Iron(III) and BF3·OEt2-Promoted O-Transfer Reaction of N-Aryl-α,ß-Unsaturated Nitrones to Prepare Difluoroboron ß-Ketoiminates.

We described an iron(III) and BF3·OEt2-promoted oxygen transfer reaction of N-aryl-α,ß-unsaturated nitrones to prepare various N,O-difluoroboron ß-ketoiminates in good yields ranging from 24% to 87%. Control experiments revealed that the enaminone was the vital intermediate for the formation of N,O-difluoroboron ß-ketoiminates, and iron(III) combined with BF3·OEt2 played as cocatalyst to promote the oxygen transfer reaction through intramolecular cyclization and N-O bond cleavage. More importantly, an estrone-derived N,O-difluoroboron ß-ketoiminate was easily prepared in 40% yield from estrone in four steps.

TRIM6 Promotes ROS-Mediated Inflammasome Activation and Pyroptosis in Renal Tubular Epithelial Cells via Ubiquitination and Degradation of GPX3 Protein.

BACKGROUND: Pyroptosis is a critical form of cell death during the development of chronic kidney disease (CKD). Tripartite motif 6 (TRIM6) is an E3-ubiquitin ligase that participates in the progression renal fibrosis (RF). The aim of this study was to investigate the roles of TRIM6 and Glutathione peroxidase 3 (GPX3) in oxidative stress-induced inflammasome activation and pyroptosis in Ang-II treated renal tubular epithelial cells. METHODS: To study its role in RF, TRIM6 expression was either reduced or increased in human kidney-2 (HK2) cells using lentivirus, and Ang-II, NAC and BMS-986299 were served as reactive oxygen species (ROS) inducer, ROS scavenger and NLRP3 agonist respectively. Pyroptosis and mitochondrial ROS were measured by flow cytometry. The levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were determined using commercial kits, while the levels of IL-1ß, IL-18, IL-6, and tumor necrosis factor-α (TNF-α) were determined by Enzyme-Linked Immunosorbent Assay (ELISA). Co-immunoprecipitation (Co-IP) assay was used to evaluate the interaction between TRIM6 and GPX3. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot were used to measure mRNA and protein expression, respectively. RESULTS: Treatment with Angiotensin II (Ang II) increased the protein and mRNA levels of TRIM6 in HK2 cells. Ang II also increased mitochondrial ROS production and the malondialdehyde (MDA) level, but decreased the levels of GSH and SOD. In addition, Ang II enhanced HK2 cell pyroptosis, increased the levels of IL-1ß, IL-18, IL-6, and TNF-α, and promoted the expression of active IL-1ß, NLRP3, caspase-1, and GSDMD-N proteins. These effects were reversed by knockdown of TRIM6 and by treatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. BMS-986299, an NLRP3 agonist treatment, did not affect ROS production in HK2 cells exposed to Ang II combined with NAC, but cell pyroptosis and inflammation were aggravated. Moreover, the overexpression of TRIM6 in HK2 cells resulted in similar effects to Ang II. NAC and GPX3 overexpression in HK2 cells could reverse ROS production, inflammation, and pyroptosis induced by TRIM6 overexpression. TRIM6 overexpression decreased the GPX3 protein level by promoting its ubiquitination, without affecting the GPX3 mRNA level. Thus, TRIM6 facilitates GPX3 ubiquitination, contributing to increased ROS levels and pyroptosis in HK2 cells. CONCLUSIONS: TRIM6 increases oxidative stress and promotes the pyroptosis of HK2 cells by regulating GPX3 ubiquitination. These findings could contribute to the development of novel drugs for the treatment of RF.

High CD133 expression in proximal tubular cells in diabetic kidney disease: good or bad?

BACKGROUND: Proximal tubular cells (PTCs) play a critical role in the progression of diabetic kidney disease (DKD). As one of important progenitor markers, CD133 was reported to indicate the regeneration of dedifferentiated PTCs in acute kidney disease. However, its role in chronic DKD is unclear. Therefore, we aimed to investigate the expression patterns and elucidate its functional significance of CD133 in DKD. METHODS: Data mining was employed to illustrate the expression and molecular function of CD133 in PTCs in human DKD. Subsequently, rat models representing various stages of DKD progression were established. The expression of CD133 was confirmed in DKD rats, as well as in human PTCs (HK-2 cells) and rat PTCs (NRK-52E cells) exposed to high glucose. The immunofluorescence and flow cytometry techniques were utilized to determine the expression patterns of CD133, utilizing proliferative and injury indicators. After overexpression or knockdown of CD133 in HK-2 cells, the cell proliferation and apoptosis were detected by EdU assay, real-time cell analysis and flow analysis. Additionally, the evaluation of epithelial, progenitor cell, and apoptotic indices was performed through western blot and quantitative RT-PCR analyses. RESULTS: The expression of CD133 was notably elevated in both human and rat PTCs in DKD, and this expression increased as DKD progressed. CD133 was found to be co-expressed with CD24, KIM-1, SOX9, and PCNA, suggesting that CD133+ cells were damaged and associated with proliferation. In terms of functionality, the knockdown of CD133 resulted in a significant reduction in proliferation and an increase in apoptosis in HK-2 cells compared to the high glucose stimulus group. Conversely, the overexpression of CD133 significantly mitigated high glucose-induced cell apoptosis, but had no impact on cellular proliferation. Furthermore, the Nephroseq database provided additional evidence to support the correlation between CD133 expression and the progression of DKD. Analysis of single-cell RNA-sequencing data revealed that CD133+ PTCs potentially play a role in the advancement of DKD through multiple mechanisms, including heat damage, cell microtubule stabilization, cell growth inhibition and tumor necrosis factor-mediated signaling pathway. CONCLUSION: Our study demonstrates that the upregulation of CD133 is linked to cellular proliferation and protects PTC from apoptosis in DKD and high glucose induced PTC injury. We propose that heightened CD133 expression may facilitate cellular self-protective responses during the initial stages of high glucose exposure. However, its sustained increase is associated with the pathological progression of DKD. In conclusion, CD133 exhibits dual roles in the advancement of DKD, necessitating further investigation.

Selenomethionine Suppress the Progression of Poorly Differentiated Thyroid Cancer via LncRNA NONMMUT014201/miR-6963-5p/Srprb Pathway.

BACKGROUND: Poorly differentiated thyroid cancer (PDTC) is a special type of thyroid cancer that threatens the life of the patients. Unfortunately, there are no effective treatments for PDTC right now, so it is urgent to search for new efficacious drugs. This experiment was designed to elucidate the effects of selenomethionine (SeMet) on PDTC in vitro and vivo. METHODS: A xenograft animal model was used to assay the volume and weight of PDTC. LncRNA NOMMMUT014201 expression was detected by fluorescence in situ hybridization and Real-time quantitative PCR (qRT-PCR). In vitro experiments were carried on in WRO cells. The Cell Counting Kit-8 assay was performed to test the effect of SeMet on the proliferation of cells. And the migration and invasion of WRO cells by the wound-healing assay, Transwell migration and invasion assays. The cell apoptosis was measured by flow cytometry. In addition, genes related to proliferation, migration, invasion and apoptosis were detected through qRT-PCR and Western Blot. RESULTS: SeMet inhibited the proliferation, migration and invasion and promoted the apoptosis of WRO cells in a dose-dependent manner. Then vivo, SeMet significantly suppressed the volume and weight of PDTC. And SeMet downregulated the expressions of Ki67, PCNA, MMP2, MMP9 and BCL2, but upregulated that of BAX and Cleaved-Caspase 3. Moreover, SeMet upregulated the level of LncRNA NOMMMUT014201 both vivo and in vitro. In addition, repression of LncRNA NOMMMUT014201 removed the inhibition effect of SeMet on WRO cell growth significantly (p<0.05). Further investigation showed that LncRNA NOMMMUT014201 downregulated the expression of miR-6963-5p in PDTC cells, but miR-6963-5p inhibited the level of Srprb. In addition, sh-LncRNA NOMMMUT014201 enhanced the proliferation, migration and invasion but inhibited the apoptosis of WRO cells. However, inhibited miR-6963-5p or overexpressed Srprb relieved the effects of sh-LncRNA NOMMMUT014201on WRO cells. CONCLUSION: Collectively, SeMet inhibits the growth of PDTC in a dose-dependent manner through LncRNA NONMMUT014201/miR-6963-5p/Srprb signal pathway, thus suggesting that SeMet might be a potential drug for PDTC treatment.

Review of published 467 achondroplasia patients: clinical and mutational spectrum.

AIM: Achondroplasia is the most common of the skeletal dysplasias that cause fatal and disabling growth and developmental disorders in children, and is caused by a mutation in the fibroblast growth factor receptor, type 3 gene(FGFR3). This study aims to analyse the clinical characteristics and gene mutations of ACH to accurately determine whether a patient has ACH and to raise public awareness of the disease. METHODS: The database of Pubmed, Cochrane Library, Wanfang and CNKI were searched with terms of "Achondroplasias" or "Skeleton-Skin-Brain Syndrome" or "Skeleton Skin Brain Syndrome" or "ACH" and "Receptor, Fibroblast Growth Factor, Type 3" or "FGFR3". RESULTS: Finally, four hundred and sixty-seven patients with different FGFR3 mutations were enrolled. Of the 138 patients with available gender information, 55(55/138, 40%) were female and 83(83/138, 60%) were male. Among the patients with available family history, 47(47/385, 12%) had a family history and 338(338/385, 88%) patients were sporadic. The age of the patients ranged from newborn babies to 36 years old. The mean age of their fathers was 37 ± 7 years (range 31-53 years). Patients came from 12 countries and 2 continents, with the majority being Asian (383/432, 89%), followed by European (49/432, 11%). Short stature with shortened arms and legs was found in 112(112/112) patients, the abnormalities of macrocephaly in 94(94/112) patients, frontal bossing in 89(89/112) patients, genu valgum in 64(64/112) patients and trident hand were found in 51(51/112) patients. The most common mutation was p.Gly380Arg of the FGFR3 gene, which contained two different base changes, c.1138G > A and c.1138G > C. Ten rare pathogenic mutations were found, including c.831A > C, c.1031C > G, c.1043C > G, c.375G > T, c.1133A > G, c.1130T > G, c.833A > G, c.649A > T, c.1180A > T and c.970_971insTCTCCT. CONCLUSION: ACH was caused by FGFR3 gene mutation, and c.1138G > A was the most common mutation type. This study demonstrates the feasibility of molecular genetic testing for the early detection of ACH in adolescents with short stature, trident hand, frontal bossing, macrocephaly and genu valgum.

Integration of ultrasound-based radiomics with clinical features for predicting cervical lymph node metastasis in postoperative patients with differentiated thyroid carcinoma.

OBJECTIVE: The primary objective was to establish a radiomics model utilizing longitudinal +cross-sectional ultrasound (US) images of lymph nodes (LNs) to predict cervical lymph node metastasis (CLNM) following differentiated thyroid carcinoma (DTC) surgery. METHODS: A retrospective collection of 211 LNs from 211 postoperative DTC patients who underwent neck US with suspicious LN fine needle aspiration cytopathology findings at our institution was conducted between June 2021 and April 2023. Conventional US and clinicopathological information of patients were gathered. Based on the pathological results, patients were categorized into CLNM and non-CLNM groups. The database was randomly divided into a training cohort (n = 147) and a test cohort (n = 64) at a 7:3 ratio. The least absolute shrinkage and selection operator algorithm was applied to screen the most relevant radiomic features from the longitudinal + cross-sectional US images, and a radiomics model was constructed. Univariate and multivariate analyses were used to assess US and clinicopathological significance features. Subsequently, a combined model for predicting CLNM was constructed by integrating radiomics, conventional US, and clinicopathological features and presented as a nomogram. RESULTS: The area under the curves (AUCs) of the longitudinal + cross-sectional radiomics models were 0.846 and 0.801 in the training and test sets, respectively, outperforming the single longitudinal and cross-sectional models (p < 0.05). In the testing cohort, the AUC of the combined model in predicting CLNM was 0.901, surpassing that of the single US model (AUC, 0.731) and radiomics model (AUC, 0.801). CONCLUSIONS: The US-based radiomics model exhibits the potential to accurately predict CLNM following DTC surgery, thereby enhancing diagnostic accuracy.

The association between serum selenium levels and pathological features of papillary thyroid cancer in 284 patients.

Objective: The relationship between serum selenium levels and papillary thyroid cancer (PTC), especially the pathological features, still remains controversial. We conducted this study to investigate the relationship between serum selenium levels and PTC in a Chinese population. Methods: Cross-sectional data of 284 patients with PTC were collected from the First Affiliated Hospital of Shandong First Medical University. The general clinical characteristics, serum selenium levels, and tumor pathological features were described in PTC. The association between serum selenium levels and pathological features in PTC was analyzed using SPSS 26.0 statistical software. Results: Our results showed that the median serum selenium level was 79.15 µg/L (IQR: 71.00 - 86.98 µg/L) in PTC patients. Serum selenium levels were lower in females than males (p = 0.035). Serum selenium levels were negatively correlated with the number of lymph node metastases (p = 0.048). High serum selenium (OR = 0.397, 95%CI: 0.217 - 0.725) and diastolic blood pressure (OR = 1.028, 95%CI: 1.005 - 1.051) were related factors for the incidence of bilateral tumors. High serum selenium (OR = 0.320, 95%CI: 0.166 - 0.617) and diastolic blood pressure (OR = 1.066, 95%CI: 1.031 - 1.103) were related factors for tumor multifocal incidence. Conclusions: The serum selenium levels of PTC patients in females were lower than males. High serum selenium levels might be a protective factor in PTC patients. Further research is necessary to better understand the influence of selenium on PTC progression.

Thyroid dysfunction induced by anti-PD-1 therapy is associated with a better progression-free survival in patients with advanced carcinoma.

PURPOSE: Thyroid dysfunction is the most common immune-related adverse event during anti-programmed cell death 1 (anti-PD-1) therapy. In this study, we monitored patients with advanced malignant tumors who received anti-PD-1 therapy to observe the characteristic of anti-PD-1 therapy-induced thyroid dysfunction and its correlation with prognosis. METHODS: Patients with advanced carcinoma treated with anti-PD-1 therapy were evaluated for thyroid function at baseline and after treatment initiation from August 2020 to March 2022. Seventy-three patients were finally included in the study. RESULTS: Among these patients, 19 (26.03%) developed thyroid dysfunction after receiving anti-PD-1 therapy. Primary hypothyroidism and thyrotoxicosis were the most common clinical manifestation. Anti-PD-1-induced thyroid dysfunction occurred 63 (26-131) days after administration; thyrotoxicosis appeared earlier than primary hypothyroidism. In Kaplan-Meier survival analysis, the progression-free survival (PFS) of the thyroid dysfunction group was better than that of the no thyroid dysfunction group (227 (95% confidence interval (CI) 50.85-403.15) days vs 164 (95% CI 77.76-250.24) days, p = 0.026). Male patients had better PFS than female patients (213 (95% CI 157.74-268.26) days vs 74 (95% CI 41.23-106.77) days, p = 0.031). In cox proportional hazards regression model, anti-PD-1-induced thyroid dysfunction remained an independent predictor of better PFS (hazard ratio (HR) = 0.339(0.136-0.848), p = 0.021). CONCLUSION: Thyroid dysfunction is a common immune-related adverse events in advanced cancer patients treated with anti-PD-1 therapy and predicts a better prognosis. TRIAL REGISTRATION: This study was retrospectively registered with Trial ClinicalTrials.gov (NCT05593744) on October 25, 2022.

Association between abnormal lipid metabolism and tumor.

Metabolic Reprogramming is a sign of tumor, and as one of the three major substances metabolism, lipid has an obvious impact. Abnormal lipid metabolism is related to the occurrence of various diseases, and the proportion of people with abnormal lipid metabolism is increasing year by year. Lipid metabolism is involved in the occurrence, development, invasion, and metastasis of tumors by regulating various oncogenic signal pathways. The differences in lipid metabolism among different tumors are related to various factors such as tumor origin, regulation of lipid metabolism pathways, and diet. This article reviews the synthesis and regulatory pathways of lipids, as well as the research progress on cholesterol, triglycerides, sphingolipids, lipid related lipid rafts, adipocytes, lipid droplets, and lipid-lowering drugs in relation to tumors and their drug resistance. It also points out the limitations of current research and potential tumor treatment targets and drugs in the lipid metabolism pathway. Research and intervention on lipid metabolism abnormalities may provide new ideas for the treatment and survival prognosis of tumors.

The relationships between thyroid functions of short-term rapid hypothyroidism and blood lipid levels in post-thyroidectomy patients of differentiated thyroid cancer.

Objective: To explore the relationship between short-term rapid hypothyroidism and blood lipid levels in patients with differentiated thyroid cancer (DTC). Methods: Seventy-five DTC patients scheduled to receive radioactive iodine ablation were enrolled. Levels of thyroid hormone and serum lipids were tested at two time points: the euthyroid before thyroidectomy, and the hypothyroid (off thyroxine). Then the collected data were analyzed. Results: Totally 75 DTC patients enrolled, among them, 5o were female (66.67%) and 25 were male (33. 33%), with an average age of 52.24 ± 1.24 years old. The short-term rapid severe hypothyroidism induced by thyroid hormone withdrawal significantly aggravated dyslipidemia, particularly in patients with dyslipidemia before thyroidectomy (All P < 0.01). However, there was no significant differences between blood lipid levels with different thyroid stimulating hormone (TSH) levels. And our study showed significant negative correlations between free triiodothyronine levels and the changes from euthyjroidism to hypothyroidism in total cholesterol (r=-0.31, P=0.03), triglycerides (r=-0.39, P=0.006), high density lipoprotein-cholesterol (HDL-C) (r=-0.29, P=0.042), and significant positive correlations between free thyroxine and the changes of HDL-C (r=-0.32, P=0.027) were identified in females, however, which were not observed in males. Conclusion: Short-term rapids severe hypothyroidism caused by thyroid hormone withdrawal can lead to rapid significant changes in blood lipid levels. It is necessary to pay attention to dyslipidemia and its long-term effects after thyroid hormone withdrawal, especially in patients with dyslipidemia before thyroidectomy. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03006289?term=NCT03006289&draw=2&rank=1, identifier NCT03006289.

Selenium and thyroid diseases.

Selenium, a non-metallic element, is a micronutrient essential for the biosynthesis of selenoproteins containing selenocysteine. In adults, the thyroid contains the highest amount of selenium per gram of tissue. Most known selenoproteins, such as glutathione peroxidase, are expressed in the thyroid and are involved in thyroid hormone metabolism, redox state regulation, and maintenance of cellular homeostasis. Some clinical studies have shown that lack of selenium will increase the prevalence of several kinds of thyroid diseases. Selenium treatment in patients with Graves' orbitopathy has been shown to delay disease progression and improve the quality of life. Selenium supplementation in Hashimoto's thyroiditis was associated with the decreased levels of anti-thyroid peroxidase antibody and improved thyroid ultrasound structure. In thyroid cancer, various selenium supplements have shown variable anticancer activity. However, published results remain the conflicting and more clinical evidence is still needed to determine the clinical significance of selenium. This article reviews the strong association between selenium and thyroid disease and provides new ideas for the clinical management of selenium in thyroid disease.

Protective effect of Cordyceps sinensis against diabetic kidney disease through promoting proliferation and inhibiting apoptosis of renal proximal tubular cells.

BACKGROUND: Diabetic kidney disease (DKD) has mainly been considered as a glomerular disease. Our previous study showed that the progression of DKD was highly correlated with the dysfunction of renal proximal tubular cells. Fermented Cordyceps sinensis (CS), a substitute for natural CS, is a prominent herb widely used in China, and has exhibited excellent efficacy on DKD. However, the underlying mechanisms remain poorly understood. METHODS: The database analysis was used to identify the main therapeutic targets and pathways of CS involved in DKD treatment. Next, the protective effects of fermented CS on high glucose (HG, 30 mM) induced HK-2 cell injury was validated through cell proliferation and apoptosis assay, including CCK-8, EdU and TUNEL. Finally, quantitative real­time PCR (qRT-PCR) and western blotting were used to verify key target genes. RESULTS: Our results revealed that 9 main targets (RELA, JNK1, PTEN, VEGFA, EGF, ERK2, CASP3, AKT1, MMP9) were recognized as key therapeutic targets with excellent binding affinity screened by database analysis and molecular docking. The biological processes were identified by Gene Ontology (GO) enrichment, which appeared mainly involved in the positive regulation of cell proliferation as well as the negative regulation of apoptosis. The verification experiments in vitro revealed that fermented CS significantly attenuated the HG-induced cytotoxicity and apoptosis, and promoted the proliferation of HK-2 cells. Moreover, fermented CS significantly downregulated the expressions of Bax, Caspase-3, VEGFA, P-AKT and P-ERK, and upregulated the expression of PTEN compared with that of HG group. CONCLUSION: Our results demonstrate that the fermented CS has nephroprotective effects significantly, which functions via promoting proliferation and inhibiting apoptosis of renal proximal tubular cells, likely by targeting Caspase-3, Bax, VEGFA and PTEN. Furthermore, AKT and ERK signaling pathway may be the critical mechanisms underlying the efficacy of fermented CS in DKD treatment.

Associations between the polymorphisms of main components in PI3K/Akt pathway and risk of diabetic kidney disease: A meta-analysis.

AIMS: Diabetic kidney disease (DKD) is a severe microvascular complication frequently associated with type 1 and type 2 diabetes mellitus. The objective of this work was to evaluate the relevance of PI3K/Akt pathway polymorphisms and DKD susceptibility by a meta-analysis. METHODS: Case-control studies related to the relationship between PI3K/Akt pathway polymorphisms and DKD risk were searched from Pubmed, Embase, Cochrane Library, SINOMED, CNKI, and Wanfang databases. Statistical analysis and heterogeneity test were conducted by Review Manager 5.4. RESULTS: Totally, 52 eligible studies were enrolled, including seven single nucleotide polymorphisms (SNPs) for four genes in the PI3K/AKT pathway (GNB3: rs5443; eNOS: rs1799983, rs869109213, rs2070744; IL-6: rs1800795, rs1800796; TNFα: rs1800629). The "M" allele of eNOS rs1799983 was related to the increased risk of DKD under random effects model, especially in Asian population (Overall:M vs. W: I2  = 75%, OR = 1.29, 95%CI 1.07-1.56; MM + WM vs. WW: I2  = 75%, OR = 1.50, 95%CI 1.21-1.86). The "M" allele of eNOS rs869109213 was implicated with higher prevalence of DKD under random effects model, especially in Asian population (Overall:M vs. W: I2  = 63%, OR = 1.43, 95%CI 1.22-1.68; MM + WM vs. WW: I2  = 50%, OR = 1.36, 95%CI 1.16-1.58; MM vs. WM + WW: I2  = 59%, OR = 2.20, 95%CI 1.41-3.43). The "M" allele of eNOS rs2070744 was implicated with higher prevalence of DKD under random effects model, especially in Indian population (Overall: M vs. W: I2  = 47%, OR = 1.35, 95%CI 1.15-1.59; MM + WM vs. WW: I2  = 45%, OR = 1.32, 95%CI 1.07-1.62; MM vs. WM + WW: I2  = 65%, OR = 2.29, 95%CI 1.39-3.77). The "M" allele of IL-6 rs1800796 was predominately associated with higher DKD risks under random effects model, especially in Asian population (Overall: M versus W: I2  = 23%, OR = 1.49, 95%CI 1.21-1.84; MM + WM vs. WW: I2  = 1%, OR = 1.43, 95%CI 1.15-1.77; MM + WM vs. WW: I2  = 71%, OR = 2.77, 95%CI 1.09-7.06). CONCLUSIONS: This meta-analysis indicated that polymorphisms in the PI3K/Akt pathway in eNOS rs1799983, rs869109213, rs2070744, and IL-6 rs1800796 were related to the increased risk of DKD.

The clinical characteristics and gene mutations associated with thyroid hormone resistance syndrome coexisting with pituitary tumors.

Aims: Resistance to thyroid hormone (RTH) and pituitary tumors are both rare diseases, and the differential diagnosis of these two diseases is difficult in some cases. There are also patients who have both conditions, making diagnosis more difficult. To better understand this aspect, we analyzed the clinical characteristics and gene mutations of RTH coexisting with pituitary tumors. Methods: Database retrieval was conducted in the PubMed, Cochrane Library, and SinoMed databases, and the search contents were case reports or case series of patients with RTH coexisting with pituitary tumors. The demographic, clinical manifestations, and imaging characteristics of pituitary tumors and gene mutations were summarized. Results: Thirteen articles involving 16 patients with RTH coexistent with pituitary tumors, consisting of 13 female patients, one male patient, and two patients with unknown sex, were included. The patients were 10 to 79 years old and most patients were 41-55 years old (43.75%). The 16 patients were from seven different countries and three continents (Asia, the Americas, and Europe). All the patients showed an abnormal secretion of TSH, and five patients underwent transsphenoidal surgery. Finally, four patients were pathologically confirmed to have TSHoma. A total of 11 different mutations occurred at nine amino acid sequence sites (251, 310, 344, 347, 383, 429, 435, 438, and 453). Two different mutations occurred in both the no. 435 and no. 453 amino acid sequences. Fourteen patients provided their treatment histories, and all had undergone different treatment regimens. Conclusions: Patients with both RTH and pituitary tumors had multiple clinical manifestations and different thyroid functions, imaging characteristics of pituitary tumors, genetic mutations of THRß, and treatments. However, due to the limited number of cases, the patients were mainly women. Further studies with more cases that focus on the mechanism are still needed.

[Application of Evidence-Based Smoking Cessation Nursing Interventions Increase the Quitting of Smoking in Hospitalized Patients].

BACKGROUND: The second-generation smoking cessation measures for inpatients in our hospital were provided primarily by physicians. Statistics from January to December 2019 showed a negative trend in the number of inpatient smoking cessation services and health education courses provided. PURPOSE: Purpose: In this study, a comprehensive systematic literature review on the application of smoking cessation interventions was conducted with the goal of helping enhance the inpatient quit rate at the author's hospital. RESOLUTION: The literature on smoking cessation interventions was reviewed, with the findings used to formulate a feasible plan for the implementation of an effective related intervention at our hospital. During the implementation process, the challenges encountered led to the formulation of strategies, including: 'conducting second-generation smoking cessation on-the-job training,' 'revising the referral process for patients taking smoking-cessation medications,' and 'adding patients who do not cease smoking to the referral process.' Data on the number of individuals attempting to quit smoking and the success rate of smoking cessation were collected. The baseline values before project implementation were compared with the values at 12 and 24-months posttest. RESULTS: The number of individuals receiving smoking cessation services increased from 85 people within 12 months to 105 people, and further increased to 125 people by the 24th month. Comparing the 3-month abstinence rates for 2019 and 2020, an increase from 31.36% before project implementation to 42.67% after implementation was observed, indicating a rise of 11.31%. Also, comparing the 6-month abstinence rates between 2019 and 2020, an increase from 27.16% before project implementation to 42.67% after implementation was observed, indicating a rise of 15.51%. The project outcomes calculated in December 2021 show a three-month abstinence rate of 44.40% and a six-month abstinence rate of 41.82%. CONCLUSIONS: The nursing interventions for smoking cessation in this project increased the abstinence rate among inpatients. Evidence-based practices, including earching for quality research evidence, utilizing the 7A framework to bridge evidence and clinical differences, and promoting the project using a collaborative cross-team approach, were the main factors contributing to the success of the project. The evidence-based application of smoking cessation strategies highlights the significant role played by nurses in enhancing the quality of care. The findings may serve as a reference for the future development of nursing project solutions.

Crosstalk between proximal tubular epithelial cells and other interstitial cells in tubulointerstitial fibrosis after renal injury.

The energy needs of tubular epithelial components, especially proximal tubular epithelial cells (PTECs), are high and they heavily depend on aerobic metabolism. As a result, they are particularly vulnerable to various injuries caused by factors such as ischemia, proteinuria, toxins, and elevated glucose levels. Initial metabolic and phenotypic changes in PTECs after injury are likely an attempt at survival and repair. Nevertheless, in cases of recurrent or prolonged injury, PTECs have the potential to undergo a transition to a secretory state, leading to the generation and discharge of diverse bioactive substances, including transforming growth factor-ß, Wnt ligands, hepatocyte growth factor, interleukin (IL)-1ß, lactic acid, exosomes, and extracellular vesicles. By promoting fibroblast activation, macrophage recruitment, and endothelial cell loss, these bioactive compounds stimulate communication between epithelial cells and other interstitial cells, ultimately worsening renal damage. This review provides a summary of the latest findings on bioactive compounds that facilitate the communication between these cellular categories, ultimately leading to the advancement of tubulointerstitial fibrosis (TIF).

Potential diagnostic of lymph node metastasis and prognostic values of TM4SFs in papillary thyroid carcinoma patients.

Background: Although the prognosis of papillary thyroid carcinoma (PTC) is relatively good, it causes around 41,000 deaths per year, which is likely related to recurrence and metastasis. Lymph node metastasis (LNM) is an important indicator of PTC recurrence and transmembrane 4 superfamily (TM4SF) proteins regulate metastasis by modulating cell adhesion, migration, tissue differentiation, and tumor invasion. However, the diagnostic and prognostic values of TM4SF in PTC remain unclear. Methods: This study aimed to identify TM4SF genes with predictive value for LNM and prognostic value in PTC using bioinformatic analysis. We screened the differentially expressed genes (DEGs) of the TM4SF family in PTC using data from TCGA, constructed a PPI network using STRING, and evaluated the predictive role of TM4SF1 in LNM via a binary logistic regression analysis and ROC curve. We assessed the association between TM4SF1 expression and DNA methylation, and determined the functional and mechanistic role of TM4SF1 in promoting LNM via GSEA, KEGG, and GO. We estimated the relationship between each TM4SF gene and overall survival (OS, estimated by Kaplan-Meier analysis) in patients with PTC and established a predictive model of prognostic indicators using a LASSO penalized Cox analysis to identify hub genes. Finally, we explored the correlation between TM4SFs and TMB/MSI. Results: We identified 21 DEGs from the 41 TM4SFs between N0 (without LNM) and N1 (with LNM) patients, with TM4SF1, TM4SF4, UPK1B, and CD151 being highly expressed in the N1 group; several DEGs were observed in the TNM, T, and N cancer stages. The "integrins and other cell-surface receptors" pathway was the most significantly enriched functional category related to LNM and TM4SFs. TM4SF1 was identified as an indicator of LNM (AUC= 0.702). High levels of TM4SF1 might be related to Wnt/ß-catenin pathway and epithelial-mesenchymal transition (EMT) process in PTC. The higher expression of TM4SF1 was also related to DNA promoter hypomethylation. CD9, TM4SF4, TSPAN2, and TSPAN16 were associated with OS in PTC patients and TSPAN2 has great potential to become a prognostic marker of PTC progression. For the prognostic model, the riskscore = (-0.0058)*CD82+(-0.4994)*+(0.1584)*TSPAN11+(1.7597)*TSPAN19+(0.2694)*TSPAN2 (lambda.min = 0.0149). The AUCs for 3-year, 5-year, and 10-year OS were 0.81, 0.851, and 0.804. TSPAN18, TSPAN31, and TSPAN32 were associated with both TMB and MSI in PTC patients. Conclusion: Our findings identified TM4SF1 as a potential diagnostic marker of LNM and TSPAN2 as a prognostic factor for patients with PTC. Our study provides a novel strategy to assess prognosis and predict effective treatments in PTC.

[Determination of Dichloromethane in Blood with Headspace Gas Chromatography and Gas Chromatography-Mass Spectrometry].

Objective: To establish a method for qualitative determination of dichloromethane (DCM) in blood by gas chromatography-mass spectrometry (GC-MS) and quantitative determination of DCM in blood by headspace gas chromatography (HS-GC), and to provide reliable support for forensic examination and analysis of poisoning or deaths caused by DCM. Methods: 0.5 mL blood sample was collected, added into headspace vial with chloroform as the internal standard, and processed by heating at 65 °C and evacuation treatment. The intermediate gas in the headspace vial was analyzed by GC-MS for qualitative validation of the method and by HS-GC for quantitative validation of the method. The method was then applied in forensic case analysis. Results: Qualitative validation of the examination method by GC-MS found that the chromatographic peak and mass spectral characteristic ions were specific in samples added with DCM, and that no interference was observed in the blank negative samples. The limit of detection (LOD) was 5 µg/mL. Quantitative method validation by HS-GC found that the chromatographic peak of DCM was well separated from those of eight other volatile compounds, with the resolution>1.5 in all cases; the lower limit of quantification (LOQ) was 20 µg/mL and good linearity was shown within the range of 20 and 1000 µg/mL, R>0.999; the intra-day test precision and inter-day test precision were good (relative standard deviation, or RSD<15% for both) and test accuracy was high (relative error, or δ<15%). With the method established in the study, DCM was detected successfully in the blood of two fatal cases caused by DCM poisoning, with the blood concentration being 470 µg/mL and 915 µg/mL, respectively. Conclusion: This method is shown to be a rapid, stable and accurate approach to the qualitative and quantitative forensic and toxicological analysis of DCM in blood in DCM poisoning cases or deaths caused by DCM.

Case Report: A case of HNF1B mutation patient with first presentation of diabetic ketosis.

Background: Maturity-onset diabetes of the young 5 (MODY5), a rare diabetes syndrome of young adults, is associated with variants in hepatocyte nuclear factor 1B (HNF1B) gene. Case Presentation: We reported a case of MODY5, which presented with diabetic ketosis, multiple renal cysts, and hypokalemia. In this case, the HNF1B score was estimated as 13 and a heterozygous variant of HNF1B in exon 4 (c.826C>T, p.Arg276*) was identified through Sanger sequencing. Conclusions: Multiple renal cysts and youth-onset diabetes are common manifestations in patients with HNF1B mutations, and insufficient insulin secretion may be a potential cause of diabetic ketosis in MODY5.