Objective This study aimed to investigate the association between long-term radon exposure and changes in peripheral blood DNA methylation levels, as well as alterations in the expression of methylation-related regulatory genes (DNMT1, DNMT3A, and MBD2) among underground non-uranium metal miners. Methods Five non-uranium metal mines with varying levels of radon exposure were enrolled in this study. From each mine, 30 underground miners and 30 aboveground workers were randomly recruited. Basic demographic information was collected via a standardized questionnaire, and peripheral venous blood samples were obtained from all participants. An enzyme-linked immunosorbent assay (ELISA) colorimetric method was used to detect peripheral blood DNA methylation levels. Real-time quantitative PCR was used to measure mRNA expression levels of DNMT1, DNMT3A, and MBD2. These indicators were compared between underground and aboveground groups and among underground miners with different radon exposure levels. Multiple linear regression analysis was conducted to examine the associations between cumulative radon dose and two outcomes: peripheral blood DNA methylation levels, and the expression levels of methylation-related regulatory genes in underground miners. Results The average radon concentration in the underground workplaces of the five mines was 4,088 Bq/m³ (range: 116-18,188 Bq/m³), corresponding to an estimated annual effective dose of approximately 25.67 mSv for miners. The average radon concentration in aboveground workplaces was 58 Bq/m³ (range: 28-1796 Bq/m³), equivalent to an annual effective dose of approximately 0.51 mSv for aboveground workers. The average cumulative radon dose of underground miners was approximately 26.56 times that of aboveground workers (Z=−12.469, P<0.001). Compared with the aboveground workers, the peripheral blood DNA methylation level of underground miners was significantly decreased, approximately 0.77 times that of the aboveground group (Z=−2.313，P<0.05), accompanied by decreased expression of DNA methyltransferase genes DNMT1 and DNMT3A, which were 0.83 and 0.68 times those of the aboveground group, respectively (Z=−3.002、−4.190，P<0.01). After adjusting for age, working years, body mass index, smoking status, and alcohol consumption, multiple linear regression analysis revealed two key findings: cumulative radon dose was significantly and inversely correlated with peripheral blood DNA methylation levels (β=−0.752, P<0.001); and cumulative radon dose was significantly negatively associated with the expression of DNMT1 and DNMT3A (β=−0.319, −0.369, P<0.01). Conclusion The reduced DNA methylation levels and downregulated expression of DNA methyltransferase genes in underground miners are closely associated with long-term radon exposure.

Objective To observe the efficacy of Hongjin Xiaojie capsules in treating hematoma after Mammotome minimally invasive excision and to determine the common clinical complications such as hematoma and pain after the surgery.Methods A total of 70 patients who developed hematoma within 72 hours after Mammotome minimally invasive excision for breast lumps at our hospital were selected.Based on different treatment methods,patients were divided into the observation group and the control group,with 35 cases in each group.The control group received only external hot compress treatment,while the observation group received local hot compress combined with oral administration of Hongjin Xiaojie Capsule for 4 weeks.Follow-up was conducted every 4 weeks postoperatively for a total of 12 weeks.Color ultrasound was performed to monitor the size of the hematoma.Changes in pain visual analog scale(VAS)scores and traditional Chinese medicine(TCM)syndrome scores for blood stasis were compared between the two groups of patients during follow-up.Results Four weeks after operation,the pain VAS score was significantly lower in the observation group than that in the control group[2(1,3)points vs.3(2,4)points,P＜0.05],and the proportion of hematoma was lower in the observation group than that in the control group(45.7%vs.82.9%,P＜0.05).At 12 weeks after surgery,there were no significant differences in pain scores or hematoma proportions between the two groups.The TCM symptom scores were lower in the observation group than those of the control group at 4 weeks and 12 weeks after operation(P＜0.05).Conclusion Hongjin Xiaojie capsule can promote the absorption of hematoma after Mammotome surgery,effectively alleviate breast hematoma and pain,and have high safety,demonstrating broad clinical application value.

This paper reported a case of juvenile trabecular ossifying fibroma（JTOF） originating from the uncinate process. The main clinical manifestation was nasal obstruction and epiphora. Contrast-enhanced sinus CT revealed an irregular heterogeneous soft tissue mass centered in the right uncinate process, with involvement of the right anterior ethmoid sinus, maxillary sinus ostium, frontal process of the maxilla, and partial nasolacrimal duct. The solid components of the tumor demonstrated enhancement on contrast imaging. The patient underwent endoscopic resection of the right sinonasal tumor under general anesthesia. Postoperative pathological examination confirmed the diagnosis of JTOF. No tumor recurrence was observed during the 3-month follow-up period.
Humans ; Ethmoid Bone/pathology* ; Fibroma, Ossifying

OBJECTIVES: To explore the value of ferroptose-related genes in the diagnosis and prediction of ulcerative colitis (UC). METHODS: We used UC dataset from the GEO database to screen for differentially expressed genes (DEGs) in UC. The DEGs related to ferroptositis were screened from the FerrDb database and their functions were analyzed. The hub genes were identified by constructing the protein-protein interaction network (PPI), the differences in immune infiltration levels between UC and the control group were evaluated using CIBERSORT, and the diagnostic values of the hub genes for UC were verified by using the training set. In a mouse model of UC, we examined the expression levels of the hub genes in the colon tissues of the mice using real-time fluorescence quantitative PCR (qPCR). RESULTS: We identified a total of 76 DEGs related to ferroptosis. Functional enrichment analysis showed that these genes were significantly enriched in ferroptosis and hypoxia pathways. The PPI network identified 10 hub genes, and 9 of them were highly expressed in UC. Analysis of immune cell infiltration showed that 27 cell types were significantly increased in UC (P<0.05), and the immune checkpoints-related genes had the strongest correlation with the hub gene PPARG (P<0.05). Verification analysis using the training set showed that P4HB, PPARG and STAT3 had the best predictive value for UC (P<0.05). In the UC mouse model, the expression of PPARG was significantly decreased and the expressions of P4HB and STAT3 were significantly increased in the colon tissues of the mice as compared with the normal mice. CONCLUSIONS Ferroptose-related genes have significant value for diagnosis and prediction of UC.
Colitis, Ulcerative/genetics* ; Animals ; Mice ; Ferroptosis/genetics* ; Humans ; Protein Interaction Maps ; Disease Models, Animal ; Gene Expression Profiling ; STAT3 Transcription Factor/genetics*

Congenital orofacial cleft, the most common birth defect in the maxillofacial region, exhibits a wide range of prognosis depending on the severity of deformity and underlying etiology. Non-syndromic congenital orofacial clefts typically present with milder deformities and more favorable treatment outcomes, whereas syndromic congenital orofacial clefts often manifest with concomitant organ abnormalities, which pose greater challenges for treatment and result in poorer prognosis. This consensus provides an elaborate classification system for varying degrees of orofacial clefts along with corresponding diagnostic and therapeutic guidelines. Results serve as a crucial resource for families to navigate prenatal screening results or make informed decisions regarding treatment options while also contributing significantly to preventing serious birth defects within the development of population.
Humans ; Cleft Lip/diagnosis* ; Cleft Palate/diagnosis* ; Consensus ; Prenatal Diagnosis ; Female

Objective:To separate and purify the polysaccharides from Polygonatum filipes,characterize their primary structure and investigate the immunomodulatory effects on RAW264.7 macrophages.Methods:Crude polysaccharides from Polygonatum filipes were extracted by ultrasound assisted method,then Polygonatum filipes polysaccharides(CSPFPs)were obtained after elimination of the proteins with combined papain-Sevag method.The total sugar content was determined by phenol-sulfuric acid method.Structures of CSPFPs were analyzed by fourier transform infrared spectroscopy(FT-IR),high performance gel permeation chromatography(HPGPC)and high performance liquid chromatography(HPLC).Effects of CSPFPs on cell viability,pinocytic activity,TNF-α secretion,MAPK and NF-κB signaling pathways of RAW264.7 cells were explored by MTT,Neutral red,ELISA and Western blot,respectively.Results:Extraction rate of CSPFPs by ultrasound-assisted method was 41.61%,which contained total sugar content of 94.00%.CSPFPs with Mw of 3 125 Da was composed of arabinose(1.85%),galactose(6.14%),glucose(56.41%)and mannose(35.60%).The in vitro experiments showed that CSPFPs were non-cytotoxic and enhanced the pinocytic activity,TNF-α secretion and phosphorylation levels of p38,ERK,JNK,p65,IκB and IKK,indicating the activation of MAPK and NF-κB signaling pathways under the concentra-tion of 2.5～200 μg/ml.Conclusion:The ultrasound-assisted method can efficiently isolate CSPFPs with immunomodulatory activity,which provides basic data for the development and application of CSPFPs as an immunostimulant.

Objective The study aimed to compare the efficacy and safety of tislelizumab combined with chemotherapy versus pembrolizumab combined with chemotherapy as first-line treatments for advanced lung squa-mous cell carcinoma.Methods We retrospectively reviewed and analyzed the medical records of 116 patients with advanced lung squamous cell carcinoma treated with first-line chemotherapy plus tislelizumab or pembrolizumab in Guangzhou Chest Hospital from September 2020 to April 2024.We focused on analysis of time to treatment failure(TTF)and objective response rate(ORR)as well as disease control rate(DCR)and treatment-related adverse events(TRAEs).Results At a median follow up of 19.7 monyhs,the median TTF was 9.7 months in the tislelizumab group and 7.7 months in the pembrolizumab group(P<0.05).In addition,the ORR in the tislelizumab group was significantly higher than that in the pembrolizumab group(77.6%vs.60.3%,P<0.05),with DCRs of 93.1%and 87.9%,respectively(P=0.342).Regarding safety,the proportions of grade 3 or higher TRAEs and any-grade TRAEs were comparable between the two groups:29.3%and 81.0%in the tislelizumab group,and 32.8%and 87.9%in the pembrolizumab group,respectively.The most common TRAEs in both groups were hematological toxicities.Conclusions Tislelizumab plus chemotherapy demonstrated better efficacy and safety compared to pembrolizumab with chemotherapy as first-line treatment for Chinese patients with advanced lung squamous cell carcinoma.

ObjectiveTo investigate the potential mechanisms and pathways through which Gandouling （GDL） exerts its effects in the treatment of liver fibrosis in Wilson disease. MethodsSixty male SD rats were randomly divided into six groups： the normal group， the model group， the GDL low-， medium-， and high-dose groups （0.24， 0.48， 0.96 g·kg^-1）， and the penicillamine group （90 mg·kg^-1）， with 10 rats in each group. A copper-loaded Wilson disease rat model was established by gavage administration of 300 mg·kg^-1 copper sulfate pentahydrate to all groups except the normal group. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathomorphological changes in the liver. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of hyaluronic acid （HA）， laminin （LN）， procollagen type-Ⅲ peptide （PC-Ⅲ）， and collagen type-Ⅳ （C-Ⅳ）. Transmission electron microscopy was used to examine the ultrastructure of liver tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression levels of liver tissues and serum exosomal long noncoding RNA H19 （LncRNA H19）， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， and mammalian target of rapamycin （mTOR）. Western blot analysis was performed to assess the expression levels of PI3K， Akt， mTOR， and their phosphorylated forms， as well as autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3B （LC3-Ⅱ/LC3-Ⅰ） in liver tissues. Beclin1 and LC3-Ⅱ fluorescence signal intensity was observed by immunofluorescence. ResultsCompared with the normal group， the model group exhibited inflammatory cell infiltration in hepatocytes， unclear nuclear boundaries with cell cleavage and necrosis， and collagen fiber deposition around confluent areas. The levels of HA， LN， PC-Ⅲ， and C-Ⅳ were significantly elevated （P<0.01）. Transmission electron microscopy revealed an increased number of autophagic vesicles， with autophagic lysosomes exhibiting a single-layer membrane structure following degradation of most envelopes. Expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ were significantly increased （P<0.01）， and fluorescence signals of Beclin1 and LC3-Ⅱ were markedly enhanced. The protein expression levels of PI3K， Akt， mTOR， p-PI3K， p-Akt， and p-mTOR were reduced （P<0.01）， while LncRNA H19 expression was increased （P<0.01）， and mRNA expression levels of PI3K， Akt， and mTOR were decreased （P<0.01）. After treatment with GDL， the degree of liver fibrosis was significantly improved， with decreased levels of HA， LN， PC-Ⅲ， and C-Ⅳ. The number of autophagic vesicles was significantly reduced， and expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ proteins were lower （P<0.01）. The fluorescence signals of Beclin1 and LC3-Ⅱ weakened dose-dependently. The protein levels of PI3K， Akt， mTOR， p-PI3K， p-Akt， and p-mTOR were elevated （P<0.01）， while the expression level of LncRNA H19 was reduced （P<0.01）. Furthermore， the mRNA expression levels of PI3K， Akt， and mTOR increased （P<0.05， P<0.01）. ConclusionGDL may alleviate liver fibrosis and reduce liver injury by regulating the PI3K/Akt/mTOR autophagy signaling pathway via LncRNA H19.

Objective To explore the five-circuit and six-qi features of birth time and onset time of children with acute lymphoblastic leukemia(ALL).Methods A total of 877 cases of children with ALL from Children's Hospital of Soochow University from June 2021 to February 2023 were collected,and their five-circuit and six-qi features of birth time and onset time were analyzed.And then the correlation of five-circuit and six-qi features of birth time and onset time with ALL was explored preliminarily,and the pathogenic characteristics of congenital factors and acquired pathogenic factors were revealed.Results(1)The children who were born in the year with the heavenly stems being bing(the 3rd of the ten heavenly stems)and ding(the 4th of the ten heavenly stems)and with the earthly branches being shen(the 8th of the twelve earthly branches)and you(the 9th of the twelve earthly branches)are prone to suffer from ALL,and the birth year of children with ALL had the five-circuit and six-qi features of the joining of guest circuit with dominant circuit being rebellious.ALL is commonly seen in the year with the heavenly stems being geng(the 7th of the ten heavenly stems)and xin(the 8th of the ten heavenly stems)and with the earthly branches being zi(the 1st of the twelve earthly branches)and chou(the 2nd of the twelve earthly branches),and the onset year of ALL in children had the five-circuit and six-qi features of the yearly circuit being gold-circuit and water-circuit,sitian-zaiquan yearly circuit qi being shaoyin monarch-fire with yangming dryness-gold,taiyin damp-earth with taiyang cold-water,and the qi-circuit assimilation relationship being celestial correspondence,same celestial correspondence,celestial correspondence in convergent year,disharmony,mildly-rebellious,and celestial restriction.Conclusion Gold-dryness and water-cold are the congenital factors and acquired pathogenic factors of ALL.The onset of ALL in children is closely related to qi insufficiency and qi stagnation of wood and fire in five-circuit and six-qi theory.

Cleidocranial dysplasia(CCD)is a rare autosomal dominant disorder mainly characterized by skeletal and dental abnormali-ties.It is caused by the runt-related transcription factor-2(Runx2)mutations.In this paper,a case of CCD syndrome is reported.The proband and his family were examined by the proband's verification method for general condition,oral specialty and genetic examination.A new nonsense mutation exon7 c.1078C＞T,p.Gln360*heterozygous variant(Q360X)was verified,the relationship between Runx2 mutation and CCD phenotype was analyzed.