[Association between sleep status in the first trimester and preterm birth].

Objective: To investigate the relationship between sleep status in the first trimester and preterm birth. Methods: Clinical data of pregnant women who received regular prenatal examination and delivered in Peking University Third Hospital from September 1, 2019 to June 10, 2020 were collected. The Pittsburgh sleep quality index (PSQI) was used to investigate their sleep status during 8-12 weeks of gestation, and the delivery outcomes were followed up. According to the gestational age at delivery and the cause of preterm birth, they were divided into full-term delivery group (204 cases), preterm birth group (13 cases) and spontaneous preterm birth group (9 cases). The correlation between the sleep status in the first trimester and preterm birth or spontaneous preterm birth was analyzed. Results: The median PSQI score of full-term delivery group was 4.0 points (3.0, 6.0 points), which was lower than those of preterm delivery group [6.0 points (4.0, 8.0 points)] and spontaneous preterm delivery group [7.0 points (4.0, 8.0 points)], and the differences were statistically significant (all P<0.05). The proportion of pregnant women with poor sleep quality (PSQI score>7 points) in full-term delivery group [14.2% (29/204)] was lower than those in preterm delivery group (5/13) and spontaneous preterm delivery group (4/9), and the differences were statistically significant (all P<0.05). Compared with the full-term delivery group [8.0 hours (7.0, 9.0 hours)], the preterm birth group [7.0 hours (7.0, 8.0 hours)] and spontaneous preterm birth group [7.0 hours (7.0, 8.0 hours)] had significantly shorter sleep duration at night (all P<0.05). Multivariate analysis showed that PSQI score in the first trimester was an independent risk factor for preterm birth (aOR=1.22, 95%CI: 1.02-1.45; P=0.026). Pregnancy with assisted reproductive technology (aOR=5.55, 95%CI: 1.22-25.31; P=0.027), gestational diabetes mellitus (aOR=9.27, 95%CI: 1.96-43.82; P=0.005), PSQI score in the first trimester (aOR=1.27, 95%CI: 1.01-1.58; P=0.039) were independent risk factors for spontaneous preterm birth. Conclusion: Attention should be paid to the decreased sleep quality in the first trimester, which might significantly increase the risk of preterm birth and spontaneous preterm birth.

[The interpretation of the updated American Urological Association guideline of interstitial cystitis/bladder pain syndrome in 2022].

In 2022, American Urological Association updated the guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). A significant change has been made in treatment recommendations. The updated guideline no longer divided treatments into first-line through sixth-line tiers. Instead, treatment is categorized into behavioral/non-pharmacologic, oral medicines, bladder instillations, procedures, and major surgery. This change emphasizes the heterogeneity of IC/BPS patients and the importance of individualized treatment, overturns traditional unreasonable ideas about hierarchical and progressive treatment, and encourages patients and physicians to make treatment decisions together. At the same time, the panel emphasized the importance of early implementation of cystoscopy in patients suspected of Hunner lesions and warned against the possibility of pentosan polysulfate causing a unique retinal pigmentary maculopathy. Urinary reconstruction surgery was considered to only be used as a last resort for the treatment of IC/BPS, and there is uncertainty about the overall balance between benefits and risks/burdens. The updated guideline provides a new understanding and decision-making basis for the diagnosis and treatment of IC/BPS. However, it should be noted that the clinical characteristics of Chinese patients should be considered in practice and the application of the guideline should be localized.

[Comparison of efficacy and safety between domestic immune checkpoint inhibitors and pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer].

Objective: To compare the efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. Methods: A retrospective analysis was conducted on the data of 1 241 patients with driver gene-negative, unresectable stage ⅢB to Ⅳ non-small cell lung cancer who were treated at the Hunan Cancer Hospital from January 1, 2017 to October 1, 2022. All patients received monotherapy or combination therapy with domestic immune checkpoint inhibitors or pembrolizumab. Among the 1 241 patients, there were 1 066 males and 175 females, with an age range of 14 to 84 years and a median age of 62 years. Among them, 67 patients received monotherapy with domestic immune checkpoint inhibitors, 695 patients received combination therapy with domestic immune checkpoint inhibitors, 102 patients received monotherapy with pembrolizumab, and 377 patients received combination therapy with pembrolizumab. The efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab monotherapy or combination therapy were compared. Results: In the immune checkpoint inhibitor monotherapy group, the objective response rate (ORR) using domestic immune checkpoint inhibitors and pembrolizumab was 43.3%(29/67) and 44.1%(45/102), respectively, and the disease control rate (DCR) was 79.1%(53/67) and 84.3%(86/102), respectively, with no statistically significant differences (both P>0.05). In the immune combination therapy group, the ORR using domestic immune checkpoint inhibitors and pembrolizumab was 60.9%(423/695) and 62.9%(237/377), respectively, and the DCR was 92.9%(646/695) and 91.0%(343/377), respectively, with no statistically significant differences (both P>0.05). In the immune checkpoint inhibitor monotherapy group, the median progression-free survival (PFS) using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 3.0-15.0) months and 7.4 (95%CI: 4.8-9.8) months, respectively, with no statistically significant differences (P=0.660). The median overall survival (OS) was 27.0 (95%CI: 25.0-29.0) months and 22.0 (95%CI: 17.1-26.9) months, respectively, with no statistically significant differences (P=0.673). In the immune combination therapy group, the median PFS using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 8.2-9.8) months and 10.5 (95%CI: 9.0-12.0) months, respectively, with no statistically significant differences (P=0.186). The median OS was 24.0 (95%CI: 19.1-28.9) months and 26.0 (95%CI: 21.3-30.7) months, respectively, with no statistically significant differences (P=0.359). The incidence of grade 1-2 reactive capillary proliferation of the skin in the domestic immune checkpoint inhibitor group and pembrolizumab group was 14.0% (107/762) and 0, respectively. The incidence of grade≥3 reactive capillary proliferation of the skin was 1.0% (7/762) and 0, respectively, with statistically significant differences (both P<0.05). No statistically significant differences were observed in other adverse reactions (all P>0.05). Conclusions: The efficacy of domestically produced immune checkpoint inhibitors is comparable to that of pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. There is little difference in safety, except for the specific difference in domestically produced immune checkpoint inhibitor, which has a unique risk of reactive cutaneous capillary endothelial proliferation.

Vegetation-fire feedbacks increase subtropical wildfire risk in scrubland and reduce it in forests.

Climate dictates wildfire activity around the world. But East and Southeast Asia are an apparent exception as fire-activity variation there is unrelated to climatic variables. In subtropical China, fire activity decreased by 80% between 2003 and 2020 amid increased fire risks globally. Here, we assessed the fire regime, vegetation structure, fuel flammability and their interactions across subtropical Hubei, China. We show that tree basal area (TBA) and fuel flammability explained 60% of fire-frequency variance. Fire frequency and fuel flammability, in turn, explained 90% of TBA variance. These results reveal a novel system of scrubland-forest stabilized by vegetation-fire feedbacks. Frequent fires promote the persistence of derelict scrubland through positive vegetation-fire feedbacks; in forest, vegetation-fire feedbacks are negative and suppress fire. Thus, we attribute the decrease in wildfire activity to reforestation programs that concurrently increase forest coverage and foster negative vegetation-fire feedbacks that suppress wildfire.

[Zellweger syndrome caused by PEX6 gene variation in 2 cases and literature review].

Objective: To summarize the clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation. Methods: This was a case series research. Clinical date and genetic results of 2 neonatal cases of Zellweger syndrome caused by PEX6 gene variation in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology and Affiliated Hospital of Guangdong Medical University from July 2021 to July 2022 were retrospectively collected and analyzed. Literature up to August 2023 was searched from electronic databases of China National Knowledge Infrastructure (CNKI), Wanfang Data and PubMed with the combined keywords of "Zellweger syndrome" "Zellweger spectrum disorder", and "PEX6 gene" both in Chinese and English. The main clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation were summarized. Results: The 2 male neonates both developed clinical manifestations as dyspnea, hypotonia, feeding difficulties, enlarged fontanelle, and high palatine arch after birth. Biochemical parameters indicated elevated bile acids, and the cranial ultrasound showed the enlarged bilateral ventricles and subependymal cyst in both 2 neonates. Zellweger syndrome was confirmed by whole exome sequencing, and the results revealed PEX6 gene variation in the 2 neonates, including compound heterozygous variants c.315G>A and c.2095-3T>G, and homozygous variant c.506_507del. Case 1 was hospitalized for 5 days, and case 2 for 32 days; they both died shortly after being discharged (the specific time is unknown). Literature review found 26 patients, including 2 neonates in this study, with Zellweger spectrum disorder caused by PEX6 gene defect reported in 1 Chinese article and 11 English articles. Clinical features included hearing loss (19 cases), developmental delay (19 cases), vision impairment (19 cases), elevated very long chain fatty acids (17 cases), brain malformations (15 cases), hypotonia (12 cases), hepatic insufficiency (12 cases), distinctive facies (10 cases), and dental impairment (9 cases). Compound heterozygous variations dominated the variation types (15 cases), and the frameshift variations (16 cases) were the main pathogenic variations. Conclusions: Zellweger spectrum disorder should be considered when neonates show hypotonia, feeding difficulty, distinctive facial appearance, brain malformations and failure of hearing screening, or when older children show retinitis pigmentosa, sensorineural hearing loss, amelogenesis imperfecta and developmental delays. Detection of genetic variation in the PEX gene is crucial for definitive diagnosis.

[Construction of natural population cohort on telephone follow-up management quality control system and discussion regarding critical issues by REDCap system].

With completing a baseline survey of a large natural population cohort, conducting regular follow-up has become a key factor in further improving the quality of cohort construction and ensuring its sustainable development. Typical cohort follow-up methods include repeat surveys, routine monitoring, and community-oriented surveillance. However, in practical applications, there are often issues such as high costs, difficulty, and high error rates. Telephone follow-up is an important supplementary method to the methods mentioned above, as it has the characteristics of low cost, fast response, and high quality. However, the with difficult organization, quality control is challenging, response rates are low, and management levels vary widely, which limits its widespread use in large-scale population cohort studies. Given the above problems, this study draws on customer relationship management based on the actual needs of the China Northwest Cohort follow-up. It relies on the REDCap electronic data collection platform to build a telephone follow-up management and quality control system. Targeted solutions are provided for key issues in telephone follow-up implementation, including organizational structure, project management, data collection, and process quality control, to improve the quality control level of telephone follow-up comprehensively and thereby enhance the quality and efficiency of follow-up. We hope to provide standardized follow-up programs and efficient quality control tools for newly established and existing cohort studies.

Pharmacological activity and clinical progress of Triptolide and its derivatives LLDT-8, PG490-88Na, and Minnelide: a narrative review.

Triptolide, a compound isolated from a Chinese medicinal herb, has potent antitumor, immunosuppressive, and anti-inflammatory properties. Due to its interesting structural features and diverse pharmacological activities, it has attracted great interest by the Society of Organic Chemistry and Pharmaceutical Chemistry. However, its clinical potential is greatly hampered by limited aqueous solubility and oral bioavailability, and multi-organ toxicity. In recent years, various derivatives of Triptolide have made varying degrees of progress in the treatment of inflammatory diseases, autoimmune diseases, and cancer. The most researched and potentially clinically valuable of them were (5R)-5-hydroxytriptolide (LLDT-8), PG490-88Na (F6008), and Minnelide. In this review, we provide an overview of the advancements made in triptolide and several of its derivatives' biological activity, mechanisms of action, and clinical development. We also summarized some prospects for the future development of triptolide and its derivatives. It is hoped to contribute to a better understanding of the progress in this field, make constructive suggestions for further studies of Triptolide, and provide a theoretical reference for the rational development of new drugs.

[Emodin alleviates joint inflammation and bone erosion in rats with collagen-induced arthritis by inhibiting ferroptosis and degrading matrix metalloproteinases].

OBJECTIVE: To investigate the osteoprotective mechanism of emodin in light of the ferroptosis signaling pathway in a rat model of rheumatoid arthritis. METHODS: SD rat models of collagen-induced arthritis (CIA) were treated with methotrexate or low or high doses of emodin, and the changes in arthritis scores and toe volume were recorded. model of CIA rats. Malondialdehyde (MDA) content in the joint cartilage was determined, and ankle joint tissue pathologies were observed using caffein solid green staining and hematoxylin-spermine red staining. MMP3 and MMP13 expressions in the ankle joint tissues were detected using immunohistochemistry, and Western blotting was used to detect the protein expressions of ACSL4, SLC7A11, GPX4, and FTH1. RESULTS: Compared with the normal control rats, the CIA rats showed significantly increased arthritis score index with obvious toe swelling (P<0.05), rough cartilage surface, and loss and irregular aligment of chondrocytes. The rat models also showed significantly increased MDA and ACSL4 contents, lowered SLC7A11, GPX4, and FTH1 contents (P<0.05), and decreased expressions of MMP3 and MMP13 in the ankle joint (P<0.05). The rat models treated with either methotrexate or emodin (40 and 80 mg/kg) had significantly reduced arthritis score index and toe swelling with smooth cartilage surface and neat arrangement of the chondrocytes. The treatments with methotrexate and emodin both decreased the contents of MDA and ACSL4 and increased the contents of SLC7A11, GPX4, and FTH1 in the joint tissues (P<0.05). CONCLUSION: Emodin can effectively control joint inflammation and improve joint bone erosion in CIA rats possibly by inhibiting the ferroptosis signaling pathways and reducing the expressions of MMP3 and MMP13.

[Effects of propofol on myelin basic protein expression in zebrafish at different developmental stages].

OBJECTIVE: To observe the effect of propofol on the expression of myelin basic protein (MBP) in developing zebrafish and explore the possible mechanisms. METHODS: A total of 180 zebrafish embryos at 6-48 h post-fertilization were randomly allocated into 3 equal groups and raised in fresh water (control group), water containing dimethyl sulfoxide (DMSO group) and water containing 30 µg/mL propofol (propofol group). On 3, 4, 5, 6, 7, 10 d post-fertilization, the juvenile fish were collected for detection of mRNA and protein expressions of MBP using RT-qPCR and Western blotting. TUNEL assay and immunofluorescence assay were used to detect apoptosis of the oligodendrocytes of the fish at 3 d post-fertilization; RT-qPCR and Western blotting were performed to detect the expressions of apoptosis-related factors caspase-8, caspase-9 and caspase-3. RESULTS: Compared with the control group, the fish with propofol exposure showed significantly decreased mRNA and protein expression of MBP at 3-7 d post-fertilization (P<0.05) with increased apoptosis of the oligodendrocytes and upregulated expressions of caspase-8, caspase-9 and caspase-3 at both the mRNA and protein levels. CONCLUSION: Propofol persistently inhibits MBP expression in developing zebrafish within a short term possibly by mediating apoptosis of the oligodendrocytes.

[A cross-sectional survey and influencing factors analysis of knowledge, attitude, and behavior of enteral nutrition implemented by nurses in burn intensive care unit].

Objective: To investigate the status of knowledge, attitude, and behavior of enteral nutrition implemented by nurses in burn intensive care unit (BICU) and analyze its influencing factors. Methods: A multi-center cross-sectional survey research method was used. On May 8th, 2022, 107 BICU nurses who met the inclusion criteria were selected from the burn departments of the First Affiliated Hospital of Army Medical University (the Third Military Medical University), Guangdong Provincial People's Hospital, the First Affiliated Hospital of Guangxi Medical University, the Affiliated Hospital of Qinghai University, the Second Affiliated Hospital of Air Force Medical University, the Affiliated Hospital of Nantong University, Guiyang Steel Factory Staff Hospital, and the Second Affiliated Hospital of Kunming Medical University. The self-made nurses' enteral nutrition nursing knowledge-attitude-behavior questionnaire for severely burned patients was used to investigate the nurses' gender, age, working years, professional title, position, highest educational background, and whether they received systematic training in knowledge of enteral nutrition, the scores of each factor, and the total scores of knowledge, attitude, and behavior dimensions of enteral nutrition in nurses. The nurses were classified according to the general data, and the total scores of their knowledge, attitude, and behavior of enteral nutrition were calculated. Data were statistically analyzed with independent sample t test, one-way analysis of variance, Mann-Whitney U test, and Kruskal-Wallis H test. According to the results of univariate analysis and combined with clinical experience and significance, the generalized linear model analysis was carried out to screen the independent influencing factors of the total scores of knowledge, attitude, and behavior of enteral nutrition in BICU nurses. Results: A total of 107 nurses were surveyed, and 107 valid questionnaires were collected, with an effective recovery rate of 100%. In the BICU nurses' enteral nutrition knowledge-attitude-behavior questionnaire, the total scores of knowledge, attitude, and behavior were 44±13, 87±15, and 70±19, respectively. Most of the BICU nurses in this survey were female, aged 22-48 (31±6) years, and the number of nurses worked for 1-5, 6-10, and ≥11 years was evenly distributed. The majority of the professional titles of nurses were nurses, positions were responsible nurses, and the highest educational background was undergraduate. Forty-four nurses received systematic training in knowledge of enteral nutrition. There were statistically significant differences in the total scores of knowledge of enteral nutrition among BICU nurses with different ages, working years, professional titles, positions, highest educational background, and whether they received systematic training in knowledge of enteral nutrition (with H values of 27.36, 15.27, and 10.19, respectively, Z values of -3.33, -2.59, and -6.46, respectively, P<0.05). There were no statistically significant differences in the total scores of attitude and behavior of enteral nutrition among BICU nurses with different gender, ages, working years, professional titles, positions, highest educational background, and whether they received systematic training in knowledge of enteral nutrition (P>0.05). Age (26-30, 31-35, and ≥36 years old), highest educational background (undergraduate), and the systematic training received in enteral nutrition knowledge were the independent influencing factors for the total score of knowledge of enteral nutrition in BICU nurses (with 95% confidence intervals of 0.12-0.36, 0-0.30, 0.03-0.31, 0.01-0.32, and 0.19-0.40, respectively, standardized regression coefficients of 0.24, 0.15, 0.17, 0.17, and 0.29, respectively, P<0.05). There were no independent influencing factors for the total scores of enteral nutrition attitude and behavior of BICU nurses in different characteristics (P>0.05). Conclusions: The BICU nurses have low cognitive level in the implementation of enteral nutrition, their concept needs to be updated in time, and their behavior needs to be further standardized. Age (26-30, 31-35, and ≥36 years old), highest educational background (undergraduate), and the systematic training received in enteral nutrition knowledge were the independent influencing factors for the knowledge of enteral nutrition in BICU nurses.

[The effect of platelet infusion on the repair of bone marrow hematopoietic niche damage in mice induced by (60)Co radiation and hematopoietic reconstruction after bone marrow transplantation].

Objective: To observe the effect of platelets on hematopoietic stem cell (HSCs) implantation in mice with radiation-induced bone marrow injury and bone marrow transplantation models. Methods: ①Male C57BL/6 mice were divided into a single irradiation group and a radiation infusion group after receiving (60)Co semimyeloablative irradiation for 18-10 weeks. The irradiation infusion group received 1×10(8) platelets expressing GFP fluorescent protein. ② The allogeneic bone marrow transplantation model was established. The experimental groups included the simple transplantation group (BMT) and the transplantation infusion group (BMT+PLT). The BMT group was infused through the tail vein only 5 × 10(6) bone marrow cells, the BMT+PLT group needs to be infused with bone marrow cells at the same time 1× 10(8) platelets. ③ Test indicators included peripheral blood cell and bone marrow cell counts, flow cytometry to detect the proportion of hematopoietic stem cell (HSC) and hematopoietic progenitor cells, bone marrow cell proliferation and apoptosis, and pathological observation of vascular niche damage and repair. Results: ①On the 3rd, 7th, 14(th), and 21st days after irradiation, the bone marrow cell count of the infusion group was higher than that in the single irradiation group (P<0.05), and the peripheral blood cell count was also higher. A statistically significant difference was found between the white blood cell count on the 21st day and the platelet count on the 7th day (P<0.05). In the observation cycle, the percentage of bone marrow cell proliferation in the infusion group was higher, while the percentage of apoptosis was lower. ② The results of bone tissue immunofluorescence after irradiation showed that the continuity of hematopoietic niche with red fluorescence was better in the irradiation infusion group. ③The chimerism percentage in the BMT+PLT group was always higher than that in the BMT group after transplantation.④ The BMT+PLT group had higher bone marrow cell count and percentage of bone marrow cell proliferation on the 7th and 28th day after transplantation than that in the BMT group, and the percentage of bone marrow cell apoptosis on the 14th day was lower than that in the BMT group (P<0.05). After the 14th day, the percentage of stem progenitor cells in the bone marrow cells of mice was higher than that in the BMT group (P<0.05). ⑤The immunohistochemical results of bone marrow tissue showed that the continuity of vascular endothelium in the BMT+PLT group was better than that in the BMT group. Conclusion: Platelet transfusion can alleviate the injury of vascular niche, promotes HSC homing, and is beneficial to hematopoietic reconstruction.

A photo-controlled, all-solid, and frequency-tunable ultra-wideband pulse generator.

With the continuous exploration of the bioelectric effect, nanosecond and picosecond pulsed electric fields used in cancer therapy and drug introduction have attracted great attention. In this paper, an ultrashort pulsed electric field generator is proposed, which connects two photoconductive semiconductor switches in parallel to generate unipolar and bipolar pulses. We described the experimental scheme of the generator and the simulation of the radio frequency combiner. A 532 nm laser with pulse widths of 1 ns and 500 ps is used to trigger the photoconductive semiconductor switches. The experimental results show that the scheme can achieve adjustments of 357 and 720 MHz for the center frequency and the 3 dB bandwidth, respectively. The results confirm that this proposed scheme can be used for unipolar/bipolar frequency-adjustable ultra-wideband pulse generation.

Anaemia prevalence and risk factors among children aged 6 to 23 months in rural China.

INTRODUCTION: Anaemia is a global public health problem among children. However, few studies have examined anaemia prevalence and risk factors among Chinese children of different ages, particularly in poor rural areas. This study investigated these two aspects among children aged 6 to 23 months in poor rural areas of China. METHODS: This cross-sectional study included 1132 children aged 6 to 23 months in three prefectures of the Qinba Mountains area. A finger prick blood test for haemoglobin and anaemia was conducted, along with household surveys of socio-demographic characteristics, illness characteristics, and feeding practices. Multiple linear and logistic regression analyses were used to determine predictors of anaemia. RESULTS: Overall, 42.6% of children in the study displayed anaemia. Children aged 6 to 11 months had the highest anaemia prevalence (53.6%). Anaemia risk factors differed among age-groups and throughout the overall sample. Bivariate and multivariable regression results showed that continued breastfeeding, any history of formula feeding, and consumption of iron-rich or iron-fortified foods were prominent risk factors for anaemia. However, continued breastfeeding and any history of formula feeding had the greatest impact across age-groups (both P<0.05). CONCLUSION: Anaemia remains a severe public health problem among children aged 6 to 23 months in rural China. Healthy feeding practices, nutritional health knowledge, and nutrition improvement projects are needed to reduce the burden of anaemia among children in rural areas of China.

[Results analysis of mNGS applied to infectious diseases].

The application of metagenomic second-generation sequencing (mNGS) is shifting from research to clinical laboratories due to rapid technological advances and significant cost reductions. Although many studies and case reports have confirmed that the success of mNGS in improving the prevention, diagnosis, treatment and tracking of infectious diseases, there are still some obstacles that must be overcome. The results of mNGS show all the possible pathogens in the sample, however, in the face of thousands of microbes that can infect humans, it remains challenging to accurately identify the key pathogens. So far, there is no unified interpretation standard for mNGS in clinical practice. This article reviews the interpretation of mNGS results for pathogen infection in different systems, the clinical interpretation and application regulations of mNGS results, and the challenges of mNGS interpretation in pathogen diagnosis.

A novel Doppler backscattering (DBS) system to simultaneously measure radio frequency plasma fluctuations and low frequency turbulence.

A novel quadrature Doppler Backscattering (DBS) system has been developed and optimized for the E-band (60-90 GHz) frequency range using either O-mode or X-mode polarization in DIII-D plasmas. In general, DBS measures the amplitude of density fluctuations and their velocity in the lab frame. The system can simultaneously monitor both low-frequency turbulence (f < 10 MHz) and radiofrequency plasma density fluctuations over a selectable frequency range (20-500 MHz). Detection of high-frequency fluctuations has been demonstrated for low harmonics of the ion cyclotron frequency (e.g., 2fci ∼ 23 MHz) and externally driven high-frequency helicon waves (f = 476 MHz) using an adjustable frequency down conversion system. Importantly, this extends the application of DBS to a high-frequency spectral domain while maintaining important turbulence and flow measurement capabilities. This unique system has low phase noise, good temporal resolution (sub-millisecond), and excellent wavenumber coverage (kθ ∼ 1-20 cm-1 and kr ≲ 30 cm-1). As a demonstration, localized internal DIII-D plasma measurements are presented from turbulence (f ≤ 5 MHz), Alfvenic waves (f ∼ 6.5 MHz), ion cyclotron waves (f ≥ 20 MHz), as well as fluctuations around 476 MHz driven by an external high-power 476 MHz helicon wave antenna. In the future, helicon measurements will be used to validate GENRAY and AORSA modeling tools for prediction of helicon wave propagation, absorption, and current drive location for the newly installed helicon current drive system on DIII-D.

Developmental programming: Impact of preconceptional and gestational exposure to a real-life environmental chemical mixture on maternal steroid, cytokine and oxidative stress milieus in sheep.

BACKGROUND: Gestational exposure to environmental chemicals (ECs) is associated with adverse, sex-specific offspring health effects of global concern. As the maternal steroid, cytokine and oxidative stress milieus can have critical effects on pregnancy outcomes and the programming of diseases in offspring, it is important to study the impact of real-life EC exposure, i.e., chronic low levels of mixtures of ECs on these milieus. Sheep exposed to biosolids, derived from human waste, is an impactful model representing the ECs humans are exposed to in real-life. Offspring of sheep grazed on biosolids-treated pasture are characterized by reproductive and metabolic disruptions. OBJECTIVE: To determine if biosolids exposure disrupts the maternal steroid, cytokine and oxidative stress milieus, in a fetal sex-specific manner. METHODS: Ewes were maintained before mating and through gestation on pastures fertilized with biosolids (BTP), or inorganic fertilizer (Control). From maternal plasma collected mid-gestation, 19 steroids, 14 cytokines, 6 oxidative stress markers were quantified. Unpaired t-test and ANOVA were used to test for differences between control and BTP groups (n = 15/group) and between groups based on fetal sex, respectively. Correlation between the different markers was assessed by Spearman correlation. RESULTS: Concentrations of the mineralocorticoids - deoxycorticosterone, corticosterone, the glucocorticoids - deoxycortisol, cortisol, cortisone, the sex steroids - androstenedione, dehydroepiandrosterone, 16-OH-progesterone and reactive oxygen metabolites were higher in the BTP ewes compared to Controls, while the proinflammatory cytokines IL-1ß and IL-17A and anti-inflammatory IL-36RA were decreased in the BTP group. BTP ewes with a female fetus had lower levels of IP-10. DISCUSSION: These findings suggest that pre-conceptional and gestational exposure to ECs in biosolids increases steroids, reactive oxygen metabolites and disrupts cytokines in maternal circulation, likely contributors to the aberrant phenotypic outcomes seen in offspring of BTP sheep - a translationally relevant precocial model.

Targeting the post-synaptic proteome has therapeutic potential for psychosis in Alzheimer Disease.

Individuals with Alzheimer Disease who develop psychotic symptoms (AD + P) experience more rapid cognitive decline and have reduced indices of synaptic integrity relative to those without psychosis (AD-P). We sought to determine whether the postsynaptic density (PSD) proteome is altered in AD + P relative to AD-P, analyzing PSDs from dorsolateral prefrontal cortex of AD + P, AD-P, and a reference group of cognitively normal elderly subjects. The PSD proteome of AD + P showed a global shift towards lower levels of all proteins relative to AD-P, enriched for kinases, proteins regulating Rho GTPases, and other regulators of the actin cytoskeleton. We computationally identified potential novel therapies predicted to reverse the PSD protein signature of AD + P. Five days of administration of one of these drugs, the C-C Motif Chemokine Receptor 5 inhibitor, maraviroc, led to a net reversal of the PSD protein signature in adult mice, nominating it as a novel potential treatment for AD + P.

The Incidence and Prognosis Value of Perineural Invasion in Rectal Carcinoma: From Meta-Analyses and Real-World Clinical Pathological Features.

AIMS: Perineural invasion (PNI) is a special type of metastasis of several cancers and has been reported as being a factor for poor prognosis in colorectal carcinoma. However, investigations of PNI in only rectal cancer and a comprehensive analysis combining meta-analyses with real-world case studies remain lacking. MATERIALS AND METHODS: First, articles from 2000 to 2020 concerning the relationship between PNI and rectal cancer prognoses and clinical features were meta-analysed. Subsequently, we carried out a retrospective analysis of 312 rectal cancer cases that underwent radical surgery in the real world. The incidence of PNI and the relationship between PNI and prognosis, as well as clinicopathological factors, were investigated. RESULTS: The incidence of PNI was 23.09% and 33.01% in the meta-analysis and clinical cases, respectively. PNI occurred as early as stage I (2.94%). Moreover, neoadjuvant therapy significantly reduced the PNI-positive rate (20.34% versus 26.54%). Both meta-analysis and real-world clinical case studies suggested that PNI-positive patients had poorer prognoses than PNI-negative patients. We established an effective risk model consisting of T stage, differentiation and lymphovascular invasion to predict PNI in rectal cancer. CONCLUSION: PNI is a poor prognostic factor for rectal cancer and could occur even in stage I. Additionally, neoadjuvant therapy could sufficiently reduce the PNI-positive rate. T stage, lymphovascular invasion and differentiation grade were independent risk factors for PNI and the risk model that included these factors could predict the probability of PNI.

Independent and combined associations of upper and lower limb strength with all-cause mortality in community-based older adults: findings from the Chinese Longitudinal Healthy Longevity Survey.

OBJECTIVES: Life expectancy is increasing around the world, and it has been projected that China will have the largest elderly population globally by 2033. This study aimed to examine the association of upper limb strength (ULS) and lower limb strength (LLS) with all-cause mortality based on data from the Chinese Longitudinal Healthy Longevity Survey (2012-2018). STUDY DESIGN: This is a prospective cohort study. METHODS: Participants were 2442 older adults (aged 84.98 ± 11.94 years) recruited from eight regions with a high elderly population in China. Limb muscle strength was evaluated using handgrip strength and objective physical examinations. Cox proportional hazards regression was used to analyse the association of limb muscle strength with all-cause mortality. Demographic characteristics, health status and biological markers were included as confounders. RESULTS: Over a median follow-up period of 42.2 months, 993 participants died. After adjusting for all covariates, low ULS was associated with a higher mortality risk (hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 1.25-1.84), and the association of low LLS with all-cause mortality was only significant for men (HR = 1.36, 95% CI = 1.04-1.79). Participants with combined low ULS and low LLS had the highest risk of mortality compared with participants with normal limb muscle strength (HR = 2.06, 95% CI = 1.61-2.63). The combined association of ULS and LLS with mortality was robust in subgroup and sensitivity analyses. CONCLUSION: Low ULS and low LLS were independently and synergistically associated with a higher all-cause mortality risk. Considering the high prevalence of limb muscle weakness among older adults in China, especially in those aged ≥80 years, limb strength could be considered as an easy-to-perform potential mortality predictor in community health care.