Objective:To explore the clinical efficacy of chemoembolization with doxorubicin-infused gelatin sponge microparticles in the amelioration of arterioportal shunting (APS) in patients afflicted with hepatocellular carcinoma (HCC).Methods:A retrospective investigation was conducted on 9 HCC patients admitted between January 2020 and December 2022 with concomitant moderate-to-severe APS who underwent GSM-transarterial chemoembolization (TACE). Hepatic artery digital subtraction angiography (DSA) was employed to ascertain the magnitude of improvement in arteriovenous shunts, utilization of modified response evaluation criteria in solid tumors facilitated the appraisal of short-term clinical outcomes. Follow-up records documented survival duration, along with quantitative parameters such as the longest diameter of tumor lesions and serum alpha-fetoprotein (AFP) levels before and after treatment. The Wilcoxon rank-sum test was utilized to compare the differences of these quantitative parameters before and after treatment.Results:The APS amelioration rates were 100% and 88.9% at immediate and recent postoperatively, respectively. The oncological response rate was 77.8% (7/9), and the complete necrosis rate was 22.2% (2/9) at three months postoperatively, the 1-year survival rate was 100%. Following treatment, a significant reduction was observed in the tumor′s longitudinal diameter [4.32(3.88,6.63)cm] and serum AFP levels [13.50 (7.55, 29.60) μg/L], compared to the pre-treatment values of the tumor′s longitudinal diameter [5.20(4.58,8.57)cm] and serum AFP levels [524.30 (320.65, 1 046.15) μg/L] ( P<0.05 for all). Conclusion:Doxorubicin-infused GSM-TACE is both feasible and efficacious in the first treatment of HCC concomitant with APS and represents a better clinical alternative.

Objective:To evaluate the efficacy and safety of unilateral adrenalectomy for treating primary bilateral macronodular adrenal hyperplasia (PBMAH) of different clinical types.Methods:The clinical and biochemical data of 54 patients with PBMAH who underwent unilateral adrenalectomy from May 2008 to March 2023 were retrospectively collected. Preoperative CT images of all patients showed enlarged bilateral adrenal glands with multiple nodules of " fused masses". Mean preoperative blood cortisol concentration at 8am was (21.5±7.7)μg/dl, urinary free cortisol concentration was (442.6±300.4)μg/24h, and mean 8am ACTH concentration was (6.4±2.3)pg/ml. Postoperative symptoms, BMI, blood pressure, mass diameter, cortisol and ACTH concentration were recorded and analyzed.Results:Compared with ordinary laparoscopic surgery, robot-assisted surgery showed shorter operation time [(115.4±22.1)min vs.(95.0±19.8)min, P=0.045]; less blood loss [(118.2±57.0)ml vs. (125.6±45.3)ml, P=0.441] and shorter hospitalization time [(5.2±0.9)day vs. (6.4±1.2)day, P=0.279]. Compared with laparoscopic surgery, open surgery showed longer operation time [(134 34.5) min vs. (104.3±20.1) min, P=0.035]; more blood loss [(305.5±85.2) ml vs. (122.5±44.3) ml, P=0.012] and longer hospitalization time[(10.4±3.2)day vs. (5.7±1.0) day, P=0.020]. The average follow-up time was (23.7±11.7) months. Sixteen cases biochemically relapsed, and the average relapse-free time was (25.4±13.4) month. Mean postoperative systolic blood pressure was (131.1±16.8)mmHg ( P=0.001) while diastolic blood pressure decreased to (82.2±11.1)mmHg ( P=0.002). Postsurgical average blood cortisol concentration decreased to (10.2±4.0)μg/dl ( P<0.01), while urine cortisol concentration decreased to (106.6±43.4)μg/24h( P<0.01). Average ACTH concentration increased to (12.6±4.1)pg/ml( P=0.005). Recurrent patients had higher preoperative blood and urine cortisol concentration(24.7±8.2)μg/dl( P=0.046), (522.8±234.2)μg/24h( P=0.028), and all of them underwent contralateral adrenalectomy. Conclusions:Unilateral adrenalectomy is safe and effective for treatment of PBMAH while part of patients biochemically relapsed. Subclinical patients were observed no recurrent cases after surgery. Recurrent patients have higher preoperative blood and urine cortisol levels and should undertake contralateral adrenalectomy and supplement corticosteroids for whole life.

Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

The monitoring unit used in the nuclear magnetic resonance system,as an important unit of the system,faces a high thermal risk during its entire life cycle.This paper ensures the high efficiency and reliability of the thermal design of the product module from the two dimensions of structural design and device derating design.In order to reduce the risk of thermal design of electronic modules and comprehensively verify the effectiveness of thermal design of electronic modules,the design verification is carried out by combining simulation and experiment.In the simulation process,by establishing a thermal simulation model at the circuit board level,the crustal temperature of the core device is numerically calculated,and the index is compared with the thermal design index value and the test value,on the one hand,to verify the correctness of the simulation model.On the other hand,the validity of thermal design is verified.In the testing process,a thermal test platform for product modules is built,and the thermal characteristics test values of the core components of the module under extreme electrical conditions are obtained,and the corresponding conversion methods are used to predict the thermal performance and thermal design margin of the product at different altitudes.The results show that the electronic module can meet the thermal design requirements in terms of structural design and derating design of core components,and can ensure that the product module can work safely and reliably during the entire life cycle of the NMR system.

Periodontitis is the most widespread oral disease and is closely related to the oral microbiota. The oral microbiota is adversely affected by some pharmacologic treatments. Systemic antibiotics are widely used for infectious diseases but can lead to gut dysbiosis, causing negative effects on the human body. Whether systemic antibiotic-induced gut dysbiosis can affect the oral microbiota or even periodontitis has not yet been addressed. In this research, mice were exposed to drinking water containing a cocktail of four antibiotics to explore how systemic antibiotics affect microbiota pathogenicity and oral bone loss. The results demonstrated, for the first time, that gut dysbiosis caused by long-term use of antibiotics can disturb the oral microbiota and aggravate periodontitis. Moreover, the expression of cytokines related to Th17 was increased while transcription factors and cytokines related to Treg were decreased in the periodontal tissue. Fecal microbiota transplantation with normal mice feces restored the gut microbiota and barrier, decreased the pathogenicity of the oral microbiota, reversed the Th17/Treg imbalance in periodontal tissue, and alleviated alveolar bone loss. This study highlights the potential adverse effects of long-term systemic antibiotics-induced gut dysbiosis on the oral microbiota and periodontitis. A Th17/Treg imbalance might be related to this relationship. Importantly, these results reveal that the periodontal condition of patients should be assessed regularly when using systemic antibiotics in clinical practice.
Humans ; Mice ; Animals ; Dysbiosis ; Anti-Bacterial Agents/pharmacology* ; Virulence ; Microbiota ; Periodontitis/chemically induced* ; Cytokines

Objective:To analyze the metabolic mechanism of papillary thyroid cancer(PTC) in normal and Hashimoto′s thyroiditis(HT) background, and to explore the relationship between HT and PTC.Methods:This study included a matched sample set collected from Tianjin Medical University General Hospital between January 2018 and January 2019, consisting of PTC and paracancular tissue from 31 cases with coexisting HT(HT group), and 30 cases without(NC group), all confirmed pathologically following thyroidectomy. The ultra-high performance liquid chromatography combined with mixed four-stage poles time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to acquire data from the samples. Metabolite differences between the two groups were compared, aiming to identify distinct metabolic mechanisms of PTC under different backgrounds. Metabolic pathway analysis was conducted using Metabo-Analyst 5.0 to explore relevant metabolic pathways.Results:The HT group and NC group shared 7 common differentially expressed metabolites, including arginine, glutamic acid, cysteine, citric acid, malic acid, uracil, and taurine. Logistic regression model combined with receiver operating characteristic(ROC) analysis of these 7 biomarkers yielded excellent discriminatory capacity for PTC(area under ROC curve of HT group and NC group were 0.867 and 0.973, respectively). The common metabolic pathways were taurine and hypotaurine metabolism, arginine biosynthesis, alanine, aspartic acid and glutamic acid metabolism, arginine and proline metabolism, and glutamine and glutamic acid metabolism. The specific metabolic pathways in HT group were aminoacyl tRNA biosynthesis, glycine, serine, and threonine metabolism.Conclusion:The metabolic profiles of thyroid cancer exhibit significant differences between cases with normal backgrounds and those with HT. The specific pathways for PTC and HT are aminoacyl tRNA biosynthesis and the metabolism of glycine, serine, and threonine.

Objective:To investigate the clinical profile of primary bilateral macronodular adrenal hyperplasia(PBMAH) and sex difference.Methods:One hundred and forty cases of PBMAH were recruited in our center from 2014, and all patients were evaluated for hormone secretion, adrenal imaging, and metabolic parameters.Results:Overt Cushing′s syndrome accounted for 76.4% of PBMAH cohort and 47.9% were female. The overt group had higher serum cortisol and 24 h urinary free cortisol levels, lower adrenocorticotropic hormone, higher serum cortisol after low-dose dexamethasone suppression tests, larger total adrenal size, and a higher percentage of obesity, hypertension, diabetes mellitus, and hypokalemia than the subclinical group(all P<0.05). When compared with the male group, the female group had smaller adrenal size( P<0.001), lower HbA 1C( P=0.003), higher total cholesterol( P=0.005), and lower density lipoprotein-cholesterol levels( P=0.035). Further, 24 h urinary free cortisol in the male group was found to be positively correlated with diastolic blood pressure, fasting glucose, 2 h postprandial glucose after oral glucose tolerance test(OGTT), and HbA 1C after adjusted for age, body mass index, and onset duration, and was negatively correlated with body mass index and potassium levels. While 24 h urinary free cortisol in the female group was positively correlated only with diastolic blood pressure, fasting glucose, and 2 h postprandial glucose after OGTT(all P<0.05). During follow-up, 80.0% of patients achieved remission after unilateral adrenalectomy, with a recurrence rate of 17.9%. Conclusion:PBMAH related metabolic disorder is more pronounced in overt Cushing′s syndrome and males. Unilateral adrenalectomy as an effective treatment can benefit the majority of patients.

Background::Heterogeneity of tumor cells and the tumor microenvironment (TME) is significantly associated with clinical outcomes and treatment responses in patients with urothelial carcinoma (UC). Comprehensive profiling of the cellular diversity and interactions between malignant cells and TME may clarify the mechanisms underlying UC progression and guide the development of novel therapies. This study aimed to extend our understanding of intra-tumoral heterogeneity and the immunosuppressive TME in UC and provide basic support for the development of novel UC therapies.Methods::Seven patients with UC were included who underwent curative surgery at our hospital between July 2020 and October 2020. We performed single-cell RNA sequencing (scRNA-seq) analysis in seven tumors with six matched adjacent normal tissues and integrated the results with two public scRNA-seq datasets. The functional properties and intercellular interactions between single cells were characterized, and the results were validated using multiplex immunofluorescence staining, flow cytometry, and bulk transcriptomic datasets. All statistical analyses were performed using the R package with two-sided tests. Wilcoxon-rank test, log-rank test, one-way analysis of variance test, and Pearson correlation analysis were used properly.Results::Unsupervised t-distributed stochastic neighbor embedding clustering analysis identified ten main cellular subclusters in urothelial tissues. Of them, seven urothelial subtypes were noted, and malignant urothelial cells were characterized with enhanced cellular proliferation and reduced immunogenicity. CD8 + T cell subclusters exhibited enhanced cellular cytotoxicity activities along with increased exhaustion signature in UC tissues, and the recruitment of CD4 + T regulatory cells was also increased in tumor tissues. Regarding myeloid cells, coordinated reprogramming of infiltrated neutrophils, M2-type polarized macrophages, and LAMP3 + dendritic cells contribute to immunosuppressive TME in UC tissues. Tumor tissues demonstrated enhanced angiogenesis mediated by KDR + endothelial cells and RGS5 +/ACTA2 + pericytes. Through deconvolution analysis, we identified multiple cellular subtypes may influence the programmed death-ligand 1 (PD-L1) immunotherapy response in patients with UC. Conclusion::Our scRNA-seq analysis clarified intra-tumoral heterogeneity and delineated the pro-tumoral and immunosuppressive microenvironment in UC tissues, which may provide novel therapeutic targets.

Objective:To compare the preliminary clinical efficacy of iodized oil embolization and improved microspheres injection embolization in patients with hepatic metastasis from gastrointestinal tumors.Methods:In total 100 patients with hepatic metastasis from gastrointestinal tumors were perspective enrolled from July 2015 to July 2017 in the First Affiliated Hospital of Henan University of Science and Technology. The patients were randomly divided into iodized oil group (45 cases) and microspheres group (55 cases) using random number table. The patients in iodized oil group were firstly received regular perfusion chemotherapy, then underwent the embolization with Iodized oil and epirubicin emulsifier. As for the microspheres group, the patients were received epirubicin and microspheres perfusion and embolization alternately after the same regular perfusion chemotherapy. The post-operation complications were observed. The effective rate of tumor controling at each time point was compared between two groups using χ 2 test. Kaplan-Meier method was used to perform the survival analysis. Log-rank test was used to compare the survival rate between two groups. Results:The operation was successfully performed in all the patients, without severe complications found. The follow up time was 18.7±3.4 months. The tumor control rates of 1, 3, 6, 12 and 24 months after operation in the iodine oil group were 71.1% (32/45), 68.9% (31/45), 51.1% (23/45), 28.9% (13/45), 6.7% (3/45) respectively; while in microspheres group were 90.9% (50/55), 89.1% (49/55), 72.7% (40/55), 49.1% (27/55), 23.6% (13/55), respectively. The tumor control rate in microspheres group was superior to that in iodine oil group ( P<0.05). The median lifetime was 12 months and 17 months for iodine oil group and microspheres group respectively, with significant difference (χ2=8.238, P=0.004) found between two groups. As for the microspheres group, the liver abscess was found in one week after operation in 4 patients, who were cured after drainage and anti-inflammatory treatment. Conclusion:The improved microspheres injection embolization is an effective method for the hepatic metastasis from gastrointestinal tumors and superior to iodized oil embolization in tumor controlling, which may prolong the median survival time.

Objective:To explore the changes of bone mineral density (BMD) and type H vessel, which was recently identified as strongly positive for CD31 and Endomucin (CD31 hiEmcn hi) in long bone from ovariectomized (OVX) mice compared withSham group. Methods:C57BL/6Jwild-type mice were used for experiments and bone tissuewas collected. Eight-week-old female mice were randomly divided into bilateral ovariectomy (OVX) and a sham operation (Sham). The bilateral ovaries were exposed and removed in the OVX group. In the sham group, the ovaries were only exposed but left intact. After 4weeks, these mice were killed for experiment and the femurs were collected for Micro CT scanning in order to observe the changes of bone mineral density (BMD) and trabecular indexes, including bone volume (BV), total volume of interest (TV), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number (Tb.N). The fresh tibia of each mouse was fixed, decalcified, dehydrated and embedded for immunostaining. All experimental data were analyzed with t-test. Results:Mouse femora from two groups were dissected at 4 week time points, and the attached soft tissue was completely removed for Micro CT scanning. BMD in OVX is 0.11±0.01 g/cm 3 and 0.21±0.01 g/cm 3 in Sham, which indicated the BMD in OVX significantly decreased. The results showed significant difference between the groups ( P=0.001). The microarchitecture in trabecular bone changed. BV/TV in OVX is 11.52%±1.77% and 25.87%±1.31% in Sham, which indicated the BV/TV in OVX significantly decreased. The results showed significant difference between the groups ( P<0.05). Tb.N in OVX is 1.67±0.33/mm and 2.95±0.82/mm in Sham, which indicated the Tb.N in OVX slightly decreased. The results showed no significant difference between the groups ( P=0.066). Tb.Th in OVX is 0.06±0.01 mm and 0.07±0.01 mm in Sham, which indicated the Tb.Th in OVX significantly thinned. The results showed significant difference between the groups ( P=0.021). Tb.Sp in OVX is 0.29±0.15 mm and 0.19±0.01 mm in Sham, which indicated the Tb.Sp in OVX significantly increased. The results showed significant difference between the groups ( P<0.05). In the groups BMD decreased and trabecular microstructure was broken. Both BMD and trabecular indexes (BV/TV, Tb. Th, Tb. Sp) showed significant changes in OVX group compared with Sham ( P<0.05) except Tb.N. We next examined the expression of CD31 and EMCN via immunostaining in order to observe the changes of type H vessel.By immunostaining, the percentage of HV/TV in OVX group was 9.14%±0.99% and 29.33%±1.22% in the sham-operated mice. Dramatically decreased type H vessels in the metaphysis of OVX mice were observed compared with that of Sham control mice. The results showed significant difference between the groups ( P<0.05). Conclusion:In this study, ovariectomized mice, a widely used model for postmenopausal osteoporosis, exhibited significantly reduced type H vessels accompanied by reduced BMD, which indicatedtype H vessel involved in the occurrence of postmenopausal osteoporosis.