Exploring symptom clusters in Chinese patients with peritoneal dialysis: a network analysis.

BACKGROUND: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management. METHODS: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis. RESULTS: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients. CONCLUSIONS: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms.

The Mechanism of SNHG8/Microrna-421-3p/Sorting Nexin 8 Axis on Dopaminergic Neurons in Substantia Nigra in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the aging population. Particularly, long non-coding RNAs (lncRNAs) have been demonstrated to play vital roles in PD, while the role of lncRNA SNHG8 in PD remains to be further explored. C57BL/6 mice were induced by rotenone to establish a PD model in vivo, and then the dopaminergic (DA) neuronal damage and locomotor dysfunction in rotenone-treated mice were evaluated. Murine DA cell line MN9D was treated with rotenone to establish a cellular PD model in vitro. Then, the viability, apoptosis, mitochondrial dysfunction, endoplasmic reticulum stress, and autophagy in rotenone-treated MN9D cells were assessed. Expression levels of SNHG8, microRNA-421-3p (miR-421-3p), and sorting nexin 8 (SNX8) in the substantia nigra (SN) of PD mice and rotenone-treated MN9D cells were detected. The interaction between SNHG8 and miR-421-3p, and the targeting relationship between SNX8 and miR-421-3p were confirmed. SNHG8 and SNX8 expression levels were decreased while miR-421-3p expression level was increased in the SN of PD mice and rotenone-treated MN9D cells. Upregulated SNHG8 ameliorated dopaminergic neuron damage and locomotor dysfunction in PD mice. Meanwhile, upregulated SNHG8 enhanced viability, diminished apoptosis, and alleviated mitochondrial dysfunction, endoplasmic reticulum stress, and autophagy in rotenone-treated MN9D cells. Mechanistically, SNHG8 bound to miR-421-3p, and miR-421-3p targeted SNX8. Overexpressed SNHG8 downregulates miR-421-3p to alleviate rotenone-induced dopaminergic neuron injury in PD via upregulating SNX8.

A protein inhibitor of activated STAT (CgPIAS) negatively regulates the expression of ISGs by inhibiting STAT activation in oyster Crassostrea gigas.

The protein inhibitor of activated STAT (PIAS) family proteins act as the important negative regulators in janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, which can be also involved in regulating the expression of interferon-stimulated genes (ISGs). In the present study, a PIAS homologue (designated as CgPIAS) was identified from oyster Crassostrea gigas. The open reading frame (ORF) of CgPIAS cDNA was of 1887 bp encoding a peptide of 628 amino acid residues. The CgPIAS protein contains a conserved scaffold attachment factor A/B/acinus/PIAS (SAP) domain, a Pro-Ile-Asn-Ile-Thr (PINIT) motif, a RING-finger-like zinc-binding domain (RLD) and two SUMO-interaction Motifs (SIMs). The deduced amino acid sequence of CgPIAS shared 74.58-81.36% similarity with other PIAS family members in the RLD domain. The mRNA transcripts of CgPIAS were detected in all the tested tissues with highest level in haemocytes (32.98-fold of mantles, p < 0.001). After poly (I:C) and recombinant Interferon-like protein (rCgIFNLP) stimulation, the mRNA expression of CgPIAS in haemocytes significantly up-regulated to the highest level at 48 h (7.38-fold, p < 0.001) and at 24 h (13.08-fold, p < 0.01), respectively. Moreover, the nuclear translocation of CgPIAS was observed in haemocytes after poly (I:C) stimulation. Biolayer Interferometry (BLI) assay revealed that the recombinant protein CgPIAS-RLD could interact with the recombinant protein CgSTAT in vitro with the KD value of 3.88 × 10-8 M. In the CgPIAS-RNAi oysters, the green signals of CgSTAT protein in nucleus of haemocytes increased compared with that in NC-RNAi group, and the mRNA expression of myxovirus resistance (CgMx1), oligoadenylate synthase-like proteins (CgOASL), CgViperin and IFN-induced protein 44-like (CgIFI44L-1) in haemocytes significantly increased at 12 h after poly (I:C) stimulation, which were 2.39-fold (p < 0.05), 2.18-fold (p < 0.001), 1.74-fold (p < 0.05), and 2.89-fold (p < 0.01) of that in control group, respectively. The above results indicated that CgPIAS negatively regulated the ISG expression by inhibiting STAT activation in oyster C. gigas.

A myxovirus resistance like protein involved in CgIFNLP mediated immune response of oyster Crassostrea gigas.

The myxovirus resistance (Mx) proteins belong to interferon (IFN)-induced dynamin GTPase and play a pivotal role in the inhibition of replication of numerous viruses. In the present study, an Mx homologue (designated as CgMx1) was identified from oyster Crassostrea gigas. The open reading frame (ORF) of CgMx1 cDNA was of 1689 bp encoding a peptide of 562 amino acid residues. There was an N-terminal dynamin GTPase domain in the predicted peptide, which consisted of a tripartite GTP-binding motif (GDXXSGKS, DLPG and T/NKXD). The deduced amino acid sequence of CgMx1 shared 30-39% similarity with other Mx family members. And CgMx1 was clustered with Mx from H. discus, and then assigned into the invertebrate branch of the phylogenetic tree. The mRNA transcripts of CgMx1 were constitutively distributed in all the tested tissues, with the highest level in haemocytes (1342.45-fold of labial palps, p < 0.05). The mRNA expression of CgMx1 in haemocytes was significantly up-regulated to the highest level at 6 h (13.14-fold, p < 0.001) after poly (I:C) treatment and at 24 h (66.28-fold, p < 0.001) after recombinant IFN-like protein (rCgIFNLP) stimulation, respectively. CgMx1 protein was found to distribute in both the cytoplasm and nucleus of haemocytes. In the oysters with CgIFNLP and signal transducer and activator of transcription (CgSTAT) silenced by RNAi, the mRNA expression of CgMx1 decreased significantly in the haemocytes at 12 h after poly (I:C) stimulation, which was 0.02-fold and 0.04-fold of that in EGFP-RNAi oysters (p < 0.001), respectively. Meanwhile, EMSA assay revealed that CgSTAT was able to transactivate CgMx1 promoter through directly binding to its interferon-stimulated response element (ISRE) and gamma interferon activation site (GAS). The above results indicated that CgMx1 participated in the immune response of C. gigas through the signal pathway mediated by CgIFNLP and CgSTAT.

Developing a research database of primary aldosteronism: rationale and baseline characteristics.

BACKGROUND: Management of primary aldosteronism (PA) has become a research hotspot in the field of endocrinology. To obtain reliable research evidence, it is necessary to establish a high-quality PA research database. METHODS: The establishment of PA research database involved two steps. Firstly, patients with confirmation of PA diagnosis between 1 Jan 2009 to 31 Aug 2019 at West China Hospital were identified and data were extracted. Secondly, patients with confirmatory testing for PA will be enrolled into a prospective cohort. Data will be prospectively collected based on the case report forms since 1 Sep 2019. We evaluated the quality of research database through assessment of quality of key variables. RESULTS: Totally, 862 patients diagnosed as PA were identified, of which 507 patients who had positive confirmatory testing for PA were included into the retrospective database. Among 862 patients diagnosed as PA, the mean systolic blood pressure (SBP) was 156.1 (21.7) mmHg, mean diastolic blood pressure (DBP) was 97.2 (14.5) mmHg. Among included patients, the mean serum potassium level was 2.85 (IQR, (2.47-3.36) mmol/L, and the mean plasma aldosterone concentration (PAC) was 28.1 (IQR, 20.0-40.4) ng/dL. The characteristics of patients with positive confirmatory testing for PA were similar. Validation of data extracting and linking showed the accuracy were 100%. Evaluation of missing data showed that the completeness of BMI (95.9%), SBP (99.4%) and DBP (99.4%) were high. CONCLUSION: Through integrating retrospective and prospective cohort of PA, a research database of PA with high quality and comprehensive data can be established. We anticipate that the research database will provide a high level of feasibility for management of PA in China.

Ammonia nitrogen exposure caused structural damages to gill mitochondria of clam Ruditapes philippinarum.

Ammonia nitrogen has been one of the key pollution indicators along the Chinese coastline for quite a few years. Our previous studies have proved that ammonia nitrogen is harmful for Ruditapes philippinarum clam in several aspects. Environmental concentrations of ammonia nitrogen were found to significantly decrease ATP contents and disturb ATP metabolism, in addition to reducing the potential across the mitochondrial membrane in clam gill tissues. Accordingly, mitochondrion is considered as one of the target organelles of ammonia nitrogen toxicity in clams. However, there is a lack of direct evidence to prove it. In order to reveal detail information of ammonia nitrogen toxicity on clam mitochondria and screen the related biomarker to indicate ammonia nitrogen pollution, mitochondrial parameters in gill tissues including swelling, mtDNA copy number and marker enzyme (succinic dehydrogenase, SDH) activity were measured after the clams were exposed to 0.1 mg/L and 0.5 mg/L ammonia nitrogen for 3 days and 21 days, respectively. Moreover, adverse effects of ammonia nitrogen exposure on clam mitochondrial ultra-structures, mitochondrial swelling and division were also discriminated under transmission electron microscope (TEM). Final results showed that ammonia nitrogen exposure to both concentrations significantly induced mitochondrial swelling, reduced the number of mitochondria and messed their normal structure, decreased the number of mtDNA copies and down-regulated SDH activity, all in a concentration and duration dependent manner. So, the present study helps us to better understand the structural damage of ammonia nitrogen on mitochondria in clam gill cells and provides fundamental data for ammonia nitrogen control in aquaculture.

Exploration Of The Seated Saline Suppression Test For The Diagnosis Of Primary Aldosteronism In The Chinese Population.

OBJECTIVE: We prospectively investigated the accuracy of the seated saline suppression test (SSST) in 113 patients with hypertension (including 93 primary aldosteronism [PA] and 20 essential hypertension patients) in the Department of Endocrinology and Metabolism. METHODS: Each patient underwent a recumbent saline suppression test (RSST) and SSST. The accuracy of the SSST for a confirmative PA diagnosis and subtype classification was evaluated and compared with the RSST. RESULTS: The area under the receiver operating characteristic (ROC) curve of plasma aldosterone concentration (PAC) for the SSST was significantly greater than that for the RSST (0.945±0.0199 vs. 0.828 ± 0.0404; P<.05). The ROC analysis showed that the optimal PAC cut-off values were 12.94 ng/dL for the SSST (sensitivity 86.02%, specificity 95%; Youden index [YI] 0.810) and 12.04 ng/dL for the RSST (sensitivity 83.15%, specificity 57%; YI 0.401). The optimal PAC cut-off value for classifying aldosterone-producing adenoma and idiopathic hyperaldosteronism was 18.12 ng/dL for the SSST (sensitivity 73.5%, specificity 79.5%). No patients experienced adverse events during the SSST. CONCLUSION: The SSST is safe and convenient for PA diagnosis. The accuracy of the SSST for a confirmatory diagnosis of PA was better than that of the RSST. The SSST is a reliable alternative for PA confirmation in Chinese individuals. ABBREVIATIONS: APA = aldosterone-producing adenoma; ARR = aldosterone to renin ratio; AVS = adrenal vein sampling; CT = computed tomography; EH = essential hypertension; IHA = idiopathic hyperaldosteronism; MRI = magnetic resonance imaging; PA = primary aldosteronism; PAC = plasma aldosterone concentration; PRA = plasma renin activity; ROC = receiver operating characteristic; RSST = recumbent saline suppression test; SSST = seated saline suppression test; YI = Youden index.

Comparison of the Cook vaginal cervical ripening balloon with prostaglandin E2 insert for induction of labor in late pregnancy.

PURPOSE: To compare the effectiveness of the Cook vaginal cervical ripening balloon (CCRB) with prostaglandin E2 (PGE2) insert for induction of labor in late pregnancy in primipara. METHODS: We evaluated the effectiveness and safety of induction of labor using the improved Bishop score after CCRB or PGE2 administration, total stage of labor, hours until delivery (hours from placement of CCRB or PGE2 insert to parturition and delivery), delivery rate within 24 h, spontaneous delivery rate, successful induction rate, overstimulation syndrome, urgent delivery rate, pain scores, cesarean section rate, and outcomes related to delivery and perinatal morbidity, such as puerperal infection rate, total cost, satisfaction survey, and so on. RESULTS: The improved Bishop Score and delivery rate within 24 h in the CCRB group were significantly higher than in the PGE2 group. The total stage of labor and hours until delivery in the CCRB group were significantly shorter than that in the PGE2 group. Rate of overstimulation syndrome and pain scores in the CCRB group were significantly lower than in the PGE2 group. Compared with the PGE2 group, the mean duration of hospitalization in the CCRB group was shorter and the total cost was less. No difference in satisfaction between the PGE2 and CCRB groups was observed. CONCLUSIONS: Compared with PGE2, CCRB reduced the total stage of labor, hours until delivery, pain scores, mean length of hospitalization, and total cost. CCRB increased the rate of delivery within 24 h with similar safety and maternal satisfaction compared with PGE2.

[Update and Research Progress in the Diagnosis of Primary Aldosteronism].

Primary aldosteronism (PA) is the most common cause of secondary hypertension. The diagnosis procedure of PA includes screening, confirmatory diagnosis and subtype classification. International and national guidelines recommended plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR) to detect possible cases of PA, and one or more tests (fludrocortisone suppression test, saline infusion test, oral sodium loading test, or captopril challenge test) to confirm ARR positive patients. Adrenal venous sampling (AVS) is also recommended as the best method to distinguish unilateral and bilateral adrenal disease when surgical treatment is feasible and desired by the patient. However, many studies find that each of the above diagnostic method has shortcomings. Recently, more and more studies are attempting to explore new methods with higher diagnostic efficiency and more conveniences, including new screening tests, new confirmatory diagnostic tests, new imaging and pathological histology methods. In our studies, the regression model, which included upright PAC, upright PRA, and lowest potassium, is superior to ARR for PA screening; the blood potassium and the ratio of blood potassium to blood sodium after the saline infusion test are not suitable for PA subtyping. This article will review the advances and progress in PA diagnosis.

[The Value of Serum Potassium and Ratio of Sodium to Potassium after Saline Infusion Test in Differential Diagnosis of Primary Hyperaldosteronism].

OBJECTIVE: To explore the electrolyte characteristics between different types of primary aldosteronism (PA), especially the value of serum potassium and the ratio of sodium to potassium after saline infusion test (SIT) in differential diagnosis of PA. METHODS: The clinical data was collected from 135 patients who received screening for the causes of hypertension from Jan. 2009 to Dec. 2018 in West China Hospital. The patients were divided into two groups: essential hypertension group (EH group, 34 patients) and primary aldosteronism group (PA group, 101 patients). PA patients were divided into aldosterone-producing adenoma group (APA group, 60 patients) and idiopathic hyperaldosteronism group (IHA group, 41 patients). To analyze the value of serum potassium and the ratio of sodium to potassium after SIT in the differential diagnosis of PA with receiver operating characteristic (ROC) curve. RESULTS: Compared with EH group, the serum potassium level of APA group was lower either before or after SIT ( P<0.01). The ratio of sodium to potassium before and after SIT in APA group were higher than that in EH group ( P<0.05). There were no differences between APA group and IHA group in the level of serum potassium and the ratio of sodium to potassium before SIT. The level of serum potassium after SIT in APA group was lower than that in IHA group ( P<0.01), and the ratio of sodium to potassium was higher ( P<0.05). The area under ROC curve ( AUC) of serum potassium level and the ratio of sodium to potassium after SIT were 0.641 and 0.646, respectively, while the AUC of aldosterone level was 0.788. The optimal cut-off value of serum sodium level was 3.56 mmol/L, with a sensitivity and specificity of 46.7% and 85.4%. The optimal cut-off value of ratio of sodium to potassium was 39.09, with 53.3% and 80.5% in sensitivity and specificity. CONCLUSION: The serum potassium and the ratio of sodium to potassium after SIT has limited diagnostic value for its low sensitivity in differential diagnosis of PA.

[Diagnosis and Treatment of Primary Aldosteronism in West China Hospital of Sichuan University from 2009 to 2018].

OBJECTIVE: To summary the clinical diagnosis and treatment of primary aldosteronism (PA) in West China Hospital (WCH) of Sichuan University during 2009-2018. METHODS: This study enrolled the patients diagnosed as PA and admitted in WCH of Sichuan University from January 2009 to December 2018. The information of the patients including epidemiological and clinical data, diagnosis and treatment as well as therapeutic outcomes were collected and analyzed. RESULTS: A total of 853 patients with 1 248 diagnostic cases were included in the analysis, and the diagnosis cases of PA increased year by year from 2009 to 2018. Most patients (74.33%) were confirmed the diagnosis in the Department of Endocrinology and Metabolism and then admitted to the hospital. PA was more frequent in female than in male, with a ratio of female to male about 1.34∶1. Hypertension was the most common chief complaint, in contrast, the proportion of fatigue and/or numbness as the symptoms of hypokalemia was declining. More and more patients were diagnosed because of imaging examination founding adrenal incidentoma. After 2016, more and more patients were diagnosed by recumbent saline suppression test and captopril challenge test, and the number of adrenal venous sampling to classify PA subtypes was increasing to help choosing different treatment options. The proportion of surgical treatment decreased year by year, and more and more patients adopted medical treatment or transferred to surgery with combined treatment instead of simple operation. CONCLUSION: During the past 10 years, remarkable progress was made in the diagnosis and treatment of PA. Hypertension was the most important clinical manifestation of PA, so the screening of PA in hypertensive patients should be strengthened. Adrenal incidentaloma has become prevalent manifestation of PA with an increasing trend, which needs more attention in clinical practice.

[Diagnostic Efficiency of Different Screening Indexes for Primary Aldosteronism].

OBJECTIVE: To investigate the the feasibility and diagnostic efficiencyvalue of different screening indexesmethods for screening primary aldosteronism (PA). METHODS: The clinical data of 499 patients with PA and 479 patients with essential hypertension diagnosed from Jan. 2009 to Dec. 2018 were retrospectively analyzed. The diagnostic performance of different screening indexs was compared by plotting receiver operating characteristic curves (ROC). RESULTS: The area under the ROC curve ( AUC) of the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR) was greater than that of the ratio of the upright PAC to the angiotensin Ⅱ (AT-Ⅱ) (AA2R), upright PRA, upright PAC, supine ARR, and lowest blood potassium ( P<0.05). The AUC of logistic regression model was greater than that of upright ARR (96.3% vs. 94.6%, P<0.05). There was no significant difference in AUC between decision tree model and upright ARR (94.1% vs. 94.6%, P>0.05). In the test set, the AUC difference between the logistic regression model and the decision tree model was not statistically significant (96.3% vs. 94.1%, P > 0.05). The calibration curve of the logistic regression model is closer to the 45 ° line, and the consistency between the prediction probability and the actual probability of the logistic regression model is better than that of the decision tree model. CONCLUSION: For the screening of PA, upright ARR seems to be the best single screening index, while AA2R (radioimmunoassay) is not recommended. The diagnostic efficacy of logistic regression model including upright PAC, PRA and lowest blood potassium is better than that of single upright ARR.

Sludge reduction by direct addition of chlorine dioxide into a sequencing batch reactor under operational mode of repeatedly alternating aeration/non-aeration.

The effect of direct addition of chlorine dioxide (ClO2) into a repeatedly alternating aeration/non-aeration sequencing batch reactor (SBR) on its sludge reduction and process performance was investigated. The experimental results showed that the sludge reduction efficiency was 32.9% and the observed growth yield (Yobs) of SBR was 0.11 kg VSS (volatile suspended solids) /kg COD (chemical oxygen demand) for 80 days' operation at the optimum ClO2 dosage of 2.0 mg/g TSS (total suspended solids). It was speculated that cell lysis and cryptic growth, uncoupled metabolism and endogenous metabolism were jointly responsible for the sludge reduction in this study. COD, NH3-N, total nitrogen (TN) and total phosphorus (TP) in the effluent increased on average 29.47, 4.44, 1.97 and 0.05 mg/L, respectively. However, the effluent quality still satisfied the first-class B discharge standards for municipal wastewater treatment plants in China. In that case, the sludge maintained fine viability with the specific oxygen uptake rate (SOUR) being 14.47 mg O2/(g VSS·h) and demonstrated good settleability with the sludge volume index (SVI) being 116 mL/g. The extra cost of sludge reduction at the optimum ClO2 dosage was estimated to be 2.24 CNY (or 0.36 dollar)/kg dry sludge.

Identification of gene fragments related to nitrogen deficiency in Eichhornia crassipes (Pontederiaceae).

Eichhornia crassipes is an aquatic plant native to the Amazon River Basin. It has become a serious weed in freshwater habitats in rivers, lakes and reservoirs both in tropical and warm temperate areas worldwide. Some research has stated that it can be used for water phytoremediation, due to its strong assimilation of nitrogen and phosphorus, and the accumulation of heavy metals, and its growth and spread may play an important role in environmental ecology. In order to explore the molecular mechanism of E. crassipes to responses to nitrogen deficiency, we constructed forward and reversed subtracted cDNA libraries for E. crassipes roots under nitrogen deficient condition using a suppressive subtractive hybridization (SSH) method. The forward subtraction included 2,100 clones, and the reversed included 2,650 clones. One thousand clones were randomly selected from each library for sequencing. About 737 (527 unigenes) clones from the forward library and 757 (483 unigenes) clones from the reversed library were informative. Sequence BlastX analysis showed that there were more transporters and adenosylhomocysteinase-like proteins in E. crassipes cultured in nitrogen deficient medium; while, those cultured in nitrogen replete medium had more proteins such as UBR4-like e3 ubiquitin-protein ligase and fasciclin-like arabinogalactan protein 8-like, as well as more cytoskeletal proteins, including actin and tubulin. Cluster of Orthologous Group (COG) analysis also demonstrated that in the forward library, the most ESTs were involved in coenzyme transportation and metabolism. In the reversed library, cytoskeletal ESTs were the most abundant. Gene Ontology (GO) analysis categories demonstrated that unigenes involved in binding, cellular process and electron carrier were the most differentially expressed unigenes between the forward and reversed libraries. All these results suggest that E. crassipes can respond to different nitrogen status by efficiently regulating and controlling some transporter gene expressions, certain metabolism processes, specific signal transduction pathways and cytoskeletal construction.

Metabolomics revealed more deleterious toxicity induced by the combined exposure of ammonia and nitrite on Ruditapes philippinarum compared to single exposure.

NH3-N and NO2-N always co-exist in the aquatic environment, but there is not a clear opinion on their joint toxicities to the molluscs. Presently, clams Ruditapes philippinarum were challenged by environmental concentrations of NH3-N and NO2-N, singly or in combination, and analyzed by metabolomics approaches, enzyme assays and transmission electron microscope (TEM) observation. Results showed that some same KEGG pathways with different enriched-metabolites were detected in the three exposed groups within one day, and completely different profiles of metabolites were found in the rest of the exposure period. The combined exposure induced heavier and more lasting toxicities to the clams compared with their single exposure. ACP activity and the number of secondary lysosomes were significantly increased after the combined exposure. The present study shed light on the joint-toxicity mechanism of NH3-N and NO2-N, and provided fundamental data for the toxicity research on inorganic nitrogen.

Comparative analysis of microRNA expression profiles in clam Ruditapes philippinarum after ammonia nitrogen exposure.

Ammonia nitrogen is a long-lasting pollutant along the Chinese coast. In our previous studies, the clam Ruditapes philippinarum exhibited several toxic responses to environmental concentrations of ammonia nitrogen. To elucidate the underlying mechanism of ammonia nitrogen toxicity in clams at the post-transcriptional level, microRNA (miRNA) expression profiles were investigated by high-throughput sequencing after the clams were exposed to 0.1 mg/L ammonia nitrogen for 30 days. A total of 238 miRNAs were identified, including 49 conserved miRNAs and 189 novel miRNAs. After comparative analysis, six miRNAs were significantly expressed after 1 day of exposure, with three up-regulated and three down-regulated miRNAs. In addition, 35 miRNAs were significantly expressed after 30 days of exposure, of which 16 were up-regulated and 19 were down-regulated. Furthermore, the target genes of each differentially expressed miRNA were predicted, followed by Gene Ontology (GO) category and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The target genes were predicted to be involved in the immune response, protein processing and transport, DNA damage repair, cellular communication, neural signaling, redox homeostasis, lipid metabolism, and biotransformation. A biological phagocytosis assay proved the speculation that ammonia nitrogen regulated the immunity of clams with the aid of a novel miRNA (novel_29). These findings support further research on miRNA levels in R. philippinarum exposed to ammonia nitrogen.

The correlation of urinary strontium with the risk of chronic kidney disease among the general United States population.

Background: This study sought to illustrate whether urinary strontium levels were related to developing chronic kidney disease (CKD) in the United States population. Methods: A total of 5,005 subjects were identified from the National Health and Nutrition Examination Survey 2011-2016. Survey-weighted logistic regression analysis, multivariate linear regression analysis, restricted cubic spline (RCS) plots curve and stratified analyses were undertaken to explicate the correlation between urinary strontium and CKD. Results: With the increase of urinary strontium, the incidence rate of CKD and urinary albumin to creatinine ratio (UACR) levels gradually decreased, and estimated glomerular filtration rate (eGFR) levels gradually increased. After controlling all confounders, only urinary strontium in the fourth quartile was correlated to a lower CKD prevalence (OR: 0.59; 95% CI, 0.44-0.79) compared to the lowest quartile. Multivariate linear regression analysis showed that urinary strontium was positively correlated with eGFR but negatively with UACR. RCS curve suggested a nonlinear relationship between urinary strontium and CKD (P for non-linearity <0.001). Stratified analyses indicated no significant difference in the correlation between urinary strontium and CKD among different subgroups. Conclusion: Urinary strontium was strongly correlated with a low risk of CKD, and this association was non-linear among the US population.

Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve: A Prospective, Open-Labeled, Randomized and Controlled Study.

OBJECTIVE: To explore the effects of Zishen Yutai Pills (ZYPs) on the quality of oocytes and embryos, as well as pregnancy outcomes in patients with diminished ovarian reserve (DOR) receiving in vitro fertilization-embryo transfer (IVF-ET). The possible mechanisms, involving the regulation of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), were also investigated. METHODS: A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio. The patients in the treatment group (60 cases) received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone (GnRH) antagonist protocol. The patients in the control group (60 cases) received the same protocol but without ZYPs. The primary outcomes were the number of oocytes retrieved and high-quality embryos. Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes. Adverse events were assessed by comparison of the incidence of ectopic pregnancy, pregnancy complications, pregnancy loss, and preterm birth. Contents of BMP15 and GDF9 in the follicle fluids (FF) were also quantified with enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group (both P<0.05). After treatment with ZYPs, a significant regulation of serum sex hormones was observed, including progesterone and estradiol. Both hormones were up-regulated compared with the control group (P=0.014 and 0.008), respectively. No significant differences were observed with regard to pregnancy outcomes including implantation rates, biochemical pregnancy rates, clinical pregnancy rates, live birth rates, and pregnancy loss rates (all P>0.05). The administration of ZYPs did not increase the incidence of adverse events. The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group (both P<0.05). CONCLUSIONS: ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET, resulting in increments of oocytes and embryos, and up-regulation of BMP15 and GDF9 expressions in the FF. However, the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes (Trial reqistration No. ChiCTR2100048441).

Xinyang tablet ameliorates sepsis-induced myocardial dysfunction by regulating Beclin-1 to mediate macrophage autophagy and M2 polarization through LncSICRNT1 targeting E3 ubiquitin ligase TRAF6.

OBJECTIVE: Xinyang Tablet (XYT) has emerged as a potential intervention to counter sepsis-induced myocardial dysfunction (SMID) by influencing macrophage autophagy and M2 polarization. This study aimed to unravel the underlying mechanism of XYT in sepsis-induced myocardial dysfunction (SIMD). METHODS: A microarray analysis was employed to explore sepsis-related changes, and bioinformatics analysis was used to predict lncRNAs binding to tumor necrosis factor receptor-associated factor 6 (TRAF6). This studio utilized SIMD mouse models induced by lipopolysaccharide (LPS) injection, followed by treatments involving varied doses of XYT, digoxin (positive control), or si-LncSICRNT1. After seven days, evaluations encompassing mouse hair/mental state/diet/weight were measured, and cardiac function via echocardiography were conducted. Myocardial tissue changes were observed using hematoxylin-eosin staining. Additionally, bone marrow-derived macrophages (BMDMs) subjected to LPS for M1 polarization were treated with oe-LncSICRNT1, si-TRAF6 and their negative control, XYT, or autophagy inhibitor 3-Methyladenine (3-MA) (positive control). RT-qPCR and Western blot analyses were employed to assess LncSICRNT1, TRAF6, Beclin-1, LC3II/LC3I, and p62 levels. Immunohistochemistry and flow cytometry were used for M1/M2 polarization markers, while enzyme-linked immunosorbent assay (ELISA) gauged inflammatory factor levels. Interaction between TRAF6 and LncSICRNT1 was probed using RNA pull-down and RNA immunoprecipitation (RIP) assays. RESULTS: Chip analysis obtained 1463 differentially expressed lncRNAs, including LINC01550 (LncSICRNT1). Further prediction indicated that LncSICRNT1 was highly likely to directly bind to TRAF6. XYT treatment in LPS-induced SIMD mice led to notable enhancements in sleep/hair/diet/activity, increased weight/left ventricular end-diastolic diameter (LVEDd)/LV ejection fraction (LVEF)/LV fraction shortening (LVFS). These improvements were associated with elevated LncSICRNT1 expression and decreased TRAF6 protein levels, culminating in reduced myocardial inflammatory responses and improved cardiac function. Notably, XYT was found to suppress macrophage M1 polarization, while enhancing M2 polarization, ultimately benefitting cardiac function via LncSICRNT1 modulation. Furthermore, the study revealed LncSICRNT1 modulated Beclin-1 ubiquitination and restrained macrophage autophagy by targeting TRAF6 expression. CONCLUSION: The study highlights XYT's potential to ameliorate LPS-induced SIMD by elevating LncSICRNT1 expression, influencing TRAF6 expression, and regulating Beclin-1 ubiquitination. These actions collectively inhibit macrophage autophagy and foster M1/M2 polarization, contributing to cardiac function improvement.

Role of adrenal venous sampling in the differential diagnosis and treatment protocol of ACTH-independent Cushing's syndrome with bilateral adrenal lesions.

PURPOSE: The diagnosis and management of adrenocorticotropic hormone-independent Cushing's syndrome (AICS) with bilateral adrenal lesions remain challenging. Some studies have explored the value of adrenal vein sampling (AVS) in patients with AICS; however, more investigations are needed to assess its benefits for diagnosis and treatment planning in this population. METHODS: Thirteen patients with clinical, biochemical and imaging evidence of AICS with bilateral adrenal lesions underwent AVS in our department from 2017-2022 were recruited. Only the data from nine patients for whom AVS succeeded were finally included in this study and further analyzed. Blood samples were successfully collected from both adrenal veins (AV) and inferior vena cava (IVC) in these nine patients, and the levels of plasma total cortisol (PTC) and plasma aldosterone concentrations (PAC) were measured. The ratio of the PAC of the AV to the IVC was calculated, and the PTC to PAC ratios were compared between AV. The surgical strategy was chosen according to the results of AVS. Postoperative histology and immunohistochemistry of the adrenal tissues were performed. The prognosis was evaluated based on the improvement of clinical symptoms and biochemical parameters (including PTC and ACTH measurements). RESULTS: Patients with AICS were clinically diagnosed based on clinical signs, results of functional tests and the presence of bilateral adrenal lesions as observed on computed tomography imaging. An AV to IVC PAC ratio greater than 2 confirmed successful AVS. The PTC to PAC ratio (high side to low side) was greater than 2 in four patients, and less than 2 in five patients. The postoperative pathological results were consistent with clinical diagnosis and AVS. During the mean follow-up of 33 months, all nine patients achieved varying degrees of clinical improvement. CONCLUSION: Our study showed that AVS helped to distinguish unilateral and bilateral lesions, identify the laterality of the autonomous hypercortisolism, and improve therapeutic strategy selection in patients with AICS and bilateral adrenal lesions.