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Hepatic proteomes are intricately controlled through biosynthesis, extracellular secretion, and intrahepatic degradation. Autophagy governs lysosome‐mediated intrahepatic degradation and the hepatic proteome. When autophagy is impaired, it leads to the accumulation of intrahepatic proteins, causing proteinopathy. This study investigates whether autophagy can modulate the hepatic proteome non‐degradatively. Utilizing conditional, inducible, and hepatotoxin models of hepatic autophagy impairment, we assessed the overall hepatic proteome expression using Coomassie brilliant blue (CBB) staining and liquid chromatography–tandem mass spectrometry (LC/MS). We pinpointed and confirmed four specific hepatic proteins—Cps1, Ahcy, Ca3, and Gstm1—that were selectively modified in autophagy‐deficient livers. Expression of Cps1, Ahcy, and Ca3 were significantly reduced, while Gstm1 expression increased in livers with autophagy impairment. Interestingly, these changes in hepatic protein levels were not due to defective autophagic degradation but were associated with alterations in mRNA transcript levels. Moreover, as a result of autophagic dysfunction, sustained activation of the nuclear erythroid‐derived 2‐like 2 (Nrf2) transcription factor, transcriptionally regulated the mRNA levels of these proteins. Our findings indicate that autophagy can influence hepatic proteins not solely via traditional degradative routes but also through non‐degradative transcriptional processes by modulating Nrf2.

Background Traditionally known for bone regeneration, the Ilizarov technique's effectiveness in nerve reconstruction, particularly for extensive nerve damage, has yet to be widely recognized. Case presentation This report presents a case study and proposes the innovative use of the Ilizarov technique for reconstructing extended nerve defects. In this study, we reviewed a 43‐year‐old male diagnosed with an open fracture of the right tibia combined with soft tissue injury resulting in a mangled injury in which a large part of his right tibial bone and nerve were lost. The patient was cured and the sensorimotor function was recovered after distraction osteogenesis by the Ilizarov technique, which is a unique application of this technique to repair a substantial long nerve defect, a rare occurrence in medical literature. It highlights the method of nerve lengthening, which is achieved by attaching the nerve stump to the bone stump. This approach allows for significant nerve regeneration and ensures a stable progression of the nerve, as the bone stump acts as a carrier, overcoming the challenges of direct nerve lengthening. Conclusions The adaptability and effectiveness of the Ilizarov technique in a new area suggests the need to reconsider traditional approaches to complex nerve reconstruction. Placing this case within the context of current medical knowledge underscores the potential of this technique to revolutionize the treatment of extended nerve defects, offering hope for improved outcomes in challenging scenarios.

Abstract Background miR-223-3p has been demonstrated as a Pseudomonas aeruginosa colonization-related miRNA in bronchiectasis (BE), but its clinical value in BE has not been revealed, which is of great significance for the clinical diagnosis and monitoring of BE. This study aimed to identify a reliable biomarker for screening BE and predicting patients’ outcomes. Methods The serum expression of miR-223-3p was compared between healthy individuals (n = 101) and BE patients (n = 133) and evaluated its potential in distinguishing BE patients. The severity of BE patients was estimated by BSI and FACED score, and the correlation of miR-223-3p with inflammation and severity of BE patients was evaluated by Pearson correlation analysis. BE patients were followed up for 3 years, and the predictive value of miR-223-3p in prognosis was assessed by logistic regression analysis. Results Significant upregulation of miR-223-3p was observed in BE patients, which significantly distinguished BE patients and showed positive correlations with C-reactive protein (CRP), procalcitonin (PCT), interleukin 6 (IL-6), and neutrophil-to-lymphocyte ratio (NLR) of BE patients. Additionally, miR-223-3p was also positively correlated with BSI and FACED scores, indicating its correlation with inflammation and severity of BE. BE patients with adverse prognoses showed a higher serum miR-223-3p level, which was identified as an adverse prognostic factor and discriminated patients with different prognoses. Conclusion Increasing serum miR-223-3p can be considered a biomarker for the onset, severity, and prognosis of BE.

Abstract Ignition electrodes have an immense impact on the accurate measurement of the flame propagation spherical radius. In this study, a flame-radius calculation method is designed. The method is able to eliminate effects due to the ignition electrodes. The adaptability and optimization effects of the proposed method are analyzed. The results show that the ratio of the angle is affected by the ignition electrodes under the Han II method. There are three obvious divisions include a high-value area, a sharp-variation area, and a mild-variation area. The ratio of the angle affected by the ignition electrodes is only applicable to the mild-variation region when the flame presents respective convex and concave distributions. For these distributions, the increment rate of the mean radius is 0.4–0.85% and 0.42–3.19%. The reduced rate of the standard deviation of the radius extraction value is 11.91–22.1% and 5.13–17.99%, and the reduced rate of the radius extraction value range is 20.32–39.51% and 0.32–8.09%.

Ophiopogonis radix has been used for both food and traditional Chinese medicine in China for millennia. Oligosaccharides of Ophiopogon japonicus (OOJ), the primary bioactive components of Ophiopogonis radix, have significant hypoglycemic and hypolipidemic effects. Insulin resistance (IR) and glucolipid metabolism were examined in vivo and in vitro in this work, utilizing IR-HepG2 cells and high-fat diet/streptozocin-induced type 2 diabetic mellitus (T2DM) rats as models. It was observed that OOJ efficiently improves various T2DM parameters, such as blood glucose, lipid profile, insulin sensitivity, glucose tolerance, glycogen content, glycogen consumption, liver index, and histopathology. These improvements may be attributed to the regulation and control of the insulin receptor substrate 1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/AKT (also known as protein kinase B, PKB)/glycogen synthase kinase-3β (GSK-3β) signaling pathways. These findings suggest that OOJ has potential as a functional food ingredient and therapeutic agent for treating metabolic syndrome and T2DM.

Understanding the connections between the built environment and travel mode choice is a major research topic in transportation. However, existing studies usually examine the relationship through trip-based analyses rather than tour-based approaches. A tour consists of multiple trips that originate and end at the same place, which is increasingly considered the more appropriate analysis unit for travel behaviors. Applying a tour-based approach, this study employs random forest to investigate the non-linear impacts of built environment factors and tour attributes on different mode combinations of a tour. We find that tour attributes and connectivity-related variables (e.g., block size and intersection density) have a strong association with the use of active travel modes when their values are within a certain threshold. In addition, capturing mode change behaviors offers more nuanced understanding of how various built environment variables shape people’s decision to combine modes in a tour.

Summary: Background: Duchenne muscular dystrophy (DMD) is a disabling and life-threatening, X-linked recessive disorder caused by mutations in dystrophin. Natural history studies can inform the disease characteristics of DMD, and data from these studies can be used to plan and design clinical trials and as external controls for long-term studies. We report 12-month results from the largest natural history study of individuals with DMD in China receiving standard of care treatment. Methods: This ongoing, multicentre, prospective, single-cohort study (ClinicalTrials.gov: NCT03760029) was conducted in Chinese male participants with DMD (ambulatory aged

SCPx deficiency is a rare disorder of peroxisomal beta-oxidation dysfunction, and it has only been documented in two patients thus far. In the previously reported patients, both patients were primarily presented with slowly progressive dystonia or ataxia, and they both displayed symmetrical lesions in the thalamus and brainstem on magnetic resonance imaging. This study presents the third patient exhibiting a similar neuroimaging abnormality but a notably different clinical phenotype characterized by episodic psychosis. Through whole-exome sequencing, we identified a homozygous splicing mutation in SCP2 (c.674 + 1G > C), and further RNA sequencing revealed exon 8 skipping in the mature transcripts of SCP2. This study significantly expands our understanding of the genotypic and phenotypic spectrum associated with SCP2-related metabolic encephalopathy.

Abstract Background Sugammadex is a newer medication used for rapid and reliable reversal of neuromuscular blockade. This study evaluated whether sugammadex could reduce the length of postoperative hospital stay in patients undergoing abdominal surgery. Methods This single center retrospective cohort study included patients who underwent major abdominal surgery between January 2015 and October 2019. Patients were randomized according to reversal with sugammadex or spontaneous recovery. The primary outcome was length of postoperative hospital stay. The secondary outcomes were length of post-anesthetic care unit (PACU) stay, postoperative ambulation time, time-to-first-defecation, and incidence of pulmonary complications. After 1:1 propensity score matching, univariate and multiple linear regression analyses estimated the differences in outcomes. Results Of the 1614 patients, 517 received sugammadex and 645 spontaneously recovered. After adjusting for potential confounders, non-linear relationship was detected between administration of sugammadex and the length of postoperative hospital stay (β = 0.29 95% confidence interval {CI}: [− 1.13, − 0.54], P = 0.4912). However, it was associated with shorter PACU stay (β = − 20.30 95% CI: [− 24.48, − 17.11], P

BackgroundPrevious studies have examined symptom clusters in children with acute leukemia, yet a knowledge gap persists regarding central symptom clusters and their influencing factors. By identifying these central clusters and associated factors, healthcare providers can enhance their understanding and effective management of symptoms. Our study seeks to address this gap by identifying symptom clusters, exploring central clusters, and investigating the demographic and health-related factors associated with these clusters in children with acute leukemia undergoing chemotherapy.MethodsA total of 586 children with acute leukemia from January 2021 to April 2023 were recruited from China. They were investigated using Memorial Symptom Assessment Scale 10-18 during chemotherapy. The principal component analysis was used to identify the symptom clusters. An association network was conducted to describe the relationships among symptoms and clusters. A multiple linear model was used to investigate the associated factors for the severity of overall symptoms and each symptom cluster.ResultsFive clusters were identified, including oral and skin cluster, somatic cluster, self-image disorder cluster, gastrointestinal cluster and psychological cluster. Gastrointestinal cluster was the most central symptom cluster. Age, sex, clinical classification, number of having chemotherapy and education degree and marital status of the primary caregiver are associated with the severity of these five symptom clusters.ConclusionOur study highlights the importance of evaluating symptom clusters in children with acute leukemia during chemotherapy. Specifically, addressing gastrointestinal symptoms is crucial for effective symptom management and overall care.

Fouling has limited the evolution of compact heat exchangers (represented by EGR cooler) to smaller and more efficient sizes, an important reason is the unclear mechanism of the effect of exhaust gas condensation on fouling and thermal performance. This paper reviews the effects of hydrocarbon vapor, water vapor and acid vapor condensation on EGR cooler fouling and thermal performance from 1998 to 2023. Three paths of vapors condensation can occurr: interaction with particles, homogeneous nucleation and interaction with fouling. Beneficial effect (3) and harmful effects (2) to EGR cooler thermal performance have identified: filling, removal and chemical are beneficial effects whereas adhesion and nucleation are harmful effects. Three pathways and five effects play a key role on the composition, the mass, the thickness, density, the morphology and thermal resistance of fouling layer. The involvement level of sub-paths and contribution degree of sub-effects of vapor condensation under different boundary conditions, standard database, holistic model and the effect of renewable synthetic fuels on fouling and thermal performance can be further explored. The results will help researchers to understand the logical relationship between exhaust vapor condensation and fouling and thermal performance from the new perspective of condensation.

IntroductionAcute and chronic otitis media (AOM and COM) are common middle ear infections that can lead to hearing loss and other complications. Recent research has shown that both macrophages and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway are involved in the immune response to and the resolution of otitis media. However, the specific effects of Nrf2 on macrophages in the transition of AOM to COM are not well understood, and a practical approach to prevent this transition by targeting Nrf2/macrophages has not been established.MethodsIn an AOM mouse model using lipopolysaccharide (LPS) injection into the middle ear, middle ear effusion (OME)-macrophages were isolated and analyzed for Nrf2 expression. M2-like polarization of macrophages was induced by Nrf2 activation and its effects on inflammatory resolution were studied by examining inflammatory neutrophils and macrophages, proinflammatory cytokines, and oxidative levels. The survival of human middle ear epithelial cells (HMMECs) co-cultured with Nrf2-modified macrophages was also evaluated. Furthermore, restoration of Nrf2 in macrophages with adeno-associated virus (AAV) vectors was performed to determine the effect on the transition of AOM to COM in experimental mice.ResultsReduced Nrf2 in OME-macrophages during the recovery phase was associated with uncured AOM or its development into COM, demonstrated by persistent increases in inflammatory neutrophils and macrophages, proinflammatory cytokines, and oxidative levels. Nrf2 activation induced M2-like polarization of macrophages, which improved the survival of co-cultured HMMECs treated with LPS in vitro. Restoration of Nrf2 in OME-derived low-Nrf2-expressing macrophages with AAV vectors significantly inhibited the transition of AOM to COM in experimental mice.DiscussionNrf2 in macrophages plays a critical role in the immune response to and resolution of otitis media Restoration of Nrf2 expression in OME-macrophages could be a promising therapeutic approach to prevent the development of COM in AOM patients.

Abstract Background HINT1 mutations cause an autosomal recessive axonal neuropathy with neuromyotonia. This is a first case report of coexistence of myasthenia gravis (MG) and HINT1-related motor axonal neuropathy without neuromyotonia. Case presentation A 32-year-old woman presented with recurrent ptosis for 8 years, diplopia for 2 years and limb weakness for 1 year and a half. Neostigmine test, elevated AChR antibody level and positive repetitive nerve stimulation supported the diagnosis of MG. Electroneurography (ENG) and electromyography (EMG) examinations revealed a motor axonal neuropathy without neuromyotonic or myokymic discharges. Next-generation sequencing and Sanger sequencing were performed to identify the gene responsible for suspected hereditary neuropathy. Genetic testing for a HINT1 mutation was performed and revealed a homozygous mutation at c.278G>T (p. G93V). The patient was treated with pyridostigmine, oral prednisolone and azathioprine. Her ptosis and diplopia have significantly improved at 6-month follow-up. Conclusions Concurrence of MG and hereditary motor axonal neuropathy without neuromyotonia is quite rare. Detection of ptosis with or without ophthalmoplegia, distribution of limb weakness, and reflex can help in recognizing the combination of MG and peripheral neuropathy. Early diagnosis is important for initial treatment and prognosis. The novel homozygous variant c.278G>T(p.G93V) contributes to the pathogenic variants spectrum of the HINT1 gene.

Background: With the development of chronic kidney disease (CKD), there are various changes in metabolites. However, the effect of these metabolites on the etiology, progression and prognosis of CKD remains unclear.Objective: We aimed to identify significant metabolic pathways in CKD progression by screening metabolites through metabolic profiling, thus identifying potential targets for CKD treatment.Methods: Clinical data were collected from 145 CKD participants. GFR (mGFR) was measured by the iohexol method and participants were divided into four groups according to their mGFR. Untargeted metabolomics analysis was performed via UPLC-MS/MSUPLC–MSMS/MS assays. Metabolomic data were analyzed by MetaboAnalyst 5.0, one-way ANOVA, principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) to identify differential metabolites for further analysis. The open database sources of MBRole2.0, including KEGG and HMDB, were used to identify significant metabolic pathways in CKD progression.Results: Four metabolic pathways were classified as important in CKD progression, among which the most significant was caffeine metabolism. A total of 12 differential metabolites were enriched in caffeine metabolism, four of which decreased with the deterioration of the CKD stage, and two of which increased with the deterioration of the CKD stage. Of the four decreased metabolites, the most important was caffeine.Conclusion: Caffeine metabolism appears to be the most important pathway in the progression of CKD as identified by metabolic profiling. Caffeine is the most important metabolite that decreases with the deterioration of the CKD stage.

Aims of the Study. Traditional Chinese medicine (TCM) has thousand years of history, and syndrome differentiation is the foundation and essence of the TCM theory. As it has distinctive advantages in diagnosing and treating the type 2 diabetes mellitus (T2DM), the purpose of this research is to distinguish T2DM patients with or without damp-heat syndrome (DHS), as well as to discover biomarkers associated with syndrome employing the metabolomics-proteomics technique. Materials and Methods. The metabolomics-proteomics of sixty patients with T2DM were acquired by high-performance liquid chromatography (HPLC). In addition, some clinical features, containing total cholesterol (TC), triglycerides (TG), hemoglobin A1c (HbA1c), body mass index (BMI), and low-density lipoprotein (LDL) together with high-density lipoprotein (HDL), were determined via clinical detection strategies. Abundant metabolites and proteins, respectively, were identified with the analysis of liquid chromatography tandem mass spectrometry (LC-MS/MS). Results. 22 differentially abundant metabolites and 15 differentially abundant proteins were determined. The analysis of bioinformatics suggested that the differentially abundant proteins were commonly associated with the renin-angiotensin system, vitamin digestion and absorption, hypertrophic cardiomyopathy, and so on. Furthermore, differentially abundant metabolites were amino acids and were associated with the biosynthesis of CoA and pantothenate, together with the metabolisms of phenylalanine, beta-alanine, proline, and arginine. Combination analysis revealed that the vitamin metabolism pathway was predominantly affected. Conclusions. DHS syndrome can be separated by certain metabolic-proteomic differences, and metabolism is particularly prominent, especially in vitamin digestion and absorption. From the molecular level, we provide preliminary data for the extensive application of TCM in the study of T2DM, and at the same time benefited in a sense diagnosis and treatment of T2DM.

Objectives Few studies have explored correlations between metabolic syndrome (MetS) alterations and renal deterioration in longitudinal cohorts. We aim to investigate associations between MetS recovery/development and rapid estimated glomerular filtration rate (eGFR) decline in the China Health and Retirement Longitudinal Study (CHARLS).Design Longitudinal cohort study.Setting This study is a secondary analysis of CHARLS.Participants After excluding individuals with age 3 mL/min/1.73 m2. The associations between rapid eGFR decline and MetS recovery/development were analysed using multivariable adjusted logistic models.Results According to MetS baseline status and follow-up, participants were divided into four groups: (1) 2460 (59.4%) in the MetS-free group, (2) 361 (8.7%) in the MetS-developed group, (3) 499 (12.0%) in the MetS recovery group and (4) 822 (19.8%) in the MetS chronic group. When compared with the MetS chronic group, the multivariable adjusted OR of rapid eGFR decline in the MetS recovery group was 0.64 (OR: 0.64; 95% CI 0.45 to 0.90, p=0.01). In contrast, when compared with the MetS-free group, the multivariable adjusted OR of rapid eGFR decline in the MetS-developed group was 1.00 (OR: 1.00; 95% CI 0.73 to 1.38, p=0.98).Conclusions Over the 4-year follow-up period, we found that MetS recovery was associated with a reduced risk of rapid eGFR decline in middle-aged and older adults, while MetS occurrence was not related to rapid eGFR decline. Recovery from MetS appeared to protect against a rapid decline in eGFR.

Abstract Scalar coupling constant (SCC), directly measured by nuclear magnetic resonance (NMR) spectroscopy, is a key parameter for molecular structure analysis, and widely used to predict unknown molecular structure. Restricted by the high cost of NMR experiments, it is impossible to measure the SCC of unknown molecules on a large scale. Using density functional theory (DFT) to theoretically calculate the SCC of molecules is incredibly challenging, due to the cost of substantial computational time and space. Graph neural networks (GNN) of artificial intelligence (AI) have great potential in constructing molecul ar-like topology models, which endows them the ability to rapidly predict SCC through data-driven machine learning methods, and avoiding time-consuming quantum chemical calculations. With a priori knowledge of angles, we propose a graph angle-attention neural network (GAANN) model to predict SCC by means of some easily accessible related information. GAANN, with a multilayer message-passing network and a self-attention mechanism, can accurately simulate the molecular-like topological structure and predict molecular properties. Our simulations show that the prediction accuracy by GAANN, with the log(MAE) = −2.52, is close to that by DFT calculations. Different from conventional AI methods, GAANN combining the AI method with quantum chemistry theory (Karplus equation) has a strong physicochemical interpretability about angles. From an AI perspective, we find that bond angle has the highest correlation with the SCC among all angle features (dihedral angle, bond angle, geometric angles) about multiple coupling types in the small molecule datasets.

Abstract Background Previous articles have focused on the diagnosis and treatment of acute hematogenous osteomyelitis. Here, we present a case of chronic hematogenous osteomyelitis in a 2-month-old girl. The diagnostic procedure was unusual and difficult due to negative culture results. Case presentation A girl aged 2 months and 23 days had fever and swelling in her right lower leg for 7 days. On the basis of her medical history, physical, and histological examination results; and radiologic and magnetic resonance imaging findings, a diagnosis of chronic osteomyelitis was made. The patient underwent surgical treatment and was discharged successfully. The patient showed good recovery and no sequelae at the 12-month follow-up. Conclusion Hematogenous osteomyelitis in babyhood is different from that at any other age. Hematogenous osteomyelitis-related bone destruction in babyhood is more serious and occurs faster. The transition from acute hematogenous osteomyelitis to chronic hematogenous osteomyelitis takes only 7 days. To the best of our knowledge, this chronic hematogenous osteomyelitis patient is the youngest ever reported.

The persistent heavy precipitation that occurred in most of West China (WC) during August 11–18, 2020, generated the highest rainfall record since recording began in 1961 and was selected as one of the top 10 worst national natural disasters of 2020 in China. Favorable circulation was sustained during August; WC was positioned between two anomalous high-pressure centers over the Tibetan Plateau and Sea of Japan and an anomalous low-pressure center over Mongolia located on its north side, which created a stable and long trough and formed a low-pressure center over WC. At 200 hPa, the subtropical westerly jet was much stronger than average and southward, and the South Asian High (SAH) was strong and extended eastward to 150°E. At 500 hPa, the western Pacific subtropical high (WPSH) was westward and exceptionally strong, which helped abundant water vapor reach the southeastern part of WC and provided favorable dynamic and thermodynamic conditions for precipitation in this region. In addition, the eastward extension of the SAH promotes the westward extension of WPSH, which collectively enhanced the precipitation in WC. At 850 hPa, the low-level jet corresponding to the west-extending subtropical high from the Sea of Japan to WC further enhanced and guided the water vapor transport to WC. In addition, the Mei-Yu front over the Yangtze River Basin in June and July strengthened the northwestward spread of diabatic heating, transient energy, and wave activity fluxes, which likely influenced the large-scale circulation factors and reinforced the precipitation in WC in August 2020.

Abstract Background Choroidal osteoma is a benign intraocular tumor that can increase risk of developing choroidal neovascularization. The visual prognosis is influenced by the tumor location, decalcification status, overlying RPE atrophy, presence of choroidal neovascularization, persistence of subretinal fluid and occurrence of subretinal hemorrhages. Case presentation The authors present a 40-year-old woman diagnosed with choroidal osteoma of the right eye. Her best corrected visual acuity was 12/20 but decreased to 5/20 due to secondary choroidal neovascularization after 8 years follow up. Fundus examination revealed an enlarged choroidal osteoma in most margins at posterior pole with schistose hemorrhage beside macula. Optical coherence tomography angiography revealed unique features in the vascular changes of choroidal neovascularization in choroidal osteoma in the outer retinal layer and choroid capillary layers, and subretinal neovascularization. Indocyanine green fluorescence angiography showed there was hypo-fluorescence at the peripapillary with faint hyper-fluorescence at the macular, corresponding to the location on the fundus photograph. The patient received 3 injections of intravitreal ranibizumab. After 1 year follow up, her visual acuity of the right eye was 18/20 and the CNV had regressed. Conclusions We present the findings and treatment of a case of choroidal osteoma with secondary choroidal neovascularization. Optical coherence tomography angiography combined with FFA and ICGA is used to analysis the characteristics of secondary choroidal neovascularization. Optical coherence tomography angiography can reveal some unique characteristics in the vascular changes compared to fundus fluorescein angiography.

Background: Treatment of lower limb post-traumatic osteomyelitis used to be a staged process, with radical debridement of bone and soft tissues at first stage, followed by a second-stage limb reconstruction operation to restore the limb integrity. Some studies recently reported that achieving infection eradication and limb reconstruction at single-stage seems to be an effective method for lower limb infection, but a comparative study remains lacking. This study aims to compare the results of radical debridement combined with a first/second-staged osteotomy and bone transport, for the management of lower limb post-traumatic osteomyelitis. Methods: From January 2013 to June 2018, a total of 102 patients with lower limb post-traumatic osteomyelitis met the criteria were included for analysis, in which 70 patients received one-stage debridement, antibiotic-loaded implantation, metaphysis osteotomy and bone transport were named as one-stage group, while 32 patients with first-stage debridement and antibiotic-loaded calcium sulfate implantation, second-stage osteotomy and bone transport were devised as two-stage group. The outcomes of hospitalization (hospital stay, costs of treatment, surgical time, antibiotic usage) and follow-up (infection-free, treatment failure, infection recurrence, external fixation index (EFI) and docking site union) between the two groups were retrospectively compared. Results: For outcomes of hospitalization, patients in the one-stage group had batter results on hospital stay (18.2 days versus 28.9 days, P ​ ​0.05) without any additional debridement operation. 94.3% (66/70) patients in the one-stage group earned wound healing after the operation, comparing to 96.9% (31/32) patients healed in the two-stage group (P ​> ​0.05). Uncontrolled infection was observed on 4 (5.7%) patients in the one-stage group and 1 (3.1%) patients in the two-stage group (P ​> ​0.05), with a result of three achieved infection free in the one-stage group and one patient suffered from amputation in each group respectively. 5 (7.2%) patients in the one-stage group and 1 (3.2%) patient in the two-stage group encountered with infection recurrence (P ​> ​0.05) and were well-managed with re-debridement and antibiotics usage. Significance was not found between two groups on EFI (74.8 days/cm versus 69.0 days/cm, P ​> ​0.05) and docking site nonunion rate (14.5% versus 18.9%, P ​> ​0.05), indicating that bone transport in different stages played a less essential role on bone generation process. The other complications, such as prolonged aseptic drainage [24.3% (17/70) versus 21.9% (7/32)], re-fracture [5.8% (4/69) versus 3.2% (1/31)], pin-tract infection [23.2% (16/69) versus 19.4% (6/31)], joint stiffness and deformity [26.1% (18/69) versus 32.3% (10/31)], also showed less significance when comparing between two groups (P ​> ​0.05), suggesting that different transport stages play little role on complications formation. Conclusions: One-stage radical debridement and bone transport was proven to be a safe and effective method for treating static (or near static) lower limb osteomyelitis. Translational potential statement: Translational potential statement One-stage debridement and bone transport is sample, effective and time-saving, with similar complications compared to conventional two-stage protocol. This treatment protocol might provide an alternative for the treatment of static (or near static) lower limb osteomyelitis.

Introduction: The glomerular filtration rate (GFR) is crucial for chronic kidney disease (CKD) diagnosis and therapy. Various studies have sought to recognize ideal endogenous markers to improve the estimated GFR (eGFR) for clinical practice. To screen out potential novel metabolites related to GFR (mGFR) measurement in CKD patients from the Chinese population, we identified more biomarkers for improving GFR estimation. Methods: Fifty-three CKD participants were recruited from the third affiliated hospital of Sun Yat-sen University in 2020. For each participant, mGFR was evaluated by utilizing the plasma clearance of iohexol and collecting serum samples for untargeted metabolomics analyses by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC–MS/MS). All participants were divided into four groups according to mGFR. The metabolite peak area data were uploaded to MetaboAnalyst5.0 for one-way ANOVA, principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) and confirmed the metabolites whose levels increased or decreased with mGFR and Variable Importance in Projection (VIP) values>1. Metabolites were ranked by correlation with the original values of mGFR, and metabolites with a correlation coefficient>0.8 and VIP >2 were identified. Results: We screened out 198 metabolites that increased or decreased with mGFR decline. After ranking by correlation with mGFR, the top 50 metabolites were confirmed. Further studies confirmed the 10 most highly correlated metabolites. Conclusion: We screened out the metabolites that increased or decreased with mGFR decline in CKD patients from the Chinese population, and 10 of them were highly correlated. They are potential novel metabolites to improve GFR estimation.

Abstract Background We present a case of an immense unprecedented tibial bone lengthening of 33.5 cm. The management of chronic osteomyelitis of the right tibia with subtotal tibial bone defect, talus defect and equinus ankle deformity. We demonstrate limb reconstruction by distraction osteogenesis and correction of ankle deformity with the Ilizarov technique. Limb salvage was preferred as an alternative to amputation to restore basic limb function. Case presentation A 16-year-old male patient fell and injured his right lower leg. He attempted to treat the symptoms with traditional home remedies. During 15 months of self-treating, he developed osteomyelitis of the right tibia and had lost function in his foot. Radiology revealed immense bone defect of the right tibia, including talus bone defect and equinus deformity of the calcaneus. The patient’s right tibia was non weight-bearing, had drainage sinus just below his knee and a large scar anteriorly along the entire length of the tibia. Conclusion Upon completion of treatment, the patient was able to avoid amputation of his leg with partially restored function for weight-bearing. He carried himself without assistance after 3 years of lost function in his right leg. Tibial bone distraction osteogenesis of 33.5 cm was done after 90% of the tibial length was defected. To the best of our best knowledge, this case is one of a kind to achieve distraction of tibial bone to such length.

ObjectivesA huge population, especially the elderly, suffers from otogenic vertigo. However, the multi-modal vestibular network changes, secondary to periphery vestibular dysfunction, have not been fully elucidated. We aim to identify potential microstate electroencephalography (EEG) signatures for otogenic vertigo in this study.Materials and MethodsPatients with recurrent otogenic vertigo and age-matched healthy adults were recruited. We performed 256-channel EEG recording of all participants at resting state. Neuropsychological questionnaires and vestibular function tests were taken as a measurement of patients’ symptoms and severity. We clustered microstates into four classes (A, B, C, and D) and identified their dynamic and syntax alterations of them. These features were further fed into a support vector machine (SVM) classifier to identify microstate signatures for vertigo.ResultsWe compared 40 patients to 45 healthy adults, finding an increase in the duration of Microstate A, and both the occurrence and time coverage of Microstate D. The coverage and occurrence of Microstate C decreased significantly, and the probabilities of non-random transitions between Microstate A and D, as well as Microstate B and C, also changed. To distinguish the patients, the SVM classifier, which is built based on these features, got a balanced accuracy of 0.79 with a sensitivity of 0.78 and a specificity of 0.8.ConclusionThere are several temporal dynamic alterations of EEG microstates in patients with otogenic vertigo, especially in Microstate D, reflecting the underlying process of visual-vestibular reorganization and attention redistribution. This neurophysiological signature of microstates could be used to identify patients with vertigo in the future.

Otosclerosis is caused by abnormal bone remodeling in the middle ear, resulting in progressive hearing loss, dizziness, balance problems, and tinnitus. Previous infection, stress fractures of the bony tissue surrounding the inner ear, immune disorders, and genetic factors are believed to contribute to this disease. Currently, no effective drug treatment for otosclerosis is known. Herein, we generated an induced pluripotent stem cell line from the peripheral blood mononuclear cells of an otosclerosis patient. The cell line exhibited normal morphology, karyotype, and pluripotency marker expression. A teratoma assay revealed successful differentiation into all three germ layers.

Diabetes is a silent killer with increased global public health burden along with several life threatening complications. Myocardial infarction was diagnosed in 60% of diabetic patients worldwide. In this study, the synthesized nanocomposites were subjected to Ultraviolet–Visible Spectroscopic analysis, Photoluminescence Spectroscopic analysis, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), dynamic light scatting (DLS) and Field Emission Scanning Electron Microscope (FE-SEM) & energy dispersive X-ray analysis (EDAX) analysis. Further in vivo studies were performed on young male Wistar rats. Young male Wistar rats were induced diabetes with streptozotocin induced diabetes model and the diabetic rats confirmed with blood glucose were utilized for further study. The rats were grouped into control, diabetic, diabetic induced treated with 5 mg/kg of SCP-D-P nanocomposites and diabetic induced treated with 10 mg/kg of SCP-D-P nanocomposites. After treatment period the rats were estimated for diabetic functioning parameters such as glucose level, insulin level, c-peptide, HOMA-IR and cardiac functioning parameters such as total cholesterol, triglycerides, CK, LDH, MDA, NO, GSH, CAT, SOD, GST. Rats were subjected to echocardiography analysis for assessing the cardiac function. Inflammatory markers TNF-α and IL-β were estimated to analyze the anti-inflammatory property of SCP-D-P nanocomposites and it is further confirmed with histopathological analysis of cardiac tissue with H&E staining. Further we assessed the impact of SCP-D-P nanocomposites on p62/Keap1/Nrf2 signaling pathway which is plays a vital role in myocardiac ischemia. Our results of nanocomposite analysis depicts SCP-D-P nanocomposites is a potent nanoparticles which persuasively decreased the diabetic inducing factors, ameliorated cardiac functioning. Histological analysis clearly depicts SCP-D-P nanocomposites prevented diabetic induced cardiac tissue damage via activating p62/Keap1/Nrf2 signaling pathway. Over all our results confirms SCP-D-P nanocomposites is potent anti-diabetic, cardioprotective molecule.

Abstract Background Neuromuscular blockade and pneumoperitoneum (PP) are important factors to ensure successful laparoscopic surgery. However, residual neuromuscular blockade (rNMB) and PP are associated with many unfavorable complications. The aim of this study is to compare the cost-effectiveness of using sugammadex versus neostigmine in laparoscopic surgery in China. Methods A decision tree model was developed with a time horizon based on laparoscopic surgery related hospitalization duration. 2000 patients using sugammadex or neostigmine were simulated within the model. The model outcomes included incidence of rNMB and PP related complications and their treatment costs. Data on clinical efficacy, safety and cost were collected from published literature and interviews of physicians. Results The model projected that treatment with sugammadex instead of neostigmine would lead to 673 fewer total complications, including rNMB/PP related complications, hospitalization, and other AEs (621 events versus 1294 events, respectively). Use of sugammadex was associated with an incremental medication cost of ¥1,360,410. However, 93.6% of the increased medication cost can be off-set by the reduced costs attributable to treatment of rNMB related complications, PP related complications, hospitalization and other adverse events in sugammadex group. In aggregate, the sugammadex group incurred an incremental cost of ¥86,610 to prevent 673 complications, (¥128.56 per one rNMB/PP related complications prevention). One-way sensitivity analysis confirmed the robustness of the model. Conclusions Use of sugammadex in replacement of neostigmine would result in significantly lower rNMB/PP related complications but at a substantially higher medication cost. Upon accounting for the costs associated with treatment of rNMB/PP related complications, 93.6% of medication cost is projected to be offset. In balance, sugammadex appears to offer good value for reversal of neuromuscular blockade for laparoscopic surgery in China.

Abstract Background The incidence of intramedullary infection is increasing with increased use of intramedullary fixation for long bone fractures. However, appropriate treatment for infection after intramedullary nailing is unclear. The purpose of this study was to report the results of our treatment protocol for infection after intramedullary nailing: intramedullary nail removal, local debridement, reaming and irrigation, and antibiotic-loaded calcium sulfate implantation with or without segmental bone resection and distraction osteogenesis. Methods We retrospectively reviewed the records of patients with an infection after intramedullary nailing treated from 2014 to 2017 at our center. Patients with follow-up of less than 24 months, received other treatment methods, or those with serious medical conditions were excluded from the analysis. Patients met the criteria were treated as described above, followed by distraction osteogenesis in 9 cases to repair bone defect. The infection remission rate, infection recurrence rate, and post-operative complication rates were assessed. Results A total of 19 patients were included in the analysis. All of patients had satisfactory outcomes with an average follow-up of 38.1 ± 9.4 months (range, 24 to 55 months). Eighteen patients (94.7%) achieved infection remission; 1 patient (5.3%) developed a reinfection that resolved after repeat debridement. Nine patients with bone defects (average size 4.7 ± 1.3 cm; range, 3.3 to 7.6 cm) were treated with bone transport which successfully restored the length of involved limb. The mean bone transport duration was 10.7 ± 4.0 months (range, 6.7 to 19.5 months). The majority of patients achieved full weight bearing and became pain free during the follow-up period. Postoperative complications mainly included prolonged aseptic drainage (7/19; 36.8%), re-fracture (1/19; 5.3%) and joint stiffness, which were successfully managed by regular dressing changes and re-fixation, respectively. Conclusion Intramedullary nail removal, canal reaming and irrigation, and antibiotic-loaded calcium sulfate implantation (with or without distraction osteogenesis) is effective for treating infections after intramedullary nailing.

Abstract Background To investigate the ability of intraoperative optical coherence tomography (iOCT) during macular hole (MH) surgery to image different hole edge configurations and predict the restoration of retinal microstructure and visual outcomes. Methods This retrospective case series study included 53 MH patients. One eye each was assessed with iOCT during vitrectomy after internal limiting membrane (ILM) peeling. The MHs were categorized into three groups according to the morphology of the hole edge. The Hole-Door group had vertical pillars of tissue that projected into the vitreous cavity after ILM peeling. The Foveal Flap group had a preoperative foveal flap that adhered to the hole edge after ILM peeling, and the Negative group had neither a hole-door nor a foveal flap. At 6 months after surgery, the retinal microstructure restoration and visual outcomes were compared among the groups. Results All eyes had MH closure, and the postoperative best corrected visual acuity (BCVA) was significantly improved compared with the preoperative BCVA (P 400-μm group (n = 28, the Hole-Door group and Foveal Flap group had significantly better final visual acuity and restoration of ELM than the Negative group (P = 0.013, P = 0.005). Conclusions The novel use of iOCT during MH surgery confirmed the presence of hole edges configured as door-holes, foveal flaps, or neither. The data acquired by iOCT can provide useful predictive information for postoperative restoration of the retinal microstructure and visual outcome of MH, especially large ones.

Abstract Background Although various methods have been introduced, the management of chronic tibial osteomyelitis remains a challenge. This study aims to assess a combined treatment method, local debridement combined with antibiotic-loaded calcium sulfate implantation, for the management of the local (Cierny-Mader type III) tibial osteomyelitis. Methods Forty-two patients (43 limbs) with type III tibial osteomyelitis, from January 2012 to December 2018, who received the treatment method mentioned above were included in the study. The infection remission rate, recurrence rate, complications rate, and bone healing rate were respectively analyzed. Results With a mean follow-up of 42.8 months, 38 limbs (37 patients) (88.4%, 38/43) achieved infection remission without recurrence. Among those patients pain, limitation of movement, sinus tracts, topical redness, and swelling were generally eliminated. Only 4 patients felt slight pain after a long-distance walk, while another 6 patients showed minor but acceptable discomfort in affected limbs. Five patients (11.6%) suffered from osteomyelitis recurrence that required secondary surgical and medical treatment, but no amputation was necessary to eliminate the infection. Prolonged aseptic drainage was the most frequent complication that was observed in 13 patients (30.0%). They were successfully managed by appropriate wound caring in 10 patients and by surgical intervention, months later, in 3 patients. According to the final X-ray examination, bone losses caused by local debridement were generally repaired, though the shape of the tibia was not well-restored to its initial form in 17 limbs. No fracture was recorded during follow-up. Conclusion Local debridement combined with antibiotic-loaded calcium sulfate implantation is effective and safe in a single-stage treatment of chronic Cierny-Mader III tibial osteomyelitis.

Purpose: To investigate the changes in choroidal vascular structures after exercise in patients with glaucoma using an image binarisation algorithm with enhanced-depth imaging optical coherence tomography.Methods: Thirty-four eyes of 19 patients with primary open-angle glaucoma and 40 eyes of 20 normal subjects were included in the glaucoma and control groups, respectively. All subjects were evaluated before, immediately after, and 30 min after 20-min running at moderate speed. The subfoveal choroidal area was segmented into the luminal area (LA) and stromal area (SA), and the choroidal vascularity index (CVI) was measured by calculating the ratio of LA to the total choroidal area (TCA). The mean intraocular pressure (IOP), subfoveal choroidal thickness, CVI, SA, CA, and TCA were compared within and between both groups. The correlation between CVI, IOP, and other vascular indexes was investigated.Results: In the glaucoma group, a significantly lower CVI was found immediately after exercise and recovered 30 min after exercise. Higher TCA and LA levels were demonstrated 30 min after exercise compared to immediately after exercise. In both groups, IOP decreased immediately after exercise but was restored after a 30-min rest. In the glaucoma group, there was a higher correlation between CVI and other choroidal vascular parameters than in the control group. There was no difference in IOP or choroidal parameters between the groups at different time points.Conclusion: In patients with glaucoma, CVI decreased significantly immediately after exercise, indicating that the choroidal layer is affected by exercise and an unhealthy vascular regulatory mechanism.

We reported a case of primary central nervous system lymphoma (PCNSL) coexistent with glial fibrillary acidic protein (GFAP) astrocytopathy, and discussed the problems needing attention in the diagnosis and differential diagnosis of GFAP astrocytopathy. Our patient was a 51-year-old female who presented with somnolence for a month, and memory declination for 10 days. Brain magnetic resonance imaging (MRI) demonstrated multiple abnormal enhancement lesions in bilateral basal ganglia and around the third ventricle, as well as transient T2-weighted hyper-intensity lesions at the splenium of the corpus callosum during the course of the disease. The cerebrospinal fluid (CSF) was positive for anti-GFAP antibodies by antigen-transfected HEK293 cell-based assay (indirect immunofluorescence assay). She was initially diagnosed with autoimmune GFAP astrocytopathy. After treatment with corticosteroids for about 2 months, she displayed poor response and even worsened clinical manifestations when the dose of prednisone reduced to 45 mg. Stereotactic brain biopsy was adopted and the diagnosis of large B-cell lymphoma, non-germinal center type was established on pathological examination. The results of brain biopsy also showed perivascular inflammation and CD8+ T cell infiltration, which also accorded with GFAP astrocytopathy. After chemotherapy with rituximab and methotrexate, the patient showed clinical and radiological improvement significantly. Our findings suggest that positivity of GFAP antibody calls for cautious interpretation. Cancer screening appropriate for age, sex, and risk factors is recommended for GFAP antibody-positive patients, especially for patients with atypical clinical and radiologic manifestations.

Background: Late-onset multiple acyl-CoA dehydrogenase deficiency (LO-MADD) describes a curable autosomal recessive genetic disease caused by ETFDH mutations that result in defects in ETF-ubiquinone oxidoreductase. Almost all patients are responsive to riboflavin. This study describes the clinical presentations and genetic characteristics of five LO-MADD patients.Methods: From 2018 to 2021, we collected clinical and genetic data on five patients diagnosed with LO-MADD at our hospital and retrospectively analyzed their clinical characteristics, laboratory examination, electromyography, muscle biopsy, genetic analysis, and outcome data.Results: This study included three males and two females with mean onset age of 37.8 years. Fluctuating exercise intolerance was the most common presentation. Serum creatine kinase (CK) levels were significantly elevated in all patients, and plasma acylcarnitine profiles revealed an increase in long-chain acylcarnitine species in three cases. The urinary organic acid study revealed a high level of hydroxyglutaric acid in all patients. Electrophysiology demonstrated myogenic impairment. Muscle biopsies revealed lipid storage myopathy. Molecular analysis identified nine mutations (three novels and six reported) in ETFDH. Exercise intolerance and muscle weakness were dramatically improved in all patients treated with riboflavin (100 mg) daily following diagnosis.Conclusions: LO-MADD is caused by ETFDH variants and responds well to riboflavin. Three novel ETFDH pathogenic variants were identified, expanding their spectrum in the Chinese population and facilitating future interpretation and analysis of ETFDH mutations.

As a life-threatening multiple organ dysfunction attributable to maladjusted host immune responses to infection, sepsis is usually the common pathway to serious prognosis and death for numerous infectious diseases all over the world. Sepsis-associated encephalopathy (SAE) is frequently complicated by septic conditions, and is one of the most important reasons for increased mortality and poor outcomes in septic patients which is still an urgent clinical problem need to be solved. In this research, a conspicuously discovery of treatment-related translational use for berberine was elaborated. The results revealed that berberine treatment significantly restored cognitive impairment in sepsis mice. Reduced expression levels of TNF-α, IL-1α, and C1qA were exhibited in the hippocampus of the berberine treatment group, and attenuated effect of declining neo-neuron, activation of microglia and astrocytes in the hippocampus of mice with sepsis were also found. Moreover, berberine inhibits microglia-stressed A1 astrocytes by inhibiting HMGB1 signaling was revealed, then the molecular mechanism of HMGB1/RAGE signaling inhibition leads to the better outcome of SAE was elucidated. To summarize, this research indicated that berberine targets HMGB1/RAGE signaling to inhibit microglia-stressed A1 astrocyte and neo-neuron decline, which consequently alleviates sepsis-induced cognitive impairment. Collectively, berberine may serve as potential therapeutic drug and HMGB1/RAGE signaling would be a novel target for medicine development for treating SAE.

Abstract Background Managing with diabetic foot osteomyelitis (DFO) is challenging. Even after infective bone resection and thorough debridement, DFO is still difficult to cure and has a high recurrence rate. This retrospective study aims to compare the outcomes of two treatment methods, infected bone resection combined with adjuvant antibiotic-impregnated calcium sulfate and infected bone resection alone, for the treatment of diabetic foot osteomyelitis. Methods Between 2015 to 2017, 48 limbs (46 patients) with DFO met the criteria were included for assessment. 20 limbs (18 patients) were included in the calcium sulfate group (the CS group) in which vancomycin and/or gentamicin-impregnated calcium sulfate was used as an adjuvant after infected bone resection while 28 limbs (28 patients) as the control group were undergone infected bone resection only. Systemic antibiotics, postoperative wound care and offloading were continued to be applied following surgery in both groups. The time to healing, healing rate, recurrence rate and amputation rate were compared between the two groups. Results In total, 90% (18/20) limbs in the CS group as compared to 78.6% (22/28) infected limbs in the control group went to heal (P = 0.513). The Mean time to healing was 13.3 weeks in the CS group and 11.2 weeks in control group (P = 0.132). Osteomyelitis recurrence rate was 0% (0/18) in the CS group and 36.4% (8/22) in the control group (P = 0.014). Postoperative leakage in calcium sulfate group was 30.0% (6/20) with a mean duration of 8.5 weeks. Amputation rate in the control group was 7.1% (2/28) compared to 0% (0/20) in the CS group (P = 0.153). Conclusions Antibiotic-impregnated calcium sulfate as an adjuvant prevents the recurrence of DFO but cannot improve the healing rate, reduce the postoperative amputation rate or shorten the time to healing. Prolonged postoperative leakage as the most common complication can be managed with regular dressing. Level of Evidence III, Retrospective Comparative Study.

Purpose: To introduce the application of intraoperative optical coherence tomography (iOCT) in pars plana vitrectomy (PPV) for various vitreoretinal diseases, and to report the 4-year assessment of feasibility and utility in Chinese population. Methods: Retrospective case series of patients who underwent PPV and iOCT scan at Eye Hospital of Wenzhou Medical College from January 2016 to January 2020. Clinical characteristics were documented before operation, and we intraoperatively recorded the time and results of iOCT scanning, specific surgical maneuvers performed, the consistency with the planned strategies before surgery, the type of OCT images obtained, and adverse events (AEs). The surgeon feedback was collected to evaluate the utility of iOCT during surgery. Results: In total 339 eyes successfully completed iOCT scan, with an average scanning time of 3.54±2.3min, including 59 cases of idiopathic macular hole (iMH), 134 cases of idiopathic epiretinal membrane (iERM), 33 cases of lamellar macular hole (LMH), 40 cases of high myopic maculopathy, 13 cases of vitreous macular traction (VMT), 60 cases of dense vitreous hemorrhage (VH). The iOCT findings were not consistent with examination under the operating microscope in 49 cases (14.5%), including 29 cases (8.6%) which changed the operation strategies during surgery. The Hole-door phenomenon arose in 20 cases (33.9%) of iMH and 3 cases (25%) of high myopic MH after ILMs peeling. Moreover, the residue ERM was observed in nine cases (6.7%) of iERM and two cases (14.3%) in high myopic ERM after ILMs peeling. Some new surgical methods could also be confirmed using iOCT. Conclusion: The application of iOCT has a significant clinical functionality in vitreoretinal surgery, providing the surgeon with a new surgical understanding, guiding the selection of a more reasonable operative procedure during surgery, predicting postoperative recovery and improving postoperative outcomes.

BackgroundTo date, the missed diagnosis rate of pulmonary hypertension (PH) was high, and there has been limited development of a rapid, simple, and effective way to screen the disease. The purpose of this study is to develop a deep learning approach to achieve rapid detection of possible abnormalities in chest radiographs suggesting PH for screening patients suspected of PH.MethodsWe retrospectively collected frontal chest radiographs and the pulmonary artery systolic pressure (PASP) value measured by Doppler transthoracic echocardiography from 762 patients (357 healthy controls and 405 with PH) from three institutes in China from January 2013 to May 2019. The wohle sample comprised 762 images (641 for training, 80 for internal test, and 41 for external test). We firstly performed a 8-fold cross-validation on the 641 images selected for training (561 for pre-training, 80 for validation), then decided to tune learning rate to 0.0008 according to the best score on validation data. Finally, we used all the pre-training and validation data (561+80 = 641) to train our models (Resnet50, Xception, and Inception V3), evaluated them on internal and external test dataset to classify the images as having manifestations of PH or healthy according to the area under the receiver operating characteristic curve (AUC/ROC). After that, the three deep learning models were further used for prediction of PASP using regression algorithm. Moreover, we invited an experienced chest radiologist to classify the images in the test dataset as having PH or not, and compared the prediction accuracy performed by deep learing models with that of manual classification.ResultsThe AUC performed by the best model (Inception V3) achieved 0.970 in the internal test, and slightly declined in the external test (0.967) when using deep learning algorithms to classify PH from normal based on chest X-rays. The mean absolute error (MAE) of the best model for prediction of PASP value was smaller in the internal test (7.45) compared to 9.95 in the external test. Manual classification of PH based on chest X-rays showed much lower AUCs compared to that performed by deep learning models both in the internal and external test.ConclusionsThe present study used deep learning algorithms to classify abnormalities suggesting PH in chest radiographs with high accuracy and good generalizability. Once tested prospectively in clinical settings, the technology could provide a non-invasive and easy-to-use method to screen patients suspected of having PH.

To investigate the potential applications and the molecular mechanisms of transcranial direct current stimulation (tDCS) on cognitive impairment in a vascular dementia (VD) animal model. Sprague-Dawley rats were used in this study. VD rat model was induced by modified permanent bilateral common carotid artery occlusion (2-VO) approach. Anodal tDCS was applied to the animals. Morris water maze was used to analyze spatial memory and navigation ability. The pathological changes in the hippocampal CA1 region and cerebral cortex were examined via Hematoxylin-Eosin staining. The rats were sacrificed for the measurement of the level of superoxide (SOD), glutathione (GSH), reactive oxidative species (ROS), malondialdehyd (MDA), Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α level in the hippocampus. Western blot was carried out to measure the hippocampal expression of microtubule-associated protein 1 light chain 3 (LC-3) and p62. Rats with VD have decreased number of neurons in the hippocampus and cerebral cortex, as well as worse cognitive impairment. The proliferation of activated microglia and astroglia, accompanied with attenuation of myelination were observed in the white matter about 1 month after 2-VO operation. These abnormalities were significantly ameliorated by tDCS treatment. Further study revealed that anodal tDCS could suppress the MDA and ROS level, while enhance the SOD and GSH level to reduce the oxidative stress. Anodal tDCS could inhibit hypoperfusion-induced IL-1β, IL-6, and TNF-α expression to attenuate inflammatory response in hippocampus. Moreover, anodal tDCS treatment could alleviate autophagy level. The study has demonstrated a possible therapeutic role of tDCS in the treatment of cognitive impairment in VD.

Abstract Background The Rab27 family of small GTPases promotes the progression of breast cancer, melanoma, and other human cancers. In this review, we discuss the role of Rab27 GTPases in cancer progression and the potential applications of these targets in cancer treatment. Main body Elevated expression of Rab27 GTPases is associated with poor prognosis and cancer metastasis. Moreover, these GTPases govern a variety of oncogenic functions, including cell proliferation, cell motility, and chemosensitivity. In addition, small GTPases promote tumor growth and metastasis by enhancing exosome secretion, which alters intracellular microRNA levels, signaling molecule expression, and the tumor microenvironment. Conclusion Rab27 GTPases may have applications as prognostic markers and therapeutic targets in cancer treatment.

Agricultural weeds pose great challenges to sustainable crop production, owing to their complex origins and abundant genetic diversity. Weedy rice (WD) infests rice fields worldwide causing tremendous losses of rice yield/quality. To explore WD origins and evolution, we analyzed DNA sequence polymorphisms of the seed shattering genes (sh4 and qsh1) in weedy, wild, and cultivated rice from a worldwide distribution. We also used microsatellite and insertion/deletion molecular fingerprinting to determine their genetic relationship and structure. Results indicate multiple origins of WD with most samples having evolved from their cultivated progenitors and a few samples from wild rice. WD that evolved from de-domestication showed distinct genetic structures associated with indica and japonica rice differentiation. In addition, the weed-unique haplotypes that were only identified in the WD samples suggest their novel mutations. Findings in this study demonstrate the key role of de-domestication in WD origins, in which indica and japonica cultivars stimulated further evolution and divergence of WD in various agroecosystems. Furthermore, novel mutations promote continued evolution and genetic diversity of WD adapting to different environments. Knowledge generated from this study provides deep insights into the origin and evolution of conspecific weeds, in addition to the design of effective measures to control these weeds.

Background/Aims: Busulfan is commonly used for cancer chemotherapy. Although it has the advantage of increasing the survival rate of patients, it can cause male infertility via damaging the testes and reducing sperm counts. Therefore, the underlying mechanism should be explored, and new agents should be developed to protect the male reproductive system from busulfan-induced damage. Endoplasmic reticulum stress (ERS) is considered a key contributor to numerous pathologies. Despite several studies linking ERS to toxicants, studies have yet to determine whether ERS is a contributing factor to busulfan-induced testicular damage. Melatonin is a well-known broad-spectrum antioxidant, anti-inflammatory and antitumour agent, but the effects of melatonin on busulfan-induced ERS in mouse testes damage are less documented. Methods: The effects of melatonin were measured by immunofluorescence staining, Western blot, qRT-PCR analysis and flow cytometry assay. The underlying mechanism was investigated by measuring ERS. Results: We found that ERS was strongly activated in mouse testes (in vivo) and the C18-4 cell line (in vitro) after busulfan administration. ERS-related apoptosis proteins such as caspase-12, CHOP and caspase-3 were activated, and the expression of apoptotic proteins such as P53 and PUMA were upregulated. Furthermore, we investigated whether melatonin reduced the extent of damage to mouse testes and improved the survival rates of busulfan-treated mice. When exploring the underlying mechanisms, we found melatonin could counteract ERS by decreasing the expression levels of the ERS markers GRP78, ATF6, pIRE1 and XBP1 in mouse testes and mouse SSCs (C18-4 cells). Moreover, it blocked the activation of ERS-related apoptosis proteins caspase-12, CHOP and caspase-3 and suppressed P53 and PUMA expression stimulated by busulfan both in vivo and in vitro. Conclusion: Our results demonstrate that ERS is an important mediator for busulfan-induced apoptosis. The attenuation of ERS by melatonin can prevent busulfan-treated SSCs apoptosis and protect busulfan-treated testes from damage. Thus, this study suggests that melatonin may alleviate the side effects of busulfan for male patients during clinical treatment.

Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum. However, their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct target. In addition, the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon exposure. To investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides, we used a C57BL/6J mouse model treated with kanamycin. We found that the mice exhibited auditory deficits following the acute loss of outer hair cells. Spiral ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over time. Transcriptomic profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response, particularly those related to the NLRP3 inflammasome. Activation of the canonical pyroptotic pathway in spiral ganglion neurons was observed, accompanied by infiltration of macrophages and the release of proinflammatory cytokines. Pharmacological intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury model. These findings suggest that NLRP3 inflammasome–mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron degeneration. Inhibition of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.

Objective To study the animal model suitable for the observation of early osteogenesis on the surface of titanium implant. Methods Modify implants mode which the outer thread of the implant next to the osteotomy bone wall while the inter thread keep a certain distance to osteotomy bone wall was adopted in the 1-year-old male Beagle dogs.After extraction of all mandibular premolars and first molar bilaterally in the 4 dogs, 20 implants replaced the position. All sections were stained for histological analysis. Results The surgical wound in the 4 dogs healed by first intention. The titanium implants have good stability. The formation of the new bone, which include the contact osteogenesis and distanceosteogenesis, was observed as it progressed not only in the surface of the osteotomy bone wall but also in the surface of the implants. Conclusion The established animal model is suitable for the observation of both early osteogenesis in implant and the influences of implant surface properties to the early osteogenesis.

Background: Amyotrophic lateral sclerosis (ALS) and some mimic disorders, such as distal-type cervical spondylotic amyotrophy (CSA), Hirayama disease (HD), and spinobulbar muscular atrophy (SBMA) may present with intrinsic hand muscle atrophy. This study aimed to investigate different patterns of small hand muscle involvement in ALS and some mimic disorders. Methods: We compared the abductor digiti minimi/abductor pollicis brevis (ADM/APB) compound muscle action potential (CMAP) ratios between 200 ALS patients, 95 patients with distal-type CSA, 88 HD patients, 43 SBMA patients, and 150 normal controls. Results: The ADM/APB CMAP amplitude ratio was significantly higher in the ALS patients (P < 0.001) than that in the normal controls. The ADM/APB CMAP amplitude ratio was significantly reduced in the patients with distal-type CSA (P < 0.001) and the HD patients (P < 0.001) compared with that in the normal controls. The patients with distal-type CSA had significantly lower APB CMAP amplitude than the HD patients (P = 0.004). The ADM/APB CMAP amplitude ratio was significantly lower in the HD patients (P < 0.001) than that in the patients with distal-type CSA. The ADM/APB CMAP amplitude ratio of the SBMA patients was similar to that of the normal controls (P = 0.862). An absent APB CMAP and an abnormally high ADM/APB CMAP amplitude ratio (≥4.5) were observed exclusively in the ALS patients. Conclusions: The different patterns of small hand muscle atrophy between the ALS patients and the patients with mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders.

This study explores the relationship between the morphology and solar potential of high-density areas in the subtropics high density city known as Shanghai. 1260 parametric scenarios were modeled and their solar irradiation potentials were simulated via a customized workflow. In addition to the five well-known morphological parameters, this study proposed two innovative morphological parameters SSU600 and SSU400, which captured the solar receiving properties of the building envelopes and could be easily calculated based on the meteorological data. For analytical purposes, the previously morphological parameters were considered as independent variables, whereas the new solar performance indicators SRU600 and SRU400 were both examined as dependent variables. The correlation analysis results suggested that the new morphological parameters displayed a strong linear correlation with the corresponding solar performance indicators, surpassing all the other morphological parameters. Two prediction models with respect to SRU600 and SRU400 were developed by multiple linear regressions using a stepwise method and their validity was verified by real residential cases. The findings provide key morphological parameters and rapid calculation tools for establishing solar energy friendly urban planning and design.