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Six pairs of previously undescribed enantiomeric phytocannabinoid-like meroterpenoids, (±)-spinulinoids A‒F, and two naturally occurring compounds, (+)-rhododaurichromanic acid A and (E)-4-((3,7-dimethylocta-2,6-dien-1-yl)oxy)benzoic acid, together with one known congener, (-)-rhododaurichromanic acid A, were obtained from the twigs and leaves of Rhododendron spinuliferum. Their structures were established by their extensive spectral data (NMR and HRESIMS), ECD calculations, and single-crystal X-ray diffraction data. Spinulinoids A and B are unprecedented phytocannabinoid-like meroterpenoids constructed by the resorcinol moiety and a β-bisabolene unit, whereas spinulinoid C represents a rare adduct of quinone and β-bisabolene with a tricyclic 6/6/6 ring 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 © 2024 Elsevier Ltd. All rights reserved.)

Background: Internet hospitals (IHs) have rapidly developed as a promising strategy to address supply-demand imbalances in China's medical industry, with their capabilities directly dependent on information platform functionality. Moreover, a novel theory of "Trinity" smart hospital has provided advanced guidelines of IHs construction., Objective: To explore the construction experience, construction models, and development prospects based on operational data from IHs., Methods: Based on existing information systems and internet service functionalities, our hospital has built a "Smart Hospital Internet Information Platform (SHIIP)" for IHs operation, actively to expand online services, digitalize traditional healthcare, and explore healthcare services modes throughout the entire process and lifecycle. This article encompasses the platform architecture design, technological applications, patient service content and processes, healthcare professional support features, administrative management tools, and associated operational data., Results: Our platform has presented a remarkable set of data, including 82,279,669 visits, 420,120 online medical consultations, 124,422 electronic prescriptions, 92,285 medication deliveries, 6,965,566 pre-diagnosis triages, 4,995,824 offline outpatient appointments, 2,025 medical education articles with a total of 15,148,310 views, and so on. These data demonstrate the significant role of IH as an indispensable component of our physical hospital services, with a deep integration between online and offline healthcare systems., Conclusions: Attributing to extreme convenience and improved efficiency, our IH has achieved a wide recognition and use from both the public and healthcare workers, and the upward trends in multiple data metrics suggest a promising outlook for its sustained and positive development in the future. Our pioneering exploration holds tremendous significance and serves as a valuable guiding reference for IHs construction and the progressive development of the internet healthcare sector.

Ammonia （NH 3 ） is an important alkaline reactive nitrogen, which, as a precursor of fine particulate matter, raises public health issues. In this study, online NH 3 , SO 2 , NO 2 , PM 2.5 , and its water-soluble inorganic ions were detected to deduce the influence of NH 3 on aerosol liquid water content （AWC） and aerosol pH, including the formation of water-soluble secondary ions in PM 2.5 in winter in Changzhou, an ammonia-rich city in the Yangtze River Delta area in winter. The results showed that NH 4 + mainly existed in the form of NH 4 NO 3 and （NH 4 ） 2 SO 4 , and the remaining NH 4 + existed as NH 4 Cl. Owing to the NH 3 -NH 4 + buffer system, the aerosol pH values were found at 4.2 ± 0.4, which was positively correlated with the NH 3 content. The aerosol pH value variation narrowed with the increase in PM 2.5 concentration and tended to be between 4 to 5. AWC increased exponentially with the increase in humidity and SNA content, among which NH 4 NO 3 , （NH 4 ） 2 SO 4 , and NH 4 Cl contributed 58.5%, 18.4%, and 8.3%, respectively, due to their hygroscopicity. Aerosol pH, AWC, and NH 3 -NH 4 + conversion promoted the gas-to-particle conversion of SO 2 and NO 2 . In Changzhou, rich NH 3 -NH 4 + were found to maintain relatively high pH values, push up AWC, and promote the heterogeneous reaction of SO 2 , whereas NO 3 - generation was dominated by a homogeneous reaction, which was accelerated by NH 3 . According to the simulation results, relatively noticeable changes in aerosol pH and AWC could be found by the reduction of up to 30% of NH 3 .

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating condition associated with antiresorptive and antiangiogenic medications that are frequently used in treating osteoporosis and cancers. With the ability to produce high-resolution images with a lower radiation dose, cone beam computed tomography (CBCT) is an emerging technology in maxillofacial imaging that offers several advantages in evaluating MRONJ. This review aims to summarise the radiological features of MRONJ as observed via CBCT and highlight its advantages over two-dimensional plain films in assessing MRONJ. CBCT has the capability to detect early MRONJ lesions, characterise the extent and nature of lesions, distinguish MRONJ from other osseous pathologies, and assist in treatment planning. By leveraging the advantages of CBCT, clinicians can enhance their understanding of MRONJ, improve decision making, and ultimately optimize patient care.

Objectives: Microvascular bone flap jaw reconstruction has achieved satisfactory clinical outcomes. However, little is known about the long-term stability of the reconstructed jaw. This prospective longitudinal study aimed to investigate the long-term stability of jaw reconstruction and factors that were associated with it., Methods: Patients with successful computer-assisted osseous free-flap jaw reconstruction in the Department of Oral and Maxillofacial Surgery, Queen Mary Hospital, Hong Kong were recruited for this prospective longitudinal study. The three-dimensional jaw models at the pre-operative plan, post-operative 1-month, and 2 years were aligned and compared., Results: A total of 69 patients were recruited, among which 48 patients were available for the long-term analysis. Compared to 1-month after surgery, further deviation from the pre-operative plan was observed at post-operative 2 years. Lack of accuracy in surgery, segmental mandible resection especially with the involvement of mandible angles, and post-operative radiation therapy were identified as the significant factors affecting the positional stability of the reconstructed jaw (p < 0.05). Stable reconstruction was observed in the subgroup analysis of patients without post-operative radiation therapy., Conclusion: Up to the best of our knowledge, this is the first prospective longitudinal study reporting the long-term stability of jaw reconstruction and its affecting factors. Our data demonstrated that the reconstructed jaw position lacked stability over the postoperative period. How to improve long-term stability of reconstructed jaw thus optimize the functional outcomes warrants further studies., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study aimed to establish a neural-related gene risk score (NRGRS) for the prediction of head and neck squamous cell carcinoma prognosis and explore its predictive value on the benefit of immune checkpoint inhibitor therapy., Methods: Based on the transcriptome data of HNSCC patients (n = 546) from The Cancer Genome Atlas database, 37 neural-related hub genes were identified by weighted gene co-expression network analysis. Four genes (ITGA5, PYGM, GNG7 and ATP2A3) were identified to construct NRGRS using Lasso-Cox regression method based on the derivation cohort and validated in the Gene Expression Omnibus cohort (n = 109). The survival analysis was performed to validate the prognostic value of NRGRS and immune characteristics in NRGRS-defined subgroups were analyzed., Results: NRGRS-high patients had a worse overall survival than NRGRS-low patients. Tumors with high NRGRS were more likely to have high infiltration of naive CD4 + T cells, M0, M2 macrophages and resting mast cells, which illustrated suppressive immunity and less benefit from immunotherapy therapy., Conclusion: NRGRS strongly correlates with survival and is a promising biomarker to predict immunotherapy benefits for head and neck cancer patients. This study provides evidence for the potential correlation between neural-related transcriptome alteration and immune activity., (© 2022 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Background: Positive bone margins have been shown to be associated with worse locoregional control and survival performance in oral oncology patients. With the application of computer-assisted surgery and patient-specific surgical guides, the authors can accurately execute the preoperative osteotomy plan. However, how well the authors can predict the margin distance in the final histopathology with a preoperative computed tomography (CT) scan, the factors associated with it, and how much leeway CT should spare when designing the osteotomy planes during virtual surgical planning (VSP) remain to be investigated., Materials and Methods: Patients from January 2021 to December 2022 with benign or malignant jaw tumors and with signs of bone marrow involvement in the preoperative CT scan in our center were prospectively recruited to the study. VSP and measurement of the closest margin distance in the CT scan were performed by the single team of surgeons. The resection specimen was processed, and the margin distances were measured by a dedicated senior pathologist with the knowledge of orientation of the osteotomy planes., Results: A total of 35 patients were recruited, with 21 malignant and 14 benign cases. Sixty-eight bone margins were quantitatively analyzed. No significant difference in margin distances measured from the CT scan and final histopathology was detected ( P =0.19), and there was a strong correlation between the two (r s =0.74, P <0.01). A considerable amount of variance was detected in the level of discrepancy between margin distances measured in the CT scan and final histopathology (overall SD=6.26 mm, malignancy SD=7.44 mm, benign SD=4.40 mm). No significant correlation existed between the two margin distances when only maxilla tumor margins were assessed ( P =0.16)., Conclusion: The bone margin distance in VSP is reliably correlated to the final pathological margin distance. A leeway distance of 15mm and 9mm should be considered when designing the osteotomy planes for malignancy and benign cases, respectively. Extra attention should be paid to maxilla cases when predetermining the osteotomy planes during VSP., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To report the planning benchmark case results of the POTENTIAL trial-a multicenter, randomized, phase 3 trial-to evaluate the value of internal mammary nodal (IMN) irradiation for patients with high-risk breast cancer., Methods: All participating institutions were provided the outlines of one benchmark case, and they generated radiation therapy plans per protocol. The plans were evaluated by a quality assurance team, after which the institutions resubmitted their revised plans. The information on beams arrangement, skin flash, inhomogeneity corrections, and protocol compliance was assessed in the first and final submission., Results: The plans from 26 institutions were analyzed. Some major deviations were found in the first submission. The protocol compliance rates of dose coverage for the planning target volume of chest wall, supraclavicular fossa plus axilla, and IMN region (PTVim) were all significantly improved in the final submission, which were 96.2% vs. 69.2%, 100% vs. 76.9%, and 88.4% vs. 53.8%, respectively. For OARs, the compliance rates of heart D mean , left anterior descending coronary artery V 40Gy , ipsilateral lung V 5Gy , and stomach V 5Gy were significantly improved. In the first and final submission, the mean values of PTVim V 100% were 79.9% vs. 92.7%; the mean values of heart D mean were 11.5 Gy vs. 9.7 Gy for hypofractionated radiation therapy and 11.5 Gy vs. 11.0 Gy for conventional fractionated radiation therapy, respectively., Conclusion: The major deviations were corrected and protocol compliance was significantly improved after revision, which highlighted the importance of planning benchmark case to guarantee the planning quality for multicenter trials., (© 2023. The Author(s).)

Circular RNA (circRNA), one of the important non-coding RNA molecules with a closed-loop structure, plays a key regulatory role in cell processing. In this study, circRNAs of Epinephelus coioides, an important marine cultured fish in China, were isolated and characterized, and the network of circRNAs and mRNA was explored during Singapore grouper iridovirus (SGIV) infection, one of the most important double stranded DNA virus pathogens of marine fish. 10 g of raw data was obtained by high-throughput sequencing, and 2599 circRNAs were classified. During SGIV infection, 123 and 37 circRNAs occurred differential expression in spleen and spleen cells, indicating that circRNAs would be involved in the viral infection. GO annotation and KEGG demonstrated that circRNAs could target E. coioides genes to regulate cell activity and the activation of immune factors. The results provide some insights into the circRNAs mediated immune regulatory network during bony fish virus infection., (Copyright © 2023. Published by Elsevier Ltd.)

Background: This study aimed to assess the prevalence and the gender-specific risk factors of alcohol abuse/dependence among medical undergraduates during the post-COVID‑19 pandemic period in China., Method: The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) was used to identify respondents with alcohol abuse/dependence. A questionnaire on basic demographics and mental distresses (learning burnout, depression symptoms, anxiety symptoms, excessive daytime sleepiness, and history of mental disorders) was used. The logistic regression model was used to explore the associations between the above characteristics and alcohol abuse/dependence., Results: A total of 3,412 medical undergraduates were included in the analysis. Males showed a higher prevalence of alcohol abuse/dependence than females (16.6% vs 7.4%, p < 0.001). Alcohol abuse/dependence was associated with learning burnout (OR: 2.168, p < 0.001) and having a partner (OR: 1.788 p = 0.001) among female medical undergraduates. Among male medical undergraduates, excessive daytime sleepiness (OR: 1.788 p = 0.001) and older age (OR: 1.788, p = 0.001) were independently associated with alcohol abuse/dependence., Conclusion: Alcohol abuse/dependence was common among medical undergraduates during the post-COVID‑19 pandemic period. Substantial gender differences in the prevalence and risk factors of alcohol abuse/dependence were found among medical undergraduates in this study, which highlighted the need for timely gender-specific screening and interventions. However, the cross-sectional design adopted in this study has limited the examination of causality, thus further longitudinal studies are warranted., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Burnout, depression, and anxiety are highly prevalent among medical students, which often leads to their attrition. We aim to assess the inter-relationships of depression, burnout, and anxiety symptoms with dropout intention among Chinese medical undergraduates using the network analysis., Method: A total of 3,648 Chinese medical undergraduates were recruited through snowball sampling. Learning burnout scale, 9-item Patient Health Questionnaire (PHQ-9), and General Anxiety Disorder Scale (GAD-7) was used to assess burnout, depression, and anxiety symptoms, respectively. We used the EBICglasso model to estimate the network. We compared the network based on gender, study phase, and clinical experience., Results: After removing repeated submissions and incorrect responses to the trap question, 3,536 participants were included in the final analysis. The prevalence of burnout, depression, anxiety, and dropout intention was 38, 62.7, 38.4, and 39% respectively, which is consistent with previous findings. Network analysis suggested that anxiety and depression items clustered together and displayed several strong bridge connections, while burnout items formed another cluster. All the strongest edges were within the respective distress. Cynicism symptoms 'I am fed up with study' and 'I want to study but I feel that studying is boring' were the most central symptoms, while 'fatigue' and 'worthless' were the bridge symptoms within the burnout-depression-anxiety network. Other central symptoms included 'worthless', 'I can handle my courses', 'nervous', and 'uncontrollable worry'. Cynicism symptoms 'I am interested in my major' and 'I feel that the knowledge I have learned is useless' were mostly related to dropout intention. Gender, study phase, and clinical experience didn't affect the global strength of the burnout-depression-anxiety network., Conclusion: Our results indicated the predominance of cynicism symptoms within the burnout-depression-anxiety network and its substantial impact on dropout intention, suggesting that early detection and intervention for cynicism symptoms in Chinese medical students are in urgent need. Other central and bridge symptoms might also serve as potential targets for the prevention and treatment of burnout, depression, and anxiety among medical students. For example, studies suggest cognitive-behavioral therapy could quickly improve 'worthless', which might be beneficial in treating burnout, depression, and anxiety in medical students.

Objectives: Oncologic risk is a serious concern of submental artery island flaps. Here, we introduce the contralateral-based submental artery island flap (C-SAIF) and demonstrate its feasibility and long-term oncological safety in reconstructing oral cancer-related defects., Methods: An anatomical study was performed concentrating on the pedicle length in seven cadavers. Then, a retrospective study was carried out on C-SAIF patients operated on by a single team. The standard surgical technique of C-SAIF was conducted. Outcomes including operative time, length of hospital stay, volume of intraoperative blood loss, and scores of the Multidisciplinary Salivary Gland Society (MSGS) questionnaire were compared with a similar cohort reconstructed with anterolateral thigh free flap (ALTF). In addition, oncological outcomes were evaluated by the 5-year cumulative survival rate between C-SAIF and ALTF patients., Results: The pedicle length of C-SAIF was sufficient for the flap to be extended to the contralateral oral cavity. Fifty-two patients were included in the retrospective study, and nineteen of them underwent reconstruction with C-SAIF. The operative time of C-SAIF was shorter (p = 0.003), and the intraoperative blood loss was less (p = 0.004) than that of ALTF. There was no difference in MSGS scores. The results of survival analysis revealed comparable survival curves for the two groups in terms of overall survival, disease-specific survival, and disease-free survival., Conclusion: C-SAIF is a feasible and reliable flap for reconstructing oral cancer-related defects. Moreover, it is an effective island flap to preserve the perforator and pedicle without compromising oncological safety., (© 2023. The Author(s).)

Aim: To evaluate the efficacy and safety of simple TaTNE in the treatment of low rectal cancer compared with laparoscopic transabdominal TME., Methods: We collected patients with low rectal cancer admitted to our hospital between January 2019 and November 2021 who received simple TaTME or laparoscopic transabdominal TME. The main outcome was the integrity of the TME specimen. Secondary outcomes were the number of lymph nodes dissected, intraoperative blood loss, operative time, surgical conversion rate, Specimen resection length, circumferential margin (CRM), and distal resection margin (DRM), complication rate. In addition, the Wexner score and LARS score of fecal incontinence were performed in postoperative follow-up., Results: Pathological tissues were successfully resected in all patients. all circumferential margins of the specimen were negative. Specimen resection length was not statistically significant (9.94 ± 2.85 vs. 8.90 ± 2.49, P  > 0.05). The incidence of postoperative complications in group A ( n  = 0) was significantly lower than that in group B ( n  = 3) ( P  > 0.05). There was no significant difference in operation time between group A and group B (296 ± 60.36 vs. 305 ± 58.28, P  > 0.05). Among the patients with follow-up time less than 1 year, there was no significant difference in Wexner score and LARS score between group A and group B ( P  > 0.05). However, in patients who were followed up for more than 1 year, the Wexner score in group A (9.25 ± 2.73) was significantly lower than that in group B (17.36 ± 10.95) and was statistically significant ( P  < 0.05)., Conclusion: For radical resection of low rectal cancer, Simple TaTME resection may be as safe and effective as laparoscopic transabdominal TME, and the long-term prognosis may be better., 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., (© 2023 Yang, Chen, He, Wu, Liu, Li and Li.)

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication associated with antiresorptive medications managing osteoporosis, such as bisphosphonates (BPs). To date, there is very limited evidence from prospective, controlled studies to support or refute the controversial prevention regimen that if a discontinuation of BPs before dentoalveolar surgery, so called "drug holiday", is effective in reducing the risk of MRONJ development in patients with osteoporosis. We proposed an experimental animal study, aiming to investigate the prevention of MRONJ following tooth extractions in osteoporotic condition, with the implementation of a BP drug holiday., Methods: Twenty rats were subjected to bilateral ovariectomy. After establishing the osteoporotic condition, all rats were exposed to weekly injections of zoledronate acid (ZA) for 8 weeks. After ZA treatment, 10 rats were subjected to dental extraction and defined as control group, and the rest 10 rats assigned to the DH group had a drug holiday of 8 weeks prior to dental extraction. Eight weeks after the dentoalveolar surgery, bone turnover biomarker in serum, occurrence of MRONJ-like lesion and histomorphometric assessment of osteonecrosis in mandible, and bone microarchitecture indices in femur, were examined., Results: Eight weeks after dental extraction, the DH group showed a recovered osteoclastic activity, indicated by significantly increased number of osteoclasts in the mandibles and serum level of C-terminal telopeptides of type I collagen, as compared to the control group. No significant differences were observed in the gross-view and histological occurrences of MRONJ-like lesions between the two groups.There was no significant difference in bone microarchitecture in the femur between the control and DH groups before ZA therapy and 8 weeks after dental extraction., Conclusion: Our data provided the first experimental evidence in the osteoporotic animal model that the implementation of a BP holiday in prior to dental extractions could partially recover osteoclastic activity, but could not alleviate the development of MRONJ-like lesion or exacerbate the osteoporotic condition in the femur. Longer-term drug holiday, or combination of drug holiday and other prophylaxes to prevent MRONJ in patients with osteoporosis could be worth exploring in future studies, to pave the way for clinical managements., The Translational Potential of This Article: This in vivo prospective study reported that a recovery of osteoclastic activity by a BP drug holiday for 8 weeks in osteoporosis rats did not alleviate the development of MRONJ-like lesion followed by dental extractions. It contributes to the understanding of regimens to prevent MRONJ., Competing Interests: 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., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Chinese Speaking Orthopaedic Society.)

Background: Workplace violence in healthcare settings is a significant public concern that profoundly impacts healthcare workers. However, there is a dearth of knowledge regarding the prevalence of workplace violence and its correlation with suicidal ideation among undergraduate medical students in China during their clinical training. The objective of this study was to evaluate the prevalence of workplace violence inflicted by patients or their family members/visitors and to assess its association with suicidal ideation among undergraduate medical students., Method: The snowballing sampling technique was used to recruit Chinese medical students. A question designed by the research team was used to ask medical students about their encounters with workplace violence. Students' basic demographic information and mental distresses (learning burnout, depression symptoms, anxiety symptoms, alcohol abuse/dependence, excessive daytime sleepiness and history of mental disorders) were also assessed. As appropriate, the data were analysed using descriptive statistics, chi-square tests, independent-sample t -tests and multiple logistic regression., Results: Out of the 1402 undergraduate medical students who participated, 493 (35.2%) reported having experienced workplace violence inflicted by patients or their family members/visitors, of which 394 (28.1%) were verbal abuse, 14 (1.0%) were physical aggression, and 85 (6.1%) were suffered from both verbal abuse and physical aggression. Furthermore, students exposed to workplace violence were more likely to report suicidal ideation and had a higher prevalence of learning burnout, depression symptoms, anxiety symptoms, alcohol abuse/dependence and excessive daytime sleepiness. Depression symptoms, history of mental disorders, learning burnout and having a partner were significantly associated with suicidal ideation in this population., Conclusion: The prevalence of workplace violence inflicted by patients or their family members/visitors was high among undergraduate medical students in China. This may be associated with their mental distress and suicidal ideation. Consequently, it is crucial to strengthen workplace safety measures and promptly implement interventions to mitigate the potentially serious consequences.

Background: A high attrition rate in medical students has exacerbated the physician shortage in China. However, few studies have explored the risk factors of dropout intention in medical postgraduates. This study compared the prevalence of dropout intention and mental distress between medical and non-medical postgraduates in China and investigated risk factors for dropout intention. This study also explored the impact of medical postgraduates' perception of the Chinese healthcare environment on their mental status and dropout intention., Methods: This cross-sectional study was conducted using online questionnaires from October 2020 to April 2021. Convenience sampling was used to recruit postgraduates in different majors. Outcomes included dropout intention and potential risk factors, including mental distress, quality of life, and fatigue. Medical postgraduates were additionally assessed for healthcare environment satisfaction, burnout, career choice regret, and experiences of workplace violence. A logistic regression model was constructed to evaluate the association between dissatisfaction, mental distress, and turnover intention., Results: A total of 740 medical and 670 non-medical postgraduates participated in the survey. The rates of depression symptoms (33.8% vs. 39.0%, p < 0.001), anxiety symptoms (22.2% vs. 32.4%, p < 0.001), and somatic symptoms (34.7% vs. 42.4%, p = 0.004) were lower in medical postgraduates, while more medical postgraduates (58.4% vs. 48.4%, p < 0.001) reported dropout intention. Dissatisfaction with the healthcare environment (odds ratio [OR]: 1.65; 95% confidence interval [CI]: 1.17-2.34, p = 0.005), career choice regret (OR: 6.23; 95% CI: 4.42-8.78, p < 0.001), and high perceived stress (OR: 2.74; 95%CI: 1.90-3.94, p < 0.001) remained independently associated with turnover intention., Conclusions: Mental distress is common among postgraduates, calling for timely interventions. Medical postgraduates reported higher turnover intention. Healthcare environment perception also affected the mental health and dropout intentions of medical students. A decent future income, reduced workload, shorter duration medical training, and better doctor-patient relationships are urgently needed.

Purpose: To estimate the variations in clinical target volumes (CTVs) and organs at risk delineation within the quality assurance (QA) program of the POTENTIAL trial, which is a multicenter, randomized phase 3 trial evaluating postmastectomy radiation therapy (RT), with or without internal mammary nodal irradiation, for patients with high-risk breast cancer., Methods and Materials: The simulating computed tomography scan data set of a benchmark case was sent to the participating centers, and the delineation of CTVs and organs at risk was required to be completed by the investigators following protocol guidelines. All submitted contours were reviewed and compared with the reference contours created by the QA team, using quantitative geometric analysis regarding volume and the Jaccard Index (JCI), Dice similarity coefficient, Geographic Miss Index, Discordance Index, and mean distance to agreement. In addition to the whole-volume analysis of all structures, the combination contour of the supraclavicular fossa and level III and II axilla (CTVsc + axIII + axII) was further analyzed on a slice-by-slice basis., Results: The contours from 26 centers were reviewed and variations were observed between submission and reference. The variations of the CTV of the chest wall, contralateral breast, and heart were small, for which the mean JCI values were 0.62, 0.68, and 0.87, respectively. However, the mean JCI values of the CTV of the internal mammary nodal region, ipsilateral brachial plexus, left anterior descending coronary artery, and right coronary artery were 0.38, 0.21, 0.29, and 0.18, respectively, suggesting marked variations. In addition, marked under- and overoutlining variations were identified on 4 slices of CTVsc + axIII + axII on slice-by-slice analysis., Conclusions: There were residual contouring variations despite a detailed protocol being provided, confirming the importance of pretrial QA in RT and highlighting the need for education and consideration of a real-time central review of the target delineation before the trial participants begin RT., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

This paper reports a novel micro/nanostructure co-hot embossing technique. Gold-capped nanostructures were used as localized surface plasmon resonance (SPR) sensors and were integrated into a microfluidic channel. The advantage of the co-hot embossing technique is that the SPR sensors do not need to be aligned with the microfluidic channel while bonding to it. The integrated SPR sensor and microfluidic channel were first characterized, and the sensitivity of the SPR sensor to the refractive index was found using different concentrations of glycerol solutions. The SPR sensor was also used to quantify latent membrane protein (LMP-1) when modifying anti-LMP-1 at the surface of the SPR sensor. Different concentrations of LMP-1 samples were used to build a calibration curve., Competing Interests: The authors declare no conflict of interest.

The outbreak of the novel coronavirus disease 2019 (COVID-19) has posed a great impact on people's mental health, especially for undergraduate students. This study aimed to compare the mental health conditions and academic burnout between medical and non-medical undergraduates in China when the COVID-19 pandemic is mitigating. A cross-sectional online survey was conducted among 4,972 undergraduates between October 2020 and April 2021, when the pandemic was basically under control. The survey included basic demographics information and standardized scales to evaluate depression, anxiety, perceived stress, daytime sleepiness, alcohol abuse/dependence, quality of life, fatigue, and academic burnout. Compared with medical undergraduates, non-medical undergraduates had higher rates of moderate to severe depression symptoms (29.1% vs. 17.9%, P < 0.001), moderate to severe anxiety symptoms (19.7% vs. 8.9%, P < 0.001), alcohol abuse/dependence (16.3% vs.10.3%, P < 0.001), excessive daytime sleepiness (47.4% vs. 43.4%, P = 0.018), high perceived stress (34.7% vs. 22.2%, P < 0.001), high level of fatigue (51.8% vs. 42.2%, P < 0.001), low QOL (35.8% vs. 21.4%, P < 0.001), and higher academic burnout score (59.4 vs. 57.5, P < 0.001). Being non-medical undergraduates, depression, alcohol abuse/dependence, excessive daytime sleepiness, and high perceived stress were positively associated with academic burnout, while high QOL was negatively associated with the burnout (all P < 0.001). Excessive daytime sleepiness was the strongest predictor for academic burnout., (© 2022. The Author(s).)

Thermosensitive hydrogel scaffolds have attracted particular attention in three-dimensional (3D) cell culture. It is very necessary to develop a type of thermosensitive hydrogel material with low shrinkage, and excellent biocompatibility and biodegradability. Here, five types of thermosensitive microgels with different volume phase transition temperature (VPTT) or particle sizes were first synthesized using 2-methyl-2-propenoic acid-2-(2-methoxyethoxy) ethyl ester (MEO 2 MA) and oligoethylene glycol methyl ether methacrylate (OEGMA) as thermosensitive monomers by free radical polymerization. Their VPTT and particle sizes were investigated by a nanometer particle size meter and an ultraviolet spectrophotometer. The feasibility of using these P(OEGMA-co-MEO 2 MA) microgels to construct thermosensitive hydrogel by means of the thermal induction method is discussed for the first time. The prepared thermosensitive hydrogel with the optimum performance was screened for in situ embedding and three-dimensional (3D) culture of MCF-7 breast cancer cells. The experimental results of AO/EB and MTT methods indicate that the pioneering scaffold material has prominent biocompatibility, and cells grow rapidly in the 3D scaffold and maintain high proliferative capacity. At the same time, there is also a tendency to aggregate to form multicellular spheres. Therefore, this original P(OEGMA-co-MEO 2 MA) thermosensitive hydrogel can serve as a highly biocompatible and easily functionalized 3D cell culture platform with great potential in the biomedical area.

A copper-catalyzed cascade reaction of α-diazocarbonyl compounds with ethenesulfonyl fluoride (ESF) is developed, affording a variety of highly functionalized pyrazolyl aliphatic sulfonyl fluorides in good to excellent yields (66-98%). This transformation features broad substrates, exclusive regioselectivity, high atom economy and operational simplicity, thus providing a straightforward method for the direct construction of pyrazole-containing aliphatic sulfonyl fluorides, which will provide great applicable value in medicinal chemistry and other related disciplines.

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication associated with antiresorptive and antiangiogenic medications, of which impaired angiogenesis is a key pathological alteration. Since Magnesium (Mg)-based implants possess proangiogenic effects, we hypothesized that the biodegradable Mg implant could alleviate the development of MRONJ via enhancing angiogenesis., Methods: MRONJ model was established and divided into the Veh ​+ ​Ti group (Vehicle-treated rat, with Titanium (Ti) implant), BP ​+ ​Ti group (Bisphosphonate (BP)-treated rat, with Ti implant), BP ​+ ​Mg group (BP-treated rat, with Mg implant), BP ​+ ​Mg ​+ ​SU5416 group (BP-treated rat, with Mg implant and vascular endothelial growth factor (VEGF) receptor-2 inhibitor), BP ​+ ​Mg ​+ ​BIBN group (BP-treated rat, with Mg implant and calcitonin gene-related peptide (CGRP) receptor antagonist), and BP ​+ ​Mg ​+ ​SU5416+BIBN group (BP-treated rat, with Mg implant and VEGF receptor-2 inhibitor and CGRP receptor antagonist). The occurrence of MRONJ, alveolar bone necrosis, new bone formation and vessel formation were assessed by histomorphometry, immunohistochemistry, and micro-CT analysis., Results: Eight weeks after surgery, the BP ​+ ​Mg group had significantly reduced occurrence of MRONJ-like lesion and histological osteonecrosis, increased bone microstructural parameters, and increased expressions of VEGFA and CGRP, than the BP ​+ ​Ti group. By simultaneously blocking VEGF receptor-2 and CGRP receptor, the vessel volume and new bone formation in the BP ​+ ​Mg group were significantly decreased, meanwhile the occurrence of MRONJ-like lesion and histological bone necrosis were significantly increased., Conclusion: Biodegradable Mg implant could alleviate the development of MRONJ-like lesion, possibly via upregulating VEGF- and CGRP-mediated angiogenesis. Mg-based implants have the translational potential to be developed as a novel internal fixation device for patients with the risk of MRONJ., The Translational Potential of This Article: This work reports a biodegradable Mg implant which ameliorates the development of MRONJ-like lesions possibly due to its angiogenic property. Mg-based implants have the potential to be developed as a novel internal fixation device for patients at the risk of MRONJ., Competing Interests: The author(s) have no conflicts of interest relevant to this article., (© 2022 The Author(s).)

Background: Computer-assisted surgery has become the mainstream in mandibular reconstruction, but the lack of a standard measuring approach for spatial deviations of mandible hinders postoperative verification and the comparison of different subjects. This study aims to set up a comprehensive approach for measuring spatial deviations of computer-assisted mandibular reconstruction., Methods: A systematic review was conducted to extract all measurements for computer-assisted mandibular reconstruction. Thereafter, eligible measurements were included in the authors' comprehensive approach, which categorized the measurements according to different anatomical structures and landmarks., Results: A total of 80 studies were included in the authors' systematic review, and 31 measurements were extracted. The authors established a comprehensive panel of anatomical landmarks to facilitate measurement, including parts, points, lines, planes, and angles. These measurements encompassed spatial deviations of the overall mandible, condyle, gonial angle, bone grafts, midline, surgical plate, osteotomy, and miscellaneous indicators. A calculation spreadsheet was developed to collect landmarks and compute deviations automatically with built-in formulas. Finally, a simplified panel of measurements was recommended for spatial deviations of mandibular reconstruction., Conclusions: A comprehensive approach for measuring spatial deviations of computer-assisted mandibular reconstruction was established. Future studies will confirm this approach as an effective and scientific system for postoperative verification of computer-assisted mandibular reconstruction., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Mandibular osteoradionecrosis (ORN) is a devastating complication secondary to the radiotherapy of head and neck cancer. The nutritional status of ORN patients is compromised, but remains rarely studied. We aimed to evaluate the overall nutritional status of patients with ORN and explore the risk factors behind poor nutrition., Methods: This is a single-institution cross-sectional study. Patients diagnosed with ORN were consecutively recruited in a tertiary teaching hospital from July 2017 to August 2019. Multiple laboratory markers and physical indicators were examined to profile their nutritional status. The potential risk factors of poor nutrition were explored by logistic regression., Results: A total of 107 patients with ORN were recruited. Among them, almost all patients (95.3%) had at least one laboratory marker lower than the normal physiological range. A total of 40 (37.5%) patients were categorized as undernutrition, who had lower serum albumin (mean difference: 1.8 ± 0.8 g/L; p = .02), prealbumin (mean difference: 26.8 ± 10.8 mg/L; p = .02), and BMI (3.8 ± 0.4 kg/m 2 ; p < .0001) compared to patients of normal nutrition. Notably, the multivariate logistic regression indicated that patients with semi-liquid diet had 14.41 (95% CI: 3.03-68.54, p = .001) times; patients with liquid diet had 5.70 (95% CI: 1.55-20.98, p = .009) times more likely to be in undernutrition, as compared to patients with regular diets., Conclusions: This is the first study characterizing the poor nutritional status in ORN patients. Patients having semi-liquid or liquid diets tended to have poorer nutritional status. The nutritional status of ORN patients should be underlined for professional nutritional supports so as to enhance their quality of life. More studies are warranted., (© 2020 Wiley Periodicals LLC.)

Background: Computer-assisted surgeries (CAS) are increasingly being adopted as the treatment of choice for jaw reconstructions with osseous free flaps. Although unexpected change of surgical plans remains a major concern of CAS, there are few studies focusing on this unfavorable clinical scenario. The aim of the present study was to investigate the rate of unexpected change of surgical plans and potential influential parameters, and to discuss the contingency strategies., Methods: A retrospective study was performed to evaluate all the patients who underwent computer-assisted jaw resections and osseous free flap reconstructions. The postoperative radiographs were reviewed and compared with the preoperative surgical plans. Operating records were examined to analyze the reasons for unexpected change of surgical plans and the management. The potential influential parameters for the change of surgical plans were analyzed using Fisher-exact test. The difference was regarded as statistically significant for a p-value less than 5%., Results: From Nov 2014 to Oct 2021, a total of 98 consecutive computer-assisted free flap jaw reconstruction cases with osseous free flaps were included in this study. Our experience showed that 5.1% of the patients (five cases) needed intra-operative change of the surgical plans. We summarized the unexpected change of surgical plans and the contingency strategies as four clinical scenarios, including extended resection and reconstruction, shortened resection and reconstruction, modified resection without changing reconstruction, and modified reconstruction without changed resection. None of the potential influential parameters was identified as significant in relation to unexpected change of surgical plans intraoperatively., Conclusion: Our experience shows that with the comprehensive methodology for computer-assisted free flap jaw reconstruction surgery planning, we can minimize the possibility of unexpected change of surgical plans during surgery. The lessons learned from our 98 consecutive cases can help beginners prevent unexpected change of surgical plans and rationalize contingency strategies in computer-assisted free flap jaw reconstruction., 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. The handling editor is currently organizing a Research Topic with one of the authors RS., (Copyright © 2022 Pu, Choi, Yang, Zhu and Su.)

Objectives: Although computer-assisted surgery using fibula flap has been widely applied for oncologic jaw reconstruction in recent years, the inaccurate positioning of the fibula harvest guide brings sliding and rotational errors, which leads to compromised accuracy in simultaneous implant placement and dental rehabilitation. This study aimed to develop a novel three-dimensional (3D)-printed patient-specific fibula malleolus cap to increase oncologic reconstruction accuracy., Methods: In this prospective comparative study with a recent historical control cohort, patients in need of oncologic jaw reconstruction with fibula free flaps were recruited. In the study group, the fibula was harvested with the guide of the malleolus cap, whereas in the control group, without the malleolus cap. Deviations of location and angulation of distal fibula osteotomies, jaw reconstruction segments, and simultaneous dental implants were compared., Results: Twenty patients were recruited, with 10 in each arm. The application of the malleolus cap significantly reduced the deviations in locations and angles of distal fibula osteotomies, from 9.5 to 4.1 mm and 25.3° to 8.7°. For the simultaneous dental implants placed in the fibula flaps, there was a significant increase in the accuracy of implant platform locations (the average deviation from 3.2 to 1.3 mm), apex locations (from 3.8 to 1.5 mm), and angles (from 11.3° to 4.6°). No significant difference was detected in the accuracy of fibula reconstruction segments., Conclusions: We developed a novel fibula malleolus cap to overcome the sliding and rotational errors during fibula flap harvesting for oncologic jaw reconstruction, with increased accuracy in simultaneous dental implants. This is a step forward to achieve a satisfactory functional outcome of jaw reconstruction with dental rehabilitation., 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 © 2022 Pu, Choi, Yeung, Yang, Zhu and Su.)

Spatial deviations of the temporomandibular joint (TMJ) after oncological mandibular reconstruction are important to the aesthetic and functional rehabilitation. The aim of this study was to clarify whether and how three dimensionally (3D) printed patient-specific surgical plates, and the preservation of the condyle or ramus, affect spatial deviations of the TMJ. A total of 33 patients who underwent mandibular reconstruction via computer-assisted surgery were included. Regarding absolute deviations, patients in the 3D-printed plate group showed smaller TMJ deviations compared to those in the conventional plate group. There was no difference in absolute deviations of the TMJ regardless of whether the condyle or ramus was preserved. Regarding physiological deviations, the impact on the contralateral TMJ was smaller in the 3D-printed plate group. Patients with both the condyle and ramus removed had significantly higher deviations of the condyle and joint space. In summary, 3D-printed patient-specific surgical plates improved the spatial accuracy of the TMJ. Under physiological conditions, TMJ deviations on the operated side were mainly affected by the preservation of the condyle. Removal of both the condyle and ramus caused more severe spatial interference to the TMJ; this should be further confirmed., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. Viruses can hijack the glycosylation machinery of host cells to shield themselves from the host's immune response and attenuate antibody efficiency. However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants., Methods: We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. Viral entry was determined by luciferase, immunoblotting, and immunofluorescence assays. Genome-wide association study (GWAS) revealed a significant relationship between STT3A and COVID-19 severity. NF-κB/STT3A-regulated N-glycosylation was investigated by gene knockdown, chromatin immunoprecipitation, and promoter assay. We developed an antibody-drug conjugate (ADC) that couples non-neutralization anti-spike antibody with NGI-1 (4G10-ADC) to specifically target SARS-CoV-2-infected cells., Findings: The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. STT3A is a key glycosyltransferase catalyzing spike glycosylation and is positively correlated with COVID-19 severity. We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity., Interpretation: Our results indicate that targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC can exert profound impacts on SARS-CoV-2 variant infectivity. Thus, we have identified a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro., Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section., Competing Interests: Declaration of Competing Interest H.-C. H., Y.-J. L., and C.-W.L. declared inventorship with US/ 63/262,926 patent listed on 2021, ANTIBODY-DRUG CONJUGATE FOR REDUCING MEMBRANE RECEPTOR GLYCOSYLATION. The remaining authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: In recent years, deep learning has been widely used in a variety of ophthalmic diseases. As a common ophthalmic disease, meibomian gland dysfunction (MGD) has a unique phenotype in in-vivo laser confocal microscope imaging (VLCMI). The purpose of our study was to investigate a deep learning algorithm to differentiate and classify obstructive MGD (OMGD), atrophic MGD (AMGD) and normal groups. Methods: In this study, a multi-layer deep convolution neural network (CNN) was trained using VLCMI from OMGD, AMGD and healthy subjects as verified by medical experts. The automatic differential diagnosis of OMGD, AMGD and healthy people was tested by comparing its image-based identification of each group with the medical expert diagnosis. The CNN was trained and validated with 4,985 and 1,663 VLCMI images, respectively. By using established enhancement techniques, 1,663 untrained VLCMI images were tested. Results: In this study, we included 2,766 healthy control VLCMIs, 2,744 from OMGD and 2,801 from AMGD. Of the three models, differential diagnostic accuracy of the DenseNet169 CNN was highest at over 97%. The sensitivity and specificity of the DenseNet169 model for OMGD were 88.8 and 95.4%, respectively; and for AMGD 89.4 and 98.4%, respectively. Conclusion: This study described a deep learning algorithm to automatically check and classify VLCMI images of MGD. By optimizing the algorithm, the classifier model displayed excellent accuracy. With further development, this model may become an effective tool for the differential diagnosis of MGD., 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 Zhang, Zhao, Lin, Wu, Liu, Zhang, Shao and Yang.)

Background: Computer-assisted jaw reconstruction (CAJR) has benefits in reducing operation time and improving reconstruction accuracy, compared to conventional freehand jaw reconstruction. However, no information is available regarding learning curves in CAJR with the use of 3D-printed patient-specific surgical plates (PSSP). The purpose of this study was to assess surgical outcomes and learning curve for the first 58 consecutive CAJR using 3D-printed PSSP performed by a single surgical team in a single institution., Methods: In a prospective study, consecutive patients who underwent free flap CAJR using 3D-printed PSSP were included. The determination of proficiency, based on the cumulative sum of surgical success (no major adjustment of 3D-printed PSSP, flap survival) passing the acceptable boundary line of cumulative sum analysis, was the primary outcome. To find out any potential factors influencing the learning curve, baseline characteristics of patients were compared before and after proficiency achievement. Secondary outcomes included inflexion points of the total operation time, blood loss, length of hospital stay, and bone graft deviation, measured by the cumulative sum analysis., Results: From December 2016 to November 2020, 58 consecutive cases underwent surgery performed by a single surgical team. The overall surgical success rate was 94.8% (55/58). A three-stage learning curve of primary outcome was observed. The proficiency was achieved after 23 cases. The proportions of advanced tumor staging and concomitant surgery after obtaining proficiency were significantly higher than those before achieving proficiency ( p = 0.046 and p < 0.001, respectively). Mean values of operation time, intraoperative blood loss, length of hospital stay, and bone graft deviation were 532.5 ± 119.2 min, 1,006.8 ± 547.2 ml, 16.1 ± 6.3 days, and 0.9 ± 1.2 mm, respectively. Two trends of learning curve were observed in the CUSUM analyses of total operation time, length of hospital stay, and bone graft deviation, in which the first and second inflexion points occurred between 8 and 17 cases and between 43 and 46 cases, respectively., Conclusion: Our results revealed a three-stage learning curve of CAJR with the use of PSSP, including initial learning, plateau, and overlearning. Based on CUSUM analysis, the surgical proficiency was achieved after 23 cases, and total operation time, length of hospital stay, and bone graft deviation stabilized after 8-17 cases., 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 Zhu, Choi, Wong, Pu, Yang and Su.)

Background: The occupancy of healthcare resources by the COVID-19 outbreak had led to the unmet health needs of non-COVID-19 diseases. We aimed to explore whether the social media information could help surveil and understand the characteristics of unmet non-COVID-19 health needs during the COVID-19 outbreak in Wuhan city., Methods: This was an observational study based on social media data. The study period was set during the 3 months of the COVID-19 outbreak. Non-COVID-19 urgent and emergent health needs in Wuhan city were derived from Sina Weibo-one of China's largest social media platforms. Lag Spearman correlation was used to investigate the epidemiological relationship between the COVID-19 outbreak and non-COVID-19 health needs. Patient's primary diseases and needed care were annotated and categorized according to the International Classification of Diseases 11th Revision. The delay time in seeking help was calculated and compared., Results: After screening 114,795 Weibo posts, a total of 229 patients with non-COVID-19 health needs were included in our study. There were significant correlations between the daily number of COVID-19 cases at a 10-day lag, deaths at a 5-day lag, and non-COVID-19 Weibo. The actual number of non-COVID-19 patients with urgent and emergent health needs was estimated to be about 6,966. Patients with non-COVID-19 health needs were skewed to those aged 50 to 70 years. The non-COVID-19 diseases were diverse, with 46.3% as non-neoplastic diseases and 53.7% as neoplasms. The most needed cares were palliative cancer care (22.7%), chemotherapy (18.8%), and critical care (17.0%). The median delay in seeking help was 3 days [interquartile range (IQR), 1 to 15 days] for acute care, and 18.5 days (IQR, 6 to 30 days) for cancer care., Conclusions: Our preliminary findings in Wuhan city indicated that the social media data might provide a viable option to surveil and understand the unmet health needs during an outbreak. Those heterogeneous health needs derived from the social media data might inspire a more resilient healthcare system to address the unmet needs promptly., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-1769). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Objective: Oral and maxillofacial surgery (OMFS) is a high-risk specialty involving airway and aerosol-generating procedures, which is potentially of more risk in the era of coronavirus disease 2019 (COVID-19). We aimed to identify the impact of COVID-19 on the disease pattern of OMFS inpatients and surgeries under general anesthesia in a comparative study. Materials and Methods: We reviewed the admission and operating theater records of OMFS patients from Jan 1 to Aug 31 in 2020 and 2019. The total number of cases, presenting disease patterns, and proportion of essential and non-essential medical services were compared between 2020 and 2019. Results: There were 664 admissions and 356 general anesthesia surgical procedures included in this study. Both admission and surgery numbers were significantly reduced in 2020, compared with 2019 ( p = 0.012 and 0.007, respectively). The proportion of malignancy cases increased significantly, whereas that of cleft lip and palate and temporomandibular disorder (TMD) decreased. There was a significant increase in the proportion of essential services compared with non-essential services in 2020 compared with 2019. Conclusion: Our results first reported the epidemiological data of the impact of COVID-19 on OMFS disease pattern in a comparative study. The change of disease pattern and caseload will have a long-term impact on OMFS patient care, education, and training during the pandemic. Our paper provides evidence for health policy makers to consider the relocation of medical resources and optimization of medical education and services., 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 Pu, McGrath, Leung, Choi, Yang, Li and Su.)

Background: Conventional freehand immediate placement of dental implants is technically challenging in the jaw reconstructive surgery. Computer-aided surgery might be the best solution, however, there has not been any standard approach to ensure the accuracy and efficiency of simultaneous dental implants in fibula flap jaw reconstruction., Purpose: We aim to evaluate the clinical outcome of simultaneous dental implant in fibula flap using the "three-in-one" patient-specific surgical guide (3-in-1-PSSG) in an open-label, prospective, single-arm, and single-center clinical trial., Materials and Methods: A novel computer-aided designed and three-dimensional (3D) printed 3-in-1-PSSG, which contains functions of fibula segmentation, surgical plate positioning and implant placement, was used to facilitate the reconstructive surgery and simultaneous dental implant placement. The intraoperative success of dental implant placement, implant survival rate and accuracy of dental implant placement were reported., Results: From November 2018 to June 2020, 15 consecutive patients with 48 dental implants were enrolled in this study. Fifteen 3-in-1-PSSGs were fabricated with a mean number of dental implants per guide of 3.2 ± 1.5. The intraoperative success rate of this approach was 14 out of 15. With an average follow-up period of 40 weeks, the overall implant survival rate was 83.3% (40/48). Eight implants were removed due to two fibula flap failures. The mean deviation at the implant platform and implant apex were 2.8 mm (interquartile range [IQR]: 1.9-3.4) and 3.2 mm (IQR: 2.0-4.6), and the angular deviation was 2.5° (IQR: 1.1-6.8)., Conclusions: Our preliminary data indicated that the 3D printed 3-in-1-PSSG facilitated simultaneous dental implant in fibula flap jaw reconstruction with a favorable intraoperative success and short-term clinical outcome. It might be a viable alternative to allow one-step immediate oral rehabilitation in patients underwent jaw reconstruction with free flaps. Long-term results with a larger sample size are warranted., (© 2020 Wiley Periodicals LLC.)

Background: Surgeons are pursuing accurate head and neck reconstruction to enhance aesthetic and functional outcomes after oncologic resection. This study aimed to investigate whether accuracy of head and neck reconstruction is improved with the use of three-dimensionally (3D)-printed patient-specific surgical plates compared with conventional plates., Methods: In this comparative study, patients were prospectively recruited into the study group (3DJP16) with 3D-printed patient-specific surgical plates. The patients in control group with conventional surgical plates were from a historic cohort in the same unit. The primary end point of the study was the accuracy of head and neck reconstruction. The secondary end points were accuracy of osteotomy, intraoperative blood loss, total operative time, and length of hospital stay., Results: The study recruited of 33 patients, including 17 in the study group and 16 in the control group. The patients' baseline characteristics were similar between the two groups. The absolute distance deviation of the maxilla or mandible was 1.5 ± 0.5 mm in the study group and 2.1 ± 0.7 mm in the control group [mean difference, - 0.7 mm; 95% confidence interval (CI) - 1.1 to - 0.3; p = 0.003], showing superior accuracy of reconstruction for the patients with 3D-printed patient-specific surgical plates. Improved accuracy of reconstruction also was detected in terms of bilateral mandibular angles and bone grafts. Concerning the secondary end points, the accuracy of the osteotomy was similar in the two groups. No difference was found regarding intraoperative blood loss, total operative time, or length of hospital stay., Conclusions: This is the first study to prove that compared with conventional plates, 3D-printed patient-specific surgical plates improve the accuracy of oncologic head and neck reconstruction.

Intensive artificial selection has been imposed in Yunshang black goats, the first black specialist mutton goat breed in China, with a breeding object of improving reproductive performance, which has contributed to reshaping of the genome including the characterization of SNP, ROH and haplotype. However, variation in reproductive ability exists in the present population. A WGS was implemented in two subpopulations (polytocous group, PG, and monotocous group, MG) with evident differences of litter size. Following the mapping to reference genome, and SNP calling and pruning, three approaches - GWAS, ROH analysis and detection of signatures of selection - were employed to unveil candidate genes responsible for litter size. Consequently, 12 candidate genes containing OSBPL8 with the minimum P-value were uncovered by GWAS. Differences were observed in the pattern of ROH between two subpopulations that shared similar low inbreeding coefficients. Two ROH hotspots and 12 corresponding genes emerged from ROH pool association analysis. Based on the nS L statistic, 15 and 61 promising genes were disclosed under selection for MG and PG respectively. Of them, some promising genes participate in ovarian function (PPP2R5C, CDC25A, ESR1, RPS26 and SERPINBs), seasonal reproduction (DIO3, BTG1 and CRYM) and metabolism (OSBPL8, SLC39A5 and SERPINBs). Our study pinpointed some novel promising genes influencing litter size, provided a comprehensive insight into genetic makeup of litter size and might facilitate selective breeding in goats., (© 2020 Stichting International Foundation for Animal Genetics.)

Background: This study aimed to investigate the effect of electroacupuncture (EA) on behavior in a rat model of chronic unpredictable mild stress (CUMS) and to explore the underlying molecular mechanisms., Methods: A total of 45 adult male Sprague-Dawley rats were randomly divided into three groups: the control, CUMS, and CUMS plus EA groups. Rats in the CUMS and EA groups were subjected to a 3-week CUMS condition, while rats in the EA group received EA at the Baihui (GV 20) acupoint (2 Hz, 0.6 mA) for 10 min once daily before being subjected to the CUMS condition. The sucrose preference test (SPT) was used as a measure to infer activation of the pleasure response to depression-like behaviour. After the behavioral test, 5-bromodeoxyuridine (BrdU) was intraperitoneally injected (100 mg/kg) and brain samples were collected 24 h later for the detection of hippocampal BrdU. Cell proliferation was determined according to the proportion of BrdU-positive cells. Brain-derived neurotrophic factor (BDNF) expression was detected., Results: The severity of anhedonia, BDNF + cells, and BrdU + neurons in DG significantly decreased in CUMS rats, and was accompanied by a reduced BDNF and BrdU + expression (P<0.05). After EA, the low levels of BDNF + cells and BrdU + expression and the depression-like behavior increased markedly (P<0.05)., Conclusions: EA contributes to neuroprotection against CUMS by enhancing BDNF expression and improving hippocampal neurogenesis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-7459). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Areca nut (AN) chewing contributes to an increase of oral squamous cell carcinoma (OSCC) cases in South and Southeast Asia; however, genomic events underlying the carcinogenesis process of AN-related OSCC remain unclear. Here, we comprehensively describe the genomic and transcriptome alterations of 113 Chinese OSCC patients (89 AN related and 24 AN negative) by whole-exome sequencing and RNA sequencing, and we compared the genomic differences between AN-related and AN-negative samples by integrating sequencing data of 325 OSCC patients from The Cancer Genome Atlas database and 50 from a published Taiwanese study. We identified 11 significantly mutated genes for OSCC, including 4 novel ones ( ATG2A, WEE1, DST , and TSC2 ), of which WEE1 and ATG2A mutated with significantly higher rates in AN-related samples ( P = 0.04 and P = 0.003, respectively). Mutational signature analysis revealed that AN-related OSCCs were specially characterized by the genomic signature of mismatch repair deficiency (dMMR), which could also predict the prognosis status of AN-related OSCC. In addition, an elevated PD-L1 expression was also observed in both AN-related patients ( P = 3.71 × 10 -11 ) and those with a high dMMR level ( P = 1.99 × 10 -4 ). Further differential expression analysis and in vitro experiments confirmed the role of dMMR in the development of OSCC induced by AN exposure. Taken together, this study first revealed the molecular profiles and highlighted the role of dMMR in AN-related OSCC among the Chinese population and identified that AN-related OSCC may represent a potential cohort for effective anti-PD-1/L1 immunotherapy.

Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China and the first-line treatment is radiotherapy. Intensity-modulated radiation therapy (IMRT) can deliver high dose to cancer and low dose to normal tissue, but xerostomia is still one of the complications after IMRT. However, how the concentration of saliva electrolytes be affected by IMRT and the effects on the quality of life are still unknown. In this prospective study, 76 NPC patients were recruited from hospitals in Hong Kong to identify the change of saliva electrolytes and xerostomia-related quality of life before and after IMRT., Methods and Materials: Saliva and questionnaire were collected before IMRT, 1 month, 3 months, 6 months and 12 months after IMRT. The concentration of saliva electrolytes was detected using inductively coupled plasma-optical emission spectroscopy (ICP-OES)., Results: Saliva flow rate significantly decreased after IMRT. Decrease in the mean value of pH was observed but the difference is not statistically significant. The concentrations of potassium, iodine, and calcium decreased and chloride concentration increased after IMRT, while the concentrations of sodium, magnesium, copper or zinc were kept at the same level before and after treatment. Xerostomia-related quality of life was adversely affected by IMRT, but partially recovered after 1 year., Conclusions: Our study revealed the change of saliva electrolytes and xerostomia-related quality of life in patients undergone IMRT for NPC., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The most effective regimen is unclear for patients with recurrent or metastatic head and neck squamous cell carcinomas (R/M HNSCC). We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating only systemic therapy for R/M HNSCC., Methods: This systematic review followed PRISMA and the Cochrane Collaboration Handbook for Systematic Reviews of Interventions. Endpoints included overall survival (OS), progression-free survival (PFS) and overall response rates (ORR)., Results: 55 RCTs from 1990-November 2019 qualified for review (n=12132). Only PD-1/PDL-1 inhibitors increased OS in R/M HNSCC platinum-resistant disease against their control (HR = 0·79, 95%CI 0·70-0.90, p<0·001), especially for PD-L1 ≥ 1% expressing tumours (HR = 0·72, 95%CI 0·60-0·86, p<0·001). PFS was prolonged for anti-EGFR agents against methotrexate when used in a second line setting (HR = 0·74, 95 %CI 0·62-0·87, p=0·001), and when cetuximab (HR = 0·60, 95%CI 0·49-0·72, p<0·0001) and panitumumab (HR = 0·76, 95%CI 0·65-0·89, p=0·001) were introduced to platinum-based regimens for first-line treatment., Conclusions: PD-1/PD-L1 inhibitors may represent the future of R/M HNSCC treatment. However, EGFR inhibitors may still play improve clinical outcomes., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Segmental mandibular defects require reconstruction. The fibula flap serves as a versatile flap in restoring mandibular contour and bony height. With the advances in computer-aided design and additive manufacturing technology, an innovative "one-piece" patient-specific reconstruction plate to facilitate double-barrel fibula flap shaping and bone securing was developed; the plate is described in this study. The "one-piece" plate is fabricated with individualized specifications and is mainly composed of three components: the long-bar reconstruction plate, a short-bar plate, and connecting bars. Our initial experiences showed that mandibular reconstructive surgery was greatly facilitated by the "one-piece" reconstruction plate for double-barrel fibula flap reconstruction and achieved satisfactory outcomes. A well-designed clinical trial is required to confirm the superiority of the "one-piece" reconstruction plate in the future. ClinicalTrials.gov registration: NCT03057223., (Copyright © 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Social media has become increasingly important as a source of information for the public and is widely used for health-related information. The outbreak of the coronavirus disease (COVID-19) has exerted a negative impact on dental practices., Objective: The aim of this study is to analyze the nature and diffusion of COVID-19-related oral health information on the Chinese social media site Weibo., Methods: A total of 15,900 tweets related to oral health and dentistry information from Weibo during the COVID-19 outbreak in China (December 31, 2019, to March 16, 2020) were included in our study. Two researchers coded 1000 of the total tweets in advance, and two main thematic categories with eight subtypes were refined. The included tweets were analyzed over time and geographic region, and coded into eight thematic categories. Additionally, the time distributions of tweets containing information about dental services, needs of dental treatment, and home oral care during the COVID-19 epidemic were further analyzed., Results: People reacted rapidly to the emerging severe acute respiratory syndrome coronavirus 2 threat to dental services, and a large amount of COVID-19-related oral health information was tweeted on Weibo. The time and geographic distribution of tweets shared similarities with epidemiological data of the COVID-19 outbreak in China. Tweets containing home oral care and dental services content were the most frequently exchanged information (n=4803/15,900, 30.20% and n=4478, 28.16%, respectively). Significant differences of public attention were found between various types of bloggers in dental services-related tweets (P<.001), and the tweets from the government and media engaged the most public attention. The distributions of tweets containing information about dental services, needs of dental treatment, and home oral care information dynamically changed with time., Conclusions: Our study overviewed and analyzed social media data on the dental services and oral health information during the COVID-19 epidemic, thus, providing insights for government organizations, media, and dental professionals to better facilitate oral health communication and efficiently shape public concern through social media when routine dental services are unavailable during an unprecedented event. The study of the nature and distribution of social media can serve as a useful adjunct tool to help make public health policies., (©Zhuo-Ying Tao, Guang Chu, Colman McGrath, Fang Hua, Yiu Yan Leung, Wei-Fa Yang, Yu-Xiong Su. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 15.06.2020.)

Three-dimensionally (3D) printed patient-specific surgical plates have been proposed to facilitate mandibular reconstruction and are attracting extensive attention. We have recently reported the high accuracy of 3D-printed patient-specific surgical plates used in head and neck reconstruction. Based on this previous work, the current study proposes a novel 'surgeon-dominated' approach to the design of 3D-printed patient-specific surgical plates. The aim of this proof-of-concept study was to explore the workflow and technical procedures of the surgeon-dominated approach. The workflow includes virtual surgery, the design and printing of patient-specific surgical devices, and real surgery. The prototype of the patient-specific surgical plate was designed by surgeons and further optimized for 3D printing by engineers. Different types of mandibular defect were tested to confirm the wide applicability of this approach. Cases in which this approach was used were reviewed and the duration of time spent on each case studied. Based on a total of 16 patients, the time spent on virtual surgery and plate design was 18.83±13.19hours, and the time taken for 3D printing, post-processing, and product delivery was 162.9±55.15hours. Therefore, this novel surgeon-dominated approach is feasible and time-saving, which would likely promote the wide application of patient-specific surgical plates and lead to a new era of 'digitization and precision' in mandibular reconstruction. ClinicalTrials.gov registration: NCT03057223., (Copyright © 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Computer-assisted mandibular reconstruction facilitates preoperative surgery simulation and transfers the virtual plan to a real operation. This systematic review and meta-analysis aimed to compare the accuracy, efficiency, postoperative complications, and economic viability between computer-assisted mandibular reconstruction and conventional freehand mandibular reconstruction., Methods: The PubMed, Embase, Cochrane Library, and Google Scholar databases were searched up to November of 2018. The accuracy, efficiency, postoperative complications, and economic viability of computer-assisted mandibular reconstruction compared to conventional freehand mandibular reconstruction were systematically reviewed. Continuous and dichotomous data were pooled in mean difference (or standardized mean difference if necessary) and odds ratio, subsequently, with 95 percent confidence interval., Results: A total of 12 studies were included in the systematic review, and data extracted from 11 of them were combined in meta-analysis. The accuracy of computer-assisted mandibular reconstruction was better than or equal to that of conventional freehand mandibular reconstruction according to qualitative analysis, although the quantitative comparison from meta-analysis was excluded because of the diversity of measurements. As for efficiency, computer-assisted mandibular reconstruction, when compared to conventional freehand mandibular reconstruction, revealed a shorter ischemic time, reconstructive time, total operative time, and length of stay. There was no difference in postoperative complication rate., Conclusions: Computer-assisted mandibular reconstruction showed increased efficiency considering the reduced ischemic time, total operative time, reconstructive time, and length of stay. However, the accuracy, reconstruction outcomes, and perioperative cost should be further elucidated because of diverse measurements and the lack of included studies.