Search

Abstract Background With the advancement of world population aging, age-related sarcopenia (SP) imposes enormous clinical burden on hospital. Clinical research of SP in non-geriatric wards has not been appreciated, necessitating further investigation. However, observational studies are susceptible to confounders. Mendelian randomization (MR) can effectively mitigate bias to assess causality. Objective To investigate the correlation between SP and comorbidities in orthopedic wards, and subsequently infer the causality, providing a theoretical basis for developing strategies in SP prevention and treatment. Methods Logistic regression models were employed to assess the correlation between SP and comorbidities. The MR analysis was mainly conducted with inverse variance weighted, utilizing data extracted from the UK and FinnGen biobank (Round 9). Results In the cross-sectional analysis, SP exhibited significant associations with malnutrition (P = 0.013) and some comorbidities, including osteoporosis (P = 0.014), body mass index (BMI) (P = 0.021), Charlson Comorbidity Index (CCI) (P = 0.006). The MR result also provided supporting evidence for the causality between SP and hypertension, osteoporosis and BMI. These results also withstood multiple sensitivity analyses assessing the validity of MR assumptions. Conclusion The result indicated a significant association between SP and BMI, CCI, malnutrition, and osteoporosis. We highlighted that SP and comorbidities deserved more attention in non-geriatric wards, urging further comprehensive investigation.

Abstract Background Language delay affects near- and long-term social communication and learning in toddlers, and, an increasing number of experts pay attention to it. The development of prosody discrimination is one of the earliest stages of language development in which key skills for later stages are mastered. Therefore, analyzing the relationship between brain discrimination of speech prosody and language abilities may provide an objective basis for the diagnosis and intervention of language delay. Methods In this study, all cases(n = 241) were enrolled from a tertiary women’s hospital, from 2021 to 2022. We used functional near-infrared spectroscopy (fNIRS) to assess children’s neural prosody discrimination abilities, and a Chinese communicative development inventory (CCDI) were used to evaluate their language abilities. Results Ninety-eight full-term and 108 preterm toddlers were included in the final analysis in phase I and II studies, respectively. The total CCDI screening abnormality rate was 9.2% for full-term and 34.3% for preterm toddlers. Full-term toddlers showed prosody discrimination ability in all channels except channel 5, while preterm toddlers showed prosody discrimination ability in channel 6 only. Multifactorial logistic regression analyses showed that prosody discrimination of the right angular gyrus (channel 3) had a statistically significant effect on language delay (odd ratio = 0.301, P

Abstract Background Cholangiocarcinoma (CCA) is a biliary epithelial malignant tumor with an increasing incidence worldwide. Therefore, further understanding of the molecular mechanisms of CCA progression is required to identify new therapeutic targets. Methods The expression of RPL35A in CCA and para-carcinoma tissues was detected by immunohistochemical staining. IP-MS combined with Co-IP identified downstream proteins regulated by RPL35A. Western blot and Co-IP of CHX or MG-132 treated CCA cells were used to verify the regulation of HSPA8 protein by RPL35A. Cell experiments and subcutaneous tumorigenesis experiments in nude mice were performed to evaluate the effects of RPL35A and HSPA8 on the proliferation, apoptosis, cell cycle, migration of CCA cells and tumor growth in vivo. Results RPL35A was significantly upregulated in CCA tissues and cells. RPL35A knockdown inhibited the proliferation and migration of HCCC-9810 and HUCCT1 cells, induced apoptosis, and arrested the cell cycle in G1 phase. HSPA8 was a downstream protein of RPL35A and overexpressed in CCA. RPL35A knockdown impaired HSPA8 protein stability and increased HSPA8 protein ubiquitination levels. RPL35A overexpression promoted CCA cell proliferation and migration. HSPA8 knockdown inhibited CCA cell proliferation and migration, and reversed the promoting effect of RPL35A. Furthermore, RPL35A promoted tumor growth in vivo. In contrast, HSPA8 knockdown suppressed tumor growth, while was able to restore the effects of RPL35A overexpression. Conclusion RPL35A was upregulated in CCA tissues and promoted the progression of CCA by mediating HSPA8 ubiquitination.

Abstract Background Neoadjuvant chemotherapy (NAC) has become a standard treatment strategy for breast cancer (BC). However, owing to the high heterogeneity of these tumors, it is unclear which patient population most likely benefit from NAC. Multi-omics offer an improved approach to uncovering genomic and transcriptomic changes before and after NAC in BC and to identifying molecular features associated with NAC sensitivity. Methods We performed whole-exome and RNA sequencing on 233 samples (including matched pre- and post-treatment tumors) from 50 BC patients with rigorously defined responses to NAC and analyzed changes in the multi-omics landscape. Molecular features associated with NAC response were identified and validated in a larger internal, and two external validation cohorts, as well as in vitro experiments. Results The most frequently altered genes were TP53, TTN, and MUC16 in both pre- and post-treatment tumors. In comparison with pre-treatment tumors, there was a significant decrease in C > A transversion mutations in post-treatment tumors (P = 0.020). NAC significantly decreased the mutation rate (P = 0.006) of the DNA repair pathway and gene expression levels (FDR = 0.007) in this pathway. NAC also significantly changed the expression level of immune checkpoint genes and the abundance of tumor-infiltrating immune and stroma cells, including B cells, activated dendritic cells, γδT cells, M2 macrophages and endothelial cells. Furthermore, there was a higher rate of C > T substitutions in NAC nonresponsive tumors than responsive ones, especially when the substitution site was flanked by C and G. Importantly, there was a unique amplified region at 8p11.23 (containing ADGRA2 and ADRB3) and a deleted region at 3p13 (harboring FOXP1) in NAC nonresponsive and responsive tumors, respectively. Particularly, the CDKAL1 missense variant P409L (p.Pro409Leu, c.1226C > T) decreased BC cell sensitivity to docetaxel, and ADGRA2 or ADRB3 gene amplifications were associated with worse NAC response and poor prognosis in BC patients. Conclusions Our study has revealed genomic and transcriptomic landscape changes following NAC in BC, and identified novel biomarkers (CDKAL1 P409L , ADGRA2 and ADRB3) underlying chemotherapy resistance and poor prognosis, which could guide the development of personalized treatments for BC.

Abstract Objective The purpose of this study was to provide evidence for early life care by meta-analyzing the relationship between infection during pregnancy and up to 2 years of age and the risk of subsequent allergic rhinitis (AR). Methods Published studies up to April 2022 were systematically searched in PubMed, Embase, Web of Science, Cochrane Library, SinoMed, CNKI, Wanfang Database, and VIP. Literature screening, including quality assessment, was performed, and the effect values (OR, HR, RR) and 95% confidence intervals (95% CI) of infection during pregnancy and up to 2 years of age and allergic rhinitis were extracted from each qualified study. Results In total, 5 studies with a sample size of 82,256 reported the relationship between infection during pregnancy and offspring AR. Meta-analysis showed that maternal infection during pregnancy was associated with an increased risk of childhood AR in offspring (OR = 1.34, 95% CI: 1.08–1.67). Altogether, 13 studies with a sample size of 78,426 reported evidence of an association between infection within 2 years of age and subsequent AR in children. A pooled meta-analysis of all studies showed that early infection within 2 years of age was closely associated with childhood AR (OR = 1.25, 95% CI: 1.12–1.40), especially upper respiratory tract infection (OR = 1.32, 95% CI: 1.06–1.65) and gastrointestinal infections (OR = 1.37, 95% CI: 1.01–1.86), but ear infection showed similar results in the cohort study (OR = 1.13, 95% CI: 1.04–1.22). Conclusion Current evidence suggests that infection during pregnancy, early upper respiratory infection, gastrointestinal infections and ear infection within 2 years of age would increase the risk of AR in children. Therefore, the prevention of infection during pregnancy and in infancy and young children needs to be emphasized.

Abstract Background The small number of samples and the curse of dimensionality hamper the better application of deep learning techniques for disease classification. Additionally, the performance of clustering-based feature selection algorithms is still far from being satisfactory due to their limitation in using unsupervised learning methods. To enhance interpretability and overcome this problem, we developed a novel feature selection algorithm. In the meantime, complex genomic data brought great challenges for the identification of biomarkers and therapeutic targets. The current some feature selection methods have the problem of low sensitivity and specificity in this field. Results In this article, we designed a multi-scale clustering-based feature selection algorithm named MCBFS which simultaneously performs feature selection and model learning for genomic data analysis. The experimental results demonstrated that MCBFS is robust and effective by comparing it with seven benchmark and six state-of-the-art supervised methods on eight data sets. The visualization results and the statistical test showed that MCBFS can capture the informative genes and improve the interpretability and visualization of tumor gene expression and single-cell sequencing data. Additionally, we developed a general framework named McbfsNW using gene expression data and protein interaction data to identify robust biomarkers and therapeutic targets for diagnosis and therapy of diseases. The framework incorporates the MCBFS algorithm, network recognition ensemble algorithm and feature selection wrapper. McbfsNW has been applied to the lung adenocarcinoma (LUAD) data sets. The preliminary results demonstrated that higher prediction results can be attained by identified biomarkers on the independent LUAD data set, and we also structured a drug-target network which may be good for LUAD therapy. Conclusions The proposed novel feature selection method is robust and effective for gene selection, classification, and visualization. The framework McbfsNW is practical and helpful for the identification of biomarkers and targets on genomic data. It is believed that the same methods and principles are extensible and applicable to other different kinds of data sets.

Abstract Background Almost all liver tumours can be removed laparoscopically, but some difficult tumour locations complicate laparoscopic surgery. Recurrent liver tumours often pose great difficulties to laparoscopic surgery due to adhesions caused by previous operations. Referring to laparoscopic adrenalectomy, a retroperitoneal approach is proposed to remove liver tumours near the adrenal gland, which will provide a new method for liver surgery. Case presentation Our case involves a patient with recurrent hepatocellular carcinoma (HCC) whose last operation was laparoscopic hepatectomy in our department, with a recurrence of HCC 2 years after the first surgery. In this case, based on preoperative CT and MRI, through a retroperitoneal approach, combined with intraoperative ultrasound (IOUS) localization and indocyanine green (ICG) fluorescence navigation, laparoscopic hepatectomy was successfully performed to precisely resect recurrent hepatocellular carcinoma in segment VII. The patient was discharged on the third day after the operation. The AFP decreased to normal levels on the 28th postoperative day. Conclusions Retroperitoneal hepatectomy has the advantages of less trauma, shorter operation times, fewer complications and faster recovery for hepatic tumours near the adrenal gland. Accurate localization of tumours is needed to ensure accurate resection; therefore, IOUS and ICG fluorescence are very important. Liver parenchyma was severed strictly according to fluorescent labelling during hepatectomy, which prevented the deviation of liver parenchyma from the plane and ensured that the margin of hepatectomy was tumour-free. In order to ensure a radical resection of the tumour, it may be necessary to enter the abdominal cavity.

Abstract Background Many studies have found an interesting issue in the Internet gaming disorder (IGD): males are always observed to be the majority. However, there are little research to exploring the differences in the neural mechanisms between males and females in decision-making process among people with IGD. Therefore, explore the reward/loss processing between different gender with IGD could help in understanding the underlying neural mechanism of IGD. Methods Data from functional magnetic resonance imaging (fMRI) were collected from 111 subjects (IGD: 29 males, 25 females; recreational internet game user (RGU): 36 males, 21 females) while they were performing a card-guessing task. We collected and compared their brain features when facing the win and loss conditions in different groups. Results For winning conditions, IGD group showed hypoactivity in the lingual gyrus than RGU group, male players showed hyperactivity in the left caudate nucleus, bilateral cingulate gyrus, right middle frontal gyrus (MFG), right precuneus and inferior parietal lobule relative to the females. And significant sex-by-group interactions results showed higher brain activities in the thalamus, parahippocampal gyrus and lower brain activities in Inferior frontal gyrus (IFG) were observed in males with IGD than females. For losing conditions, IGD group showed hypoactivity in the left lingual gyrus, parahippocampal gyrus and right anterior cingulate cortex (ACC) compared to the RGU group, male players showed hyperactive left caudate nucleus and hypoactive right middle occipital gyrus relative to females. And significant sex-by-group interactions results showed that compared to females with IGD, males with IGD showed decreased brain activities in the IFG and lingual gyrus. Conclusions First, there appeared to be no difference in reward processing between the IGD and RGU group, but IGD showed less sensitivity to loss. Secondly, male players showed more sensitivity to rewards and less sensitivity to losses. Last but not least, males and females showed opposite activation patterns in IGD degree and rewards/losses processing. And male IGD subjects are more sensitive to reward and less sensitive to loss than females, which might be the reason for the gender different rates on IGD.

Abstract Background Renal transplant lithiasis is a rather unusual disease, and the recurrence of lithiasis presents a challenging situation. Methods We retrospectively analyzed the medical history of one patient who suffered renal transplant lithiasis twice, reviewed the relevant literature, and summarized the characteristics of this disease. Results We retrieved 29 relevant studies with an incidence of 0.34 to 3.26% for renal transplant lithiasis. The summarized incidence was 0.52%, and the recurrence rate was 0.082%. The mean interval after transplantation was 33.43 ± 56.70 mo. Most of the patients (28.90%) were asymptomatic. The management included percutaneous nephrolithotripsy (PCNL, 22.10%), ureteroscope (URS, 22.65%), extracorporeal shockwave lithotripsy (ESWL, 18.60%) and conservative treatment (17.13%). In our case, the patient suffered from renal transplant lithiasis at 6 years posttransplantation, and the lithiasis recurred 16 months later. He presented oliguria, infection or acute renal failure (ARF) during the two attacks but without pain. PCNL along with URS and holmium laser lithotripsy were performed. The patient recovered well after surgery, except for a 3 mm residual stone in the calyx after the second surgery. He had normal renal function without any symptoms and was discharged with oral anticalculus drugs and strict follow-up at the clinic. Fortunately, the calculus passed spontaneously about 1 month later. Conclusions Due to the lack of specific symptoms in the early stage, patients with renal transplant lithiasis may have delayed diagnosis and present ARF. Minimally invasive treatment is optimal, and the combined usage of two or more procedures is beneficial for patients. After surgery, taking anticalculus drugs, correcting metabolic disorders and avoiding UIT are key measures to prevent the recurrence of lithiasis.

Abstract Background Bone wax is the most widely used hemostatic bone sealant because of its availability, ease of use, immediate action, and minimal adverse effects. Several complications have been reported to be associated with the use of bone wax, such as infection, osteohypertrophy, pain, granuloma formation, allergic reaction, and thrombosis. Here, we present a rare complication, namely, bone wax migration, which developed after a craniotomy on a patient who had a frontal sinus abnormality. Case presentation A 51-year-old woman complained of pain and swelling in her left eye accompanied by difficulty opening the left eyelid after undergoing a craniotomy. An examination revealed left eye proptosis with ptosis, eyelid swelling, and increases in intraorbital pressure and intraocular pressure (IOP). According to a CT and an MRI of the orbit, we found that the intraoperative bone wax had migrated to the orbit, thereby causing compression. We also found that the basal frontal sinus of the patient was congenitally defective, which may have induced the migration of the bone wax. Given that the patient recently underwent a craniotomy and given the risks associated with orbital surgery, she refused to undergo a surgery to remove the bone wax. Thus, the patient was administered mannitol intravenously daily, accompanied by topical Timolol, to reduce the intraorbital pressure and IOP. This treatment led to a gradual decrease in IOP and intraorbital pressure, and these parameters remained stable after treatment ended. During the 6-month follow-up, the best corrected visual acuity improved, and ptosis and restricted eye movements also improved significantly. Conclusions We report a case of bone wax migration that developed after a craniotomy on a patient who had a congenital defect in the basal frontal sinus. Extra caution should be taken when using bone wax, and a comprehensive understanding of the patient’s intracranial anatomy is important for decreasing the incidence of bone wax migration. Additionally, when a patient presents with symptoms of ocular compression, bone wax migration should be considered in addition to typical radiological changes.

Abstract Background The dysregulation of miR-663a is frequently observed in many human cancers. However, the functional role and precise mechanism of miR-663a have been controversial in hepatocellular carcinoma (HCC) and need to be studied in depth. Methods The expression of miR-663a was detected in human cell lines and HCC tissues by quantitative RT-PCR (qRT-PCR), and data from the Cancer Genome Atlas (TCGA). Cell proliferation was investigated using MTS, EdU, colony formation assays, and xenograft animal experiments, and the cell invasion capacity was evaluated using the transwell assay. The target gene of miR-663a was identified by qRT-PCR, Western blot, and dual-luciferase reporter assays. The clinicopathological features of miR-663a and the correlation between miR-663a and TGF-β1 expression were also investigated in the clinical samples of HCC. Results miR-663a was significantly downregulated in HCC cells relative to immortal normal liver cells, as indicated using qRT-PCR, and the lower expression of miR-663a was also confirmed in HCC tissue samples and the data from TCGA. The expression of miR-663a in HCC tissue samples was statistically significantly associated with size and the number of tumors. In addition, the upregulation of miR-663a inhibited the proliferation and invasion of HCC cells in vitro. Further study showed that miR-663a directly targeted transforming growth factor beta 1 (TGF-β1) to suppress HCC invasion, and that the inhibitory effect of miR-663a on cell invasion could be regulated by TGF-β1. In vivo studies showed that miR-663a significantly inhibited tumor growth. A negative correlation between miR-663a and TGF-β1 expression was also confirmed from the clinical samples of HCC. Conclusions miR-663a acts as a tumor suppressor and exerts a substantial role in inhibiting the proliferation, invasion, and tumorigenesis of HCC by regulating TGF-β1 in vitro and in vivo. These observations indicate that miR-663a may be a suitable diagnostic, therapeutic, and prognostic target for the treatment of HCC.

Abstract Background Bladder cancer often recurs due to incomplete elimination of the cancer stem cells (CSCs). Therefore, new strategies targeting bladder CSCs are needed and the aim of this study was to investigate the effect of S100A4 on the proliferation capacity of MB49 bladder cancer stem cells (MCSCs). Methods MCSCs were established and validated. The expression level of S100A4 in MCSCs and MB49 cells was evaluated using Western blotting and quantitative polymerase chain reaction (QPCR). S100A4 was overexpressed or knocked-down by transfection of pCMV6-XL5-S100A4 plasmid or RNA interference (RNAi) respectively. Proliferation capacity of MCSC was evaluated by cell proliferation assay and in vivo tumorigenicity study. Transcriptional activity of nuclear factor kappa B (NF-κB) was analyzed using luciferase reporter assay, and the level of interleukin (IL)-2 as well as tumor necrosis factor (TNF) was quantified by QPCR. Protein-protein interaction of S100A4 and inhibitor of nuclear factor kappa B NF-κB kinase (IKK) was analyzed by immunoprecipitation. Results S100A4 was significantly up-regulated in MCSCs, which positively associated with the proliferation capacity, as well as the level of NF-κB, IKK, IL-2 and TNF in MCSCs. Knock-down of S100A4 could reverse such effects. Using immunoprecipitation assay, an interaction between S100A4 and IKK could be observed. Conclusions S100A4 is upregulated in MCSCs and possibly enhance the proliferation ability of MCSCs by way of activating the IKK/NF-κB signaling pathway, and S100A4 maybe a hopeful therapeutic target for MCSCs.

Abstract Background Renal transplant is the preferred treatment option for these patients with end-stage renal disease. Transplant renal artery stenosis (TRAS) is one of the most common and serious vascular complications after renal transplantation, and most of the TRAS occurred in the anastomosis. The complication must be diagnosed and treated timely, otherwise the function of transplanted kidney may be losed. Case presentation A 46-year-old male with end-stage renal disease of unknown cause received a cadaveric renal transplant one year ago. Although three antihypertensive medications were administrated, his blood pressure gradually increased to 190/120 mmHg 3 weeks posttransplantation. Also the level of creatinine increased to 194 μmol/L.Color Doppler ultrasonography indicated a decreased resistance index (RI) in intrarenal arteries and increased blood flow of the transplant renal artery, therefore, a vascular complication of TRAS was suspected. Arteriography was performed and demonstrated TRAS caused by stretch of an artery branch, and the TRAS occurred in the distal site of the anastomosis instead of the anastomosis. Percutaneous transluminal bare stent implantation treatment was successfully performed. Satisfactory clinical efficacy with improvement in transplant renal function and renovascular hypertension was achieved after the interventional treatment. Conclusion To our knowledge this is the first reported case of TRAS caused by stretch of an artery branch. When refractory hypertension and allograft dysfunction are presented posttransplantation, TRAS should be suspected. Color Doppler ultrasonography as a non-invasive examination may provide some valuable information, three-dimention CT can be useful for further diagnosis, but is seldom necessary. Arteriography provides the definitive diagnosis of TRAS. Percutaneous transluminal stent implantation treatment of TRAS has high success rate with minimal invasion and complications. When an artery branch situated on the stenosis, a bare stent rather than covered stent is the preferred choice.

Abstract Background Hirame rhabdovirus virus (HIRRV) is a rhabdovirus that causes acute hemorrhage disease in fish culture, resulting in a great economic loss in parts of Asia and Europe. Methods In this study, we isolated a virus strain named as CNPo2015 from cultured Japanese flounder in Shandong province, China. Cell isolation, electron microscopic observation, RT-PCR detection and phylogenetic analysis were used for virus identification. Further, artificial infection experiment was conducted for virulence testing. Results The gross signs included abdominal distension, fin reddening and yellow ascitic fluid in the abdominal cavity. Histopathological examination revealed marked cell degeneration and necrosis in the kidney. The tissue homogenates induced obvious cytopathic effects in EPC, FHM and FG cell lines. Electron microscopic observation showed the virus had a bullet-like shape with a capsule membrane. RT-PCR and sequencing analysis revealed that CNPo2015 belonged to the HIRRV with high sequence identity to HIRRV isolates. Infection experiment confirmed that the HIRRV CNPo2015 strain was virulent to flounder juveniles with a LD50 value of 1.0 × 105.9 TCID50/fish. Conclusion In conclusion, we described the first isolation and characterization of a HIRRV from Japanese flounder in China. This will provide a candidate material for further research on the infection mechanism and preventive strategies of HIRRV.