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Background Due to its occult position, complex anatomical structure, and spatial relationships, the causative tumor of Tumor-Induced Osteomalacia (TIO) in the hip region is quite difficult to detect and qualitatively diagnose in clinical practice. In this regard, clinicians often lack sufficient knowledge about such tumors, leading to frequent missed diagnoses, misdiagnoses, and unreasonable treatment. Objective This study aimed to investigate the clinical characteristics of TIO patients with culprit soft tissue tumors in the hip region and evaluate the effect of surgical treatment on these individuals to improve clinicians’ understanding of the rare phenomenon. Methods The clinical data of all patients, from January 2013 to January 2023, who underwent surgical treatment for hip located culprit soft tissue tumors by the subspecialty group on bone and soft tissue tumors at our institution, were retrospectively analysed. Specifically, the clinical characteristics and therapeutic effects were examined and the patients’ clinical experience was summarized. Results Twenty-two patients, who met the inclusion criteria, were included. All patients experienced varying degrees of bone pain, commonly accompanied by weakness (16/22) and limited mobility (21/22), and 10 patients (45.5%) experienced a significant reduction in body height during the course of the disease. All patients underwent orthopedic surgery in the hip region, as hypophosphatemia occurred in all of them. Pathological diagnosis was confirmed to be consistent with causative tumors of TIO. All patients experienced a gradual increase in serum phosphorus postoperatively during short-term follow-up. The follow-up period was between 1 and 10 years, and the postoperative serum phosphorus levels were monitored at our hospital or other facilities close to the patients. Conclusions Oncogenic soft tissue tumors for TIO in the hip region are occult, making clinical misdiagnoses or missed diagnoses highly likely. Therefore, enhancing the clinician’s understanding of this rare condition is imperative. Notably, for TIO patient whose culprit tumor can be located, complete surgical resection of the causative tumor is the best treatment option. Furthermore, close postoperative monitoring of serum phosphorus is necessary, and patients should be subjected to long-term follow-up for prompt detection of recurrent conditions. Highlights Tumor-induced osteomalacia caused by causative soft tissue tumor in the hip region is a rare entity, resulting in great challenges to orthopedists. Qualitative and localized diagnosis led by multi-disciplinary team is a prerequisite for subsequent surgical intervention. For the inguinally located culprit tumors, it may be quite effective after remove the culprit tumor directly and surgical resection may bring huge benefit. Exploring the site of onset of the causative tumor is beneficial for improving the treatment strategy of orthopedic surgery and understanding the prognostic characteristics of TIO patients.

Establishing genotype-phenotype relationship is the key to understand the molecular mechanism of phenotypic adaptation. This initial step may be untangled by analyzing appropriate ancestral molecules, but it is a daunting task to recapitulate the evolution of non-additive (epistatic) interactions of amino acids and function of a protein separately. To adapt to the ultraviolet (UV)-free retinal environment, the short wavelength-sensitive (SWS1) visual pigment in human (human S1) switched from detecting UV to absorbing blue light during the last 90 million years. Mutagenesis experiments of the UV-sensitive pigment in the Boreoeutherian ancestor show that the blue-sensitivity was achieved by seven mutations. The experimental and quantum chemical analyses show that 4,008 of all 5,040 possible evolutionary trajectories are terminated prematurely by containing a dehydrated nonfunctional pigment. Phylogenetic analysis further suggests that human ancestors achieved the blue-sensitivity gradually and almost exclusively by epistasis. When the final stage of spectral tuning of human S1 was underway 45-30 million years ago, the middle and long wavelength-sensitive (MWS/LWS) pigments appeared and so-called trichromatic color vision was established by interprotein epistasis. The adaptive evolution of human S1 differs dramatically from orthologous pigments with a major mutational effect used in achieving blue-sensitivity in a fish and several mammalian species and in regaining UV vision in birds. These observations imply that the mechanisms of epistatic interactions must be understood by studying various orthologues in different species that have adapted to various ecological and physiological environments.

Augmented reality (AR) technology is gradually being applied in surgical teaching as an innovative teaching method. Developing innovative teaching methods to replicate clinical theory and practical teaching scenarios, simulate preoperative planning and training for bone tumor surgery, and offer enhanced training opportunities for young physicians to acquire and apply clinical knowledge is a crucial concern that impacts the advancement of the discipline and the educational standards for young orthopedic physicians. This study explores the application effect of augmented reality technology in anatomy teaching and surgical clinical teaching for spinal tumor. The method utilizes virtual reality and augmented reality technology to present a spinal tumor model and the surgical process of percutaneous vertebroplasty. We conducted a random selection of 12 students forming into the augmented reality teaching group and 13 students forming into the traditional teaching group among the 8-year medical students from Peking Union Medical College and Tsinghua University, ensuring that the age and learning stage of the students in both groups were similar. Two groups of students were taught using traditional teaching methods and augmented reality technology-assisted teaching methods, respectively. A questionnaire survey was conducted after class to assess the quality of course instruction, student motivation in learning, their proficiency in anatomical structures, their comprehension of spinal tumor growth and metastasis, and their understanding and proficiency in percutaneous vertebroplasty. This study was the first to apply augmented reality technology in teaching, using spinal tumors and percutaneous vertebroplasty as examples, a head-mounted augmented reality device was used to create learning scenarios, presenting the complex three-dimensional spatial structure intuitively. The two groups of students differ significantly in their rating of teaching quality, enthusiasm for learning, knowledge of anatomical features, understanding of spinal trabecular structure, and understanding of steps in percutaneous vertebroplasty. The augmented reality technology-assisted teaching system demonstrates outstanding advantages. Augmented reality technology has great potential and broad prospects in teaching bone tumors, which can help improve the visualization, interactivity, and three-dimensional spatial sense of medical teaching in spinal tumor. The application and development prospects of using augmented reality technology for anatomy instruction, surgical teaching, and simulation training are extensive.

Objective The orthopedic surgical treatment strategies for patients with tumor‐induced osteomalacia (TIO) require improvement, especially for patients where the causative tumors are located in surgically challenging areas, requiring a greater degree of in‐depth investigation. This work aims to summarize and investigate clinical features and orthopedic surgical treatment effects of patients with tumor‐induced osteomalacia (TIO), whose causative tumors are located in the hip bones. Methods A retrospective analysis was conducted on the clinical data of all patients diagnosed with culprit tumors located in the hip bones who underwent surgical treatment at the orthopedic bone and soft tissue tumor sub‐professional group of Peking Union Medical College Hospital from January 2013 to January 2023. This retrospective study summarized the clinical data, preoperative laboratory test results, imaging findings, surgery‐related data, perioperative changes in blood phosphorus levels, and postoperative follow‐up data of all patients who met the inclusion criteria. Normally distributed data are presented as mean and standard deviation, while non‐normally distributed data are shown as the means and 25th and 75th interquartile ranges. Results The clinical diagnostic criteria for TIO were met by all 16 patients, as confirmed by pathology after surgery. Among the 16 patients, we obtained varying degrees of bone pain and limited mobility (16/16), often accompanied by difficulties in sitting up, walking, and fatigue. An estimated 62.5% (10/16) of patients had significantly shorter heights during the disease stages. All 16 patients underwent surgical treatment for tumors in the hip bones, totaling 21 surgeries. In the pathogenic tumor, there were 16 cases of skeletal involvement and none of pure soft tissue involvement. Out of the 16 patients, 13 cases had a gradual increase in blood phosphorus levels following the latest orthopedic surgery, which was followed up for 12 months to 10 years. Due to unresolved conditions after the original surgery, four patients received reoperation intervention. Two cases of refractory TIO did not improve in their disease course. Conclusion In summary, the location of the causative tumor in the hip bone is hidden and diverse, and there is no defined orthopedic surgical intervention method for this case in clinical practice. For patients with TIO where the tumors are located in the hip bones, surgical treatment is difficult and the risk of postoperative recurrence is high. Careful identification of the tumor edge using precise preoperative positioning and qualitative diagnosis is crucial to ensure adequate boundaries for surgical resection to reduce the likelihood of disease recurrence and improve prognosis. The location of the causative tumor in the hip bone is hidden and diverse, resulting in great challenges to endocrinologists and orthopedists. For the intraosseous tumor in hip bone, it may be quite difficult to remove the culprit tumor. In this situation, the proportion of recurrent/refractory cases has significantly increased, posing a huge challenge to the diagnosis and treatment of patients with this type of disease.

Folic acid (FA) is an important water-soluble vitamin and plays an important role as a cofactor and coenzyme in animal growth and development, and regulation of gene expression and methylation. A total of 270 female broiler chickens (1-day-old) were randomly allotted to three dietary treatments supplemented with 0 mg/kg (control group), 5 mg/kg, and 10 mg/kg FA in basal diets for 42 days, respectively. Each treatment had six replicate cages with 15 birds per cage. Dietary supplementation of 5 mg/kg FA significantly enhanced average body weight and average daily gain of 21-day-old broilers (P < 0.05), but significantly reduced subcutaneous fat thickness and widths of an intermuscular fat band of 42-day-old broilers by dietary FA treatments (P < 0.05). Also, a diet with 10 mg/kg FA supplementation significantly increased the relative heart weight of 42-day-old chickens (P < 0.05). Furthermore, dietary FA supplementation significantly improved the serum insulin-like growth factor 2 (IGF2) concentrations (P < 0.01) and IGF2 mRNA expression in the abdominal fat (P < 0.05), but no statistical differences were found in the methylation of IGF2 promoter (P > 0.05). The present study demonstrated that dietary FA supplementation may have positive effects on chicken growth through increased IGF2 gene expression.

Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) is an infectious disease characterized by severe reproductive deficiency in pregnant sows, typical respiratory symptoms in piglets, and high mortality rate of piglets. In this study, we employed an Affymetrix microarray chip to compare the gene expression profiles of lung tissue samples from Dapulian (DPL) pigs (a Chinese indigenous pig breed) and Duroc×Landrace×Yorkshire (DLY) pigs after infection with PRRSV. During infection with PRRSV, the DLY pigs exhibited a range of clinical features that typify the disease, whereas the DPL pigs showed only mild signs of the disease. Overall, the DPL group had a lower percentage of CD4(+) cells and lower CD4(+)/CD8(+)ratios than the DLY group (p<0.05). For both IL-10 and TNF-α, the DLY pigs had significantly higher levels than the DPL pigs (p<0.01). The DLY pigs have lower serum IFN-γ levels than the DPL pigs (p<0.01). The serum IgG levels increased slightly from 0 dpi to 7 dpi, and peaked at 14 dpi (p<0.0001). Microarray data analysis revealed 16 differentially expressed (DE) genes in the lung tissue samples from the DLY and DPL pigs (q≤5%), of which LOC100516029 and LOC100523005 were up-regulated in the PRRSV-infected DPL pigs, while the other 14 genes were down-regulated in the PRRSV-infected DPL pigs compared with the PRRSV-infected DLY pigs. The mRNA expression levels of 10 out of the 16 DE genes were validated by real-time quantitative RT-PCR and their fold change was consistent with the result of microarray data analysis. We further analyzed the mRNA expression level of 8 differentially expressed genes between the DPL and DLY pigs for both uninfected and infected groups, and found that TF and USP18 genes were important in underlying porcine resistance or susceptibility to PRRSV.

In silico models are presented for modeling and predicting thyroid hormone receptor (TR) agonists and antagonists. A data set consisting of 258 compounds is used in the present work. The C4.5, random forest (RF) and support vector machine (SVM) statistical methods were used for evaluation. The performance of the quantitative structure–activity relationships was further validated with fivefold cross-validation and an independent external test set. The C4.5 model is slightly weak, and the prediction accuracies of the agonists and antagonists are 93.2 and 57.8% for cross-validation, respectively, averaging 83.1% of correctly classified compounds in the test set. The RF model possesses an average prediction accuracy of 84.0 and 87.1% for the cross-validation and external validation, respectively. Furthermore, the overall prediction accuracy and the external prediction accuracy are 96.6 and 97.2%, respectively, for the SVM model. The results would validate the reliability of the derived models, further demonstrating that RF and SVM models are useful tools capable of classifying TR-binding ligands as agonists or antagonists.

Experiments were conducted to investigate the effect of betaine supplementation on mRNA expression levels of lipogenesis genes and CpG methylation of lipoprotein lipase gene (LPL) in broilers. From 22 days of age, 78 broilers were feed basal diet without betaine and basal diet supplemented with 0.1% betaine, respectively, and at 56 and 66 days of age, the traits of 15 chickens (7 males and 8 females) of each group were recorded and abdominal fat pads were collected. The mRNA expression levels of several lipogenesis gene were analyzed by semi-quantitative RT-PCR and real-time quantitative RT-PCR (qPCR), respectively. The CpG methylation profile at the promoter region of LPL gene in 66-day-old broilers was determined by bisulfite sequencing. The average daily gain and percent abdominal fat traits were slightly improved in 56-day-old and 66-day-old broilers after dietary supplementation of betaine to diet. After adding 0.1% betaine to diet, the mRNA levels of fatty acid synthase (FAS) and adipocyte-type fatty acid-binding protein genes in abdominal adipose were significantly decreased in 56-day-old broilers, and those of LPL and FAS genes in abdominal adipose were significantly decreased in 66-day-old broilers comparing with the control group (P < 0.05 and P < 0.001). Moreover, in 66-day-old broilers fed 0.1% betaine diet, a different CpG methylation pattern was observed: the CpG dinucleotides of 1st, 6th, 7th, 8th and from 10th to 50th were less methylated; however, those of 2nd, 5th and 9th were more heavily methylated. The results suggest that transcription of some lipogenesis genes was decreased by betaine supplementation and betaine may decrease LPL mRNA expression by altering CpG methylation pattern on LPL promoter region.

As a transcription factor regulating circadian rhythm, brain and muscle Arnt-like protein-1 (BMAL1) plays an important role in lipid homeostasis. The Chinese indigenous and western pig breeds show marked difference in fat deposition, the structure and function of porcine BMAL1 (pBMAL1) between them might be different. In present study, the molecular characteristics and chromosomal location of pBMAL1 were analyzed. The results indicated that pBMAL1 cDNA had a coding region of 1,878 bp and shared 94.36, 89.85 and 89.79% identity with human, mouse and rat BMAL1 , respectively, and the pBMAL1 protein had 99.20, 98.24 and 97.92% identity to those of human BMAL1b, mouse BMAL1b and rat BMAL1b, respectively. Compared with other mammals, pBMAL1 was more closely related to human BMAL1 . The expression of pBMAL1 was detected in kidney, stomach, spleen, bladder, gallbladder, lumbar spinal cord, medulla oblongata, heart, longissimus dorsi muscle, liver, small intestine, large intestine, lung and backfat tissues. In adipose tissues, it was detected in mesentery fat, leaf fat, caul fat, backfat and cardiac fat, however, the expression level was not significantly different. Alternative usage of exon 2 was revealed to result in two pBMAL1 transcripts. Finally, by using a whole genome porcine radiation hybrid (RH) panel (IMpRH), the pBMAL1 gene was mapped to SSC 2p11-q21.