Dorsal raphe nucleus to basolateral amygdala 5-HTergic neural circuit modulates restoration of consciousness during sevoflurane anesthesia.

The advent of general anesthesia (GA) has significant implications for clinical practice. However, the exact mechanisms underlying GA-induced transitions in consciousness remain elusive. Given some similarities between GA and sleep, the sleep-arousal neural nuclei and circuits involved in sleep-arousal, including the 5-HTergic system, could be implicated in GA. Herein, we utilized pharmacology, optogenetics, chemogenetics, fiber photometry, and retrograde tracing to demonstrate that both endogenous and exogenous activation of the 5-HTergic neural circuit between the dorsal raphe nucleus (DR) and basolateral amygdala (BLA) promotes arousal and facilitates recovery of consciousness from sevoflurane anesthesia. Notably, the 5-HT1A receptor within this pathway holds a pivotal role. Our findings will be conducive to substantially expanding our comprehension of the neural circuit mechanisms underlying sevoflurane anesthesia and provide a potential target for modulating consciousness, ultimately leading to a reduction in anesthetic dose requirements and side effects.

Sirtuin 6 Deacetylates Apoptosis-Associated Speck-Like Protein (ASC) to Inhibit Endothelial Cell Pyroptosis in Atherosclerosis.

Endothelial cell dysfunction is the main pathology of atherosclerosis (AS). Sirtuin 6 (SIRT6), a deacetylase, is involved in AS progression. This study aimed to investigate the impacts of SIRT6 on the pyroptosis of endothelial cells and its underlying mechanisms. ApoE-/- mice were fed a high-fat diet (HFD) to establish the AS mouse model, atherosclerotic lesions were evaluated using oil red O staining, and blood lipids and inflammatory factors were measured using corresponding kits. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to establish the cell model, and pyroptosis was evaluated by flow cytometry, ELISA, and western blot. Immunoprecipitation (IP), co-IP, western blot, and immunofluorescence were used to detect the molecular mechanisms. The results showed that SIRT6 expression was downregulated in the blood of HFD-induced mice and ox-LDL-induced HUVECs. Overexpression of SIRT6 reduced atherosclerotic lesions, blood lipids, and inflammation in vivo and suppressed pyroptosis of HUVECs in vitro. Moreover, SIRT6 interacted with ASC to inhibit the acetylation of ASC, thus, reducing the interaction between ASC and NLRP3. Moreover, SIRT6 inhibits endothelial cell pyroptosis in the aortic roots of mice by deacetylating ASC. In conclusion, SIRT6 deacetylated ASC to inhibit its interaction with NLRP3 and then suppressed pyroptosis of endothelial cells, thus, decelerating the progression of AS. The findings provide new insights into the function of SIRT6 in AS.

TIF1γ and SMAD4 regulation in colorectal cancer: impact on cell proliferation and liver metastasis.

We investigated the effects of transcriptional intermediary factor 1γ (TIF1γ) and SMAD4 on the proliferation and liver metastasis of colorectal cancer (CRC) cells through knockdown of TIF1γ and/or SMAD4 and knockdown of TIF1γ and/or restoration of SMAD4 expression. Furthermore, we examined TIF1γ and SMAD4 expression in human primary CRC and corresponding liver metastatic CRC specimens. TIF1γ promoted but SMAD4 inhibited the proliferation of CRC cells by competitively binding to activated SMAD2/SMAD3 complexes and then reversely regulating c-Myc, p21, p27, and cyclinA2 levels. Surprisingly, both TIF1γ and SMAD4 reduced the liver metastasis of all studied CRC cell lines via inhibition of MEK/ERK pathway-mediated COX-2, Nm23, uPA, and MMP9 expression. In patients with advanced CRC, reduced TIF1γ or SMAD4 expression was correlated with increased invasion and liver metastasis and was a significant, independent risk factor for recurrence and survival after radical resection. Patients with advanced CRC with reduced TIF1γ or SAMD4 expression had higher recurrence rates and shorter overall survival. TIF1γ and SMAD4 competitively exert contrasting effects on cell proliferation but act complementarily to suppress the liver metastasis of CRC via MEK/ERK pathway inhibition. Thus, reduced TIF1γ or SMAD4 expression in advanced CRC predicts earlier liver metastasis and poor prognosis.

Effect of Infliximab on Radiation-Induced Submandibular Gland Dysfunction in Rats.

Inflammatory response is one of the essential parts of various pathogenic mechanisms of radiation-induced salivary dysfunction. The effect of decreasing the levels of inflammatory cytokines on alleviating submandibular gland injuries after irradiation is unclear. This study aimed to explore the effect of the antibody against tumor necrosis factor-alpha, infliximab, on radiation-induced submandibular gland dysfunction in rats. Male Wistar rats received a single 20 Gy dose to the right submandibular gland region or sham irradiated. Meanwhile, the irradiated group was divided into infliximab treatment groups or untreated groups. Animals were euthanized at 1, 6, and 12 weeks postirradiation, and the irradiated submandibular gland was dissected for subsequent detection. Submandibular gland exposure caused obvious pathological changes. The increased levels of inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1ß, and interleukin-6, represent an aggravated inflammatory response. The results of the western blot, reverse transcription-quantitative polymerase chain reaction, and immunofluorescence staining showed upregulated levels of claudin-1, claudin-3, and aquaporin 5 and downregulated levels of claudin-4. Moreover, nuclear factor kappa-B phosphorylation levels were also up-regulated. In subsequent experiments, we found that infliximab alleviated inflammatory response, up-regulated tumor necrosis factor-alpha, interleukin-1ß, and interleukin-6 levels, and improved claudin-1, claudin-3, claudin-4, and aquaporin 5 expression. Our results indicate that infliximab might improve the para-cellular pathway and trans-cellular pathway destruction by reducing the inflammatory.

Resveratrol, a novel inhibitor of fatty acid binding protein 5, inhibits cervical cancer metastasis by suppressing fatty acid transport into nucleus and downstream pathways.

BACKGROUND AND PURPOSE: Because of cervical cancer (CC) metastasis, the prognosis of diagnosed patients is poor. However, the molecular mechanisms and therapeutic approach for metastatic CC remain elusive. EXPERIMENTAL APPROACH: In this study, we first evaluated the effect of resveratrol (RSV) on CC cell migration and metastasis. Via an activity-based protein profiling (ABPP) approach, a photoaffinity probe of RSV (RSV-P) was synthesized, and the protein targets of RSV in HeLa cells were identified. Based on target information and subsequent in vivo and in vitro validation experiments, we finally elucidated the mechanism of RSV corresponding to its antimetastatic activity. KEY RESULTS: The results showed that RSV concentration-dependently suppressed CC cell migration and metastasis. A list of proteins was identified as the targets of RSV, through the ABPP approach with RSV-P, among which fatty acid binding protein 5 (FABP5) attracted our attention based on The Cancer Genome Atlas (TCGA) database analysis. Subsequent knockout and overexpression experiments confirmed that RSV directly interacted with FABP5 to inhibit fatty acid transport into the nucleus, thereby suppressing downstream matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) expression, thus inhibiting CC metastasis. CONCLUSIONS AND IMPLICATIONS: Our study confirmed the key role of FABP5 in CC metastasis and provided important target information for the design of therapeutic lead compounds for metastatic CC.

Comparative effectiveness of ustekinumab vs. vedolizumab for anti-TNF-naïve or anti-TNF-exposed Crohn's disease: a multicenter cohort study.

Background: Ustekinumab and vedolizumab are both effective for treating Crohn's disease (CD). However, no head-to-head trials have been conducted thus far. We aimed to compare the effectiveness of ustekinumab and vedolizumab in CD patients either naïve or exposed to tumor necrosis factor-alpha inhibitors (TNFi). Methods: Patients treated with vedolizumab or ustekinumab for luminal CD were included from six centers in China from May 2020 to July 2023. Steroid-free remission, clinical remission, objective response, and remission at Weeks 26 and 52 were evaluated in a retrospective multicenter propensity score-weighted cohort. Findings: A total of 536 patients were included (386 ustekinumab, and 150 vedolizumab). After adjustment, ustekinumab showed higher rates of clinical remission (56.4% vs. 47.8%, P = 0.005), steroid-free remission (55.4% vs. 46.1%, P = 0.003), and objective response (67.8% vs. 42.7%, P < 0.001) than vedolizumab at Week 26. At Week 52, ustekinumab exhibited significantly higher rates of clinical remission (65.8% vs. 37.5%, P < 0.001), steroid-free remission (65.8% vs. 37.5%, P < 0.001), objective response (66.7% vs. 23.8%, P < 0.001), and objective remission (31.4% vs. 12.7%, P < 0.001). Subgroup analyses revealed that ustekinumab had higher rates of clinical remission, steroid-free remission, and objective response at Weeks 26 and 52, and objective remission at Week 52 in TNFi-exposed patients, while ustekinumab showed higher rates of objective response at Weeks 26 and 52 and clinical remission, steroid-free remission and objective remission at Week 52 in TNFi-naïve patients. Adverse event rates were similar between the groups (4.9% ustekinumab vs. 6.7% vedolizumab, P = 0.423). Interpretation: Ustekinumab showed superior clinical and objective outcomes compared to vedolizumab, with comparable safety outcomes. The therapeutic superiority was observed in both short-term and long-term phases in TNFi-exposed patients, and the long-term phase in TNFi-naïve patients. Funding: National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Key Research Projects of the Sixth Affiliated Hospital, Sun Yat-sen University, the program of Guangdong Provincial Clinical Research Center for Digestive Diseases, and National Key Clinical Discipline.

The Underexplored Mechanisms of Wheat Resistance to Leaf Rust.

Wheat leaf rust, caused by the obligate biotrophic fungus Puccinia triticina Eriks. (Pt), is one of the most common wheat foliar diseases that continuously threatens global wheat production. Currently, the approaches used to mitigate pathogen infestation include the application of fungicides and the deployment of resistance genes or cultivars. However, the continuous deployment of selected resistant varieties causes host selection pressures that drive Pt evolution and promote the incessant emergence of new virulent races, resulting in the demise of wheat-resistant cultivars after several years of planting. Intriguingly, diploid wheat accessions were found to confer haustorium formation-based resistance to leaf rust, which involves prehaustorial and posthaustorial resistance mechanisms. The prehaustorial resistance in the interaction between einkorn and wheat leaf rust is not influenced by specific races of the pathogen. The induced defense mechanism, known as systemic acquired resistance, also confers durable resistance against a wide array of pathogens. This review summarizes the host range, pathogenic profile, and evolutionary basis of Pt; the molecular basis underlying wheat-Pt interactions; the cloning and characterization of wheat leaf rust resistance genes; prehaustorial and posthaustorial resistance; systemic acquired resistance; and the role of reactive oxygen species. The interplay between climatic factors, genetic features, planting dates, and disease dynamics in imparting resistance is also discussed.

An ultra-sensitive ratiometric fluorescent thermometer based on monomer and excimer dual emission.

By leveraging natural saturated fatty acids with distinct melting points and swift reversible phase transitions, we correlated external thermal cues to monomer and excimer emissions of difluoroboron ß-diketonate fluorophores. This integration yielded a ratiometric fluorescent thermometer showcasing unparalleled sensitivity and thermochromism in the physiological temperature range.

Research on water quality improvement of plain irrigation area based on multi-scenario simulation.

Water diversion projects have proven to be effective interventions to improve water quality in irrigation ditches. This study focused on quantifying the water quality improvement by utilizing a hydrodynamic water quality model in Funing County, Yancheng City. The model performed a spatial analysis of pollution concentrations across the study area. Various optimization scenarios were designed based on the diversion project and hydrological structure connectivity. The model was used to simulate changes in nutrient concentrations under different scenarios. The findings of this study were as follows: (1) Rural areas had lower nutrient concentrations and superior hydrological connectivity than urban areas. (2) The effect of water quality improvement correlated positively with increased flow rates introduced by the diversion project. Specifically, when the flow rate increased by 50%, the average reductions were 20% for NH4+, 5.2% for TN, and 5.1% for TP. Furthermore, introduced clean water led to more pronounced improvements in the overall regional water quality. (3) Although increasing the number of ditches improved water pollution concentration, the impact was not significant. (4) Model simulation results showed that 18 to 45% water diversion intensity effectively improved water quality, and the optimal water diversion intensity was 27 to 30%. The optimal water diversion intensities offered valuable insights for managing this region. The study's methods contributed to the promotion of sustainable development in regional water resources and the integrated management of the water environment.

Biocontrol of bacterial wilt disease in tomato using Bacillus subtilis strain R31.

Bacterial wilt disease caused by Ralstonia solanacearum is a widespread, severe plant disease. Tomato (Solanum lycopersicum), one of the most important vegetable crops worldwide, is particularly susceptible to this disease. Biological control offers numerous advantages, making it a highly favorable approach for managing bacterial wilt. In this study, the results demonstrate that treatment with the biological control strain Bacillus subtilis R31 significantly reduced the incidence of tomato bacterial wilt. In addition, R31 directly inhibits the growth of R. solanacearum, and lipopeptides play an important role in this effect. The results also show that R31 can stably colonize the rhizosphere soil and root tissues of tomato plants for a long time, reduce the R. solanacearum population in the rhizosphere soil, and alter the microbial community that interacts with R. solanacearum. This study provides an important theoretical basis for elucidating the mechanism of B. subtilis as a biological control agent against bacterial wilt and lays the foundation for the optimization and promotion of other agents such as R31.

Diagnostic performances of D-dimer, prothrombin time, and red blood cell distribution width for coronary artery lesion in children with acute stage Kawasaki disease.

Aim: To evaluate the performances of D-dimer, prothrombin time (PT), and red blood cell distribution width (RDW) for the diagnosis of coronary artery lesion (CAL) in acute stage Kawasaki disease (KD). Methods: Between January 2018 and January 2021, a total of 102 children with acute stage KD were included in this retrospective study. Among them, 36 KD children with CAL were divided into the CAL group, and 66 KD children without CAL were divided into the NCAL group. Independent predictors of CAL in acute stage KD were identified by using univariate and multivariate logistic regression analysis. Spearman correlations were used to evaluate the association between CAL in acute stage KD and different indicators. The diagnostic performance of different indicators for CAL in acute stage KD was analyzed by the receiver operating characteristic (ROC) curve. Results: Compared with the NCAL group, children in the CAL group had significantly higher white blood cell count, lymphocyte count, platelet count, D-dimer, and RDW levels, but lower PT levels (all p < 0.05). Logistic regression analysis revealed that D-dimer (OR = 1.0, 95% CI: 1.004-1.012, p < 0.001), PT (OR = 0.4, 95% CI: 0.2-0.8, p = 0.01), and RDW (OR = 7.0, 95% CI: 2.6-19.2, p < 0.001) were independent predictors of CAL in children with acute stage KD. CAL showed a positive correlation with D-dimer (r = 0.4, p < 0.001) and RDW (r = 0.5, p < 0.001), and had a negative association with PT (r = -0.2, p < 0.05). The ROC curve analysis showed that the combination of the three indicators had the highest diagnostic performance for CAL in acute stage KD with an area under the curve (AUC) of 0.922 (sensitivity, 86.1%; specificity, 89.4%), compared with D-dimer (AUC = 0.736), PT (AUC = 0.640), and RDW (AUC = 0.819) alone. Conclusion: A combination of D-dimer, PT, and RDW may help predict CAL in children with acute stage KD.

Preparation of Thin Film Composite (TFC) Membrane with DESPs Interlayer and Its Forward Osmosis (FO) Performance for Organic Solvent Recovery.

To explore the application of forward osmosis (FO) technology in the organic solvent recovery field, we prepared a new solvent-resistant triple layer thin film composite (TFC) membrane on the PI (polyimide) substrate. The deep eutectic supramolecular polymers (DESPs) interlayer was constructed on the substrate to improve the separation performance and solvent resistance. DESPs interlayer was formed by mixing and heating with cyclodextrin as the hydrogen bond acceptor and L-malic acid as the hydrogen bond donor. The chemical changes, surface property and morphology of the composite membrane with DESPs interlayer were characterized. The separation performance and stability of the triple layer composite membrane in organic solvent FO were studied. For the monascorubrin-ethanol system, the permeation flux of TFC/DESPs5-PI membrane could reach 9.51 LMH while the rejection rate of monascorubrin was 98.4% (1.0 M LiCl/ethanol as draw solution), which was better than the pristine membrane. Therefore, this solvent-resistant triple layer composite FO membrane has good potential for the recovery of organic solvents.

MicroRNA-188-5p inhibits hepatocellular carcinoma proliferation and migration by targeting forkhead box N2.

BACKGROUND: This study aimed to identify the biological functions, expression modes, and possible mechanisms underlying the relationship between metastatic human hepatocellular carcinoma (HCC) and MicroRNA-188-5p (miR-188) dysregulation using cell lines. METHODS: A decrease in miR-188 was detected in low and high metastatic HCC cells compared to that in normal hepatic cells and non-invasive cell lines. Gain- and loss-of-function experiments were performed in vitro to investigate the role of miR-188 in cancer cell (Hep3B, HepG2, HLF, and LM3) proliferation and migration. RESULTS: miR-188 mimic transfection inhibited the proliferation of metastatic HLF and LM3 cells but not non-invasive HepG2 and Hep3B cells; nonetheless, miR-188 suppression promoted the growth of HLF and LM3 cells. miR-188 upregulation inhibited the migratory rate and invasive capacity of HLF and LM3, rather than HepG2 and Hep3B cells, whereas transfection of a miR-188 inhibitor in HLF and LM3 cells had the opposite effects. Dual-luciferase reporter assays and bioinformatics prediction confirmed that miR-188 could directly target forkhead box N2 (FOXN2) in HLF and LM3 cells. Transfection of miR-188 mimics reduced FOXN2 levels, whereas miR-188 inhibition resulted in the opposite result, in HLF and LM3 cells. Overexpression of FOXN2 in HLF and LM3 cells abrogated miR-188 mimic-induced downregulation of proliferation, migration, and invasion. In addition, we found that miR-188 upregulation impaired tumor growth in vivo. CONCLUSIONS: In summary, this study showed thatmiR-188 inhibits the proliferation and migration of metastatic HCC cells by targeting FOXN2.

The Application of the Insulin to C-Peptide Molar Ratio (ICPR) in Primary Screening for Insulin Antibodies in Type 2 Diabetes Mellitus Patients: A Further Quantitative Study on the Relationship Between ICPR and Insulin Antibodies.

Purpose: This study aimed to further quantify the relationship between insulin antibodies (IAs) and the 2-hour insulin to C-peptide molar ratio (2h-ICPR) using a multiple linear regression model in T2DM patients. Methods: A total of 274 T2DM patients from April 2019 to December 2022 in Xiang'an Hospital of Xiamen University were included in this study. Multiple Linear Model Fitting was conducted on the candidate independent variables (age, BMI, HbA1c, and 2h-ICPR) for the multiple linear regression. The linear relationship between insulin antibodies (IAs) and the significant independent variables was presented by making multiple linear regression equations. Results: The total demographic characteristics of the included patients were as follows: age (51.92±13.10 years), BMI (24.94±3.99 kg/m2), HbA1c (9.70±2.39%), 2h-ICPR (0.12±0.11), and IAs (0.37±1.12COI). Linear relationships of independent variables: age (r=0.163, p=0.007), 2h-ICPR (r=0.259, p=0.001), BMI (r=0.007, p=0.907) and 2h-ICPR (r=0.092, p=0.129). Multiple linear regression: age (unstandardized ß=0.014, 95% CI: 0.004-0.024, p=0.004), 2h-ICPR (unstandardized ß=2.758, 95% CI: 1.555-3.962, p≤0.001). The regression equation: . Conclusion: The quantitative relationship between 2h-ICPR and insulin antibodies was . 2h-ICPR can be a preliminary screening indicator for insulin antibody testing in patients with type 2 diabetes.

Impact of endometriosis on female sexual function: an updated systematic review and meta-analysis.

Introduction: Endometriosis can lead to a state of chronic inflammation marked by the presence of scarring and adhesions within the pelvis and/or other parts of the body. Recent estimates suggest that globally this condition affects approximately 10% of women in the reproductive age group. Aims: In this study we sought updated evidence on the association between endometriosis and sexual function in female patients. Methods: We used standard assessment tools to conduct a systematic search of the PubMed, EMBASE, and Scopus databases for observational studies that documented the association of endometriosis with female sexual function. A random-effects model was used for the analysis, and effect sizes were reported as the weighted mean difference (WMD) or OR with 95% CIs. Results: A total of 13 studies were selected for inclusion in our investigation. All of the included studies were cross-sectional in design. The data on sexual function in most of the studies were collected by using the Female Sexual Function Index (FSFI) tool, for which higher scores suggest better sexual function. The risk of sexual dysfunction (based on specific cutoffs for the FSFI score) was higher in women with than in women without endometriosis (OR 1.71; 95% CI, 1.21-2.43). In addition, when we used continuous scores to examine the risk of sexual dysfunction, diagnosis of endometriosis was associated with significantly lower overall FSFI scores (WMD, -3.40; 95% CI, -5.13 to -1.66) and lower scores on all of its 6 domains, ie, desire (WMD, -0.27; 95% CI, -0.53 to -0.02), arousal (WMD, -0.43; 95% CI, -0.79 to -0.07), lubrication (WMD, -0.49; 95% CI, -0.66 to -0.31), orgasm (WMD, -0.65; 95% CI, -1.07 to -0.23), satisfaction (WMD, -0.52; 95% CI, -0.77 to -0.26), and pain (WMD, -1.06; 95% CI, -1.57 to -0.55). Conclusion: The findings of this study suggest that female patients with endometriosis have suboptimal sexual function compared with healthy female subjects. Patients with endometriosis should be offered sexual counseling and supportive care by a multidisciplinary team of gynecologists, psychologists, and sexual therapists.

Detection of fungicide resistance to fludioxonil and tebuconazole in Fusarium pseudograminearum, the causal agent of Fusarium crown rot in wheat.

Fusarium crown rot (FCR) on wheat is a soil-borne disease that affects the yield and quality of the produce. In 2020, 297 Fusarium pseudograminearum isolates were isolated from diseased FCR wheat samples from eight regional areas across Hebei Province in China. Baseline sensitivity of F. pseudograminearum to fludioxonil (0.0613 ± 0.0347 µg/mL) and tebuconazole (0.2328 ± 0.0840 µg/mL) were constructed based on the in vitro tests of 71 and 83 isolates, respectively. The resistance index analysis showed no resistance isolate to fludioxonil but two low-resistance isolates to tebuconazole in 2020. There was an increased frequency of resistant isolates from 2021 to 2022 based on the baseline sensitivity for tebuconazole. There was no cross-resistance between fludioxonil and tebuconazole. This study provides a significant theoretical and practical basis for monitoring the resistance of F. pseudograminearum to fungicides, especially the control of FCR.

The value of luteinizing hormone basal values and sex hormone-binding globulin for early diagnosis of rapidly progressive central precocious puberty.

Objective: This study aimed to investigate the diagnostic value of luteinizing hormone (LH) basal values and sex hormone-binding globulin (SHBG) for rapidly progressive central precocious puberty (RP-CPP). Methods: A total of 121 girls presenting with secondary sexual characteristics were selected from the Department of Pediatric Endocrinology, Lianyungang Clinical Medical College of Nanjing Medical University, from May 2021 to June 2023. The children were followed up for 6 months and were divided into three groups: RP-CPP group (n=40), slowly progressive central precocious puberty (SP-CPP) group (n=40), and premature thelarche (PT) group (n=41). The differences in LH basal values and SHBG among girls in the three groups were compared. ROC curves were drawn to analyze the value of LH basal values and SHBG in identifying RP-CPP. Results: Significant differences were observed in age, height, predicted adult height (PAH), weight, body mass index (BMI), bone age (BA), BA-chronological age (CA), LH basal, LH peak, FSH basal, LH peak/FSH peak, estradiol (E2), testosterone, and SHBG levels between the RP-CPP group and the SP-CPP and PT groups (P < 0.05). The LH basal value in the RP-CPP group was higher than that in the SP-CPP group and the PT group, while SHBG levels were lower than in the latter two groups, and these differences were statistically significant (P < 0.05). When the LH basal value was ≥0.58 IU/L and SHBG was ≤58.79 nmol/L, the sensitivity for diagnosing RP-CPP was 77.5% and 67.5%, and the specificity was 66.7% and 74.1%. Conclusion: Detection of basal LH and SHBG levels allows for early diagnosis of the progression of central precocious puberty.

Clinical diagnostic value of liquid chromatography-tandem mass spectrometry method for primary aldosteronism in patients with hypertension: A systematic review and meta-analysis.

Background: Primary aldosteronism (PA) is currently considered the most common cause of secondary and endocrine hypertension. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a new detection technique has been gradually applied in the diagnosis of PA. However, the diagnostic value of LC-MS/MS methods for PA has not been systematically clinically validated. The aim was to access the diagnostic accuracy, sensitivity, and specificity of LC-MS/MS methods as screening tools in PA. Materials and methods: A literature search of PubMed, Embase, Medline, Web of Science, Scopus, Science Direct, and Chinese databases was carried out to June 2022 with no language restriction. Data on sensitivity and specificity and other evaluation indicators were extracted and pooled with STATA and Meta-disc software. Heterogeneity was evaluated and meta-regression and subgroup analysis was performed to elucidate sources of heterogeneity. Results: 12 studies of the diagnostic test were suitable and included in the meta-analysis. Pooled sensitivity, specificity, and diagnostic odds ratio were 0.89 (95% CI: 0.83-0.93), 0.87 (95% CI: 0.82-0.91), and 55 (95% CI: 28-110), respectively. Subgroup analysis assessed the diagnostic power of LC-MS/MS based on the type of detection index. ARR and PAC based on LC-MS/MS methods have the higher diagnostic value compared with other indices, diagnostic odds ratios were 121.65 (95% CI: 36.28-407.98) and 49.85 (95% CI: 24.87-99.93). There was considerable heterogeneity among studies. Conclusion: LC-MS/MS methods had higher accuracy and reliability in the diagnosis of primary aldosteronism. LC-MS/MS-based ARR and PAC can be further promoted and applied in the diagnosis of primary aldosteronism.

Characteristics of OGTT and Correlation Between the Insulin to C-Peptide Molar Ratio, HOMA-IR, and Insulin Antibodies in T2DM Patients.

Purpose: The purpose of our study was to analyze the characteristics of OGTT and the correlation between the insulin to C-peptide molar ratio (ICPR), HOMA-IR and insulin antibodies (IAs) in T2DM patients. Patients and Methods: A total of 77 T2DM patients were included and divided into the IA+ group (25 patients) and IA- group (52 patients). The values of serum glucose, insulin, and C-peptide testing during 2-h OGTT were summarized comparatively, and ROC was made to analyze the predictive value of ICPR for IAs. Results: At each time point of OGTT, there was no significant difference in serum glucose and C-peptide changes (p>0.05). Serum insulin levels in positive patients were elevated or not at different time points of the OGTT but ICPR was significantly different (P<0.05) in the two groups. Spearman correlation coefficient analysis showed that the presence of insulin antibodies was correlated with ICPR, but not with HOMA-IR, and ICPR-2h had a better prediction capacity (AUC=0.735, the optimal cutoff-point=0.11, Se=0.760, Sp=0.635). Conclusion: T2DM patients with IAs showed no difference in serum glucose and serum C-peptide changes, but elevated or not insulin levels on the OGTTs, compared with negative patients. ICPR-2h can be a preliminary diagnostic index to timely predict IAs in T2DM patients.

Prolonged low-salt immersion effectively controls Flavobacterium columnare infection in Murray cod Maccullochella peelii peelii.

A disease outbreak occurred in Murray cod Maccullochella peelii peelii in a recirculating aquaculture farm in Tianjin city, China, in 2019. Strain MRX-2019 was isolated and considered to be the etiological pathogen; it was identified as Flavobacterium columnare based on a 16S rDNA gene sequence analysis and physiological and biochemical tests. The effect of salinity on the growth of MRX-2019 was investigated in vitro. Salinity >4‰ (i.e. 6‰) inhibited MRX-2019 growth, whereas 8 and 10‰ salinity killed it. The effect of 4‰ salinity on F. columnare was not significant (p > 0.05). When MRX-2019-infected Murray cod were treated with 4, 6, or 8‰ salinity, the mortality rate was reduced by 8.9, 67.76, or 75.56%, respectively, compared with that of the control. However, the mortality rate increased by 7.77% at 10‰ salinity. In this study, we found that maintaining the fish in freshwater with 6-8‰ salinity effectively reduced the mortality of these fish when infected with F. columnare. The findings provide an environmentally friendly control strategy for columnaris disease in Murray cod.