Objective To explore the pathophysiological molecular mechanism of the up-regulation of CircPDS5B level involved in premature birth.Methods The placental tissues of full-term infants(Group 1,gestational age≥37 weeks),late premature infants(Group 2,34 weeks≤gestational age<37 weeks),premature infants(Group 3,32 weeks

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

A novel analytical method was developed in this study by combining online solid phase extraction with ultra performance liquid chromatography-tandem mass spectrometry(Online SPE-UPLC-MS/MS)for simultaneous determination of 50 kinds of steroid hormones in surface water.Specifically,after high-speed centrifugation of 4 mL water samples,the supernatant was directly injected into an Oasis HLB online SPE column for enrichment and purification.Subsequently,the target compounds were transferred to the analytical column via valve switching for separation and analysis.The chromatographic separation was performed on a Thermo Acclaim RSLC C18 column(100 mm×2.1 mm,2.2 μm),using a mobile phase composed of 5 mmol/L ammonium fluoride aqueous solution and acetonitrile.Mass spectrometric detection was conducted in positive ion mode,utilizing multiple reaction monitoring(MRM)with quantification achieved by the internal standard method.The method validation demonstrated that the limits of detection(LOD)for the 50 kinds of steroid hormones ranged from 0.02 to 0.50 ng/L,while the limits of quantification(LOQ)were between 0.08 and 1.67 ng/L.The average recoveries in surface water samples at spiked concentrations of 5,20 and 200 ng/L were between 74.1％and 119％,with relative standard deviations(RSDs)of 0.2％to 9.9％.This method was applied to analyze 11 surface water samples collected from sites surrounding a pharmaceutical and chemical industrial park.A total of 44 kinds of steroid hormones were detected,with concentrations ranging from 0.11 to 88.6 ng/L,revealing the presence of hormone contamination in the environmental waters surrounding industrial areas.Compared with the traditional offline SPE methods,the proposed online SPE technique significantly reduced sample volume requirements and pretreatment time,while minimizing the loss of target compounds during the pretreatment process.Moreover,compared to reported online SPE techniques,this method achieved high-throughput analysis of multiple classes of steroid hormones,with lower detection limits and higher recoveries.Overall,this method provided rapid sample preparation,high sensitivity,and excellent stability,making it suitable for the direct analysis of trace steroid hormones in surface water.

Objective To explore the pathophysiological molecular mechanism of the up-regulation of CircPDS5B level involved in premature birth.Methods The placental tissues of full-term infants(Group 1,gestational age≥37 weeks),late premature infants(Group 2,34 weeks≤gestational age<37 weeks),premature infants(Group 3,32 weeks

AIM To investigate the effects of dried extract powder of Qingre Xiaoyanning on a mouse model of rhinovirus (RhV) infection.METHODS Ninety-six BALB/c mice,half males and half females,were randomly divided into the normal group,the model group,the ribavirin group (60 mg/kg) and the low,medium and high dose groups of dried extract powder of Qingre Xiaoyanning (8.72,17.44,34.89 g/kg) for the administration of the corresponding doses of drugs once daily for 7 days.Except for those of the normal group,the mice of the other groups were intranasally instilled with VR-1187 RhV on the fourth day of the administration.On the second day to the day of the last administration,the mice had their left bronchus and left lung procured for pathological examination;their right lung taken for PCR detection of viral load;their levels of inflammatory factors TNF-α,IL-1β,IL-4,VCAM-1 and IFN-γ in alveolar lavage fluid detected by ELISA;their levels of macrophages,NK cells and lymphocytes detected by flow cytometry;and their pulmonary protein expressions of TLR4,MYD88,IKK-β,IκB and p-IκB detected by Western blot.RESULTS Compared with the model group,the group intervened with high dose dried extract powder of Qingre Xiaoyanning displayed decreased viral load (P<0.01);decreased levels of IL-4,VCAM-1 and IL-1β in bronchoalveolar lavage fluid (P<0.05,P<0.01);decreased proportion of pulmonary macrophages (P<0.01);increased proportion of lymphocytes and NK cells (P<0.05);and decreased protein expressions of TLR4,MYD88,IκB,p-IκB and ratio of p-IκB/IκB in lung tissue (P<0.05).Additionally,the medium dose group of dried extract powder of Qingre Xiaoyanning shared decreased pulmonary IKK-β protein expression (P<0.05).CONCLUSION The dried extract powder of Qingre Xiaoyanning can reduce the inflammatory reaction in mice to protect their lung tissue because of its obvious anti-RhV effect in vivo by inhibiting the RhV replication via TLR4/MYD88/NF-κB signaling pathway.

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.

AIM To investigate the effects of dried extract powder of Qingre Xiaoyanning on a mouse model of rhinovirus (RhV) infection.METHODS Ninety-six BALB/c mice,half males and half females,were randomly divided into the normal group,the model group,the ribavirin group (60 mg/kg) and the low,medium and high dose groups of dried extract powder of Qingre Xiaoyanning (8.72,17.44,34.89 g/kg) for the administration of the corresponding doses of drugs once daily for 7 days.Except for those of the normal group,the mice of the other groups were intranasally instilled with VR-1187 RhV on the fourth day of the administration.On the second day to the day of the last administration,the mice had their left bronchus and left lung procured for pathological examination;their right lung taken for PCR detection of viral load;their levels of inflammatory factors TNF-α,IL-1β,IL-4,VCAM-1 and IFN-γ in alveolar lavage fluid detected by ELISA;their levels of macrophages,NK cells and lymphocytes detected by flow cytometry;and their pulmonary protein expressions of TLR4,MYD88,IKK-β,IκB and p-IκB detected by Western blot.RESULTS Compared with the model group,the group intervened with high dose dried extract powder of Qingre Xiaoyanning displayed decreased viral load (P<0.01);decreased levels of IL-4,VCAM-1 and IL-1β in bronchoalveolar lavage fluid (P<0.05,P<0.01);decreased proportion of pulmonary macrophages (P<0.01);increased proportion of lymphocytes and NK cells (P<0.05);and decreased protein expressions of TLR4,MYD88,IκB,p-IκB and ratio of p-IκB/IκB in lung tissue (P<0.05).Additionally,the medium dose group of dried extract powder of Qingre Xiaoyanning shared decreased pulmonary IKK-β protein expression (P<0.05).CONCLUSION The dried extract powder of Qingre Xiaoyanning can reduce the inflammatory reaction in mice to protect their lung tissue because of its obvious anti-RhV effect in vivo by inhibiting the RhV replication via TLR4/MYD88/NF-κB signaling pathway.

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.

Objective: To evaluate the clinical effects of low- and intermediate-dose factor Ⅷ (F Ⅷ) prophylaxis in Chinese adult patients with severe hemophilia A. Methods: Thirty adult patients with severe hemophilia A who received low- (n=20) /intermediate-dose (n=10) F Ⅷ prophylaxis at Nanjing Drum Tower Hospital affiliated with Nanjing University Medical College were included in the study. The annual bleeding rate (ABR), annual joint bleeding rate (AJBR), number of target joints, functional independence score of hemophilia (FISH), quality of life score, and health status score (SF-36) before and after preventive treatment were retrospectively analyzed and compared. Results: The median follow-up was 48 months. Compared with on-demand treatment, low- and intermediate-dose prophylaxis significantly reduced ABR, AJBR, and the number of target joints (P<0.05) ; the improvement in the intermediate-dose prophylaxis group was better than that in the low-dose prophylaxis group (P<0.05). Compared with on-demand treatment, the FISH score, quality of life score, and SF-36 score significantly improved in both groups (P<0.05), but there was no significant difference between the two groups (P>0.05) . Conclusion: In Chinese adults with severe hemophilia A, low- and intermediate-dose prophylaxis can significantly reduce bleeding frequency, delay the progression of joint lesions, and improve the quality of life of patients as compared with on-demand treatment. The improvement in clinical bleeding was better with intermediate-dose prophylaxis than low-dose prophylaxis.
Humans ; Hemophilia A/drug therapy* ; Factor VIII/therapeutic use* ; Quality of Life ; Retrospective Studies ; Hemarthrosis/prevention & control* ; Hemorrhage/drug therapy*

Acephalic spermatozoa syndrome is a rare type of teratozoospermia that severely impairs the reproductive ability of male patients, and genetic defects have been recognized as the main cause of acephalic spermatozoa syndrome. Spermatogenesis and centriole-associated 1 like (SPATC1L) is indispensable for maintaining the integrity of sperm head-to-tail connections in mice, but its roles in human sperm and early embryonic development remain largely unknown. Herein, we conducted whole-exome sequencing (WES) of 22 infertile men with acephalic spermatozoa syndrome. An in silico analysis of the candidate variants was conducted, and WES data analysis was performed using another cohort consisting of 34 patients with acephalic spermatozoa syndrome and 25 control subjects with proven fertility. We identified biallelic mutations in SPATC1L (c.910C>T:p.Arg304Cys and c.994G>T:p.Glu332X) from a patient whose sperm displayed complete acephalia. Both SPATC1L variants are rare and deleterious. SPATC1L is mainly expressed at the head-tail junction of elongating spermatids. Plasmids containing pathogenic variants decreased the level of SPATC1L in vitro. Moreover, none of the patient's four attempts at intracytoplasmic sperm injection (ICSI) resulted in a transplantable embryo, which suggests that SPATC1L defects might affect early embryonic development. In conclusion, this study provides the first identification of SPATC1L as a novel gene for human acephalic spermatozoa syndrome. Furthermore, WES might be applied for patients with acephalic spermatozoa syndrome who exhibit reiterative ICSI failures.
Centrioles/genetics* ; Homozygote ; Humans ; Infertility, Male/genetics* ; Male ; Mutation ; Spermatogenesis/genetics* ; Spermatozoa