Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Aim To explore the in vitro anti-human triple-negative breast cancer(TNBC)effect and mech-anism of Austocystin R.Methods MTT assay was used to evaluate the anti-tumor potential of Austocystin R for various human tumor cells and normal cells.Flow cytometry was employed to evaluate the influence on cell cycle progression.mRFP-GFP-LC3 adenovirus transfection was used to evaluate the autophagic flux process.Western blot assay was used to verify the effect of Austocystin R on the expression of related pro-teins.Results The results showed that Austocystin R significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner,especially for the MDA-MB-231 cells with an IC50 of 1.45μmol·L-1.In addition,Austocystin R increased the protein expression of PTEN,p53,p-p53,p27,p21,and down-regulated the expression of p-PI3K,p-AKT and p-mTOR.Austocystin R can significantly increase the proportion of S-phase MDA-MB-231 cells,inhibit the expression of Cyclin D1,CDK4,CDK6,Rb,Cyclin B1 and CDK1,and promote the expression of Cyclin E1 and CDK2.Austocystin R can promote the autophagic flux process of MDA-MB-231 cells,promote the expres-sion of LC3 Ⅰ/Ⅱ,p-Beclin-1,p-ULK1,HMGB-1 and Atg 14 proteins,and inhibit the expression of Beclin-1,ULK1,p62,ATG 3,ATG 4B,ATG 5,ATG 7,ATG 12,ATG 13 and ATG 16L1 proteins.Conclusion Austo-cystin R can exhibit its anti-TNBC activity by inhibi-ting the PI3K/AKT/mTOR signaling pathway,blocking the cell cycle at the S phase and inducing autophagic cell death.

Objective:To explore the feasibility of shortening the time of long exercise test (LET) from 120 to 60 minutes by analyzing the positive rate within 60 minutes among periodic paralysis (PP) patients who were positive in 120-minute test.Methods:The data of patients undergoing 120-minute LET from January 2015 to October 2021 in Beijing Tiantan Hospital, Capital Medical University were retrospectively analyzed, with 30%, 33%, and 40% as diagnostic cut-off values, respectively. PP patients with positive results within 120 minutes after exercise were enrolled in the study. The positive rate within 30 minutes and 60 minutes after exercise was calculated. The change rates of compound muscle action potential (CMAP) amplitude and the sensitivity and specificity of LET at 30 minutes, 60 minutes, and 120 minutes after exercise were analyzed. The change rate of CMAP amplitude in PP patients who did not show positive results within 60 minutes was further calculated.Results:A total of 254 patients were examined, including 114 PP patients. With 30%, 33%, and 40% as diagnostic cut-off values, the results showed that there were 88, 88, and 82 positive PP patients, respectively. Under each diagnostic cut-off values, the age of positive PP patients was (32±10) years, with a male proportion of 98% (86/88), 98% (86/88), and 99% (81/82), respectively; the positive rate of PP patients within 30 minutes after exercise was 60% (53/88), 58% (51/88), and 41% (34/82), respectively; the positive rate of PP patients within 60 minutes after exercise was 91% (80/88), 86% (76/88), and 83% (68/82), respectively. At the cut-off values of 30%, 33% and 40%, the change rate of CMAP amplitude at 30 minutes [-36% (-49%, -23%), -36% (-49%, -23%), -37% (-51%, -24%)], 60 minutes [-51% (-66%, -40%), -51% (-66%, -40%), -53% (-66%, -42%)] and 120 minutes [-57% (-67%, -45%), -57% (-67%, -45%), -58% (-67%, -46%)] after exercise showed statistically significant difference among 3 time points ( H=57.764, 57.764, 59.616, respectively, all P<0.001); the further comparison between time points showed that there was statistically significant difference in the change rate of CMAP amplitude between 60 minutes ( Z=5.419, 5.419, 5.531, respectively, all P<0.001), 120 minutes ( Z=7.325, 7.325, 7.431, respectively, all P<0.001) and 30 minutes after exercise, but there was no statistically significant difference in the change rate of CMAP amplitude between 120 minutes and 60 minutes after exercise ( Z=1.906, 1.906, 1.899, respectively, all P>0.05); the sensitivity of LET for the diagnosis of PP at 60 minutes after exercise was 70.2% (80/114), 66.7% (76/114) and 59.6% (68/114), and the specificity of LET for the diagnosis of PP was 77.9% (109/140), 84.3% (118/140) and 91.4%(128/140), respectively. When 30%, 33% and 40% were used as the diagnostic cut-off values, and the change rate of CMAP amplitude at 60 minutes after exercise fell below these cut-off values but showed a decline of ≥20%, ≥22% and ≥24%, respectively, the detection time should be extended to 120 minutes. Conclusions:Whether using 30%, 33%, or 40% as diagnostic cut-off values, it is feasible to shorten the LET time from 120 minutes to 60 minutes. The 60-minute LET has good sensitivity and specificity for the diagnosis of PP. It is recommended to extend the detection time to 120 minutes for patients with a ≥20%, ≥22%, or ≥24% decline in CMAP amplitude at 60 minutes after exercise while falling short of corresponding diagnostic cut-off values when 30%, 33%, and 40% are used as diagnostic cut-off values. This method can not only improve the examination efficiency of LET, but also minimize the missed diagnosis as much as possible.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective To analyze the correlation between lesion volume,lesion mass,and maximum lesion diameter in the assessment of advanced hepatocarcinoma with lung metastasis,and to evaluate the application value of total volume response and total mass response of lung metastatic lesions in efficacy assessment.Methods A retrospective analysis was conducted on the CT imaging data of 20 patients clinically confirmed with hepatocarcinoma and lung metastases,followed by subsequent follow-up to monitor their survival outcomes.Volume measurement software was used to measure the volume of lesions before and after treatment.We recored lesion diameter,volume measurements and CT values,calculated the mass of the lesions.The correlation between lesion volume,mass and diameter was analyzed,as well as the correlation between the change rates of volume,mass and lesion diameter.Additionally,the total volume and total mass of all lesions were calculated.The correlation between the change rates of total volume/total mass and the change rate of pulmonary lesion diameter under the RECIST 1.1 criteria,as well as the correlation with changes in patients'tumor markers,were analyzed.Furthermore,the overall volume response and overall mass response of lesions were evaluated based on changes in total volume and total mass,and their consistencies with the RECIST 1.1 criteria for efficacy evaluation were analyzed.Finally,univariate Cox regression analysis was performed to explore the association between these variables and patient survival outcomes.Results There was strong correlation between lesion volume,mass and tumor diameter(r=0.771,0.775),between the rate of change in mass and the rate of change in lesion diameter(r=0.846),and between the rates of change in total volume/total mass and the rate of change in pulmonary lesion diameter under the RECIST 1.1 criteria(r=0.800,0.896).The correlation between the rates of change in total volume/total mass and patients'tumor markers was not statistically significant.There was moderate correlation between the rate of change in volume and the rate of change in lesion diameter(r=0.692).The evaluation results of total volume response and total mass response for pulmonary lesions in advanced hepatocarcinoma with lung metastasis were generally consistent with the RECIST 1.1 criteria(Kappa=0.486,0.426).Univariate Cox regression analysis revealed that total lesion volume(P=0.047)and total lesion mass(P=0.049)were independent prognostic factors for survival outcomes.Conclusion Lesion volume,mass,and diameter,as well as their respective change rates,were found to be interrelated.Furthermore,total lesion volume and total lesion mass were identified as independent prognostic factors for survival outcomes.The total volume response and total mass response are promising evaluation methods in evaluating the efficacy of lung metastasis of hepatocarcinoma,which are different from the RECIST 1.1 evaluation criteria.

Objective:To explore the impact of a three-dimensional management based on a perinatal one-day clinic on pregnancy outcomes in overweight and obese pregnant women.Methods:It was a randomized controlled trial. A simple random sampling method was used to select 460 singleton pregnant women with a pre-pregnancy body mass index≥24 kg/m2 who had regular prenatal check-ups at the Obstetrics and Gynecology Center of the Third Affiliated Hospital of Chongqing Medical University from June 1, 2018, to December 31, 2022. The women were randomly divided into an experimental group and a control group (230 cases each) using a computer-generated random number table. The control group received regular prenatal check-ups according to the pregnancy care guidelines (once every 4 weeks during mid-pregnancy, once every 2 weeks during late pregnancy, with additional frequency as needed based on the condition). The control group also received a one-time body composition analysis and dietary guidance from a nutritionist at the time of registration. In addition to the control group′s interventions, the experimental group received three-dimensional management based on a perinatal one-day clinic. It included an intensive one-day clinic session, a traditional plus internet-based re-education model (as needed based on the condition), individualized guidance from obstetrics and clinical nutrition clinics (once every 2 weeks), a free body composition test at 24 weeks of pregnancy, and weekly WeChat group push of health care knowledge during pregnancy. A total of 55 cases dropped out, leaving 200 cases in the experimental group and 205 cases in the control group for analysis. General information, pregnancy-related, and postpartum indicators were collected in the two groups. The effect of three-dimensional management based on a perinatal one-day clinic on pregnancy outcomes in overweight and obese pregnant women was analyzed using t-tests and chi-square tests. Results:There was no significant differences in baseline age, pre-pregnancy body mass index, initial blood glucose, initial glycated hemoglobin, or initial gestational age between the two groups (all P>0.05). The experimental group showed significantly lower gestational weight gain, neonatal weight, and proportion of excessive pregnancy weight gain compared to those in the control group [(11.41±5.23) vs (13.22±4.51) kg, (3 352.1±465.3) vs (3 489.5±464.0) g, 48.00% vs 73.17%] (all P<0.05). There were no significant differences in hospitalization days, gestational age at delivery, incidence of gestational diabetes, incidence of hypertensive disorders of pregnancy, incidence of premature rupture of membranes, incidence of preterm birth, incidence of macrosomia, vaginal delivery rate and rate of neonatal transfer to the pediatric department between the two groups (all P>0.05). Conclusion:Early intervention with the three-dimensional management based on the one-day perinatal clinic can effectively control gestational weight gain and neonatal weight in overweight and obese pregnant women.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Purpose: This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. Methods: Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. Results: Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). Conclusion Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.