Objective To externally validate a prediction model based on clinical and CT imaging features for the preoperative identification of high-grade patterns (HGP), such as micropapillary and solid subtypes, in early-stage lung adenocarcinoma, in order to guide clinical treatment decisions. Methods This study conducted an external validation of a previously developed prediction model using a cohort of patients with clinical stage ⅠA lung adenocarcinoma from the Fourth Hospital of Hebei Medical University. The model, which incorporated factors including tumor size, density, and lobulation, was assessed for its discrimination, calibration performance, and clinical impact. Results A total of 650 patients (293 males, 357 females; age range: 30-82 years) were included. The validation showed that the model demonstrated good performance in discriminating HGP (area under the curve>0.7). After recalibration, the model's calibration performance was improved. Decision curve analysis (DCA) indicated that at a threshold probability>0.6, the number of HGP patients predicted by the model closely approximated the actual number of cases. Conclusion This study confirms the effectiveness of a clinical and imaging feature-based prediction model for identifying HGP in stage ⅠA lung adenocarcinoma in a clinical setting. Successful application of this model may be significant for determining surgical strategies and improving patients' prognosis. Despite certain limitations, these findings provide new directions for future research.

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Objective To investigate whether Heshouwuyin can delay the aging of Leydig cells in rat testis through DNA methyltransferase 1(DNMT1).Methods Totally 40 male Wistar rats were randomly divided into 4 groups,with 10 rats in each group.Immunohistochemistry was used to detect the expression levels of DNMT1 in testis tissue of rats.Testosterone content in serum of rats in each group was detected by ELISA test.A rat Leydig cell aging model was established by free radical oxidative damage.DNMT1 was knocked down by lentivirus in Leydig cells,and the cell senescence status and the testosterone content and testosterone synthesis key enzyme 3β-hydroxysteroid dehydrogenase(3β-HSD),cytochrome P450 family member 11A1(CYP11A1)content secreted by cells were detected by β-galactosidase(β-GAL)staining,immunofluorescenct staining and ELISA.Results Compared with the young control group(YCG),the expression of P16 protein and the positive rate of β-GAL in the testis tissue of rats in the natural aging group(NAG)increased significantly,and the expression of DNMT1 and serum testosterone levels decreased(P＜0.05).However,after Heshouwuyin intervention,the expression of P16 protein and the positive rate of β-GAL in the testis of aging rats were reduced,and DNMT1 expression and the serum testosterone levels increased(P＜0.05).The same trend was observed in Leydig cells.Knockdown of DNMT1 in Leydig cells,β-GAL positivity and P16 protein expression increased significantly,and testosterone secretion and testosterone synthesis key enzymes 3β-HSD,CYP11A1 content from Leydig cells decreased significantly,compared with the normal control group(NCG)(P＜0.05).When Heshouwuyin was added,the above phenomenon was improved.Conclusion Heshouwuyin can delay the aging of rat Leydig cells through DNMT1.

Chronic kidney disease（CKD）has a significant impact on global public health and is one of the important factors leading to the rise of incidence rate and mortality of non communicable diseases.Intestinal microecology is involved in many pathophysiological activities，such as immunity and nutrient absorption.With proposal of the concept of intestine-kidney axis in 2002，researchers found that the decline of glomerular filtration rate led to accumulation of uremic toxins in intestine，destroyed the intestinal mucosal barrier，led to the translocation of toxins，activated the systemic oxidative stress response，further promoted the progress of CKD.This article reviewed the function of gut microbiota，intestine-gut kidney axis，and the application of microbial preparations in CKD.

Objective To investigate the microbiome composition of deep invasive endometriosis lesions,offering novel insights into its pathogenesis,diagnosis,and treatment strategies.Methods From May 2021 to May 2022,we collected samples of normal endometrium(normal group,n=10),endometrium from patients with deep infiltrating endometriosis(DIE endometrium group,n=14),and lesions from these patients(DIE lesion group,n=10)for 16s rRNA sequencing analysis.We employed the bacterial community diversity algorithm(alpha diversity and beta diversity),principal coordinate analysis(PCoA)distance matrix algorithms(Bray-Curtis and Unifrac matrices),as well as the biological identification algorithm(LeFSe)to investigate microbiome differences between groups and identify differentially abundant bacteria and enriched KEGG functions.Results The diversity of the three groups did not show any significant difference,while the β diversity exhibited a statistically significant distinc-tion(P=0.005 5).The focus group had a relatively low abundance of Firmicutes at the phylum level and a relatively increased abundance of Fusobacteria.At the genus level,there was an increased relative abundance of Enterococcus and Prevotella.LEFse analysis suggested that Proteobacteria and Gammaproteobacteria were the main dominant in the lesion group.Notably,Gamma proteobacteria emerged as a key differential species among the three groups'microbial flora with statistical significance(P=0.021 2).Conclusion Compared to the normal group and DIE group,there was a significant increase in the abundance of Fusobacteria,Proteobacteria,Gammaproteobacteria,Enterococcus,and Prevotella.These findings offer novel therapeutic targets for the prevention and intervention of deep infiltrating endometriosis.

Objective To investigate the effect of E2 signaling in myofibers on muscular macrophage efferocytosis in mice with cardiotoxin-induced acute skeletal muscle injury.Methods Female wild-type C57BL/6 mice with and without ovariectomy and male C57BL/6 mice were given a CTX injection into the anterior tibial muscle to induce acute muscle injury,followed by intramuscular injection of β-estradiol(E2)or 4-hydroxytamoxifen(4-OHT).The changes in serum E2 of the mice were detected using ELISA,and the number,phenotypes,and efferocytosis of the macrophages in the inflammatory exudates and myofiber regeneration and repair were evaluated using immunofluorescence staining and flow cytometry.C2C12 cells were induced to differentiate into mature myotubes,which were treated with IFN-γ for 24 before treatment with β-Estradiol or 4-OHT.The treated myotubes were co-cultured with mouse peritoneal macrophages in a 1:2 ratio,followed by addition of PKH67-labeled apoptotic mouse mononuclear spleen cells induced by UV irradiation,and macrophage efferocytosis was observed using immunofluorescence staining and flow cytometry.Results Compared with the control mice,the female mice with ovariectomy showed significantly increased mononuclear macrophages in the inflammatory exudates,with increased M1 cell percentage,reduced M2 cell percentage and macrophage efferocytosis in the injured muscle,and obviously delayed myofiber regeneration and repair.In the cell co-culture systems,treatment of the myotubes with β-estradiol significantly increased the number and proportion of M2 macrophages and macrophage efferocytosis,while 4-OHT treatment resulted in the opposite changes.Conclusion In injured mouse skeletal muscles,myofiber E2 signaling promotes M1 to M2 transition to increase macrophage efferocytosis,thereby relieving inflammation and promoting muscle regeneration and repair.

[摘 要] 目的：本研究旨在探讨转录因子HOXC13在喉鳞状细胞癌（LSCC）中的表达、功能及可能的调控机制。方法：常规培养LSCC细胞，将其分为sh-NC组、sh-HOXC13组、pcDNA3.1-NC组、pcDNA3.1-HOXC13组、pcDNA3.1-PCNA组和sh-HOXC13+pcDNA3.1-PCNA组，用转染试剂将相应核酸和质粒转染各组细胞。用数据库数据分析HOXC13 mRNA在LSCC组织中的表达；收集2019年1月至2022年12月在联勤保障部队第九八〇医院耳鼻咽喉头颈外科手术切除的62对LSCC组织及配对的癌旁组织，免疫组织化学法检测中国人LSCC组织中HOXC13蛋白的表达，qPCR检测中国人LSCC组织、癌旁组织以及各组细胞中HOXC13和PCNA mRNA的表达，MTS法检测各组AMC-HN-8细胞的增殖能力，平板克隆实验检测各组AMC-HN-8细胞的克隆形成能力，Transwell小室实验检测各组AMC-HN-8细胞的迁移和侵袭能力，双萤光素酶报告基因实验和染色质免疫沉淀技术（ChIP）验证HOXC13与PCNA之间的结合关系。结果：HOXC13和PCNA在LSCC组织和细胞中均呈高表达（P<0.05或P<0.01）且两者的表达水平呈正相关（P<0.01），HOXC13的表达水平与TNM分期有明显关联（P<0.01）。敲减HOXC13可明显抑制AMC-HN-8细胞的增殖、迁移和侵袭能力（均P<0.01），过表达HOXC13则促进TU686细胞的增殖、迁移和侵袭能力（均P<0.01）。HOXC13可与PCNA启动子区结合并调控其转录。敲低PCNA可部分逆转HOXC13对AMC-HN-8细胞的恶性生物学行为的促进作用（均P<0.01）。结论：HOXC13通过上调PCNA促进LSCC细胞的恶性生物学行为，HOXC13是LSSC临床诊断和治疗的潜在靶点。

Objective To investigate the relationship of miRNA gene polymorphisms with blood pressure(BP)responses to the sodium and potassium diet intervention.Methods In 2004,we recruited 514 participants from 124 families in seven villages of Baoji,Shaanxi Province,China.All subjects were given a three-day normal diet,followed by a seven-day low-salt diet,a seven-day high-salt diet,and finally a seven-day high-salt and potassium supplementation.A total of 19 miRNA single nucleotide polymorphisms(SNPs)were selected for analysis.Results Throughout the sodium-potassium dietary intervention,the BP of the subjects fluctuated across all phases,showing a decrease during the low-salt period and an increase during the high-salt period,followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet.MiR-210-3p SNP rs 12364149 was significantly associated with systolic BP(SBP),diastolic BP(DBP)and mean arterial pressure(MAP)responses to low-salt diet.MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention.In addition,miR-26b-3p SNP rs115254818 was significantly correlated with SBP,DBP and MAP responses to high-salt intervention.MiR-1307-5p SNPs rs1 1191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet.MiR-4638-3p SNP rs6601178,miR-210-3p SNP rs12364149,miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet.In addition,miR-26b-3p SNP rs115254818 was significantly associated with SBP,DBP and MAP responses to potassium supplementation.MiR-1307-5p SNPs rs11191676,rs2292807,and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation.Conclusion miRNA gene polymorphisms are associated with BP response to sodium and potassium,suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.

Objective:To investigate the efficiency and safety of the pulsatile GnRH therapy in the treatment of male congeni-tal hypogonadotropic hypogonadism(CHH).Methods:We retrospectively analyzed the clinical data on 45 CHH males treated by pulsatile GnRH therapy in our hospital from January 2013 to March 2023.We treated the patients with gonadorelin at 7-15 μg,one pulse/90 min,and followed them up every month in the first 3 months and then every 3 to 6 months after treatment,for an average of 19.1±4.3 months,during which we recorded the height,body weight,penile length,testis volume,Tanner stages,levels of FSH,LH and T,semen parameters and adverse reactions of the patients,followed by comparison of the data obtained with the baseline.Results:The levels of FSH,LH and T of the patients were dramatically elevated after treatment(P<0.01).The T level of the6 ca-ses of cryptorchidism,however,failed to reach the normal value within 18.2±8.6 months of follow-up.Significant improvement was seen in the external genitalia and secondary sexual characteristics of all the patients,and spermatogenesis was observed in the semen in 33 cases(73.3% ),with a mean sperm concentration of(18.2±6.2)106/ml,sperm progressive motility of(19.7±6.5)%,and semen volume of(1.8±0.6)ml.Eight of the cases achieved natural fertility,and another 3 achieved childbirth by assisted re-productive technology.As for adverse events,gynecomastia was observed in 8,subcutaneous induration in 6,and allergic reaction to therapeutic agent in 3 cases.Conclusion:Pulsatile GnRH therapy is an effective and safe strategy for male CHH.However,clini-cians should choose appropriate approaches to different individual cases.

Aim To investigate the changes in the proliferation and apoptosis of Siha cells after knocking down Rho GTPase-activating protein 30(ARHGAP30).Methods After designing specific shARHGAP30 primers and connecting them to the pLKO.1 vector,we transformed them into Escherichia coli competent cells,then co-transfecting them with lentiviral helper plasmids into HEK-293T cells.We collected and filtered cell supernatant to obtain the vi-rus to infect Siha cells.RT-qPCR and Western blot were used to detect knockdown efficiency,as well as changes in the expression of Bax and Bcl-2 after trans-fection.The CCK-8 method was employed to measure the proliferation level of cells after knockdown.Results After successful construction of a lentiviral plasmid with knockdown of the ARHGAP30 gene and establish-ment of stably transfected Siha cells,ARHGAP30 tran-scription and translation(P＜0.01)in Siha cells de-creased,Bax/Bcl-2 significantly decreased(P＜0.01),indicating decreased apoptosis and increased cell proliferation(P＜0.01).Conclusions This study suggests the involvement of ARHGAP30 in the proliferation and apoptosis of Siha cells,and regulating the ARHGAP30 gene may interfere with the occurrence and development of cervical cancer.