Time-Varying Proteinuria and Progression of IgA Nephropathy: A Cohort Study.

RATIONALE & OBJECTIVE: Proteinuria is a surrogate end point for predicting long-term kidney outcomes in IgA nephropathy (IgAN) with levels<1g/day identified as a therapeutic target. However, this threshold has not been sufficiently studied. We quantified the associations of progression of IgAN with various levels of proteinuria. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 1,530 patients with IgAN and at least 12 months of follow-up at Peking University First Hospital. EXPOSURE: Proteinuria levels updated over time (time-varying proteinuria, TVP). OUTCOME: A composite kidney outcome of a 50% reduction in the estimated glomerular filtration rate or end-stage kidney disease. ANALYTICAL APPROACH: Marginal structural models. RESULTS: After a median follow-up period of 43.5 (IQR, 27.2-72.8) months, 254 patients (16.6%) developed the composite kidney outcome. A graded association was observed between TVP and composite kidney outcomes with higher risk among those with proteinuria of≥0.5g/day. Compared with TVP<0.3g/day, the HRs for proteinuria levels of 0.3 to<0.5g/day, 0.5 to<1.0g/day, 1.0 to<2.0g/day, and≥2.0g/day were 2.22 (95% CI, 0.88-5.58), 4.04 (95% CI, 1.93-8.46), 8.46 (95% CI, 3.80-18.83), and 38.00 (95% CI, 17.62-81.95), respectively. The trend was more pronounced in patients with baseline proteinuria of≥1.0g/day, among whom a higher risk was observed with TVP of 0.3 to<0.5g/day compared with TVP<0.3g/day (HR, 3.26 [95% CI, 1.07-9.92], P=0.04). However, in patients with baseline proteinuria levels of<1g/day, the risk of composite kidney outcome only began to increase when TVP was≥1.0g/day (HR, 3.25 [95% CI, 1.06-9.90]). LIMITATIONS: Single-center observational study, selection bias, and unmeasured confounders. CONCLUSIONS: This study showed that patients with IgAN and proteinuria levels of>0.5g/day, have an elevated risk of kidney failure especially among patients with proteinuria levels≥1.0g/day before initiating treatment. These data may serve to inform the selection of proteinuria targets in the treatment of IgAN. PLAIN-LANGUAGE SUMMARY: The presence of proteinuria has often been considered a surrogate end point and a possible therapeutic target in clinical trials in IgA nephropathy (IgAN). Some guidelines recommend a reduction in proteinuria to<1g/day as a treatment goal based on the results of previous longitudinal studies. However, these findings may have been biased because they did not properly adjust for time-dependent confounders. Using marginal structural models to appropriately account for these confounding influences, we observed that patients with IgAN and proteinuria levels≥0.5g/day have an elevated risk of kidney failure, especially among patients who had proteinuria levels of≥1.0g/day before initiating treatment. These data may serve to inform the selection of proteinuria targets in the treatment of IgAN.

Characteristics of Trypsin genes and their roles in insecticide resistance based on omics and functional analyses in the malaria vector Anopheles sinensis.

Trypsin is one of the most diverse and widely studied protease hydrolases. However, the diversity and characteristics of the Trypsin superfamily of genes have not been well understood, and their role in insecticide resistance is yet to be investigated. In this study, a total of 342 Trypsin genes were identified and classified into seven families based on homology, characteristic domains and phylogenetics in Anopheles sinensis, and the LY-Domain and CLECT-Domain families are specific to the species. Four Trypsin genes, (Astry2b, Astry43a, Astry90, Astry113c) were identified to be associated with pyrethroid resistance based on transcriptome analyses of three field resistant populations and qRT-PCR validation, and the knock-down of these genes significantly decrease the pyrethroid resistance of Anopheles sinensis based on RNAi. The activity of Astry43a can be reduced by five selected insecticides (indoxacarb, DDT, temephos, imidacloprid and deltamethrin); and however, the Astry43a could not directly metabolize these five insecticides, like the trypsin NYD-Tr did in earlier reports. This study provides the overall information frame of Trypsin genes, and proposes the role of Trypsin genes to insecticide resistance. Further researches are necessary to investigate the metabolism function of these trypsins to insecticides.

Social anxiety modulating early processing for social threat words: an ERP study.

Even though some recent research revealed individuals with HSA typically display enhanced processing in the early stages of emotional information processing due to hypervigilance and vulnerability to negative stimuli, it is still unclear whether social anxiety affects the time course underlying processing bias for emotional stimuli. Therefore, the present study aimed to explore the early stage of processing social threat stimuli in high social anxiety (HSA) individuals by recording RTs and EEG data in the emotional Stroop task. Behavioral data showed that the HSA group responded to the threat words faster than neutral words (i.e. negative bias), but no emotional effects in the low social anxiety (LSA) group. Although the P1 component did not show any early effects, ERP data exhibited an enhanced N170 for HSA than for LSA groups. Threat words elicited larger N170 than neutral words in the LSA group only; this emotion effect was not evident in the HSA group. These findings indicated that social anxiety modulates early processing for social threat words. This study revealed the neural mechanisms underlying early emotional processing in individuals with social anxiety, providing insights for the evaluation and intervention of social anxiety.

Integration of 3D printing and case-based learning in clinical practice for the treatment of developmental dysplasia of the hip.

BACKGROUND: Case-based learning (CBL) utilizing three-dimensional (3D) printed hip joint models is a problem-solving teaching method that combines the tactile and visual advantages of 3D-printed models with CBL. This study aims to investigate the impact of integrating 3D printing with CBL on learning developmental dysplasia of the hip (DDH). METHODS: We conducted a prospective study from 2022 to 2023, including 120 fourth-year clinical medical students at Xuzhou Medical University. Students were randomly allocated into two groups of 60 participants each. The CBL group received conventional CBL teaching methods, while the 3D + CBL group utilized 3D-printed models in conjunction with CBL. Post-teaching, we analyzed and compared the theoretical and practical achievements of both groups. A questionnaire was designed to assess the impact of the educational approach on orthopedic surgery learning. RESULTS: The theory scores of the CBL group (62.88 ± 7.98) and 3D + CBL group (66.35 ± 8.85) were significantly different (t = 2.254, P = 0.026); the practical skills scores of the CBL group (57.40 ± 8.80) and 3D + CBL group (63.42 ± 11.14) were significantly different (t = 3.283, P = 0.001). The questionnaire results showed that the 3D + CBL group was greater than the CBL group in terms of hip fundamentals, ability to diagnose cases and plan treatments, interesting teaching content, willingness to communicate with the instructor and satisfaction. CONCLUSIONS: The integration of 3D printing with case-based learning has yielded positive outcomes in teaching DDH, providing valuable insights into the use of 3D-printed orthopedic models in clinical education.

Impacts of continuous quality improvement on wound pain in the puncture site of arteriovenous fistula in haemodialysis patient.

This study analyses the effects of a continuous quality improvement nursing model on wound pain at the arteriovenous fistula (AVF) puncture site in patients undergoing haemodialysis. Forty haemodialysis patients from the First Affiliated Hospital of Chongqing Medical University, from September 2020 to December 2022, were selected as study subjects. They were randomly divided into an observation group and a control group. The control group received conventional nursing care, while the observation group was treated with a continuous quality improvement nursing model. The study compared the impact of these nursing approaches on pain intensity post-AVF puncture, wound visual analogue scale scores, self-rating anxiety scale, self-rating depression scale, quality of life scores and patient satisfaction with nursing care. In the observation group, the proportion of patients experiencing moderate to severe pain during AVF puncture was lower than that in the control group, whereas the proportion of patients with no pain or mild pain was higher (P = 0.008). After nursing, the observation group exhibited significantly lower wound visual analogue scale scores, self-rating anxiety scale scores, and self-rating depression scale scores compared to the control group (P < 0.001), with a significantly higher quality of life score (P < 0.05). The nursing satisfaction rate was 95.00% in the observation group, significantly higher than the 65.00% in the control group (P = 0.018). The continuous quality improvement nursing model significantly reduces wound pain at the AVF puncture site in haemodialysis patients, alleviates negative emotions, enhances the quality of life, and achieves high patient satisfaction. It is thus a highly recommendable approach in nursing practice.

Intensive blood pressure control and the progression of IgA nephropathy: a cohort study using marginal structural models.

BACKGROUND: In chronic kidney disease, current guidelines recommend systolic blood pressure (SBP) below 120 mmHg. However, the renoprotective effect of intensive blood-pressure (BP) lowering on immunoglobulin A nephropathy (IgAN) remains undetermined. We aimed to determine the effect of intensive BP control on the progression of IgAN. METHODS: At Peking University First Hospital, 1530 patients with IgAN were enrolled. An examination of the relationship between baseline and time-updated BP and composite kidney outcomes, defined as development of end-stage kidney disease (ESKD) or a 30% decline in estimated glomerular filtration rate (eGFR), was conducted. Baseline and time-updated BPs were modeled using multivariate causal hazards models and marginal structural models (MSMs). RESULTS: In a median follow-up of 43.5 (interquartile range 27.2, 72.7) months, 367 (24.0%) patients experienced the composite kidney outcomes. No significant associations were found between baseline BP and the composite outcomes. Using MSMs with time-updated SBP for analysis, a U-shaped association was found. In reference to SBP 110-119 mmHg, hazard ratios (95% confidence intervals) for the SBP categories <110, 120-129, 130-139 and ≥140 mmHg were 1.48 (1.02-2.17), 1.13 (0.80-1.60), 2.21 (1.54-3.16) and 2.91 (1.94-4.35), respectively. The trend was more prominent in patients with proteinuria ≥1 g/day and eGFR ≥60 mL/min/1.73 m2. After analyzing time-updated diastolic BP, no similar trend was observed. CONCLUSIONS: In patients with IgAN, intensive BP control during the treatment period may retard the kidney disease progression, but the potential risk of hypotension still needs to be considered.

Comparison between hydroxychloroquine and systemic corticosteroids in IgA nephropathy: a two-year follow-up study.

BACKGROUND: Hydroxychloroquine (HCQ) is recommended as a treatment for IgA nephropathy (IgAN) to control proteinuria. The long-term effects of HCQ compared to systemic corticosteroid therapy remain unclear. METHODS: We conducted a retrospective case‒control study at Peking University First Hospital. Thirty-nine patients with IgAN who received HCQ for at least 24 months without corticosteroids (CSs) or other immunosuppressive agents were included. Thirty-nine matched patients who received systemic CS therapy were selected using propensity score matching. Clinical data over a 24-month period were compared. RESULTS: In the HCQ group, the level of proteinuria decreased from 1.72 [1.44, 2.35] to 0.97 [0.51, 1.37] g/d (-50.5 [-74.0, -3.4] %, P < 0.001) at 24 months. A significant decline in proteinuria was also found in the CS group, but no significant differences were found between the HCQ group and CS group in the levels of proteinuria (0.97 [0.51, 1.37] vs. 0.53 [0.25, 1.81] g/d, P = 0.707) and change rates (-50.5% [-74.0%, -3.4%] vs. -63.7% [-78.5%, -24.2%], P = 0.385) at 24 months. In addition, the decline rates of eGFR between the HCQ and CS groups were comparable (-7.9% [-16.1%, 5.8%] vs. -6.6% [-14.9%, 5.3%], P = 0.758). More adverse events were observed in the CS group. CONCLUSIONS: Long-term use of HCQ can maintain stable renal function with minimal side effects. In patients who cannot tolerate corticosteroids, HCQ might be an effective and safe supportive therapy for IgAN.

ABT-263 exerts a protective effect on upper urinary tract damage by alleviating neurogenic bladder fibrosis.

This study investigated the mechanism of action of ABT-263 in the treatment of neurogenic bladder fibrosis (NBF)and its protective effects against upper urinary tract damage (UUTD). Sixty 12-week-old Sprague-Dawley (SD) rats were randomly divided into sham, sham + ABT-263 (50 mg/kg), NBF, NBF + ABT-263 (25 mg/kg, oral gavage), and NBF + ABT-263 (50 mg/kg, oral gavage) groups. After cystometry, bladder and kidney tissue samples were collected for hematoxylin and eosin (HE), Masson, and Sirius red staining, and Western Blotting (WB) and qPCR detection. Primary rat bladder fibroblasts were isolated, extracted, and cultured. After co-stimulation with TGF-ß1 (10 ng/mL) and ABT-263 (concentrations of 0, 0.1, 1, 10, and 100 µmol/L) for 24 h, cells were collected. Cell apoptosis was detected using CCK8, WB, immunofluorescence, and annexin/PI assays. Compared with the sham group, there was no significant difference in any physical parameters in the sham + ABT-263 (50 mg/kg) group. Compared with the NBF group, most of the markers involved in fibrosis were improved in the NBF + ABT-263 (25 mg/kg) and NBF + ABT-263 (50 mg/kg) groups, while the NBF + ABT-263 (50 mg/kg) group showed a significant improvement. When the concentration of ABT-263 was increased to 10 µmol/L, the apoptosis rate of primary bladder fibroblasts increased, and the expression of the anti-apoptotic protein BCL-xL began to decrease.ABT-263 plays an important role in relieving NBF and protecting against UUTD, which may be due to the promotion of myofibroblast apoptosis through the mitochondrial apoptosis pathway.

The efficacy and safety of hydroxychloroquine in pregnant patients with IgA nephropathy: A retrospective cohort study.

AIM: Hydroxychloroquine (HCQ) is used to control proteinuria in IgA Nephropathy (IgAN) However, its efficacy and safety in pregnant IgAN patients remains unknown. This study aimed to verify the safety of HCQ in pregnant IgAN patients and compare renal function and pregnancy outcomes with those of patients not treated with HCQ. METHODS: We retrospectively reviewed medical records of all pregnant IgAN patients and singleton gestations at Peking University First Hospital from 2003-2021. Patients who did and did not receive HCQ treatment during pregnancy were compared. RESULTS: We found no significant pre- or post-pregnancy differences in proteinuria or renal function between the two groups. However, the HCQ (+) group had higher proteinuria at the time of kidney biopsy (2.04 [1.26, 2.56] g/d vs. 0.80 [0.44, 1.11] g/d, P < .001); the proteinuria level at HCQ therapy initiation was also higher than that at the beginning of pregnancy (1.87 [1.30, 2.59] g/d vs. 1.08 [0.75, 1.50] g/d, P = .001). Despite no difference in preterm birth, birth weight, preeclampsia or postpartum haemorrhage, the proportion of patients with a previous history of spontaneous abortion was higher in the HCQ (+) group than in the HCQ (-) group (48.0% vs. 20.6%, P = .010). The eGFR (regression coefficient, 0.981; 95%CI 0.964-0.998) was a predictive factor for obstetrical complications. CONCLUSION: HCQ is safe for IgAN treatment during pregnancy with effective reduction of proteinuria. HCQ might also be helpful in patients with a history of spontaneous abortion.

HSP superfamily of genes in the malaria vector Anopheles sinensis: diversity, phylogenetics and association with pyrethroid resistance.

BACKGROUND: Heat shock proteins (HSPs) are molecular chaperones that are involved in many normal cellular processes and various kinds of environmental stress. There is still no report regarding the diversity and phylogenetics research of HSP superfamily of genes at whole genome level in insects, and the HSP gene association with pyrethroid resistance is also not well known. The present study investigated the diversity, classification, scaffold location, characteristics, and phylogenetics of the superfamily of genes in Anopheles sinensis genome, and the HSP genes associated with pyrethroid resistance. METHODS: The present study identified the HSP genes in the An. sinensis genome, analysed their characteristics, and deduced phylogenetic relationships of all HSPs in An. sinensis, Anopheles gambiae, Culex quinquefasciatus and Aedes aegypti by bioinformatic methods. Importantly, the present study screened the HSPs associated with pyrethroid resistance using three field pyrethroid-resistant populations with RNA-seq and RT-qPCR, and looked over the HSP gene expression pattern for the first time in An. sinensis on the time-scale post insecticide treatment with RT-qPCR. RESULTS: There are 72 HSP genes in An. sinensis genome, and they are classified into five families and 11 subfamilies based on their molecular weight, homology and phylogenetics. Both RNA-seq and qPCR analysis revealed that the expression of AsHSP90AB, AsHSP70-2 and AsHSP21.7 are significantly upregulated in at least one field pyrethroid-resistant population. Eleven genes are significantly upregulated in different period after pyrethroid exposure. The HSP90, sHSP and HSP70 families are proposed to be involved in pyrethroid stress response based in expression analyses of three field pyrethroid-resistant populations, and expression pattern on the time scale post insecticide treatment. The AsHSP90AB gene is proposed to be the essential HSP gene for pyrethroid stress response in An. sinensis. CONCLUSIONS: This study provides the information frame for HSP superfamily of genes, and lays an important basis for the better understanding and further research of HSP function in insect adaptability to diverse environments.

UDP-glycosyltransferase genes and their association and mutations associated with pyrethroid resistance in Anopheles sinensis (Diptera: Culicidae).

BACKGROUND: UDP-glycosyltransferase (UGT) is an important biotransformation superfamily of enzymes. They catalyze the transfer of glycosyl residues from activated nucleotide sugars to acceptor hydrophobic molecules, and function in several physiological processes, including detoxification, olfaction, cuticle formation, pigmentation. The diversity, classification, scaffold location, characteristics, phylogenetics, and evolution of the superfamily of genes at whole genome level, and their association and mutations associated with pyrethroid resistance are still little known. METHODS: The present study identified UGT genes in Anopheles sinensis genome, classified UGT genes in An. sinensis, Anopheles gambiae, Aedes aegypti and Drosophila melanogaster genomes, and analysed the scaffold location, characteristics, phylogenetics, and evolution of An. sinensis UGT genes using bioinformatics methods. The present study also identified the UGTs associated with pyrethroid resistance using three field pyrethroid-resistant populations with RNA-seq and RT-qPCR, and the mutations associated with pyrethroid resistance with genome re-sequencing in An. sinensis. RESULTS: There are 30 putative UGTs in An. sinensis genome, which are classified into 12 families (UGT301, UGT302, UGT306, UGT308, UGT309, UGT310, UGT313, UGT314, UGT315, UGT36, UGT49, UGT50) and further into 23 sub-families. The UGT308 is significantly expanded in gene number compared with other families. A total of 119 UGTs from An. sinensis, An. gambiae, Aedes aegypti and Drosophila melanogaster genomes are classified into 19 families, of which seven are specific for three mosquito species and seven are specific for Drosophila melanogaster. The UGT308 and UGT302 are proposed to main families involved in pyrethroid resistance. The AsUGT308D3 is proposed to be the essential UGT gene for the participation in biotransformation in pyrethroid detoxification process, which is possibly regulated by eight SNPs in its 3' flanking region. The UGT302A3 is also associated with pyrethroid resistance, and four amino acid mutations in its coding sequences might enhance its catalytic activity and further result in higher insecticide resistance. CONCLUSIONS: This study provides the diversity, phylogenetics and evolution of UGT genes, and potential UGT members and mutations involved in pyrethroid resistance in An. sinensis, and lays an important basis for the better understanding and further research on UGT function in defense against insecticide stress.

Pre-existing interleukin 10 in cerebral arteries attenuates subsequent brain injury caused by ischemia/reperfusion.

Recurrent stroke is difficult to treat and life threatening. Transfer of anti-inflammatory gene is a potential gene therapy strategy for ischemic stroke. Using recombinant adeno-associated viral vector 1 (rAAV1)-mediated interleukin 10 (IL-10), we investigated whether transfer of beneficial gene into the rat cerebral vessels during interventional treatment for initial stroke could attenuate brain injury caused by recurrent stroke. Male Wistar rats were administered rAAV1-IL-10, rAAV1-YFP, or saline into the left cerebral artery. Three weeks after gene transfer, rats were subjected to occlusion of the left middle cerebral artery (MCAO) for 45 min followed by reperfusion for 24 h. IL-10 levels in serum were significantly elevated 3 weeks after rAAV1-IL-10 injection, and virus in the cerebral vessels was confirmed by in situ hybridization. Pre-existing IL-10 but not YFP decreased the neurological dysfunction scores, brain infarction volume, and the number of injured neuronal cells. AAV1-IL-10 transduction increased heme oxygenase (HO-1) mRNA and protein levels in the infarct boundary zone of the brain. Thus, transduction of the IL-10 gene in the cerebral artery prior to ischemia attenuates brain injury caused by ischemia/reperfusion in rats. This preventive approach for recurrent stroke can be achieved during interventional treatment for initial stroke.

Quercetin inhibits proliferation and invasion acts by up-regulating miR-146a in human breast cancer cells.

Breast cancer is the most common female malignancies in the world which seriously impacts the female health. In recent years, various studies have been reported to determine the relevance of miRNAs to human cancer. One of these miRNAs, miR-146a has been down-regulated in multiple human cancer types, but up-regulation showed inducing apoptosis. To determine the role of quercetin treated on breast cancer, we investigated the effect of quercetin on cell proliferation in human breast cancer cell lines MCF-7 and MDA-MB-231 with/without transfection of miR-146a mimic or anti-miR-146a. Furthermore, the expressions of bax and cleaved-caspase-3, mainly were increased in control and overexpression miR-146a groups, however, the expression of EGFR was inverse. All the results demonstrated that quercetin exhibited excellent effect on inhibiting cell proliferation in human breast cancer cells, which was performed by up-regulating miR-146a expression, then via inducing apoptosis through caspase-3 activation and mitochondrial-dependent pathways, and inhibiting invasion through down-regulating the expression of EGFR.

High-strength bolt corrosion fatigue life model and application.

The corrosion fatigue performance of high-strength bolt was studied. Based on the fracture mechanics theory and the Gerberich-Chen formula, the high-strength bolt corrosion fracture crack model and the fatigue life model were established. The high-strength bolt crack depth and the fatigue life under corrosion environment were quantitatively analyzed. The factors affecting high-strength bolt corrosion fatigue life were discussed. The result showed that the high-strength bolt corrosion fracture biggest crack depth reduces along with the material yield strength and the applied stress increases. The material yield strength was the major factor. And the high-strength bolt corrosion fatigue life reduced along with the increase of material strength, the applied stress or stress amplitude. The stress amplitude influenced the most, and the material yield strength influenced the least. Low bolt strength and a low stress amplitude level could extend high-strength bolt corrosion fatigue life.

Hysteretic behavior of prestressed concrete bridge pier with fiber model.

The hysteretic behavior and seismic characteristics of the prestressed concrete bridge pier were researched. The effects of the prestressed tendon ratio, the longitudinal reinforcement ratio, and the stirrup reinforcement ratio on the hysteretic behavior and seismic characteristics of the prestressed concrete bridge pier have been obtained with the fiber model analysis method. The analysis show some results about the prestressed concrete bridge pier. Firstly, greater prestressed tendon ratio and more longitudinal reinforcement can lead to more obvious pier's hysteresis loop "pinching effect," smaller residual displacement, and lower energy dissipation capacity. Secondly, the greater the stirrup reinforcement ratio is, the greater the hysteresis loop area is. That also means that bridge piers will have better ductility and stronger shear capacity. The results of the research will provide a theoretical basis for the hysteretic behavior analysis of the prestressed concrete pier.

Do color enhancement algorithms improve the experience of color-deficient people? An empirical study based on smartphones.

Approximately 8% of the global population experiences color-vision deficiency. It is important to note that "color-vision deficiency" is distinct from "color blindness," as used in this article, which refers to the difficulty in distinguishing certain shades of color. This study explores color enhancement algorithms based on the neural mechanisms of color blindness and color deficiency. The algorithms are then applied to smartphones to improve the user experience (UX) of color-enhancing features in different top-selling smartphone brands with different operating systems (OS). A color-enhancing application program was developed for individuals with color-vision deficiency and compared to two other mature color-enhancing programs found in top-selling smartphones with different mainstream operating systems. The study included both objective and subjective evaluations. The research materials covered three aspects: daily life, information visualization, and videos. Additionally, this research study examines various levels of color enhancement through three dimensions of subjective evaluation: color contrast, color naturalness, and color preference. The results indicate that all color-enhancing features are beneficial for individuals with color-vision deficiencies due to their strong color contrast. The users' color preference is closely linked to color naturalness. The application program preserves the naturalness of colors better than the other two color-enhancing features. The subjective evaluations show similar trends across different operating systems, with differences arising from the use of different color-enhancing algorithms. Therefore, different algorithms may result in different sizes of the color gamut.

Identification and functional validation of P450 genes associated with pyrethroid resistance in the malaria vector Anopheles sinensis (Diptera Culicidae).

Cytochrome P450 monooxygenases (P450s), a multifunctional protein superfamily, are one of three major classes of detoxification enzymes. However, the diversity and functions of P450 genes from pyrethroid-resistant populations of Anopheles sinensis have not been fully explored. In this study, P450 genes associated with pyrethroid resistance were systematically screened using RNA-seq in three field pyrethroid-resistant populations (AH-FR, CQ-FR, YN-FR) and one laboratory resistant strain (WX-LR) at developmental stages, tissues, and post blood-meal in comparison to the laboratory susceptible strain (WX-LS) in An. sinensis. Importantly, the expression of significantly upregulated P450s was verified using RT-qPCR, and the function of selected P450s in pyrethroid detoxification was determined with RNA interference using four laboratory pyrethroid-resistant strains (WX-LR, AH-LR, CQ-LR, YN-LR). Sixteen P450 genes were significantly upregulated in at least one field-resistant population, and 44 were significantly upregulated in different developmental stages, tissues or post blood-meal. A total of 19 P450s were selected to verify their association with pyrethroid resistance, and four of them (AsCYP6P3v1, AsCYP6P3v2, AsCYP9J10, and AsCYP9K1) demonstrated significant upregulation in laboratory pyrethroid-resistant strains using RT-qPCR. Knockdown of these four genes all significantly reduced pyrethroid resistance and increased the mortality by 57.19% (AsCYP6P3v1 and AsCYP6P3v2 knockdown group), 38.39% (AsCYP9K1 knockdown group) and 48.87% (AsCYP9J10 knockdown group) in An. sinensis by RNAi, which determined the pyrethroid detoxification function of these four genes. This study revealed the diversity of P450 genes and provided functional evidence for four P450s in pyrethroid detoxification in An. sinensis for the first time, which increases our understanding of the pyrethroid resistance mechanism, and is of potential value for pyrethroid resistance detection and surveillance.

Pharmaceutical treatment status of patients with COPD in the community based on medical Internet of Things: a real-world study.

This study aimed to investigate the real-world standardisation and adherence of medical treatment regimens in patients with chronic obstructive pulmonary disease (COPD) in the community for making future management strategy. The follow-up data and treatment information of patients with COPD, which were collected through the Management Information Center of COPD (MICCOPD) in 21 community health service centres in Songjiang District, a countryside region of Shanghai. Concordance between the pharmaceutical treatment plan and recommendation of 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report during the follow-up management period, as well as the medication adherence by patients,were analysed. Out of the 2044 patients diagnosed with COPD, 814 patients (39.8%) who had an initial record of medication use were found to meet the inclusion criteria. The most common medication regimens were long-acting beta-agonist plus inhaled corticosteroids (35.9%) and oral bronchodilators (41.9%). Among these 814 patients, 45.7%, 38.0%, 31.6% and 14.6% adhered to the treatment after 6, 12, 18 and 24 months of follow-up, respectively. The concordance rate with the regimens recommended by the 2017 GOLD guidelines was 35.5% at baseline, 35.5% at 6 months, 32.7% at 12 months, 35.4% at 18 months and 37% at 24 months. The compliance and guideline consistency rates of patients with COPD in the community under the management of general practitioners need to be improved. Enhancing general practitioner proficiency in the prevention and management of COPD and increasing patient awareness of the condition, are crucial standardising and improving adherence to initial and follow-up COPD treatments.

Application of deep learning classification model for regional evaluation of roof pressure support evolution effects over time in coal mining face.

Hydraulic support leg pressure serves as a crucial indicator for assessing work face support quality. Current evaluation methods for support quality primarily concentrate on static analyses-like inadequate initial support force, pressure overrun, and uneven bracket force-while neglecting dynamic column pressure changes. This paper introduces a model for assessing hydraulic support quality using deep learning techniques. Real-time data is preprocessed into a spatio-temporal pressure sub-matrix sample, which is then inputted into the model. This process assesses the support quality type and characterizes its dynamic evolution within the area. The model facilitates the identification of dynamic support quality effects in the working face area, aiding operators in making targeted adjustments to hydraulic support status. Experimental results revealed that the optimized LeNet-5 network-adjusting parameters like convolutional layer count, kernel size, and ReLU activation function-achieved the highest classification accuracy of 85.25 % for support quality, surpassed other networks. Furthermore, the improved LeNet-5 network outperformed other networks in both F1 score and recall. Additionally, the improved LeNet-5 network achieved faster convergence to the optimal solution, accelerated training speed. This highlighted its advantages in evaluating the spatio-temporal support quality of hydraulic supports in smart mining operations.

Geometric nonlinear analysis of self-anchored cable-stayed suspension bridges.

Geometric nonlinearity of self-anchored cable-stayed suspension bridges is studied in this paper. The repercussion of shrinkage and creep of concrete, rise-to-span ratio, and girder camber on the system is discussed. A self-anchored cable-stayed suspension bridge with a main span of 800 m is analyzed with linear theory, second-order theory, and nonlinear theory, respectively. In the condition of various rise-to-span ratios and girder cambers, the moments and displacements of both the girder and the pylon under live load are acquired. Based on the results it is derived that the second-order theory can be adopted to analyze a self-anchored cable-stayed suspension bridge with a main span of 800 m, and the error is less than 6%. The shrinkage and creep of concrete impose a conspicuous impact on the structure. And it outmatches suspension bridges for system stiffness. As the rise-to-span ratio increases, the axial forces of the main cable and the girder decline. The system stiffness rises with the girder camber being employed.