This article reported a prenatally diagnosed case of complete ring chromosome 15. A 38-year-old woman who conceived by in vitro fertilization and frozen embryo transfer underwent amniocentesis for prenatal diagnosis at 18 +5 weeks of gestation due to advanced maternal age. The result of G-banding karyotyping was mos 46,XX,r(15)[88]/45,X,-15[11]/46,XX,r(15;15)[1]. No numerical abnormalities of chromosomes or definite pathogenic copy number variations (CNVs) were detected by chromosomal microarray analysis. Amniocentesis was performed again at 31 +6 weeks of gestation. The result of genome copy number variation sequencing indicated no pathogenic CNV and fluorescence in situ hybridization on cultured amniocytes revealed nuc ish(15q)×1[15]/(15q)×3[5]/(15q)×2[80]. Based on all the prenatal diagnosis results, it was suggested that the fetus carried a complete ring chromosome 15. As the peripheral blood chromosomes of the couple were normal and no obvious abnormalities were detected by the prenatal ultrasound either in our hospital or another hospital, the pregnant woman decided to continue the pregnancy after genetic counseling and delivered a baby girl at 41 weeks of gestation. The girl showed no physical abnormalities during a seven-month follow-up.

Objective To observe prenatal ultrasonic manifestations of fetal rhomboencephalosynapsis(RES).Methods Data of 15 singletons with RES were retrospectively analyzed,and the prenatal intracranial and extracranial ultrasonic manifestations were observed.Results All 15 fetuses were found with transverse cerebellar diameter lower than the 3rd percentile of normal value in the same gestational week and bilateral cerebellar hemisphere fusion(15/15,100％).Cerebellar vermis completely loss was observed in 14 fetuses(14/15,93.33％),while partially loss was noticed in 1 fetus(1/15,6.67％).Invisible of the fourth cerebral ventricle was detected in 4 fetuses(4/15,26.67％),while the fourth cerebral ventricular index(4Vi)＜1 was found in 11 fetuses(11/15,73.33％).No"split line"sign between vermis and cerebellar hemisphere was detected.A total of 14(14/15,93.33％)were found with combining intracranial or extracranial malformations,including 13(13/14,92.86％)with other intracranial malformations,10(10/14,71.43％)with extracranial malformations,whereas 1(1/15,6.67％)fetus had no other malformation.Conclusion Prenatal ultrasonic manifestations of fetal RES mainly included small cerebellum transverse diameter,complete or partial loss of vermis,invisible or dysplasia of the fourth cerebral ventricle,fusion of bilateral cerebellar hemispheres,as well as combining with other intracranial and extracranial malformations.

Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1^highCD11b⁺ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8⁺ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1^highCD11b⁺ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1^highCD11b⁺ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.

Objective:To investigate the correlations between level of serum heparin binding protein (HBP), procalcitonin (PCT), interleukin-18 (IL-18) and the severity of acute pancreatitis (AP).Methods:A total of 86 patients with AP admitted to the First Affiliated Hospital, University of Science and Technology of China from December 2017 to May 2019 were included and divided into mild AP group (MAP) with 36 cases, moderate AP group (MSAP) with 26 cases, and severe AP group (SAP) with 24 cases. There were 25 healthy subjects were chosen as the control group. Serum HBP, PCT, and IL-18 levels were dynamically monitored in all patients at 1, 3 and 7 days after admission. The Spearman correlation analysis was conducted to detect the correlation between the three indicators and inflammatory factors IL-6, IL-8, TNF-α, and APACHEII and Ranson score, and analyzed the early diagnostic value of HBP, PCT, and IL-18 in SAP patients.Results:In 86 AP patients, 53 were males and 33 were females, aged (48.3±8.0) years. In 25 healthy subjects, 15 were males and 10 were females, aged (40.5±5.9) years. Serum levels of HBP, PCT and IL-18 in AP patients were significantly higher than those of healthy control group at 1, 3 and 7 days after admission ( P<0.05), and the most significant increase was observed on the 1st day. At the meanwhile, HBP, PCT, and IL-18 were positively correlated with level of IL-6, IL-8, TNF-α, APACHEII and Ranson scores ( P<0.05). The AUC area of SAP diagnosis by using HBP, PCT or IL-18 alone was respectively 0.825, 0.896, 0.799, the Yoden index was respectively 0.605, 0.628, 0.583, the sensitivity and specificity were 75.3%, 76.2%, 74.8% and 85.2%, 86.6%, 83.5%. The AUC area, Yoden index, sensitivity and specificity of joint detection were 0.923, 0.787, 85.5%, 93.2%, and the positive predictive value and negative predictive value were also increased. Conclusion:Monitoring of serum HBP, PCT and IL-18 can predict the severity of AP patients, and it may serve as an early diagnostic marker for AP.

Chordotonal neurons are responsible for sound sensation in Drosophila. However, little is known about how they respond to sound with high sensitivity. Using genetic labeling, we found one of the Drosophila axonemal dynein heavy chains, CG9492 (DNAH5), was specifically expressed in larval chordotonal neurons and showed a distribution restricted to proximal cilia. While DNAH5 mutation did not affect the cilium morphology or the trafficking of Inactive, a candidate auditory transduction channel, larvae with DNAH5 mutation had reduced startle responses to sound at low and medium intensities. Calcium imaging confirmed that DNAH5 functioned autonomously in chordotonal neurons for larval sound sensation. Furthermore, disrupting DNAH5 resulted in a decrease of spike firing responses to low-level sound in chordotonal neurons. Intriguingly, DNAH5 mutant larvae displayed an altered frequency tuning curve of the auditory organs. All together, our findings support a critical role of DNAH5 in tuning the frequency selectivity and the sound sensitivity of larval auditory neurons.

Objective: To investigate the role of the bone morphogenetic protein 2 (BMP2)⁃Smad1/5 and p38MAPK signaling pathways in the osteogenic differentiation of MSMSCs by insulin⁃like growth factor 1 (IGF1). Methods : A re⁃ combinant adenovirus (RAD) and IGF1 expressing IGF1 gene were constructed. After osteogenic induction, qRT⁃PCR and Western blot were used to detect the phosphorylation level of Smad1/5 and the expression of the BMP⁃2 protein in the BMP⁃Smad signaling pathway; immunohistochemistry was used to observe the nuclear translocation of Smad1/5; qRT⁃PCR and Western blot were used to detect IGF with Noggin and SB203580, inhibitors of the p38MAPK signaling path⁃ way 1⁃mediated osteogenic differentiation of MSMSCs Results: The recombinant IGF1 adenovirus was constructed suc⁃ cessfully. MSMSCs were cultured in inductive medium after infection with different concentrations of Ad⁃IGF1, and then, the protein levels of BMP2 and p⁃Smad1/5 increased. IGF1 can also induce nuclear translocation of Smad1/5. In addition, Noggin significantly reduced the phosphorylation level of Smad1/5 and the formation of mineralized nodules in the MSMSCs. The mRNA levels of Runx2, OPN and ALP also decreased. In contrast, SB203580 decreased neither the phosphorylation level of p38 nor the mRNA expression of Runx2, OPN and ALP in the Ad⁃IGF1 MSMSCs Conclu⁃sion IGF1 can promote the osteogenic differentiation of MSMSCs via the BMP2⁃Smad1/5 signaling pathway. In con⁃ trast, IGF1 may not promote the osteogenic differentiation of MSMSCs via the p38MAPK signaling pathway.

Although the dental lamina of permanent teeth in human being has been developed as early as the embryo stage, the replacement of the deciduous teeth by permanent teeth does not take place untill the age of 6 to 12 years old. The molecular mechanism of the initiation of permanent teeth is still unclear. The rodent species are usually used for the tooth development research in the past. However, this animal model is not suitable for the tooth replacement study because of the absence of tooth replacement in rodents. After 10 years of efforts, our team has established the animal model of miniature pig for tooth replacement research. Using this model, we firstly defined the spatiotemporal pattern of teeth replacement. In the further mechanism research, results showed that the growing rate of the deciduous teeth was faster than that of the surrounding alveolar bone, and biomechanical stress inside mandible was generated due to the fast growth of deciduous teeth. The stress might up-regulate the signal of Runt-related transcription factor 2 (RUNX2)-Wnt pathway in the mesenchyme between the deciduous and permanent teeth, sustain the successional dental lamina at the resting stage and inhibit the development of permanent teeth. A similar expression pattern was also found in the mesenchyme between the deciduous and permanent teeth in human. Our findings demonstrated that the eruption of deciduous tooth released the stress inside mandible, thus induced the "Wnt translocation" from the mesenchyme into the epithelium of permanent counterpart and therefore initiated the development of permanent teeth. The underlying mechanism of the replacement of deciduous teeth by permanent teeth is the regulation of biomechanical stress throughout the initiation process. Based on the findings, we proposed the theory of "biomechanical stress regulation of the tooth replacement" . The replacement pattern and regulatory mechanism provide a scientific foundation for the organ development and regeneration by regulating the biomechanical stress and Wnt pathway in the future.

Sialorrhea is a group of symptoms characterized by excessive accumulation of saliva in the mouth and unconscious overflow from the mouth. It can be divided into physiological sialorrhea and pathological sialorrhea. The etiology of sialorrhea is complex. Local oral factors, systemic diseases, drug induction or psycho-physiological factors can lead to excessive saliva secretion or excessive saliva storage in the mouth, which can lead to sialorrhea. Physiological sialorrhea generally does not require treatment, while different treatment strategies are needed in cases of pathological sialorrhea. There are many treatments for sialorrhea, including oral and maxillofacial system training, drugs, botulinum toxin injection, surgical treatment, and less commonly, traditional Chinese medicines, radiotherapy and neuromuscular electrical stimulation therapy. For different patients, different treatment methods should be adopted, and the treatment should be gradual. To correct the abnormalities in the oral and maxillofacial regions, the primary disease should be treated, contact with/the use of substances inducing salivation should be stopped, or psychological treatment should be administered, combined with oral and maxillofacial system training; if the effect is not good, invasive treatment, such as surgery, should be considered. At present, there are no unified, clear diagnostic criteria or simple and effective treatments in the clinic. In this paper, the etiology, diagnosis and treatment of sialorrhea, combined with our group′s many years of experience in the diagnosis and treatment of sialorrhea, are reviewed to provide a useful reference for the clinical diagnosis and treatment of sialorrhea.

To evaluate the clinical results of reconstruction orbital defect with craniomaxillofacial implant. Three patients with orbital defect were treated with ten implants. The magnetic abutments were attached six months after one stage operation and the prostheses were fabricated. Within 11 to 47 months of follow up, all implants were stable with successful osseointegration. The prosthesis fit the orbital defects well. Reconstruction of orbital defect with craniomaxillofacial implant can be considered as a viable alternative treatment.

Objective: To detect the expression level of miR-27a during the osteogenic differentiation of beagle maxillary sinus membrane stem cells (MSMSCs) and explore the role of miR-27a in the osteogenic differentiation of MSMSCs. Methods: Beagle MSMSCs were cultured in vitro. The expression level of miR-27a was detected via RT-PCR after an osteogenic inductive culture was prepared. The mRNA expression levels of Runx2 and OPN were examined via RT-PCR, and the protein expression levels of Runx2 and OPN were examined via Western blot after the cells were transfected with pre-miR-27a or anti-miR-27a. Finally, osteoprogenitor cells transfected with pre-miR-27a were composited with Bio-Oss particles and subcutaneously implanted into nude mice to form ectopic bone formation models, and then the inhibition of bone formation from miR-27a was observed in vivo. Results: The expression level of miR-27a in the beagle MSMSCs decreased after osteogenic inductive culturing. The relative miR-27a levels were significantly decreased at day 1 (t=3.795, P=0.023), day 3 (t=4.493, P=0.011), day 7 (t=11.591, P < 0.001), day 14 (t=12.542, P < 0.001), and day 21 (t=5.621, P=0.008) compared with day 0. In addition, the expression levels of Runx2 mRNA (t=4.923, P=0.007) and protein (t=4.425, P=0.008) were reduced after the cells were transfected with pre-miR-27a. The expression levels OPN mRNA (t=5.253, P=0.006) and protein (t=5.132, P=0.006) were also reduced. In contrast, the mRNA expression levels of Runx2 (t=3.925, P=0.013) and OPN (t=3.712, P=0.019) were increased after the cells were transfected with anti-miR-27a, and bone formation was observed after the subcutaneous implantation of beagle MSMSCs composited with Bio-Oss in nude mice. Nevertheless, ectopic bone formation was inhibited by pre-miR-27a-transfected beagle MSMSCs composited with Bio-Oss (t=7.219, P=0.0020). Conclusion MiR-27a negatively regulates the osteogenic differentiation of MSMSCs.