Consumption of soya isoflavones improved polycystic ovary syndrome-associated metabolic disorders in a rat model.

Polycystic ovary syndrome is associated with increased risks for certain metabolic disorders such as insulin resistance, non-alcoholic fatty liver disease and suppressed ovarian follicular development. This study aimed to examine whether soya isoflavones (ISF) mitigate these polycystic ovary syndrome-associated metabolic disorders in a rat model. Weanling Sprague-Dawley female rats were randomly divided into six groups and were treated with either 0 or 83 µg/d dihydrotestosterone (DHT) to induce polycystic ovary syndrome and fed diets containing 0, 0·5, or 1 g ISF/kg diet for 8 weeks. DHT treatment increased food intake, body weight gain (P < 0·001), percentage of primordial follicles (60 % v. 50·9 %, P < 0·05) and accumulation of lipid droplets in the livers. It also elevated serum total cholesterol, free cholesterol, TAG, NEFA and leptin and hepatic total cholesterol and NEFA. Additionally, DHT treatment reduced the percentage of primary follicles (13·8 % v. 30·2 %, P < 0·05), ovary weight and length (P < 0·001), as well as insulin sensitivity (P < 0·01) compared with the Control. ISF intake at 1 g/kg reduced body weight gain, serum total cholesterol, free cholesterol, NEFA, leptin and hepatic TAG and DHT-induced insulin resistance (P < 0·01). ISF intake at both levels decreased DHT-induced lipid droplet accumulation in the livers and changes in the percentages of primordial and primary follicles. Dietary soya ISF alleviated DHT-induced body weight gain, insulin resistance and hepatic lipid droplet accumulation, as well as suppressed ovarian follicular development. This suggests that the consumption of soya foods or ISF supplements may be beneficial for individuals with polycystic ovary syndrome, mitigating the associated metabolic disorders such as diabetes and non-alcoholic fatty liver disease.

Application and advantages of a joystick-controlled robotic scope holder in transoral endoscopic thyroidectomy vestibular approach: a comparative study.

Transoral endoscopic thyroidectomy has gained popularity due to its scarless nature, but the use of a handheld endoscope can lead to an unstable visual field. Soloassist II, a robotic scope holder, enables precise control using a joystick, ensuring stable vision. This study aims to evaluate the application and the advantages of Soloassist II in transoral thyroidectomy. Patients who underwent transoral thyroidectomy with Soloassist II or human assistance between June 2019 and May 2021 were reviewed. Patient demographics and surgical outcomes were compared. The ergonomic stress of the assistant in both groups was also measured. A total of 100 consecutive patients were included: 32 were assisted by Soloassist II and 68 by humans. The Soloassist II group demonstrated significantly shorter operation times (median [IQR]) (165 [149,179] vs. 181 [165,204] min, P = 0.004) in unilateral lobectomy and less blood loss (median [IQR]) (2 [2,2] vs. 2 [2,3] ml, P = 0.002) than the human-assisted group. Postoperative course and complication rates were similar. The musculoskeletal pain of the assistant was significantly higher and involved more areas in the human-assisted group. The utilization of Soloassist II in transoral endoscopic thyroidectomy is easy to set up and leads to shorter operation times, reduced blood loss, and decreased musculoskeletal pain compared to human handheld endoscope. These findings support the potential of Soloassist II in improving surgical outcomes and minimizing physical strain during transoral thyroidectomy.

Discovery of novel anaplastic lymphoma kinase (ALK) and histone deacetylase (HDAC) dual inhibitors exhibiting antiproliferative activity against non-small cell lung cancer.

A series of novel benzimidazole derivatives were designed and synthesised based on the structures of reported oral available ALK inhibitor and HDAC inhibitor, pracinostat. In enzymatic assays, compound 3b, containing a 2-acyliminobenzimidazole moiety and hydroxamic acid side chain, could inhibit both ALK and HDAC6 (IC50 = 16 nM and 1.03 µM, respectively). Compound 3b also inhibited various ALK mutants known to be involved in crizotinib resistance, including mutant L1196M (IC50, 4.9 nM). Moreover, 3b inhibited the proliferation of several cancer cell lines, including ALK-addicted H2228 cells. To evaluate its potential for treating cancers in vivo, 3b was used in a human A549 xenograft model with BALB/c nude mice. At 20 mg/kg, 3b inhibited tumour growth by 85% yet had a negligible effect on mean body weight. These results suggest a attracting route for the further research and optimisation of dual ALK/HDAC inhibitors.

Performance of a multigene genomic classifier and clinical parameters in predicting malignancy in a Southeast Asian cohort of patients with cytologically indeterminate thyroid nodules.

BACKGROUND: Most thyroid nodules are benign. It is important to determine the likelihood of malignancy in such nodules to avoid unnecessary surgery. The primary objective of this study was to characterize the genetic landscape and the performance of a multigene genomic classifier in fine-needle aspiration (FNA) biopsies of cytologically indeterminate thyroid nodules in a Southeast Asian cohort. The secondary objective was to assess the predictive contribution of clinical characteristics to thyroid malignancy. METHODS: This prospective, multicenter, blinded study included 132 patients with 134 nodules. Molecular testing (MT) with ThyroSeq v3 was performed on clinical or ex-vivo FNA samples. Centralized pathology review also was performed. RESULTS: Of 134 nodules, consisting of 61% Bethesda category III, 20% category IV, and 19% category V cytology, and 56% were histologically malignant. ThyroSeq yielded negative results in 37.3% of all FNA samples and in 42% of Bethesda category III-IV cytology nodules. Most positive samples had RAS-like (41.7%), followed by BRAF-like (22.6%), and high-risk (17.9%) alterations. Compared with North American patients, the authors observed a higher proportion of RAS-like mutations, specifically NRAS, in Bethesda categories III and IV and more BRAF-like mutations in Bethesda category III. The test had sensitivity, specificity, negative predictive value, and positive predictive value of 89.6%, 73.7%, 84.0%, and 82.1%, respectively. The risk of malignancy was predicted by positive MT and high-suspicion ultrasound characteristics according to American Thyroid Association criteria. CONCLUSIONS: Even in the current Southeast Asian cohort with nodules that had a high pretest cancer probability, MT could lead to potential avoidance of diagnostic surgery in 42% of patients with Bethesda category III-IV nodules. MT positivity was a stronger predictor of malignancy than clinical parameters.

A novel HDAC6 inhibitor interferes microtubule dynamics and spindle assembly checkpoint and sensitizes cisplatin-induced apoptosis in castration-resistant prostate cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer (CRPC), the most refractory prostate cancer, inevitably progresses and becomes unresponsive to hormone therapy, revealing a pressing unmet need for this disease. Novel agents targeting HDAC6 and microtubule dynamics can be a potential anti-CRPC strategy. METHODS: Cell proliferation was examined in CRPC PC-3 and DU-145 cells using sulforhodamine B assay and anchorage-dependent colony formation assay. Flow cytometric analysis of propidium iodide staining was used to determine cell-cycle progression. Cell-based tubulin polymerization assay and confocal immunofluorescence microscopic examination determine microtubule assembly/disassembly status. Protein expressions were determined using Western blot analysis. RESULTS: A total of 82 novel derivatives targeting HDAC6 were designed and synthesized, and Compound 25202 stood out, showing the highest efficacy in blocking HDAC6 (IC50, 3.5 nM in enzyme assay; IC50, 1.0 µM in antiproliferative assay in CRPC cells), superior to tubastatin A (IC50, 5.4 µM in antiproliferative assay). The selectivity and superiority of 25202 were validated by examining the acetylation of both α-tubulin and histone H3, detecting cell apoptosis and HDACs enzyme activity assessment. Notably, 25202 but not tubastatin A significantly decreased HDAC6 protein expression. 25202 prolonged mitotic arrest through the detection of cyclin B1 upregulation, Cdk1 activation, mitotic phosphoprotein levels, and Bcl-2 phosphorylation. Compound 25202 did not mimic docetaxel in inducing tubulin polymerization but disrupted microtubule organization. Compound 25202 also increased the phosphorylation of CDC20, BUB1, and BUBR1, indicating the activation of the spindle assembly checkpoint (SAC). Moreover, 25202 profoundly sensitized cisplatin-induced cell death through impairment of cisplatin-evoked DNA damage response and DNA repair in both ATR-Chk1 and ATM-Chk2 pathways. CONCLUSION: The data suggest that 25202 is a novel selective and potent HDAC6 inhibitor. Compound 25202 blocks HDAC6 activity and interferes microtubule dynamics, leading to SAC activation and mitotic arrest prolongation that eventually cause apoptosis of CRPC cells. Furthermore, 25202 sensitizes cisplatin-induced cell apoptosis through impeding DNA damage repair pathways.

Comparison of Surgical Outcomes of Transoral Versus Open Thyroidectomy for Graves Disease.

INTRODUCTION: The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a safe alternative to thyroidectomy for thyroid goiter and provides the benefit of being scarless. However, the data on the use of TOETVA in patients with Graves disease are limited. This retrospective study compared the outcomes of Graves disease patients who underwent TOETVA versus those who underwent open thyroidectomy (OT). MATERIALS AND METHODS: Patients with Graves disease who received TOETVA or OT for bilateral total thyroidectomy between September 2017 and October 2022 were included. Patient demographics and surgical outcomes, including operation time, blood loss, length of stay, and complications, were compared. RESULTS: There were 15 patients in each group. The mean age in the TOETVA group was 35.80±8.13 years, which was significantly younger than that in the OT group, which was 51.53±14.22 years. Females predominated in both groups. The other demographic characteristics were similar in both groups. The operation time and intraoperative blood loss were also comparable. The postoperative stay and complications, including hypoparathyroidism, recurrent laryngeal nerve injury, surgical site infection, postoperative hemorrhage, and recurrence of hyperthyroidism, were not different between the 2 groups. There were 11 patients in the TOETVA group and 10 in the OT group who had thyroglobulin levels <0.1 ng/dL, indicating the completeness of total thyroidectomy in the 2 groups. There was no conversion of TOETVA to an open procedure. CONCLUSIONS: For carefully selected Graves patients, TOETVA offers a safe, scarless, and feasible alternative to conventional open thyroidectomy.

A network analysis bridging the gap between the big five personality traits and burnout among medical staff.

BACKGROUND: Burnout is a common issue among medical professionals, and one of the well-studied predisposing factors is the Big Five personality traits. However, no studies have explored the relationships between these traits and burnout from a trait-to-component perspective. To understand the specific connections between each Big Five trait and burnout components, as well as the bridging effects of each trait on burnout, we employed network analysis. METHODS: A cluster sampling method was used to select a total of 420 Chinese medical personnel. The 15-item Chinese Big Five Personality Inventory-15 (CBF-PI-15) assessed the Big Five personality traits, while the 15-item Maslach Burnout Inventory-General Survey (MBI-GS) assessed burnout components. Network analysis was used to estimate network structure of Big Five personality traits and burnout components and calculate the bridge expected influence. RESULTS: The study revealed distinct and clear relationships between the Big Five personality traits and burnout components. For instance, Neuroticism was positively related to Doubt significance and Worthwhile, while Conscientiousness was negatively related to Accomplish all tasks. Among the Big Five traits, Neuroticism displayed the highest positive bridge expected influence, while Conscientiousness displayed the highest negative bridge expected influence. CONCLUSIONS: The network model provides a means to investigate the connections between the Big Five personality traits and burnout components among medical professionals. This study offers new avenues for thought and potential targets for burnout prevention and treatment in medical personnel, which can be further explored and tested in clinical settings.

J24335 exerts neuroprotective effects against 6-hydroxydopamine-induced lesions in PC12 cells and mice.

Parkinson's disease is the second most prevalent age-related neurodegenerative disease and disrupts the lives of people aged >60 years. Meanwhile, single-target drugs becoming inapplicable as PD pathogenesis diversifies. Mitochondrial dysfunction and neurotoxicity have been shown to be relevant to the pathogenesis of PD. The novel synthetic compound J24335 (11-Hydroxy-1-(8-methoxy-5-(trifluoromethyl)quinolin-2-yl)undecan-1-one oxime), which has been researched similarly to J2326, has the potential to be a multi-targeted drug and alleviate these lesions. Therefore, we investigated the mechanism of action and potential neuroprotective function of J24335 against 6-OHDA-induced neurotoxicity in mice, and in PC12 cell models. The key target of action of J24335 was also screened. MTT assay, LDH assay, flow cytometry, RT-PCR, LC-MS, OCR and ECAR detection, and Western Blot analysis were performed to characterize the neuroprotective effects of J24335 on PC12 cells and its potential mechanism. Behavioral tests and immunohistochemistry were used to evaluate behavioral changes and brain lesions in mice. Moreover, bioinformatics was employed to assess the drug-likeness of J24335 and screen its potential targets. J24335 attenuated the degradation of mitochondrial membrane potential and enhanced glucose metabolism and mitochondrial biosynthesis to ameliorate 6-OHDA-induced mitochondrial dysfunction. Animal behavioral tests demonstrated that J24335 markedly improved motor function and loss of TH-positive neurons and dopaminergic nerve fibers, and contributed to an increase in the levels of dopamine and its metabolites in brain tissue. The activation of both the CREB/PGC-1α/NRF-1/TFAM and PKA/Akt/GSK-3ß pathways was a major contributor to the neuroprotective effects of J24335. Furthermore, bioinformatics predictions revealed that J24335 is a low toxicity and highly BBB permeable compound targeting 8 key genes (SRC, EGFR, ERBB2, SYK, MAPK14, LYN, NTRK1 and PTPN1). Molecular docking suggested a strong and stable binding between J24335 and the 8 core targets. Taken together, our results indicated that J24335, as a multi-targeted neuroprotective agent with promising therapeutic potential for PD, could protect against 6-OHDA-induced neurotoxicity via two potential pathways in mice and PC12 cells.

Quantitative detection of tiny amounts of tritium in hydrogen using the catalytic oxidation-liquid scintillation counting method / 中国辐射卫生

Objective To establish a method for quantitative analysis of tiny amounts of tritium in hydrogen below the detection limit of isotope ratio mass spectrometer. Methods Hydrogen was oxidized to produce water in a self-developed catalytic oxidation device filled with platinum hydrophobic catalyst. The effects of different experimental conditions on hydrogen conversion rate were investigated. The tritium concentration in the synthetic water was measured using a liquid scintillation counter. The tritium concentration in hydrogen was calculated according to the measurement of the synthetic water. Results When the flow rate of hydrogen was fixed, the conversion rate of hydrogen increased with the increase of the reaction temperature but increased and then decreased with the increase of the flow rate of oxygen. Hydrogen could be completely converted under optimal experimental conditions. The hydrogen samples with volumetric tritium concentrations in the range of 1 × 10−7 to 2 × 10−14 were converted to water at the reaction temperature of 110 ℃ and hydrogen/oxygen flow rate of 100 mL/min. The resulting water was measured using a liquid scintillation counter. The measurement accuracy was better than 2%. Conclusion This method can be used to measure hydrogen samples with tiny amounts of tritium below the detection limit of isotope ratio mass spectrometer. Our results provide data support for the calculation of the separation capacity of cryogenic distillation process.

Advances in the treatment of KPC-producing Klebsiella pneumoniae infec-tion / 中国感染控制杂志

In recent years,the isolation rate of carbapenem-resistant Klebsiella pneunoniae(CRKP)in China has increased year by year.Due to its multidrug resistance and high mortality in patients,CRKP brings severe challen-ges to the clinical treatment.The major mechanism of drug resistance in CRKP is the production of carbapenemases,with Ambler A,B,and D being the common types while Ambler type C comparativly rare.Klebsiella pneumoniae carbapenemase(KPC)is the most common carbapenemase,which belongs to type A.KPC-producing Klebsiella pneumoniae(KPC-KP)widely spreads in the world,with very limited number of effective clinical drugs.In this re-view,advances in the treatment KPC-KP were summarized to provide reference for clinical treatment.

Effect of circDCUN1D4 on proliferation,apoptosis and immune escape of lung cancer cells by regulating the miR-18a-5p/FBP1 axis / 局解手术学杂志

Objective To investigate the influences of circular RNA(circRNA)DCUN1D4 on the proliferation,apoptosis and immune escape of lung cancer cells by regulating the microRNA(miR)-18a-5p/fructose-1,6-bisphosphatase 1(FBP1)axis.Methods The human lung cancer cell lines H1975,H1650,A549 and SPCA-1 and human normal lung epidermal cells HPL-1 were selected,qRT-PCR was used to detect the expression levels of circDCUN1D4,miR-18a-5p and FBP1 mRNA in various cells.A549 cells in logarithmic growth phase were selected and divided into the blank group,circDCUN1D4 overexpression plasmid(circDCUN1D4)group,overexpression plasmid negative control(NC)group,circDCUN1D4+miR-18a-5p mimics negative control(circDCUN1D4+mimics NC)group,and circDCUN1D4+miR-18a-5p mimics group.The cell viability of each group was detected by CCK-8 method,the cell apoptosis was detected by flow cytometry,the expression levels of circDCUN1D4,miR-18a-5p and FBP1 mRNA of cells in each group were detected by qRT-PCR,the expression levels of FBP1,caspase-3,Ki67,proliferating cell nuclear antigen(PCNA)and programmed death ligand-1(PD-L1)were detected by Western blot,the targeting relationships of miR-18a-5p with circDCUN1D4 and FBP1 were verified by dual luciferase assay.Results Compared with HPL-1 cells,the mRNA expressions of circDCUN1D4 and FBP1 were significantly decreased(P<0.05),and the expression of miR-18a-5p was significantly increased(P<0.05).miR-18a-5p had targeting relationships with circDCUN1D4 and FBP1,respectively.Compared with the blank group and NC group,the OD values at 24 hours and 48 hours,and the expressions of Ki67,PCNA,miR-18a-5p and PD-L1 of cells in the circDCUN1D4 group were significantly decreased(P<0.05),and the apoptosis rate,and the expressions of circDCUN1D4,FBP1 and caspase-3 were significantly increased(P<0.05).Overexpression of miR-18a-5p reversed the inhibitory effect of circDCUN1D4 on the malignant behavior of lung cancer cells(P<0.05).Conclusion Overexpression of circDCUN1D4 can promote lung cancer cell apoptosis,inhibit lung cancer cell proliferation and immune escape,and its mechanism may be related to the regulation of miR-18a-5p/FBP1 axis.

Application of microchannel technique in minimally invasive resection of cervical intraspinal tumors / 北京大学学报(医学版)

Objective:To explore the application and key points of microchannel approaches in resec-tion of cervical intraspinal tumors.Methods:A retrospective analysis was performed on 51 cases of cervi-cal spinal canal tumors from February 2017 to March 2020.Among them,5 cases were located epidural space,6 cases were located epidural and subdural space,and 40 cases were located under the subdural extramedullary space(6 cases were located on the ventral side of the spinal cord).The maximum diameter ranged from 0.5 to 3.0 cm.The clinical manifestations included neck,shoulder or upper limb pain 43 cases,sensory disturbance(numbness)in 22 cases,and limb weakness in 8 cases.The micro-channel keyhole technique was used to expose the tumor,and the tumor was resected microscopically.Results:In this study,35 patients underwent hemilaminectomy,12 patients underwent interlaminar fenestration,2 patients underwent medial 1/4 facetectomy on the basis of hemilaminectomy or interlaminar fenestration.Two tumors were resected through anatomy space(no bone was resected).The degree of tumor resection included total resection in 50 cases and subtotal resection in 1 case.The type of the tumor included 36 schwannomas,12 meningiomas,2 enterogenic cysts and 1 dermoid cyst.There was no infec-tion and cerebrospinal fluid leakage postoperatively.Limb numbness occurred in 7 patients.The average follow-up time was 15 months(3 to 36 months).No deformity such as cervical instability or kyphosis was found.The tumor had no recurrence.Conclusion:The cervical spinal canal is relatively wide,cervical tumors with no more than three segments can be fully exposed by means of microchannel technology.Besides intramedullary or malignant tumors,they can be microsurgically removed.Preservation of the skeletal muscle structure of cervical spine is beneficial to recover the anatomy and function of cervical spine.The electrophysiological monitoring helps to avoid spinal cord or nerve root injury.

Clinical characteristics and prognostic factors of young patients with sporadic rectal cancer liver metastasis / 解放军医学杂志

Objective To identify the clinical characteristics and prognostic factors of young patients with sporadic rectal cancer liver metastasis(RCLM).Methods The clinical data of young RCLM patients at 45 years or under(n=40,as younger patient group)in Peking University First Hospital from January 2016 to January 2021 were reviewed,meanwhile,elder RCLM patient group were comprised of 82 patients older than 45-year-old in a 1:2 ratio.Proportions of categorical variables were compared between young patients and old patients.The clinicopathologic parameters were analyzed with univariate and multivariate Cox regression models and Kaplan-Meier method for demonstrating survival differences between the maximum diameter of liver metastasis and local therapy.Results One hundred and twenty-two RCLM patients were identified,the 1-,3-and 5-year survival rates of young patient group were 97.5%,47.5%,15.0%,those of elder patient group were 84.1%,26.8%,9.8%,respectively.The differences in BMI(P=0.008),primary tumor with obstruction and bleeding(P=0.006),synchronous rectal cancer liver metastases(P=0.005),the maximum diameter of liver metastasis>3 cm(P=0.019)were statistically significant between the two groups.And univariate and multivariate analyses showed that age(P=0.003),N stage(P=0.007),local therapy for liver metastases(P=0.047)and the maximum diameter of liver metastasis(P=0.030)were independent risk factors for influencing the prognosis of RCLM patients;curative resection or not of primary tumor(P=0.035)and the maximum diameter of liver metastasis(P=0.041)were independent risk factors for influencing the prognosis of young RCLM patients.Kaplan-Maier curve demonstrated survival differences between the maximum diameter of liver metastasis and local therapy for liver metastasis in RCLM patients(log-rank P=0.000).Conclusions Although with later staging of initial tumor station,young RCLM patients may obtain better survival benefit compared with old patients.Higher degree of lymph node metastasis,local therapy for liver metastases and the maximum diameter of liver metastasis>3 cm indicates poor prognosis in RCLM patients,and without curative resection of primary tumor and maximum diameter of liver metastasis are also considered as the independent poor prognostic factors of young RCLM patients.Local therapy for liver metastases appears to play an important role in the treatment strategy of RCLM patients.

Research progress of natural product evodiamine-based antitumor drug design strategies / 药学学报

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Antagonizing pathological α-synuclein-mediated neurodegeneration by J24335 via the activation of immunoproteasome.

The aggregation of misfolded proteins, such as α-synuclein in Parkinson's disease (PD), occurs intracellularly or extracellularly in the majority of neurodegenerative diseases. The immunoproteasome has more potent chymotrypsin-like activity than normal proteasome. Thus, degradation of α-synuclein aggregation via immunoproteasome is an attractive approach for PD drug development. Herein, we aimed to determine if novel compound, 11-Hydroxy-1-(8-methoxy-5-(trifluoromethyl)quinolin-2-yl)undecan-1-one oxime (named as J24335), is a promising candidate for disease-modifying therapy to prevent the pathological progression of neurodegenerative diseases, such as PD. The effects of J24335 on inducible PC12/A53T-α-syn cell viability and cytotoxicity were evaluated by MTT assay and LDH assay, respectively. Evaluation of various proteasome activities was done by measuring the luminescence of enzymatic activity after the addition of different amounts of aminoluciferin. Immunoblotting and real-time PCR were employed to detect the expression of various proteins and genes, respectively. We also used a transgenic mouse model for behavioral testing and immunochemical analysis, to assess the neuroprotective effects of J24335. J24335 inhibited wild-type and mutant α-synuclein aggregation without affecting the growth or death of neuronal cells. The inhibition of α-synuclein aggregation by J24335 was caused by activation of immunoproteasome, as mediated by upregulation of LMP7, and increased cellular chymotrypsin-like activity in 20S proteasome. J24335-enhanced immunoproteasome activity was mediated by PKA/Akt/mTOR pathway activation. Moreover, animal studies revealed that J24335 treatment markedly mitigated both the loss of tyrosine hydroxylase-positive (TH-) neurons and impaired motor skill development. This is the first report to use J24335 as an immunoproteasome enhancing agent to antagonize pathological α-synuclein-mediated neurodegeneration.

L-Lysine supplementation affects dietary protein quality and growth and serum amino acid concentrations in rats.

Single amino acid (AA) supplementations in foods are increasing, however their potential nutritional and physiological impacts are not fully understood. This study examined the effects of L-lysine (Lys) supplementation on protein quality of diets, serum AA concentrations and associations between the ratio of supplemental Lys to dietary protein (X) with body weight gain (BWG) in Sprague-Dawley male rats. Rats were fed one of 10 diets containing either 7% or 20% casein and supplemented with 0% (Control), 1.5%, 3%, 6% Lys or 6% Lys + 3% L-arginine (Arg) (8 rats/diet group) for 1 week. Lys supplementation reduced the protein quality of the casein-based diets (p < 0.01). BWG was reduced by supplemental Lys when X > 0.18. Free Lys supplementation dose-dependently increased serum Lys levels (p < 0.01), while increased protein-bound Lys (1.4% vs 0.52%) had little effect on serum Lys (p > 0.05). In the 7% casein diets, ≥ 1.5% supplemental Lys reduced serum alanine, asparagine, glycine, isoleucine, leucine, serine, tyrosine, valine, carnitine, ornithine, and increased urea. Supplementation of ≥ 3% Lys additionally reduced tryptophan and increased histidine, methionine and α-aminoadipic acid (α-AAA) compared to the Control (p < 0.05). In the 20% casein diets, addition of ≥ 1.5% Lys reduced serum asparagine and threonine, and ≥ 3% Lys reduced leucine, proline, tryptophan, valine, and ornithine, and 6% Lys reduced carnitine, and increased histidine, methionine, and α-AAA. Overall, this study showed that free Lys supplementation in a Lys-sufficient diet reduced the protein quality of the diets and modified the serum concentrations of many amino acids. Excess free Lys intake adversely affected growth and utilization of nutrients due to AA imbalance or antagonism. Overall lower protein intake increases susceptibility to the adverse effects of Lys supplementation.

Identification of tumor antigens and immune subtypes of hepatocellular carcinoma for mRNA vaccine development.

BACKGROUND: mRNA vaccines have been investigated in multiple tumors, but limited studies have been conducted on their use for hepatocellular carcinoma (HCC). AIM: To identify candidate mRNA vaccine antigens for HCC and suitable subpopulations for mRNA vaccination. METHODS: Gene expression profiles and clinical information of HCC datasets were obtained from International Cancer Genome Consortium and The Cancer Genome Atlas. Genes with somatic mutations and copy number variations were identified by cBioPortal analysis. The differentially expressed genes with significant prognostic value were identified by Gene Expression Profiling Interactive Analysis 2 website analysis. The Tumor Immune Estimation Resource database was used to assess the correlation between candidate antigens and the abundance of antigen-presenting cells (APCs). Tumor-associated antigens were overexpressed in tumors and associated with prognosis, genomic alterations, and APC infiltration. A consensus cluster analysis was performed with the Consensus Cluster Plus package to identify the immune subtypes. The weighted gene coexpression network analysis (WGCNA) was used to determine the candidate biomarker molecules for appropriate populations for mRNA vaccines. RESULTS: AURKA, CCNB1, CDC25C, CDK1, TRIP13, PES1, MCM3, PPM1G, NEK2, KIF2C, PTTG1, KPNA2, and PRC1 were identified as candidate HCC antigens for mRNA vaccine development. Four immune subtypes (IS1-IS4) and five immune gene modules of HCC were identified that were consistent in both patient cohorts. The immune subtypes showed distinct cellular and clinical characteristics. The IS1 and IS3 immune subtypes were immunologically "cold". The IS2 and IS4 immune subtypes were immunologically "hot", and the immune checkpoint genes and immunogenic cell death genes were upregulated in these subtypes. IS1-related modules were identified with the WGCNA algorithm. Ultimately, five hub genes (RBP4, KNG1, METTL7A, F12, and ABAT) were identified, and they might be potential biomarkers for mRNA vaccines. CONCLUSION: AURKA, CCNB1, CDC25C, CDK1, TRIP13, PES1, MCM3, PPM1G, NEK2, KIF2C, PTTG1, KPNA2, and PRC1 have been identified as candidate HCC antigens for mRNA vaccine development. The IS1 and IS3 immune subtypes are suitable populations for mRNA vaccination. RBP4, KNG1, METTL7A, F12, and ABAT are potential biomarkers for mRNA vaccines.

Digital measurement and clinical significance of proximal femur in the older people of Inner Mongolia population, China.

OBJECTIVE: This study aimed to measure the parameters of the proximal femur in the older people of Inner Mongolia, China and understand the influence of age and gender so as to provide guidance for the design and improvement of prosthesis for total hip arthroplasty. METHODS: A total of 236 patients who underwent CT angiography of lower limbs in the Department of Imaging, Affiliated Hospital of Inner Mongolia Medical University of China were collected. They were divided into 4 groups according to age: < 60 (group A), 60-69 (group B), 70-79 (group C), and > 80 years (group D). Four anatomical parameters, including femoral head diameter (FHD), femoral neck-shaft angle (FNSA), femoral offset (FO), femoral neck anteversion (FNA), were measured by Mimics 21.0. Comparisons were made between age groups of the same gender and between genders in the same age group to analyze the correlation of the 4 parameters of proximal femur with age and gender. In addition, the results of this study were compared with previous studies. RESULTS: There were no significant differences in FHD and FO between age groups, indicating no correlation with age. FNSA and FNA were no significantly different between group C and group D in the same gender, whereas there were significant differences between other age groups and were negatively correlated with age. There were significant differences in FHD and FO between genders in the same age group, with the males being larger than the females. FNSA and FNA were no significant differences between genders in the same age group. CONCLUSIONS: FNSA and FNA decrease with age. FHD and FO were larger in males than in females in all age groups. Age and gender should be considered in the design of prosthesis.

Long-term survival of patients with hepatocellular carcinoma with hepatic, pulmonary, peritoneal and rare colon metastasis: A case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly malignant cancer that often metastasizes and has a poor prognosis. Gastrointestinal tract metastases are rare, and colon metastases are even rarer. The long-term survival of patients with multiple intrahepatic and extrahepatic metastases, especially to the colon, has not been previously reported. CASE SUMMARY: We present an atypical clinical case of a patient with liver, right lung, peritoneal, and colon metastases diagnosed successively following hepatic resection for primary HCC. Comprehensive treatment, including partial liver, lung and colon resection, palliative management such as systemic chemotherapy, trans-arterial chemoembolization, targeted therapy with sorafenib, and cryotherapy were attempted. Despite his early metastases, the patient remained relatively healthy for 8 years after diagnosis. CONCLUSION: This case indicates that comprehensive treatment is beneficial for certain patients with metastatic HCC. Clinicians should be alert as to the possibility of rare site metastatic tumors that may be easily misdiagnosed as primary tumors.

Transoral endoscopic and robotic thyroidectomy for thyroid cancer: the mid-term oncological outcome.

BACKGROUND: Traditional open thyroidectomy is the surgical standard for thyroid cancer; however, it inevitably leaves a visible scar on the neck and affects the patient's quality of life. Therefore, to avoid making a neck incision, the transoral endoscopic thyroidectomy vestibular approach (TOETVA) and transoral robotic thyroidectomy (TORT) have been developed recently, and the surgical outcomes of these techniques are as favorable as open surgery for benign disease. Additionally, positive short-term surgical outcomes have also been achieved in a few patients with thyroid cancer. However, no data on the mid-to-long-term recurrence and survival rates of transoral thyroidectomy in thyroid cancer are available. Therefore, in this study, we analyzed the surgical outcomes and mid-term oncological results of the TOETVA and TORT in patients with thyroid cancer. METHODS: We reviewed patients who had received TOETVA or TORT between July 2017 and November 2021 and followed up on their oncological outcomes until December 2022. Perioperative surgical and mid-term oncological outcomes were analyzed. RESULTS: The 115 patients underwent 122 operations (57 TOETVAs and 65 TORTs), including seven complete thyroidectomies for differentiated thyroid cancer (DTC), Stage I-II, including T1-T3, N0-N1a, and initial low- to high-risk groups. There was no conversion from transoral to open surgery. TORT required a longer operating time (median [interquartile range]) than TOETVA (lobectomy: 279 [250, 318] vs. 196 [173, 253] min, p < 0.001; bilateral total thyroidectomy: 375 [309, 433] vs. 279 [238, 312] min, p < 0.001); however, no difference was found between the two groups regarding perioperative complications. Complete thyroidectomy with a second transoral approach was safe. TOETVA and TORT achieved favorable oncological outcomes with 100% survival and 98.2% acceptable response (excellent and indeterminate response) during a mean 37.88 ± 12.42 months mid-term follow-up. CONCLUSIONS: Transoral endoscopic and robotic thyroidectomy was safe and achieved favorable mid-term oncological outcomes in a selected cohort of patients with early-stage DTC.