Amyotrophic lateral sclerosis (ALS) is a chronic, progressive degenerative disease affecting both upper and lower motor neurons, primarily characterized by skeletal muscle weakness and atrophy. Notably, the same muscle group may exhibit asynchronous involvement. This study aims to investigate the involvement patterns of the orbicularis oculi (OOc) and orbicularis oris (OOr) in ALS patients, compare the findings with healthy controls (HCs) and myasthenia gravis (MG) patients, and explore the characteristics and clinical significance of facial muscle involvement in ALS.

Background Long-term exposure to ambient fine particulate matter (PM_2.5) is a significant risk factor for cardiometabolic disorders. However, the mechanisms of its interaction with the endogenous circadian system remain incompletely understood. Objective To investigate whether chronic PM_2.5 exposure interferes with the rhythmic expression of the cardiac circadian clock, thereby disrupting downstream antioxidant defenses and metabolic homeostasis, and ultimately driving cardiometabolic dysfunction. Methods Seventy-two male C57BL/6 mice were randomly divided into a PM_2.5 exposure group (PM group) and a filtered air control group (FA group). Whole-body exposure was conducted for 8 weeks in a meteorological environmental animal exposure system. Samples were collected at six distinct zeitgeber time (ZT) points post-exposure. The 24 h ambulatory blood pressure and serum lipid profiles were monitored. Rhythm parameters were derived via cosinor analysis to compare differences in Midline statistic of rhythm (Mesor), amplitude, and phase between the two groups. The rhythmic expression of core circadian clock genes and antioxidant genes in the myocardium was detected by quantitative polymerase chain reaction (qPCR). Myocardial reactive oxygen species (ROS) levels and downstream pathway protein expression were analyzed by immunofluorescence and Western blot (WB), respectively. The expression changes of the clock gene retinoic acid receptor-related orphan receptor α (RORα) were assessed at both the mRNA and protein levels. Finally, Spearman correlation analysis was used to explore the relationships among myocardial RORα expression, lipid profiles, and oxidative stress indicators. Results Compared to the FA group, mice in the PM group exhibited a blunted circadian rhythm in blood pressure, characterized by sustained elevation throughout the day. Chronic PM_2.5 exposure showed a significant interaction with ZT on systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) (F-interaction=9.11, 5.70, and 6.02, respectively; P<0.05), as well as on serum triglycerides (TG), total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) (F-interaction=16.32, 11.12, 15.39, and 28.09, respectively; P<0.05). Cosinor analysis further revealed that the Mesor values of T-CHO, TG, and LDL-C were significantly increased (P<0.05), while that of HDL-C was significantly decreased in the PM group (P<0.05). The oscillation amplitudes of SBP, DBP, and MAP showed a decreasing trend, whereas those of TG and LDL-C were significantly increased (P<0.05). Furthermore, SBP, T-CHO, and HDL-C all exhibited a significant phase delay (P<0.05). Mechanistically, PM_2.5 exposure significantly suppressed the expression of the positive circadian regulator RORα in the myocardium, leading to disordered rhythmic expression of core clock genes (Bmal1, Clock, Per1/2, and Cry1/2). This exposure also inhibited the rhythmic expression of antioxidant genes (GPX1, SOD2, and CAT), resulting in increased ROS generation and elevated expression of calcium/calmodulin-dependent protein kinase II (CaMKII) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) proteins. Correlation analysis further revealed that myocardial RORα expression level was negatively correlated with T-CHO, TG, and LDL-C (r=−0.55, −0.63, and −0.51, respectively; P<0.001), and positively correlated with HDL-C (r=0.37, P=0.010), and antioxidant genes GPX1, SOD2, and CAT expression (r=0.34, 0.35, and 0.56, respectively; P < 0.001). Conclusion Chronic PM_2.5 exposure induces cardiometabolic dysfunction by suppressing myocardial RORα expression. This suppression disrupts the cardiac circadian clock and the diurnal balance of oxidative stress, triggering oxidative damage and elevating expression of CaMKII/NADPH pathway proteins. Collectively, these alterations precipitate the loss of cardiac metabolic rhythms and subsequent functional impairment.

Objective:To compare the effects of standard cognitive behavioral therapy for insomnia (CBT-I) and enhanced cognitive behavioral therapy for insomnia(CBT-I Plus) in patients with chronic insomnia disorder comorbid anxiety or depressive symptoms.Methods:This prospective study included 148 patients with chronic insomnia disorder and anxiety/depression symptoms who were treated at the Sleep Disorder clinic of Shanghai Mental Health Center between July 2020 and August 2023. Participants (56 males, 92 females; aged 18-65 years, mean age 35.08±10.30 years) were randomly assigned in a 1∶2 ratio to the CBT-I group ( n=54) or CBT-I Plus group ( n=94). The CBT-I Plus group received additional treatments targeting anxiety and depressive symptoms. Treatment lasted 8 weeks, with assessment conducted at baseline, weeks 2, 4, and 8. Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HAMD 17), anxiety severity with the Hamilton Anxiety Scale (HAMA), and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Paired sample t-tests were used to evaluate within-group changes, repeated-measures ANOVA compared treatment effects between groups, and ANCOVA was employed to adjust for confounding variables. Results:Significant reductions in PSQI, HAMD 17, and HAMA scores were observed in both groups after treatment: CBT-I group: PSQI ((14.15±2.54) vs. (7.50±3.35), t=13.25), HAMD 17 ((14.70±4.09) vs. (7.40±4.61), t=9.33), and HAMA ((14.94±4.11) vs. (5.56±3.67), t=12.38) (all P<0.001).CBT-I Plus group: PSQI ((14.87±3.01) vs. (7.19±3.86), t=18.75), HAMD 17 ((16.84±3.91) vs. (6.84±4.79), t=17.42), and HAMA ((15.57±3.93) vs. (6.10±4.57), t=18.39) (all P<0.001). After adjusting for HAMD 17 scores and medication use, no statistically significant between-group differences were observed in changes in PSQI, HAMD 17, and HAMA scores ( P>0.05). A significant time-by-group interaction was found for the PSQI daytime dysfunction subscale ( F=4.87, P<0.01). Conclusion:Both CBT-I and CBT-I Plus improve sleep and emotional symptoms in patients with chronic insomnia disorder and comorbid anxiety/depression symptoms. However, CBT-I Plus has no significant advantages over standard CBT-I. Further studies are needed to refine the timing and content of interventions.

Objective:To explore the effects and safety of Qigong Pills in IVF-ET outcome of PCOS infertility patients with phlegm-dampness type.Methods:A randomized controlled trial study was carried out. In the Reproductive and Genetic Medicine Center of Dalian Women and Children Medical Center (Group) from January 2021 to December 2023, 60 patients with sputum and damp-induced PCOS infertility assisted by in-vitro fertilization and embryo transfer (IVF-ET) were enrolled and randomly divided into 2 groups by block randomization method, with 30 cases in each group. Patients in both groups took ethinylestradiol cyproterone tablets orally on the 2nd to 5th day of the 1st menstrual cycle before IVF-ET cycle, and received down-regulation treatment on the 18th to 20th day of menstruation. After confirming that the down-regulation standard was reached, Qigong Pills was added to the treatment group, and placebo was taken orally until the trigger day. Two groups of patients underwent transvaginal ultrasound-guided ovarian aspiration after injection of chorionic gonadotropin (hCG) for 24-36 h. The total amount of Gn, the days of Gn, the endometrial thickness of HCG, the number of eggs obtained, the rate of diprokaryotic (2PN) fertilization, the number of transferable embryos, the number of high-quality embryos, the rate of high-quality embryos, the incidence of OHSS and the clinical pregnancy rate were compared between the two groups.Results:Among the 60 patients, 28 cases in the final treatment group and 27 cases in the control group were included in the outcome index evaluation. During controlled hyperstimulation (COH), the total Gn [2 025 (1 575, 2 325) U vs. 2 700 (2 025, 3 150) U, Z=-3.67] and the number of Gn days of the treatment group [10 (8,11) d vs. 11 (9,13) d, Z=-2.31] were lower than those in control group ( P<0.001 or P<0.05). There was no statistical significance in endometrial thickness between 2 groups on HCG day ( P>0.05); the number of high-quality embryos [3 (3, 4) vs. 2 (2, 3), Z=0.11] and the rate of high-quality embryos [46.28% (87/188) vs. 35.19% (57/162), Z=4.42] in the treatment group were higher than those in the control group ( P<0.05). There was no statistical significance in the number of eggs obtained, the fertilization rate of 2PN and the number of transferable embryos between the two groups ( P>0.05). The incidence of OHSS was 3.6% (1/28) in the treatment group and 11.1% (3/27) in the control group, without statistical significance ( P=0.352). The clinical pregnancy rate was 53.6% (15/28) in the treatment group and 37.0% (10/27) in the control group, without statistical significance ( P=0.218). There was no significant difference in the safety indexes of liver and kidney function between 2 groups ( P>0.05). Conclusion:Qigong Pills combined with IVF-ET can effectively reduce the total amount of Gn and the number of days of treatment in PCOS infertility patients with phlegm-dampness type, increase the number and rate of high-quality embryos, and improve the outcome of IVF-ET, and it is safe and effective.

Inflammatory bowel disease (IBD) is a chronic, relapsing intestinal disorder driven by multiple factors including genetics, immunity, and environment, and is clinically classified into ulcerative colitis and Crohn's disease. Currently, mice and zebrafish are the primary experimental animals used in IBD research, among which zebrafish have emerged as an ideal model due to their unique advantages. Compared with rodent models, zebrafish serve as an effective and convenient model, offering advantages such as a short life cycle, robust reproductive capacity, small size, and transparent embryos. These characteristics make zebrafish highly suitable for dynamic tracking of continuous pathological progression and high-throughput drug screening. Zebrafish share over 70% genetic homology with humans, and their intestinal cellular composition and ontogeny closely resemble those of humans. Moreover, the structure and characteristics of their gut microbiota are similar to the human intestinal microbiome, providing a solid foundation for studying the relationship between gut microbiota and IBD. With advances in biotechnology, zebrafish IBD models generated by chemical induction or genetic engineering can accurately simulate the core pathological features of human IBD, such as intestinal wall thickening, inflammatory cell infiltration, and elevated expression of pro-inflammatory factors. These models have played a significant role in revealing the pathogenesis of IBD as well as the development of targeted therapeutic drugs. This article first outlines the intestinal characteristics of zebrafish and features of zebrafish IBD models, then provides an in-depth analysis of their application in IBD pathogenesis research from multiple aspects, including genetics, immunity, environment and diet, and infection. It also reviews research progress on the application of zebrafish in the development of anti-inflammatory drugs, probiotics, and traditional Chinese medicine therapies, aiming to provide researchers with references for the rational use of zebrafish models at all stages of preclinical research, to advance fundamental IBD research and accelerate breakthroughs in this field.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Objective:To observe the effects of acupuncture on the motor function of Parkinson disease(PD)model mice and to investigate the neuroprotective effects of acupuncture on PD from the perspective of cellular senescence.Methods:C57BL/6J mice were randomly divided into a normal control(NC)group,a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)group,an acupuncture(ACU)group,and a rasagiline(RAS)group,with 6 mice in each group.Except for the mice in the NC group,all mice were injected intraperitoneally with MPTP[30 mg/(kg·bw)]to establish a PD mouse model.After the models were successfully established,mice in the ACU group received acupuncture at Baihui(GV20)and bilateral Yanglingquan(GB34)for 15 min,once a day for 14 consecutive days.Mice in the RAS group were treated with gavage of rasagiline mesylate[0.5 mg/(kg·bw)],once daily for 14 d.Mouse balance and motor functions were detected using the mouse fatigue rotating rod apparatus.Immunohistochemistry staining was used to detect the number of tyrosine hydroxylase(TH)-positive neurons and the protein expression levels of special AT-rich sequence-binding protein 1(SATB1),p21,and p53 in the substantia nigra(SN)region of the mouse brain in each group.The glutathione peroxidase(GSH-Px)activity of mouse brain SN tissue was detected by enzyme-linked immunosorbent assay.The protein expression levels of interleukin(IL)-6 and senescence-associated β-galactosidase(SA-β-gal)in the SN tissue of mice in each group were detected by Western blotting.The relative expression of SATB1,p21,and p53 mRNA in the SN of each group was detected by real-time quantitative polymerase chain reaction.Results:Compared to the NC group,the overall rod performance(ORP)score,the number of TH-positive neurons,and GSH-Px activity in the SN region were significantly lower in the mice in the MPTP group(P<0.01);compared to the MPTP group,the ORP score,the number of TH-positive neurons,and GSH-Px activity were significantly increased in the ACU group and the RAS group(P<0.01 or P<0.05).Compared to the NC group,the protein levels of IL-6 and SA-β-gal in the SN tissue,the protein and mRNA expression levels of p21 and p53 were significantly increased(P<0.01);compared to the MPTP group,the protein levels of IL-6 and SA-β-gal in the SN tissue,the protein and mRNA expression levels of p21 and p53 were significantly decreased in the ACU group and the RAS group(P<0.01 or P<0.05).Compared to the NC group,the relative expression of SATB1 protein and mRNA in the SN of mice in the MPTP group was significantly decreased(P<0.01);compared to mice in the MPTP group,mice in the ACU group and the RAS group showed significant increases in the relative expression of SATB1 protein and mRNA(P<0.01 or P<0.05).Conclusion:Acupuncture can improve motor function and increase the number of TH-positive neurons in the SN of PD model mice.Its neuroprotective effect may relate to the regulation of the SATB1/p21 signaling pathway and the inhibition of cellular senescence-related biomarker expression in the SN.

OBJECTIVE To investigate the result of human immunodeficiency virus(HIV)screening for the people visiting to a three-A hospital of Sichuan Province and analyze the prevalence of complications with hepatitis B virus(HBV)infection,hepatitis C virus(HCV)infection and Treponema pallidum(TP)infection in the emerging HIV infection patients.METHODS The result of HIV screening for the people who visited to Ziyang Central Hos-pital from Jan.1,2020 to Dec.31,2024 and the test results of HBV,HCV and TP for the emerging HIV infec-tion patients were collected and were summarized and statistically analyzed by SPSS.0 software.RESULTS Totally 289 891 case-times were tested for HIV,1529 cases were previously diagnosed with HIV,465 of whom were tested posi-tive for the first time,there was significant difference in the positive rate of test for the first time among the 5 years(x2=15.998,P=0.003).Totally 353 cases were confirmed positive among the 465 primary positive screening cases.Among the emerging HIV infection patients,the positive rate was higher in the male than in the female(x2=141.141,P＜0.001),and the positive rate was high among the population aged more than 40 year old(x2=11.448,P＜0.001),mi-grant workers(x2=270.110,P＜0.001)and low education level population(x2=25.911,P＜0.001).The detection rate of gp41 was up to 100.00％in strip type testing.The analysis of the ratio of relative light unit(RLU)to Cutoff val-ue(COI)in the initial screening experiment showed that when COI was greater than 50,all of the confirmed tests were positive,when COI ranged between 1 and 5,the false positive rate was 97.06％.The incidence of complica-tion with HBV infection in the emerging HIV infection patients was increased year by year(x2=20.355,P＜0.001),and the incidence of complication with HCV infection was increased in recent two years(x2=10.690,P=0.030).CONCLUSIONS There is no obvious rise of positive rate of HIV screening among the people visiting to the hospital in recent 5 years.The sensitivity of the primary screening of clinical laboratory is high without posi-tive missing test.The positive rates of HBV and HCV are increased among the emerging HIV infection patients.

Right heart dysfunction is a key impact factor of prognosis of various cardiovascular diseases,yet the assessment of right heart function has long been overlooked in management of cardiovascular diseases.Cardiac MR feature tracking(CMR-FT)is an emerging technique that enables quantitative analysis of global and regional strain without the need for additional imaging sequences.The advancements of CMR-FT for assessing right heart strain were reviewed in this article.

Objective To investigate the expression levels of LINC02009 and LOC107984895 in peripheral lymphocytes of patients with atrial fibrillation and their clinical significance.Methods A total of 75 hospitalized patients with atrial fibrillation(50 with persistent atrial fibrillation and 25 with paroxysmal atrial fibrillation)from Kunming First People's Hospital between January 2023 and December 2023 were selected as study subjects,along with 50 normal control patients.Real-time quantitative PCR was used to detect the expression levels of LINC02009 and LOC107984895 in peripheral blood leukocytes of patients with atrial fibrillation.Logistic regression analysis was employed to assess the relationship between expression levels and risk factors for atrial fibrillation,and ROC curves were used to predict the diagnostic cut-off values for LINC02009 and LOC107984895 in diagnosing atrial fibrillation.Results There were statistically significant differences in baseline diseases such as hypertension and coronary heart disease,biochemical indicators such as Cr and BNP,and myocardial remodeling indicators such as LAd and LVEF between the AF(paroxysmal atrial fibrillation and persistent atrial fibrillation)group and the Normal group(P＜0.05).The expression levels of LINC02009 and LOC 107984895 in the plasma of the atrial fibrillation group were significantly higher than those in the control group(P＜0.05)and were negatively correlated with LVEF(P＜0.05).The areas under the curve(AUC)of LINC02009 and LOC 107984895 in predicting atrial fibrillation were 0.967(95％CI:0.938～0.995)and 0.900(95％CI:0.838～0.963),respectively.The optimal cut-off values were 1.985 and 0.915,with sensitivities of 88％and 76％,respectively,and specificities of 94％and 90％,respectively.Conclusion LINC02009 and LOC 107984895 are independent risk factors for atrial fibrillation and have certain predictive value for the occurrence of atrial fibrillation.