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Abstract Background At present, research comparing the short-term postoperative outcomes of anatomical resection in lung cancer under different ports of da Vinci robot-assisted surgery is insufficient. This report aimed to compare the outcomes of three-port and four-port da Vinci robot-assisted thoracoscopic surgery for radical dissection of lung cancer. Methods 171 consecutive patients who presented to our hospital from January 2020 to October 2021 with non-small cell lung cancer and treated with da Vinci robot-assisted thoracoscopic surgery for radical resection of lung cancer were retrospectively collected and divided into the three-port group (n = 97) and the four-port group (n = 74). The general clinical data, perioperative data and life quality were individually compared between the two groups. Results All the 171 patients successfully underwent surgeries. Compared to the four-port group, the three-port group had comparable baseline characteristics in terms of age, sex, tumor location, tumor size, history of chronic disease, pathological type, and pathological staging. The three-port group also had shorter operation time, less intraoperative blood loss, lower chest tube drainage volume, shorter postoperative hospitalization stay durations, but showed no statistically significant difference (P > 0.05). Postoperative 24, 48 and 72 h visual analogue scale pain scores were lower in the three-port group (p 0.05) and postoperative respiratory complications (P > 0.05). Conclusions The three-port robot-assisted thoracoscopic surgery is safe and effective and took better outcomes than the four-port robot-assisted thoracoscopic surgery in non-small cell lung cancer.

Abstract The utilization and development of urban underground space play a crucial role in optimizing the layout of civic architecture and enhancing the urban ecological environment, which contributes toward increasing the overall carrying capacity and promoting sustainable development in megacities. To delve into the research progress of urban underground space, knowledge maps were created using the information visualization software VOSviewer. The literature was systematically extracted from three prominent databases, namely, Web of Science, Scopus, and China National Knowledge Infrastructure. According to the bibliometric analysis of the co‐citation and core words co‐occurrence, the trends and challenges of research on urban underground space were identified. As highlighted by the results obtained, it still remains highly challenging to achieve interdisciplinary collaboration in urban underground space research; the research trends of urban underground space consist of collaborative planning and whole life cycle sustainable development, multisource geological data informatization and resource evaluation, infrastructure design optimization, and intelligent construction. The knowledge map, drawn using bibliometric methods, offers a quantitative analysis of literature retrieval across various levels. It is recognized as an essential tool for exploring and identifying challenges and trends in urban underground space.

Abstract Background The association between bone fracture and cardiovascular diseases is examined in this study. While basic research has established a connection between fractures and heart attacks through the linkage between bones and arteries, population studies have not provided clear evidence. The aim of the present study is to investigate the association between bone fracture and the occurrence of myocardial infarction in a natural population during long-term follow-up. Methods A total of 13,196 adult participants with bone fracture history at baseline from the China Health and Nutrition Survey (CHNS) prospective cohort were included in this study. Baseline investigation was performed in 1997–2009 and the outcome was followed up till 2015. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Results From 1997 to 2015, a total of 329 incident myocardial infarction cases were identified. In univariate and multivariate Cox regression analysis, a history of bone fracture was associated with an increased risk of myocardial infarction incidence in the total population (for the crude model: HR = 2.56, 95% CI 1.83–3.53, P

Based on the urban morphology theory of the Conzen School and the actual situation of the Tangjiawan Ancient Town, a morphological process analysis of the Tangjiawan Ancient Town was conducted. The end result is a visualization of the process of urban form evolution. The first objective is to describe the morphological framework of Tangjiawan Ancient Town and the morphological changes that occurred during its development. The current urban landscape is divided into units by superimposing morphological units, building types, and land use. The results of the division also reflect the morphological development, structure, and compositional characteristics of the ancient city of Tangjiawan. Using Tangjiawan Ancient Town in Zhuhai city as an example, on-site research, historical evidence, urban morphology analysis methods, and interviews were used to elaborate and analyze the spatial structure and evolution process of traditional ancient towns in South China. In particular, morphological units, building types, and land use are included. The morphological map of the Tangjiawan ancient town is inconsistent with the current economic-oriented development of ancient town planning. This shows that current planning is less concerned with the physical form of architectural heritage, which may lead to further damage to the landscape of the ancient town. This study provides a strong reference for the follow-up planning of ancient town protection of the same type from the perspective of morphology and area and provides ideas for the subsequent preparation of protection plans.

Abstract With the rapid development of machine learning technology, it has become possible to automatically identify cultural heritage elements in traditional buildings. This research aimed to develop a machine learning model based on the YOLOv4 architecture to identify the traditional Chinese porcelain inlay pattern in the Lingnan region. The researchers collected and annotated a large quantity of Lingnan Chinese porcelain inlay image data and then used these data to train the studied model. The research results show that (1) the model in this study was specifically adjusted to effectively identify a variety of Chinese porcelain inlay pattern types, including traditional patterns such as plum blossoms and camellias. (2) In the 116th epoch, the model showed excellent generalization ability, and the verification loss reached the lowest value of 0.88. The lowest training loss in the 195th epoch was 0.99, indicating that the model reached an optimal balance point for both recognition accuracy and processing speed. (3) By comparing different models for detecting Chinese porcelain inlay images across 581 pictures, our YOLOv4 model demonstrated greater accuracy in most classification tasks than did the YOLOv8 model, especially in the classification of chrysanthemums, where it achieved an accuracy rate of 87.5%, significantly outperforming YOLOv8 by 58.82%. However, the study also revealed that under certain conditions, such as detecting apples and pears in low-light environments, YOLOv8 showed a lower missing data rate, highlighting the limitations of our model in dealing with complex detection conditions.

In this paper, Macau Taipa Village, a historical district in an island-type city, is the research focus, and a parametric design-based method for designing historical districts is proposed. First, the shape and distribution of roads in historical districts is studied through on-the-spot investigation and measurement and data are collected on the width, depth, and area of street blocks, average street length and width, street orientation, building width, depth, acreage, and height, and building orientation. Second, the acquired data are transmitted to the Grasshopper parameterization platform, and an intelligently generated program produces calculations. Through multiple iterations and evaluations of genetic algorithms based on the needs of modern urban design and planning constraints, the building density is further reduced, and more landscape areas are added. The parametric model is optimized to gradually generate the urban spatial design that meets contemporary requirements. The research reveals that (1) the grasshopper algorithm’s generated block design inherits the characteristics of the conventional historical block. (2) The historical block where the data were collected on site and the block where Grasshopper is applied should maintain the consistency of the regional context. (3) This method can be applied to the design of new urban areas, and the scope of application can be further adjusted through collaboration and the needs of the owners at a later stage.

Recent research shows that China is experiencing significant greening, with afforestation initiatives being the main cause. Quantitative calculation of vegetation change influencing factors and evaluation of the contribution of afforestation to vegetation greening in China are critical to coping with climate change and improving the implementation and efficacy of forestry projects. We investigated the temporal and spatial dynamics of the Normalized Difference Vegetation Index (NDVI) from 1982 to 2020, and quantified the contribution of afforestation initiatives, a typical human activity, to the dynamic changes of vegetation. The results showed that NDVI in China has primarily increased in the last 39 years. 57% of the pixels increased, 27% were stable and unchanged, and 16% decreased. Climate change was responsible for 72.34% of vegetation restoration, while human activities were responsible for 27.36% of vegetation restoration, according to residual analysis. In the future, only 14% of the regions showed continuous growth of the NDVI, while the remaining regions showed obvious antipersistence (59% will go from increasing to decreasing, and 22% will go from decreasing to increasing). The contribution of climate factors to vegetation change will decrease in the future, and human activities will become more complex. Except for Huaihe River and Taihu Lake (SPHRTL), other forestry projects showed an increasing trend of NDVI after the implementation of ecological engineering. However, due to differences in climate conditions and ecological engineering implementation, there are differences in the benefits of forestry projects. Some forestry project areas still have obvious vegetation degradation, and appropriate forestry management is necessary. This work provides a quantitative analysis of vegetation change and its driving factors in China, which will help to cope with future climate change and provide a reference for the implementation and management of ecological projects.

Abstract Background Mesenchymal stem cells (MSCs) hold a great promise for cell-based therapy in the field of regenerative medicine. In this study, we aimed to evaluate the safety and efficacy of intravenous infusion of human umbilical cord-derived MSCs (HUC-MSCs) in patients with aging frailty. Methods In this randomized, double-blind, placebo-controlled trial, participants diagnosed with aging frailty were randomly assigned to receive intravenous administrations of HUC-MSCs or placebo. All of serious adverse events and AEs were monitored to evaluate the safety of treatment during the 6-month follow-up. The primary efficacy endpoint was alteration of physical component scores (PCS) of SF-36 qualities of life at 6 months. The secondary outcomes including physical performance tests and pro-inflammatory cytokines, were also observed and compared at each follow-up visits. All evaluations were performed at 1 week, 1, 2, 3 and 6 months following the first intravenous infusion of HUC-MSCs. Results In the MSCs group, significant improvements in PCS of SF-36 were observed from first post-treatment visit and sustained throughout the follow-up period, with greater changes compared to the placebo group (p = 0.042). EQ-VAS scores of MSCs group improved significantly at 2 month (p = 0.023) and continued until the end of the 6-month visit (p = 0.002) in comparison to the placebo group. The timed up and go (TUG) physical performance test revealed significant group difference and showed continual enhancements over 6 months (p

Abstract Background Toxoplasma gondii and Neospora caninum are closely related protozoan parasites that are considered important causes of abortion in livestock, causing huge economic losses. Hunan Province ranks 12th in the production of beef and mutton in China. However, limited data are available on the seroprevalence, risk factors and molecular characterization of T. gondii and N. caninum in beef cattle and goats in Hunan province, China. Methods Sera of 985 beef cattle and 1147 goats were examined for the presence of specific antibodies against T. gondii using indirect hemagglutination test (IHAT) and anti-N. caninum IgG using competitive-inhibition enzyme-linked immunoassay assay (cELISA). Statistical analysis of possible risk factors was performed using PASW Statistics. Muscle samples of 160 beef cattle and 160 goats were examined for the presence of T. gondii DNA (B1 gene) and N. caninum DNA (Nc-5 gene) by nested PCR. The B1 gene-positive samples were genotyped at 10 genetic markers using the multilocus nested PCR-RFLP (Mn-PCR-RFLP). Results Specific IgG against T. gondii were detected in 8.3% (82/985) and 13.3% (153/1147) and against N. caninum in 2.1% (21/985) and 2.0% (23/1147) of the beef cattle and goats, respectively. Based on statistical analysis, the presence of cats, semi-intensive management mode and gender were identified as significant risk factors for T. gondii infection in beef cattle. Age was a significant risk factor for T. gondii infection in goats (P 3 years was a significant risk factor for N. caninum infection in beef cattle (P

Abstract The association between high blood pressure and fracture showed obvious discrepancies and were mostly between hypertension with future fracture, but rarely between fracture and incident hypertension. The present study aims to investigate the associations of hypertension with future fracture, and fracture with incident hypertension. We included adult participants from the China Health and Nutrition Survey (CHNS) prospective cohort in 1997–2015 (N = 10,227), 2000–2015 (N = 10,547), 2004–2015 (N = 10,909), and 2006–2015 (N = 11,121) (baseline in 1997, 2000, 2004, 2006 respectively and outcome in 2015). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. In the analysis of the association between hypertension and future fracture, the adjusted HRs (95% CIs) were 1.34 (0.95–1.90) in 1997–2015, 1.40 (1.04–1.88) in 2000–2015, 1.32 (0.98–1.78) in 2004–2015, and 1.38 (1.01–1.88) in 2006–2015. In the analysis of the association between fracture and incident hypertension, the adjusted HRs (95% CIs) were 1.28 (0.96–1.72) in 1997–2015, 1.18 (0.94–1.49) in 2000–2015, 1.12 (0.89–1.40) in 2004–2015, and 1.09 (0.85–1.38) in 2006–2015. The present study showed that hypertension history was associated with increased risk of future fracture, but not vice versa.

Abstract In computer artificial intelligence, there is great potential in research on the protection of Suzhou's traditional gardens, a world cultural heritage site. As a special material in Suzhou's traditional garden architecture, shedthin tile is widely used in roof base laying and is one of the important materials for building roofs. However, professionals need to reach the roof and spend much time and effort assessing the damage before repairing it. Therefore, the main goals of this study are to investigate a machine learning-based method for finding targets and determining the type of surface damage on a shedthin tile using the YOLOv4 model trained in this study. Using 500 shedthin tile on-site photos as training samples, the model was trained for 750 epochs. The main results of this study are as follows: (1) An object detection method based on machine learning can efficiently and accurately identify damage content, overcoming the manpower and time–cost limitations of traditional assessment methods. (2) The detection model in this study has an accuracy of 85.89% for water stain recognition of shedthin tiles, 93.29% for surface scaling, 87.37% for color aberration, and 96.15% for too wide a gap. The comprehensive accuracy is 90.20%, which meets the basic testing requirements. (3) The model demonstrated its robustness and reliability in complex environments in application tests in actual scenarios, providing a methodological reference for computer vision and target detection technology in cultural heritage protection.

Abstract Fumarate hydratase (FH) deficient renal cell carcinoma (RCC) is a type of tumor with definite metabolic disorder, but the mechanism of metabolic remodeling is still unclear. LncRNA was reported to closely correlate with cancer metabolism, however the biological role of LncRNA in the development of progression of FH-deficent RCC was not well studied either. FH-deficient RCC samples were collected in my hospital and used for RNA-sequencing and Mass spectrometry analysis. FH-deficient RCC cell line UOK262 and control pFH cells were used for in vitro experiments, including proliferation assay, transwell assay, western-blot, mass spectrometry and so on. PDX mouse model was used for further drug inhibition experiments in vivo. In this study, we analyzed the profiles of LncRNA and mRNA in FH-deficienct RCC samples, and we found that the LncRNA-MIR4435-2GH was specifically highly expressed in FH-deficient RCC compared with ccRCC. In vitro experiments demonstrated that MIR4435-2HG was regulated by Fumarate through histone demethylation, and the deletion of this gene could inhibit glutamine metabolism. RNA-pulldown experiments showed that MIR4435-2HG specifically binds to STAT1, which can transcriptionally activate GLS1. GLS1 inhibitor CB-839 could significantly suppress tumor growth in PDX tumor models. This study analyzed the molecular mechanism of MIR4435-2HG in regulating metabolic remodeling of FH-deficient RCC in clinical samples, cells and animal models by combining transcriptional and metabolic methods. We found that that GLS1 was a therapeutic target for this tumor, and MIR4435-2HG can be used as a drug sensitivity marker.

BackgroundHemorrhagic Fever with Renal Syndrome (HFRS) continues to pose a significant public health threat to the well-being of the population. Given that the spread of HFRS is susceptible to meteorological factors, we aim to probe into the meteorological drivers of HFRS. Thus, novel techniques that can discern time-delayed non-linear relationships from nonlinear dynamical systems are compulsory.MethodsWe analyze the epidemiological features of HFRS in Weifang City, 2011-2020, via the employment of the Empirical Dynamic Modeling (EDM) method. Our analysis delves into the intricate web of time-delayed non-linear associations between meteorological factors and HFRS. Additionally, we investigate the repercussions of minor perturbations in meteorological variables on future HFRS incidence.ResultsA total of 2515 HFRS cases were reported in Weifang from 2011 to 2020. The number of cases per week was 4.81, and the average weekly incidence was 0.52 per 1,000,000. The propagation of HFRS is significantly impacted by the mean weekly temperature, relative humidity, cumulative rainfall, and wind speed, and the ρCCM converges to 0.55,0.48,0.38 and 0.39, respectively. The graphical representation of the relationship between temperature (lagged by 2 weeks) and the incidence of HFRS exhibits an inverted U-shaped curve, whereby the incidence of HFRS culminates as the temperature reaches 10 °C. Moreover, temperature, relative humidity, cumulative rainfall, and wind speed exhibit a positive correlation with HFRS incidence, with a time lag of 4-6 months.ConclusionsOur discoveries suggest that meteorological factors can drive the transmission of HFRS both at a macroscopic and microscopic scale. Prospective alterations in meteorological conditions, for instance, elevations in temperature, relative humidity, and precipitation will instigate an upsurge in the incidence of HFRS after 4-6 months, and thus, timely public health measures should be taken to mitigate these changes.

COVID-19 patients often suffer from post-COVID-19 acute sequelae (PASC). Pulmonary fibrosis has the most significant long-term impact on the respiratory health of patients, known as post-COVID-19 pulmonary fibrosis (PC19-PF). PC19-PF can be caused by acute respiratory distress syndrome (ARDS) or COVID-19-induced pneumonia. Individuals who experience COVID-19 pneumonia symptoms (including cough, shortness of breath, dyspnea on exertion, and desaturation) for at least 12 weeks after diagnosis, almost all develop PC19-PF. Extracellular matrix molecules: laminin (LN), type IV collagen (IV Col), procollagen III N-terminal peptide (PIIINP), and hyaluronic acid (HA) are involved in the development and progression of PC19-PF. This study aimed to investigate the relationship between the progression of PC19-PF and serum levels of laminin, IV COL, PIIINP, and hyaluronic acid. This retrospective study included 162 PC19-PF patients treated and 160 healthy controls who received treatment at Shenzhen Longgang District Third People’s Hospital, Hebei PetroChina Central Hospital and Changzhi People’s Hospital from January 2021 to December 2023. Serum levels of LN, IV COL, PIIINP, and HA were detected by chemiluminescence immunoassay using commercial kits. Predicted forced vital capacity percentage (FVC% pred), predicted carbon monoxide lung diffusion capacity percentage (DLCO% pred), high-resolution computed tomography (HRCT) scores were assessed, and patient mortality was compared with healthy controls. Serum levels of LN, IV Col, PIIINP, and HA were significantly higher in PC19-PF or CTD-ILD patients than in healthy controls (all p < 0.05), and they were further elevated in acute exacerbation cases (all p < 0.01). In patients, HA was positively associated with HRCT scores and negatively associated with FVC% pred and DLCO% pred (all p < 0.05). Serum levels of LN, IV COL, PIIINP, and HA were significantly lower in surviving patients than in those who deceased (all p > 0.05). Serum levels of LN, IV C, PIIINP, and HA may affect the progression of PC19-PF and may serve as indicators of PC19-PF severity.

In the 16^th^ and 17^th^ centuries, under the influence of the Portuguese Empire's overseas expansion and cultural integration, the island city of Macau became an important international trading port in the Eastern Sea, with close ties to the Asian port cities governed by Portugal. This study introduces a new method for comparing urban morphological layouts using machine learning and investigates the potential benefits of combining urban morphological analysis with machine learning techniques. In addition, a combination of urban morphology theory and machine learning is used to excise samples of urban morphology from Portuguese urban geographical information maps. The morphological characteristics of port city areas are further extracted, and training labels for typical Portuguese urban textures are established. Using the YOLOv4 object detection algorithm, the results are compared with the urban textures of typical island and port cities of the Asian Silk Road---Goa in India, Malacca in Malaysia, Macau in China, and Dili in Timor-Leste---revealing the similarities and differences among the port cities in Asia influenced by traditional Portuguese urban practices. The results reveal the relationship between maritime trade and urban form.

Biotic stresses caused by bacterial and fungal pathogens damage crops; identifying treatments that enhance disease resistance provides important information for understanding plant defenses and sustainable agriculture. Salt stress affects crop yields worldwide; however, studies have focused on the toxic sodium ion, leaving the effects of the chloride ion unclear. In this study, we found that irrigation with a combination of chloride salts (MgCl2, CaCl2, and KCl) suppressed the cell death phenotype of the ceramide kinase mutant acd5. Chloride salt pre-irrigation also significantly limited the cell death caused by Pseudomonas syringae pv maculicola infection and inhibited the multiplication of this bacterial pathogen in a mechanism partially dependent on the salicylic acid pathway. Moreover, chloride salt pre-irrigation improved plant defenses against the fungal pathogen challenge, confining the lesion area caused by Botrytis cinerea infection. Furthermore, the growth of herbivorous larvae of Spodoptera exigua was retarded by feeding on chloride salt irrigated plants. Thus, our data suggest that treatment with Cl- increases broad spectrum resistance to biotic challenges.

Objectives The study aimed to understand the composition, epidemiological characteristics and disease burden of chronic non-communicable diseases and to evaluate the association between sociodemographic factors and chronic non-communicable diseases.Design A cross-sectional study.Setting and participants Medical records of 196 761 residents were collected from Dongfang disease surveillance system from January to December 2021.Primary outcome Prevalence and disability burden were recorded. Logistic regression was used to investigate the relationship between sociodemography factors and diseases.Results Cardiovascular diseases, chronic lower respiratory diseases and other upper respiratory tract diseases were the main chronic non-communicable diseases. In multivariable analysis, men were associated with increased risk of cardiovascular diseases (OR=1.210, 95% CI 1.162 to 1.261) and chronic lower respiratory diseases (OR=1.128, 95% CI 1.079 to 1.180). Older age was associated with increased risk of cardiovascular diseases (OR=83.952, 95% CI 58.954 to 119.550), whereas was associated with decreased risk of chronic lower respiratory diseases (OR=0.442, 95% CI 0.415 to 0.471) and other upper respiratory tract diseases (OR=0.450, 95% CI 0.411 to 0.493). The unemployed and poor household were associated with decreased risk of cardiovascular diseases (OR=0.463, 95% CI 0.412 to 0.521 and OR=0.390, 95% CI 0.342 to 0.444, respectively), whereas were associated with increased risk of chronic lower respiratory diseases (OR=12.219, 95% CI 6.343 to 23.539 and OR=10.954, 95% CI 5.666 to 21.177, respectively) and other upper respiratory tract diseases (OR=2.246, 95% CI 1.719 to 2.936 and OR=3.035, 95% CI 2.308 to 3.991, respectively). Gender and age moderated the association between personnel category and major diseases.Conclusions The spectrum and epidemiological characteristics of chronic diseases observed in Dongfang is good evidence for developing prevention guides and health policies for region.

Objective: The increasing identification of pulmonary nodules has led to a growing emphasis on segmentectomy. Nevertheless, the surgical process for segmentectomy is complex and optimizing segmentectomy is a critical clinical concern. This study aimed to evaluate the safety and short- and long-term efficacy of V6-preserving superior segmentectomy. Methods: We performed a retrospective analysis of patients who underwent thoracoscopic superior segmentectomy at our hospital between January 2019 and June 2020. Eligible patients were categorized into an V6 vein-preserving segmentectomy (VVPS) group and a Non V6 vein-preserving segmentectomy (NVVPS) group depending on the preservation of V6. Primary outcome measures encompassed the evaluation of surgical safety (surgical margins, 3-year overall survival, and disease-free survival), whereas secondary measures included postoperative complication rates, operative time, estimated intraoperative blood loss, length of hospital stay, and associated costs. Results: The analysis included a final cohort of 78 patients. In the NVVPS group (n = 43), 95.3 % of patients exceeded the tumor diameter, and no positive surgical margins were observed. The 3-year overall survival (OS) and disease-free survival (DFS) rates for the NVVPS group were 95.3 %, with no significant differences in OS (p = 0.572) and DFS (P = 0.800) compared with the VVPS group. Additionally, the median total hospitalization cost for the NVVPS group was 41,400 RMB (IQR, 38,800–43,400), which was significantly lower than that of the VVPS group, showing statistical significance (P 0.05). Conclusion: V6-preserving superior segmentectomy is a secure and optimized surgical alternative. Its streamlined procedure facilitates easier adoption in primary healthcare facilities, rendering it a superior choice for superior segmentectomy.

ObjectivesCodeine, a prodrug used as an opioid agonist, is metabolized to the active product morphine by CYP2D6. This study aimed to establish physiologically based pharmacokinetic (PBPK) models of codeine and morphine and explore the influence of CYP2D6 genetic polymorphisms on the pharmacokinetics of codeine and morphine.MethodsAn initial PBPK modeling of codeine in healthy adults was established using PK-Sim® software and subsequently extrapolated to CYP2D6 phenotype-related PBPK modeling based on the turnover frequency (Kcat) of CYP2D6 for different phenotype populations (UM, EM, IM, and PM). The mean fold error (MFE) and geometric mean fold error (GMFE) methods were used to compare the differences between the predicted and observed values of the pharmacokinetic parameters to evaluate the accuracy of PBPK modeling. The validated models were then used to support dose safety for different CYP2D6 phenotypes.ResultsThe developed and validated CYP2D6 phenotype-related PBPK model successfully predicted codeine and morphine dispositions in different CYP2D6 phenotypes. Compared with EMs, the predicted AUC0-∞ value of morphine was 98.6% lower in PMs, 60.84% lower in IMs, and 73.43% higher in UMs. Morphine plasma exposure in IMs administered 80 mg of codeine was roughly comparable to that in EMs administered 30 mg of codeine. CYP2D6 UMs may start dose titration to achieve an optimal individual regimen and avoid a single dose of over 20 mg. Codeine should not be used in PMs for pain relief, considering its insufficient efficacy.ConclusionPBPK modeling can be applied to explore the dosing safety of codeine and can be helpful in predicting the effect of CYP2D6 genetic polymorphisms on drug–drug interactions (DDIs) with codeine in the future.

Here, we presented 6 patients who were admitted to our institution and diagnosed as myasthenia gravis (MG) with tongue muscle atrophy. All these 6 patients developed symptoms of bulbar muscle weakness in acetylcholine receptor antibodies positive MG (AChR-MG) (3/6), muscle-specific receptor tyrosine kinase antibodies positive MG (MuSK-MG) (1/6), and sero-negative MG (2/6). Most of patients had “triple-furrowed” tongue except for patient 2 with irregular atrophy of tongue muscle. Tongue muscle atrophy occurs in patients with MuSK-MG, AChR-MG, and sero-negative MG. Atrophied tongue muscles of five patients with MG were reversible after immunotherapy.