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Abnormal widening of the mandibular canal (MC) is rarely observed on radiography. Nonetheless, as most of the current research on abnormal mandibular widening is limited to case reports and MCs have relatively deep and hidden positions, there are challenges in diagnosing and formulating treatment plans for patients with abnormal MC widening. To provide ideas for the differential diagnosis and treatment choices of the characteristic clinical sign, this study included patients with abnormal widening of the MC between July 2014 and October 2023. The patient's medical records were reviewed, general information, disease details and radiographic features (panoramic reconstructive computed tomography) of MC widening were collected. Patients were followed up to assess treatment outcomes. In conclusion, the abnormal widening of the MC often implies a pathological state of the mandible. And different morphologies of the widened MC are helpful for differential diagnosis of protential mandibular disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: RA is a recurrent autoimmune disease that has significant adverse effects on the physical and mental health of patients. Traditional Chinese medicine has shown significant advantages in the prevention and treatment of RA. Numerous clinical and experimental studies have confirmed that traditional Chinese medicine components have clear therapeutic effects and minimal adverse reactions in treating RA. The research on traditional Chinese medicine for the prevention and treatment of RA has become a hot topic in the field of autoimmune diseases., Methods: The related references about the mechanisms and Q-markers of anti-RA of traditional Chinese medicine in this review were collected from Willy, SpringLink, Web of Science, Elsevier, PubMed, SciFinder, Scopus, ACS publications, Baidu Scholar, Google Scholar, and CNKI., Results: The traditional Chinese medicine components such as terpenoids, flavonoids, and alkaloids have significant anti-RA effects, and their mechanisms are mainly to inhibit NF-κB signaling pathway, inhibit the proliferation of RA fibroblasts like synovial cells, and regulate Th1/Th2 cell balance, and so on. Predicting and studying the Q-markers of traditional Chinese medicine anti-RA by plant phylogeny and chemical componentss, traditional medicinal properties, pharmacokinetics, component measurability, correlation between composition and efficacy, and gut microbiota will provide scientific foundations for the research and further development of anti-RA traditional Chinese medicine., Conclusions: The active components of traditional Chinese medicine exhibited the characteristic of multiple mechanisms in the treatment of RA, such as terpenoids had anti-angiogenesis effects, flavonoids had anti-inflammatory and cartilage protective effects, and alkaloids had antiinflammatory and analgesic effects. The proposal of Q-markers for anti-RA provided new research ideas for promoting the development of new drugs for anti-RA and ensuring the safety and effectiveness of clinical medications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: We aimed to evaluate the histopathological alterations in human salivary glands after radioactive iodine (RAI) treatment for thyroid diseases., Study Design: We retrospectively selected patients with a history of RAI treatment for thyroid diseases from a database of patients who underwent surgery for oral and maxillofacial diseases and had specimens of salivary glands at Peking University School of Stomatology between December 2012 and July 2023. The patients' clinical records and histopathological slides of the salivary glands were carefully reviewed., Results: Sixteen patients were included. Three symptomatic patients showed duct cell cytoplasmic vacuolization and increased numbers of disordered duct cell layers (3/3), severe duct stenosis and dilation (2/3), and exfoliated epithelial cells in the duct lumen (1/3). The glandular parenchyma showed severe acinar atrophy (2/2), fat content enhancement (2/2), and severe periductal fibrosis (3/3). Thirteen asymptomatic patients showed duct cell cytoplasmic vacuolization (5/13), acinar atrophy and increased fat content in the parenchyma (5/13), and periductal fibrosis (5/13)., Conclusion: Main histopathologic changes in the salivary glands after RAI treatment for thyroid diseases are cytoplasmic vacuolization of duct cells, acinar atrophy, fat content enhancement, and periductal fibrosis. These changes were evident in symptomatic cases, and were also seen in some asymptomatic patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Although low-level laser therapy (LLLT) is a widely used noninvasive treatment because of photobiomodulation effects, its application for xerostomia remained uncertain. Tight junctions (TJs), mainly composed of claudins, occludin, and ZO family members, are crucial structures that determine material transport through paracellular pathway in salivary gland epithelial cells. This work aimed to investigate whether LLLT affected salivary secretion through epithelial TJs. Methods: Transepithelial electrical resistance (TER) measurement and paracellular permeability assay were applied to evaluate paracellular permeability in submandibular gland (SMG)-C6 cells after irradiation with 540 nm green light. Immunofluorescence and western blot were used to detect the expression of TJ proteins. Quantitative phosphoproteomics were performed to explore possible intracellular signals. Results: We found that irradiation with 540 nm green light significantly decreased TER values while increased paracellular transport in SMG-C6 cells. 540 nm green light-induced redistribution of claudin-1, -3, and -4, but not occludin or ZO-1. Moreover, above phenomena were abolished by preincubation with capsazepine, an antagonist of transient receptor potential vanilloid subtype 1. Notably, irradiation with 540 nm green light on the skin covering the whole submandibular gland regions promoted salivary secretion and attenuated lymphocytic infiltration in 21-week-old non-obese diabetic mice ( n = 5 per group), a xerostomia animal model for Sjögren's syndrome. Through in-depth bioinformatics analysis and expression verification, ERK1/2 and EphA2 served as potential canonical and noncanonical signals underlying 540 nm green light. Conclusions: Our findings uncovered the novel therapeutic effects of 540 nm green light on xerostomia through regulation on the expression and distribution of TJs.

Objective: To investigate the expression and secretion of epidermal growth factor (EGF) in major and minor salivary gland tissues of human subjects and to examine the potential influence of sex and age on EGF expression and secretion., Design: Saliva samples from the oral cavity at rest and after citric acid stimulation, as well as serum samples, were collected from 150 healthy subjects, and the concentrations of EGF were measured with enzyme-linked immunosorbent assay (ELISA) and compared. The expression of EGF mRNA and protein in normal salivary gland tissues was measured by real-time polymerase chain reaction (RT-PCR), Western blot (WB), and immunohistochemistry (IHC)., Results: The EGF concentration in acid-stimulated saliva was significantly higher than that in resting saliva (P < 0.001), and significantly higher than that in serum (P < 0.001). No sex difference was observed in EGF levels of whole saliva and serum, whereas the EGF levels in saliva and serum were decreased with age (P < 0.001 and P < 0.001, respectively). The EGF concentration and compound secretion rate (CSR) in resting submandibular glands saliva were significantly higher than those in resting parotid glands saliva (P = 0.002 and P < 0.001, respectively). The EGF was expressed in all major and minor salivary glands and ranked in order of submandibular, parotid, sublingual, and labial glands., Conclusion: All salivary glands have the function of secreting EGF, and the submandibular gland is the main source of salivary EGF. Aging is a factor influencing the expression and secretion of EGF., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The neuromuscular junction (NMJ) has an elaborate anatomy to ensure agile and accurate signal transmission. Based on our formerly obtained expressions of the thermal and conductance induced voltage fluctuations, in this paper, the mechanisms underlying the conductance-induced voltage fluctuation are characterized from two aspects: the scaling laws with respect to either of the two system-size factors, the number of receptors or the membrane area; and the "seesaw effect" with respect to the intensive parameter, the concentration of acetylcholine. According to these mechanisms, several aspects of the NMJ anatomy are explained from a denoising perspective. Finally, the power spectra of the two types of voltage fluctuations are characterized by their specific scaling laws, based on which we explain why the endplate noise has the low-frequency property that is described by the term "seashell sound"., (© 2024. European Biophysical Societies' Association.)

Phyllanthus emblica Linn is not only an edible fruit with high nutritional value, but also a medicinal plant with multiple bioactivities. It is widely used in clinical practice with functions of clearing heat, cooling blood, digesting food, strengthening stomach, promoting fluid production, and relieving cough. This review summarized a wide variety of phytonutrients, including nutritional components (mineral elements, amino acids, vitamins, polysaccharides, unsaturated free fatty acids) and functional components (phenolic acids (1-34), tannins (35-98), flavonoids (99-141), sterols (142-159), triterpenoids (160-175), lignans (176-183), alkaloids (184-197), alkanes (198-212), aromatic micromolecules (213-222), other compounds (223-239)). The isolated compounds and the various extracts of P. emblica Linn presented a diverse spectrum of biological activities such as anti-oxidant, anti-cancer, anti-inflammatory, anti-bacterial, hepatoprotective, hypoglycemic, anti-atherosclerosis, neuroprotective, enhancing immunity, anti-fatigue, anti-myocardial fibrosis. The quality markers of P. emblica Linn were predicted and analyzed based on traditional medicinal properties, traditional efficacy, plant genealogy and chemical component characteristics, biogenic pathway of chemical components, measurability of chemical components, transformation characteristics of polyphenolic components, homologous characteristics of medicine and food, compound compatibility environment, and clinical applications. This review also summarized and prospected applications of P. emblica Linn in beverages, preserved fruits, fermented foods, etc. However, the contents of mechanism, structure-activity relationship, quality control, toxicity, extraction, processing of P. emblica Linn are not clear, and are worth further studies in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Long non-coding RNAs (lncRNAs) are a sort of transcripts that are more than 200 nucleotides in length. In recent years, many studies have revealed the modulatory role of lncRNAs in cancer. Typically, lncRNAs are linked to a variety of essential events, such as apoptosis, cellular proliferation, and the invasion of malignant cells. Simultaneously, autophagy, an essential intracellular degradation mechanism in eukaryotic cells, is activated to respond to multiple stressful circumstances, for example, nutrient scarcity, accumulation of abnormal proteins, and organelle damage. Autophagy plays both suppressive and promoting roles in cancer. Increasingly, studies have unveiled how dysregulated lncRNAs expression can disrupt autophagic balance, thereby contributing to cancer progression. Consequently, exploring the interplay between lncRNAs and autophagy holds promising implications for clinical research. In this manuscript, we methodically compiled the advances in the molecular mechanisms of lncRNAs and autophagy and briefly summarized the implications of the lncRNA-mediated autophagy axis., 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 © 2024 Liu, Tang, Yang, Yang and Xia.)

Background: Elsholtzia belongs to the Labiatae family, which consists of herbaceous subshrubs and shrubs. Among them, volatile oils are an important chemical component in Elsholtzia, which have various bioactive medicinal and developmental values., Methods: The references about volatile oils of Elsholtzia in this review were obtained from Web of Science, SciFinder, PubMed, Willy, Elsevier, SpringLink, ACS publications, Google Scholar, Baidu Scholar, Scopus, and CNKI. The other information about Elsholtzia was obtained from classical works or ancient books., Results: Traditionally, the volatile oils from Elsholtzia were used in Chinese medicine to treat cholera, abdominal pain, vomiting, and scattered edema. Relevant research revealed that Elsholtzia contains many different types of volatile oils, and most of them display bioactivities, including anti-oxidant, anti-bacterial, anti-viral, hypolipidemic, insecticidal, and antiinflammatory activities, treating spleen and stomach. Furthermore, the applications of volatile oils were summarized and analyzed in this paper., Conclusion: The contents of traditional use, constituent analysis, bioactivity, and application of volatile oils from Elsholtzia were reviewed in this paper. This will provide important research value and a scientific basis for the in-depth study of the plants of Elsholtzia in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Demand for less-invasive procedures for treating gummy smile, such as botulinum toxin A injections, has increased substantially over the years. Meanwhile, the optimal injection site for botulinum toxin A injection is debated. The authors aimed to investigate the efficacy of botulinum toxin A injection at the Yonsei point for treating gummy smile., Methods: In this double-blind, single-site, randomized clinical trial, healthy participants with a gummy smile (anterior gingival exposure of ≥3.0 mm) were enrolled and randomized (1:1 ratio) into two groups. The experimental group was administered 6 U of botulinum toxin A at the Yonsei point (a single-site injection of 3 U to the right Yonsei point and 3 U to the left Yonsei point), and the control group received the same dose in the bilateral levator labii superioris alaeque nasi muscle sites. The patients were assessed at baseline and 4, 12, 24, and 48 weeks after the first injection using a digital vernier caliper., Results: A total of 49 participants were enrolled. Anterior and bilateral posterior gingival exposure were reduced at 4, 12, and 24 weeks ( P ≤ 0.05) and returned to baseline at 48 weeks in both groups; there was no difference between the groups at these time points. The increase in satisfaction among patients was significant, and few adverse events were observed., Conclusion: Both the Yonsei point and the levator labii superioris alaeque nasi muscle site can be used as botulinum toxin A injection sites for treating gummy smile., Clinical Question/level of Evidence: Therapeutic, I., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Hand, foot, and mouth disease is a serious public health problem, and the main pathogen is enterovirus 71 (EV71). Its capsid assembly mechanism including capsid protein processing has been widely studied. Full and empty capsids have different immunological efficacy. Therefore, tracking full/empty capsid ratio throughout the EV71 production process is important to ensure consistent product quality and proper dosing response. The analysis of full/empty capsid ratio of intact virus has been widely reported as well. A variety of techniques have been employed to evaluate the full/empty capsid ratios. However, there has not been a rapid, reproducible, and robust assay to determine the full/empty capsid ratios of final and in-process products. In this study, a novel assay based on capillary zone electrophoresis was established. The separation of full and empty species could be achieved within 10 min and the ratio of peak areas was used to calculate the full/empty capsid ratio directly. The results showed good reproducibility and linearity for the determination of full/empty capsid ratios., (© 2023 Wiley-VCH GmbH.)

Background: Microvascular submandibular gland transplantation (SMGT) for severe dry eye disease (DED) has rarely been reported in the literature. The aim of this study was to report a case series of SMGT with the special focus on monitoring and management of postoperative vascular compromise., Methods: Using a retrospective single-cohort study design, the investigators enrolled a sample of DED patients undergoing SMGT in a Chinese university hospital during 1999 and 2021. The main outcomes were baseline and surgical data, post-operative manifestations, and surgical results. Descriptive, uni- and bivariate statistics were computed with the significant P < 0.05., Results: During the study period, 220 DED patients (55.9% female) with a mean age of 32.66±14.47 years underwent SMGT. Vascular compromises occurred in 27 grafted glands (12.3%; 22 venous compromises and 5 arterial compromises) at a median of 27 h(range, 3.3 to 288 h) after surgery. Harden texture and swelling of the covering skin flap of the donor indicated venous compromises, while some specific sign was absent for arterial compromise. The accompanying vein of the facial artery (FAV) as a donor's vein was associated with less vascular compromise compared to the anterior facial vein (AFV). Timely reexploration was performed in 25 glands (92.6%), with a salvaged rate of 48%, and more venous compromises were salvaged compared to artery compromises (54.6% vs. 0%, P = 0.047). Temporary hypersecretion on postoperative 2-5 days was noticed in the grafted glands with no or salvaged vascular compromise (Schirmer's test, 35 mm/5 min and 37 mm/5 min, respectively, P = 0.749), while they were absent for the 15 surgically failed grands (Schirmer's test 0 mm/5 min, P<0.001)., Conclusions: Vascular compromise appears to be a common complication of SMGT. Postoperative hypersecretion of the grafted glands may indicate good circulation, and the use of FAV as the donor's vein could help to decrease the risk of vascular compromise., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

In recent years, optical tweezers have become a novel tool for biodetection, and to improve the inefficiency of a single trap, the development of multitraps is required. Herein, we constructed a set of hybrid multitrap optical tweezers with the balance of stability and flexibility by the combination of two different beam splitters, a diffraction optical element (DOE) and galvano mirrors (GMs), to capture polystyrene (PS) microbeads in aqueous solutions to create an 18-trap suspended array. A sandwich hybridization strategy of DNA-miRNA-DNA was adopted to detect three kinds of target miRNAs associated with triple negative breast cancer (TNBC), in which different upconversion nanoparticles (UCNPs) with red, green, and blue emissions were applied as luminescent tags to encode the carrier PS microbeads to further indicate the levels of the targets. With encoded luminescent microbeads imaged by a three-channel microscopic system, the biodetection displayed high sensitivity with low limits of detection (LODs) of 0.27, 0.32, and 0.33 fM and exceptional linear ranges of 0.5 fM to 1 nM, 0.7 fM to 1 nM, and 1 fM to 1 nM for miR-343-3p, miR-155, and miR-199a-5p, respectively. In addition, this bead-based assay method was demonstrated to have the potential for being applied in patients' serum by satisfactory standard addition recovery experiment results.

Purpose: To establish a Beagle dog model of dry eye disease (DED)., Methods: DED models were induced by surgical removal of orbital lacrimal glands and entire resection of third eyelids in the left eyes of six Beagle dogs. Intact right eyes served as self-controls. Non-anaesthetized Schirmer test (STT), tear break-up time (TBUT), and fluorescein staining grading were performed monthly after operation. Interleukin (IL)-1β, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) levels were detected in tears and conjunctiva tissues. Six months after surgery, conjunctiva and cornea were collected and histopathologically analyzed., Results: Signs of DED appeared within one month after surgery and then remained stable. STT values were significantly reduced by 88% within 3 weeks after operation and remained stable over months with 1.6 ± 0.4 mm. Mean TBUT decreased significantly within two months after operation and maintained 5.2 ± 1.1 seconds. The mean fluorescein staining score was highest at the first month and then was reduced, eventually reaching a balance with 11.0 ± 1.3 points. Elevated levels of IL-1β, IL-8, IL-10, and TNF-α were detected in tears and conjunctivas of operated eyes. Hematoxylin and eosin staining showed cornea neovascularization in the corneal stroma with thickened stroma layer and disorganized collagen bundles. Periodic acid-Schiff staining revealed a reduced function of conjunctival goblet cells., Conclusions: A combined type of DED model on the Beagle dog was established by removal of the orbital lacrimal gland and resection of the third eyelid. This DED model is easily accessible and is stable at six-month observation., Translational Relevance: The surgery-induced Beagle dog DED model is easily accessible and stable over a relatively long time.

Cerebral hemorrhage is a fatal disease that causes severe damage to local nerve function. The purpose of this research is to analyze the effect of kurarinone on hemin-induced neuroinflammation and neurotoxicity. In our study, according to the results of bioinformatics analysis, we hypothesized that kurarinone might modulate cerebral hemorrhage advancement via the insulin-like growth factor 1/phosphoinositide 3-kinase/protein kinase B (IGF1/PI3K/Akt) signaling. Kurarinone promoted M2 microglia polarization, and curbed M1 polarization and inflammation in human microglial cells (HMC3) cells with hemin treatment. Besides, kurarinone upregulated IGF1 expression and activated the PI3K/Akt signaling pathway in hemin-treated HMC3 cells. In addition, downregulation of IGF1 or inhibition of the PI3K/Akt signaling weakened the effects of kurarinone on microglia polarization and inflammation in HMC3 cells with hemin treatment. Kurarinone alleviated apoptosis and oxidative damage of SH-SY5Y cells co-cultured with hemin-treated HMC3 cells. In conclusion, kurarinone lessened hemin-induced neuroinflammation and microglia-mediated neurotoxicity by regulating microglial polarization through modulating the IGF1/PI3K/Akt signaling. These results delivered a new prospective therapeutic drug for the treatment of cerebral hemorrhage., (© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Although gastric cancer with para-aortic lymph node (PAN) metastasis is commonly regarded as unresectable, surgeons have explored the optimal treatment for patients with PAN metastases limited to No.16a2/b1 in the past few decades. Preoperative systemic therapy combined with D2 gastrectomy plus PAN dissection may improve the prognosis of these patients. In this multicenter phase II trial, 29 gastric cancer patients with PAN metastasis limited to No.16a2/b1 will receive preoperative treatment with nab-paclitaxel, oxaliplatin, S-1 (nab-POS: nab-paclitaxel, oxaliplatin, S-1) and sintilimab followed by D2 gastrectomy plus PAN dissection; and postoperative treatment with oral S-1, intravenous sintilimab and intraperitoneal paclitaxel. The end points for the study are 3-year overall survival, 3-year disease-free survival, pathological response rate, incidence of postoperative complications and adverse events.

Purpose: To compare submandibular gland (SMG) transplantation with minor salivary gland (MSG) transplantation for the treatment of different dry eye diseases (DED)., Design: Retrospective clinical cohort study., Methods: A total of 73 refractory DED eyes were divided into 3 groups. Group A comprised 35 end-stage DED eyes that underwent SMG transplantation. Group B comprised 20 end-stage DED eyes with MSG transplantation. Group C comprised 18 non-end-stage DED eyes with MSG transplantation. Schirmer test (ST), tear break-up time (TBUT), corneal fluorescein staining (FL), and best-corrected visual acuity (BCVA) were measured before and after surgery., Results: Hospital length of stay, length of operation, and hospital fee were significantly higher in group A than in group B or C. Eyes in group A showed the most severe DED disease, with preoperative ST, TBUT, FL, and BCVA of 0.36 mm per 5 minutes, 0.03 seconds, 10.97, and 0.11, respectively, which improved significantly to 20.23 mm per 5minutes, 1.74 seconds, 7.58, and 0.2 at >2-year follow-up. Group B had similar baseline data, and significant but limited improvement only in the ST (0.55 mm per 5 minutes to 3.79 mm per 5 minutes) and FL (11.10 to 9.58) after the operation. Group C had better baseline ST, TBUT, FL, and BCVA of 0.89 mm per 5min, 3.49 seconds, 1.83, and 0.81, respectively, which improved significantly (except for BCVA) to 9.35 mm per 5min, 9.08 s, 0.53, and 0.89 after MSG transplantation., Conclusion: SMG transplantation could be recommended to treat end-stage refractory DED. MSG transplantation may provide satisfying results for refractory DED with relatively less severe impairment of the eye., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: To use minor salivary glands' flow rate (MSGFR) measurement in minor salivary glands (MSGs) autotransplantation for the treatment of severe dry eye disease (DED)., Methods: MSGs autotransplantations were performed in 18 eyes (17 patients) with severe DED. MSGFR were measured before operation. The upper or lower lip with higher MSGFR was selected as the donor site. Buccal mucosa was the back-up in cases labial MSGs showing markedly decreased MSGFRs. Two pieces of salivary lobules with the covering mucosa were harvested and transplanted to the recipient beds prepared in both upper and lower lids., Results: The donor sites included lower lip in 12 eyes, upper lip in 5 eyes and buccal mucosa in 1 eye. Postoperative follow-up confirmed viable grafts in all cases. The overall subjective relief rate of DED symptoms was 58.8%, with Schirmer test values increasing from 0 mm to 4 mm (p<0.05). The mean preoperative MSGFR was 1.7 (range: 0.9-3.3) µL/min/cm 2 . ROC analysis indicated an outstanding discrimination power for preoperative MSGFR to predicate postoperative relief of DED symptoms (area under the curve (AUC)=0.948, p<0.01). The maximum sensitivity (100%) and specificity (72.7%) were reached at a cut-off of 1.785 µL/min/cm 2 . Patients with preoperative MSGFR >1.785 µL/min/cm 2 showed greater improvement of Schirmer test values after surgery than those with MSGFR ≤1.785 µL/min/cm 2 (p<0.05)., Conclusion: MSGs transplantation proved to be useful for treating severe DED. The amount of postoperative lubrication and the treatment effect were positively correlated with preoperative MSGFR. MSGFR measurement and donor-site selection should be critical steps before the operation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We construct a compact model to mimic the membrane voltage response to the concentration of acetylcholine ([ACh]) which is mediated by the stochastic gating of acetylcholine (ACh) receptors. The patterns of the voltage depolarization against [ACh] as well as the accompanying voltage noises are presented. The mechanism of the voltage fluctuation that caused by the stochastic gating of receptors is explained. We consider that our results explain the frequently observed "end-plate (potential) noise" in physiology and electromyographic literature. These results, together with the requirements of evolution pressure on the motor units, explain reasonably the anatomical structure of the neuromuscular junction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The objective of this study was to investigate the clinical manifestations and pathologic appearances of the submandibular gland (SMG) in Stevens-Johnson syndrome (SJS)., Study Design: Patients with autologous transplantation of SMG for treatment of severe dry eye between March 1998 and May 2018 were divided into the SJS group (70 cases) and non-SJS group (50 cases) according to the history of SJS. The SMG weight and computed tomography volume and salivary flow rate were measured. The concentration index and secretion index were estimated using scintigraphy with technetium-99m-pertechnetate. Histopathology studies of SMG tissues were conducted, and the acini parameters were measured using a digital image analyzer., Results: A decreased computed tomography volume and weight was observed in 48.57% the SJS group and 2% in the non-SJS group (P < .01). The rest whole, acid-stimulated whole, and SMG rest salivary flow rates decreased in the SJS group (P < .05). The normal SMG concentration index (37.5% vs 96.67%, P < .001) and secretion index (35% vs 96.67%, P < .001) rates were lower in the SJS group than in the non-SJS group. The glandular parenchyma was reduced, the acinar space was widened, and the fat content was increased in the SJS group., Conclusion: SMG atrophic and degenerative changes occurred in the SJS group, with a decrease in salivary secretion function in more than half of the patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Chlordimeform is a chemical pesticide that is highly carcinogenic and toxic. The purpose of this study was to establish an enzyme-linked immunosorbent assay (ELISA) method for the detection of chlordimeform in aquaculture and fish farming., Methods: Chlordimeform was coupled with bovine serum albumin (BSA) and ovalbumin (OVA) as carrier proteins. A chlordimeform-BSA conjugate was used as an immunogen, and chlordimeform-OVA was used as a coating antigen. Chlordimeform-BSA was used to immunize rabbits, and a polyclonal antibody was prepared. An indirect competitive enzyme-linked immunosorbent assay (IC-ELISA) was established to detect chlordimeform., Results: The working range of the established IC-ELISA method for chlordimeform detection was 1-20 ng/mL. The IC 50 was 3.126 ng/mL, and the lower limit of detection (LOD) of chlordimeform was 0.637 ng/mL. The recovery of chlordimeform from spiked water samples ranged from 81% to 107%., Conclusion: An anti-chlordimeform polyclonal antibody was successfully developed, and a novel IC-ELISA was established to detect chlordimeform in aquaculture.

The depolarization of the postsynaptic membrane potential in neuromuscular junction, which is conducted by the (stochastic) opening of nicotinic acetylcholine (nACh) receptors distributed in postsynaptic folds, is an inevitable stage in transmitting the electric signals from neural ends to muscle fibers. To perform this work, free energy must be dissipated. Being the first step in understanding the speech-accuracy-energy trade-off, we calculate the energy dissipation of a tiny membrane system that contains a single nACh receptor, i which firstly the stationary distribution of voltage is calculated based on our new method on solving the high-dimensional ODEs with variable coefficients. The ratio of the extent of depolarized-potential to the dissipated power is used to characterize the energy consuming efficiency of the system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to evaluate the long-term outcome and quality of life of IgG4-related sialadenitis (IgG4-RS) patients after submandibular gland (SMG) excision without immunomediate therapy., Materials and Methods: This retrospective review included patients with IgG4-RS who did not undergo further treatment following SMG excision. All patients diagnosed with IgG4-RS between January 1955 and December 2012 at the Department of Oral and Maxillofacial Surgery, Peking University School of Stomatology, were enrolled. The main outcome measures included postoperative IgG4-RS progression rate and differences between patients with and without recurrent disease. The degree of subjective oral dryness was evaluated using the summated xerostomia inventory (SXI); the objective secretory function was assessed by whole saliva flow rate measurements. Serological findings were analyzed during the follow-up., Results: SMG excision was adopted in all of the 83 patients. The median follow-up period was 108 (range 7-396) months. Clinical progression was observed in 54.2% of cases. Patients with other organ involvement (OOI) indicated higher progression rate to a significant extent (P = 0.015, HR = 2.108). The annual progression rate was 20.7% in the group with OOI and was 14.1% in the group without OOI. All cases showed higher levels of serum IgG4; the level was in positive correlation with follow-up time when no therapy was added. 82.4% of cases experienced xerostomia after the surgery, and the degree of dry mouth in patients underwent bilateral resection was significantly more severe than those in unilateral resection., Conclusions: Surgical excision of involved SMG cannot control the disease progression, which is not recommended for treatment of IgG4-RS. Differential diagnosis is crucial in order to prevent irreversible organ loss and relevant salivary gland dysfunction. Key Points • Surgical excision of involved SMG cannot control progression of IgG4-RS., (© 2021. International League of Associations for Rheumatology (ILAR).)

Mitochondrial permeability transition pore (PTP), a key regulator of cell life and death processes, is triggered by calcium ions (Ca 2+ ) and potentiated by reactive oxygen species (ROS). Although the two modes of PTP opening, i.e., transient and persistent, have been identified for a long time, its dynamical mechanism is still not fully understood. To test a proposed hypothesis that PTP opening acts as a tristable switch, which is characterized by low, medium, and high open probability, we develop a three-variable model that focused on PTP opening caused by Ca 2+ and ROS. For the system reduced to two differential equations for Ca 2+ and ROS, both the stability analysis and the potential landscape feature that it exhibits tristability under standard parameters. For the full system, the bifurcation analysis suggests that it can achieve tristability over a wide range of input parameters. Furthermore, parameter sensitivity analysis demonstrates that the existence of tristability is a robust property. In addition, we show how the deterministic tristable property can be understood within a stochastic framework, which also explains the PTP dynamics at the level of a single channel. Overall, this study may yield valuable insights into the intricate regulatory mechanism of PTP opening.

Background: C1q/tumour necrosis factor-related protein 3 (CTRP3) plays important roles in metabolism and inflammatory responses in various cells and tissues. However, the expression and function of CTRP3 in salivary glands have not been explored., Methods: The expression and distribution of CTRP3 were detected by western blot, polymerase chain reaction, immunohistochemical and immunofluorescence staining. The effects of CTRP3 on tumour necrosis factor (TNF)-α-induced apoptosis and barrier dysfunction were detected by flow cytometry, western blot, co-immunoprecipitation, and measurement of transepithelial resistance and paracellular tracer flux., Results: CTRP3 was distributed in both acinar and ductal cells of human submandibular gland (SMG) and was primarily located in the ducts of rat and mouse SMGs. TNF-α increased the apoptotic rate, elevated expression of cleaved caspase 3 and cytochrome C, and reduced B cell lymphoma-2 (Bcl-2) levels in cultured human SMG tissue and SMG-C6 cells, and CTRP3 further enhanced TNF-α-induced apoptosis response. Additionally, CTRP3 aggravated TNF-α-increased paracellular permeability. Mechanistically, CTRP3 promoted TNF-α-enhanced TNF type I receptor (TNFR1) expression, inhibited the expression of cellular Fas-associated death domain (FADD)-like interleukin-1β converting enzyme inhibitory protein (c-FLIP), and increased the recruitment of FADD with receptor-interacting protein kinase 1 and caspase 8. Moreover, CTRP3 was significantly increased in the labial gland of Sjögren's syndrome patients and in the serum and SMG of nonobese diabetic mice., Conclusions: These findings suggest that the salivary glands are a novel source of CTRP3 synthesis and secretion. CTRP3 might promote TNF-α-induced cell apoptosis through the TNFR1-mediated complex II pathway., (Copyright © 2021 Elsevier Inc. All rights reserved.)

C1q/tumor necrosis factor-related protein-6 (CTRP6) is a newly identified adipokine involved in diverse biological processes. However, its role in salivary glands remains unknown. Here, we demonstrated that CTRP6 was mainly distributed in the nuclei, apicolateral membranes, and cytoplasm of human submandibular glands (SMGs), serous cells of parotid glands, and ducts and apicolateral membranes of serous cells in rats and mice. CTRP6 inhibited the apoptosis rate and reversed the increased levels of cleaved caspase 3, caspase 8, caspase 9, and cytochrome C and the decreased Bcl-2 expression induced by tumor necrosis factor (TNF)-α in both SMG-C6 cells and cultured human SMG tissues. Microarray analysis identified 43 differentially expressed microRNAs (miRNAs) in the SMGs of nonobese diabetic mice. miR-34a-5p was selected due to its upregulation by TNF-α, which was abolished by CTRP6. The miR-34a-5p inhibitor promoted whereas the miR-34a-5p mimic suppressed the effects of CTRP6 on TNF-α-induced apoptosis. CTRP6 increased AMP-activated protein kinase (AMPK) phosphorylation and reversed TNF-α-induced SIRT1 downregulation in salivary cells. AraA, an AMPK inhibitor, reversed the effects of CTRP6 on TNF-α-induced alterations in the levels of SIRT1, miR-34a-5p, Bcl-2, and cleaved caspase 3 in vitro and ex vivo, whereas activating AMPK by AICAR reversed the decrease in SIRT1 expression and increase in miR-34a-5p expression induced by TNF-α. Inhibition of SIRT1 by EX527 suppressed the effects of CTRP6 on TNF-α-induced changes in miR-34a-5p and apoptosis-related proteins. Our findings indicate that salivary glands are novel sites for CTRP6 synthesis and secretion. CTRP6 protects acinar cells against TNF-α-induced apoptosis via AMPK/SIRT1-modulated miR-34a-5p expression., (© 2021 Wiley Periodicals LLC.)

The impetus of this study is to gauge the nexus between economic policy uncertainty (EPU) and financial innovation in Brazil, Russia, India, China, and South Africa (BRIC) nations for the period from 2004M1 to 2018M12. This study utilizes both the linear and non-linear autoregressive distributed lag (ARDL) models to evaluate the long-run and the short-run association between EPU and financial innovation; furthermore, the causal effects are investigated by following the non-Granger casualty framework. The results of long-run cointegration, i.e., the test statistics of modified F -test (FPSS), standard Wald test (WPSS), and tBDM, reject the null hypothesis and establish the presence of the long-run association between EPU and financial innovation. Conversely, long-run asymmetry cointegration revealed the test statistics of FPSS, WPSS, and tBDM in non-linear estimation. Furthermore, both in the long run and short run, the Wald test results disclose asymmetric effects running from EPU to financial innovation. In regards to the asymmetric impact of EPU on financial innovation, this study documents that the positive and negative shocks in EPU are negatively linked with financial innovation in the long run but are insignificant for short-run effects. Besides, financial innovation measured by R&D investment exhibits a positive linkage with shocks in EPU, implying that uncertainty induces innovation in the economy. Referring to causality effects, this study divulges the feedback hypothesis , i.e., bidirectional causality prevails between EPU and financial innovation in all sample countries., 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 Jia, Mehta, Qamruzzaman and Ali.)

In this paper we present the properties of the voltage fluctuations driven by a cluster of ligand-gated channels. First, the second-order moment of the voltage is expressed in form of the integrated resistance and the random force. Then the power spectrum of the voltage noise is obtained analytically, and it is proved to have the 1/ω^{4}-form. Its mechanism lies in that the randomness of the voltage fluctuation is weaker than channel (conductance) noise, which can be approximately described by the Ornstein-Ulenbeck process.

Cardiovascular diseases (CVD), especially acute myocardial infarction, are the leading cause of death, morbidity and disability across the world, affecting millions of people each year. Atherosclerosis (AS) is the major cause of CVD, and is a chronic inflammation involving different cell types and various molecular mechanisms. Ca 2+ dynamics of endothelial cells (ECs) and smooth muscle cells (SMCs) exert a significant influence on many aspects of CVD. Transient receptor potential channel 5 (TRPC5) is a member of the transient receptor potential (TRP) channels, which consists of a large number of nonselective cation channels with variable degrees of Ca 2+ -permeability. As a Ca 2+ -permeable cation channel, Human TRPC5 is expressed in a number of cell types, including ECs and muscle cells, as well as lungs and kidneys. TRPC5 is involved in renal, tumorous, neuronal and vascular diseases. In recent years, the roles of TRPC5 in CVD have been widely implicated in various disorders, such as AS, cardiac hypertrophy and blood pressure regulation. The TRPC5 mechanism of action may be associated with regulation of calcium homeostasis, oxidative stress and apoptosis. In this review, we highlight the significant roles of TRPC5 in the heart, and evaluate the potential of therapeutics targets which block TRPC5 for the treatment of CVD and related diseases., Competing Interests: The author declares no conflicts of interests., (© 2021 The Authors. Published by IMR Press.)

Being the primary mean of translating the chemical signal into the electric signal in neuromuscular junction, the nACh receptor is the first kind of ligand-gated channel that its kinetic structure has been known clearly. The next problem is to know quantitatively how it works in a living system. In this paper, we construct a piece-wise deterministic process to mimic the membrane voltage fluctuation driven by a single nACh receptor. The power spectrum of the voltage fluctuation is solved analytically, which reveals the 1/ω 4 -type noise., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: The diagnostic utility of labial salivary gland (LSG) biopsy for IgG4-related sialadenitis remains undetermined. The purpose of the present study was to determine whether submandibular gland biopsy could be replaced by LSG biopsy for diagnosing IgG4-RS., Patients and Methods: Medical records of two groups of patients were reviewed. Group A contained 45 patients suspected to have IgG4-RS who underwent both SMG and LSG biopsies. Group B contained 25 patients who were clinically and pathologically diagnosed with Sjögren syndrome (SS). Biopsy samples were stained using hematoxylin and eosin (HE) and immunohistochemical techniques and observed under an optical microscope. Relevant data describing histopathological characteristics were collected and analyzed., Results: SMG of IgG4-RS patients presented typical histopathological characteristics of fibrosis and IgG4-positive plasmacytic infiltration, while LSG showed varied characteristics. The sensitivity and accuracy of SMG for diagnosing IgG4-RS were greater than those of LSG (100% and 100% versus 55.3% and 75.7%, respectively, P < 0.05)., Conclusions: Biopsy of SMG showed greater sensitivity and specificity, whereas LSG biopsy showed varied histopathological and immunohistochemical characteristics; thus, SMG biopsy cannot be replaced by LSG biopsy for diagnosis of IgG4-RS.

Background: Linc00261 is a lncRNA that plays key roles in tumor suppression. While gallbladder carcinoma (GBC) is one of the most common cancer of the bile duct. However, the study about Linc00261's correlation with the clinicopathological characteristics and postoperative outcomes of the GBC patients is few. Therefore, we want to explore Linc00261 in GBC and assess its potential of clinical diagnosis., Methods: Quantitative real-time PCR (qRT-PCR) was used to detect the expression of Linc00261 in specimens of GBC and adjacent tissues as well as cell lines. Chi-square test has been used to research the correlation of the Linc00261 expression in GBC with the clinicopathological features. The Cox model was used to assess the value of Linc00261 in predicting the prognosis of GBC patients. ROC curve analysis was used to test the specificity and sensitivity of diagnostic method of serum Linc00261 expression., Results: The expression level of Linc00261 in GBC was significantly lower than normal tissues' and it was also up-regulated after surgery. The Linc00261 expression was significantly correlated with large tumor size (P<0.0001), late TNM stage (P=0.008), negative liver metastasis (P=0.027) and well differentiated phenotype (P=0.017). The patients with lower Linc00261 expression had significantly worse outcomes in terms of overall survival (P=0.0188) and progression-free survival (P=0.0029), and the low expression of Linc00261 was identified as an independent risk factor affecting postoperative survival rate of the patients (P<0.01). The expression of Linc00261 in serum was down-regulated of GBC patients and increased in the patients after operation. Linc00261 expressed in serum was also positively associated with its expression in GBC tissue of patients (P<0.0001). The GBC diagnosis efficacy of using the serum Linc00261 level to identify the GBC has high specificity and sensitivity (AUC 0.805)., Conclusions: Linc00261 could be identified a novel gene associated with GBC development and progression. It also may serve as a new diagnostic and prognostic biomarker for patients with GBC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-20-1091). The authors have no conflicts of interest to declare., (2020 Translational Cancer Research. All rights reserved.)

Purpose: Submandibular gland (SMG) transplantation improves the tear film and other ocular-surface features for patients with severe dry eye disease (DED). Using the dry eye-related quality of life (QOL) questionnaire, we aimed to evaluate whether DED patients' QOL would benefit from SMG transplantation and determine whether preoperative ophthalmologic and QOL measurements could predict which patients would be most satisfied with this surgery., Methods: This prospective study included DED patients with successful SMG transplantation. Using the Chinese version of the Dry Eye Related Quality of Life (CDERQOL) instrument, QOL was measured before and 1-year after surgery., Results: The QOL data of 51 consecutive patients were analyzed. Before surgery, all the patients had a poor QOL. One year after surgery, all five QOL domains (Dry Eye Symptom Bother, Impact on Daily Activities, Emotional Impact, Impact on Work, and Satisfaction with Treatment) showed significant improvement (P < 0.01). Unsuccessful treatment experience with cyclosporin eyedrops as well as pre-surgical low scores of visual acuity and all five QOL domains (except for "Satisfaction with Treatment") were found to significantly increase the post-surgical QOL scores (P < 0.01); however, pre-surgical Schirmer's test, break-up times of tear-film, and corneal fluorescein staining measurements showed no effects or contradictory correlations with post-surgical QOL scores., Conclusion: The life quality and satisfaction of DED patients showed significant improvement after SMG transplantation. Patients with severe and refractory DED could reap the benefits of surgery. A subjective QOL questionnaire is very valuable for predicting and evaluating the treatment effect., (Copyright © 2019. Published by Elsevier Inc.)

In this paper, we construct a piecewise deterministic Markov process to model the membrane voltage fluctuations driven by two ligand-gated channels. The series-solution method is applied to the third-order ordinary differential equations to get its general solutions. Also, the stationary probability density function (PDF) is just the special solution that satisfies certain boundary conditions. The bifurcation conditions of the PDF at the boundary are obtained analytically. As an application, the PDF is used to calculate the power dissipation of the ionic currents in the (nonequilibrium) steady states.

Purpose: Whether the submandibular gland (SMG) can be preserved during neck dissection in the surgical treatment of oral squamous cell carcinoma (OSCC) is controversial. This study investigated the SMG involvement rate and provides a basis for preserving the SMG during neck dissection in appropriate cases of OSCC., Materials and Methods: A comprehensive systematic review was conducted on the PubMed and MEDLINE, Embase, and Cochrane Library databases for studies on SMG involvement in OSCC published before December 2017 with a data analysis technique. Predictor variables were numbers of patients and resected SMGs, primary site, and tumor, node, and metastasis stage. Outcome variables were the number of involved SMGs and mode of involvement. Other variables, namely first author, publication year, mean age, and condition of neck lymph nodes at level Ib, also were extracted. A random-effects model was used to analyze the rate of SMG involvement in OSCC., Results: Twelve studies involving 2,126 patients with OSCC who underwent neck dissection were included in the study. Fifty-two SMGs were involved, and the pooled involvement rate was 2% (I 2  = 73%; 95% confidence interval [CI], 1-3). Forty-eight SMGs were involved through direct spread from the primary site or extracapsular spread of positive lymph nodes, and the pooled involvement rate was 1.9% (I 2  = 72%; 95% CI, 0.9-3.1). Except for direct spread, 4 SMGs were involved through the intraglandular lymph node or carcinoma growing along Wharton ducts, and the pooled involvement rate was only 0.1% (I 2  = 0%; 95% CI, 0-0.2)., Conclusions: The rate of SMG involvement in OSCC is very low, and the most common mode of involvement is by direct spread. The SMG might be preserved during neck dissection in OSCC when it is unlikely to be involved through direct spread., (Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Tight junction (TJ) proteins play a dynamic role in paracellular fluid transport in salivary gland epithelia. Most TJ studies are carried out in mice and rats. However, the morphology of rodent salivary glands differs from that of human glands. This study aimed to compare the histological features and the expression pattern of TJ proteins in porcine salivary glands with those of human and mouse. The results showed that porcine parotid glands were pure serous glands. Submandibular glands (SMGs) were serous acinar cell-predominated mixed glands, whereas sublingual glands were mucous acinar cell-predominated. Human SMGs were mixed glands containing fewer mucous cells than porcine SMGs, whereas the acinar cells of murine SMGs are seromucous. The histological features of the duct system in the porcine and human SMGs were similar and included intercalated, striated and excretory ducts, but the murine SMG contained a specific structure, the granular convoluted tubule. TJ proteins, including claudin-1 to claudin-12, occludin and zonula occludin-1 (ZO-1), were detected in the porcine major salivary glands and human SMGs by RT-PCR; however, claudin-6, claudin-9 and claudin-11 were not detected in the murine SMG. As shown by immunofluorescence, claudin-1, claudin-3, claudin-4, occludin and ZO-1 were distributed in both acinar and ductal cells in the porcine and human SMGs, whereas claudin-1 and claudin-3 were mainly present in acinar cells, and claudin-4 was mainly distributed in ductal cells in the murine SMG. In addition, 3D images showed that the TJ proteins arranged in a honeycomb-like structure on the luminal surface of the ducts, whereas their arrangements in acini were irregular in porcine SMGs. In summary, the expression pattern of TJ proteins in salivary glands is similar between human and miniature pig, which may be a candidate animal for studies on salivary gland TJ function., (© 2018 Anatomical Society.)

Background: Submandibular gland (SMG) transplantation is a successful treatment approach for patients with severe dry eye. However, duct obstruction can occur post-transplant., Methods: We studied nineteen patients with duct obstruction of transplanted SMGs, including five interventional modalities: stone removal; secretory stimulation (to mimic "internal irrigation" with substantial secretory flow); irrigation; surgical opening of stenosis and orifice reconstruction; cephalic vein bypass and Wharton's duct reconstruction., Results: A solitary stone was found and removed in one patient. Duct blockages like mucus plug were cleared by secretory stimulation in three patients, and by normal saline irrigation in two grafts. In the remaining 13 patients, irrigation failed and surgical opening was performed. Orifice reconstruction succeeded in six of the eight patients, whose stenosis was near the orifice. Wharton's duct reconstruction was successful in two of the five cases where stenosis was located in the middle segment of the duct., Conclusion: Transplanted SMGs obstruct for various reasons. Stone, which is easy to diagnose and treat, should be excluded first. Non-organic blockage and stenosis were semblable in clinic. Therefore, subsequent steps should be a diagnostic/therapeutic trial of secretory stimulation, followed by irrigation; failure of these interventions suggests the diagnosis of duct stenosis, necessitating surgical recanalization., (Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Potassium channels mainly contribute to the resting potential and re-polarizations, with the potassium electrochemical gradient being maintained by the pump Na + /K + -ATPase. In this paper, we construct a stochastic model mimicking the kinetics of a potassium channel, which integrates temporal evolving of the membrane voltage and the spontaneous gating of the channel. Its stationary probability density functions (PDFs) are found to be singular at the boundaries, which result from the fact that the evolving rates of voltage are greater than the gating rates of the channel. We apply PDFs to calculate the power dissipations of the potassium current, the leakage, and the gating currents. On a physical perspective, the essential role of the system is the K + -battery charging the leakage (L-)battery. A part of power will inevitably be dissipated among the process. So, the efficiency of energy transference is calculated.

Background: Immunoglobulin G4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated systemic disease. Despite its good response to steroid therapy, its treatment protocol is not standardized and the long-term outcome is controversial. The study was conducted to determine the short-term and long-term outcomes of IgG4-RS patients treated with glucocorticoids and steroid-sparing immunosuppressive agents, to analyze secretory function, serological and radiological changes in salivary glands and to assess the usefulness of serum IgG4 level as an indicator of disease activity., Methods: IgG4-RS patients who were treated for more than 3 months were enrolled. Serological tests, salivary gland function assessment and computed tomography (CT) were performed before treatment and during follow up. The treatment outcomes in the short and the long term were evaluated, and the relationship between serum IgG4 level and salivary gland volume was analyzed., Results: Glucocorticoids were used in all 43 patients and steroid-sparing immunosuppressive agents in 38 patients (88.4%). The follow-up period was 24.6 ± 14.9 months. Clinical remission was achieved in all patients after induction therapy. During short-term observation, salivary gland secretion significantly increased, and the serum IgG4 levels, the volumes and CT values of submandibular and parotid gland decreased significantly (P < 0.001). For long term, relapse occurred in 32.5% patients within 55 months in the regularly treated group, while all seven irregularly treated patients relapsed. However, the relapse-free survival curves were not significantly different between the steroid monotherapy and the combination therapy groups (P = 0.566). Submandibular glands, lacrimal glands, sublingual glands, nasal and paranasal cavity were commonly relapsing organs. In clinically stable patients, a serologically unstable condition occurred in 54.9% patients within 55 months and medication adjustment was performed accordingly. Volume changes in the submandibular and parotid glands were associated with serum IgG4 levels and time of follow up (R 2 adjusted  = 0.905, P < 0.0001 and R 2 adjusted  = 0.9334, P < 0.0001, respectively)., Conclusions: The combination of glucocorticoid and steroid-sparing agents could be effective for treating IgG4-RS, and restoring salivary gland function. Serum IgG4 levels could predict disease activity.

Background: The clinicopathological features and outcomes of squamous cell carcinoma (SCC) of the tongue in patients of different age groups remain debatable., Methods: Medical records of 457 patients with tongue SCC were reviewed, grouped by age, followed up, and compared., Results: Sex and TNM stage showed no intergroup differences. Tongue SCC in patients ≤30 years had the most advanced TNM classification and greatest proportion of poorly differentiation tumors. Both disease-free survival (DFS) and disease-specific survival (DSS) showed no statistically significant difference between the youngest and the oldest groups (P = .605 and P = .520). However, there was a tendency of higher death rate caused by recurrence or metastasis in the youngest group compared with the others (91.7% vs 75.4% and 77.4%)., Conclusion: Young patients had a tendency of higher death rate caused by recurrence or metastasis than middle-age and older patients; therefore, a larger case sample is needed for further confirmation., (© 2017 Wiley Periodicals, Inc.)

Background: A reliable anterior facial vein (AFV, donor vein) is cardinal for the success of submandibular gland (SMG) transplantation. This study determined the impact of computed tomographic (CT) venography in identifying AFV variations for SMG transplantation., Methods: CT venography was performed in consecutive patients with severe dry eye prior to SMG transplantation in order to identify disadvantageous AFV variations for vascular anastomosis, namely, AFVs that did not drain the SMG and those that did not match the superficial temporal vein (STV, recipient vein; AFV:STV caliber ratio, ≥3). The CT results were compared with the intraoperative findings for the diagnostic accuracy., Results: Forty-two donors were included. Compared with the intraoperative findings, the CT results accurately identified AFV-STV caliber mismatches (P = 1.00; sensitivity and specificity, 100%). In the identification of AFVs not draining the SMG, CT showed 94.7% sensitivity and 100% specificity (P = 0.25). According to the CT findings, 10 contralateral SMGs with AFVs (23.8%), instead of ipsilateral donors, were selected for transplantations (conventionally ipsilateral donor was the first choice). The surgical success rate was 95.2% (40/42)., Conclusion: CT venography is valuable in determining disadvantageous AFV variations for anastomosis and choosing a reliable donor for SMG transplantation., (Copyright © 2017. Published by Elsevier Ltd.)

Background: To develop the Chinese version of quality of life scale for dry eye patients based on the Impact of Dry Eye on Everyday Life (IDEEL) questionnaire and to assess the reliability and validity of the developed scale., Methods: The original IDEEL was adapted cross-culturally to Chinese language and further developed following standard procedures. A total of 100 Chinese patients diagnosed with dry eye syndrome were included to investigate the psychometric properties of the Chinese version of scale. Psychometric tests included internal consistency (Cronbach's ɑ coefficients), construct validity (exploratory factor analysis), and known-groups validity (the analysis of variance)., Results: The Chinese version of Dry Eye Related Quality of Life (CDERQOL) Scale contains 45 items classified into 5 domains. Good to excellent internal consistency reliability was demonstrated for all 5 domains (Cronbach's ɑ coefficients range from 0.716 to 0.913). Construct validity assessment indicated a consistent factorial structure of the CDERQOL scale with hypothesized construct, with the exception of "Dry Eye Symptom-Bother" domain. All domain scores were detected with significant difference across three severity groups of dry eye patients (P < 0.05) except for "Satisfaction with Treatment" domain, indicating good known-groups validity., Conclusions: The results indicated that the CDERQOL scale is a reliable and valid instrument for patients with dry eye syndrome among Chinese population, and could be used as a supplementary diagnostic and treatment-effectiveness measure.

An analytical steady-state solution of the stochastic model describing the integrated dynamics of the membrane voltage and the gating of a single channel is presented. The voltage density function experiences bifurcation in the parameter space, and the threshold is determined by the comparison between the rates of the voltage evolution and that of the channel gating. It is singular at the reversal potential if the voltage evolves faster than the channel gating. As an application, the entropy production rate associated with the gating currents is calculated; its variation tendency in parameter space is consistent to that of the number of transitions counted from the sample paths. The analysis in this paper identifies the values of parameters that justify the formation of the voltage pulse and the efficient energy cost, which is associated with the singularity of the voltage density functions.

Objectives: The aim of this cross-sectional study was to investigate the relationship between minor salivary gland (MSG) flow rates and oral dryness degrees in patients with xerostomia induced by primary Sjögren's syndrome (pSS), IgG4-related sialadenitis (IgG4-RS), radiation therapy-induced dry mouth (RTDM), or Steven-Johnson syndrome (SJS)., Design: 160 patients with pSS, IgG4-RS, RTDM, or SJS and their age- and sex-matched healthy control subjects were enrolled. The whole saliva flow rates and MSG flow rates were measured in four locations, including the upper labial, lower labial, buccal, and palatal mucosae. The degree of oral dryness was assessed in patient groups using the summated xerostomia inventory (SXI)., Results: The flow rates of whole saliva and most MSGs in patient groups were significantly lower than the flow rates in healthy control groups (P<0.05). The mean relative percentage of decrease in saliva flow rates was smaller in MSGs than in whole saliva in patient groups (P<0.05), indicating that these disorders have less impact on MSGs. Among the four MSG locations (the upper labial, lower labial, buccal, and palatal), buccal glands showed the highest flow rates in patient groups (P<0.05). SXI scores were significantly higher in pSS and RTDM patients than in IgG4-RS and SJS patients (P<0.05). The degree of xerostomia varied among different patient groups (P<0.05) and there was no clear correlation between MSG flow rates and SXI scores (P>0.05)., Conclusions: MSG function is significantly reduced in pSS, RTDM, IgG4-RS, and SJS patients, but this reduction is more pronounced in the major salivary glands., (Copyright © 2016. Published by Elsevier Ltd.)

Background: The findings of currently available studies are not consistent with regard to the association between the risk of cancer and ginseng consumption. Therefore, we aimed to evaluate this association by conducting a meta-analysis of different studies., Methods: To systematically evaluate the effect of ginseng consumption on cancer incidence, six databases were searched, including PubMed, Ovid Technologies, Embase, The Cochrane Library, China National Knowledge Infrastructure, and Chinese VIP Information, from 1990 to 2014. Statistical analyses based on the protocol employed for a systematic review were conducted to calculate the summary relative risks (RRs) and 95% confidence intervals (CIs)., Results: We identified nine studies, including five cohort studies, three case-control studies, and one randomized controlled trial, evaluating the association between ginseng consumption and cancer risk; these studies involved 7,436 cases and 334,544 participants. The data from the meta-analysis indicated a significant 16% lower risk of developing cancer in patients who consumed ginseng (RR = 0.84, 95% CI = 0.76-0.92), with evidence of heterogeneity (p = 0.0007, I (2) = 70%). Stratified analyses suggested that the significant heterogeneity may result from the incidence data for gastric cancer that were included in this study. Publication bias also showed the same result as the stratified analyses. In addition, subgroup analyses for four specific types of cancer (colorectal cancer, lung cancer, gastric cancer, and liver cancer) were also performed. The summary RRs for ginseng intake versus no ginseng consumption were 0.77 for lung cancer, 0.83 for gastric cancer, 0.81 for liver cancer, and 0.77 for colorectal cancer., Conclusion: The findings of this meta-analysis indicated that ginseng consumption is associated with a significantly decreased risk of cancer and that the effect is not organ specific.

Purpose: To investigate whether capsaicin and carbachol promote secretion from and prevent duct obstruction in transplanted submandibular glands (SMGs)., Methods: This retrospective cohort study included consecutive patients with severe keratoconjunctivitis sicca and successful SMG transplantation. Patients were divided into 2 groups: an exposed group receiving both capsaicin and carbachol after surgery and an unexposed group receiving neither. Secretion changes in response to capsaicin and carbachol administration were recorded in the exposed group. The main outcome measures were the secretory flow rate and duct obstruction rate in the transplanted SMGs., Results: Forty-four patients (44 eyes) in the unexposed group and 115 patients (128 eyes) in the exposed group were followed up for more than 3 months postoperatively. The baseline characteristics were similar between the groups. The secretory flow rate before and 5, 25, 55 minutes after administration was 1 mm (0-2 mm) (median with interquartile range), 3 mm (1-5 mm), 4 mm (2-5 mm), 1 mm (0-2.5 mm), respectively, for capsaicin and 1 mm (0-3 mm), 1050 mm (450-1500 mm), 375 mm (150-600 mm), 0 mm (0-150 mm), respectively, for carbachol (P < 0.001 for both). In the exposed group, 6.2% of eyes had duct obstruction, whereas 18.2% of eyes in the unexposed group had duct obstruction (P = 0.031) (odds ratio = 0.3, 95% confidence interval, 0.105-0.856)., Conclusions: This study provides evidence that capsaicin and carbachol effectively promote secretion from and prevent duct obstruction in transplanted SMGs during at least 3 months after transplantation.

Objective: To investigate the distribution and drug resistance of anaerobic bacteria in the patients with oral and maxillofacial infection., Methods: Aerobic and anaerobic bacteria cultures from 61 specimens of pus from the patients with oral and maxillofacial infection in the Department of Oral and Maxillofacial Surgery, Peking University School of Stomatology were identified. The culture type was evaluated by API 20A kit and drug resistance test was performed by Etest method. The clinical data and antibacterial agents for the treatment of the 61 cases were collected, and the final outcomes were recorded., Results: The bacteria cultures were isolated from all the specimens, with aerobic bacteria only in 6 cases (9.8%), anaerobic bacteria only in 7 cases (11.5%), and both aerobic and anaerobic bacteria in 48 cases (78.7%). There were 55 infected cases (90.2%) with anaerobic bacteria, and 81 anaerobic bacteria stains were isolated. The highest bacteria isolation rate of Gram positive anaerobic bacteria could be found in Peptostreptococcus, Bifidobacterium and Pemphigus propionibacterium. No cefoxitin, amoxicillin/carat acid resistant strain was detected in the above three Gram positive anaerobic bacteria. The highest bacteria isolation rate of Gram negative anaerobic bacteria could be detected in Porphyromonas and Prevotella. No metronidazole, cefoxitin, amoxicillin/carat acid resistant strain was found in the two Gram negative anaerobic bacteria. In the study, 48 patients with oral and maxillofacial infection were treated according to the results of drug resistance testing, and the clinical cure rate was 81.3%., Conclusion: Mixed aerobic and anaerobic bacteria cultures are very common in most oral and maxillofacial infection patients. Anaerobic bacteria culture and drug resistance testing play an important role in clinical treatment.

Ultraviolet B (UVB) irradiation is the most common cause of radiation damage to the eyeball and is a risk factor for human corneal damage. We determined the protective effect of fucoxanthin, which is a carotenoid found in common edible seaweed, on ocular tissues against oxidative UVB-induced corneal injury. The experimental rats were intravenously injected with fucoxanthin at doses of 0.5, 5 mg/kg body weight/day or with a vehicle before UVB irradiation. Lissamine green for corneal surface staining showed that UVB irradiation caused serious damage on the corneal surface, including severe epithelial exfoliation and deteriorated epithelial smoothness. Histopathological lesion examination revealed that levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF), significantly increased. However, pretreatment with fucoxanthin inhibited UVB radiation-induced corneal disorders including evident preservation of corneal surface smoothness, downregulation of proinflammatory cytokine expression, and decrease of infiltrated polymorphonuclear leukocytes from UVB-induced damage. Moreover, significant preservation of the epithelial integrity and inhibition of stromal swelling were also observed after UVB irradiation in fucoxanthin-treated groups. Pretreatment with fucoxanthin may protect against UVB radiation-induced corneal disorders by inhibiting expression of proinflammatory factors, TNF-α, and VEGF and by blocking polymorphonuclear leukocyte infiltration.

The aim of this study was to determine the role of ultrasonography in the diagnosis and follow-up evaluation of immunoglobulin G4-related sialadenitis. In this study, 42 patients with immunoglobulin G4-related sialadenitis underwent ultrasonography of the parotid and submandibular glands, and the sonographic appearance was compared with the pathologic findings. Post-treatment ultrasonographic appearance was compared with the pre-treatment findings in 30 patients who received immunomodulatory therapy. The ultrasonographic appearance of the affected glands was divided into five patterns: superficial hypo-echoic, multiple hypo-echoic foci, whole-gland heterogeneity, space occupying and normal echo. Histopathologic examination revealed marked lymphoplasmacytic inflammation and inter-lobular fibrosis, which were more severe in the superficial than deep portion of the affected glands. After treatment, the volume of the affected gland decreased significantly, the internal echo became more homogeneous and the superficial hypo-echoic area disappeared or was reduced. In conclusion, ultrasonography may play an important role in the diagnosis and follow-up evaluation of immunoglobulin G4-related sialadenitis., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)