Disruption of DNA-PKcs-mediated cGAS retention on damaged chromatin potentiates DNA damage-inducing agent-induced anti-multiple myeloma activity.

BACKGROUND: Targeting DNA damage repair factors, such as DNA-dependent protein kinase catalytic subunit (DNA-PKcs), may offer an opportunity for effective treatment of multiple myeloma (MM). In combination with DNA damage-inducing agents, this strategy has been shown to improve chemotherapies partially via activation of cGAS-STING pathway by an elevated level of cytosolic DNA. However, as cGAS is primarily sequestered by chromatin in the nucleus, it remains unclear how cGAS is released from chromatin and translocated into the cytoplasm upon DNA damage, leading to cGAS-STING activation. METHODS: We examined the role of DNA-PKcs inhibition on cGAS-STING-mediated MM chemosensitivity by performing mass spectrometry and mechanism study. RESULTS: Here, we found DNA-PKcs inhibition potentiated DNA damage-inducing agent doxorubicin-induced anti-MM effect by activating cGAS-STING signaling. The cGAS-STING activation in MM cells caused cell death partly via IRF3-NOXA-BAK axis and induced M1 polarization of macrophages. Moreover, this activation was not caused by defective classical non-homologous end joining (c-NHEJ). Instead, upon DNA damage induced by doxorubicin, inhibition of DNA-PKcs promoted cGAS release from cytoplasmic chromatin fragments and increased the amount of cytosolic cGAS and DNA, activating cGAS-STING. CONCLUSIONS: Inhibition of DNA-PKcs could improve the efficacy of doxorubicin in treatment of MM by de-sequestrating cGAS in damaged chromatin.

The ratio of serum urea nitrogen to albumin is a better predictor of OS in MM patients than urea nitrogen alone.

Introduction Multiple myeloma (MM) is a malignant proliferative disease of plasma cells. Abnormally cloned plasma cells secrete large amounts of monoclonal immunoglobulins in the bone marrow of MM patients. Serum urea nitrogen (sUN) is a byproduct of protein metabolism, and its effect on MM patients' prognoses remains unknown. Therefore, we analysed MM patients' clinical data to explore the role of sUN and serum urea nitrogen/serum albumin (sUAR) in the baseline tumor load and MM prognosis of MM patients. Methods We downloaded the clinical data of 762 MM patients from the MMRF database. After excluding those without baseline sUN, 452 patients were finally included in the study. Smoothed curve fitting, threshold analysis, Tamhane's T2 test, multivariate adjusted Cox regression analysis, Kaplan‒Meier (K-M) curves, and receiver operating characteristic (ROC) analysis were applied in the study. Results There were 452 newly diagnosed MM patients included in this study. In most patient groups, sUN and sUAR were positively linked with ß2-microglobulin (ß2-MG) and lactic dehydrogenase (LDH) according to smoothing curve fitting and threshold analysis. The higher the ISS stage, the greater the values of sUN and sUAR. Furthermore, smoothed curve fitting and threshold analysis showed that sUN was correlated with OS, although sUAR had a stronger correlation with OS and could be applied to a broader group. The results of a multivariate adjusted Cox regression analysis demonstrated that sUN and sUAR were independent prognostic factors for OS. The K-M curve confirmed the correlation between higher sUN and sUAR levels and worse OS. ß2-MG and LDH are generally recognized prognostic factors of OS. ROC analysis revealed that sUN might boost ß2-MG and LDH's predictive value and sUAR had a higher predictive value. Conclusion This retrospective study based on the MMRF database showed that high sUN and sUAR levels were positively associated with ß2-MG, LDH, and ISS staging, and sUAR exhibited a stronger correlation with OS than sUN alone.

Effects and mechanisms of endocrine disruptor bisphenol AF on male reproductive health: A mini review.

Bisphenol AF (BPAF), an analogue of bisphenol A (BPA), is commonly found in manufacturing industries and known for its endocrine-disrupting properties. Despite potential similarities in adverse effects with BPA, limited toxicological data exist specifically for BPAF and its impact on male reproductive physiology. This mini-review aims to elucidate the influence of BPAF on the male reproductive system, focusing on estrogenic effects, effects on the hypothalamus-pituitary-gonad (HPG) axis, steroidogenesis, spermatogenesis, and transgenerational reproductive toxicity. Additionally, we outline the current insights into the potential mechanisms underlying BPAF-induced male reproductive disorders. BPAF exposure, either directly or maternally, has been associated with detrimental effects on male reproductive functions, including damage to the blood-testis barrier (BTB) structure, disruptions in steroidogenesis, testis dysfunction, decreased anogenital distance (AGD), and defects in sperm and semen quality. Mechanistically, altered gene expression in the HPG axis, deficits in the steroidogenesis pathway, activation of the aromatase pathway, cascade effects induced by reactive oxygen species (ROS), activation of ERK signaling, and immunological responses collectively contribute to the adverse effects of BPAF on the male reproductive system. Given the high prevalence of male reproductive issues and infertility, along with the widespread environmental distribution of bisphenols, this study provides valuable insights into the negative effects of BPAF. The findings underscore the importance of considering the safe use of this compound, urging further exploration and regulatory attention to decrease potential risks associated with BPAF exposure.

The relationship between longer leukocyte telomeres and dNCR in non-cardiac surgery patients: a retrospective analysis.

BACKGROUND: Cognitive decline following surgery is a common concern among elderly individuals. Leukocyte telomere length (LTL) can be assessed as a biological clock connected to an individual lifespan. However, the mechanisms causing this inference are still not fully understood. As a result of this, LTL has the potential to be useful as an aging-related biomarker for assessing delayed neurocognitive recovery (dNCR) and related diseases. METHODS: For this study, 196 individuals over 60 who were scheduled due to major non-cardiac surgical operations attended neuropsychological testing before surgery, followed by additional testing one week later. The finding of dNCR was based on a measured Z-score ≤ -1.96 on two or more separate tests. The frequency of dNCR was presented as the primary outcome of the study. Secondly, we evaluated the association between dNCR and preoperative LTL. RESULTS: Overall, 20.4% [40/196; 95% confidence interval (CI), 14.7-26.1%] of patients exhibited dNCR 1-week post-surgery. Longer LTL was identified as a predictor for the onset of early cognitive impairment resulting in postoperative cognitive decline [odds ratio (OR), 14.82; 95% CI, 4.01-54.84; P < 0.001], following adjustment of age (OR, 12.33; 95% CI, 3.29-46.24; P < 0.001). The dNCR incidence based on LTL values of these patients, the area under the receiver operating characteristic (ROC) curve was 0.79 (95% CI, 0.722-0.859; P < 0.001). At an optimal cut-off value of 0.959, LTL values offered respective specificity and sensitivity values of 64.7% and 87.5%. CONCLUSIONS: In summary, the current study revealed that the incidence of dNCR was strongly associated with prolonged LTL. Furthermore, this biomarker could help identify high-risk patients and offer insight into the pathophysiology of dNCR.

Prenatal exposure to bisphenol AF induced male offspring reproductive dysfunction by triggering testicular innate and adaptive immune responses.

As an emerging endocrine-disrupting component with a chemical structure related to Bisphenol A (BPA), Bisphenol AF (BPAF) has become widely distributed in the environment and human surroundings. Although numerous studies have focused on its reproductive toxicity, the impact of prenatal BPAF exposure on the reproductive system of adult male offspring, particularly testicular morphology and function, as well as the underlying mechanisms, remains largely understudied. This study found prenatal BPAF exposure at a dose of 300 µg/kg b.w. induced a 32% loss of seminal vesicle weight, a 12% reduction in the anogenital distance index (AGI), and impairments to testicular morphology, such as a reduced diameter of seminiferous tubules and thickness of the seminiferous epithelium, as well as a more than 2 - fold decrease in testosterone level, and 41% and 19% reduction of sperm count and vitality, respectively, in the 10 week-old male offsprings. Testicular RNA-Seq data showed that 334 differential expressed genes (DEGs) were primarily involved in several immunological processes, including host defense response, innate and adaptive immune response, cellular response to interferon (IFN)-ß and γ, antigen processing and presentation, regulation of T cell activation, etc. Importantly, our results revealed a pattern recognition receptor - absent in melanoma-2 (Aim2) was significantly increased in the testes of exposed males, thus triggering a testicular innate antiviral immunological response, leading to an increase of F4/80+ and CD11b+ macrophage. Subsequently, Aim2 activated the downstream signaling nuclear factor kappa-B (NF-κB), stimulated the transcription of IFN-ß and -γ, and then induced cytokine production while upregulating MHC class II molecules to activate CD4+ and CD8+ Tcells, suggesting that an adaptive immune response was also elicited. The results demonstrated that prenatal BPAF exposure could provoke innate and adaptive immunological responses in the testes of adult males through the Aim2-NF-κB-IFNs signaling pathway. Our work provided insights into understanding the reproductive toxicity caused by BPAF and clarified the possible mechanisms, which offered a potential therapeutic target and treatment strategy for BPAF exposure-induced reproductive dysfunction.

[The impact of anxiety levels in male soldiers with infertility on stress coping strategies and the quality of fertility life].

OBJECTIVE: To explore and analyze the correlation between anxiety levels, coping strategies, and fertility quality of life in male soldiers with infertility. METHODS: A questionnaire survey was conducted on 480 male soldiers with infertility who visited the Reproductive Medicine Department of the Eastern Theater Command General Hospital from June 2022 to February 2023, analyze the impact of anxiety levels on stress coping strategies and fertility quality of life in male officers and soldiers with infertility. RESULTS: Self evaluation scale score is (43.06 ± 15.02), Fertility Quality of Life Scale score is （52.11 ± 36.68）, Trait Coping Style Questionnaire score is (48.45 ± 23.15). The relevant analysis results show that there is a negative correlation between the scores of the Self Rating Anxiety Scale and the Reproductive Quality of Life Scale, a positive correlation between the scores of the Self Rating Anxiety Scale and the Trait Coping Style Questionnaire, and a positive correlation between the scores of the Reproductive Quality of Life Scale and the Trait Coping Style Questionnaire. The results of multiple regression analysis showed that years of infertility, history of childbirth, anxiety level, and coping strategies entered the regression equation. The anxiety level of male officers and soldiers with infertility has a mediating effect on the relationship between stress coping styles and quality of life during childbirth. CONCLUSION: The mental health status of male officers and soldiers with infertility is poor, and their coping strategies and quality of life during childbirth are at a moderate to low level. This indicates that more attention should be paid to the special group of male officers and soldiers with infertility, and psychological intervention should be strengthened in routine treatment. Provide support from different perspectives to address concerns and enhance the combat effectiveness of the military.

Endophytic fungus Pseudodidymocyrtis lobariellae KL27 promotes taxol biosynthesis and accumulation in Taxus chinensis.

BACKGROUND: Taxol from Taxus species is a precious drug used for the treatment of cancer and can effectively inhibit the proliferation of cancer cells. However, the growth of Taxus plants is very slow and the content of taxol is quite low. Therefore, it is of great significance to improve the yield of taxol by modern biotechnology without destroying the wild forest resources. Endophytic fungus which symbiosis with their host plants can promote the growth and secondary metabolism of medicinal plants. RESULTS: Here, an endophytic fungus KL27 was isolated from T. chinensis, and identified as Pseudodidymocyrtis lobariellae. The fermentation broth of KL27 (KL27-FB) could significantly promote the accumulation of taxol in needles of T. chinensis, reaching 0.361 ± 0.082 mg/g·DW (dry weight) at 7 days after KL27-FB treatment, which is 3.26-fold increase as compared to the control. The RNA-seq and qRT-PCR showed that KL27-FB could significantly increase the expression of key genes involved in the upstream pathway of terpene synthesis (such as DXS and DXR) and those in the taxol biosynthesis pathway (such as GGPPS, TS, T5OH, TAT, T10OH, T14OH, T2OH, TBT, DBAT and PAM), especially at the early stage of the stimulation. Moreover, the activation of jasmonic acid (JA) biosynthesis and JA signal transduction, and its crosstalk with other hormones, such as gibberellin acid (GA), ethylene (ET) and salicylic acid (SA), explained the elevation of most of the differential expressed genes related to taxol biosynthesis pathway. Moreover, TF (transcriptional factor)-encoding genes, including MYBs, ethylene-responsive transcription factors (ERFs) and basic/helix-loop-helix (bHLH), were detected as differential expressed genes after KL27-FB treatment, further suggested that the regulation of hormone signaling on genes of taxol biosynthesis was mediated by TFs. CONCLUSIONS: Our results indicated that fermentation broth of endophytic fungus KL27-FB could effectively enhance the accumulation of taxol in T. chinensis needles by regulating the phytohormone metabolism and signal transduction and further up-regulating the expression of multiple key genes involved in taxol biosynthesis. This study provides new insight into the regulatory mechanism of how endophytic fungus promotes the production and accumulation of taxol in Taxus sp.

Near work induces myopia in Guinea pigs.

The association between near work activities and myopia has not been clearly established. This study establishes a model for near work myopia (NWM) induced by short viewing distance in guinea pigs with a carefully controlled visual environment, and evaluates the effect of viewing distance in myopia development. Pigmented guinea pigs (3 weeks old) were randomly assigned to 3 groups: near work (NW)-, form-deprivation (FD)-, and -4D hyperopic-defocus (HD)-induced myopia. Animals in NW groups were kept in cylindrical cages with vertical square-wave gratings, providing short- (S, d = 18 cm), middle- (M, d = 44 cm), and long- (L, d = 88 cm) mean viewing distances, all at the same illuminance, during daily treatment for 14 days. Biometric parameters, including refraction, anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD), and axial length (AL), were measured at the beginning and end of 14 days' treatment. Choroidal thickness (ChT) and choroidal blood perfusion (ChBP) were measured by optical coherence tomography (OCT) and OCT-angiography (OCTA), respectively, at the end of treatment. Refraction was shifted towards myopia in the S-cage group, compared with the M- and L-cage groups; refractions in the L-, M- and S-cage groups were 5.19 ± 0.65 D, 4.30 ± 0.64 D, and 0.53 ± 0.61 D, respectively (p < 0.001). VCD and AL in the S-cage group increased in parallel with the myopic shift (L vs M vs S: VCD: 3.15 ± 0.02 mm vs 3.17 ± 0.02 mm vs 3.26 ± 0.02 mm, p < 0.001; AL: 7.99 ± 0.03 mm vs 8.03 ± 0.03 mm vs 8.15 ± 0.02 mm, p = 0.001). In FD and HD eyes, changes similar to those in the S-cage group (near-work group, NW) were seen in refraction (NW vs FD vs HD: 5.36 ± 0.82 D vs -5.78 ± 0.44 D vs -4.96 ± 0.54 D, p = 0.734), ACD, LT, VCD and AL. Also, ChT and ChBP were significantly less in the S-cage group than in the M- and L-cage groups after 14 days' treatment (L vs M vs S: ChT: 74.84 ± 3.27 vs 76.07 ± 3.49 vs 61.95 ± 3.31, P = 0.002; ChBP: 48.32 ± 2.23 vs 48.66 ± 2.30 vs 38.14 ± 2.06, p = 0.002). Rearing in S-cages induced myopia in guinea pigs and correspondingly decreased ChBP and ChT. The present study provides objective evidence that short viewing distance could be a risk factor for myopia, and describes a useful model for studying the underlying mechanisms.

Characterisation of the gut microbial community of rhesus macaques in high-altitude environments.

BACKGROUND: The mammal intestinal microbiota is involved in various physiological processes and plays a key role in host environment adaption. However, for non-human primates (NHPs), little is known about their gut microbial community in high-altitude environments and even less about their adaption to such habitats. We characterised the gut microbial community of rhesus macaques from multiple high-altitude environments and compared it to those of low-altitude populations. RESULTS: We collected faecal samples of rhesus macaques from four high-altitude populations (above 3000 m) and three low-altitude populations (below 500 m). By calculating the alpha diversity index, we found that high-altitude populations exhibited a higher diversity. Statistical analysis of beta diversity indicated significant differences between high- and low-altitude populations. Significant differences were also detected at the phylum and family levels. At the phylum level, the high-altitude gut microbial community was dominated by Firmicutes (63.42%), while at low altitudes, it was dominated by Bacteroidetes (47.4%). At the family level, the high-altitude population was dominated by Ruminococcaceae (36.2%), while the low-altitude one was dominated by Prevotellaceae (39.6%). Some families, such as Christensenellaceae and Rikenellaceae, were consistently higher abundant in all high-altitude populations. We analysed the overlap of operational taxonomic units (OTUs) in high-altitude populations and determined their core OTUs (shared by all four high-altitude populations). However, when compared with the low-altitude core OTUs, only 65% were shared, suggesting a divergence in core OTUs. Function prediction indicated a significant difference in gene copy number of 35 level-2 pathways between high- and low-altitude populations; 29 of them were higher in high altitudes, especially in membrane transport and carbohydrate metabolism. CONCLUSIONS: The gut microbial community of high-altitude rhesus macaques was significantly distinct from that of low-altitude populations in terms of diversity, composition and function. High-altitude populations were dominated by Firmicutes and Ruminococcace, while in low-altitude populations, Bacteroidetes and Prevotellaceae were dominant. The difference in gut microbiota between these two populations may be caused by differences in host diet, environmental temperature and oxygen pressure. These differentiated gut microbial microorganisms may play a critical role in the adaptive evolution of rhesus macaques to high-altitude environments.

Puerarin Decreases Collagen Secretion in AngII-Induced Atrial Fibroblasts Through Inhibiting Autophagy Via the JNK-Akt-mTOR Signaling Pathway.

Puerarin is used to treat cardiovascular diseases due to its anti-inflammatory and antifibrotic effects. However, its mechanism of action in atrial fibroblasts is unknown. In this study, we investigated the autophagy pathway and molecular changes in angiotensin II (AngII)-stimulated atrial fibroblasts in response to puerarin treatment. Atrial fibroblasts were cultured and then subjected to stimulation with AngII and puerarin or other chemical drugs (3-MA, CQ, and SP600125). Quantitative real-time polymerase chain reaction and Western blot experiments were used to quantify the expression levels of mRNA and protein. mCherry-GFP-LC3 adenovirus was applied to reflect the autophagic flux. The results showed aggravating levels of autophagy and collagen deposit in the presence of AngII. Puerarin inhibited autophagy and decreased collagen secretion in a dose-dependent manner in atrial fibroblasts. Furthermore, phosphorylation of JNK was down-regulated in response to puerarin, whereas phosphorylation of Akt and mammalian target of rapamycin (mTOR) was upregulated. Interestingly, reduced autophagy and collagen secretion were observed when the JNK signaling pathway was blocked using SP600125. We also observed upregulation of Akt and mTOR phosphorylation in the presence of SP600125. These results suggest that puerarin exerts its antifibrotic effect in atrial fibroblasts partly through the inhibition of autophagy. Furthermore, the mechanism of action of puerarin in fibroblast autophagy seems to be mediated partly through JNK-Akt-mTOR signaling.

Preoperative Salivary Cortisol AM/PM Ratio Predicts Early Postoperative Cognitive Dysfunction After Noncardiac Surgery in Elderly Patients.

BACKGROUND: The diagnosis of postoperative cognitive dysfunction (POCD) requires complicated neuropsychological testing and is often delayed. Possible biomarkers for early detection or prediction are essential for the prevention and treatment of POCD. Preoperative screening of salivary cortisol levels may help to identify patients at elevated risk for POCD. METHODS: One hundred twenty patients >60 years of age and undergoing major noncardiac surgery underwent neuropsychological testing 1 day before and 1 week after surgery. Saliva samples were collected in the morning and the evening 1 day before surgery. POCD was defined as a Z-score of ≤-1.96 on at least 2 different tests. The primary outcome was the presence of POCD. The primary objective of this study was to assess the relationship between the ratio of AM (morning) to PM (evening) salivary cortisol levels and the presence of POCD. The secondary objective was to assess the relationship between POCD and salivary cortisol absolute values in the morning or in the evening. RESULTS: POCD was observed in 17.02% (16 of 94; 95% confidence interval [CI], 9.28%-24.76%) of patients 1 week after the operation. A higher preoperative AM/PM salivary cortisol ratio predicted early POCD onset (odds ratio [OR], 1.56; 95% CI, 1.20-2.02; P = .001), even after adjusting for the Mini-Mental Sate Examination score (odds ratio, 1.55; 95% CI, 1.19-2.02; P = .001). The area under the receiver operating characteristic curve for the salivary cortisol AM/PM ratio in individuals with POCD was 0.72 (95% CI, 0.56-0.88; P = .006). The optimal cutoff value was 5.69, with a sensitivity of 50% and specificity of 91%. CONCLUSIONS: The preoperative salivary cortisol AM/PM ratio was significantly associated with the presence of early POCD. This biomarker may have potential utility for screening patients for an increased risk and also for further elucidating the etiology of POCD.

Comparison of a loading dose of dexmedetomidine combined with propofol or sevoflurane for hemodynamic changes during anesthesia maintenance: a prospective, randomized, double-blind, controlled clinical trial.

BACKGROUND: There may be great individual variability in the hemodynamic effects of this dexmedetomidine. For this reason, the dose must be carefully adjusted to achieve the desired clinical effect. Whether a loading dose of dexmedetomidine produces hemodynamic side effects during the anesthesia maintenance is unknown. The aim of this study was to compare the effects of a loading dose of dexmedetomidine combined with propofol or sevoflurane on hemodynamics during anesthesia maintenance. METHODS: Eighty-four patients who were scheduled for general surgery under balanced general anesthesia were randomly allocated into 4 groups (n = 21): the propofol and dexmedetomidine group, the sevoflurane and dexmedetomidine group, the propofol and normal saline group, or the sevoflurane and normal saline group. The hemodynamic indexes at the time of just before, 5 min after and the end of study drug infusion (dexmedetomidine or normal saline) were recorded. The incidence rates of increasing blood pressure at the end of study drug infusion (greater than 20% compared to baseline or before study drug infusion) were evaluated. RESULTS: Mean arterial pressure increased significantly (P < 0.01) only in the propofol and dexmedetomidine group after intravenous dexmedetomidine compared administration. 80% of cases with propofol and dexmedetomidine had increased mean arterial blood pressure compared to only 5% of cases in the sevoflurane and dexmedetomidine group (P < 0.05). Heart rates in the propofol and dexmedetomidine and the sevoflurane and dexmedetomidine groups decreased significantly after dexmedetomidine infusion (P < 0.01). CONCLUSIONS: Intraoperative administration of a loading dose of dexmedetomidine combined with propofol in anesthesia maintenance proceeded a significant increase in blood pressure. In contrast, it combines with sevoflurane didn't produce increased blood pressure. Meanwhile it is not unexpected that dexmedetomidine combined with propofol or sevofurance decreased heart rate, due to the known side effects of DEX. Therefore, dexmedetomidine should be used cautiously during the entire intravenous anesthesia maintenance period, especially during maintenance with propofol. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IOR-17010423 , registered on 13 January 2017.

HJH-1, a Broad-Spectrum Antimicrobial Activity and Low Cytotoxicity Antimicrobial Peptide.

With the overuse of antibiotics, multidrug-resistant bacteria pose a significant threat to human health. Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics. This study examines the antimicrobial and membrane activity of HJH-1, a cationic peptide derived from the hemoglobin α-subunit of bovine erythrocytes P3. HJH-1 shows potent antimicrobial activity against different bacterial species associated with infection and causes weaker hemolysis of erythrocytes, at least five times the minimum inhibitory concentration (MIC). HJH-1 has good stability to tolerance temperature, pH value, and ionic strength. The anionic membrane potential probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol [DiBAC4(3)] and propidium iodide are used as indicators of membrane integrity. In the presence of HJH-1 (1× MIC), Escherichiacoli membranes rapidly depolarise, whereas red blood cells show gradual hyperpolarisation. Scanning electron microscopy and transmission electron micrographs show that HJH-1 (1× MIC) damaged the membranes of Escherichia coli, Staphylococcus aureus, and Candida albicans. In conclusion, HJH-1 damages the integrity of the bacterial membrane, preventing the growth of bacteria. HJH-1 has broad-spectrum antibacterial activity, and these activities are performed by changing the normal cell transmembrane potential and disrupting the integrity of the bacterial membrane.

[Study on proficiency test for determination of aluminum in drinking water in 2016].

OBJECTIVE: To evaluate the capacity of national laboratories for determination of aluminum in drinking water using proficiency testing program. METHODS: The preparation method of the secondary standard materials were used as the reference for the sample preparation in this proficiency testing program. The homogeneity and stability of the samples were tested by single factor analysis of variance( ANOVA) and linear regression. The result provided by participant laboratories were analyzed by robust statistics and assessed using the Z-score. RESULTS: 590 laboratories throughout the country participated in the proficiency testing program. 533 laboratories, or 90. 3% of total participating laboratories, obtained satisfactory result. Results provided by 7 laboratories, or 1. 2% of total participating laboratories, were found to suggest doubts in their capacities. Finally, there were 50 laboratories, constituting 7. 6% of total participating laboratories, with result that were found to be outliers. CONCLUSION: The capacity of national laboratories for determination of aluminum in drinking water has been ranked as satisfactory according to statistical analysis of the proficiency testing program result. Only a small portion of the participants require further improvement in their capacities.

[Analysis results of proficiency test for determination of lindane in drinking water in 2016].

OBJECTIVE: To evaluate the capacity of national laboratories for determination of lindane in drinking water using proficiency testing program. METHODS: The preparation method of the secondary standard materials were used as the reference for the sample preparation in this proficiency testing program. The homogeneity and stability of the samples were tested by single factor analysis of variance( ANOVA) and linear regression. The result provided by participant laboratories were analyzed by robust statistics and assessed using the Z-score. RESULTS: 309 laboratories throughout the country participated in the proficiency testing program. 286 laboratories, or 92. 6% of total participating laboratories, obtained satisfactory result. Results provided by 10 laboratories, or 3. 2% of total participating laboratories, were found to suggest doubts in their capacities. Finally, there were 13 laboratories, constituting 4. 2% of total participating laboratories, with result that were found to be outliers. CONCLUSION: The capacity of national laboratories for determination of lindane in drinking water has been ranked as satisfactory according to statistical analysis of the proficiency testing program result. Only a small portion of the participants require further improvement in their capacities.

Combined spinal-epidural anesthesia for cesarean delivery in a patient with cor triloculare biventriculare.

BACKGROUND: Cor triloculare biventriculare accounts for approximately 0.31% of cases of congenital heart disease (CHD). Moreover, people with cor triloculare biventriculare always have shorter life spans, and cases of gestation are rare. There have been various related reports of cor triloculare biventriculare in recent years. CASE PRESENTATION: We described an emergency cesarean section of a 30-year-old, 38-weeks-pregnant woman suffering from cardiac insufficiency and fetal distress. Combined spinal-epidural anesthesia was performed safely, and a male baby was smoothly delivered 10 min after the procedure without any adverse outcome on the mother or newborn. After surgery, we advised that the patient submit to an echocardiogram examination, which revealed the congenital heart disease cor triloculare biventriculare. CONCLUSIONS: Combined spinal-epidural anesthesia was administered to a patient with cor triloculare biventricularethis with good effect, ensuring the patient's safety and meeting the need for emergency surgery.

Role of estrogen in treatment of female depression.

Depression is a neurological disorder that profoundly affects human physical and mental health, resulting in various changes in the central nervous system. Despite several prominent hypotheses, such as the monoaminergic theory, hypothalamic-pituitary-adrenal (HPA) axis theory, neuroinflammation, and neuroplasticity, the current understanding of depression's pathogenesis remains incomplete. Importantly, depression is a gender-dimorphic disorder, with women exhibiting higher incidence rates than men. Given estrogen's pivotal role in the menstrual cycle, it is reasonable to postulate that its fluctuating levels could contribute to the pathogenesis of depression. Estrogen acts by binding to a diversity of receptors, which are widely distributed in the central nervous system. An abundance of research has established that estrogen and its receptors play a crucial role in depression, spanning pathogenesis and treatment. In this comprehensive review, we provide an in-depth analysis of the fundamental role of estrogen and its receptors in depression, with a focus on neuroinflammation, neuroendocrinology, and neuroplasticity. Furthermore, we discuss potential mechanisms underlying the therapeutic effects of estrogen in the treatment of depression, which may pave the way for new antidepressant drug development and alternative treatment options.

Effect of early peri-operative arterial lactate concentration level ratios on post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a serious complication after hepatectomy and a major cause of death. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data of elevated INR level and hyperbilirubinemia on or after postoperative day 5. This study aims to propose a new indicator for the early clinical prediction of PHLF. METHODS: The peri-operative arterial lactate concentration level ratios were derived from time points within the 3 days before surgery and within POD1, the patients were divided into two groups: high lactate ratio group (≥ 1) and low lactate ratio group (< 1). We compared the differences in morbidity rates between the two groups. Utilized logistic regression analysis to identify the risk factors associated with PHLF development and ROC curves to compare the predictive value of lactate ratio and other liver function indicators for PHLF. RESULTS: A total of 203 patients were enrolled in the study. Overall morbidity and severe morbidity occurred in 64.5 and 12.8 per cent of patients respectively. 39 patients (19.2%) met the criteria for PHLF, including 15 patients (7.4%) with clinically relevant Post-hepatectomy liver failure (CR-PHLF). With a significantly higher incidence of PHLF observed in the lactate ratio ≥ 1 group compared to the lactate ratio < 1 group (n = 34, 26.8% vs. n = 5, 6.6%, P < 0.001). Multivariable logistic regression analysis revealed that a lactate ratio ≥ 1 was an independent predictor for PHLF (OR: 3.239, 95% CI 1.097-9.565, P = 0.033). Additionally, lactate ratio demonstrated good predictive efficacy for PHLF (AUC = 0.792). CONCLUSIONS: Early assessment of peri-operative arterial lactate concentration level ratios may provide experience in early intervention of complications in patients with hepatocellular carcinoma, which can reduce the likelihood of PHLF occurrence and improve patient prognosis.

Metabolic rearrangements and intratumoral heterogeneity for immune response in hepatocellular carcinoma.

Liver cancer is one of the most common malignant tumors globally. Not only is it difficult to diagnose, but treatments are scarce and the prognosis is generally poor. Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Aggressive cancer cells, such as those found in HCC, undergo extensive metabolic rewiring as tumorigenesis, the unique feature, ultimately causes adaptation to the neoplastic microenvironment. Intratumoral heterogeneity (ITH) is defined as the presence of distinct genetic features and different phenotypes in the same tumoral region. ITH, a property unique to malignant cancers, results in differences in many different features of tumors, including, but not limited to, tumor growth and resistance to chemotherapy, which in turn is partly responsible for metabolic reprogramming. Moreover, the different metabolic phenotypes might also activate the immune response to varying degrees and help tumor cells escape detection by the immune system. In this review, we summarize the reprogramming of glucose metabolism and tumoral heterogeneity and their associations that occur in HCC, to obtain a better understanding of the mechanisms of HCC oncogenesis.

Evaluation of the efficacy of the antimicrobial peptide HJH-3 in chickens infected with Salmonella Pullorum.

As a promising substitute for antibiotics, increasing attention has been given to the clinical application of antimicrobial peptides (AMPs). In this study, the mode of action of the HJH-3 against Salmonella Pullorum was investigated. The structure and properties of HJH-3 were examined in silico, and minimum inhibitory concentrations (MICs) were determined to evaluate its antimicrobial spectrum. The time-kill kinetics of HJH-3 was determined. The hemolytic activity of HJH-3 was determined by measuring the hemoglobin ultraviolet absorption value, and the cytotoxicity was determined using a CCK-8 kit. The protective effect of HJH-3 on chickens infected with S. Pullorum was evaluated in vivo. The results demonstrated that HJH-3 exhibited strong antibacterial activity against Gram-negative pathogens at MIC values of 1.5625-25 µg/mL and against Gram-positive pathogens at MIC values of 25-50 µg/mL. HJH-3 also showed activity against the Candida albicans (100 µg/mL) and Bacillus subtilis (6.25-12.5 µg/mL). HJH-3 at 100 µg/mL completely killed S. Pullorum after co-incubation for 6 h. Likewise, the hemolysis rate of CRBCs treated with 100 µg/mL HJH-3 (7.31%) was lower than that of CRBCs treated with 100 µg/mL pexiganan (40.43%). Although the hemolysis rate of CRBCs treated with 400 µg/mL HJH-3 was increased to 13.37%, it was much lower than that of 400 µg/mL pexiganan (57.27%). In regards to cytotoxicity, HJH-3 had almost no-effect on the CEF proliferation, pexiganan decreased CEFs proliferation from 56.93 to 31.00% when increasing the concentration from 50 to 200 µg/mL. In a chicken infection model, the results showed that the antibiotic prevention and HJH-3 prevention groups exhibited the best treatment effect, with the chickens being protected from the lethal dose of S. Pullorum, a decreased number of bacteria in the blood and spleen, and less pathological changes in intestinal segments. The prevention of infection by HJH-3 was similar to that by Ampicillin; the effect of treatment after infection was lower than that of treatment before infection, and the survival rate of infected chicks treated with HJH-3 was 70%, which was still higher than that of the infected chickens. These results suggest that HJH-3 has good clinical application potential and can be used as a substitute for antibiotics for the prevention and treatment of S. Pullorum infection.