Search

Primary patellar dislocation has a certain recurrence rate after either conservative or surgical treatment, and the optimal treatment for patients with primary patellar dislocation of different ages remains unclear. This study aims to compare the clinical efficacy of surgical and conservative treatments for primary patellar dislocation across different age groups. According to the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) checklist, we conducted a systematic search for randomized controlled trials. We searched the PubMed, EMBASE, Cochrane Library, and Web of Science databases for randomized controlled trials of primary patellar dislocation treated surgically or conservatively up to January 2023. Data searching, extraction, analysis, and quality assessment were carried out in accordance with the Cochrane Collaboration guidelines. A total of nine studies with 433 patients were included in our study. There was no statistically significant difference between the two treatment modalities in terms of Kujala score, pain score, patient satisfaction, reoperation, and Tegner score. The rate of re‐dislocation after surgical treatment is lower than that after conservative treatment. Subgroup analysis based on mean age showed that when the age was >20 years, Kujala scores were higher after surgical treatment than after conservative treatment (p 20 years, the recurrence rate of patellar dislocation was lower after surgical treatment than after conservative treatment (p = 0.009, 95% CI = 0.08–0.70). When the age was ≤20 years, the difference in the recurrence rate of patellar dislocation between the two treatment modalities was not statistically significant. When the age of patients with primary patellar dislocation is ≤20 years, both surgical and conservative treatments result in similar clinical outcomes. When the age is >20 years, better clinical outcomes can be achieved by opting for surgical treatment. Therefore, surgery may be a better option for patients with primary patellar dislocation whose age is >20 years.

Abstract Background Acute bulbar palsy-plus (ABPp) syndrome is an unusual variant of Guillain-Barré syndrome (GBS). Anti-GT1a and anti-GQ1b antibodies have been reported in patients with ABPp, but without reports related to GD3 antibodies. Methods Clinical data of a patient diagnosed as ABPp syndrome were reviewed clinically. And we summarized the GBS patients with ABP and facial paralysis reported in the literature. Results We reported a 13-year-old girl presented with asymmetric bifacial weakness, bulbar palsy and transient limb numbness, and had positive serum IgG anti-GD3 antibody. Through reviewing the GBS patients with ABP and facial paralysis reported previously, we found that facial palsy could be unilateral or bilateral. The bilateral facial palsy could present successively or simultaneously, and could be symmetrical or asymmetrical. Other common symptoms included ophthalmoplegia, sensory abnormality and ataxia. IgG anti-GT1a and IgG anti-GQ1b antibodies were the most frequent. Most of the patients had full recovery within two weeks to one year of follow-up. Conclusions We reported a patient with asymmetric bifacial palsy and bulbar palsy, which seemed to fit the diagnosis of ABPp syndrome. This was the first report of ABPp variant of GBS with positive serum ganglioside GD3 IgG antibody.

Abstract Senile osteoporosis is mainly caused by osteoblasts attenuation, which results in reduced bone mass and disrupted bone remodeling. Numerous studies have focused on the regulatory role of m6A modification in osteoporosis; however, most of the studies have investigated the differentiation of bone marrow mesenchymal stem cells (BMSCs), while the direct regulatory mechanism of m6A on osteoblasts remains unknown. This study revealed that the progression of senile osteoporosis is closely related to the downregulation of m6A modification and methyltransferase-like 3 (METTL3). Overexpression of METTL3 inhibits osteoblast aging. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) revealed that METTL3 upregulates the stability of Hspa1a mRNA, thereby inhibiting osteoblast aging. Moreover, the results demonstrated that METTL3 enhances the stability of Hspa1a mRNA via m6A modification to regulate osteoblast aging. Notably, YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) participates in stabilizing Hspa1a mRNA in the METTL3-mediated m6A modification process, rather than the well-known degradation function. Mechanistically, METTL3 increases the stability of Hspa1a mRNA in a YTHDF2-dependent manner to inhibit osteoblast aging. Our results confirmed the significant role of METTL3 in osteoblast aging and suggested that METTL3 could be a potential therapeutic target for senile osteoporosis.

Abstract Purpose The purpose of the study was to summarize the available evidence and identify risk factors for osteochondral injuries (OCIs) after patellar dislocations. Methods A systematic literature review was conducted in PubMed, Embase, Web of Science, Cochrane Library, and China national knowledge infrastructure from inception to December 22, 2022, according to the preferred reporting items for systematic reviews and meta-analyses guidelines. Studies regarding risk factors for OCIs after patellar dislocations were included. Literature search, data extraction, and quality assessment were performed independently by two authors. Results A total of 16 studies with 1945 patients were included. The risk factors for OCIs after patellar dislocation were categorized into four main categories, including demographic characteristics, patellar depth and position, femoral trochlear morphology, and other risk factors in this study. Five and three studies supported the idea that male sex and skeletal maturation may be risk factors, respectively. Normal femoral trochlea (two studies) and complete medial patellofemoral ligament (MPFL) injuries (two studies) may be associated with the development of OCIs. Three studies show that ligamentous laxity or joint hypermobility may prevent OCIs. Patellar depth and position (eight studies) may not be associated with the development of OCIs. Conclusions Based on the available evidence, an increased risk of OCIs following patellar dislocation may be associated with male sex and skeletal maturation. Furthermore, normal femoral trochlea and complete MPFL injuries may increase the risk of OCIs, while factors such as ligamentous laxity or joint hypermobility may reduce the risk. Level of Evidence Level IV, systematic review of Level II and IV studies.

Abstract Although the potential for cities and regions to contribute to global mitigation efforts is widely acknowledged, there is little evidence on the effectiveness of subnational mitigation strategies. Here we address this gap through a systematic review of 234 quantitative mitigation case studies. We use a meta-analytical approach to estimate expected greenhouse gas emissions reductions from 12 categories of mitigation strategies. We find that strategies related to land use and development, circular economy, and waste management are most effective and reliable for reducing emissions. The results demonstrate that cities and regions are taking widespread action to reduce emissions. However, we find misalignment between the strategies that policymakers and researchers focus on, compared to those with the highest expected impacts. The results inform climate action planning at the city and regional level and the evaluation of subnational climate targets.

Abstract Background Microbes have fundamental roles underpinning the functioning of our planet, they are involved in global carbon and nutrient cycling, and support the existence of multicellular life. The mangrove ecosystem is nutrient limited and if not for microbial cycling of nutrients, life in this harsh environment would likely not exist. The mangroves of Southeast Asia are the oldest and most biodiverse on the planet, and serve vital roles helping to prevent shoreline erosion, act as nursery grounds for many marine species and sequester carbon. Despite these recognised benefits and the importance of microbes in these ecosystems, studies examining the mangrove microbiome in Southeast Asia are scarce.cxs Results Here we examine the microbiome of Avicenia alba and Sonneratia alba and identify a core microbiome of 81 taxa. A further eight taxa (Pleurocapsa , Tunicatimonas , Halomonas , Marinomonas , Rubrivirga , Altererythrobacte , Lewinella, and Erythrobacter) were found to be significantly enriched in mangrove tree compartments suggesting key roles in this microbiome. The majority of those identified are involved in nutrient cycling or have roles in the production of compounds that promote host survival. Conclusion The identification of a core microbiome furthers our understanding of mangrove microbial biodiversity, particularly in Southeast Asia where studies such as this are rare. The identification of significantly different microbial communities between sampling sites suggests environmental filtering is occurring, with hosts selecting for a microbial consortia most suitable for survival in their immediate environment. As climate change advances, many of these microbial communities are predicted to change, however, without knowing what is currently there, it is impossible to determine the magnitude of any deviations. This work provides an important baseline against which change in microbial community can be measured.

Abstract Background Kashin–Beck disease (KBD) is an endemic deformable bone and joint disease, which affects the quality of life (QOL) of patients. We conducted a cross-sectional study of the QOL of KBD patients by a new KBD quality of life (KBDQOL) questionnaire. Methods A total of 252 KBD patients and 248 OA patients came from Northwest China, and 260 healthy people living in the same area as KBD and osteoarthritis (OA) patients served as the controls. KBDQOL questionnaire was used to evaluate the QOL of all objects. Results The average scores for physical functions, activity limitations, support of society, mental health and general health were significantly lower in KBD patients than that in OA patients and healthy people except for economics. Monofactor analysis showed that age, height, weight status, education level and grade of KBD had a significant effect on KBDQOL score. Multivariate analysis showed that grade of KBD was the influencing factor of physical function score; gender, age, height, grade of KBD and duration of symptoms were the influencing factors of activity restriction score; age and grade of KBD were factors affecting the general health score. Conclusion The QOL of KBD patients was significantly lower than that of OA patients and healthy people. The KBDQOL questionnaire may be a promising tool for assessing the QOL of KBD patients.

Abstract Background Cryopyrin-associated periodic syndrome (CAPS), a rare genetic autoimmune disease, is composed of familial cold autoinflammatory syndrome (FCAs), Muckle-Wells syndrome (MWS), and neonatal onset multisystem inflammatory disease (NOMID). MWS is caused by dominantly inherited or de novo gain-of-function mutations in the NOD-like receptor 3 (NLRP3) gene. At present, there is no report about the variation of R262W in China. Case presentation We reported a 3-year-old Chinese boy who had recurrent fever without obvious inducement, bilateral conjunctival congestion, and urticarial-like rash. Laboratory examination showed elevation in leukocyte count, neutrophil count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) and serum amyloid protein (SAA) levels. Whole exome sequencing identified a missense variation c.784-786delinsTGG (p.R262W) in the coding region of the NLRP3 gene. Conclusion A classical variant of the NLRP3 gene in a patient with MWS was first reported in China.

Abstract A low‐cost and feasible method to fabricate three‐dimensional (3D) hierarchical composites composed of CoSe2 nanoparticles embedded in rice‐derived hard carbon (HC) interconnected with carbon nanotubes (CNTs) is devised in this study. The deployment of CoSe2 in the elecrode has provided a very high rate capacity, which is crucial for sodium‐ion commercialization. The deployment of HC with CNTs further provides a 3D hierarchical structure effective in shortening the diffusion paths of both electrons and Na+ ions, offering abundance of active sodium storage sites. Consequently, the CoSe2 acted as an active material with the carbonaceous template, a commonly utilized sodium‐ion battery anode material, which exhibited a superior reversible capacity of 550 mAh g−1 at 0.5 A g−1, outstanding rate performance (451 mAh g−1 at 20 A g−1) and excellent cycling performance (~100% capacity retention over 2500 cycles at 20 A g−1 after electrochemical stabilization).

Abstract Background Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of severe disorders that are characterized by early-onset, refractory seizures and developmental slowing or regression. Genetic variations are significant causes of these changes. De novo variants in an increasing number of candidate genes have been found to be causal. The YWHAG gene is one such gene that has been reported to cause developmental and epileptic encephalopathy 56 (DEE56). Here, we report a heterozygous missense variant, c.170G > A (p.R57H), in the YWHAG gene that caused early-onset epilepsy and developmental delay in a Chinese family. Methods We described the clinical manifestations of the proband and his mother in detail. Then, we use trio-based whole-exome sequencing to search the etiology of this family. Results Both the proband and his mother exhibited early-onset seizures, intellectual disability, and developmental delay. While the proband attained seizure control with sodium valproate, his mother's seizures were not well controlled. Trio-based whole-exome sequencing revealed a heterozygous missense variant, c.170G > A (p.R57H), in the YWHAG gene, which was considered as the cause of early-onset epilepsy and developmental delay in this family. Conclusions Our report further confirmed that YWHAG haploinsufficiency results in developmental and epileptic encephalopathy 56.

Objective To study the epidemiological correlation and drug resistance of external factors of infection caused by open injury of limbs to pathogens. Methods This experiment is a retrospective study. We took the geographical location and climate of Nanchang, Jiangxi Province, China as the background, analyzed 2017 strains of pathogens from 1589 patients with limb trauma infection in a University Affiliated Hospital from 2012 to 2017. Patients were divided into three groups according to the type of incision: I, In‐hospital infection of clean limb incision, II, In‐hospital infection with open injury, III, Community infection with open injury of the limb. Groups II and Groups III were divided into six subgroups according to the causes of trauma, including: accidents from non‐motor vehicles, machinery, cutting/piercing, pedestrian injuries, struck by/against, pedal cycles, and other injuries. We found eight common pathogens of orthopedic infection, which were mainly divided into Gram‐positive bacteria (G+, mainly including Staphylococcus) and Gram‐negative bacteria (G‐, mainly Enterobacteriaceae). The relationship between main pathogens and damage mechanism, apparent temperature and relative humidity was discussed in this study. SPSS v22.0 was used for statistical analysis of the data. Friedman's two‐way ANOVA was used to analyze the difference between the injury mechanism and incidence of pathogenic bacteria. Linear regression was used to determine the trend between the incidence of major pathogens and seasonal temperature and humidity. The level of significance was set as P 0.05). The drug resistance of Groups III was significantly higher than that of Groups II and Groups I. G+ bacteria were resistant to cephalosporin, ceftriaxone and other cephalosporins and erythromycin and other macrolides. They were sensitive to vancomycin and linezolid. G‐ were resistant to the first‐ and the second‐generation cephalosporins, including cefotetan and cefazolin, and ampicillin and other penicillins, while they were sensitive to third‐generation cephalosporins, such as ceftazidime, as well as to levofloxacin and other quinolones, meropenem, and other beta‐lactamases. The correlation between the injury mechanism and infection of pathogenic bacteria was not significant. The monthly average apparent temperature and relative humidity were correlated with the infection rate of pathogenic bacteria. Conclusion In open injury of extremities, apparent temperature and relative humidity is an important risk factor for infection by pathogenic bacteria and the drug resistance of pathogenic bacteria in out‐of‐hospital infection was lower than that of hospital infection.

IntroductionHemiplegic migraine (HM) is a rare subtype of migraine. HM in children may be atypical in the initial stage of the disease, which could easily lead to misdiagnosis.MethodsWe report two cases of atypical hemiplegic migraine that onset as an acute encephalopathy. And a comprehensive search was performed using PubMed, Web of Science, and Scopus. We selected only papers that reported complete clinical information about the patients with CACNA1A or ATP1A2 gene mutation.ResultsPatient #1 showed a de novo mutation, c.674C>A (p. Pro225His), in exon 5 of the CACNA1A gene. And patient #2 showed a missense mutation (c.2143G>A, p. Gly715Arg) in exon 16 of the ATP1A2. Together with our two cases, a total of 160 patients (73 CACNA1A and 87 ATP1A2) were collected and summarized finally.DiscussionAcute encephalopathy is the main manifestation of severe attacks of HM in children, which adds to the difficulty of diagnosis. Physicians should consider HM in the differential diagnosis of patients presenting with somnolence, coma, or convulsion without structural, epileptic, infectious, or inflammatory explanation. When similar clinical cases appear, gene detection is particularly important, which is conducive to early diagnosis and treatment. Early recognition and treatment of the disease can help improve the prognosis.

Abstract Objective To establish a digital model of the ankle joint through 3D imaging technology and explore the preoperative placement of ankle replacement prostheses. Methods Computed tomography images of intact ankle joints from 54 cases in the outpatient and inpatient departments of our hospital were collected; according to the INBONE® total ankle system surgery process, the surgery model and surgical osteotomy were finished using MIMICS based on computer simulation method. The shortest distance was measured between the center point and the anterior, posterior, medial, and lateral, respectively, to ensure the precise position of the ankle replacement prosthesis by digital simulation surgery. The relationship between the two variables was analyzed by bivariate correlation analysis. Results The dataset of this study included 48 cases of the sub‐data set (26 males and 22 females) and included 27 cases of left ankle and 21 cases of right ankle. The average medial malleolar angle was 18.67°± 2.87°, the average amount of bone resection was 12.13 ± 1.86 cm3, the mid‐anterior distance was 1.72 ± 0.19 cm, the mid‐posterior distance was 2.00 ± 0.19 cm, the ratio of mid‐anterior to mid‐posterior was 0.87, the mid‐medial distance was 1.26 ± 0.17 cm, the mid‐lateral distance was 1.19 ± 0.16 cm, and the ratio of mid‐medial to mid‐lateral was 1.06. After osteotomy, the anteroposterior diameter was 3.73 ± 0.32 cm, the transverse diameter was 2.46 ± 0.27 cm, and the ratio of anteroposterior diameter to transverse diameter was 1.53. In the bottom view, the shape after osteotomy is rectangular. The mid‐anterior distance was strongly negatively correlated with age, the mid‐anterior distance and the amount of bone resection, the mid‐medial distance and the amount of bone resection, the mid‐lateral distance and the amount of bone resection, the mid‐lateral distance and the anteroposterior diameter, the anteroposterior diameter and the transverse diameter were all strongly positively correlated. Conclusion The projection point of the lower tibia centerline on the tibial horizontal osteotomy surface is located at a position slightly anterior to the midpoint of the transverse diameter after ankle arthroplasty. The rational positioning of the total ankle replacement is located at both a position slightly anterior to the midpoint of the transverse diameter and midpoint of the anteroposterior diameter, which can be used as a reference method before total ankle arthroplasty surgery.

Nasopharyngeal carcinoma (NPC) is a metastasis-prone malignancy closely associated with the Epstein–Barr virus (EBV). Despite ubiquitous infection of EBV worldwide, NPC incidences displayed predominance in certain ethnic groups and endemic regions. The majority of NPC patients are diagnosed with advanced-stage disease, as a result of anatomical isolation and non-specific clinical manifestation. Over the decades, researchers have gained insights into the molecular mechanisms underlying NPC pathogenesis as a result of the interplay of EBV infection with several environmental and genetic factors. EBV-associated biomarkers were also used for mass population screening for the early detection of NPC. EBV and its encoded products also serve as potential targets for the development of therapeutic strategies and tumour-specific drug delivery. This review will discuss the pathogenic role of EBV in NPC and efforts in exploiting the potential of EBV-associated molecules as biomarkers and therapeutic targets. The current knowledge on the role of EBV and its associated products in NPC tumorigenesis, development and progression will offer a new outlook and potential intervention strategy against this EBV-associated malignancy.

Fibroblasts are known for their ability to make and modify the extracellular matrix. However, there is more to them than meets the eye. It is now clear that they help define tissue microenvironments and support immune responses in organs. As technology advances, we have started to uncover the secrets of fibroblasts. In this Essay, we present fibroblasts as not only the builders and renovators of tissue environments but also the rheostat cells for immune circuits. Although they perform location-specific functions, they do not have badges of fixed identity. Instead, they display a spectrum of functional states and can swing between these states depending on the needs of the organ. As fibroblasts participate in a range of activities both in health and disease, finding the key factors that alter their development and functional states will be an important goal to restore homeostasis in maladapted tissues.

Abstract Background Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) has been reported worldwidely. However, the data about recurrent cases is limited. We aimed to analyze the clinical and radiographic features of recurrent MERS, and its possible mechanisms. Case presentation Two patients with clinically recurrent MERS were reported here, exhibiting neurological symptoms such as limbs weakness and numbness, stand/walk unsteadily, slurred speech and irritability, and typical lesions in the corpus callosum and white matter. One of them experienced another four episodes with a similar clinical course and magnetic resonance imaging findings over a period of 10 years. The Na levels in the present two patients were normal. Discussion and conclusion Combined with the patients reported previously, recurrence could be seen in both MERS type 1 and type 2 patients, from two to multiple times, with the latter possibly more common. It suggested that some genetic factors might be involved in MERS, especially for MERS type 2 or familial MERS.

Objective To prepare mesoporous silica nanoparticles (MSN) loaded with doxorubicin (DOX) and to evaluate their physical properties, drug release, uptake by tumor cells, inhibition of cell proliferation and promotion of apoptosis. Methods DOX was loaded into the channels of MSN by infiltration to prepare mesoporous silica nanocomposites (MSN-DOX), whose morphology was then observed using transmission electron microscopy (TEM), and the size and surface charge of nanocomposites were measured with a nano particle size analyzer. Dialysis bag was applied to study drug release behavior of the nanocomposites under different pH conditions. Laser confocal microscopy was used to observe the uptake of MSN-DOX by bladder cancer cells. CCK-8 assay was carried out to detect the biocompatibility of MSN and the inhibitory effect of MSN-DOX on cell proliferation. Finally, the expression of apoptosis-related proteins was tested to analyze the effect of MSN-DOX on apoptosis. Results The prepared nanocomposites were spherical, uniform in size, in a size of 203.6±3.0 nm, with a surface charge of -8.1±4.7 mV. The DOX loading was 4.83%, and the encapsulation efficiency was 10.15%. In vitro studies showed that DOX was slowly released from the nanocomposites, and the release rate and total release amount were correlated with the environmental pH value. Lower pH value led to faster drug release rate and more total release amount. Cellular uptake experiments indicated the nanocomposites were efficiently ingested by tumor cells, thereby increasing the intracellular drug accumulation. In addition, MSN had good biocompatibility, and MSN-DOX significantly inhibited the proliferation and promoted the apoptosis of tumor cells, with increased expression levels of apoptosis-related proteins. Conclusion Our prepared MSN-DOX nanocomposites have good properties and stable structure, which can be efficiently ingested by bladder cancer cells, thus effectively inhibiting proliferation and promoting apoptosis of tumor cells.

Objective To study the anti-tumor effect of IR-780, a mitochondrial targeting small molecule, on cisplatin-resistant T24 cell line (T24/DPP). Methods T24/DPP cell line was constructed by repeated and discontinuous stimulation of T24 cells with cisplatin. After the drug-resistant cells were treated with different concentrations of IR-780, cell viability was detected by CCK-8 assay and cell migration was measured by wound healing assay. The suborganelle localization of IR-780 was determined by confocal fluorescence microscopy with aid of mitotracker treatment. Cell apoptosis and production of mitochondrial reactive oxygen species (ROS) were determined by flow cytometry. T24/DPP cells were injected subcutaneously into 6-~8-week-old male nude mice to establish a tumor-bearing nude mouse model. The tumor-bearing mice were randomly divided into 3 groups, including control group (5 mg/kg PBS), DOX group (5 mg/kg DOX) and IR-780 group (5 mg/kg IR-780). After intraperitoneal administration of IR-780, the accumulation of IR-780 were detected by near-infrared in vivo imaging system and confocal fluorescence microscopy, while the tumor volume and weight were measured. Results ① In vitro, IR-780 inhibited the proliferation and migration of T24/DPP cells in a dose-dependent manner (P < 0.05). IR-780 was selectively accumulated in the mitochondria of T24/DPP cells. With the increase of IR-780 concentration, the production of mitochondrial ROS and the rate of apoptosis in T24/DDP cells were increased (P < 0.05). ② In vivo, near-infrared imaging and frozen sections of tumor tissue showed that IR-780 preferentially accumulated in the tumor of tumor-bearing nude mouse model. The tumor volume and weight of the IR-780 group were significantly less and lower when compared with the control group (P < 0.05) and DOX group (P < 0.05). Conclusion IR-780 can significantly inhibit the growth of T24/DDP cells and subcutaneous tumor xenografts in nude mice, and the mitochondrial pathway might be involved in the apoptosis of T24/DPP cells induced by IR-780.

Chronic infection with hepatitis B virus (HBV) is incurable, as the current therapeutics cannot eliminate its persistent genomic material, cccDNA. Screening systems for cccDNA-targeting therapeutics are unavailable, as low copies of cccDNA in vitro complicate detection. To address this, cccDNA copies were massively increased to levels detectable via automated plate readers. This was achieved via continuous infection in a contact-free co-culture of an HBV generator (clone F881), which stably produced clinically relevant amounts of HBV, and HBV acceptors selected to carry high cccDNA loads. cccDNA-targeted therapeutics were then identified via reduced cccDNA-specific fluorescence, taking differences in the cell numbers and viability into account. Amongst the drugs tested, the H1 antihistamine Bilastine, HBVCP inhibitors and, surprisingly, current HBV therapeutics downregulated the cccDNA significantly, reflecting the assay’s accuracy and sensitivity in identifying drugs that induce subtle changes in cccDNA levels, which take years to manifest in vivo. Bilastine was the only therapeutic that did not reduce HBV production from F881, indicating it to be a novel direct suppressor of cccDNA levels. When further assessed, only the structurally similar antihistamines Pitolisant and Nizatidine suppressed cccDNA levels when other H1 antihistamines could not. Taken together, our rapid fluorescence cccDNA-targeted drug screen successfully identified a class of molecules with the potential to treat hepatitis B.

Abstract Non-communicable diseases (NCDs) are an increasing problem worldwide, including in Malaysia. National surveys have been performed by the government but had poor coverage in east Malaysia, particularly in rural regions. This study aimed to describe the achievement of target therapeutic outcomes in the control of diabetes mellitus (DM), hypertension (HPT), and dyslipidemia (DLP) among diabetic patients in rural east Malaysia. A cross-sectional study was conducted among DM patients who visited the NCDs clinic in Lundu Hospital, Sarawak, Malaysia, from Jan to March 2016. In total, 214 patients (male, 37.9%; female, 62.1%) were recruited using a systemic sampling method. Multiple logistic regression models were applied to estimate the adjusted odds ratio (AOR) and confidence interval (CI) for the target therapeutic achievement in the control of DM, HPT, and DLP. Compared to the national average, therapeutic target achievement in Lundu was higher for DM (43.0% vs. 23.8%), equal for DLP (35.8% vs. 37.8%) but lower for HPT (30.9% vs. 47.9%). DM patients who had at least yearly HbA1c monitoring (AOR 2.30, 95% CI 1.04–5.06, P = 0.039), and those 58.7 years or older (AOR 2.50, 95% CI 1.32–4.74, P = 0.005) were more likely to achieve the therapeutic target for DM. Health promotion and public education regarding HPT needs to be emphasized in rural Malaysia. HbA1c monitoring at least once a year was one of the important factors associated with achieving DM control in rural east Malaysia. Accessibility to HbA1c tests and monitoring should be ensured for diabetic patients.

Abstract The aim of this study was to investigate the clinical efficacy of single posterior debridement, bone grafting and instrumentation for the treatment of thoracic spinal tuberculosis in adult patients. A retrospective analysis was conducted between June 2013 and September 2017of 88 adult patients with thoracic spinal tuberculosis. All patients were treated with single posterior debridement, bone grafting and instrumentation. The clinical manifestations and laboratory and imageological results were subsequently analysed. All patients were followed for 40.6 ± 4.1 months (range, 36–48 m). Bony fusion was achieved in all bone grafts of thoracic vertebrae. The visual analogue scale scores, erythrocyte sedimentation rate and C-reactive protein levels 6 weeks after surgery and at the final follow up were significantly lower than the preoperative levels (P

Objective: To investigate the effects of visual feedback training on knee function and balance ability in postoperative patients with knee fracture. Methods: A clinical randomized controlled trial with 104 participants, randomly assigned (1:1) to a visual feedback training group or a control group. Eligible participants were evaluated using Lysholm scores, the Tinetti scale, and the evaluation module of TecnoBody® to demonstrate dynamic balance function in a standing position before treatment and after 4 and 8 weeks of treatment. Results: Both visual feedback training and control groups improved significantly in the Lysholm and Tinetti scores after 8 weeks. Compared with the control group, the TecnoBody® tests included centre of pressure path length, and the area over centre of pressure movement, both of which significantly improved in the visual feedback training group at 8 weeks after treatment. There was no difference between the 2 groups in terms of their Lysholm scores and Tinetti gait before the intervention and 4 weeks after treatment. Conclusion: Applying visual feedback training in conjunction with traditional rehabilitation strategies may improve knee function and motor control in postoperative patients with knee fracture. Although visual feedback training does not have a short-term effect on knee function and gait, this method could be a useful addition for rehabilitation of knee fracture patients. LAY ABSTRACT This study used the TecnoBody® (PK-254P, Bergamo, Italy) to evaluate balance in the standing position of all participants. This equipment provides data on the centre of pressure path length and the area over which the centre of pressure moves. The Lysholm score was used to assess knee function, and the Tinetti scale to assess motor control. Applying visual feedback training in conjunction with traditional rehabilitation strategies could decrease postural sway and increase motor control in postoperative patients with knee fracture, as well as subsequently improve knee function and balance ability. There were no adverse effects due to the combined rehabilitation programme.

In the production process of steel pipe, the quenching is of significance to improve the quality of steel pipe. Therefore, the dynamic thermal behavior of the steel pipe in quenching furnace is studied in this work. The coupled conduction-radiation heat transfer model of steel pipe in walking beam quenching furnace is established. The thermal contact resistance, radiative heat transfer between the steel pipe and the tooth groove, the rotation process and the heating process of steel pipe are considered in this model. The effects of the rotation conditions, tooth groove temperature and size of the steel pipe on thermal behavior of steel pipe are investigated thoroughly. It can be found that keeping the rotation direction of the steel pipe unchanged can reduce the section temperature difference of steel pipe; When the loading of steel pipes is stopped for a period of time, the section temperature difference of the first steel pipe entering the furnace is very large; The large-size steel pipe usually has a large section temperature difference in the initial heating process, which means a lower temperature of tooth grooves in contact with the steel pipe during the initial heating process is required. This work can provide valuable reference for the improvement of quenching quality of steel pipe and on-line supervisory control of the production process.

Abstract Background Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infections in children, especially bronchiolitis. Our study aimed to identify the key genes and upstream transcription factors in RSV. Methods To screen for RSV pathogenic genes, an integrated analysis was performed using the RSV microarray dataset in GEO. Functional annotation and potential pathways for differentially expressed genes (DEGs) were further explored by GO and KEGG enrichment analysis. We constructed the RSV-specific transcriptional regulatory network to identify key transcription factors for DEGs in RSV. Results From three GEO datasets, we identified 1059 DEGs (493 up-regulated and 566 down-regulated genes, FDR 0.8) between RSV patients and normal controls. GO and KEGG analysis revealed that ‘response to virus’ (FDR = 7.13E-15), ‘mitochondrion’ (FDR = 1.39E-14) and ‘Asthma’ (FDR = 1.28E-06) were significantly enriched pathways for DEGs. The expression of IFI27, IFI44, IFITM3, FCER1A, and ISG15 were shown to be involved in the pathogenesis of RSV. Conclusions We concluded that IFI27, IFI44, IFITM3, FCER1A, and ISG15 may play a role in RSV. Our finding may contribute to the development of new potential biomarkers, reveal the underlying pathogenesis and also identify novel therapeutic targets for RSV.

Abstract Background MED13L-related intellectual disability is a new syndrome that is characterized by intellectual disability (ID), motor developmental delay, speech impairment, hypotonia and facial dysmorphism. Both the MED13L haploinsufficiency mutation and missense mutation were reported to be causative. It has also been reported that patients carrying missense mutations have more frequent epilepsy and show a more severe phenotype. Case presentation We report a child with ID, speech impairment, severe motor developmental delay, facial deformity, hypotonia, muscular atrophy, scoliosis, odontoprisis, abnormal electroencephalogram (EEG), and congenital ureteropelvic junction obstruction (UPJO) combined with high ureter attachment. We used whole-exome sequencing (WES) to detect the genetic aberration of the child and found a de novo mutation, c.2605C > T (p.Pro869Ser), in the MED13L gene. Neither of her parents carried the mutation. Additionally, we review the literature and summarize the phenotypes and features of reported missense mutations. After reviewing the literature, approximately 17 missense mutations in 20 patients have been reported thus far. For 18 patients (including our case) whose clinical manifestations were provided, 100% of the patients had ID or developmental delay (DD). A total of 88.9, 83.3 and 66.7% of the patients had speech impairment, delayed milestones and hypotonia, respectively. A total of 83.3% of the patients exhibited craniofacial deformity or other dysmorphic features. Behavioral difficulties and autistic features were observed in 55.6% of the patients. Cardiac anomalies were seen in only 27.8% of the patients. Of these patients, 44.4% had epileptic seizures. Of the 17 mutations, 2 were located in the N-terminal domain, 8 were located in the C-terminal domain, and 1 was located in an α-helical sequence stretch. One of them was located in the MID domain of the MedPIWI module. Conclusions We report a new patient with a reported missense mutation, c.2605C > T (p.Pro869Ser), who exhibited some infrequent manifestations except common phenotypes, which may broaden the known clinical spectrum. Additionally, by reviewing the literature, we also found that patients with missense mutations have a higher incidence of seizures, MRI abnormalities, autistic features and cardiac anomalies. They also have more severe ID and hypotonia. Our case further demonstrates that Pro869Ser is a hotspot mutation of the MED13L gene.

Abstract Background Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome that requires prompt diagnosis and appropriate treatment. A risk-stratification model that could be used to identify high-risk pediatric patients with HLH who should be considered for second-line therapies, including salvage regimens and allogeneic hematopoietic cell transplantation (HCT), was developed. Methods The medical records of 88 pediatric patients (median age 1.4 years, range 0.2–15 years) with non-malignancy associated secondary HLH were retrospectively reviewed. Treatment strategies included dexamethasone, etoposide, and cyclosporine. Results Survival analysis showed HLH patients with infections other than Epstein-Barr virus (EBV) and unknown causes experienced better 5-year overall survival (OS) than patients with HLH due to autoimmune disease, EBV or immunodeficiency (76% vs. 65, 33.3, 11%, p

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy that raises public health concerns in endemic countries. Despite breakthroughs in therapeutic strategies, late diagnosis and drug resistance often lead to unsatisfactory clinical outcomes in NPC patients. The tumor microenvironment (TME) is a complex niche consisting of tumor-associated cells, such as fibroblasts, endothelial cells, leukocytes, that influences tumor initiation, progression, invasion, and metastasis. Cells in the TME communicate through various mechanisms, of note, exosomes, ligand-receptor interactions, cytokines and chemokines are active players in the construction of TME, characterized by an abundance of immune infiltrates with suppressed immune activities. The NPC microenvironment serves as a target-rich niche for the discovery of potential promising predictive or diagnostic biomarkers and the development of therapeutic strategies. Thus, huge efforts have been made to exploit the role of the NPC microenvironment. The whole picture of the NPC microenvironment remains to be portrayed to understand the mechanisms underlying tumor biology and implement research into clinical practice. The current review discusses the recent insights into the role of TME in the development and progression of NPC which results in different clinical outcomes of patients. Clinical interventions with the use of TME components as potential biomarkers or therapeutic targets, their challenges, and future perspectives will be introduced. This review anticipates to provide insights to the researchers for future preclinical, translational and clinical research on the NPC microenvironment.

Objective Kashin–Beck disease (KBD) is an endemic degenerative joint disease with a high disability rate. We retrospectively evaluated the 18-year clinical follow-up outcomes of adult patients with KBD who underwent arthroscopic debridement for knee osteoarthritis. Methods Thirty-one patients with KBD (31 knees) underwent arthroscopy for knee osteoarthritis. The visual analog scale (VAS) score, walking distance, knee mobility, and patients’ self-evaluated improvement in clinical symptoms were retrospectively evaluated before and 18 years after the operation. Results The patients’ self-evaluated clinical symptoms showed considerable improvement at 2, 6, and 8 years after surgery but deteriorated at 10 and 18 years after surgery. Knee mobility was greater after than before arthroscopy but decreased from 6 to 18 years postoperatively. The VAS score for knee pain was high before the operation, decreased at 2 years postoperatively, increased at 6 years postoperatively, and was significantly lower at 18 years postoperatively than before surgery. The walking distance was significantly longer at 2, 6, and 8 years postoperatively than preoperatively. Conclusions Arthroscopic treatment may be an effective therapy for adult patients with KBD who develop knee osteoarthritis. In this study, arthroscopy had a long-term effect on patients with KBD who had Kellgren–Lawrence grade

Abstract Purpose To investigate the clinical features, imaging features, and prognosis of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in children Methods The clinical and imaging data of a cohort of 28 children diagnosed as MERS from January 2019 to October 2020 were retrospectively analyzed Results Of the 28 patients, 17 were males and 11 were females. The onset age ranged from 8 months to 12 years old, with an average age of 4 years and 2 months. All children developed normally before onset, and three of them had a history of febrile convulsion. More than half of the patients (62.9%) had preceding infections of gastrointestinal tract. All the cases developed seizures, and most (71.4%) had more than one time. Other neurological symptoms included dizziness/headache, consciousness disorder, limb weakness, blurred vision, and dysarthria. Cranial magnetic resonance imaging (MRI) showed lesions in the splenium of the corpus callosum in all, extending to other areas of the corpus callosum, bilateral semi‐ovoid center, and adjacent periventricular in two cases. The clinical symptoms were relieved after steroids, intravenous immunogloblin, and symptomatic treatment, without abnormal neurodevelopment during the followed‐up (2 months–2 years). Complete resolution of the lesions was observed 8–60 days after the initial MRI examinations Conclusion MERS in children is related to prodromal infection mostly, with a wide spectrum of neurologic symptoms, characteristic MRI manifestations, and good prognosis.

Abstract Background Congenital nephrotic syndrome (CNS), which is defined as heavy proteinuria, hypoalbuminemia, hyperlipidemia and edema, is most caused by monogenic defects in structural proteins of the glomerular filtration barrier in the kidneys. 22q11.2 duplication syndrome was a chromosomal disease with variable clinical featuresranging from normal to mental retardation and with congenital defects. Co-occurrence of two genetic disorders in a single patient is rare. Case presentation The proband was born at 36 weeks of gestational age spontaneously and weighed 2350 g at birth. Six days after birth, the proband was admitted to our hospital due to fever of 38.5 °C lasting for 6 h. Physical examination at admission time showed dysmorphic features of hypertelorism, palpebral edema, broad nose bridge, upturned nose, dysmorphic auricle, long philtrum, and a thin upper lip. Additionally, we found left wrist drop and bilateral strephexopodia, bilateral knee joint flexion contracture in this patient. A series of indicators were detected and showed abnormalities. Albumin was used to remit the hypoproteinemia and edema. However, the parents refused to accept further therapy and the boy died at age 3 months due to cachexy. To confirm the pathogenesis, genetic analysis were performed and revealed two mutations of NPHS1 gene: Exon18: c.2386G > C; p. (Gly796Arg) inherited from mother, and intron24: c.3286 + 5G > A; p.? inherited from father. And he also had a 22q11.2 duplication which was inherited from his mild affected mother. The pathogenesis of the intronic mutation has been further identified that it can defect alternative splicing of NPHS1. Conclusions We present a patient who was caught in congenital nephrotic syndrome and 22q11.2 duplication syndrome simultaneously, emphasizing the importance of new sequencing technology on diagnosis of different genetic disorders.

Abstract Bone marrow mesenchymal stem cells (BMSCs), which were first discovered in bone marrow, are capable of differentiating into osteoblasts, chondrocytes, fat cells, and even myoblasts, and are considered multipotent cells. As a result of their potential for multipotential differentiation, self-renewal, immune regulation, and other effects, BMSCs have become an important source of seed cells for gene therapy, tissue engineering, cell replacement therapy, and regenerative medicine. MicroRNA (miRNA) is a highly conserved type of endogenous non-protein-encoding RNA of about 19–25 nucleotides in length, whose transcription process is independent of other genes. Generally, miRNA plays roles in regulating cell proliferation, differentiation, apoptosis, and development by binding to the 3′ untranslated region of target mRNAs, whereby they can degrade or induce translational silencing. Although miRNAs play a regulatory role in various metabolic processes, they are not translated into proteins. Several studies have shown that miRNAs play an important role in the osteogenic differentiation of BMSCs. Herein, we describe in-depth studies of roles for miRNAs during the osteogenic differentiation of BMSCs, as they provide new theoretical and experimental rationales for bone tissue engineering and clinical treatment.

Regenerative heating furnace as a high-efficiency and energy-saving heating equipment is widely applied in iron and steel industry. Accurate knowledge of total heat exchange factor of regenerative heating furnace is of great significance to improve its on-line control performance. Therefore, determination of total heat exchange factor of regenerative reheating furnace is investigated in this work. A three-dimensional mathematical model of regenerative reheating furnace based on the analysis of heat transfer process is established. The zonal method is used to solve the temperatures of gas zone, slab surface zone and wall surface zone, in which the Monte Carlo method is used to compute the total radiant exchange areas of thermocouple to all other zones in the furnace. The total heat exchange factors of regenerative reheating furnace are determined and the effects of thermal and operational parameters, such as productivity, fuel consumption and slab hot charging temperature are analyzed. The results show that the total heat transfer factor increases with the decrease of fuel consumption or slab hot charging temperature, and increases with the increase of productivity. The present work is valuable for dynamical compensation of total heat exchange factor of the online control mathematical models in regenerative reheating furnace.

Background Japanese Encephalitis (JE) is a mosquito-borne vi- ral disease that can affect the central nervous system and cause several complications and death. In Indonesia, particularly in Bali, studies of JE in humans are still very limited. Objective To assess the clinical manifestations and outcome of JE in Bali and to identify some possible associated factors and monthly distribution of admission to the hospitals. Methods A cross-sectional study was conducted in 8 district hospi- tals, army hospital, and Sanglah central hospital, as surveillance cen- ters in Bali, from July 2001 through January 2003. Subjects less than 12 years of age and residences of Bali province who were suspected of having acute viral encephalitis, aseptic meningitis, and acute flac- cid paralysis referred from all health facilities were included in this study. The diagnosis of JE was established by detection of virus-spe- cific IgM in CSF and serum, with IgM capture enzyme-linked immunosorbent assay (MAC ELISA) Results During the study, 158 subjects with encephalitis were in- cluded; 55 (34.8%) were caused by JE and 103 (65.2%) were caused by non-JE. It showed that pig owning and rice farming were signifi- cantly associated with JE (PR= 3.02, 95% CI 1.29; 7.10; P= 0.009 and PR= 2.86, 95% CI 1.30; 6,31, P= 0.008, respectively). Most subjects (46.2%) were under 2 years old with mean age of 37.24 (SD 32.24) months. Forty-two (26.6%) subjects had nuchal rigidity, and all of them had aseptic meningitis. Denpasar had the highest prevalence of non-JE cases. Bangli and Klungkung had the lowest prevalence of JE and non-JE. The highest prevalence of JE was in Gianyar. Peak prevalences of JE were in April and May 2002. Peak prevalences of non-JE were during August-October 2001 and in March-April 2002. Four (7.3%) subjects of JE group and 25 (24.3%) subjects of non-JE died. There were 25 (45.5%) out of 55 subjects who survived with disability. Twenty-four (43.6%) JE subjects and 34 (33.0%) non-JE subjects had good outcome. Conclusions Around one third of the subjects were positively di- agnosed as JE. The highest prevalence of JE was found in Gianyar. Peak prevalences of JE are in April and May 2002. Pig owning and rice farming are associated factors. Almost half of JE subjects sur- vived with disability

Lysozymes are important proteins of the innate immune system for the defense against bacterial infection. We cloned and analyzed chicken-type (c-type) and goose-type (g-type) lysozymes from Asian seabass (Lates calcarifer). The deduced amino acid sequence of the c-type lysozyme contained 144 residues and possessed typical structure residues, conserved catalytic residues (Glu(50) and Asp(67)) and a "GSTDYGIFQINS" motif. The deduced g-type lysozyme contained 187 residues and possessed a goose egg white lysozyme (GEWL) domain containing three conserved catalytic residues (Glu(71), Asp(84), Asp(95)) essential for catalytic activity. Real time quantitative PCR (qRT-PCR) revealed that the two lysozyme genes were constitutively expressed in all the examined tissues. The c-type lysozyme was most abundant in liver, while the g-type lysozyme was predominantly expressed in intestine and weakly expressed in muscle. The c-type and g-type transcripts were up-regulated in the kidney, spleen and liver in response to a challenge with Vibrio harveyi. The up-regulation of the c-type lysozyme was much stronger than that of the g-type lysozyme in kidney and spleen. The recombinant proteins of the c-type and g-type lysozymes showed lytic activities against the bacterial pathogens Vibrio harveyi and Photobacterium damselae in a dosage-dependent manner. We identified single nucleotide polymorphisms (SNPs) in the two lysozyme genes. There were significant associations of these polymorphisms with resistance to the big belly disease. These results suggest that the c- and g-type genes play an important role in resistance to bacterial pathogens in fish. The SNP markers in the two genes associated with the resistance to bacterial pathogens may facilitate the selection of Asian seabass resistant to bacterial diseases.

BackgroundMicroRNAs (miRNAs) play an important role in the regulation of many fundamental biological processes. So far miRNAs have been only identified in a few fish species, although there are over 30,000 fish species living under different environmental conditions on the earth. Here, we described an approach to identify conserved miRNAs and characterized their expression patterns in different tissues for the first time in a food fish species Asian seabass (Lates calcarifer).Methodology/principal findingsBy combining a bioinformatics analysis with an approach of homolog-based PCR amplification and sequencing, 63 novel miRNAs belonging to 29 conserved miRNA families were identified. Of which, 59 miRNAs were conserved across 10-86 species (E value ≤ 10⁻⁴) and 4 miRNAs were conserved only in fish species. qRT-PCR analysis showed that miR-29, miR-103, miR-125 and several let-7 family members were strongly and ubiquitously expressed in all tissues tested. Interestingly, miR-1, miR-21, miR-183, miR-184 and miR-192 showed highly conserved tissue-specific expression patterns. Exposure of the Asian seabass to lipopolysaccharide (LPS) resulted in up-regulation of over 50% of the identified miRNAs in spleen suggesting the importance of the miRNAs in acute inflammatory immune responses.Conclusions/significanceThe approach used in this study is highly effective for identification of conserved miRNAs. The identification of 63 miRNAs and determination of the spatial expression patterns of these miRNAs are valuable resources for further studies on post-transcriptional gene regulation in Asian seabass and other fish species. Further identification of the target genes of these miRNAs would shed new light on their regulatory roles of microRNAs in fish.

ABSTRACT Cyclin-dependent kinase-like 5 (CDKL5) is a protein kinase that is homologous to mitogen-activated protein kinases (MAPKs) and cyclin-dependent kinases (CDKs). Mutations in the CDKL5 gene cause X-linked infantile spasms and phenotypes that overlap with that of Rett syndrome, which is a neurodevelopmental disorder caused primarily by mutations in the methyl CpG binding protein 2 gene (MECP2). Previous studies in transfected cell lines showed that CDKL5 interacts with MeCP2 and DNA (cytosine-5)-methyltransferase 1 (Dnmt1). However, little is known about the relationships of CDKL5 with interacting proteins in primary neuronal cultures. In this study, we investigated the expression patterns of CDKL5, MeCP2 and Dnmt1, and their interaction in cultured rat cortical neurons. Using real-time PCR analysis, we found that CDKL5, MeCP2 and Dnmt1 have similar expression patterns at the mRNA level. In contrast, the expression patterns of those proteins at the protein level are different and could be inversely correlated, as shown by western blotting. Using co-immunoprecipitation, we further demonstrated that CDKL5 interacts with MeCP2 and Dnmt1 in primary rat cortical neurons. These data suggest that a functional link exists among CDKL5, MeCP2 and Dnmt1 during neuronal development and may provide further insight into the pathogenesis of Rett syndrome.

Abstract Sterile alpha and Toll/interleukin-1 receptor motif containing 1 (SARM1), a nicotinamide adenine dinucleotide (NAD)-utilizing enzyme, mediates axon degeneration (AxD) in various neurodegenerative diseases. It is activated by nicotinamide mononucleotide (NMN) to produce a calcium messenger, cyclic ADP-ribose (cADPR). This activity is blocked by elevated NAD level. Here, we verified this metabolic regulation in somatic HEK-293T cells by overexpressing NMN-adenyltransferase to elevate cellular NAD, which resulted not only in inhibition of their own SARM1 from producing cADPR but, surprisingly, also in the 5–10 neighboring wildtype cells in mixed cultures via connexin (Cx)-43. Direct visualization of gap junction intercellular communication (GJIC) was achieved by incubating cells with a permeant probe, PC11, which is converted by SARM1 into PAD11, a fluorescent NAD analog capable of traversing GJs. Extending the findings to dorsal root ganglion neurons, we further showed that CZ-48, a permeant NMN analog, or axotomy, activated SARM1 and the produced PAD11 was transferred to contacting axons via GJIC. The gap junction involved was identified as Cx36 instead. This neuronal GJIC was demonstrated to be functional, enabling healthy neurons to protect adjacent axotomized axons from degeneration. Inhibition of GJIC in mice by AAV-PHP.eB-mediated knockdown of Cx36 in brain induced neuroinflammation, which in turn activated SARM1 and resulted in axon degeneration as well as behavioral deficits. Our results demonstrate a novel intercellular regulation mechanism of SARM1 and reveal a protective role of healthy tissue against AxD induced by injury or neuroinflammation.

Modeling the gravitational field of irregular celestial bodies is a common problem currently faced by the researchers in the fields of Earth science and deep space exploration. This paper reviews the developmental history of gravitational field modeling theory in these two fields. It summarizes research progress in the last decade, focusing on multipole expansion and potential-flow simulation theories. The gravitational field multipole expansion theory introduces the complex algebraic function commonly used in electromagnetism and quantum mechanics to the gravitational field modeling research field, which can express the (internal and external) gravitational field of celestial bodies more concisely. The calculation rules and mathematical tools from the complex function theory make solving the gravitational dynamics problems in Earth and planetary science more convenient. The potential-flow simulation theory is proposed on top of the equivalence of the Earth's external gravitational vector field and the potential-flow velocity field. That is, both are source- and curl-free vector fields. It introduces the numerical algorithms of computational fluid dynamics to model the external gravitational fields of celestial bodies. Because the potential-flow simulation theory is not established based on the perturbation theory, it can overcome the divergence problem of conventional methods, especially when inverting for the gravitational field of an irregularly shaped celestial body. The two theories expand the theoretical research of gravitational field modeling by using seemingly irrelevant knowledge from other research fields, and such methodology is instructive for Earth or deep-space science researchers to make subsequent theoretical improvements. Moreover, we also systematically categorize, compare, and analyze the existing gravitational field modeling methods based on the mathematical definition of the gravitational field, as well as its variants, and summarize their advantages and disadvantages, helping to select proper gravitational field modeling methods for the Earth and deep-space science researchers.

Acinetobacter baumannii is a major pathogen of nosocomial meningitis and ventriculitis. Due to very limited antibiotic treatment options, polymyxins are often used as a last-line therapy. To optimise polymyxin use in the intraventricular environment, cerebrospinal fluid (CSF) proteomics was employed to investigate host-pathogen-polymyxin interactions in a 69-year-old patient with multidrug-resistant A. baumannii ventriculitis treated with a combination of intrathecal (ITH; 50,000 IU q24h/q48h), intraventricular (IVT; 50,000 IU q48h), and intravenous (500,000 IU, q12h) polymyxin B. CSF was collected before the first ITH dose in the ICU (0 h) and at 24 h, Day 7 and Day 26. The proteome was quantified at each time point and proteins with Qvalue 1.2 were considered differentially expressed. Within 24 h of ITH/IVT polymyxin B administration, the innate immune system and neuroimmunity were highly active, evidenced by up-regulation of various pathways related to pathogen invasion, endocytosis and neutrophil degranulation. Blood-brain barrier impairment had worsened at 24 h but signs of repair were evident on Day 7 and Day 26. This is the first CSF proteomic study with polymyxins. Our findings provide critical mechanistic insights into optimizing ITH/IVT polymyxin administration.

Article Highlights - Accurate gender identification supports effective breeding programs and ensures snakes' welfare. - This study emphasizes that probing is more reliable and efficient than contrast radiography for gender determination in reticulated pythons. - The probing method proved to have 100% accuracy in determining the gender of reticulated pythons, outperforming contrast radiography, which only achieved 75% accuracy. Abstract Reticulated pythons, like most snakes, do not exhibit noticeable sexual differences, which makes gender determination necessary. Probing and contrast radiography were chosen as methods to determine sex and to compare their accuracy. Six reticulated pythons with body lengths of 128-167 cm, tail lengths of 5.4-9.6 cm, and body diameters of 1.4-3.4 cm were examined twice by probing and contrast radiography. The results showed that probing had 100% accuracy, with probe lengths ranging from 1.37-3.60 cm for male snakes and 0.3-0.76 cm for female snakes. Contrast radiography had 75% accuracy, with the hemipenis appearing as a white silhouette and female snakes appearing colorless. The accuracy rates highlight the effectiveness of probing over contrast radiography for reliable gender determination in reticulated pythons

Abstract Quantum computing, with its superior computational capabilities compared to classical approaches, holds the potential to revolutionize numerous scientific domains, including pharmaceuticals. However, the application of quantum computing for drug discovery has primarily been limited to proof-of-concept studies, which often fail to capture the intricacies of real-world drug development challenges. In this study, we diverge from conventional investigations by developing a hybrid quantum computing pipeline tailored to address genuine drug design problems. Our approach underscores the application of quantum computation in drug discovery and propels it towards more scalable system. We specifically construct our versatile quantum computing pipeline to address two critical tasks in drug discovery: the precise determination of Gibbs free energy profiles for prodrug activation involving covalent bond cleavage, and the accurate simulation of covalent bond interactions. This work serves as a pioneering effort in benchmarking quantum computing against veritable scenarios encountered in drug design, especially the covalent bonding issue present in both of the case studies, thereby transitioning from theoretical models to tangible applications. Our results demonstrate the potential of a quantum computing pipeline for integration into real world drug design workflows.

Water level adjustment downstream of dams significantly impacts river regimes and flood control. However, due to constant strong scouring, our quantitative understanding of the characteristics of water level variations and their causes in the Chenglingji–Jiujiang Reach of the Yangtze River remains limited. Here, we analyzed the water level change trend via the Mann–Kendall method and analyzed geomorphic change and river resistance using 406 cross-sectional profiles as well as data on discharge and water levels from 1991 to 2022. Results showed that the critical conversion discharges (CCD) in the Chenglingji-Hankou Reach and the Hankou-Jiujiang Reach were approximately 35,000 and 30,000 m3/s, respectively, after the operation of the Three Gorges Dam. The water level exhibited an overall decline mainly due to river erosion when the discharge was lower than the CCD. The water level exhibited a nonsignificant upward trend mainly due to increased river resistance (7–20%) when the discharge was higher than the CCD. The obvious increase in the floodwater level in individual years was caused by the effect of downstream water level increase. Our findings further the understanding of downstream geomorphic response to dam operation and their impacts on water levels and have important implications for flood management in such rivers worldwide. HIGHLIGHTS The critical conversion discharges of the water level changes in the Chenglingji-Hankou Reach and Hankou-Jiujiang Reach are approximately 35,000 and 30,000 m3/s, respectively.; The dominant cause of the water level decrease below or increase above the critical conversion discharge is river erosion or greater increase in resistance.; The obvious increase in the floodwater level in individual years was due to the more obvious increase of downstream water level.;

Abstract Purpose Sepsis is a global public health burden. The sequential organ failure assessment (SOFA) is the most commonly used scoring system for diagnosing sepsis and assessing severity. Due to the widespread use of endotracheal intubation and sedative medications in sepsis, the accuracy of the Glasgow Coma Score (GCS) is the lowest in SOFA. We designed this multicenter, cross-sectional study to investigate the predictive efficiency of SOFA with or without GCS on ICU mortality in patients with sepsis. Methods First, 3048 patients with sepsis admitted to Peking Union Medical College Hospital (PUMCH) were enrolled in this survey. The data were collected from June 8, 2013 to October 12, 2022. Second, 18,108 patients with sepsis in the eICU database were enrolled. Third, 2397 septic patients with respiratory system ≥ 3 points in SOFA in the eICU database were included. We investigated the predictive efficiency of SOFA with or without GCS on ICU mortality in patients with sepsis in various ICUs of PUMCH, and then we validated the results in the eICU database. Main results In data of ICUs in PUMCH, the predictive efficiency of SOFA without GCS (AUROC [95% CI], 24 h, 0.724 [0.688, 0.760], 48 h, 0.734 [0.699, 0.769], 72 h, 0.748 [0.713, 0.783], 168 h, 0.781 [0.747, 0.815]) was higher than that of SOFA with GCS (AUROC [95% CI], 24 h, 0.708 [0.672, 0.744], 48 h, 0.721 [0.685, 0.757], 72 h, 0.735 [0.700, 0.757], 168 h, 0.770 [0.736, 0.804]) on ICU mortality in patients with sepsis, and the difference was statistically significant (P value, 24 h, 0.001, 48 h, 0.003, 72 h, 0.004, 168 h, 0.005). In septic patients with respiratory system ≥ 3 points in SOFA in the eICU database, although the difference was not statistically significant (P value, 24 h, 0.148, 48 h, 0.178, 72 h, 0.132, 168 h, 0.790), SOFA without GCS (AUROC [95% CI], 24 h, 0.601 [0.576, 0.626], 48 h, 0.625 [0.601, 0.649], 72 h, 0.639 [0.615, 0.663], 168 h, 0.653 [0.629, 0.677]) had a higher predictive efficiency on ICU mortality than SOFA with GCS (AUROC [95% CI], 24 h, 0.591 [0.566, 0.616], 48 h, 0.616 [0.592, 0.640], 72 h, 0.628 [0.604, 0.652], 168 h, 0.651 [0.627, 0.675]). Conclusions In severe sepsis, it is realistic and feasible to discontinue the routine GCS for SOFA in patients with a respiratory system ≥ 3 points, and even better predict ICU mortality.

Abstract Background A malignancy might be found at surgery in cases of atypical ductal hyperplasia (ADH) diagnosed via US-guided core needle biopsy (CNB). The objective of this study was to investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in predicting ADH diagnosed by US-guided CNB that was upgraded to malignancy after surgery. Methods In this retrospective study, 110 CNB-diagnosed ADH lesions in 109 consecutive women who underwent US, CEUS, and surgery between June 2018 and June 2023 were included. CEUS was incorporated into US BI-RADS and yielded a CEUS-adjusted BI-RADS. The diagnostic performance of US BI-RADS and CEUS-adjusted BI-RADS for ADH were analyzed and compared. Results The mean age of the 109 women was 49.7 years ± 11.6 (SD). The upgrade rate of ADH at CNB was 48.2% (53 of 110). The sensitivity, specificity, positive predictive value, and negative predictive value of CEUS for identification of malignant upgrading were 96.2%, 66.7%,72.9%, and 95.0%, respectively, based on BI-RADS category 4B threshold. The two false-negative cases were low-grade ductal carcinoma in situ. Compared with the US, CEUS-adjusted BI-RADS had better specificity for lesions smaller than 2 cm (76.7% vs. 96.7%, P = 0.031). After CEUS, 16 (10 malignant and 6 nonmalignant) of the 45 original US BI-RADS category 4A lesions were up-classified to BI-RADS 4B, and 3 (1 malignant and 2 nonmalignant) of the 41 original US BI-RADS category 4B lesions were down-classified to BI-RADS 4A. Conclusions CEUS is helpful in predicting malignant upgrading of ADH, especially for lesions smaller than 2 cm and those classified as BI-RADS 4A and 4B on ultrasound.

When light passes through air–glass and glass–water interfaces, refraction occurs, which affects the accuracy of stereo vision three-dimensional measurements of underwater targets. To eliminate the impact of refraction, we developed a refractive stereo vision measurement model based on light propagation paths, utilizing the normalized coordinate of the underwater target. This model is rigorous in theory, and easy to understand and apply. Additionally, we established an underwater simulation imaging model based on the principle that light travels the shortest time between two points. Simulation experiments conducted using this imaging model verified the performance of the underwater stereo vision measurement model. The results demonstrate that the accuracy achieved by the new measurement model is comparable to that of the stereo vision measurement model in the air and significantly higher than that of the existing refractive measurement model. This is because the light rays from the camera’s optical center to the refraction point at the air–glass interface do not always intersect. The experiments also indicate that the deviation in the refractive index of water lead to corresponding systematic errors in the measurement results. Therefore, in real underwater measurements, it is crucial to carefully calibrate the refractive index of water and maintain the validity of the calibration results.

BackgroundThe role of macrophages in the symptomatic and structural progression of pulmonary fibrosis (PF) has garnered significant scholarly attention in recent years. This study employs a bibliometric approach to examine the present research status and areas of focus regarding the correlation between macrophages and PF, aiming to provide a comprehensive understanding of their relationship.MethodologyThe present study employed VOSviewer, CiteSpace, and Microsoft Excel software to visualize and analyze various aspects such as countries, institutions, authors, journals, co-cited literature, keywords, related genes, and diseases. These analyses were conducted using the Web of Science core collection database.ResultsA comprehensive collection of 3,479 records pertaining to macrophages and PF from the period of 1990 to 2023 was obtained. Over the years, there has been a consistent increase in research literature on this topic. Notably, the United States and China exhibited the highest level of collaboration in this field. Through careful analysis, the institutions, authors, and prominent journals that hold significant influence within this particular field have been identified as having the highest publication output. The pertinent research primarily concentrates on the domains of Biology and Medicine. The prevailing keywords encompass pulmonary fibrosis, acute lung injury, idiopathic pulmonary fibrosis, and others. Notably, TGFβ1, TNF, and CXCL8 emerge as the most frequently studied targets, primarily associated with signaling pathways such as cytokine–cytokine receptor interaction. Additionally, cluster analysis of related diseases reveals their interconnectedness with ailments such as cancer.ConclusionThe present study employed bibliometric methods to investigate the knowledge structure and developmental trends in the realm of macrophage and PF research. The findings shed light on the introduction and research hotspots that facilitate a more comprehensive understanding of macrophages and PF.

There has been substantial research on multi-medium visual measurement in fields such as underwater three-dimensional reconstruction and underwater structure monitoring. Addressing the issue where traditional air-based visual-measurement models fail due to refraction when light passes through different media, numerous studies have established refraction-imaging models based on the actual geometry of light refraction to compensate for the effects of refraction on cross-media imaging. However, the calibration of refraction parameters inevitably contains errors, leading to deviations in these parameters. To analyze the impact of refraction-parameter deviations on measurements in underwater structure visual navigation, this paper develops a dual-media stereo-vision measurement simulation model and conducts comprehensive simulation experiments. The results indicate that to achieve high-precision underwater-measurement outcomes, the calibration method for refraction parameters, the distribution of the targets in the field of view, and the distance of the target from the camera must all be meticulously designed. These findings provide guidance for the construction of underwater stereo-vision measurement systems, the calibration of refraction parameters, underwater experiments, and practical applications.