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Primary microcephaly is characterized by a head circumference prenatally or at birth that falls below three standard deviations from age-, ethnic-, and sex-specific norms. Genetic defects are one of the underlying causes of primary microcephaly. Since 2014, five variants of the SASS6 gene have been identified as the cause of MCPH 14 in three reported families. In this study, we present the genetic findings of members of a nonconsanguineous Chinese couple with a history of microcephaly and fetal growth restriction (FGR) during their first pregnancy. Utilizing trio whole-exome sequencing, we identified compound heterozygous variants involving a frameshift NM_194292.3:c.450_453del p.(Lys150AsnfsTer7) variant and a splice region NM_194292.3:c.1674+3A>G variant within the SASS6 gene in the affected fetus. Moreover, reverse transcriptase-polymerase chain reaction from RNA of the mother's peripheral blood leukocytes revealed that the c.1674+3A>G variant led to the skipping of exon 14 and an inframe deletion. To the best of our knowledge, the association between FGR and SASS6-related microcephaly has not been reported, and our findings confirm the pivotal role of SASS6 in microcephaly pathogenesis and reveal an expanded view of the phenotype and mutation spectrum associated with this gene., (© 2024 Wiley Periodicals LLC.)

Objective: To evaluate the clinical value of ultrasound findings in the screening of fetal chromosomal abnormalities and the analysis of risk factors for chromosome microarray analysis (CMA) abnormalities., Methods: We retrospectively analyzed the datasets of 15,899 pregnant women who underwent prenatal evaluations at Affiliated Maternity and Child Health Care Hospital of Nantong University between August 2018 and December 2022. Everyone underwent ultrasound screening, and those with abnormal findings underwent CMA to identify chromosomal abnormalities., Results: The detection rates for isolated ultrasound anomalies and combined ultrasound and CMA anomalies were 11.81% (1877/15,899) and 2.40% (381/15,899), respectively. Among all ultrasound abnormalities, detection rates for isolated ultrasound soft marker anomalies, isolated structural abnormalities, and both ultrasound soft marker anomalies with structural abnormalities were 82.91% (1872/2258), 15.99% (361/2258), and 1.11% (25/2258), respectively. The detection rate of abnormal chromosomes in pregnant women with abnormal ultrasound results was 16.87% (381/2258). The detection rates were 13.33% in cases with two or more ultrasound soft markers anomalies, 47.37% for two or more structural anomalies, and 48.00% for concomitant ultrasound soft marker and structural anomalies., Conclusions: Enhanced detection rates of chromosomal anomalies in fetal malformations are achieved with specific ultrasound findings (NT thickening, cardiovascular abnormalities, and multiple soft markers) or when combined with high-risk factors (advanced maternal age, familial history, parental chromosomal anomalies, etc.). When the maternal age is over 35 and with ≥2 ultrasound soft marker anomalies accompanied with any high-risk factors, CMA testing can aid in the diagnosis of prenatal chromosomal abnormalities.

Background: Patients with primary hyperparathyroidism (PHPT) are at risk for severe hypocalcemia (SH) following parathyroidectomy (PTX), but limited data exist on the predictors of SH. We aimed to identify risk factors for early postoperative SH after PTX in patients with PHPT and to evaluate the predictive value of clinical parameters., Methods: A retrospective review of patients with PHPT who underwent PTX between January 2010 and December 2022 was performed. A total of 46 patients were included in the study, with 15 (32.6%) experiencing postoperative SH, 19 (41.3%) having calculi in the ureter or kidney, and 37 (80.4%) having osteoporosis. Patients were divided into SH and non-SH groups based on postoperative serum calcium levels. Preoperative biochemical indicators, bone turnover markers, and renal function parameters were analyzed and correlated with postoperative SH., Results: Statistically significant (P < 0.05) differences were found in preoperative serum calcium (serum Ca), intact parathyroid hormone, serum phosphorus (serum P), serum Ca/P, percentage decrease of serum Ca, total procollagen type 1 intact N-terminal propeptide, osteocalcin (OC), and alkaline phosphatase levels between the two groups. Multivariate analysis showed that serum P (odds ratio [OR] = 0.989; 95% confidence interval [95% CI] = 0.981-0.996; P = 0.003), serum Ca (OR = 0.007; 95% CI = 0.001-0.415; P = 0.017), serum Ca/P (OR = 0.135; 95% CI = 0.019-0.947; P = 0.044) and OC levels (OR = 1.012; 95% CI = 1.001-1.024; P = 0.036) were predictors of early postoperative SH. The receiver operating characteristic curve analysis revealed that serum P (area under the curve [AUC] = 0.859, P < 0.001), serum Ca/P (AUC = 0.735, P = 0.010) and OC (AUC = 0.729, P = 0.013) had high sensitivity and specificity., Conclusion: Preoperative serum P, serum Ca/P and osteocalcin levels may identify patients with PHPT at risk for early postoperative SH after PTX., (© 2024. The Author(s).)

Early fluctuations in blood glucose levels increased susceptibility to macrophage dysfunction. However, the underlying pathological mechanisms linking glucose variations and macrophage dysregulation remains elusive. In current study, we established an animal model of transient intermittent hyperglycaemia (TIH) to simulate early fluctuations in blood glucose levels. Our findings revealed that both TIH and diabetic group exhibited more severe periodontal lesions and increased secretion of pro-inflammatory cytokines compared to healthy controls. In immortalized bone marrow-derived macrophages (iBMDMs), phagocytosis and chemotaxis were impaired with transient and lasting hyperglycaemia, accompanied by enhanced glycolysis. We also found that TIH activated pyruvate kinase M2 (PKM2) through the phosphorylation of extracellular regulated protein kinase (ERK) in vivo, particularly at dimeric levels. In macrophage cultured with TIH, PKM2 translocated into the nucleus and involved in the regulating inflammatory genes, including TNF-α, IL-6 and IL-1β. PKM2 translocation and secretion of inflammatory cytokines were attenuated by PD98059, while PKM2 tetramer activator TEPP-46 prevented the formation of dimeric PKM2 in macrophages. Moreover, inhibition of glycolysis alleviated the TIH-induced pro-inflammatory cytokines. In conclusion, our manuscript provides a rationale for understanding how TIH modulates metabolic rewiring and dysfunction in macrophages via ERK-dependent PKM2 nuclear translocation., (© 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Metabolic diseases and their complications impose health and economic burdens worldwide. Evidence from past experimental studies and clinical trials suggests our body may have the ability to remember the past metabolic environment, such as hyperglycemia or hyperlipidemia, thus leading to chronic inflammatory disorders and other diseases even after the elimination of these metabolic environments. The long-term effects of that aberrant metabolism on the body have been summarized as metabolic memory and are found to assume a crucial role in states of health and disease. Multiple molecular mechanisms collectively participate in metabolic memory management, resulting in different cellular alterations as well as tissue and organ dysfunctions, culminating in disease progression and even affecting offspring. The elucidation and expansion of the concept of metabolic memory provides more comprehensive insight into pathogenic mechanisms underlying metabolic diseases and complications and promises to be a new target in disease detection and management. Here, we retrace the history of relevant research on metabolic memory and summarize its salient characteristics. We provide a detailed discussion of the mechanisms by which metabolic memory may be involved in disease development at molecular, cellular, and organ levels, with emphasis on the impact of epigenetic modulations. Finally, we present some of the pivotal findings arguing in favor of targeting metabolic memory to develop therapeutic strategies for metabolic diseases and provide the latest reflections on the consequences of metabolic memory as well as their implications for human health and diseases., (© 2024. The Author(s).)

Diabetes mellitus (DM) is a chronic age-related disease that was recently found as a secondary aging pattern regulated by the senescence associated secretory phenotype (SASP). The purpose of this study is to detect the potential efficacy and the specific mechanisms of low-level laser therapy (LLLT) healing of age-related inflammation (known as inflammaging) in diabetic periodontitis. Diabetic periodontitis (DP) mice were established by intraperitoneal streptozotocin (STZ) injection and oral P. gingivalis inoculation. Low-level laser irradiation (810 nm, 0.1 W, 398 mW/cm 2 , 4 J/cm 2 , 10 s) was applied locally around the periodontal lesions every 3 days for 2 consecutive weeks. Micro-CT and hematoxylin-eosin (HE) stain was analyzed for periodontal soft tissue and alveolar bone. Western blots, immunohistochemistry, and immunofluorescence staining were used to evaluate the protein expression changes on SASP and GLUT1/mTOR pathway. The expression of aging-related factors and SASP including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were reduced in periodontal tissue of diabetic mice. The inhibitory effect of LLLT on GLUT1/mTOR pathway was observed by detecting the related factors mTOR, p-mTOR, GLUT1, and PKM2. COX, an intracytoplasmic photoreceptor, is a key component of the anti-inflammatory effects of LLLT. After LLLT treatment a significant increase in COX was observed in macrophages in the periodontal lesion. Our findings suggest that LLLT may regulate chronic low-grade inflammation by modulating the GLUT1/mTOR senescence-related pathway, thereby offering a potential treatment for diabetic periodontal diseases., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Cancer is one of the leading causes of human death worldwide. One of the most common types of malignancy among women is breast cancer, which is the third most common cancer in the world after lung and stomach cancer. This study aimed to evaluate the expression level of Tissue Differentiation-Inducing Non-Protein Coding RNA (TINCR) in adjacent tumor and non-tumor tissues of 60 women with invasive ductal breast cancer. The relationship between TINCR expression and the clinical characteristics of patients has also been studied. For this purpose, total RNA was isolated from breast cancer patients' adjacent tumor and non-tumor tissue. RT Prime Script reagent was then used to convert total RNA to cDNA. The qRT-PCR quantified the TINCR expression level and analyzed the results by paired t-test. In addition, ROC curve analysis was used to evaluate the biomarker power of TINCR in breast cancer tumor tissues. According to the results, a decrease in the level of TINCR was obtained in the tumor tissue of breast cancer patients compared to the adjacent non-tumor tissue (P<0.001). TINCR expression was negatively correlated with tumor size and lymph node metastasis in breast cancer tumor tissue. In general, the decrease in the expression level of TINCR in the tumor tissue of breast cancer patients shows that its expression level can differentiate the adjacent tumor and non-tumor tissue from each other. In addition, TINCR has a lower expression level in breast cancer patients with large tumors, lymph node metastasis, and luminal subgroups A and B.

Background: To measure total type 1 serum amino-terminal propeptide procollagen (t-P1NP), β- type 1 cross-linked C-terminal telopeptide collagen (β-CTX), N-terminal osteocalcin (OC), and 25-(OH)-VD3 levels before parathyroidectomy (PTX) in patients with PHPT, and correlate these measurements with bone mineral density (BMD) changes at 1-year post-PTX., Methods: Patients with primary hyperparathyroidism (PHPT) were followed from diagnosis to 12 months after surgery. Serum levels of calcium, parathyroid hormone (PTH), vitamin 25-(OH)-VD3, OC, β-CTX, t-P1NP, and BMD were measured before and 1 year after surgery., Results: One year after PTX, mean BMD increased by 25.7, 27.7, and 33.5% in the lumbar spine (L1-L4), femoral neck (FN), and greater trochanter (GT), respectively. Percent BMD change 1-year post-PTX was significant correlated with preoperative levels of β-CTX (L1-L4: r = 0.41 , P < 0.0001; FN: r = 0.54 , P = 0.0003; GT: r = 0.46 , P = 0.0029), t-P1NP (L1-L4: r = 0.58 , P < 0.0001; FN: r = 0.73 , P < 0.0001; GT: r = 0.65 , P < 0.0001), 25-(OH)-VD3 (L1-L4: r = -0.33 , P = 0.034; FN: r = -0.48 , P = 0.002; GT: r = -0.52 , P = 0.0007), and OC (L1-L4: r = 0.49 , P = 0.0013; FN: r = 0.55 , P = 0.0002; GT: r = 0.47 , P = 0.002)., Conclusions: Preoperative levels of turnover markers and BMD improvements were significantly correlated in patients with PHPT 1 year after PTX.

Objective: To explore the difference in parathyroid tissue-derived cells between male and female PHPT patients., Methods: Resected parathyroid tissues were collected from PHPT patients of both sexes. Single cells were isolated and sequenced for RNA expression profiles. The cell sequencing data were annotated by cell type, followed by population analysis, functional analysis, pathway analysis, cell communication analysis, differential gene expression analysis, and pseudotime trajectory analysis. The subcluster analyses were also performed in the parathyroid cells., Results: No substantial difference in the cell population, function, or communication is found between the two sexes. The interferon-a response, oxidative phosphorylation, and reactive oxygen species pathways are up-regulated in females than in male patients, mainly contributed by fibroblast cells, endothelial cells, parathyroid cells, and myeloid cells, which also have significantly more up-regulated pathways and cellular interactions than the other three cell types. The subcluster analysis of parathyroid cells identified five subpopulations: SPARCL1-OC and ISG15-OC are predominant in females, while more S100A13-PCC and PTHLH-OC are found in males. The cellular functions are also elevated in females compared with males. Cells from female patients show a higher expression level of parathyroid hormone (PTH) but a lower expression level of parathyroid hormone-like hormone (PTHLH). The cell pseudotime trajectory and pathway analyses show that the oxyphil cells may be more mature and functionally active than the chief cells in both sexes., Conclusion: These findings suggest that the sex difference in PHPT may be caused by the differentially expressed genes and activated pathways in different cell types in the parathyroid tissue. The heterogeneity of parathyroid cell subpopulations, especially in oxyphil cells, may be associated with the sex differences in PHPT pathogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lu, Chen, Gong, Chen, Zhang, Zhang, Wu, Cui and Jiang.)

It was to investigate the value of quantitative fluorescence PCR (QF-PCR) for the selection of specific short tandem repeat (STR) in prenatal diagnosis of fetal chromosomal diseases. Amniotic fluid (AF) and villus samples were obtained from 80 pregnant women at 16-20 weeks of gestation, and venous blood samples were obtained from 60 normal individuals to extract and prepare peripheral blood chromosome, AF cell chromosome, and villus cell chromosome samples for specific STR locus detection. It showed that the area ratio of AMX peak to AMY peak in the Genescan typing map of peripheral blood DNA of normal males was close to 1:1, while the Genescan typing map of peripheral blood DNA of normal females had only AMX peak and no AMY peak. Normal heterozygous individuals had an area ratio between 1 and 1.45 for venous blood, 1.002 and 1.27 for villous samples, and 1 and 1.35 for AF samples. The karyotype of a male fetus was 46, XY, inv [9] (p11: q13), and the structure of fetal chromosome 9 was inverted (interarm), and the site of structural inversion was band 1 in the short breech 1 region and band 3 in the long arm 1 region of chromosome 9. It suggested that QF-PCR can effectively identify the normal human body and cases by selecting specific STR locus detection, which has a good application value for prenatal diagnosis of fetal chromosomal diseases.

Background: The staging system for patients with anaplastic thyroid cancer (ATC) was updated in the 8 th edition of the American Joint Committee on Cancer Staging Manual. A cut-off age of 55 years was stipulated as a prognostic factor for differentiated thyroid cancer; however, age was not considered for ATC patients. To this end, this study investigated the relationship between age at diagnosis and prognosis of ATC patients., Methods: The clinical information on ATC patients was acquired from the Surveillance, Epidemiology, and End Results Program public database. Youden's index and X-tile analyses were used to calculate the high-point age at diagnosis associated with prognosis. Cox proportional hazards models, Kaplan-Meier curves, and 1000-person-year were then used for verifying the accuracy of the high-point age., Results: After inclusion/exclusion criteria was applied, 586 patients were included in this study. The high-point age was determined to be 70 years by both the Youden's index and X-tile plot methods. The hazard ratio was 1.662 (95% confidence interval [CI]: 1.321-2.092), indicating that there was an increased risk of poor prognosis for patients > 70 years of age. The cancer-specific mortality rates per 1000-person-years for patients ≤ and > 70 years-old were 949.980 (95% CI: 827.323-1090.822) and 1546.667 (95% CI: 1333.114-1794.428), respectively. P-values were < 0.001 for the results shown above., Conclusion: Our study found that age influenced the prognosis of ATC patients. Furthermore, we determined that the high-point age at diagnosis was 70 years and that > 70 years of age was associated with a poor prognosis. These results provide a useful addition to the staging manual and can improve the diagnosis, treatment strategies and prognosis of ATC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kong, Xu, Zhang, Cui, Tan and Bai.)

Background: Multiple pathological manifestations are rarely present in patients with primary hyperparathyroidism (PHPT). Here we described a case of a young woman who presented with multiple skeletal destructions and received an unclear diagnosis at several hospitals., Case Presentation: A 30-year-old woman was admitted to our hospital due to pain in both knees and walking difficulty that lasted for 6 and 2 years, respectively. Her laboratory test results revealed a high parathyroid hormone level (822 pg/ml) and hypercalcemia (2.52 mmol/L) in the blood. Parathyroid imaging revealed a lumpy concentration of radioactive uptake detected at the lower pole in the right lobe of the thyroid, and was nearly 2.2 cm * 2.4 cm in size. Next, the patient was treated with parathyroidectomy that resulted in a significant improvement in physiological and clinical symptoms. Moreover, the skeletal destruction and bone mineral density were significantly improved after a 5-years follow-up period., Conclusions: Multiple skeletal destructions can be caused by PHPT that should be taken into consideration in young patients with complex bone lesions.

Rationale: In this report, a combination of platelet-rich fibrin (PRF) membrane and semi-open flap technique was used to improve soft tissue regeneration in immediate implant placement in the molar region. PRF, an autologous fibrin matrix, has been widely used for soft tissue wound healing and regeneration. Semi-open flap technique is beneficial to eliminating exudates and relieving the swelling after surgery., Patient Concerns: Case 1 was a 45-year-old female with a residual crown in the posterior maxillary region that desired a dental implant operation. Case 2 was a 24-year-old male with retained deciduous tooth that requested a restoration of his congenital absent tooth., Diagnoses: In case 1, the tooth 16 was diagnosed with a residual crown, while in case 2, a deciduous tooth 75 was a retained deciduous tooth and 35 was congenital absent., Interventions: In both cases, immediate implant placement was installed and PRF membranes were made to improve soft tissue augmentation with semi-open flap technique. In case 1, the mixture of an organic bovine bone and blood was filled in the gap between the implant and the socket wall. Subsequently, 2 PRF membranes covered the open wound with semi-open flap. Similarly, in case 2, another 2 PRF membranes were used to improve the soft tissue regeneration, with the same semi-open flap technique as mentioned above., Outcomes: In both cases, successfully soft tissue regeneration was obviously observed without postoperative infection., Lessons: Utilizing the PRF membrane combined with semi-open flap technique can achieve excellent soft tissue augmentation around immediate implant placement in the molar regions.

Objective: Primary hyperparathyroidism (PHPT) is relatively common in China and results in severe damage to the skeletal system. This study aimed to investigate changes in bone mineral density (BMD) over 2 years in patients with PHPT after parathyroidectomy., Methods: This retrospective cohort study included patients with PHPT who underwent parathyroidectomy between January 2010 and December 2015. BMD and T-scores and Z-scores of the lumbar spine (L1, L2, L3, and L4) and total hip (femoral neck, great trochanter, and Ward's triangle) at baseline and 2 years after surgery were measured by dual-energy X-ray absorptiometry., Results: Thirty patients with moderate to severe PHPT (17 men and 13 women) aged 38.90±15.48 years were included. BMD, and T-score and Z-score values at the lumbar spine and total hip at 6 months, 1 year, and 2 years after parathyroidectomy were significantly improved compared with preoperative values. Improvement in BMD was largest at L4 (46.7%) and smallest at L1 (37.4%) in the lumbar spine 2 years after parathyroidectomy. For the total hip, the increase in BMD was largest at Ward's triangle (42.6%) and smallest at the femoral neck (37.5%)., Conclusions: BMD of the lumbar spine and total hip is improved after parathyroidectomy in patients with PHPT.

Background: Studies have shown that the response of bone mineral density (BMD) to parathyroidectomy for symptomatic primary hyperparathyroidism (PHPT) is heterogeneous and difficult to predict. However, the independent factors affecting BMD in PHPT patients after parathyroidectomy remains limited and inconclusive. This study aimed to explore the independent factors affecting BMD changes in symptomatic PHPT patients after parathyroidectomy., Methods: This study retrospectively analyzed 105 patients with symptomatic PHPT treated at Beijing Jishuitan Hospital between January 2010 and December 2015. The primary outcome was a > 10% increase in BMD at 3 years after parathyroidectomy compared with the preoperative value, whereas the secondary outcomes were BMD changes at various measurement sites., Results: A total of 105 patients with a mean age of 46.37 years were included in this study. Univariate logistic regression analysis indicated that hypertension (odds ratio [OR[: 0.032; 95% confidence interval [CI]: 0.001-0.475; P = 0.012), and parathyroid hormone level (OR: 1.006; 95% CI: 1.004-1.009; P = 0.044) were associated with the > 10% BMD increase. However, these results were not significant after adjustments for potential confounders. Moreover, the BMD values at the lumbar spine, femoral neck, femoral trochanter, Ward's triangle, and whole body after parathyroidectomy were significantly greater than those before the operation (P < 0.05)., Conclusions: This study suggests that patient characteristics were not associated with the > 10% BMD increase. However, the BMD values of the femur and lumbar spine were significantly increased in symptomatic PHPT patients after parathyroidectomy.

Background: Sugarcane mosaic virus (SCMV) is responsible for large-scale economic losses in the global production of sugarcane, maize, sorghum, and some other graminaceous species. To understand the evolutionary mechanism of SCMV populations, this virus was studied in Shanxi, China. A total of 86 maize leaf samples (41 samples in 2012 and 45 samples in 2013) were collected from 4 regions of Shanxi., Results: Double-antibody sandwich (DAS)-ELISA and RT-PCR showed 59 samples (30 samples in 2012 and 29 samples in 2013) to be positive for SCMV, from which 10 new isolates of SCMV were isolated and sequenced. The complete genomes of these isolates are 9610 nt long, including the 5' and 3' non-coding regions, and encode a 3063-amino acid polyprotein. Phylogenetic analyses revealed that 24 SCMV isolates could be divided on the basis of the whole genome into 2 divergent evolutionary groups, which were associated with the host species. Among the populations, 15 potential recombination events were identified. The selection pressure on the genes of these SCMV isolates was also calculated. The results confirmed that all the genes were under negative selection., Conclusions: Negative selection and recombination appear to be important evolutionary factors shaping the genetic structure of these SCMV isolates. SCMV is distributed widely in China and exists as numerous strains with distinct genetic diversity. Our findings will provide a foundation for evaluating the epidemiological characteristics of SCMV in China and will be useful in designing long-term, sustainable management strategies for SCMV.