77). Spearman’s rank correlation analysis revealed that the body length (rs = 0.74, P < 0.05) and weight (rs = 0.79, P < 0.01) of the monkfish correlated positively with the intensity of Anisakis infections, and the body length (rs = 0.68, P < 0.05) of the flatfish correlated positively with the intensity of Anisakis infections, while no correlations were examined between the body length or weight of other marine fishes and the intensity of Anisakis infections. Of all respondents, 53.38% men and 56.67% women did not know anisakiasis control knowledge at all, and there was a significant difference in the proportion of respondents using separate chopping boards for raw and cooked food from different villages (χ2 = 17.89, P < 0.01), while there was an age-specific proportion of respondents with habitats of eating raw or semi-raw seafood (χ2 = 28.27, P < 0.01). Conclusions The prevalence and intensity of Anisakis infections were high in coastal marine fishes in Yantai City in 2021, and the awareness of anisakiasis control knowledge was low among local residents. Intensified health education pertaining to anisakiasis control knowledge is recommended to reduce the risk of Anisakis infections.
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Stroke is a disease with a high disability rate, and often leads to limb dysfunction, especially upper limb motor dysfunction, which significantly affects the patients’ abilities and quality of life. With patients' increasing demand for functional recovery, various therapeutic techniques of rehabilitation medicine have been rapidly developed. As an important active central intervention technology, motor imagery training can be initiated by the patient's brain and activate the sensorimotor network to accelerate the repair of limb functions. The development of preventive medicine has promoted the continuous evolution of the concept of rehabilitation. The strategies of full cycle functional protection and disability prevention have been improved and developed in the clinical and scientific research practice of upper limb rehabilitation after stroke. The motor imagery training can activate the upper limb motor neural network in the early stage of stroke to prevent functional loss; In the recovery period, it can accelerate the neural function remodeling and reduce the upper limb disability; In the later stage after stroke, it can improve the performance of upper limb function in daily life, thus helping patients return to family life and society. This article reviews the research progress in recent years in China and abroad in the application of motor imagery training for the full cycle function protection and disability prevention of stroke.
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This case report presents the diagnosis and treatment of a case of cystic echinococcosis misdiagnosed as hepatic cyst. The case had anaphylactic shock caused by extravasation of cyst fluid during extraction of hepatic cyst and suffered from postoperative recurrence of echinococcosis. This case report may provide insights into diagnosis and treatment of cystic echinococcosis among healthcare workers in non-endemic areas.
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OBJECTIVE@#To investigate the clinical and genetic characteristics of a patient with STISS syndrome due to variant of PSMD12 gene.@*METHODS@#Clinical data and result of genetic testing of a patient who was admitted to Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine on October 4, 2020 were analyzed, together with a review of relevant literature.@*RESULTS@#The patient was found to harbor a heterozygous c.601C>T (p.Arg201*) nonsense variant of the PSMD12 gene, which was unreported previously. Clinically, the height of the patient has differed significantly from reported in the literature. An extremely rare case of STISS syndrome due to variant of the PSMD12 gene has been diagnosed.@*CONCLUSION@#Whether the severely short stature is part of the clinical spectrum for PSMD12 gene variants needs to be further explored, and the efficacy and safety of growth hormone therapy has yet to be determined.
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Child , Humans , China , Dwarfism , Genetic Testing , Heterozygote , SyndromeABSTRACT
Objective:To investigate the efficacy and related influencing factors of autologous hematopoietic stem cell transplantation(auto-HSCT)as first-line consolidation therapy for newly diagnosed elderly patients with diffuse large B cell lymphoma(DLBCL).Methods:Retrospective study of clinical characteristics, therapeutic effect, and prognostic factors of newly diagnosed DLBCL elderly patients with an International Prognostic Index(IPI)score≥3 who underwent auto-HSCT in the Affiliated People's Hospital of Ningbo University from January 2015 to August 2020.Results:Among the 31 patients, 18 were males and 13 were females, with a median age of 65(60-75)years.The 13 cases(41.9%)were involved in 2 sites outside lymph nodes, and 13 cases(41.9%)were involved in bone marrow.IPI medium and high risk(IPI=3 points)was found in 21 cases(67.7%), high risk(≥4 points)in 10 cases(32.2%). Before transplantation, 21(67.7%)patients achieved complete remission(CR), and the other 10(32.3%)patients were in the partial remission(PR). All patients after transplantation achieved hematopoietic reconstitution.The median time for neutrophil and platelet engraftment were 10(9-16)days and 12(8-58)days respectively.During a median follow-up of 20.9(3.1 to 73.0)months after transplantation, transplant-related mortality within 100 days was 3.2%(1/31). The 2-year overall survival(OS)and progression-free survival(PFS)were(77.2±8.4)% and(72.7±8.3)%, respectively.Multivariate Cox analysis showed that the achieved partial remission status before auto-hematopoietic stem cell transplantation[OS( HR=30.064, 95% CI: 2.231-405.209, P=0.010), PFS( HR=9.165, 95% CI: 1.926-43.606, P=0.005)], and CD34 + cell count in graft <3×10 6/kg[OS( HR=12.004, 95% CI: 1.234-116.807, P=0.032), PFS( HR=6.115, 95% CI: 1.325-28.221, P=0.020)]were the independent poor prognostic factor affecting both OS and PFS in elderly lymphoma patients. Conclusions:Auto-HSCT may improve the survival rate of carefully selected elderly patients with DLBCL.Pretransplant disease status and the number of CD34 + cells in the graft are important factors to predict the efficiency of auto-HSCT of the patients.
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This study aims to explore the anti-depression mechanism of Zuojin Pills based on the plasma constituents, network pharmacology, and experimental verification. UHPLC-TOF-MS was used for qualitative analysis of Zuojin Pills-containing serum. Targets of the plasma constituents and the disease were retrieved from PharmMapper and GeneCards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.7.2 was employed construct the "compound-target-pathway" network and the targets and signaling pathways of Zuojin Pills against depression were predicted. CUMS-induced depression mouse model was established to verify the key targets. The results showed that a total of 21 constituents migrating to blood of Zuojin Pills were identified, which were mainly alkaloids. A total of 155 common targets of the constituents and the disease and 67 core targets were screened out. KEGG enrichment and PPI network analysis showed that Zuojin Pills may play a role in the treatment of depression through AMPK/SIRT1, NLRP3, insulin and other targets and pathways. Furthermore, the results of animal experiments showed that Zuojin Pills could significantly improve the depression behaviors of depression, reduce the levels of IL-1β, IL-6 and TNF-α in hippocampus and serum, activate AMPK/SIRT1 signaling, and reduce the protein expression of NLRP3. In conclusion, Zuojin Pills may play a role in the treatment of depression by activating AMPK/SIRT1 signaling pathway, and inhibiting NLRP3 activation and neuroinflammation in the hippocampus of mice.
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Animals , Mice , Network Pharmacology , AMP-Activated Protein Kinases , Chromatography, High Pressure Liquid , NLR Family, Pyrin Domain-Containing 3 Protein , Sirtuin 1 , Drugs, Chinese Herbal/pharmacology , Molecular Docking SimulationABSTRACT
Objective: To assess the feasibility of using donors with novel coronavirus disease 2019 (COVID-19) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) when there are no other available donors and allo-HSCT cannot be delayed or discontinued. Methods: Seventy-one patients with malignant hematological diseases undergoing allo-HSCT between December 8, 2022, and January 10, 2023, were included. Of these, 16 received grafts from donors with mild COVID-19 (D-COVID(+) group) and 55 received grafts from donors without COVID-19 (D-COVID(-) group). The graft compositions were compared between the two groups. Engraftment, acute graft-versus-host disease (aGVHD), overall survival (OS), and relapse were also evaluated. Results: There were no serious side effects or adverse events in the D-COVID(+) group. The mononuclear cell dose and CD34(+) cell dose were comparable between the two groups, and no additional apheresis was required. There were no significant differences in the lymphocyte, monocyte, and T-cell subset doses between the two groups. The median natural killer cell dose in the D-COVID(+) group was significantly higher than that in the D-COVID(-) group (0.69×10(8)/kg vs. 0.53×10(8)/kg, P=0.031). The median follow-up time was 72 (33-104) days. All patients achieved primary engraftment. The 60-day platelet engraftment rates in the D-COVID(+) and D-COVID(-) groups were 100% and (96.4±0.2) %, respectively (P=0.568). There were no significant differences in neutrophil (P=0.309) and platelet (P=0.544) engraftment times. The cumulative incidence of grade 2-4 aGVHD was (37.5±1.6) % vs. (16.4±0.3) % (P=0.062), and of grade 3-4 aGVHD was 25.0% ±1.3% vs. 9.1% ±0.2% (P=0.095) in the D-COVID(+) and D-COVID(-) groups, respectively. The probabilities of 60-day OS were 100% and 98.1% ±1.8% (P=0.522) in the D-COVID(+) and D-COVID(-) groups, respectively. There was no relapse of primary disease during the study period. Conclusion: When allo-HSCT cannot be delayed or discontinued and no other donor is available, a donor with mild COVID-19 should be considered if tolerable. Larger sample sizes and longer follow-up periods are required to validate these results.
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Humans , COVID-19 , SARS-CoV-2 , Hematopoietic Stem Cell Transplantation , Tissue Donors , Graft vs Host DiseaseABSTRACT
The current status of the application of machine learning was reviewed when used for the analysis of risk factors of kidney stone formation and the early diagnosis and compositional analysis of kidney stones.The deficiencies of machine learning were analyzed during kidney stone diagnosis and compositional analysis.It's pointed out machine learning would be improved in data quality and scale,algorithmic interpretability and security and interdisciplinary cooperation in the future.
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Objective:To investigate the application value of auricular point pressing with beans combined with Chinese medicine for rehabilitation in older adults after total hip arthroplasty.Methods:This is a prospective case-control study. A total of 80 older adult patients with femoral neck fractures who underwent total hip arthroplasty at Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from September 2020 to January 2022 were included in this study. These patients were randomly divided into a control group and an observation group, with 40 patients per group. The control group underwent conventional interventions, while the observation group underwent auricular point pressing with beans combined with Chinese medicine. Clinical efficacy was compared between the two groups.Results:The overall response rate in the observation group was 85.00% (34/40), which was significantly higher than 65.0% (26/40) in the control group ( χ2 = 4.27, P = 0.036). Before surgery, there were no significant differences in various indicators between the two groups (all P > 0.05). At 2 weeks after surgery, the hemoglobin level and Harris scores in the observation group were higher than those in the control group ( t = -7.11, -5.81, both P < 0.05). At 1 and 3 days and 2 weeks after surgery, the D-dimer level, prothrombin time, activated partial thrombin time, thrombin time, Visual Analogue Scale score, and Pittsburgh Sleep Quality Index (PSQI) in the observation group were significantly lower than those in the control group (all P < 0.05). At 3 days and 2 weeks after surgery, C-reactive protein, thigh and calf circumference of the affected limb in the observation group were significantly lower than those in the control group ( t = 2.34, 6.85, 4.47, 3.89, 6.63, 4.35, all P < 0.05). After surgery, the time to get off the bed and the length of hospital stay in the observation group were (3.58 ± 2.43) days and (7.14 ± 2.18) days, respectively, which were significantly shorter than (5.47 ± 2.35) days and (9.13 ± 2.14) days in the control group ( t = 3.54, 4.12, both P < 0.001). The incidence of postoperative deep vein thrombosis in the observation group was 5.00% (2/40), which was significantly lower than 10.00% (4/40) in the control group ( χ2 = 0.72, P = 0.396). Conclusion:Auricular point pressing with beans combined with Chinese medicine can promote rapid rehabilitation of older adult patients with femoral neck fractures after total hip arthroplasty.
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Objective:To investigate the effect of gallic acid on the morphology, proliferation and cell cycle of keloid fibroblasts, as well as on collagen contraction and the transforming growth factor-β (TGF-β) /Sma- and Mad-related proteins (Smads) signaling pathway, and to explore the role and mechanisms of action of gallic acid in the treatment of keloids.Methods:From August to December 2022, 3 keloid tissue samples were collected from 3 patients with clinically and pathologically confirmed keloids after surgery in the Department of Dermatologic Surgery, Wuhan No.1 Hospital. Primary fibroblasts were isolated and cultured by using the tissue culture method, and 3- to 8-passage fibroblasts were used for subsequent experiments. Cultured keloid fibroblasts were divided into 4 groups: low-, medium- and high-dose gallic acid groups treated with 0.025, 0.05 and 0.1 mg/ml gallic acid respectively, and a control group cultured with Dulbecco′s modified Eagle′s medium (DMEM) containing 10% fetal calf serum. After 24-, 48-, and 72-hour treatment, cellular proliferative activity was evaluated by cell counting kit 8 (CCK8) assay, and collagen contraction by using a three-dimensional culture method. After 24-hour treatment in the above groups, pictures were taken using a differential interference inverted fluorescence microscope, and changes in the cell cycle were analyzed by flow cytometry. Some keloid fibroblasts were divided into 2 groups: an experimental group (high-dose gallic acid group) treated with 0.1 mg/ml gallic acid, and a control group cultured with DMEM containing 10% fetal calf serum. After 24-hour treatment, enzyme-linked immunosorbent assay (ELISA) was performed to determine the changes in supernatant concentrations of TGF-β1, TGF-β2, and TGF-β3 in the two groups, real-time fluorescence-based quantitative PCR to detect the relative mRNA expression levels of TGF-β1, TGF-β2, TGF-β3, Smad2, Smad3, Smad4, and α-smooth muscle actin (α-SMA). Statistical analysis was carried out using t test, one-way analysis of variance and two-way analysis of variance, and least significant difference (LSD) - t test was used for multiple comparisons. Results:Compared with the control group, the gallic acid groups showed gradual changes in the shape of keloid fibroblasts under the microscope as the dose of gallic acid increased, including gradually shrinking cell bodies, enlarged intercellular spaces, cell atrophy, increased number of apoptotic cells, etc. CCK8 assay showed that the cellular proliferative activity changed significantly as the dose of gallic acid increased and the treatment time was prolonged ( Fgroup = 78.31, P < 0.001; Ftime = 4.17, P = 0.037), and the proliferative activity of keloid fibroblasts was significantly lower in the high-dose gallic acid group than in the control group at 24, 48, and 72 hours (all P < 0.05). The three-dimensional culture showed that different degrees of collagen contraction occurred in all groups over time, marked collagen contraction was observed in the control group, and a lower degree of collagen contraction in the gallic acid groups; the collagen contraction indices were significantly lower in the medium- and high-dose gallic acid groups than in the control group at 24, 48, and 72 hours (all P < 0.05). Flow cytometry showed that the cell apoptosis rates were significantly higher in the low-, medium- and high-dose gallic acid groups (38.68% ± 3.05%, 41.82% ± 2.19%, 43.56% ± 3.58%, respectively) than in the control group (12.58% ± 1.56%, all P < 0.001) after 24-hour treatment; compared with the control group, the medium- and high-dose gallic acid groups showed significantly decreased proportions of cells in the G0/G1 phase (both P < 0.01), but significantly increased proportions of cells in the S phase and G2/M phase (all P < 0.05). ELISA revealed that the TGF-β1 concentration was significantly lower in the high-dose gallic acid group (758.58 ± 31.42 pg/ml) than in the control group (1 081.30 ± 44.72 pg/ml, t = 11.81, P<0.001), there was no significant difference in the TGF-β2 concentration between the high-dose gallic acid group (71.05 ± 7.40 pg/ml) and the control group (76.43 ± 6.51 pg/ml, t = 1.09, P = 0.317), while the TGF-β3 concentration was significantly higher in the high-dose gallic acid group (5.70 ± 3.87 pg/ml) than in the control group (0.00 ± 0.00 pg/ml, t = 2.94, P = 0.026). As real-time fluorescence-based quantitative PCR revealed, the high-dose gallic acid group showed significantly decreased mRNA expression levels of TGF-β1, Smad2, Smad3, Smad4, and α-SMA (all P < 0.05), but significantly increased mRNA expression level of TGF-β3 ( t = 6.78, P = 0.002) compared with the control group; however, there was no significant difference in the TGF-β2 mRNA expression level between the above two groups ( t = 0.05, P = 0.962) . Conclusion:Gallic acid could change the cell cycle, inhibit the proliferative activity, promote apoptosis and change the shape of keloid fibroblasts, and thus inhibit scar formation and contraction, which may be related to the inhibition of TGF-β/Smads signaling pathway.
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The United States is the country with the most pilot practices in value-based healthcare payment reform, and value-based purchasing (VBP) is one of its pilot projects. The authors introduced the basic situation and implementation effects of the pilot projects of VBP payment reform in the United States from the hospital and physician levels respectively, and analyzed the causes for their unsatisfactory implementation effects. Then, the authors proposed its enlightenments for China from such aspects as the construction of value-based medical payment index system, implementation of value-based medical payment reform, and management costs, to provide reference for the construction of high-quality value-based medical service system in China.
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The pilot project for alternative payment models was originated from the implementation of the 2010 Affordable Care Act in the United States, which aimed to establish a new payment mode to replace the traditional payment based on service fees, thereby achieving the goals of ensuring healthcare quality, reducing healthcare costs, and improving healthcare equity. The pilot projects of alternative payment models included two types: accountable care organizations and bundled payments for care improvement. The authors introduced their profile and implementation effects, analyzed the causes of the current implementation effects, and then proposed enlightenments for the value-based medical payment reform in China, with the aim of providing reference for the construction of a high-quality value based medical service system in China.
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Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ2=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.
Subject(s)
Female , Humans , Adult , Medroxyprogesterone Acetate/adverse effects , Endometrial Hyperplasia/pathology , Dydrogesterone/adverse effects , Hyperplasia , Prospective StudiesABSTRACT
Objective:To investigate the prognosis of childhood adrenoleukodystrophy (ALD) with cognitive disorder after haploidentical allogenic hematopoietic stem cell transplantation (haplo-HSCT), and to identify risk factors affecting the prognosis.Methods:It was a single-center retrospective study involving 31 ALD children receiving haplo-HSCT in Peking University People′s Hospital from January 2014 to October 2022.Survival analysis was performed by Kaplan-Meier method. Cox regression analysis was performed to identify risk factors for the prognosis of childhood ALD following haplo-HSCT. Results:Among the 31 children with ALD, 1 case died of cardiogenic shock during the transplantation, and the remaining had a successful haplo-HSCT.Ten children with ALD had cognitive disorder before haplo-HSCT, including 3 cases with the minimal LOES score ≥10 points and 8 cases with the Neurologic Function Score (NFS)>0 point before haplo-HSCT.Six children had major functional disability (MFD) and 2 cases died due to progression of ALD after haplo-HSCT.Twenty children did not have cognitive disorder before haplo-HSCT, of whom 3 cases had the LOES score≥10 points and 6 cases had NFS>0 before haplo-HSCT.Four children had MFD and 2 cases died due to progression of ALD after haplo-HSCT.For ALD patients without cognitive disorder after haplo-HSCT, the 3-year and 5-year survival rate were 100.0% and 72.9%, respectively, and the 5-year MFD-free survival was 61.6%.For ALD patients with cognitive disorder after haplo-HSCT, the 3-year survival rate was 83.3%.Compared with ALD patients with the LOES score<10 points before haplo-HSCT, those with the LOES score≥10 points had 9.243 times the risk of developing MFD after haplo-HSCT ( P=0.024, 95% CI: 1.332-64.127). Compared with ALD patients without cognitive disorder before haplo-HSCT, ALD patients with cognitive disorder had 9.749 times the risk of developing MFD after haplo-HSCT ( P=0.023, 95% CI: 1.358-66.148). Conclusions:Cognitive disorder and LOES score≥10 points before haplo-HSCT are risk factors for developing MFD in children with ALD following haplo-HSCT.