Jinfeng Li

Background: Enucleation, a surgical procedure, is commonly used to treat large jaw cysts, unicystic ameloblastomas and keratocysts. However, it remains unclear to what extent the jaw bone regenerates after enucleation. We aimed to evaluate the percentage and the survival analysis of jaw bone regeneration, in terms of cavity volume residual (CVR), in patients who underwent enucleation of large jaw cysts, unicystic ameloblastomas and keratocysts. Methods: We collected data longitudinally from 75 patients who underwent jaw cystic lesions enucleation at the Stomatological Hospital of Xi’an Jiaotong University, between January 2015 and June 2021. All patients had both preoperative and postoperative cone-beam computed tomography (CBCT) imaging data. CBCT images were analyzed using Image J. Changes in the CVR were assessed at various follow-up time points, and the Kaplan-Meier method was utilized to evaluate the CVR over time. Results: The patients had a mean age of 31.7 years (range: 5.5–72 years) with 58.66% of them being male. The postoperative CVR was 32.20% at three months, 21.10% at six months, 15.90% at 12 months, and 5.60% at 24 months. The percentage of CVR during follow-up periods for the initial size Quartile (Q)1 (212.54-1569.60 mm³) was substantially lower than those of Q2 and Q3 at and after seven months of follow-up and became statistically significant at the 12-month mark. Conclusion: This study demonstrates that spontaneous bone regeneration can occur after enucleation of large jaw cysts, unicystic ameloblastomas and keratocysts, even without the use of filler materials. The initial size of the lesion had a significant impact on the outcome of cystic lesion enucleation over time. To minimize the risks associated with radiation exposure and expenses, we recommend reducing the frequency of CT imaging follow-ups for patients with small initial cavity sizes (ranging from 212.54 to 1569.60 mm³).

The cell of origin and the development of breast cancer are not fully elucidated in BRCA1 mutation carriers, especially for estrogen receptor (ER)–positive breast cancers. Here, we performed single-cell RNA sequencing (RNA-seq) on 82,122 cells isolated from the breast cancer tissues and adjacent or prophylactic normal breast tissues from four BRCA1 mutation carriers and three noncarriers. Whole-exome sequencing was performed on breast tumors from the four BRCA1 mutation carriers; for validation, bulk RNA-seq was performed on adjacent normal breast tissues from eight additional BRCA1 mutation carriers and 14 noncarriers. Correlation analyses suggested that breast cancers in BRCA1 mutation carriers might originate from luminal cells. The aberrant luminal progenitor cells with impaired differentiation were significantly increased in normal breast tissues in BRCA1 mutation carriers compared with noncarriers. These observations were further validated by the bulk RNA-seq data from additional BRCA1 mutation carriers. These data suggest that the cell of origin of basal-like breast tumors (ERneg) in BRCA1 mutation carriers might be luminal progenitor cells. The expression of TP53 and BRCA1 was decreased in luminal progenitor cells from normal breast tissue in BRCA1 mutation carriers, which might trigger the basal/mesenchymal transition of luminal progenitors and might result in basal-like tumor development. Furthermore, ERhigh luminal tumors might originate from mature luminal cells. Our study provides in-depth evidence regarding the cells of origin of different breast cancer subtypes in BRCA1 mutation carriers.Significance:Single-cell RNA-seq data indicate that basal-like breast cancer (ERneg) might originate from luminal progenitors, and ERhigh luminal breast cancer might originate from mature luminal cells in BRCA1 mutation carriers.

Table S8. Somatic mutations detected in the tumor tissues from the four BRCA1 mutation carriers by whole-exome sequencing.

Figure S1. Known cell type specific makers used to define clusters; Figure S2. The aberrant proportions of epithelial cells in normal breast tissues from BRCA1 mutation carriers validated by immunohistochemistry staining and bulk RNA-seq data; Figure S3. Impaired differentiation processes of luminal and basal/myoepithelial lineages in normal breast tissue from BRCA1 mutation carriers; Figure S4. Identification and characterization of the tumor cells in BRCA1 mutation carriers; Figure S5. Upregulated and downregulated pathways in tumor cells compared with their putative cells of origin in each BRCA1 mutation carrier; Figure S6. Comparison of the expression levels of KRT14/17 in luminal progenitor cells in normal breast tissue between BRCA1 mutation carriers and non-carriers; Figure S7. Comparison of the basal/mesenchymal features of luminal progenitor cells in normal breast tissue between BRCA1 mutation carriers and non-carriers; Figure S8. Validation of the heterogeneity of basal/mesenchymal features in normal mammary tissue from BRCA1 mutation carriers by bulk RNA-seq

Table S1. Detailed information on the BRCA1 germline mutation and clinicopathological characteristics of seven patients; Table S2. Cell numbers detected by single cell RNA-seq; Table S3. List of cell type specific marker genes identified at a single cell resolution; Table S4. EMT signature gene set; Table S5. Clinicopathologic information of 8 additional BRCA1 mutation carriers and 14 non-carriers for bulk RNA-seq; Table S6. Clinico-pathologic information of the breast cancers from BRCA1/2 germline mutation carriers from The Cancer Genome Atlas (TCGA) database included in this study for comparisons; Table S7. Clinicopathologic information of 7 BRCA1 mutation carriers and 10 non-carriers whose samples for immunohistochemistry staining.

Table S1. Detailed information on the BRCA1 germline mutation and clinicopathological characteristics of seven patients; Table S2. Cell numbers detected by single cell RNA-seq; Table S3. List of cell type specific marker genes identified at a single cell resolution; Table S4. EMT signature gene set; Table S5. Clinicopathologic information of 8 additional BRCA1 mutation carriers and 14 non-carriers for bulk RNA-seq; Table S6. Clinico-pathologic information of the breast cancers from BRCA1/2 germline mutation carriers from The Cancer Genome Atlas (TCGA) database included in this study for comparisons; Table S7. Clinicopathologic information of 7 BRCA1 mutation carriers and 10 non-carriers whose samples for immunohistochemistry staining.

Figure S1. Known cell type specific makers used to define clusters; Figure S2. The aberrant proportions of epithelial cells in normal breast tissues from BRCA1 mutation carriers validated by immunohistochemistry staining and bulk RNA-seq data; Figure S3. Impaired differentiation processes of luminal and basal/myoepithelial lineages in normal breast tissue from BRCA1 mutation carriers; Figure S4. Identification and characterization of the tumor cells in BRCA1 mutation carriers; Figure S5. Upregulated and downregulated pathways in tumor cells compared with their putative cells of origin in each BRCA1 mutation carrier; Figure S6. Comparison of the expression levels of KRT14/17 in luminal progenitor cells in normal breast tissue between BRCA1 mutation carriers and non-carriers; Figure S7. Comparison of the basal/mesenchymal features of luminal progenitor cells in normal breast tissue between BRCA1 mutation carriers and non-carriers; Figure S8. Validation of the heterogeneity of basal/mesenchymal features in normal mammary tissue from BRCA1 mutation carriers by bulk RNA-seq

Table S8. Somatic mutations detected in the tumor tissues from the four BRCA1 mutation carriers by whole-exome sequencing.

The ability to determine the prognosis of lean nonalcoholic fatty liver disease (NAFLD) is essential for decision making in clinical settings. Using a large community‐based Chinese cohort, we aimed to investigate NAFLD outcomes by body mass index (BMI). We used the restricted cubic splines method to investigate the dose–response relationship between BMI and outcomes in subjects with NAFLD and those without NAFLD. We included 73,907 subjects from the Kailuan cohort and grouped all subjects into four phenotypes by using NAFLD and BMI (2). The probability of developing outcomes for individuals with lean NAFLD (LN), overweight/obese NAFLD (ON), overweight/obese non‐NAFLD (ONN), and lean non‐NAFLD (LNN) was estimated. We found a U‐shaped association between BMI and death but a linear positive association concerning cardiovascular disease (CVD) after adjusting for age and other covariates. Compared with the LNN group, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of the LN, ON, and ONN groups were 1.30 (1.14–1.49), 0.86 (0.80–0.91), 0.84 (0.80–0.89) for all‐cause death, 2.61 (1.13–6.03), 0.74 (0.44–1.26), 1.10 (0.70–1.74) for liver‐related death, 2.12 (1.46–3.08), 1.23 (0.99–1.54), 1.19 (0.98–1.43) for digestive system cancers, and 2.04 (1.40–2.96), 1.30 (1.05–1.61), 1.21 (1.01–1.46) for obesity‐related cancers. Subjects with LN had a significantly higher risk of colorectal cancer and esophagus cancer. However, the ON group had the highest CVD risk (HR, 1.39; 95% CI, 1.27–1.52). The LN group with hypertension had a higher risk of adverse outcomes, and those without hypertension had a similar risk compared to LNN. Conclusion: Subjects with LN may experience a higher risk of all‐cause death, digestive system cancers, and obesity‐related cancers than the other three groups but a lower risk of CVD than ON subjects. LN with hypertension may be a high‐risk phenotype.

Epigenetic regulation of gene expression has been implicated in the development of chronic pain. However, little is known about whether this regulation is involved in the development and treatment of chronic pain comorbidities such as fibromyalgia syndrome (FMS) and temporomandibular disorder (TMD), a comorbidity predominantly occurring among women. Here we explored the impact of the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) on somatic hyperalgesia induced by stress or stress combined with orofacial inflammation, which mimicked the comorbidity of FMS and TMD in rats. Our data showed that somatic thermal hyperalgesia and mechanical allodynia induced by both conditions were completely prevented by intrathecal injection of SAHA, which upregulated 5-HT_2C receptors but downregulated 5-HT₃ receptors in the spinal dorsal horn. Subsequent spinal administration of RS102221 to inhibit 5-HT_2C receptors or SR57227 to activate 5-HT₃ receptors reversed the analgesic effect of SAHA under both conditions. These results indicate that SAHA attenuates the pro-nociceptive effects of stress combined with orofacial inflammation and the effects of stress alone. This likely occurs through epigenetic regulation of spinal 5-HT_2C and 5-HT₃ receptor expression, suggesting that SAHA has potential therapeutic value in FMS or comorbid FMS-TMD patients with somatic hyperalgesia.