Real-Space Mapping of Local Subdegree Lattice Rotations in Low-Angle Twisted Bilayer Graphene.

In two-dimensional small-angle twisted bilayers, van der Waals (vdW) interlayer interaction introduces an atomic-scale reconstruction, which consists of a moiré-periodic network of local subdegree lattice rotations. However, real-space measurement of the subdegree lattice rotation requires extremely high spatial resolution, which is an outstanding challenge in an experiment. Here, a topmost small-period graphene moiré pattern is introduced as a magnifying lens to magnify sub-Angstrom lattice distortions in small-angle twisted bilayer graphene (TBG) by about 2 orders of magnitude. Local moiré periods of the topmost graphene moiré patterns and low-energy van Hove singularities of the system are spatially modified by the atomic-scale reconstruction of the underlying TBG, thus enabling real-space mapping of the networks of the subdegree lattice rotations both in structure and in electronic properties. Our results indicate that it is quite facile to study subdegree lattice rotation in vdW systems by measuring the periods of the topmost moiré superlattice.

Kinetics of Nanobubbles in Tiny-Angle Twisted Bilayer Graphene.

Realization of high-quality van der Waals (vdWs) heterostructures by stacking two-dimensional (2D) layers requires atomically clean interfaces. Because of strong adhesion between the constituent layers, the vdWs forces could drive trapped contaminants together into submicron-size "bubbles", which leaves large interfacial areas atomically clean. Here, we study the kinetics of nanobubbles in tiny-angle twisted bilayer graphene (TBG) and our results reveal a substantial influence of the moiré superlattice on the motion of nanoscale interfacial substances. Our experiments indicate that the bubbles will mainly move along the triangular network of domain boundaries in the tiny-angle TBG when the sizes of the bubbles are comparable to that of an AA-stacking region. When the size of the bubble is smaller than that of an AA-stacking region, the bubble becomes motionless and is fixed in the AA-stacking region, because of its large out-of-plane corrugation.

Comparative study of abdominal CT enhancement in overweight and obese patients based on different scanning modes combined with different contrast medium concentrations.

PURPOSE: To compare image quality, iodine intake, and radiation dose in overweight and obese patients undergoing abdominal computed tomography (CT) enhancement using different scanning modes and contrast medium. METHODS: Ninety overweight and obese patients (25 kg/m2≤body mass index (BMI)< 30 kg/m2 and BMI≥30 kg/m2) who underwent abdominal CT-enhanced examinations were randomized into three groups (A, B, and C) of 30 each and scanned using gemstone spectral imaging (GSI) +320 mgI/ml, 100 kVp + 370 mgI/ml, and 120 kVp + 370 mgI/ml, respectively. Reconstruct monochromatic energy images of group A at 50-70 keV (5 keV interval). The iodine intake and radiation dose of each group were recorded and calculated. The CT values, contrast-to-noise ratios (CNRs), and subjective scores of each subgroup image in group A versus images in groups B and C were by using one-way analysis of variance or Kruskal-Wallis H test, and the optimal keV of group A was selected. RESULTS: The dual-phase CT values and CNRs of each part in group A were higher than or similar to those in groups B and C at 50-60 keV, and similar to or lower than those in groups B and C at 65 keV and 70 keV. The subjective scores of the dual-phase images in group A were lower than those of groups B and C at 50 keV and 55 keV, whereas no significant difference was seen at 60-70 keV. Compared to groups B and C, the iodine intake in group A decreased by 12.5% and 13.3%, respectively. The effective doses in groups A and B were 24.7% and 25.8% lower than those in group C, respectively. CONCLUSION: GSI +320 mgI/ml for abdominal CT-enhanced in overweight patients satisfies image quality while reducing iodine intake and radiation dose, and the optimal keV was 60 keV.

Porphyromonas gingivalis predicts local recurrence after endoscopic submucosal dissection of early esophageal squamous cell carcinoma or precancerous lesion.

BACKGROUND: Porphyromonas gingivalis plays an oncogenic role in development and progression of esophageal squamous cell carcinoma (ESCC). However, the impact of P. gingivalis on local recurrence of early ESCC or precancerous lesion after ESD treatment remains unknown. The present study aimed to evaluate the impact of P. gingivalis on local recurrence after ESD treatment of early ESCC or high-grade dysplasia (HGD). METHODS: The amount of P. gingivalis was assessed by immunohistochemistry in 205 patients with early ESCC or HGD. Univariate and multivariate Cox regression analyses were performed to determine the effect of P. gingivalis on local recurrence. Propensity score matching analysis was performed to reduce the imbalance of baseline characteristics. A nomogram integrating significant prognostic factors was built for local recurrence prediction. RESULTS: The amount of P. gingivalis increased significantly in neoplasms that invaded up to muscularis mucosa and submucosa compared with lesions confined to epithelium or lamina propria. Overabundance of P. gingivalis was positively associated with invasion depth, post-ESD stricture and local recurrence. Univariate and multivariate Cox regression analyses revealed that P. gingivalis, longitudinal length of lesion and lymphovascular invasion were independent predictors for post-ESD recurrence. A nomogram comprising P. gingivalis, lymphovascular involvement, and lesion length performed well for prediction of post-ESD local recurrence with the concordance indices of 0.72 (95%CI, 0.62 to 0.80), 0.72 (95%CI, 0.63 to 0.80), and 0.74 (95%CI, 0.65 to 0.83) in the validation cohort, the entire cohort, and the subcohort after PSM, respectively. CONCLUSION: P. gingivalis overabundance is a risk factor and a potential predictor for local recurrence of early ESCC or HGD after ESD treatment. Thus, clearance of P. gingivalis represents an attractive strategy for prognosis improvement and for prevention of ESCC.

Realizing One-Dimensional Electronic States in Graphene via Coupled Zeroth Pseudo-Landau Levels.

Strain-induced pseudomagnetic fields can mimic real magnetic fields to generate a zero-magnetic-field analog of the Landau levels (LLs), i.e., the pseudo-Landau levels (PLLs), in graphene. The distinct nature of the PLLs enables one to realize novel electronic states beyond what is feasible with real LLs. Here, we show that it is possible to realize exotic electronic states through the coupling of zeroth PLLs in strained graphene. In our experiment, nanoscale strained structures embedded with PLLs are generated along a one-dimensional (1D) channel of suspended graphene monolayer. Our results demonstrate that the zeroth PLLs of the strained structures are coupled together, exhibiting a serpentine pattern that snakes back and forth along the 1D suspended graphene monolayer. These results are verified theoretically by large-scale tight-binding calculations of the strained samples. Our result provides a new approach to realizing novel quantum states and to engineering the electronic properties of graphene by using localized PLLs as building blocks.

Parecoxib expresses anti-metastasis effect through inhibition of epithelial-mesenchymal transition and the Wnt/ß-catenin signaling pathway in human colon cancer DLD-1 cell line.

Colorectal cancer is the third leading cause of cancer death in Taiwan. Current treatments involve combination of surgical resection, radiation, and chemotherapy. These treatments have demonstrated to increased five-year survival of a patient with colorectal cancer. However, metastasis is a major capability of cancer cells that causes poor prognosis, recurrence, and even death. Epidemiological and clinical studies have suggested the use of non-steroidal anti-inflammatory drugs (NSAIDs) as an effective class of compounds to prevent colon cancer. Parecoxib is an NSAID and the only parenterally administered selective cyclooxygenase (COX)-2 inhibitor. In this study, we evaluated whether parecoxib inhibits the metastasis of DLD-1 human colon cancer cells, a COX-2 null cell line, and the underlying mechanism. Cell migration of the DLD-1 cells was significantly inhibited by parecoxib treatment as shown by the Transwell migration assay. This enhanced anti-migration effect was correlated with the attenuated phosphorylation of Akt, expression of vimentin (a mesenchymal marker), and ß-catenin, and corresponded with the upregulated GSK3ß and E-cadherin (an epithelial marker). These findings suggested that parecoxib could inhibit the epithelial-mesenchymal transition (EMT) and metastasis in human colon cancer cells by downregulating ß-catenin. Thus, parecoxib could provide a novel prospective strategy for a combination treatment with chemotherapeutic drugs against metastasis of human colon cancer.

Diagnosis, treatment and genetic analysis of two cases of congenital hyperinsulinemic hypoglycemia caused by GCK gene mutation.

Congenital hyperinsulinemia (CHI) is a heterogeneous disorder characterized by persistent hypoglycemia due to inappropriate insulin secretion. A total of 15 gene mutations have already been reported to be associated with CHI. Among them, CHI caused by the GCK mutation is named GCK-CHI, which is considered to be a rare form of CHI. Here, we reported two cases of GCK-CHI diagnosed by genetic testing and summarized the clinical characteristics. In patients with recurrent or persistent hypoglycemia, CHI should be taken into consideration. Genetic testing should be perfomed in these patients to avoid misdiagnosis and provide accurate intervention, thus to improve prognosis.

Alterations in the intestinal microbiome and mental health status of workers in an underground tunnel environment.

BACKGROUND: Working in an underground tunnel environment is unavoidable in professions such as miners and tunnel workers, and there is a concern about the health of these workers. Few studies have addressed alterations in the intestinal microbiome of workers within that environment. RESULTS: Fecal samples were collected from the workers before they entered the tunnel (baseline status, BS) and after they left the tunnel (exposed status, ES), respectively (a time period of 3 weeks between them). We analyzed 16S rRNA sequencing to show the changes in microbial composition and self-evaluation of mental health questionnaire was also performed. The results showed that Shannon and Simpson indices decreased significantly from BS to ES. A higher abundance was found in the phylum Actinobacteria, classes Actinobacteria and Deltaproteobacteria, orders Bifidobacteriales, Coriobacteriales, and Desulfovibrionales, families Bifidobacteriaceae, Peptostreptococcaceae, Coriobacteriaceae, Clostridiaceae_1, Desulfovibrionaceae, Pseudomonadaceae, and Microbacteriaceae, and genera Bifidobacterium, Romboutsia, Clostridium sensu stricto, and Leucobacter in ES, while BS showed greater levels of genera Faecalibacterium and Roseburia. The self-evaluation showed that at least one-half of the tunnel workers experienced one or more symptoms of mental distress (inattention, sleeplessness, loss of appetite, headache or dizziness, irritability) after working in the underground tunnel environment. CONCLUSIONS: Collectively, the underground tunnel environment led to alterations in the intestinal microbiome, which might be relevant to symptoms of mental distress in underground-tunnel workers.

Denoising click-evoked otoacoustic emission signals by optimal shrinkage.

Click-evoked otoacoustic emissions (CEOAEs) are clinically used as an objective way to infer whether cochlear functions are normal. However, because the sound pressure level of CEOAEs is typically much lower than the background noise, it usually takes hundreds, if not thousands, of repetitions to estimate the signal with sufficient accuracy. In this paper, we propose to improve the signal-to-noise ratio (SNR) of CEOAE signals within limited measurement time by optimal shrinkage (OS) in two different settings: covariance-based optimal shrinkage (cOS) and singular value decomposition-based optimal shrinkage (sOS). By simulation, the cOS consistently enhanced the SNR by 1-2 dB from a baseline method that is based on calculating the median. In real data, however, the cOS cannot enhance the SNR over 1 dB. The sOS achieved a SNR enhancement of 2-3 dB in simulation and demonstrated capability to enhance the SNR in real recordings. In addition, the level of enhancement increases as the baseline SNR decreases. An appealing property of OS is that it produces an estimate of all single trials. This property makes it possible to investigate CEOAE dynamics across a longer period of time when the cochlear conditions are not strictly stationary.

Anti-Cancer Effects and Tumor Marker Role of Glutathione S-Transferase Mu 5 in Human Bladder Cancer.

Our previous study demonstrated that the glutathione S-transferase Mu 5 (GSTM5) gene is highly CpG-methylated in bladder cancer cells and that demethylation by 5-aza-dC activates GSTM5 gene expression. The aim of the present study was to investigate the role of GSTM5 in bladder cancer. The levels of GSTM5 gene expression and DNA methylation were analyzed in patients with bladder cancer, and functional studies of GSTM5 were conducted using GSTM5 overexpression in cultured bladder cancer cells. Clinical analysis revealed that the GSTM5 mRNA expression was lower in bladder cancer tissues than in normal tissues and that the level of GSTM5 DNA methylation was higher in bladder cancer tissues than in normal urine pellets. Overexpression of GSTM5 decreased cell proliferation, migration and colony formation capacity. Glutathione (GSH) assay results indicated that cellular GSH concentration was decreased by GSTM5 expression and that GSH supplementation reversed the decrease in proliferation and migration of cells overexpressing GSTM5. By contrast, a GSH synthesis inhibitor significantly decreased 5637 cell GSH levels, survival and migration. Furthermore, GSTM5 overexpression inhibited the adhesion of cells to the extracellular matrix protein fibronectin. To elucidate the effect of GSTM5 on anticancer drugs used to treat bladder cancer, cellular viability was compared between cells with or without GSTM5 overexpression. GSTM5-overexpressed cells showed no significant change in the cytotoxicity of cisplatin or mitomycin C in 5637, RT4 and BFTC 905 cells. Though a degree of resistance to doxorubicin was noted in 5637 cells overexpressing GSTM5, no such resistance was observed in RT4 and BFTC 905 cells. In summary, GSTM5 plays a tumor suppressor role in bladder cancer cells without significantly affecting chemoresistance to cisplatin and mitomycin C, and the cellular GSH levels highlight a key mechanism underlying the cancer inhibition effect of GSTM5. These findings suggest that low gene expression and high DNA methylation levels of GSTM5 may act as tumor markers for bladder cancer.

Movable Valley Switch Driven by Berry Phase in Bilayer-Graphene Resonators.

Berry phase, the geometric phase accumulated over a closed loop in parameter space during an adiabatic cyclic evolution, has been demonstrated to play an important role in many quantum systems since its discovery. In gapped Bernal bilayer graphene, the Berry phase can be continuously tuned from zero to 2π, which offers a unique opportunity to explore the tunable Berry phase on physical phenomena. Here, we report experimental observation of Berry-phase-induced valley splitting and crossing in movable bilayer-graphene p-n junction resonators. In our experiment, the resonators are generated by combining the electric field of a scanning tunneling microscope tip with the gap of bilayer graphene. A perpendicular magnetic field changes the Berry phase of the confined bound states in the resonators from zero to 2π continuously and leads to the Berry phase difference for the two inequivalent valleys in the bilayer graphene. As a consequence, we observe giant valley splitting and unusual valley crossing of the lowest bound states. Our results indicate that the bilayer-graphene resonators can be used to manipulate the valley degree of freedom in valleytronics.

Tunable Lattice Reconstruction, Triangular Network of Chiral One-Dimensional States, and Bandwidth of Flat Bands in Magic Angle Twisted Bilayer Graphene.

The interplay between interlayer van der Waals interaction and intralayer lattice distortion can lead to structural reconstruction in slightly twisted bilayer graphene (TBG) with the twist angle being smaller than a characteristic angle θ_{c}. Experimentally, the θ_{c} is demonstrated to be very close to the magic angle (θ≈1.08°). Here we address the transition between reconstructed and unreconstructed structures of the TBG across the magic angle by using scanning tunneling microscopy (STM). Our experiment demonstrates that both structures are stable in the TBG around the magic angle. By using a STM tip, we show that the two structures can be changed to each other and a triangular network of chiral one-dimensional states hosted by domain boundaries can be switched on and off. Consequently, the bandwidth of the flat band, which plays a vital role in the emergent strongly correlated states in the magic angle TBG, is tuned. This provides an extra control knob to manipulate the exotic electronic states of the TBG near the magic angle.

Deficiency of lrp4 in zebrafish and human LRP4 mutation induce aberrant activation of Jagged-Notch signaling in fin and limb development.

Low-density lipoprotein receptor-related protein 4 (LRP4) is a multi-functional protein implicated in bone, kidney and neurological diseases including Cenani-Lenz syndactyly (CLS), sclerosteosis, osteoporosis, congenital myasthenic syndrome and myasthenia gravis. Why different LRP4 mutation alleles cause distinct and even contrasting disease phenotypes remain unclear. Herein, we utilized the zebrafish model to search for pathways affected by a deficiency of LRP4. The lrp4 knockdown in zebrafish embryos exhibits cyst formations at fin structures and the caudal vein plexus, malformed pectoral fins, defective bone formation and compromised kidney morphogenesis; which partially phenocopied the human LRP4 mutations and were reminiscent of phenotypes resulting form a perturbed Notch signaling pathway. We discovered that the Lrp4-deficient zebrafish manifested increased Notch outputs in addition to enhanced Wnt signaling, with the expression of Notch ligand jagged1b being significantly elevated at the fin structures. To examine conservatism of signaling mechanisms, the effect of LRP4 missense mutations and siRNA knockdowns, including a novel missense mutation c.1117C > T (p.R373W) of LRP4, were tested in mammalian kidney and osteoblast cells. The results showed that LRP4 suppressed both Wnt/ß-Catenin and Notch signaling pathways, and these activities were perturbed either by LRP4 missense mutations or by a knockdown of LRP4. Our finding underscore that LRP4 is required for limiting Jagged-Notch signaling throughout the fin/limb and kidney development, whose perturbation representing a novel mechanism for LRP4-related diseases. Moreover, our study reveals an evolutionarily conserved relationship between LRP4 and Jagged-Notch signaling, which may shed light on how the Notch signaling is fine-tuned during fin/limb development.

Synthesis and In Vitro Photocytotoxicity of 9-/13-Lipophilic Substituted Berberine Derivatives as Potential Anticancer Agents.

The objective of this study was to synthesize the 9-/13-position substituted berberine derivatives and evaluate their cytotoxic and photocytotoxic effects against three human cancer cell lines. Among all the synthesized compounds, 9-O-dodecyl- (5e), 13-dodecyl- (6e), and 13-O-dodecyl-berberine (7e) exhibited stronger growth inhibition against three human cancer cell lines, (HepG2, HT-29 and BFTC905), in comparison with structurally related berberine (1). These three compounds also showed the photocytotoxicity in human cancer cells in a concentration-dependent and light dose-dependent manner. Through flow cytometry analysis, we found out a lipophilic group at the 9-/13-position of berberine may have facilitated its penetration into test cells and hence enhanced its photocytotoxicity on the human liver cancer cell HepG2. Further, in cell cycle analysis, 5e, 6e, and 7e induced HepG2 cells to arrest at the S phase and caused apoptosis upon irradiation. In addition, photodynamic treatment of berberine derivatives 5e, 6e, and 7e again showed a significant photocytotoxic effects on HepG2 cells, induced remarkable cell apoptosis, greatly increased intracellular ROS level, and the loss of mitochondrial membrane potential. These results over and again confirmed that berberine derivatives 5e, 6e, and 7e greatly enhanced photocytotoxicity. Taken together, the test data led us to conclude that berberine derivatives with a dodecyl group at the 9-/13-position could be great candidates for the anti-liver cancer medicines developments.

[The Monitoring and Application of Transcranial Doppler Ultrasound in Patients with Severe Neurovascular Diseases].

OBJECTIVE: To investigate the monitoring effect and application of transcranial Doppler ultrasound (TCD) in patients with severe neurovascular cerebrovascular diseases. METHODS: From December 2016 to October 2018, 96 patients with cerebrovascular disease in Department of Neurology and ICU, West China Hospital, Sichuan University were monitored by bedside TCD, including the detection of bilateral middle cerebral arteries (MCAs) through temporal window, and the detection of the basilar artery (BA) through occipital window, characterized by the peak systolic blood flow velocity, peak diastolic blood flow velocity, average peak blood flow velocity, vascular pulsatility index, vascular pulsatility index, vascular resistance index and blood flow spectrum morphology in local hemodynamic changes. According to the monitoring results, it was divided into vasospasm group, increased blood flow group and insufficient blood supply group. Relevant data of monitoring results were analysed. RESULTS: Bedside TCD monitoring was successfully used to all cerebrovascular diseases patients. Among 96 patients, 37 patients (38.54%) had increased cerebral blood flow, 15 patients (15.62%) had cerebral vasospasm, and 93 patients had insufficient cerebral blood supply (90.62%, including insufficient blood supply to the MCA and BA). Patients mainly with cerebral aneurysm and hypertensive intracerebral hemorrhage types contributed the highest proportion of insufficient blood supply, followed by the increase of blood flow, and the incidence of vasospasm was relatively low. In cerebral aneurysm group and hypertensive intracerebral hemorrhage group, and differences in the incidence of insufficient blood supply, increased blood flow, and vasospasm were statistically significant ( P<0.05). CONCLUSION: The bedside TCD monitoring can assess the patient's craniocerebral hemodynamic information and provide a clinical guidance.

Synthesis of 1,4- and 1,5-Amino Alcohols via Nucleophilic Addition of Semicyclic N,O-Acetal with Organozinc Reagents.

An efficient approach to access functionalized 1,4- and 1,5-amino alcohols has been developed through the nucleophilic addition of semicyclic N,O-acetal with organozinc reagents. A number of substituted benzyl zinc reagents (including nitrile and ester substituted) could react with semicyclic N,O-acetals 1 and 2, affording the desired products 3a-3p and 4a-4o in good to excellent yields.

Approach to Tertiary-Type ß-Hydroxyl Carboxamides Through Sc(OTf)3-Catalyzed Addition of Ynamides and Ketones.

An efficient approach to access functionalized tertiary-type ß-hydroxyl carboxamides has been developed through Sc(OTf)3-catalyzed addition of ynamides and substituted ketones. Water was found to be an important reaction substrate, and the solvent was not needed in this process. A broad range of substituted ynamides and ketones was well applicable to the reaction with excellent chemical selectivities. Moreover, several chiral ß-hydroxyl carboxamides 3j-3r were prepared with excellent regioselectivities and outstanding diastereoselectivities.

2-O-Methylmagnolol Induces Apoptosis and Inhibits IL-6/STAT3 Signaling in Oral Squamous Cell Carcinoma.

BACKGROUND/AIMS: 2-O-methylmagnolol (MM1), a derivative of magnolol bearing one methoxy moiety, has been shown to display improved anti-tumor activity against skin cancers. In this study, we examined the anti-tumor effects of magnolol and MM1 on oral squamous cell carcinoma (OSCC). METHODS: Trypane blue staining and clonogenic assays were performed to determine the cytotoxic effects of magnolol and MM1 in OSCC cells. Migration and matrigel invasion assays were carried out to examine the metastasis effects of magnolol and MM1 in OSCC cells. IL6-stimulation, Western blot, and immunohistochemistry were used to investigate the IL-6/STAT3 signaling and apoptosis. A bioluminescent mouse model of orthotopically implanted SAS cells was used to determine the anti-tumor activity of MM1 in vivo. RESULTS: MM1 displays greater activity than magnolol on affecting the cytotoxicity, migration, and invasion of OSCC cells cultured in vitro. The improved anti-tumor activity of MM1 was shown to associate with its greater activity to inhibit STAT3 signaling and to induce apoptosis in the OSCC. In addition, we presented evidence that MM1 is effective in inhibiting the growth of orthotopic implanted OSCC cells in vivo. CONCLUSION: Our data indicate that MM1 displays greater anti-tumor activity than magnolol in OSCC and is an attractive agent to be further explored for its potential clinical application.

Asymmetric synthesis of (-)-sedacryptine through a diastereoselective Mannich reaction of N,O-acetals with ketones.

An efficient diastereoselective approach to access the 3-hydroxy-2,6-disubstituted piperidine scaffold 1 has been developed through the Mannich process involving N,O-acetal (2S,3R)-6 and ketones in excellent yield with high diastereoselectivity (dr > 99 : 1). In addition, the utility of this convenient one-pot process is demonstrated by the asymmetric synthesis of (-)-sedacryptine 3.

Mandibular Coronoidectomy Could Significantly Accelerate the Healing Process of Infratemporal Fossa Abscess.

PURPOSE: Management of an infratemporal fossa abscess (IFA), which is a specific form of severe and advanced deep fascial space infection (DFI), is based mainly on traditional methods. The purpose of this study was to investigate the role of mandibular coronoidectomy in accelerating IFA healing. PATIENTS AND METHODS: This research is a single-center retrospective study composed of 23 patients with IFA. The predictor variables were gender, age, diabetes, severity score, and mandibular coronoidectomy. The outcome variables included hospitalization time (HT) and irrigating time (IT). A comparison of treatment outcomes between the improved and traditional surgical interventions for IFA was performed. RESULTS: Compared with patients who did not receive mandibular coronoidectomy (NC group; HT, 17.54 ± 1.80 days; IT, 38.54 ± 3.73 days), patients who underwent mandibular coronoidectomy (AC group) had significantly decreased HT (7.20 ± 1.19 days) and IT (15.10 ± 1.27 days; P < .01). In addition, 4 patients (31%) in the NC group received reoperation for osteomyelitis, whereas no osteomyelitis and DFI recurrence occurred in the AC group. CONCLUSIONS: Mandibular coronoidectomy with extra intraoral drainage could considerably accelerate the healing process of IFAs and obviously decrease the reoperation rate for osteomyelitis.