Background Intrauterine growth restriction (IUGR) is closely associated with placental dysfunction. However, the effects of preconception co-exposure to β-cypermethrin (β-CYP) and emamectin benzoate (EMB) on fetal growth and placental function remain unclear. Objective To investigate the effects of prenatal exposure to β-CYP and EMB on embryonic development in female rats and to elucidate the mechanisms by which these substances cause IUGR from the perspectives of placental structure, progesterone synthesis, and mitochondrial autophagy. Methods Forty-eight specific pathogen-free (SPF) adult female Sprague-Dawley (SD) rats were randomly assigned to a control group, a β-CYP group, an EMB group, and a co-exposure group (n=12 per group). A whole-body dynamic inhalation exposure system was used to simulate greenhouse exposure. Rats in the control group were exposed to clean air, whereas those in the exposure groups were exposed to β-CYP (55 mg·m⁻³), EMB (7.8 mg·m⁻³), or their combination for 2 h per day for 90 consecutive days. After exposure, ovarian and serum estradiol (E₂) levels were determined in six rats from each group, while the remaining six rats were mated. Of the mated rats, three per group were sacrificed on gestational day 18, and the other remaining three were allowed to deliver naturally. Pregnancy outcomes and fetal development were evaluated. Placental morphology, progesterone (Prog) levels, progesterone synthesis-related factors, oxidative stress, mitochondrial function, and mitophagy-related indicators were subsequently assessed. Results Compared with the control group, fetal body weight on gestational day 18 and neonatal body weight were significantly decreased, whereas the incidence of IUGR was significantly increased in the β-CYP, EMB, and co-exposure groups (P<0.05). The EMB and co-exposure groups exhibited an increased proportion of the placental junctional zone thickness to total placental thickness and a reduced proportion of the labyrinth zone (P<0.05). Ovarian E₂ and placental Prog levels were decreased in all three exposure groups. In addition, the placental expression of cytochrome P450 family 11 subfamily A member1(CYP11A1)、3β-hydroxysteroid dehydrogenase type 1(HSD3B1)、progesterone receptor(PgR) was downregulated, catalase (CAT) activity and adenosine triphosphate (ATP) content were reduced, and lactate dehydrogenase (LDH) activity was increased in all exposure groups (P < 0.05). Furthermore, the expression of translocase of outer mitochondrial membrane 2 was decreased, whereas the expression levels of microtubule-associated protein 1 light chain 3 (LC3), PTEN-induced kinase 1 (PINK1), parkin RBR E3 ubiquitin-protein ligase (Parkin), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) were increased in all exposure groups (P<0.05). Conclusion Prenatal exposure to β-CYP and EMB can cause structural damage to the rat placenta, affect the expression of markers related to progesterone synthesis, and is accompanied by oxidative stress, mitochondrial dysfunction, and alterations in PINK1/Parkin-mediated mitochondrial autophagy, ultimately affecting the intrauterine growth and development of the fetus.

Objective To investigate the relationship between the mean platelet volume(MPV)to platelet count(PLT)ratio(MPV/PLT),blood urea nitrogen(BUN)to lipoprotein a[Lp(a)]ratio[BUN/Lp(a)]and the prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease(COPD).Methods A total of 106 patients with acute exacerbation of COPD admitted to the hospital from January 2021 to January 2024 were selected as the research objects.According to the prognosis,they were divided into sur-vival group(72 cases)and death group(34 cases).The results of routine laboratory tests,blood lipid and lipo-protein levels were compared between the two groups.Multivariate Logistic regression was used to analyze the influencing factors of death in patients with acute exacerbation of COPD.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of MPV/PLT and BUN/Lp(a)for the prognosis of pa-tients with acute exacerbation of COPD.Results Compared with the survival group,the invasive ventilation rate,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,C reactive protein(CRP),white blood cell count(WBC),MPV,BUN,MPV/PLT and BUN/Lp(a)were significantly increased in the death group(P＜0.05).The non-invasive ventilation rate,lymphocyte count,PLT and Lp(a)levels were signifi-cantly decreased(P＜0.05).Multivariate Logistic regression analysis showed that APACHE Ⅱ score,CRP,WBC,lymphocyte count,MPV,PLT,MPV/PLT,BUN,Lp(a)and BUN/Lp(a)were the influencing factors of death in patients with acute exacerbation of COPD(P＜0.05).ROC curve results showed that the sensitivity and specificity of MPV/PLT combined with BUN/Lp(a)for predicting the prognosis of patients with acute exacerbation of COPD were 88.2％and 84.7％,respectively,and the area under curve was 0.887.Conclusion MPV/PLT and BUN/Lp(a)are closely related to the prognosis of patients with acute exacerbation of COPD.The combination of MPV/PLT and BUN/Lp(a)has a high predictive value for the prognosis of patients.

Objective:To evaluate the role of cannabinoid receptor 1 (CB1) in the spinal membrane in electroacupuncture (EA)-induced alleviation of morphine-triggered opioid-induced hyperalgesia (OIH) and the relationship with phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) in rats.Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 240-260 g, in which intrathecal catheters were successfully implanted, were divided into 4 groups ( n=12 each) using a random number table method: normal saline group (NS group), morphine group (M group), morphine+ EA group (ME group), and morphine+ EA+ CB1 antagonist group (MEA group). The OIH model was established by intrathecal injection of morphine 15 μg (10 μl) twice a day for 7 consecutive days. The equal volume of normal saline 10 μl was given instead in NS group. EA of the " Yanglingquan" (GB34) and " Zusanli" (ST36) acupoints lasting 30 min was performed after the first administration of medication each day, with a current intensity of 2 mA and frequency of 2 Hz in ME group. In MEA group, morphine (15 μg) and CB1 antagonist AM251 30 μg (10 μl) were intrathecally injected twice a day for 7 consecutive days, with other treatments similar to those previously described in ME group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before administration (T 0) and on days 1, 3, 5 and 7 after administration (T 1-4). Rats were deeply anesthetized and sacrificed at T 3, 4 after administration, and the L 4-6 spinal cord tissues were collected for determination of the expression of membrane CB1, ERK1/2 and p-ERK1/2 by Western blot. Results:Compared with NS group, the MWT was significantly decreased and the TWL was shortened at T 3, 4 in M, ME and MEA groups, the expression of spinal membrane CB1 and p-ERK1/2 was significantly up-regulated at T 4 after administration in M group, and the expression of spinal membrane CB1 was significantly up-regulated at T 3, 4 after administration in ME and MEA groups ( P<0.05). Compared with M group, the MWT was significantly increased and the TWL was prolonged at T 3, 4, and the expression of p-ERK1/2 was down-regulated at T 4 after administration in ME group ( P<0.05), no significant change was found in MWT or TWL at T 3, 4 in MEA group ( P>0.05), and the expression of spinal membrane CB1 was significantly up-regulated at T 3, 4 after administration in ME and MEA groups ( P<0.05). Compared with ME group, the MWT was significantly decreased and the TWL was shortened at T 3, 4, and the expression of spinal membrane CB1 and p-ERK1/2 was up-regulated at T 4 after administration in MEA group ( P<0.05). Conclusions:Up-regulation of spinal membrane CB1 expression is involved in EA-mediated alleviation of morphine-induced OIH, which is associated with the inhibition of ERK1/2 phosphorylation in rats.

Acute kidney injury(AKI)is a syn-drome characterized by rapid decline in renal excre-tory function.Its pathogenesis is still unclear.Stud-ies have shown that macrophages are major play-ers in AKI inflammation,regulating tissue damage and regeneration repair.During AKI inflammation,macrophages can be activated into different func-tional phenotypes through molecular and signaling pathways,regulate different molecules and signal-ing pathways,and determine the progression of AKI.In this paper,the activation of macrophages and the molecular signaling pathways involved in the regulation of AKI in the past five years are re-viewed,and the mechanism of action of macro-phages in AKI is determined,which provides ideas for the study of macrophages as therapeutic tar-gets.

Objective To reveal the detailed histological characteristics of pyramidal neuron cell bodies and their axonal projections along the corticospinal tract in the primary motor cortex(M1)of the brain,by using the biotinylated dextran amine(BDA)neural tracing technique combined with panoramic and local microscopic imaging technologies.Methods A total of 100 nL of 10％BDA(10,000 molecular weight)was injected into M1 region using stereotaxic system.The distribution of BDA labeling along the corticospinal tract was continuously tracked with panoramic tissue scanning analysis system.Detailed observations of the histological characteristics of BDA labeling were carried out with laser confocal microscope.Results It is more convenient to observe the overall distribution of BDA neural labeling by using the panoramic tissue scanning analysis system.Around the injection site in M1,the BDA labeling was shown in the somas of pyramidal neurons in layer V.In the M1 region corresponding to the contralateral site of the injection site and ipsilateral primary sensory cortex,BDA showed predominantly the anterograde labeled nerve fibers accompanied by a few retrograde labeled neurons.Besides,BDA labeled nerve fibers-including bundles and terminals-projecting to regions such as the ipsilateral striatum,thalamus,internal capsule,cerebral peduncle,and pons,and further reaching the contralateral spinal cord via the brainstem pyramidal decussation.Confocal microscopy and its 3D reconstruction system facilitated detailed analysis of the local microscopic features of BDA labeling,revealing retrograde labeled neuron cell bodies,dendrites and their spines,as well as anterograde labeled nerve fibers and their terminals.Conclusions These findings demonstrated that the integration of traditional BDA neural tracing with panoramic tissue scanning analysis and confocal microscopy provided an effective approach to the observation and analysis of long-projection neural circuits from panoramic to local perspectives,with broad application prospects.

Objective:To evaluate the role of cannabinoid receptor 1 (CB1) in the spinal membrane in electroacupuncture (EA)-induced alleviation of morphine-triggered opioid-induced hyperalgesia (OIH) and the relationship with phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) in rats.Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 240-260 g, in which intrathecal catheters were successfully implanted, were divided into 4 groups ( n=12 each) using a random number table method: normal saline group (NS group), morphine group (M group), morphine+ EA group (ME group), and morphine+ EA+ CB1 antagonist group (MEA group). The OIH model was established by intrathecal injection of morphine 15 μg (10 μl) twice a day for 7 consecutive days. The equal volume of normal saline 10 μl was given instead in NS group. EA of the " Yanglingquan" (GB34) and " Zusanli" (ST36) acupoints lasting 30 min was performed after the first administration of medication each day, with a current intensity of 2 mA and frequency of 2 Hz in ME group. In MEA group, morphine (15 μg) and CB1 antagonist AM251 30 μg (10 μl) were intrathecally injected twice a day for 7 consecutive days, with other treatments similar to those previously described in ME group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before administration (T 0) and on days 1, 3, 5 and 7 after administration (T 1-4). Rats were deeply anesthetized and sacrificed at T 3, 4 after administration, and the L 4-6 spinal cord tissues were collected for determination of the expression of membrane CB1, ERK1/2 and p-ERK1/2 by Western blot. Results:Compared with NS group, the MWT was significantly decreased and the TWL was shortened at T 3, 4 in M, ME and MEA groups, the expression of spinal membrane CB1 and p-ERK1/2 was significantly up-regulated at T 4 after administration in M group, and the expression of spinal membrane CB1 was significantly up-regulated at T 3, 4 after administration in ME and MEA groups ( P<0.05). Compared with M group, the MWT was significantly increased and the TWL was prolonged at T 3, 4, and the expression of p-ERK1/2 was down-regulated at T 4 after administration in ME group ( P<0.05), no significant change was found in MWT or TWL at T 3, 4 in MEA group ( P>0.05), and the expression of spinal membrane CB1 was significantly up-regulated at T 3, 4 after administration in ME and MEA groups ( P<0.05). Compared with ME group, the MWT was significantly decreased and the TWL was shortened at T 3, 4, and the expression of spinal membrane CB1 and p-ERK1/2 was up-regulated at T 4 after administration in MEA group ( P<0.05). Conclusions:Up-regulation of spinal membrane CB1 expression is involved in EA-mediated alleviation of morphine-induced OIH, which is associated with the inhibition of ERK1/2 phosphorylation in rats.

Objective:To evaluate the causal relationship between IL-7 and IL-7Rα and ankylosing spondylitis(AS)using the Mendelian randomization(MR)method.Methods:This study was based on gene-wide association study(GWAS)summary data,con-structing instrumental variables(IV)using single nucleotide polymorphisms(SNPs).We respectively adopt Inverse variance weighted(IVW),MR-Egger mode and Weighted median(WM)mode to assess the causal relation between IL-7/IL-7Rα and AS.In addition,we also conducted sensitivity tests,including the heterogeneity test,the pleiotropy test,the leave-one-out approach and the MR-PRESSO test.Results:IL-7 and IL-7Rα were respectively included in 9 and 5 IVs that could be used for MR analysis.Results of IVW analysis revealed a reliable causal relationship between IL-7 and IL-7Rα and AS[IL-7:P=0.025 2,OR(95%CI)=0.999 4(0.989 1～0.999 9);IL-7Rα:P=0.008 3,OR(95%CI)=1.000 6(1.000 2～1.001 0)].Cochranes Q test(IL-7:P=0.999 7;IL-7Rα:P=0.946 9)showed that all studies had good homogeneity.The results of a leave-one-out sensitivity analysis suggested that causal associations were not strongly influenced by any selected IVs.The intercept of the MR-Egger regression further showed that pleiotropy did not bias the causal effect in this study.Conclusion:Both IL-7 and IL-7Rα have a strong causal relationship with AS,among which IL-7 is a protec-tive factor for AS,and IL-7Rα is a risk factor for AS.

Objective:To evaluate the causal relationship between IL-7 and IL-7Rα and ankylosing spondylitis(AS)using the Mendelian randomization(MR)method.Methods:This study was based on gene-wide association study(GWAS)summary data,con-structing instrumental variables(IV)using single nucleotide polymorphisms(SNPs).We respectively adopt Inverse variance weighted(IVW),MR-Egger mode and Weighted median(WM)mode to assess the causal relation between IL-7/IL-7Rα and AS.In addition,we also conducted sensitivity tests,including the heterogeneity test,the pleiotropy test,the leave-one-out approach and the MR-PRESSO test.Results:IL-7 and IL-7Rα were respectively included in 9 and 5 IVs that could be used for MR analysis.Results of IVW analysis revealed a reliable causal relationship between IL-7 and IL-7Rα and AS[IL-7:P=0.025 2,OR(95%CI)=0.999 4(0.989 1～0.999 9);IL-7Rα:P=0.008 3,OR(95%CI)=1.000 6(1.000 2～1.001 0)].Cochranes Q test(IL-7:P=0.999 7;IL-7Rα:P=0.946 9)showed that all studies had good homogeneity.The results of a leave-one-out sensitivity analysis suggested that causal associations were not strongly influenced by any selected IVs.The intercept of the MR-Egger regression further showed that pleiotropy did not bias the causal effect in this study.Conclusion:Both IL-7 and IL-7Rα have a strong causal relationship with AS,among which IL-7 is a protec-tive factor for AS,and IL-7Rα is a risk factor for AS.

Objective To explore the potential mechanisms of hypoxic adaptive metabolic changes in the kidneys of plateau pikas at different altitudes using non-targeted metabolomics analysis via ultra-high-performance liquid chromatography coupled with quadrupole electrostatic field orbital trap-mass spectrometry (UHPLC-QE-MS). Methods 10 plateau pikas were captured at an altitude of 4 360 m in Xingxiuhai area, Maduo County, Guoluo Tibetan Autonomous Prefecture, Qinghai Province (MD group), and 10 plateau pikas were captured at an altitude of 2 900 m in Menyuan area, Haibei Tibetan Autonomous Prefecture, Qinghai Province (MY group). After anesthesia, serum samples were collected, and kidney samples were collected after euthanasia. General physiological and biochemical indicators were measured and metabolomics analysis was performed. Part of the serum samples was used for hematology analysis, another part for blood gas analysis, and the remaining part for biochemical indicator detection. Metabolites were extracted from the kidney tissue samples and then analyzed using UHPLC-QE-MS. Differential metabolites were analyzed using metabolomics principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), with screening criteria set as variable importance in projection (VIP)>1.5 and fold change (FC)>1.5, or VIP>1.5 and FC<1/1.5. Correlation analysis heatmaps, significance analysis volcano plots, signaling pathway recognition bubble charts, and rectangular graphs were used for the analysis of differential metabolites and related signaling pathways. Results The red blood cell count, glucose, urea nitrogen, uric acid, and homocysteine levels in the MD group plateau pikas were higher than those in the MY group, while hemoglobin, hematocrit, creatinine, and carbon dioxide combining power were lower than those in the MY group. This indicated a significant difference in the blood oxygen-carrying capacity of plateau pikas at different altitudes. The principal component pattern recognition analyses, and OPLS-DA permutation test showed that the kidney metabolites of the MD and MY groups of plateau pikas had distinct clustering distributions (R²Y=0.930, Q²=0.655). According to the screening criteria and database comparison, 46 differential metabolites were identified in the kidneys of plateau pikas at different altitudes. In the MD group of plateau pikas, the expression levels of bufadienolide, adenosine, adenine, diosgenin, berberine chloride, carnosol, and astaxanthin were significantly increased (VIP>1.5, P<0.05), while the levels of arachidonic acid, histamine, and coumarin were significantly decreased (VIP>1.5, P<0.05). The analysis of related signaling pathways showed that the biosynthetic pathways of valine, leucine, and isoleucine had the largest impact factors (P<0.05), while the biosynthetic pathways of pantothenate and coenzyme A showed the most significant enrichment (P<0.05). Conclusion The differential metabolites of amino acids, pantothenate, and coenzyme A pathways in the kidneys of plateau pikas at different altitudes may be involved in the metabolic mechanisms of plateau pikas' hypoxia adaptation in high-altitude environments.

Avian coccidiosis, an acute parasitic disease that mainly harms chicks, is widely prevalent across the world, which poses a serious threat to poultry industry. Because of the single prophylactic formulations, veterinary clinical treatment of coccidiosis mainly relies on chemically synthesized agents, polyether ionophores and Chinese herbal medicines. The introduction of novel anticoccidial drugs is slow for a long period of time, and there is an increasing problem of anticoccidial drug resistance following long-term use, which has become an urgent problem to be solved in poultry industry. This review summarizes the levels of anticoccidial drug resistance across China from 2018 to 2023, and analyzes the resistance to various anticoccidial agents in coccidia. It is indicated that the overall prevalence of anticoccidial drug resistance is high in coccidia, and development of novel anticoccidial agents and products with reduced antibiotics use and alternatives of antibiotics is of an urgent need.