Care, control and complications of hospitalised patients with type 1 diabetes in China: A nationwide-based registry study.

AIMS: To evaluate the status quo of type 1 diabetes (T1D) management and characteristics of hospitalised patients with T1D in China through a nationwide multicentre registry study, the China Diabetes Type 1 Study (CD1S). MATERIALS AND METHODS: Clinical data from the electronic hospital records of all people with T1D were retrospectively collected in 13 tertiary hospitals across 7 regions of China from January 2016 to December 2021. Patients were defined as newly diagnosed who received a diagnosis of diabetes for less than 3 months. RESULTS: Among the 4993 people with T1D, the median age (range) at diagnosis was 23.0 (1.0-87.0) years and the median disease duration was 2.0 years. The median haemoglobin A1c (HbA1c) level was 10.7%. The prevalence of obesity, overweight, dyslipidemia, and hypertension were 2.5%, 10.8%, 62.5% and 25.9%, respectively. The incidence rate of diabetic ketoacidosis at disease onset was 41.1%, with the highest in children <10 years of age (50.6%). In patients not newly diagnosed, 60.7% were diagnosed with at least one chronic diabetic complication, with the highest proportion (45.3%) of diabetic peripheral neuropathy. Chronic complications were detected in 79.2% of people with T1D duration ≥10 years. CONCLUSIONS: In the most recent years, there were still unsatisfactory metabolic control and high incidence of diabetic ketoacidosis as well as chronic diabetic complications among inpatients with T1D in China. The ongoing CD1S prospective study aims to improve the quality of T1D management nationally.

Human placenta-derived mesenchymal stem cells ameliorate diabetic kidney disease by modulating the T helper 17 cell/ regulatory T-cell balance through the programmed death 1 / programmed death-ligand 1 pathway.

AIM: To investigate the therapeutic effects and immunomodulatory mechanisms of human placenta-derived mesenchymal stem cells (PMSCs) in diabetic kidney disease (DKD). METHODS: Streptozotocin-induced DKD rats were administered an equivalent volume of saline or PMSCs (1 × 106 in 2 mL phosphate-buffered saline per rat) for 3 weeks. Eight weeks after treatment, we examined the biochemical parameters in the blood and urine, the ratio of T helper 17 cells (Th17) and regulatory T cells (Treg) in the blood, cytokine levels in the kidney and blood, and renal histopathological changes. In addition, we performed PMSC tracing and renal transcriptomic analyses using RNA-sequencing. Finally, we determined whether PMSCs modulated the Th17/Treg balance by upregulating programmed death 1 (PD-1) in vitro. RESULTS: The PMSCs significantly improved renal function, which was assessed by serum creatinine levels, urea nitrogen, cystatin C levels, urinary albumin-creatinine ratio, and the kidney index. Further, PMSCs alleviated pathological changes, including tubular vacuolar degeneration, mesangial matrix expansion, and glomerular filtration barrier injury. In the DKD rats in our study, PMSCs were mainly recruited to immune organs, rather than to the kidney or pancreas. PMSCs markedly promoted the Th17/Treg balance and reduced the levels of pro-inflammatory cytokines (interleukin [IL]-17A and IL-1ß) in the kidney and blood of DKD rats. In vitro experiments showed that PMSCs significantly reduced the proportion of Th17 cells and increased the proportion of Treg cells by upregulating PD-1 in a cell-cell contact manner and downregulating programmed death-ligand 1 (PD-L1) expression in PMSCs, which reversed the Th17/Treg balance. CONCLUSION: We found that PMSCs improved renal function and pathological damage in DKD rats and modulated Th17/Treg balance through the PD-1/PD-L1 pathway. These findings provide a novel mechanism and basis for the clinical use of PMSCs in the treatment of DKD.

Landscape of infiltrating immune cells and related genes in diabetic kidney disease.

INTRODUCTION: Diabetic kidney disease (DKD) is one of the prominent microvascular complications of diabetes and the leading cause of end-stage renal disease. Inflammation plays a crucial role in the development and progression of DKD. Currently, only a few studies depict the landscape of infiltrating immune cells and their potential regulatory network in DKD. To gain a better understanding of the role of immune cells in the renal microenvironment, we sought to reveal the profile of infiltrating immune cells and their potential regulatory network in DKD. METHODS: We obtained the transcriptomes and the corresponding clinical data of 19 DKD and 25 control samples from the Gene Expression Omnibus and Nephroseq databases, respectively. Thereafter, we conducted an analysis on the infiltrating immune cells and identified immune-related differentially expressed genes through bioinformatics. Finally, correlation analyses among immune cells, immune genes, and clinical manifestations were performed, and differentially infiltrating immune cell subsets were verified through multiplex immunofluorescence staining. RESULTS: We demonstrated the landscape of infiltrating immune cells in patients with DKD and identified the top five hub immune regulatory genes (C3, IL7R, TYROBP, BMP2, and CXCL6). Three of the core genes (C3, BMP2, and CXCL6) were significantly correlated with the estimated glomerular filtration rate. Through multiplex immunofluorescence staining, we verified that macrophage numbers were remarkably elevated, whereas Treg cells were remarkably reduced in diabetic kidney tissues. Th2 cells were scarce in the kidney tissue. CONCLUSION: Collectively, our findings shed light on new, possible therapeutic strategies for DKD, from an immune microenvironment perspective.

Association between previous consumption of sugar-sweetened beverages and diabetes remission in patients with newly diagnosed type 2 diabetic ketoacidosis.

This study examined the potential correlation between the immoderate intake of sugar-sweetened beverages (SSBs) and the subsequent rate of diabetes remission (DR). 206 individuals who met the eligibility criteria between January 2019 and June 2022 were recruited. Inquiries were conducted to gather information on the participants' beverage consumption before the onset. Subsequently, the participants were separated into the diabetes remission group (DR group) and nondiabetes remission group (NDR group) depending on whether they met the diagnostic criteria for diabetes remission. Baseline clinical elements within the two groups were juxtaposed, and factors influencing diabetes remission were identified through logistic regression analyses. The cutoff values of each critical factor were determined based on the receiver operating characteristic curve. One hundred and nine patients reported a history of SSB consumption, while the remaining 58 reported no such history. After 1 year, 40 patients achieved remission from diabetes. Compared with the NDR group, a higher SSBs ratio, body mass index (BMI), and blood creatinine (BCr) was observed in the DR group after adjusting for confounders, SSBs (odds ratio [OR] = 3.503; 95% confidence interval [CI] = 1.334-9.202; p = 0.011) and BCr (OR = 1.038; 95% CI = 1.003-1.079; p = 0.042) emerged as independent predictors of DR. The composite index of SSBs and BCr efficaciously predicted DR (area under the ROC curve [AUC] = 0.810, p < 0.001). SSBs and BCr were independent risk factors for DR. The amalgamation of these markers could more accurately predict DR.

Placenta-derived mesenchymal stem cells protect against diabetic kidney disease by upregulating autophagy-mediated SIRT1/FOXO1 pathway.

Diabetic kidney disease (DKD) is a common chronic microvascular complication of diabetes mellitus. Although studies have indicated the therapeutic potential of mesenchymal stem cells (MSCs) for DKD, the underlying molecular mechanisms remain unclear. Herein, we explored the renoprotective effect of placenta-derived MSCs (P-MSCs) and the potential mechanism of SIRT1/FOXO1 pathway-mediated autophagy in DKD. The urine microalbumin/creatinine ratio was determined using ELISA, and renal pathological changes were detected by special staining techniques. Immunofluorescence was used for detecting the renal tissue expression of podocin and nephrin; immunohistochemistry for the renal expression of autophagy-related proteins (LC3, Beclin-1, SIRT1, and FOXO1); and western blotting and PCR for the expression of podocyte autophagy- and pathway-related indicators. We found that P-MSCs ameliorated renal tubular injury and glomerular mesangial matrix deposition and alleviated podocyte damage in DKD rats. PMSCs enhanced autophagy levels and increased SIRT1 and FOXO1 expression in DKD rat renal tissue, whereas the autophagy inhibitor 3-methyladenine significantly attenuated the renoprotective effect of P-MSCs. P-MSCs improved HG-induced Mouse podocyte clone5(MPC5)injury, increased podocyte autophagy, and upregulated SIRT1 and FOXO1 expression. Moreover, downregulation of SIRT1 expression blocked the P-MSC-mediated enhancement of podocyte autophagy and improvement of podocyte injury. Thus, P-MSCs can significantly improve renal damage and reduce podocyte injury in DKD rats by modulating the SIRT1/FOXO1 pathway and enhancing podocyte autophagy.

Occurrence and risk assessment of azole fungicides during the urban water cycle: A year-long study along the Yangtze River, China.

Azole fungicides (AFs) play an important role in the prevention and treatment of fungal diseases in agricultural crops. However, limited studies are addressing the fate and ecological risk of AFs in the urban water cycle at a large watershed scale. To address this gap, we investigated the spatiotemporal distribution and ecological risk of twenty AFs in the lower reaches of the Yangtze River across four seasons. Carbendazim (CBA), tebuconazole (TBA), tricyclazole (TCA), and propiconazole (PPA) were found to be the dominant compounds. Their highest concentrations were measured in January (188.3 ng/L), and November (2197.1 ng/L), July (162.0 ng/L), and November (1801.9 ng/L), respectively. The comparison between wastewater treatment plants (WWTPs) effluents and surface water suggested that industrial WWTPs are major sources of AFs in the Yangtze River. In particular, TBA and PPA were found to be the most recalcitrant AFs in industrial WWTPs, while difenoconazole (DFA) was found to be the most potent pollutant in municipal WWTPs, with an average removal rate of less than 60%. The average risk quotient (RQ) for the entire AFs was 6.45 in the fall, which was higher than in January (0.98), April (0.61), and July (0.40). This indicates that AFs in surface water posed higher environmental risks during the dry season. Additionally, the exposure risk of AFs via drinking water for sensitive populations deserves more attention. This study provides benchmark data on the occurrence of AFs in the lower reaches of the Yangtze River, and offers suggestions for better reduction of AFs.

Placental Mesenchymal Stem Cells Alleviate Podocyte Injury in Diabetic Kidney Disease by Modulating Mitophagy via the SIRT1-PGC-1alpha-TFAM Pathway.

The use of mesenchymal stem cells (MSCs) has become a new strategy for treating diabetic kidney disease (DKD). However, the role of placenta derived mesenchymal stem cells (P-MSCs) in DKD remains unclear. This study aims to investigate the therapeutic application and molecular mechanism of P-MSCs on DKD from the perspective of podocyte injury and PINK1/Parkin-mediated mitophagy at the animal, cellular, and molecular levels. Western blotting, reverse transcription polymerase chain reaction, immunofluorescence, and immunohistochemistry were used to detect the expression of podocyte injury-related markers and mitophagy-related markers, SIRT1, PGC-1α, and TFAM. Knockdown, overexpression, and rescue experiments were performed to verify the underlying mechanism of P-MSCs in DKD. Mitochondrial function was detected by flow cytometry. The structure of autophagosomes and mitochondria were observed by electron microscopy. Furthermore, we constructed a streptozotocin-induced DKD rat model and injected P-MSCs into DKD rats. Results showed that as compared with the control group, exposing podocytes to high-glucose conditions aggravated podocyte injury, represented by a decreased expression of Podocin along with increased expression of Desmin, and inhibited PINK1/Parkin-mediated mitophagy, manifested as a decreased expression of Beclin1, the LC3II/LC3I ratio, Parkin, and PINK1 associated with an increased expression of P62. Importantly, these indicators were reversed by P-MSCs. In addition, P-MSCs protected the structure and function of autophagosomes and mitochondria. P-MSCs increased mitochondrial membrane potential and ATP content and decreased the accumulation of reactive oxygen species. Mechanistically, P-MSCs alleviated podocyte injury and mitophagy inhibition by enhancing the expression of the SIRT1-PGC-1α-TFAM pathway. Finally, we injected P-MSCs into streptozotocin-induced DKD rats. The results revealed that the application of P-MSCs largely reversed the markers related to podocyte injury and mitophagy and significantly increased the expression of SIRT1, PGC-1α, and TFAM compared with the DKD group. In conclusion, P-MSCs ameliorated podocyte injury and PINK1/Parkin-mediated mitophagy inhibition in DKD by activating the SIRT1-PGC-1α-TFAM pathway.

The value of neutrophil-to-lymphocyte ratio combined with the thyroid imaging reporting and data system in the diagnosis of the nature of thyroid nodules.

OBJECTIVE: The aim of this study was to investigate the diagnostic value of peripheral blood neutrophil-to-lymphocyte ratio (NLR) combined with the thyroid imaging reporting and data system (TIRADS) for benign and malignant thyroid nodules. METHODS: A total of 585 adults were enrolled in the study. The receiver operating characteristic curves were used to determine the optimal cut-off values for NLR and Kwak TIRADS (K-TIRADS) grades, which were 1.87 and 4a, respectively. Thyroid nodules were scored as follows: NLR-K-TIRADS score is 2 (both elevated K-TIRADS grade and NLR), NLR-K-TIRADS score is 1 (one of these was elevated) and NLR-k-TIRADS score is 0 (neither were elevated). RESULTS: The proportions of malignant nodules with NLR-K-TIRADS scores of 2, 1 and 0 were 98.59%, 69.62% and 10.19%, and the difference was statistically significant (p < 0.001). In terms of the sensitivity of diagnosis of malignant nodules, NLR-K-TIRADS 1 tends to increase relative to K-TIRADS grades ≥ 4a; in terms of specificity and positive predictive value for the diagnosis of malignant nodules, NLR-K-TIRADS 2 was significantly higher than K-TIRADS grades ≥ 4a (all p < 0.05). CONCLUSIONS: NLR combined with K-TIRADS grades may be a novel method for screening benign and malignant thyroid nodules.

Effects of topical insulin on wound healing: a meta-analysis of animal and clinical studies.

Various researches have reported that the application of topical insulin improves wound healing. Considering the lack of a quantitative comprehensive research on this matter, we conducted a meta-analysis of clinical research and experimental animal studies. Prospective and randomized controlled trials of PubMed, Embase, and Cochrane Library were conducted using appropriate search strategies to compare the effectiveness of topical application of saline and insulin on wounds. The standardized mean difference was calculated as follows: wound healing time, wound healing rate, wound area, and the percentage of wound contraction. Each study used the Cochrane risk-of-bias tool and RevMan 5.3 software to create aggregated assessments and forest plots. The quality of evidence was evaluated in accordance with the methods of the Grading of Recommendations, Assessment, Development and Evaluation working group. Four clinical and nine animal studies eligible for inclusion were included in the meta-analysis. The assessments for clinical studies were as follows: wound healing time, -2.48 [-3.44, -1.51] and wound healing rate, 22.23 [18.17, 26.28]. Meanwhile, for animal studies, the following assessments were noted: wound healing time, -1.27 [-1.75, -0.79]; wound contraction rate, 15.91 [13.88, 17.95]; and wound area, -19.3 [-21.16, -17.44]. For the measurement of the following results, only one animal study was performed, pericyte recruitment of microvessels. Based on the analysis, it can be preliminarily judged that application of topical insulin can aid wound healing.

RAGE/NF-κB pathway mediates hypoxia-induced insulin resistance in 3T3-L1 adipocytes.

There is growing evidence in support of an independent association between obstructive sleep apnea (OSA) and type 2 diabetes, and in which hypoxia may play an important role. Hypoxia is the hallmark feature and the most important pathophysiologic pathway of OSA. Recently, receptor for advanced glycation end products (RAGE) was found to be involved in the pathogenesis of insulin resistance (IR). However, whether RAGE contributes to the IR of adipocytes under hypoxia remains unknown. In the present study, we found that hypoxia reduced glucose consumption and upregulated RAGE expression in 3T3-L1 adipocytes in a time-dependent manner. RAGE knockdown efficiently attenuated hypoxia-induced IR, including inhibiting serine phosphorylation of insulin receptor substrate-1 (IRS-1), increasing the expression of phosphorylated Akt (Ser473), and improving insulin-stimulated glucose uptake. In addition, hypoxia activated nuclear transcription factor κB (NF-κB). However, RAGE knockdown inhibited hypoxia-induced NF-κB activity in adipocytes. Finally, an NF-κB inhibitor (PDTC) significantly reduced the hypoxia-induced upregulation of RAGE expression and IR. Therefore, this study indicates that the RAGE/NF-κB pathway mediates hypoxia-induced IR in 3T3-L1 adipocytes, and suggests that RAGE may be a potential therapeutic target for suppressing IR in OSA.

Effects of different obesity-related adipokines on the occurrence of obstructive sleep apnea.

Obstructive sleep apnea (OSA), characterized by recurrent episodes of apnea during sleep and daytime sleepiness, seriously affects human health and may lead to systemic organ dysfunction. The pathogenesis of OSA is complex and still uncertain, but multiple surveys have shown that obesity is an important factor, and the incidence of OSA in people with obesity is as high as 30%. Adipokines are a group of proteins secreted from adipocytes, which are dysregulated in obesity and may contribute to OSA. Here, we review the most important and representative research results regarding the correlation between obesity-related adipokines including leptin, adiponectin, omentin-1, chemerin, and resistin and OSA in the past 5 years, provide an overview of these key adipokines, and analyze possible intrinsic mechanisms and influencing factors. The existing research shows that OSA is associated with an increase in the serum levels of leptin, chemerin, and resistin and a decrease in the levels of adiponectin and omentin-1; the findings presented here can be used to monitor the development of OSA and obesity, prevent future comorbidities, and identify risk factors for cardiovascular and other diseases, while different adipokines can be linked to OSA through different pathways such as insulin resistance, intermittent hypoxia, and inflammation, among others. We hope our review leads to a deeper and more comprehensive understanding of OSA based on the relevant literature, which will also provide directions for future clinical research.

Prion protein is essential for diabetic retinopathy-associated neovascularization.

Diabetic retinopathy (DR), a major complication of diabetes caused by vascular damage and pathological proliferation of retinal vessels, often progresses to vision loss. Vascular endothelial growth factor (VEGF) signaling plays a pivotal role in the development of DR, but the exact underlying molecular mechanisms remain ill-defined. Cellular prion protein (PrPc) is a surface protein expressed by vascular endothelial cells, and the increased expression of PrPc is associated with physiological and pathological vascularization. Nevertheless, a role for PrPc in the development of DR has not been appreciated. Here, we addressed this question. We found that the development of streptozocin (STZ)-induced DR, but not the STZ-induced hyperglycemia/diabetes itself, was significantly attenuated in PrPc-KO mice, compared to control wildtype (WT) mice, evident by measurement of retinal vascular leakage, retinal neovascularization, a retinopathy score and visual acuity assessment. Moreover, the attenuation of DR severity seemingly resulted from attenuation of retinal neovascularization via VEGF/ras/rac signaling. Together, our study suggests a previously unappreciated role for PrPc in the development of DR.

Circulating omentin-1 levels in women with polycystic ovary syndrome: a meta-analysis.

To investigate the association between circulating omentin-1 levels and polycystic ovary syndrome (PCOS) in women, a meta-analysis was performed. A systematic literature search using PubMed, Embase and Web of Science was carried out. Ten articles with 13 studies were included in this meta-analysis, which included a total of 1264 subjects (733 patients with PCOS and 531 controls). The pooled standard mean difference (SMD) and 95% confidence interval (CI) were used to estimate the association between omentin-1 levels and PCOS. Circulating omentin-1 levels were lower in PCOS with an SMD (95% CI) of -0.67 (-0.91, -0.43) and p = 0.000 (random-effects). However, significant heterogeneity was detected across studies (I2=73.6% and p = 0.000). The subgroup analysis suggested that omentin-1 levels in PCOS patients were associated with HOMA-IR ratio. Meta-regression analysis indicated region was the main source of heterogeneity (p = 0.048). The results of this meta-analysis suggested that circulating omentin-1 levels are significantly lower in women with PCOS compared with controls, which indicated that omentin-1 may play a role in the pathologic processes of PCOS.

Serum advanced glycation end products are associated with insulin resistance in male nondiabetic patients with obstructive sleep apnea.

PURPOSE: Advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic vascular complications. Recently, growing evidence has shown that AGEs could be involved in the pathogenesis of insulin resistance. It has also been suggested that circulating AGE are associated with insulin resistance in nondiabetic patients. This study investigated whether serum AGEs levels are associated with insulin resistance in nondiabetic patients with obstructive sleep apnea (OSA). METHODS: A total of 139 male nondiabetic patients with OSA were recruited for participation in the study. Serum AGE levels were examined using an enzyme-linked immunosorbent assay. Insulin resistance was determined using the homeostasis model assessment index (HOMA-IR). RESULTS: There was a significant correlation between serum AGEs and the apnea-hypopnea index (AHI) (r = 0.281, p = 0.014), duration of SaO2 < 90% (r = 0.267, p = 0.018), minimum SaO2 (r = -0.188, p = 0.046), high-sensitivity C-reactive protein (hsCRP) (r = 0.274, p = 0.012), and HOMA-IR (r = 0.303, p < 0.001). Multiple regression analysis showed that serum AGEs (p = 0.011), AHI (p = 0.024), waist circumference (p = 0.040), and hsCRP (p = 0.046) were independently associated with HOMA-IR (R(2) = 0.392). In addition, the strength of the correlation between serum AGEs and HOMA-IR was related to the severity of OSA. CONCLUSIONS: The present study indicated that serum AGE levels were associated with insulin resistance in male nondiabetic patients with OSA. These findings suggest that AGEs may play a role in insulin resistance in OSA and may also be a biomarker for patients with OSA with high risk of developing type 2 diabetes.

Pituitary Stalk Interruption Syndrome with Excessive Height Growth Combined with Congenital Absence of the Uterus and Ovaries: A Rare Case Report and Review of the Literature.

Aim: Pituitary stalk interruption syndrome is a relatively rare disease. Patients with this disease usually have different degrees of short stature in adulthood. The purpose of this case report is to highlight a special case of unusually elongated limbs with excessive height growth and congenital absence of uterus and ovary, so as to improve clinicians understanding of the atypical manifestations of pituitary stalk interruption syndrome and provide reference for the clinical diagnosis and treatment of the disease. Case Presentation: The 30-year-old female patient exhibited disproportionate growth in height, with a significant increase from 140 cm at the age of 16 to 180 cm currently. Physical examination revealed widened bilateral eye fissures, underdeveloped secondary sexual characteristics, and absence of menstruation. The patient 's parents are cousins, belonging to consanguineous marriage. The patient 's hypoglycemia provocation test suggested the lack of growth hormone and cortisol. Gonadorelin provocation test suggested hypogonadism, and thyroid function test showed hypothyroidism. Pituitary MRI plain scan and enhancement suggested pituitary stalk interruption syndrome, and abdominal and urinary color Doppler ultrasound suggested no echo of uterus and bilateral appendages in the pelvic cavity. The karyotype of peripheral blood was 45, X[3] / 46, XX [117]. The patient was diagnosed with pituitary stalk interruption syndrome, congenital uterine and ovarian deficiency, bone overgrowth, hypothyroidism and secondary osteoporosis. During hospitalization, the symptoms were improved and discharged after hormone replacement therapy such as physiological dose of glucocorticoid, estradiol valerate tablets and levothyroxine sodium tablets. Now the patient is still in our hospital endocrinology outpatient follow-up, no special discomfort. Conclusion: The patient had special clinical manifestations and was clinically confirmed as pituitary stalk interruption syndrome. The patient 's height continues to grow in the absence of growth hormone in the body, and its mechanism remains to be further studied.

Urine-derived stem cell therapy for diabetes mellitus and its complications: progress and challenges.

Diabetes mellitus (DM) is a chronic and relentlessly progressive metabolic disease characterized by a relative or absolute deficiency of insulin in the body, leading to increased production of advanced glycosylation end products that further enhance oxidative and nitrosative stresses, often leading to multiple macrovascular (cardiovascular disease) and microvascular (e.g., diabetic nephropathy, diabetic retinopathy, and neuropathy) complications, representing the ninth leading cause of death worldwide. Existing medical treatments do not provide a complete cure for DM; thus, stem cell transplantation therapy has become the focus of research on DM and its complications. Urine-derived stem cells (USCs), which are isolated from fresh urine and have biological properties similar to those of mesenchymal stem cells (MSCs), were demonstrated to exert antiapoptotic, antifibrotic, anti-inflammatory, and proangiogenic effects through direct differentiation or paracrine mechanisms and potentially treat patients with DM. USCs also have the advantages of simple noninvasive sample collection procedures, minimal ethical issues, low cost, and easy cell isolation methods and thus have received more attention in regenerative therapies in recent years. This review outlines the biological properties of USCs and the research progress and current limitations of their role in DM and related complications. In summary, USCs have shown good versatility in treating hyperglycemia-impaired target organs in preclinical models, and many challenges remain in translating USC therapies to the clinic.

Thermal ablation for multifocal papillary thyroid microcarcinoma: a systematic review and meta-analysis.

BACKGROUND: Clinical studies have indicated the potential safety and efficacy of thermal ablation (TA) in treating multifocal papillary thyroid microcarcinoma (MPTMC). However, a comprehensive systematic evaluation of its effectiveness was still lack. METHODS: PubMed, EMBASE and Cochrane Library databases were systematically searched for studies published until October 23, 2023, that reported on the effectiveness of thermal ablation in the management of MPTMC. Data extraction and methodological quality assessment were independently conducted by two reviewers following the guidelines outlined in the PRISMA. RESULTS: This systematic review and meta-analysis identified 389 tumors in 169 patients from four studies. After treatment with different TA, the combined rate of complete disappearance of MPTMC was 92.8% [95% confidence interval (CI): 68.2-100] and the combined rate of overall complications was 4.4% [95% CI: 1.5-8.5]. During the follow-up period, local tumor recurrence was observed in only 2 patients with a combined rate of 0.2% [95% CI: 0.0-2.6]; lymph node metastasis (LNM) was observed in 3 patients with a combined rate of 1.2% [95% CI: 0-4.1]. Additionally, 6 patients developed new PTMC. It is noteworthy that no patients were observed to develop distant metastases during the follow-up period, and no patients had delayed surgery after underwent ablation. CONCLUSIONS: For patients grappling with MPTMC, TA emerges as an excellent approach for achieving localized tumor control. Nonetheless, achieving favorable outcomes necessitates stringent inclusion criteria and a profound level of expertize.

Body mass index modifies the effect of urinary protein-to-creatinine ratio on chronic kidney disease progression.

BACKGROUND: This study aimed to determine the association between the urinary protein-to-creatinine ratio (UPCR) and chronic kidney disease (CKD) progression in a cohort study, and to determine whether body mass index (BMI) modifies this association. METHODS: The study population consisted of 856 hypertensive patients with CKD stages 2-5, enrolled between 2010 and 2011 in Japan. Generalized linear models with a logit link were used to evaluate the independent and combined effects of the UPCR and BMI on CKD progression RESULTS: During a median follow-up of 25 months, 242 patients developed CKD progression during follow-up. A notably higher risk of CKD progression was found in participants in tertiles 2 [odds ratio (OR): 5.46, 95% confidence interval (95% CI): 2.49-11.99] and 3 (OR 27.74, 95% CI 12.34-62.38) comparing with tertiles 1 for UPCR levels. Moreover, an interaction was found between UPCR and BMI on CKD progression (P for interaction = 0.006). Participants in both the highest tertile of UPCR and overweight (UPCR ≥ 248.9 mg/mmol and BMI ≥ 25 kg/m2) had a 45.59-times higher risk of CKD progression compared with those in the lowest tertile of UPCR and nonoverweight (UPCR < 36.2 mg/mmol and BMI < 25 kg/m2) CONCLUSIONS: The present study demonstrates that the combination of elevated UPCR and BMI may contribute to an increased risk of CKD progression.

From disruption to adaptation: Response of phytoplankton communities in representative impounded lakes to China's South-to-North Water Diversion Project.

Impounded lakes are often interconnected in large-scale water diversion projects to form a coordinated system for water allocation and regulation. The alternating runoff and transferred water can significantly impact local ecosystems, which are initially reflected in the sensitive phytoplankton. Nonetheless, limited information is available on the temporal dynamics and assembly patterns of phytoplankton community in impounded lakes responding to continuous and periodic water diversion. Herein, a long-term monitoring from 2013 to 2020 were conducted to systematically investigate the response of phytoplankton community, including its characteristics, stability, and the ecological processes governing community assembly, in representative impounded lakes to the South-to-North Water Diversion Project (SNWDP) in China. In the initial stage of the SNWDP, the phytoplankton diversity indices experienced a decrease during both non-water diversion periods (8.5 %∼21.2 %) and water diversion periods (5.6 %∼12.2 %), implying a disruption in the aquatic ecosystem. But the regular delivery of high-quality water from the Yangtze River gradually increased phytoplankton diversity and mediated ecological assembly processes shifting from stochastic to deterministic. Meanwhile, reduced nutrients restricted the growth of phytoplankton, pushing species to interact more closely to maintain the functionality and stability of the co-occurrence network. The partial least squares path model revealed that ecological process (path coefficient = 0.525, p < 0.01) and interspecies interactions in networks (path coefficient = -0.806, p < 0.01) jointly influenced the keystone and dominant species, ultimately resulting in an improvement in stability (path coefficient = 0.878, p < 0.01). Overall, the phytoplankton communities experienced an evolutionary process from short-term disruption to long-term adaptation, demonstrating resilience and adaptability in response to the challenges posed by the SNWDP. This study revealed the response and adaptation mechanism of phytoplankton communities in impounded lakes to water diversion projects, which is helpful for maintaining the lake ecological health and formulating rational water management strategies.

Prediction of TNFRSF9 expression and molecular pathological features in thyroid cancer using machine learning to construct Pathomics models.

BACKGROUND: The TNFRSF9 molecule is pivotal in thyroid carcinoma (THCA) development. This study utilizes Pathomics techniques to predict TNFRSF9 expression in THCA tissue and explore its molecular mechanisms. METHODS: Transcriptome data, pathology images, and clinical information from the cancer genome atlas (TCGA) were analyzed. Image segmentation and feature extraction were performed using the OTSU's algorithm and pyradiomics package. The dataset was split for training and validation. Features were selected using maximum relevance minimum redundancy recursive feature elimination (mRMR_RFE) and modeling conducted with the gradient boosting machine (GBM) algorithm. Model evaluation included receiver operating characteristic curve (ROC) analysis. The Pathomics model output a probabilistic pathomics score (PS) for gene expression prediction, with its prognostic value assessed in TNFRSF9 expression groups. Subsequent analysis involved gene set variation analysis (GSVA), immune gene expression, cell abundance, immunotherapy susceptibility, and gene mutation analysis. RESULTS: High TNFRSF9 expression correlated with worsened progression-free interval (PFI) and acted as an independent risk factor [hazard ratio (HR) = 2.178, 95% confidence interval (CI) 1.045-4.538, P = 0.038]. Nine pathohistological features were identified. The GBM Pathomics model demonstrated good prediction efficacy [area under the curve (AUC) 0.819 and 0.769] and clinical benefits. High PS was a PFI risk factor (HR = 2.156, 95% CI 1.047-4.440, P = 0.037). Patients with high PS potentially exhibited enriched pathways, increased TIGIT gene expression, Tregs infiltration (P < 0.0001), and higher rates of gene mutations (BRAF, TTN, TG). CONCLUSIONS: The GBM Pathomics model constructed based on the pathohistological features of H&E-stained sections well predicted the expression level of TNFRSF9 molecules in THCA.