ObjectiveTo observe the clinical efficacy of Tongfu Xiezhuo enema in treating stage 3-4 chronic kidney disease （CKD） and the effect of the therapy on the neutrophil-to-lymphocyte ratio （NLR） as an inflammation marker. MethodSixty patients diagnosed with stage 3-4 CKD who visited the Nephrology Department of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from December 2022 to June 2023 were included and randomly assigned into observation and control groups in a ratio of 1∶1. The control group received conventional therapy plus Shenkang suppositories， while the observation group received conventional therapy plus Tongfu Xiezhuo enema. After 8 weeks of treatment， the clinical efficacy was assessed based on the changes in traditional Chinese medicine （TCM） symptom scores， renal function indicators， and NLR. Result① Both groups showed decreases in TCM symptom scores after treatment （P<0.01）， and the decreases were more significant in the observation group than in the control group （P<0.05）. The total response rate of TCM symptoms in the observation group was 79.31% （23/29）， which was higher than that （62.96%， 17/27） in the control group （Z=0.604，P<0.05）. ② After treatment， the observation group showed declined serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， and cystatin C （Cys C） and increased glomerular filtration rate （GFR） （P<0.01）， and the control group showed lowered SCr level and increased GFR （P<0.05）. The observation group had lower SCr level and higher GFR than the control group after treatment （P<0.05）. The total response rate of renal function in the observation group was 79.31% （23/29）， which was higher than that （55.56%， 15/27） in the control group （Z=1.127，P<0.01）. ③ The NLR in the observation group decreased after treatment （P<0.05）， and it was lower than that in the control group （P<0.05）. ④ There were no significant differences in safety indicators between the two groups before and after treatment. ConclusionTongfu Xiezhuo enema ameliorated symptoms and improved renal function indicators in the patients with stage 3-4 CKD by reducing the NLR and inhibiting inflammation.

Objective·To explore EDAR(ectodysplasin A receptor)gene variants that lead to congenital tooth agenesis,and preliminarily analyze the reasons why variants in EDAR can cause both syndromic and non-syndromic tooth agenesis.Methods·Patients with congenital tooth agenesis admitted to the Department of 2nd Dental Center,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine and their family members were included,and genomic DNA from their peripheral blood was extracted for whole exome sequencing(WES).After preliminary screening,PolyPhen-2,Mutation Taster,and Provean were used to predict the harmfulness of potential variants.The screened variants in patients and their families were verified by Sanger sequencing.Conservation analysis of variants was performed,and Swiss-Model was used to analyze the changes in the three-dimensional structure of EDAR.The teeth and syndromic phenotype of the patients and their family members were investigated.Results·Among the included congenital tooth agenesis patients,five patients with EDAR mutations were found,one with EDAR frameshift mutation c.368_369insC(p.L123fs)and the other four with EDAR missense mutations.Two of these four patients were diagnosed as non-syndromic tooth agenesis(NSTA),resulted from c.77C＞A(p.A26E)homozygous mutation and c.380C＞T(p.P127L)heterozygous mutation,respectively.The other two patients with two variants were diagnosed as hypohidrotic ectodermal dysplasia(HED).One compound heterozygous missense mutation patient carried EDAR c.77C＞T(p.A26V)from her father andEDAR c.1281G＞C(p.L427F)from her mother;the other patient with both EDAR and EDA mutations carried EDAR c.1138A＞C(p.S380R)heterozygous mutation and EDA c.1013C＞T(p.T338M)hemizygous mutation.Both variants were from his mother and were reported to be related with NSTA.Two of these missense mutations,EDAR c.1281G＞C(p.L427F)and EDAR c.77C＞A(p.A26E),had not been reported before.The missense mutations affected the protein's spatial conformation by altering the polarity,charge,or volume of the amino acid residues.The frameshift mutation caused a non-triplet base addition,which probably led to protein truncation or degradation.Conclusion·Two new EDAR missense mutations are discovered.An NSTA patients with EDAR homozygous mutations and an HED patient with both EDA and EDAR mutations are reported.It expands the understanding of pathogenic mechanisms of EDAR mutations causing HED and NSTA.

Aim To investigate the value of ultrasound in the diagnosis of congenital internal carotid artery hypo-plasia(CICAH).Methods Patients diagnosed with CICAH by ultrasound in Baotou Central Hospital,Inner Mongolia from July 2022 to December 2023 were retrospectively collected.The general data,ultrasound and imaging data of all patients were recorded.Results Among the 25 317 carotid artery ultrasonography subjects,13 patients were di-agnosed as CICAH.The ultrasonic detection rate of CICAH was 0.051％.The 13 cases of CICAH included 11 cases of unilateral internal carotid artery hypoplasia and 2 cases of bilateral internal carotid artery hypoplasia.CT scan of carotid canal confirmed that all 13 cases of internal carotid artery hypoplasia were unilateral lesions,among which 2 cases of unilat-eral lesions were misdiagnosed as bilateral lesions by ultrasound,with a misdiagnosis rate of 15％.Taking carotid canal dysplasia as the gold standard,ROC curve was plotted to evaluate the diagnostic value of ultrasound in CICAH.The area under the curve(AUC)was 0.941,and the optimal diagnostic threshold value of CICAH was 3.2 mm,sensitivity was 100％,and specificity was 85％.The consistency test between ultrasonic examination and gold standard test method for CT scanning of carotid artery canal showed that Kappa value was 0.846.Conclusion Ultrasound has a high diagnostic value in the diagnosis of CICAH,and can be used as the first choice of clinical examination.

ObjectiveTo observe the effect of Banxia Xiexintang containing intestinal absorption solution （BXCIAS） on migration and invasion of polymorphonuclear myeloid-derived suppressor cells （PMN-MDSCs） in gastric cancer microenvironment. MethodThe complex solution （containing 0.63 g·mL^-1 crude drug） was prepared. Gastric cancer cells were subjected to non-contact co-culture with PMN-MDSCs in Transwell chamber to create gastric cancer microenvironment. Cell counting kit-8 （CCK-8） assay was used to screen the optimal intervention concentration and time of BXCIAS on PMN-MDSCs for subsequent experiment. The blank group， model group， FAK inhibitor group， and BXCIAS groups （26%， 18%， and 10%） were designed. Scratch assay and Transwell assay were employed to detect the migration and invasion ability of PMN-MDSCs， and enzyme-linked immunosorbent assay （ELISA） to measure the expression of vascular endothelial cell growth factor （VEGF） and matrix metalloproteinase-9 （MMP-9） in tumor microenvironment. The expression levels of PMN-MDSCs pathway-related proteins FAK， phosphorylated （p）-FAK， protein tyrosine kinase （Src）， and p-Src were detected by Western blot. ResultThe inhibition rates of PMN-MDSCs by 5%， 50%， 75%， and 100% BXCIAS at 48 h were higher than those at 24 h （P<0.05， P<0.01）. The inhibition rate of PMN-MDSCs by 50% BXCIAS at 72 h was lower than that at 48 h （P<0.01）， and the inhibition rates by 5% and 100% BXCIAS at 72 h were higher than those at 48 h （P<0.05， P<0.01）. There was no significant difference in the inhibition rate by other concentration levels at 48 h. The half-maximal inhibitory concentration （IC₅₀） at 48 h was 18.09%， indicating that 18% BXCIAS and 48 h were the optimal concentration and time， respectively. The migration distance of PMN-MDSCs was large （P<0.01）， and the number of migrating and invading cells increased （P<0.01） in the mode group compared with those in the blank group. Compared with model group， FAK inhibitor and BXCIAS at different concentration decreased the migration distance of PMN-MDSCs （P<0.01）， and the number of migrating and invading cells （P<0.01）， especially the 26% BXCIAS （P<0.01）. The expression of PMN-MDSCs pathway-related proteins FAK， p-FAK， Src and p-Src （P<0.01） and the expression of VEGF and MMP-9 （P<0.01） were higher in the model group than in the blank group. Compared with model group， FAK inhibitor and BXCIAS （26%， 18%， 10%） decreased the expression of FAK， p-FAK， and Src （P<0.01）， and FAK inhibitor and 18% BXCIAS reduced the expression of p-Src （P<0.01）， and the expression of VEGF and MMP-9 （P<0.01）. ConclusionBXCIAS can inhibit the migration and invasion of PMN-MDSCs by down-regulating the expression of FAK， p-FAK， Src， and p-Src proteins in the FAK signaling pathway of PMN-MDSCs in gastric cancer microenvironment.

ObjectiveTo observe the effect of Banxia Xiexintang （BXT）-containing intestinal absorption solution on the apoptosis of polymorphonuclear myeloid-derived suppressor cells （PMN-MDSCs） in gastric cancer microenvironment. MethodBXT-containing intestinal absorption solution was prepared， and gastric cancer cells and PMN-MDSCs were non-contact co-cultured in Transwell chamber to establish gastric cancer microenvironment. Cell counting kit-8 （CCK-8） assay was used to screen the optimal intervention concentration and time of 0-100% BXT-containing intestinal absorption solution prepared by 0.63 g·mL^-1 reconstitution solution. Cells were classified into blank group， model group， oxaliplatin group （10 mg·L^-1）， and BXT （26%， 18%， 10% BXT-containing intestinal absorption solution） group， and the apoptosis of PMN-MDSCs was detected by flow cytometry. The expression of apoptosis-related B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cysteine-aspartic acid protease-3 （Caspase-3） in PMN-MDSCs was detected by Western blot. ResultAfter treatment for 24 h and 48 h， the PMN-MDSCs-inhibiting rate was increased by 5%， 50%， 75%， and 100% BXT-containing intestinal absorption solution compared with that in the blank group （P<0.05， P<0.01）. At 72 h， the PMN-MDSCs-inhibiting rate by 50% BXT-containing intestinal absorption solution was lower than that at 48 h （P<0.01）， and the PMN-MDSCs-inhibiting rate by 5%， 75%， and 100% BXT-containing intestinal absorption solution showed no significant difference from that at 48 h. Moreover， the half-maximal inhibitory concentration （IC₅₀） at 48 h was 18.40%. Thus， 18% BXT-containing intestinal absorption solution and 48 h were the optimal intervention concentration and time. The survival rate of PMN-MDSCs in model group was higher than that in the blank group （P<0.05）， and the apoptosis rate was lower than that in the blank group （P<0.05）. Compared with model group， BXT containing intestinal absorption solution lowered the survival rate and raised apoptosis rate of PMN-MDSCs （P<0.05）， particularly the 26% BXT-containing intestinal absorption solution （P<0.05）. The expression of Bax and Caspase-3 in PMN-MDSCs was lower in the model group than in the blank group （P<0.05）， and the expression of Bcl-2 was higher in the model group than in the blank group （P<0.05）. The expression of Caspase-3 in PMN-MDSCs increased （P<0.05） and the expression of Bcl-2 decreased （P<0.05） in oxaliplatin group and BXT group compared with those in the model group. The expression of Bax rose in oxaliplatin group and BXT group （10% BXT-containing intestinal absorption solution） （P<0.05）. ConclusionBXT can induce the apoptosis of PMN-MDSCs by regulating the expression of apoptosis-related proteins Bax， Caspase-3， and Bcl-2 in gastric cancer microenvironment.

Regenerative endodontic procedures, based on dental pulp biology, use the basic principles of tissue engineering to promote the functional regeneration of dental pulp-dentin complexes. Good results have been achieved in the treatment of young permanent teeth with pulp necrosis or apical periodontitis. There have also been preliminary clinical explorations of the treatment of mature permanent teeth in recent years. The key to successful treatment is controlling infection as well as promoting tissue repair and regeneration. Moderate root canal mechanical preparation is allowed in the therapy of mature permanent teeth, while it is not recommended in the treatment of young permanent teeth. The choice of root canal irrigation and intracanal antisepsis requires a comprehensive consideration of the antibacterial effects, biological safety, and possible complications, such as crown discoloration and root canal calcification. The development of bioceramic materials provides more options for crown sealing materials, but further clinical evaluation is needed. In addition to traditional blood clot scaffolds, new types of tissue scaffolds represented by platelet-rich plasma, platelet-rich fibrin, concentrated growth factors and other platelet concentrates have been developed. Long-term and large-scale studies are needed to evaluate the actual clinical efficacy of these new scaffolds and the efficacy of their combined application with blood clots.

OBJECTIVE: To assess the practical and health economical values of non-invasive prenatal test (NIPT) in Changsha Municipal Public Welfare Program. METHODS: A retrospective analysis was carried out on 149 165 women undergoing NIPT test from April 9, 2018 to December 31, 2019. For pregnant women with high risks, invasive prenatal diagnosis and follow-up of pregnancy outcome were conducted. The cost-benefit of NIPT for Down syndrome was analyzed. RESULTS: NIPT was carried out for 149 165 pregnant women and succeeded in 148 749 cases (99.72%), for which outcome were available in 148 538 (99.86%). 90% of pregnant women from the region accepted the screening with NIPT. 415 (0.27%) were diagnosed as high risk. Among these, 381 (91.81%) accepted amniocentesis, which led to the diagnosis of 212 cases of trisomy 21 (PPV=85.14%), 41 cases with trisomy 18 (PPV=48.81%) and 10 cases with trisomy 13 (PPV=20.83%). The sensitivity and specificity of NIPT for trisomy 21, trisomy 18 and trisomy 13 were (97.70%, 99.98%), (97.62%, 9.97%) and (100%, 99.97%), respectively. In addition, 213 and 30 cases were diagnosed with sex chromosomal aneuploidies (PPV=46.2%) and other autosomal anomalies (PPV=16.57%), respectively. For Down syndrome screening, the cost and benefit of the project was 120.79 million yuan and 1,056.95 million yuan, respectively. The cost-benefit ratio was 1: 8.75, and safety index was 0.0035. CONCLUSION NIPT is a highly accurate screening test for trisomy 21, which was followed by trisomy 18 and sex chromosomal aneuploidies, while it was less accurate for other autosomal aneuploidies. The application of NIPT screening has a high health economical value.
Aneuploidy ; Cost-Benefit Analysis ; Female ; Humans ; Noninvasive Prenatal Testing ; Pregnancy ; Retrospective Studies ; Trisomy 18 Syndrome/genetics*

Objective:To explore the marking method for magnetically controlled capsule gastroscopy (MCCG) pictures with artificial intelligence (AI), so as to improve the work efficiency of endoscopist and to reduce the blind area of AI image reading.Methods:According to the consensus of MCCG, 24 parts of stomach in 14 775 pictures of MCCG from 35 subjects in Shenzhen Zifu Medical Technology Co., Ltd received MCCG from March to August, 2020 were marked by ten gastroenterologists and one developer of MCCG with medical background, the marking shape included rectangles and polygons. Among the ten gastroenterologists, three were senior endoscopist (the total number of gastroenteroscopy operations over 80 000, chief physician or associate chief physician), four were medium seniority endoscopist (the total number of gastroenteroscopy operations between 10 000 and 80 000, associate chief physician), and three were junior endoscopist (the total number of gastroenteroscopy operations less than 10 000, attending physician). The pictures of the same subject were pre-marked by two selected senior endoscopists with blind method, and the standard of marking with most appropriate coincidence rate was determined. The qualified marked pictures were automatically learn with AI deep learning method, and the learning results were fed back. Chi square test was used for statistical analysis.Results:According to the pre-marked results, the standard of coincidence rate for rectangular marking area was set as 50.0% and that for polygon marking area was 70.0%. The first correction for qualified rate was 39.0% (5 762/14 775). A total of 9 013 pictures were corrected. After repeated training and correction for one to five times, all pictures were qualified marked. The marking qualified rate of senior endoscopist partners was higher than that of partners of different qualifications (48.7%, 1 200/2 466 vs. 19.0%, 825/4 337), and the difference was statistically significant ( χ2=659.20, P<0.001). There was no statistically significant difference in the marking qualified rate between the senior endoscopist partners and partners of senior endoscopist and capsule developer (48.7%, 1 200/2 466 vs. 49.6%, 1 496/3 019; P>0.05). Conclusions:Establishment of AI marking method for MCCG can provide technical support for AI non-blind area reading, and AI non-blind area monitoring during the operation of MCCG.

Objective:To correlate bone mineral density with serum bone metabolism indexes in patients with hyperthyroidism.Methods:Thirty patients with hyperthyroidism who received treatment in the General Hospital of Taiyuan Iron and Steel (Group) Co., Ltd. from January 2018 to August 2019 were included in the hyperthyroidism group. Additional 30 healthy subjects who concurrently received routine physical examination were included in the control group. Bone mineral density in all subjects was measured by dual energy X-ray absorptiometry. Bone metabolism indexes in all subjects were measured using a Roche chemiluminescence instrument: 25-hydroxyvitamin D level [25(OH)D], aminoterminal propeptide of type I procollagen (PINP) and beta-cardiotoxin (β-CTX). Correlation between bone mineral density and serum bone metabolism indexes was analyzed using Spearman method.Results:Bone mineral density in lumbar vertebrae 1-4 [(0.86 ± 0.14) g/cm 3], left femoral neck [(0.79 ± 0.07) g/cm 3] and left hip joint [(0.72 ± 0.10) g/cm 3] in the hyperthyroidism group was significantly lower than that in the control group [(1.28 ± 0.21) g/cm 3, (1.03 ± 0.18) g/cm 3, (0.86 ± 0.13) g/cm 3, t = 9.115, 6.806, 4.675, all P < 0.001]. There were 6 cases of osteoporosis, 12 cases of osteopenia and 12 cases of normal bone in the hyperthyroidism group. There was 1 case of osteoporosis, 6 cases of osteopenia and 23 cases of normal bone in the control group. There was significant difference in the number of cases developing osteoporosis between hyperthyroidism and control groups ( Z = 2.968, P < 0.05). Serum level of 25(OH)D in the hyperthyroidism group was significantly lower than that in the control group [(16.89 ± 4.31) μg/L vs. (24.13 ± 5.48) μg/L, t = 5.688, P < 0.001]. Serum levels of PINP and β-CTX in the hyperthyroidism group were significantly lower than those in the control group [PINP: (49.37 ± 10.23) μg/L vs. (47.68 ± 6.49) μg/L; β-CTX: (774.56 ± 159.67) ng/L vs. (534.32 ± 167.48) ng/L, t = 45.974 and 5.687, both P < 0.001]. In the hyperthyroidism group, bone mineral density at lumbar vertebrae 1-4, left femoral neck and left hip joint was positively correlated with serum level of 25(OH)D ( r = 0.417, 0.396, 0.401, all P < 0.05), and it was negatively correlated with serum levels of PINP and β-CTX ( r = -0.414, -0.399, -0.432, -0.404, -0.387, -0.412, all P < 0.05). Conclusion:Hyperthyroidism patients generally have low bone mineral density and accelerated bone metabolism. It is of great significance to regularly monitor bone mineral density and serum bone metabolism indexes in hyperthyroidism patients to prevent osteoporosis.

Objective:To investigate the expression and ratio of CD4 +CD25 +Foxp3 +regulatory T cells (Tregs) to helper T cells 17 (Th17) in the peripheral blood of children with B-cell acute lymphoblastic leukemia (B-ALL). Method:54 children with newly diagnosed B-ALL in Children′s Hospital Capital Institute of Pediatrics from February 2017 to October 2019 were selected as the research subjects, with a median age of 4.9 (3.1 to 7.4) years. These children were divided into a pre-treatment group and a post-treatment group. According to the disease outcome after treatment, they were further divided into a complete remission group (45 cases), and a relapse/refractory group (9 cases). 20 healthy children were selected as the control group. Flow cytometry (FCM) was used to detect the proportions of CD4 +CD25 +Foxp3 +Treg cells and Th17 cells. The ratio of Treg/Th17 cells was calculated. Result:Before treatment, the proportion of Treg cells in the relapse/refractory group and the complete remission group (respectively 6.11±0.48, 6.20±1.16) were higher than those in the control group (4.89±1.46) (P<0.05), and the ratio of Treg/Th17 cells in peripheral blood of children with B-ALL in relapse/refractory stage and complete remission stage (respectively 8.34±2.14, 5.91±1.92) were higher than those in the control group (3.55±1.68) (P<0.05); The ratio of Treg/Th17 cells in the relapsed/refractory group was higher than that in the complete remission group (P<0.05). After treatment, the proportion of Treg cells and ratio of Treg/Th17 cells in peripheral blood of children with B-ALL in relapse/refractory stage (respectively 6.09±0.80, 7.37±1.19) were higher than those in complete remission stage (respectively 5.25±0.87, 4.22±1.50) and control group (respectively 4.89±1.46, 3.55±1.68) (P<0.05). Compared with that before treatment, children in complete remission stage after treatment had lower proportions of Treg cells and the ratio of Treg/Th17 cells, as well as higher proportions of Th17 cells in the peripheral blood (P<0.05). There were no significant differences in the proportions of Treg cells and Treg/Th17 ratio between the pre-treatment group and the post-treatment group of children in relapse/refractory stage (P>0.05).Conclusion:In peripheral blood of children with B-ALL, there is a ratio change of Treg/Th17 cells caused by the increase of CD4 +CD25 +Foxp3 +Treg cells and the decrease of Th17 cells, which tends to be normal with the remission of the disease. Regular detection of Treg and Th17 cells helps to monitor the immune status and provide prognosis of children with B-ALL, and may provide a basis for the immunotherapy of B-ALL.