Objective To examine the significance of susceptible gene detection for hereditary cancer syndrome (HCS) among general population. Methods A total of 2 928 individuals undergoing routine health examinations in Healthcare Center of Zhongshan Hospital, Fudan University, from September 2021 to April 2024 were enrolled retrospectively. Next generation sequencing was employed to identify susceptible genes for HCS. American College of Medical Genetics and Genomics (ACMG) guideline was used to analyze the pathogenicity of variants. Clinical data, imagings, follow-up data were also collected. Results The overall mutation rate of HCS panel was 3.59% (105/2 928), with 0.61% (18/2 928) for MutY DNA glycosylase (MUTYH), 0.27% (8/2 928) for breast cancer susceptibility gene 1/2 (BRCA1/2) and 0.23% (7/2 928) for mismatch repair (MMR) genes. Conclusions Healthy individuals carrying tumor susceptible genes usually lack the relevant clinical phenotypes. Whether comprehensive testing needs to be carried out among healthy people remains to be further explored.

Objective : To explore the polymorphism of endothelial nitric oxide synthase(eNOS) gene in umbilical cord blood of preterm infants and its relationship with major complications in preterm infants. Methods : A total of 254 preterm infants(<37 weeks) who were hospitalized were selected as the study subjects. Umbilical cord blood was collected at delivery to determine the genotypes and alleles of eNOS gene at three loci: rs61722009, rs2070744,and rs1799983. Clinical data of the preterm infants were recorded, and the relationship between eNOS gene polymorphism and major complications in preterm infants was analyzed. Results: (1) The TC+CC genotype at locus rs2070744 was an independent risk factor for bronchopulmonary dysplasia(BPD) in preterm infants, with an OR(95%CI) of 1.266(1.017-1.577).(2) The GT+TT genotype at locus rs1799983 was an independent risk factor for retinopathy prematurity(ROP), with an OR(95%CI) of 1.184(1.008-1.391).(3) The AB+AA genotype at locus rs61722009 was also an independent risk factor for ROP,with an OR(95%CI) of 1.335(1.033-1. 726).(4) There was no significant relationship between gene polymorphism and the occurrence of respiratory distress syndrome( RDS) and periventricular-intraventricular hemorrhage( PIVH). Conclusion eNOS gene polymorphism is associated with the occurrence of BPD and ROP in preterm infants. The evaluation of e NOS gene polymorphism by umbilical cord blood measurement is helpful for the prevention and correct management of some serious complications.

BACKGROUND:Rheumatoid arthritis is an inflammatory disease.Many studies have shown that wogonin has a good anti-inflammatory effect on rheumatoid arthritis,but its exact efficacy and specific mechanism of action remain to be clarified. OBJECTIVE:To investigate the mechanism of wogonin ameliorating joint inflammation by regulating endoplasmic reticulum stress pathway in rats with collagen-induced arthritis. METHODS:(1)At the animal level:Female Wistar rats were divided into healthy control group,arthritis model group and wogonin treatment group.Rat models of arthritis in the latter two groups were established by subcutaneous injection of bovine type Ⅱ collagen and adjuvant.In the wogonin group,wogonin was given by gavage for 28 consecutive days after modeling.During this period,the rats in each group were weighed,and arthritis score and ankle swelling were measured every 7 days.After the experiment,the pathological changes of the joint were observed,the mRNA and protein levels of endoplasmic reticulum stress pathway GRP78 and CHOP were detected by qRT-PCR,western blot,and immunohistochemistry.(2)At the cellular level,cell counting kit-8 was used to detect the cytotoxic effect of wogonin on fibroblast-like synoviocytes from rats with collagen-induced arthritis.The fibroblast-like synoviocytes induced by thapsigargin were treated with different concentrations of wogonin.The levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant were detected by ELISA,and the intracellular reactive oxygen species in each group were determined by DCFH-DA probe method.The mRNA and protein levels of GRP78,IRE1α,XBP1s and CHOP were detected by qRT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the healthy control group,arthritis index score and ankle swelling degree in the arthritis model group were increased(P<0.01),synovial hyperplasia,inflammatory cell infiltration,cartilage destruction and bone erosion were observed in pathological sections,and the mRNA and protein expressions of GRP78 and CHOP in the ankle were significantly increased(P<0.01),which were mainly located in synovial tissue and articular surface.Compared with the arthritis model group,the arthritis index score and ankle swelling degree in the wogonin treatment group were decreased(P<0.05),synovial hyperplasia and the number of inflammatory cells were decreased,cartilage destruction and bone erosion were alleviated,the mRNA and protein expression levels of GRP78 and CHOP in the ankle were decreased(P<0.05),particularly in synovial tissue and on the articular surface.There was no significant difference in body mass among the three groups(P>0.05).In the cell experiment,200 μmol/L wogonin significantly reduced the survival rate of fibroblast-like synoviocytes(P<0.01).Compared with the blank control group,the levels of interleukin-1β,tumor necrosis factor-α,content of reactive oxygen species,and mRNA and protein expression of GRP78,IRE1α,XBP1s,and CHOP in the thapsigargin group were significantly increased(P<0.05);compared with the thapsigargin group,50 and 100 μmol/L wogonin significantly reduced the levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant(P<0.05,P<0.01),and 100 μmol/L wogonin significantly reduced the content of reactive oxygen species(P<0.01)and down-regulated the mRNA and protein expression levels of GRP78,IRE1α,XBP1s and CHOP(all P<0.05).These results suggest that wogonin can effectively alleviate joint inflammatory responses in rats with collagen-induced arthritis,and the endoplasmic reticulum stress pathway may be the key target of its intervention.

BACKGROUND:Our previous study found that Modified Erxian Pill could alleviate inflammation in collagen-induced arthritis rats,but its mechanism needs to be further verified. OBJECTIVE:To analyze the components absorbed in the blood of Modified Erxian Pill,and observe the effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages. METHODS:(1)Analysis of components absorbed in the blood of Modified Erxian Pill:Ultra-high performance liquid chromatography-high resolution mass spectrometry was used to detect and identify Modified Erxian Pill and its components absorbed in the blood.(2)Effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages:Molecular docking technology was used to initially verify the sesquiterpenoids and NLRP3 in components absorbed in the blood of Modified Erxian Pill.J774A.1 macrophages were randomly divided into blank control group,lipopolysaccharide+adenosine triphosphate group,and lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill with low(2.5%),medium(5%),and high(10%)dose groups.The release of lactate dehydrogenase in the cell supernatant of each group was detected according to the kit instructions.The levels of interleukin-1β and interleukin-18 in cell supernatant were detected in each group by ELISA.The cell membrane damage was detected by Hoechst/PI staining.The expression levels of NLRP3,Caspase-1,GSDMD,and GSDMD-N protein in the cells of each group were detected by western blot assay. RESULTS AND CONCLUSION:(1)A total of 32 active components of Modified Erxian Pill were identified,and 21 components entered the blood.The main components into blood included a variety of sesquiterpenoids.(2)Molecular docking results showed that 3-O-Acetyl-13-deoxyphomenone,Incensol oxide,Atractylenolide III,Rupestonic acid,and 3,7-Dihydroxy-9,11-eremophiladien-8-one had good binding activity with NLRP3.(3)Compared with the blank control group,lactate dehydrogenase activity and the expression levels of interleukin-1β and interleukin-18 were significantly increased in cell supernatant of lipopolysaccharide+adenosine triphosphate group(P<0.001).Hoechst/PI staining showed that the number of PI-positive cells was significantly increased.After the intervention of lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group,all of them showed different degrees of reduction.(4)Compared with the blank control group,NLRP3,Caspase-1,GSDMD,and GSDMD-N protein expression levels were significantly increased in the lipopolysaccharide+adenosine triphosphate group(P<0.05).Compared with lipopolysaccharide+adenosine triphosphate group,the protein expressions of NLRP3,Caspase-1,GSDMD,and GSDMD-N were significantly decreased in the lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group(P<0.05),and had a certain dose dependence.These findings verify that the drug-containing serum of Modified Erxian Pill may inhibit the pyroptosis of J774A.1 macrophages by regulating the NLRP3/Caspase-1/GSDMD pathway.

It is believed that patients with cirrhotic ascites exhibit a pathological mechanism characterized by the decline of healthy qi and the accumulation of pathogenic factors. Clinically， treatment should be based on the theory of tonification and purging， with a staged approach distinguishing between the active phase and the remission phase. The balance between tonification and purging should be adjusted according to the progression of pathogenic and healthy actors. In the acute phase， purging should take precedence over tonification， using purging as a means of tonification to facilitate the flow of water and qi through the triple energizer. The severity of water retention， dampness， blood stasis， and heat should be carefully assessed to ensure thorough elimination of pathogenic factors while avoiding harm to healthy qi. Medication adjustments should be made once the pathogenic factors are significantly weakened. In the remission phase， an integrated approach combining both tonification and purging should be adopted， incorporating purging within tonification to clear residual pathogens and prevent recurrence. Concurrently， proactive treatment of the underlying disease is essential to achieve complete recovery and prevent the recurrence of ascites.

[Objective] To explore the key factors affecting the efficiency and safety of hematopoietic stem cell apheresis. [Methods] The clinical data of 59 healthy donors who underwent allogeneic hematopoietic stem cell donation in the First Affiliated Hospital of Anhui Medical University from January 2021 to June 2024 were retrospectively analyzed. The number of CD34⁺ cells was used to evaluate the eligibility of stem cell collection. The effects of donor gender, age, patient weight, as well as the number of WBC, MNC, RBC, Hb, HCT, PLT, CD34⁺ cells, CD34⁺ percentage and instrument operating parameters on collection efficiency were analyzed. [Results] A total of 59 donors were enrolled, and 68 occasions of stem cell apheresis were performed, with a qualified collection rate of 56%. Donor gender, age, patient weight, total blood circulation volume, anticoagulant dosage, collection time, calcium gluconate dosage and RBC, Hb, HCT levels were not significantly correlated with the collection effect (P>0.05). Multivariate logistic regression analysis showed that the number of MNC cells, CD34⁺ cells and stem cell product volume were the key factors affecting the efficiency and safety. A total of 12 donors had mild adverse reactions during the collection process, and all of them were improved after treatment. [Conclusion] Optimizing apheresis strategy based on the three factors of MNC, WBC count and stem cell product volume on the day of collection will help to achieve high-quality collection and improve the success rate of transplantation.

Objective:To explore the correlation among SMAD4 gene polymorphisms, early life traumatic experience and their interactions with clinical feature of obsessive-compulsive disorder (OCD). Methods:Totally 484 OCD patients who met the DSM-Ⅳ diagnostic criteria and 368 health controls who met the enrollment criteria were recruited from September 2013 to September 2018. The Yale-Brown obsessive-compulsive scale (Y-BOCS) was used to assess the severity of obsessive-compulsive symptoms, the Beck depression inventory Ⅱ (BDI-Ⅱ) was used to assess the severity of depressive symptoms, the Beck anxiety inventory (BAI) was used to assess the severity of anxiety symptoms, and early trauma inventory-short form (ETI-SF) was used to assess early traumatic experience. SMAD4: rs12452684, rs2276163, rs17663887 and rs3819122 were genotyped using the Taqman genotyping technique. Data were analyzed using SPSS 20.0 software, and comparisons among groups were performed using chi-square test, t-test, Mann-Whitney U non-parametric test and analysis of covariance. Correlation was analyzed using Spearman correlation analysis, and interactions were analyzed using general linear model. Results:All sites except rs17663887 met the Hardy-Weinberg equilibrium (rs12452684: χ2=0.29, P=0.59; rs2276163: χ2=2.58, P=0.11; rs3819122: χ2=0.22, P=0.64).Allele, genotype frequencies of SMAD4: rs12452684, rs2276163 and rs3819122 were not statistically significant between the OCD and the health control groups ( χ2=0.02, 1.20, 0.04, all P>0.05; χ2=1.85, 3.98, 1.45, all P>0.05). The results of covariance analysis (corrected for age and gender) showed that there were significantly differences in compulsion (CC: 12.47±4.23, CT: 12.53±4.15, TT: 13.97±3.11; AA: 12.63±4.08, AC: 12.49±4.19, CC: 13.87±2.93) and total Y-BOCS scores(CC: 25.31±6.42, CT: 25.68±5.90, TT: 27.75±6.01; AA: 25.54±6.52, AC: 25.56±5.98, CC: 27.63±5.75) among the three genotypes of the SMAD4: rs2276163 and rs3819122 between the two groups ( F=3.58, 3.87, 3.48, 3.73, all P<0.05). Emotional abuse in the ETI-SF was positively correlated with obsession and total Y-BOCS scores( r=0.14, 0.14, both P<0.05). The interactions of rs2276163, rs3819122 and emotional abuse were associated with obsession scores ( F=4.65, 3.63, 2.93, all P<0.01). Conclusions:The more emotional abuse experienced in early life, the more severe obsessive-compulsive symptoms, and the interaction between the SMAD4 gene and early traumatic experience is involved in the development of OCD.

ObjectiveTo explore a rapid and accurate method for evaluating the quality of Prunus mandshurica (Maxim.) Koehne (P. mandshurica, Ku Xing Ren) during rancidity using machine vision and learning.MethodsSensory evaluation and chemometrics were used to classify P. mandshurica quality grades after rancidity. Chemical indicators of the P. mandshurica quality change were determined to verify the obtained grades and support the subsequent modeling. The International Commission on Illumination color space was used to extract the color features of the P. mandshurica. Discrimination and prediction models based on color features combined with multiple machine learning algorithms were established using 10-fold cross-validation and external test set validation.ResultsThe P. mandshurica rancidity samples were allocated to three quality grades. The Bayes net model based on powder color successfully identified the P. mandshurica at different grades with an accuracy of 88.89% and 100% using two validations, and the naive Bayes model based on section color achieved the same accuracy with an receiver operating characteristic area of 0.979. The instance-based k-nearest neighbors model based on powder color performed best in predicting the amygdalin content [R2 = 0.9801, mean absolute error (MAE) = 0.2071, root mean squared error (RMSE) = 0.4170], followed by the random committee model in predicting the acid value (R2 = 0.9580, MAE = 1.5121, RMSE = 1.9099) and the random forest model in predicting the peroxide value (R2 = 0.8857, MAE = 0.0027, RMSE = 0.0035).ConclusionThis study demonstrates that color digitization analysis is a potential method for rapidly evaluating the quality of P. mandshurica across the rancidity process, providing a new reference for the quality assessment of traditional Chinese medicines.

Objective To understand the detection rate of children with phenylketonuria(PKU)in southern Xinjiang in recent 10 years,and analyze the mutation of phenylalanine hydroxylase(PAH)gene in children with classical PKU in southern Xinjiang,so as to provide effective reference for clinical treatment.Methods The concentration of phenylalanine(PHE)in dried filter paper blood was de-tected by chemical fluorescence method for PKU screening of live births in southern Xinjiang.The heel blood or venous blood of 29 Uygur PKU children diagnosed in southern Xinjiang were collected.The exons 10,11,12 of PAH gene and the intron junction region of Uygur PKU children were sequenced by polymerase chain reaction(PCR)product direct sequencing method to determine the mutation site.Results A total of 5gene mutation types and 13mutation sites were detected in 58 chromosomes,and the mutation detection rate was 44.83％(13/29).The five mutations were divided into two mutation sites of ivs10-1(c.1066-11g＞a)in the junction region be-tween exon 10 and intron,and four P L3851(c.1155g＞c)mutation site,4 exon 12 P R413p(c.1238g＞c)mutation site,1 exon 12 P T418p(c.1252a＞c)mutation site,two ivs12+1(c.1315+1g＞a)mutation sites in exon 12;Two site mutations were detected in 2 of 29 children.Conclusion The detection rate of PKU in southern Xinjiang in recent 10 years was retrospectively analyzed.The mutation types and characteristics of exons 10,11 and 12 of PAH gene and the intron junction region of PAH gene in Xinjiang Uygur children with phenylketonuria were clarified,which laid the foundation for further study of phenylketonuria in Uygur families.

Objective To analyze the changes and clinical significance of aqueous humor stromal cell-de-rived factor-1(SDF-1),macrophage chemoattractant protein-1(MCP-1)and soluble adhesion molecule CD44(sCD44)in patients with diabetic cataract(DC).Methods A total of 80 patients with DC admitted to the hos-pital from January 2021 to January 2023 were selected as the DC group,and 40 patients with simple cataract during the same period were selected as the age-related cataract group.According to the stage of cataract,DC patients were divided into group A(incipient stage,32 cases),group B(intumescent stage,26 cases)and group C(mature stage and over mature stage,22 cases).According to the presence or absence of macular ede-ma after treatment,the patients were divided into occurrence group(20 cases)and non-occurrence group(60 cases).The levels of SDF-1,MCP-1 and sCD44 in each group were detected by enzyme-linked immunosorbent assay.The receiver operating characteristic curve and area under the curve(AUC)were used to analyze the value of SDF-1,MCP-1 and sCD44 levels in the diagnosis of DC.Results The levels of SDF-1,MCP-1 and sCD44 in the DC group were higher than those in the age-related cataract group(P<0.05),and the levels of SDF-1,MCP-1 and sCD44 in the A,B and C groups increased sequentially(P<0.05).The level of MCP-1 in the occurrence group was higher than that in the non-occurrence group(P<0.05).The AUC of MCP-1,sCD44 and SDF-1 in the diagnosis of DC was 0.869,and the diagnostic efficiency was better.Conclusion The changes of aqueous SDF-1,MCP-1 and sCD44 levels are related to the stage of cataract in DC patients.Dynam-ic monitoring of these three indexes,especially MCP-1,is helpful to judge the condition and prognosis of DC patients.