Objective:To investigate the clinical applicability of the four-grade grading(G4) advocated by the academy in recent years compared with the guideline-recommended three-grade grading(G3) in functional tricuspid regurgitation (FTR).Methods:A total of 137 consecutive patients were prospectively included from outpatient and inpatient clinics at Tangdu Hospital, Air Force Medical University from May to December 2023. All patients underwent echocardiography and were graded for regurgitation based on the 2017 American Society of Echocardiography Valve Evaluation Guidelines as the reference standard. The patients with regurgitation were grouped according to the G3 based on the guidelines and the G4 advocated by the academic community in recent years, respectively. The consistency of the regurgitation grading between multi-indicators and single-indicators was analyzed using the Kappa test for both G3 and G4. The quantitative regurgitation relevant parameters were analyzed using ROC curves to evaluate the diagnostic efficacies for G4, including the vena contracta width (VCW), the area of the color flow jet (A Jet), and the radius of the PISA (R PISA). Results:The results of consistency analysis showed that the consistency of regurgitation volume (RVol) was significantly higher in the G4 multi-indicators comprehensive assessment versus the single-indicators assessment compared with the G3, with a Kappa value of 0.84 vs. 0.30. The consistency of effective regurgitant orifice area (EROA) and VCW remained unchanged, with a Kappa value of 0.76 vs. 0.89, 0.51 vs. 0.66. ROC curve analysis showed that for the G4, the area under the curve (AUC) for moderate regurgitation were 0.854, 0.993, and 0.894, respectively, while for moderate-severe regurgitation, these values were 0.899, 0.979, and 0.917, respectively.Conclusions:For FTR, the G4 currently advocated by the academic community has better consistency between single-indicators and comprehensive indicators grading than the G3 based on the guideline, which is clinically applicable; A Jet, R PISA, and VCW can be supplemented to the G4, which helps to improve the quantitative assessment system.

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.
Humans ; Pyroptosis ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Gasdermins ; Chemoradiotherapy/adverse effects* ; Rectal Neoplasms/surgery* ; Caspases/metabolism* ; Diarrhea/chemically induced* ; Leukopenia/genetics* ; Genetic Variation ; Dermatitis

Background and Objectives: Osteoblasts are derived from bone marrow mesenchymal stem cells (BMMSCs) and playimportant role in bone remodeling. While our previous studies have investigated the cell subtypes and heterogeneity in osteoblasts and BMMSCs separately, cell-to-cell communications between osteoblasts and BMMSCs in vivo in humans have not been characterized. The aim of this study was to investigate the cellular communication between human primary osteoblasts and bone marrow mesenchymal stem cells. Methods: and Results: To investigate the cell-to-cell communications between osteoblasts and BMMSCs and identifynew cell subtypes, we performed a systematic integration analysis with our single-cell RNA sequencing (scRNA-seq) transcriptomes data from BMMSCs and osteoblasts. We successfully identified a novel preosteoblasts subtype which highly expressed ATF3, CCL2, CXCL2 and IRF1. Biological functional annotations of the transcriptomes suggested that the novel preosteoblasts subtype may inhibit osteoblasts differentiation, maintain cells to a less differentiated status and recruit osteoclasts. Ligand-receptor interaction analysis showed strong interaction between mature osteoblasts and BMMSCs. Meanwhile, we found FZD1 was highly expressed in BMMSCs of osteogenic differentiation direction. WIF1 and SFRP4, which were highly expressed in mature osteoblasts were reported to inhibit osteogenic differentiation. We speculated that WIF1 and sFRP4 expressed in mature osteoblasts inhibited the binding of FZD1 to Wnt ligand in BMMSCs, thereby further inhibiting osteogenic differentiation of BMMSCs. Conclusions Our study provided a more systematic and comprehensive understanding of the heterogeneity of osteogenic cells. At the single cell level, this study provided insights into the cell-to-cell communications between BMMSCs and osteoblasts and mature osteoblasts may mediate negative feedback regulation of osteogenesis process.

This study aims to investigate the mechanism of Astragali Radix-Curcumae Rhizoma(HQEZ) in the treatment of gastric cancer based on network pharmacology. Further, the SGC7901 cell model of gastric cancer was employed to validate the efficacy and key targets of the herb pair. Firstly, the CCK-8 assay was employed to evaluate the direct effect of HQEZ on the proliferation of gastric cancer SGC7901 cells. Then, network pharmacology methods were employed to investigate the active ingredients, key targets, and key signaling pathways involved in the treatment of gastric cancer with HQEZ. The results showed that HQEZ contained 18 potential active ingredients, such as quercetin, naringenin, and curcumin. The results of gene ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment suggested that the main targets of HQEZ in treating gastric cancer were involved in the regulation of protein serine/threonine kinase activity, activation of mitogen-activated protein kinase(MAPK) activity, cysteine-type endopeptidase activity, and negative regulation of protein serine/threonine kinase activity. The hypoxia-inducible factor-1(HIF-1) signaling pathway, ATP-binding cassette(ABC) transporters, cytochrome P450-mediated metabolism of xenobiotics, p53 signaling pathway, and cell apoptosis were key signaling pathways of HQEZ in treating gastric cancer. The cell experiments demonstrated that HQEZ significantly downregulated the expression of ATP-binding cassette subfamily B member 1(ABCB1), epidermal growth factor receptor(EGFR), phosphorylated serine/threonine kinase(p-AKT), hypoxia inducible factor 1 subunit alpha(HIF1A), B-cell lymphoma 2(BCL2), breast cancer susceptibility protein 1(BRCA1), DNA polymerase theta(POLH), ribonucleotide reductase M1(RRM1), and excision repair cross-complementation group 1(ERCC1), and upregulated the expression of tumor protein P53(TP53) and cysteinyl aspartate-specific proteinase(CAPS3). Finally, a multivariate COX regression model was adopted to study the relationship between gene expression and clinical information data of gastric cancer patients in the TCGA database, which demonstrated that the key targets of HQEZ were associated with the poor prognosis in gastric cancer patients. Further feature selection using the LASSO algorithm showed that EGFR, HIF1A, TP53, POLH, RRM1, and ERCC1 were closely associated with the survival of gastric can-cer patients. In conclusion, HQEZ regulates the expression of genes involved in DNA repair, survival, and apoptosis in gastric cancer cells via multiple targets and pathways, assisting the treatment of gastric cancer.
Humans ; Stomach Neoplasms/genetics* ; Tumor Suppressor Protein p53 ; Network Pharmacology ; ErbB Receptors ; Protein Serine-Threonine Kinases ; Serine ; Adenosine Triphosphate ; Molecular Docking Simulation ; Drugs, Chinese Herbal/pharmacology*

Objective: To evaluate the diagnostic value of transient elastography, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) for liver fibrosis in children with non-alcoholic fatty liver disease (NAFLD). Methods: A retrospective study was conducted on 100 cases of nonalcoholic fatty liver disease in Hunan Children's Hospital between August 2015 to October 2020 to collect liver tissue pathological and clinical data. The receiver operating characteristic curve (ROC curve) was used to analyze the diagnostic value of liver stiffness measurement (LSM), APRI and FIB-4 in the diagnosis of different stages of liver fibrosis caused by NAFLD in children. Results: The area under the ROC curve (AUC) value of LSM, APRI and FIB-4 for diagnosing liver fibrosis (S≥1) were 0.701 [95% confidence interval (CI): 0.579 ~ 0.822, P = 0.011], 0.606 (95%CI: 0.436 ~ 0.775, P = 0.182), and 0.568 (95%CI: 0.397 ~ 0.740, P = 0.387), respectively. The best cut-off values were 6.65 kPa, 21.20, and 0.18, respectively. The AUCs value of LSM, APRI, and FIB-4 for diagnosing significant liver fibrosis (S≥ 2) were 0.660 (95% CI: 0.552 ~ 0.768, P = 0.006), 0.578 (95% CI: 0.464 ~ 0.691, P = 0.182) and 0.541 (95% CI: 0.427 ~ 0.655, P = 0.482), respectively. The best cut-off values were 7.35kpa, 24.78 and 0.22, respectively. The AUCs value of LSM, APRI and FIB-4 for the diagnosis of advanced liver fibrosis (S≥ 3) were 0.639 (95% CI: 0.446 ~ 0.832, P = 0.134), 0.613 (95% CI: 0.447 ~ 0.779, P = 0.223) and 0.587 (95% CI: 0.411 ~ 0.764, P = 0.346), respectively. The best cut-off values were 8.55kpa, 26.66 and 0.27, respectively. Conclusion: The transient elastography technique has a better diagnostic value than APRI and FIB-4 for liver fibrosis in children with NAFLD.
Aspartate Aminotransferases ; Biomarkers ; Child ; Elasticity Imaging Techniques ; Humans ; Liver/pathology* ; Liver Cirrhosis/pathology* ; Liver Function Tests ; Non-alcoholic Fatty Liver Disease/pathology* ; ROC Curve ; Retrospective Studies

OBJECTIVE: To study the clinical features of catch-up growth of body height after kidney transplantation in children and related influencing factors. METHODS: A retrospective analysis was performed from the chart review data of 15 children who underwent kidney transplantation in Guangzhou Women and Children's Medical Center from July 2017 to November 2019. According to whether the increase in height standard deviation score (ΔHtSDS) in the first year after kidney transplantation reached ≥0.5, the children were divided into a catch-up group with 8 children and a non-catch-up group with 7 children. According to whether final HtSDS was ≥-2, the children were divided into a standard group with 6 children and a non-standard group with 9 children. The features of catch-up growth of body height and related influencing factors were compared between groups. RESULTS: The data showed that median ΔHtSDS was 0.8 in the first year after transplantation, which suggested catch-up growth of body height. There was a significant difference in HtSDS between the non-catch-up and catch-up groups (P<0.05). Baseline HtSDS before transplantation was positively correlated with HtSDS at the end of follow-up (r=0.622, P<0.05) and was negatively correlated with ∆HtSDS in the first year after transplantation (r=-0.705, P<0.05). Age of transplantation and mean dose of glucocorticoid (GC) per kg body weight were risk factors for catch-up growth after kidney transplantation (OR=1.23 and 1.74 respectively; P<0.05), while baseline HtSDS and use of antihypertensive drugs were independent protective factors for catch-up growth (OR=0.08 and 0.18 respectively; P<0.05); baseline HtSDS and ΔHtSDS in the first year after kidney transplantation were influencing factors for final HtSDS (β=0.984 and 1.271 respectively; P<0.05). CONCLUSIONS Kidney transplantation should be performed for children as early as possible, growth retardation before transplantation should be improved as far as possible, and multiple treatment methods (including the use of GC and antihypertensive drugs) should be optimized after surgery, in order to help these children achieve an ideal body height.
Body Height ; Body Weight ; Child ; Glucocorticoids ; Growth Disorders ; Humans ; Kidney Transplantation ; Retrospective Studies

Objective:To understand the prevalence and epidemiological characteristics of glaucoma among people over 40 years old in rural areas of Chongqing.Methods:From August to October 2018, a stratified cluster random sampling method was used to investigate the cases of glaucoma among people over 40 years old in a rural population of the Rongchang and Qijiang Districts in Chongqing.The subjects had been living in the local area for over ten years.Basic information for each patient, including gender and age was documented, and their visual acuity and intraocular pressure were routinely measured.The Van Herick method was used to evaluate the depth of the central and peripheral anterior chamber, a preset lens was used to examine the fundus, and the cup to disc ratio(C/D) of the optic disc was emphasized.All suspected glaucoma patients underwent further standard glaucoma examinations.This study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Army Medical University.Results:A total of 4 680 people were identified, and 4 073 respondents participated in the survey, and the response rate was 87%.The prevalence of glaucoma was 1.72% (70/4 073). There were no significant differences in the prevalence of primary angle-closure glaucoma (PACG) and primary open angle glaucoma (POAG) between different genders ( χ2=0.042, P=0.837; χ2=2.838, P=0.092). The prevalence of glaucoma in people over 70 years old was 2.5%, significantly higher than that in other age groups.In patients with glaucoma, the rate of visual impairment was 68.57%(48/70), and the rate of blindness was 47.14%(33/70). There was no significant difference in the incidence of low vision between different types of glaucoma ( χ2=2.785, P=0.248), but there was a significant difference in the rate of blindness ( χ2=10.668, P=0.005). The highest rate of blindness was found in secondary glaucoma.The detection rate of intraocular pressure, anterior chamber depth and C/D was statistically significant ( χ2=43.325, P<0.001), and the positive rate of C/D was the highest.When the factors of intraocular pressure, and C/D were considered jointly, the detection rate of glaucoma could be increased to 55.88%. Conclusions:The prevalence of glaucoma is 1.72% among people over 40 years old in rural areas of Chongqing, the prevalence of PACG is lower than previously recorded, but the proportion of glaucoma-induced visual impairment is higher.In field screening, the morphological examination of the fundus optic nerve is very important for the diagnosis of glaucoma.

Objective::To observe the effect of Bimin decoction(BMD) on nuclear factor-kappa B(NF-κB) signaling pathway and aquaporin 5(AQP5) expression in allergic rhinitis (AR) rats with lung and spleen Qi deficiency syndrome(LSQDS), in order to study the mechanism in treating AR. Method::Fifty-six SD rats were randomly divided into seven groups: control group, AR group, LSQDS AR group, BMD low dose two weeks group and four weeks group, BMD high dose two weeks group and four weeks group. The control group did not intervened, the AR group established the AR disease model with ovalbumin (OVA) as the allergen, the other five groups established the LSDQS model with smoke and senna gavage, and also established the AR disease model with OVA sensitization at the same time as the AR group. After the model was established successfully, four BMD intervention groups were separately given low dose BMD (11.3 g·kg^-1) for 2 weeks and 4 weeks, and high dose BMD (22.6 g·kg^-1) for 2 weeks and 4 weeks. To observe the general situation of the rats, hematoxylin eosin (HE) staining was used to observe the pathological changes of the nasal mucosa, immunohistochemistry and Western blot were used to detect the expression levels of NF-κB and AQP5, real-time fluorescent quantitative polymerase chain reaction technique (Real-time PCR)was used to detect mRNA levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6). Result::The typical AR symptoms were found in AR rats, the AR symptoms and lung and spleen Qi deficiency symptoms were found in AR rats with LSQDS at the same time, and the AR symptoms and lung and spleen Qi deficiency symptoms were significantly improved after the intervention of BMD. Compared with the control group, the typical histopathological changes of nasal mucosa were found in AR group and LSQDS AR group, with a higher behavioral score (P<0.05), and the expression of NF-κB and AQP5 protein increased (P<0.05), the expression of IL-1β, TNF-α, IL-6 and AQP5 mRNA increased (P<0.05). Compared with AR group, the pathological changes of nasal mucosa in LSQDS AR group were more serious, and the expression of NF-κB protein in nucleus increased (P<0.05), the expression of TNF-α and AQP5 mRNA increased (P<0.05). Compared with LSQDS AR group, the pathological changes of nasal mucosa in the groups which interfered by BMD were improved, and the expression of NF-κB and AQP5 protein decreased (P<0.05), the expression of IL-1β, TNF-α, IL-6 and AQP5 mRNA decreased (P<0.05). Compared with BMD low-dose two-week group, the expression of NF-κB protein in nucleus decreased (P<0.05) in BMD high dose four week group. Conclusion::Compared with AR group, the AR condition of the rats with LSQDS is more serious under the same allergen stimulation, BMD can treat AR and reduce the over secretion of glands, which may be related to inhibit the expression of AQP5 by inhibiting the NF-κB signaling pathway.