Malignant insulinoma is a kind of rare and challenging neuroendocrine tumor. It is often accompanied by distant metastasis, among which liver metastasis is most common, and the prognosis is often non-promising. In this paper, we report a case of multiple liver metastases from malignant insulinoma. The patient, a 70-year-old male, was admitted to the hospital due to "episodic consciousness disorder for more than four months." Blood glucose monitoring revealed recurrent hypoglycemia in the early morning, after meals, and at night. Pancreatic perfusion CT and dynamic enhanced MRI of the liver revealed a mass in the uncinate process of the pancreatic head and multiple liver metastases. Percutaneous liver biopsy confirmed the diagnosis of insulinoma. After multidisciplinary discussions, hepatic artery embolization and radiofrequency ablation were performed in stages, in combination with everolimus treatment. Thereafter, the enhanced CT demonstrated that some liver metastases shrank. The patient had regular meals, and the blood sugar gradually increased and remained normal thereafter. This article discusses this case's clinical characteristics and multidisciplinary collaborative diagnosis and treatment, aiming to provide experience for the comprehensive clinical diagnosis and treatment of malignant insulinoma patients.

Polygoni multiflori radix praeparata is a processed product of Polygoni multiflori radix(Polygonum multiflorum Thunb.),and its main components include stilbene glycosides,anthraquinones,flavonoids,alkaloids,phenolic acids,etc.It has antioxidant,antianemic,anti-tumor,hypoglycemic,anti-inflammatory effects,etc,and is widely used in clinical practice.The processing technology is mainly stewinging with black bean juice,steaming,processing for 9 times and braising and simmering.After processing,the color deepens and the content of composition changes.By consulting domestic and foreign literature,the research on Polygoni multiflori radix praeparata is not comprehensive enough compared with Polygoni multiflori radix.Therefore,this paper mainly summarizes the processing technology,chemical composition and pharmacological activity of Polygoni multiflori radix preparata reported in the past 20 years,and provides a reference for further development of Polygoni multiflori radix preparata.

Objective:To investigate the risk factors for postoperative fever in patients with negative preoperative urine culture undergoing flexible ureteroscopy (fURS), and construct a nomogram prediction model to predict the risk of postoperative fever.Methods:The clinical data of 308 patients who underwent flexible ureteroscopy (fURS) at the Second Affiliated Hospital of Zhengzhou University from January 2019 to March2023, were retrospectively analyzed. Among these patients, there were 235 males and 73 females, with an average age of (46.4±12.1) years old. Additionally, 86 cases had concomitant hypertension, 41 cases had diabetes, and 12 cases had coronary heart disease. A history of urinary stone surgery was present in 57 cases, and 91 cases exhibited severe hydronephrosis. The distribution of stones included 164 cases on the left side and 144 cases on the right side, with 88 cases of renal stones, 124 cases of ureteral stones, and 96 cases of renal-ureteral stones. Among them, 243 cases had ≤2 stones, while 65 cases had >2 stones, with a maximum stone diameter of 12.0 (9.0, 15.0) mm. Urine leukocyte-positive cases were 109, and urine leukocyte-negative cases were 199. Two cases were positive for nitrite, and 308 cases were negative. The occurrence of postoperative fever within 48 hours was recorded, and differences between the fever and non-fever groups were compared. Logistic regression analysis was employed to identify risk factors for post-fURS fever. A nomogram prediction model based on independent risk factors was constructed, and internal validation was conducted using 1 000 bootstrap resamples. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC). Model stability was assessed using calibration curves.Results:The surgeries for all 308 cases were successfully completed with a median operative time of 60.0 (40.0, 75.0) minutes. Complete stone clearance was achieved in 221 cases. Among them, 14 cases (4.5%) experienced postoperative fever, while 294 cases did not. The fever group had a higher proportion of females [57.1% (8/14) vs. 22.1% (65/294), P=0.007], more cases with comorbid diabetes [50.0% (7/14) vs. 11.6% (34/294), P<0.001], a higher proportion of renal stones [64.3% (9/14) vs. 26.9% (79/294), P=0.022], a lower intraoperative stone clearance rate [42.9% (6/14) vs. 73.1% (215/294), P=0.031], larger stone diameter [15.5 (12.5, 19.3) mm vs. 11.0 (9.0, 15.0) mm, P=0.004], longer operative time [87.5 (58.8, 106.3) min vs. 55.0 (40.0, 75.0) min, P<0.001], higher platelet count [267.0 (225.8, 354.0) ×10 9/L vs. 233.0 (197.8, 272.0) ×10 9/L, P=0.026], lower creatinine levels [67.5 (52.5, 72.3) umol/L vs. 73.0 (62.0, 84.0) umol/L, P=0.026], and a higher platelet lymphocyte ratio [148.8 (118.3, 189.3) vs. 119.5 (93.2, 156.0), P=0.030]. Results of univariate analysis showed that female gender, diabetes, stone location, incomplete stone clearance, maximum stone diameter, operative time, platelet count, creatinine, platelet lymphocyte ratio, and positive nitrite in urine (all P<0.05)were risk factors for postoperative fever. Multivariate regression analysis revealed that female gender ( OR=11.073, 95% CI 1.623-75.521, P=0.014), diabetes ( OR=5.995, 95% CI 1.441-24.952, P=0.014), and operative time ( OR=1.024, 95% CI 1.003-1.046, P=0.024) were independent risk factors for post-fURS fever. The nomogram exhibited excellent predictive performance (AUC=0.866, 95% CI 0.781-0.935), and the calibration curve demonstrated good consistency. Conclusions:Female gender, longer operative time, and diabetes are risk factors for post-fURS fever in patients with preoperative negative urine culture. The nomogram demonstrates excellent predictive performance.

BACKGROUND: Oral submucous fibrosis (OSF) is a chronic disease with carcinogenic tendency that poses a non-negligible threat to human health. Exosomes derived from human adipose mesenchymal stem cells (ADSC-Exo) reduces visceral and cutaneous fibroses, but their role in OSF has received little attention. The aim of this study was to investigate the effects of ADSC-Exo on OSF and elucidate the mechanism. METHODS: In brief, ADSCs were extracted from adipose tissues and subjected to flow cytometry and induction culture. Fibroblasts were isolated from human buccal mucosa and subjected to immunofluorescence. Myofibroblasts were obtained from fibroblasts induced by arecoline and identified. Immunofluorescence assay confirmed that myofibroblasts could take up ADSC-Exo. The effects of ADSC-Exo on the proliferative and migratory capacities of myofibroblasts were examined using the Cell Counting Kit-8 and scratch assay. Real-time quantitative polymerase chain reaction (qPCR) was performed to evaluate mothers against decapentaplegic homolog 2 (Smad2), Smad3, Smad7, collagen type 1 (Col1), Col3, alpha smooth muscle actin (α-SMA), fibronectin, and vimentin. Western blotting was performed to detect phospho (p)-Smad2, Smad2, p-Smad2/3, Smad2/3, Smad7, Col1, Col3, α-SMA, fibronectin, and vimentin. Furthermore, the dual-luciferase reporter assay was performed to prove that miR-181a-5p in ADSC-Exo directly inhibited the expression of Smad2 mRNA to regulate the transforming growth factor beta (TGF-β) pathway. We also performed qPCR and western blotting to verify the results. RESULTS: ADSC-Exo could promote the proliferation and migration of myofibroblasts, reduce the expressions of p-smad2, Smad2, p-smad2/3, Smad2/3, Col1, αSMA, fibronectin, and vimentin and elevated the levels of Smad7 and Col3. In addition, miR-181a-5p was highly expressed in ADSC-Exo and bound to the 3'-untranslated region of Smad2. ADSC-Exo enriched with miR-181a-5p reduced collagen production in myofibroblasts and modulated the TGF-β pathway. CONCLUSIONS ADSC-Exo promoted the proliferative and migratory capacities of myofibroblasts and inhibited collagen deposition and trans-differentiation of myofibroblasts in vitro. miR-181a-5p in exosomes targets Smad2 to regulate the TGF-β pathway in myofibroblasts. ADSC-Exo perform antifibrotic actions through the miR-181a-5p/Smad2 axis and may be a promising clinical treatment for OSF.

Objective To investigate the attitudes and influencing factors of transplantation-related populations towards kidney xenotransplantation. Methods From June 2022 to January 2023, stratified random sampling was performed from patients awaiting kidney transplantation, patients after kidney transplantation, patients' relatives and medical students. Four hundred subjects were collected from each population and 1600 subjects were investigated using a self-designed questionnaire. Baseline data of the respondents, their attitudes towards kidney xenotransplantation and the reasons of rejecting kidney xenotransplantation were analyzed. The influencing factors of attitudes towards kidney xenotransplantation were also identified. Results A total of 1 493 valid questionnaires were collected, and the questionnaire retrieval rate was 93.31%. About 93.10% of the respondents accepted allogeneic kidney transplantation, and 66.78% had heard of kidney xenotransplantation. Seven hundred and ninety-five respondents suggested that they could accept kidney xenotransplantation "when kidney xenotransplantation and allogeneic kidney transplantation yielded the same results and risks". Six hundred and ninety-eight respondents indicated that they were "unable" or "uncertain" whether they could accept kidney xenotransplantation (χ²=16.409，P=0.001). Among these 698 respondents, the proportion of them who were willing to accept kidney xenotransplantation when they did not meet the conditions of allogeneic kidney transplantation was 10.9%. About 35.8% of respondents were willing to accept kidney xenotransplantation if it yielded less risk and better prognosis compared with allogeneic kidney transplantation. If the time of awaiting kidney xenotransplantation was shorter than that of allogeneic kidney transplantation, 21.2% were willing to accept kidney xenotransplantation. If the cost of kidney xenotransplantation was less than that of allogeneic kidney transplantation, 24.5% of them were willing to accept kidney xenotransplantation. The main reasons of rejecting kidney xenotransplantation included surgical risk and other unknown risks. Multivariate analysis showed that respondents residing in cities and towns for a long period of time, those who accept allogeneic kidney transplantation and those who have heard of kidney xenotransplantation showed more positive attitudes towards kidney xenotransplantation. Conclusions Different transplantation-related populations have different attitudes towards kidney xenotransplantation, and the overall attitudes are positive. Active promotion of kidney xenotransplantation research and carrying out relevant popular science education contribute to improving public attitudes towards the acceptance of kidney xenotransplantation.

Resveratrol (RES), a natural polyphenolic phytochemical, has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer's disease (AD) by the activation of sirtuin 1 (Sirt1/Sir2). In this study, we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase of Drosophila Sir2 (dSir2) by RES supplementation for up to 17 days in APP flies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies. We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons. Interestingly, RES increased sleep in the absence of dSir2 in dSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies. Finally, we showed that Aβ aggregates in APP flies were reduced by RES and dSir2, probably via inhibiting Drosophila β-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely, but not exclusively, via dSir2.
Animals ; Alzheimer Disease/metabolism* ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor/metabolism* ; Drosophila/physiology* ; Drosophila Proteins/metabolism* ; Resveratrol/pharmacology* ; Sirtuin 1 ; Sleep

RNA-binding protein exerts important biological function by specifically recognizing RNA motif. SELEX (Systematic evolution of ligands by exponential enrichment), an in vitro selection method, can obtain consensus motif with high-affinity and specificity for many target molecules from DNA or RNA libraries. Here, we combined SELEX with next-generation sequencing to study the protein-RNA interaction in vitro. A pool of RNAs with 20 bp random sequences were transcribed by T7 promoter, and target protein was inserted into plasmid containing SBP-tag, which can be captured by streptavidin beads. Through only one cycle, the specific RNA motif can be obtained, which dramatically improved the selection efficiency. Using this method, we found that human hnRNP A1 RRMs domain (UP1 domain) bound RNA motifs containing AGG and AG sequences. The EMSA experiment indicated that hnRNP A1 RRMs could bind the obtained RNA motif. Taken together, this method provides a rapid and effective method to study the RNA binding specificity of proteins.
Aptamers, Nucleotide ; Gene Library ; Heterogeneous Nuclear Ribonucleoprotein A1 ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; RNA ; SELEX Aptamer Technique

Objective To evaluate the influence of simple subtalar arthrodesis to the motion and degeneration of midfoot.Methods Data of 37 patients (27 males,10 females) with an average age of 42.6 years who had undergone subtalar joint fusion from January 1996 to August 2011 were retrospectively analyzed.The MOS item short form health survey (SF-36),American Orthopaedic Foot and Ankle Society (AOFAS) midfoot score were used.Midfoot sagittal and coronal motion were measured on ankle radiographs of maximum plantar flexion and dorsiflexion.On sagittal plane,the Meary angle was measured and the bilateral tarsometatarsal joints mobility was compared.On coronal plane,tibio-plantar angles (TPA) on 30 degrees varus slope and 30 degrees valgus slope were respectively measured on the anterio-posterior ankle X-ray films to observe the changes of midfoot activities.Besides,single photon emission computed tomography/computed tomography (SPECT/CT) of bilateral foot and ankle was taken to estimate the degeneration of midfoot joint.Results All the 37 patients were followed-up,with mean follow-up period of 9.2 years.The average SF-36 scores was increased from 34.26± 11.02 points preoperatively to 77.59± 12.57 points postoperatively.The average AOFAS midfoot scores were 86.14± 16.79 points preoperatively and 86.43± 16.70 points postoperatively without any statistical significant difference.On sagittal plane,medial tarsometatarsal joints mobility was limited by 20％.According to coronal plane of varus slope,the average TPA of healthy side and operated side were 61.32° and 64.91°,respectively,so the varus mobility of operated side was limited by 12.5％.While standing on the valgus slope,the average TPA of both sides were 76.54° and 82.28°,which indicated that valgus mobility of operated side was reduced by 42.6％.35.1％ patients of talonavicular joint,56.8％ patients of calcaneocuboid joint,and 27.0％ patients of metatarsal cuboid joint were found mild joint degeneration on SPECT/CT images without any clinical symptoms.Conclusion Subtalar arthrodesis can affect midfoot with less limit of sagittal mobility and more limit of coronal movement.And the lateral joints degeneration is more likely to happen for their compensatory activity.

Objective To study on the different results of a minimally invasive method to reconstruct the ligaments of the lateral ankle using semitendinosus tendon autograft and tendon allograft.Methods Data of 68 patients with chronic ankle instability who had undergone lateral ligament reconstruction from September 2006 to June 2011 were retrospectively analyzed.In the group of semitendinosus autograft,there were 32 patients (19 males,13 females) with an average age of 32.4 years old.Semitendinosus was harvested through 2 small knee incisions.While in the group of tendon allograft,there were 36 patients (22 males,14 females) with an average age of 34.2 years old.For the ankle reconstruction,4 small incisions of 5 mm each were made at the medial and lateral side of the fibular tip,the talar neck,and the middle of the calcaneus.Anatomical reconstruction of the anterior talofibular ligament and calcaneofibular ligament was then performed through these small incisions.AOFAS questionnaires were used to measure clinical outcomes,donor site morbidity and patients' satisfaction.Preoperative and postoperative stress tests were performed and radiographic parameters were measured.Results The average operation time of the autograft group 85.5 ± 11.5 min was significantly longer than that in the allograft group 58.1±10.2 min,but the fever days in the latter 5.5±1.5 d was significantly longer than in the former 2.5±1.2 d.In autograft group,23 patients got followed up,and the mean period of follow-up was 33.5±6.7 months.The mean AOFAS score increased from 62.3±8.2 to 95.1 ±7.5.In allograft group,26 patients got followed up,and the mean period of follow-up was 28.5±6.7 months.The mean AOFAS score increased from 60.2±8.4 to 94.8±5.5.There were 5 patients (3 of autugraft group and 2 of allograft group) with residual instability on uneven ground.One case of the autologous group had instability in daily life.No patient presented weakness or disability in the donor site.The satisfaction level of the autograft group was excellent in 16,good in 5 and bad in 2.Significant improvement in stress radiographic parameters was noted for the talar tilt angle,with reduction from a mean of 14.0° to 3.8°; anterior talar displacement reduced from a mean of 12.3 to 4.6 mm.The satisfaction level of the allograft group was excellent in 17,good in 5 and bad in 4.The talar tilt angle reduced from 13.0° to 3.6°; anterior talar displacement reduced from 11.5 to 4.3 mm.Conclusion There is no differences in efficacy could we found in using these 2 kinds of materials.The process of healing and rehabilitation of tendon autograft is slightly faster than the tendon allograft,but the allograft tendon has many advantages such as limited injury,simple procedure andavoiding of donor site morbidity.