Objective:To predict the therapeutic targets and potential mechanism of Yi medicine Tiaojing Yangyan Capsules in treating primary dysmenorrhea, menstrual disorders and oligomenorrhea using UPLC-Q-TOF-MS combined with network pharmacology.Methods:Using UPLC-Q-TOF-MS method, the chemical components in Tiaojing Yangyan Capsules were identified through automatic matching and retrieval from Waters UNIFI Chinese Materia Medica Database based on chromatographic peak retention time, precise relative molecular weight, characteristic fragment ions, and other information. TCMSP and SwissTarget Prediction databases were used to obtain chemical component targets, constructing a "drug-active component-target-disease" visual regulatory network and PPI network through databases such as GeneCards, DrugBank, TTD, PharmGKB, and Cytoscape 3.8.0 software. Metascape database was used to perform GO functional and KEGG pathway enrichment analysis on intersecting targets, and the potential mechanism of Tiaojing Yangyan Capsules in the treatment of primary dysmenorrhea was predicted.Results:Totally 67 components components were analyzed and identified from the Tiaojing Yangyan Capsules, which acted on 350 targets related to primary dysmenorrhea and menstrual disorders. The 15 main active components, including Ginsenoside Rg1, Ginsenoside Re, and Notoginsenoside Fe, targeted key proteins such as TNF, HSP90AA1, and STAT3, which would treat primary dysmenorrhea by regulating pathways such as the PI3K-Akt, FoxO, and Calcium.Conclusion:Tiaojing Yangyan Capsules may alleviate inflammatory reactions, alter hormone levels, regulate ovarian function, promote blood circulation, remove blood stasis, and regulate qi and blood through multiple components, targets, and pathways, thereby playing a preventive and therapeutic role in primary dysmenorrhea, menstrual disorders, and other conditions.

Objective:To investigate the effects of human glycolipid transfer protein(GLTP)on proliferation,migration and invasion of pancreatic cancer(PC)cells,and to elucidate their mechanisms.Methods:The difference in the expression levels of GLTP proteins between PC tissue and normal pancreas tissue was analyzed by University of Alabama at Birmingham Cancer Data Analysis Platform(UALCAN)Database,as well as the difference in the expression levels of GLTP protein between PC tissue and normal pancreas tissue of the PC patients with different clinicopathological characteristics.The PANC-1 cells were cultured in vitro and divided into control group(transfected with pFLAG-CMV4 plasmid)and GLTP-overexpression(GLTP-OE)group(transfected with pFLAG-GLTP plasmid).The stably GLTP transfected cells were established using the antibiotic screening method.Knock-down experiments were performed using non-specific siRNA transfected PANC-1 cells as control group and si-GLTP transfected PANC-1 cells as si-GLTP group.Western blotting method was used to detect the expression of GLTP protein in the cells in various groups,cell counting kit-8(CCK-8)method was used to detect the proliferation activities of PANC-1 cells,clone formation assay was used to detect the number of clone formation,and Transwell chamber assay were used to detect the numbers of migration and invasion cells in various groups.Transcriptomics sequencing analyses were conducted to assess the possible mechanism of GLTP in the PANC-1 cells.Western blotting method was employed to detect the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt)proteins in the PANC-1 cells in various groups;Real-time fluorescence quantitative PCR(RT-qPCR)was used to assess the expression levels of amphiregulin(AREG)and kinase insertion domain receptor(KDR)mRNA in the cells in various groups.The mice were randomly divided into control group(injected with pFLAG-GMV4 transfected PANC-1 cells)and experimental group(injected with pFLAG-GLTP stably transfected PANC-1 cells),and the subcutaneously transplanted tumor models were prepared;the volumes and weights of the transplanted tumors of the mice in two groups were measured.Results:UALCAN database analysis showed that the expression level of GLTP protein in PC tissue was lower than that in normal pancreas tissue(P＜0.01),and there were statistically significant differences in the GLTP protein expression between PC tissue and normal pancreas tissue of the PC patients with different cancer stages(P＜0.05),tumor grades(P＜0.05),ages(P＜0.001),and genders(P＜0.05).Compared with control group,the proliferation activity(P＜0.01)and the number of clone formation(P＜0.001)of the cells in GLTP-OE group were decreased,while the numbers of migration cells(P＜0.001)and invasion cells(P＜0.01)were decreased.In the knock-down experiment,compared with control group,the proliferation activity(P＜0.01)and the number of clone formation(P＜0.05)of the cells in GLTP-OE group were increased,while the numbers of migration cells(P＜0.001)and invasion cells(P＜0.001)were increased.Compared with control group,the tumor weight and volume of the mice in experimental group were decreased(P＜0.01),following the injection of tumor cells for a period of four weeks.In the over-expression experiment,compared with control group,the expression levels of p-PI3K(P＜0.01),p-Akt-S473(P＜0.01),and p-Akt-T308(P＜0.05)proteins in the cells in GLTP-OE group were decreased;the expression levels of AREG(P＜0.01)and KDR(P＜0.01)mRNA were decreased.In the knock-down experiment,compared with control group,the expression levels of p-PI3K(P＜0.01),p-Akt-S473(P＜0.01),and p-Akt-T308(P＜0.01)in the cells in si-GLPT group were increased,and the expression levels of AREG(P＜0.01)and KDR(P＜0.05)mRNA were increased.Conclusion:Low expression levels of GLTP in PC tissue are present.The over-expression of GLTP can inhibit the proliferation,migration and invasion of PANC-1 cells,as well as the growth of subcutaneously transplanted tumors in the nude mice;its possible mechanism may be related to decreasing the activity of the PI3K/Akt signaling pathway.

Objective To compare the clinical efficacy of high-dose tigecycline(TGC)and polymyxin B(PMB)in the treatment of pulmonary infection due to carbapenem-resistant organism(CRO).Methods Clinical data of pa-tients with CRO pulmonary infection and received PMB or high-dose TGC combined with other antimicrobial treat-ment regimens in Department of Critical Care Medicine of Xiangya Hospital,Central South University from January 2019 to March 2022 were analyzed retrospectively,including basic information,pathogen detection results,antimi-crobial use regimen,clinical efficacy,30-day mortality,bacterial clearance rate,etc.Results A total of 173 pa-tients were included in analysis,with 103 in the TGC group and 70 in the PMB group.Compared with TGC group,PMB group had a higher score of acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)(25.0 vs 20.0,P＜0.001),but clinical efficacy rates were not statistically different(67.1％vs 52.4％,P=0.054).Stratified analysis revealed that when the APACHE Ⅱ score was ≥15 points,compared with TGC group(n=78),PMB group(n=66)had a higher APACHE Ⅱ score(27.0 vs 22.0,P=0.005)and a higher clinical efficacy rate(66.7％vs 47.4％,P=0.020).After adjusting confounding factors through logistic regression analysis,it was found that PMB treatment was a protective factor for clinical efficacy rate compared with TGC treatment.Conclusion For treating pulmonary infection caused by CRO in patients,PMB-based treatment regimen has a significant protec-tive effect on the clinical efficacy rate compared with the high-dose TGC-based treatment regimen.

The prevalence of chronic constipation among the elderly is significant, exerting adverse effects on both their physical and mental health.Presently, pharmacological therapy remains the predominant treatment modality for elderly patients with chronic constipation; however, prolonged use can lead to drug dependence, tolerance, and adverse effects.This article systematically reviews non-pharmacological interventions for chronic constipation in elderly patients, both domestically and internationally, aiming to provide a comprehensive reference for clinical practice.

BACKGROUND: The role of inflammation in the development of gestational diabetes mellitus (GDM) has recently become a focus of research. The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI), novel indices, reflect the body's chronic immune-inflammatory state. This study aimed to investigate the associations between the SII or SIRI and GDM. METHODS: A prospective birth cohort study was conducted at Beijing Obstetrics and Gynecology Hospital from February 2018 to December 2020, recruiting participants in their first trimester of pregnancy. Baseline SII and SIRI values were derived from routine clinical blood results, calculated as follows: SII = neutrophil (Neut) count × platelet (PLT) count/lymphocyte (Lymph) count, SIRI = Neut count × monocyte (Mono) count/Lymph count, with participants being grouped by quartiles of their SII or SIRI values. Participants were followed up for GDM with a 75-g, 2-h oral glucose tolerance test (OGTT) at 24-28 weeks of gestation using the glucose thresholds of the International Association of Diabetes and Pregnancy Study Groups (IADPSG). Logistic regression was used to analyze the odds ratios (ORs) (95% confidence intervals [CIs]) for the the associations between SII, SIRI, and the risk of GDM. RESULTS: Among the 28,124 women included in the study, the average age was 31.8 ± 3.8 years, and 15.76% (4432/28,124) developed GDM. Higher SII and SIRI quartiles were correlated with increased GDM rates, with rates ranging from 12.26% (862/7031) in the lowest quartile to 20.10% (1413/7031) in the highest quartile for the SII ( Ptrend <0.001) and 11.92-19.31% for the SIRI ( Ptrend <0.001). The ORs (95% CIs) of the second, third, and fourth SII quartiles were 1.09 (0.98-1.21), 1.21 (1.09-1.34), and 1.39 (1.26-1.54), respectively. The SIRI findings paralleled the SII outcomes. For the second through fourth quartiles, the ORs (95% CIs) were 1.24 (1.12-1.38), 1.41 (1.27-1.57), and 1.64 (1.48-1.82), respectively. These associations were maintained in subgroup and sensitivity analyses. CONCLUSION The SII and SIRI are potential independent risk factors contributing to the onset of GDM.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/immunology* ; Prospective Studies ; Adult ; Inflammation/immunology* ; Glucose Tolerance Test ; Birth Cohort

Objective To compare the clinical efficacy of high-dose tigecycline(TGC)and polymyxin B(PMB)in the treatment of pulmonary infection due to carbapenem-resistant organism(CRO).Methods Clinical data of pa-tients with CRO pulmonary infection and received PMB or high-dose TGC combined with other antimicrobial treat-ment regimens in Department of Critical Care Medicine of Xiangya Hospital,Central South University from January 2019 to March 2022 were analyzed retrospectively,including basic information,pathogen detection results,antimi-crobial use regimen,clinical efficacy,30-day mortality,bacterial clearance rate,etc.Results A total of 173 pa-tients were included in analysis,with 103 in the TGC group and 70 in the PMB group.Compared with TGC group,PMB group had a higher score of acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)(25.0 vs 20.0,P＜0.001),but clinical efficacy rates were not statistically different(67.1％vs 52.4％,P=0.054).Stratified analysis revealed that when the APACHE Ⅱ score was ≥15 points,compared with TGC group(n=78),PMB group(n=66)had a higher APACHE Ⅱ score(27.0 vs 22.0,P=0.005)and a higher clinical efficacy rate(66.7％vs 47.4％,P=0.020).After adjusting confounding factors through logistic regression analysis,it was found that PMB treatment was a protective factor for clinical efficacy rate compared with TGC treatment.Conclusion For treating pulmonary infection caused by CRO in patients,PMB-based treatment regimen has a significant protec-tive effect on the clinical efficacy rate compared with the high-dose TGC-based treatment regimen.

The prevalence of chronic constipation among the elderly is significant, exerting adverse effects on both their physical and mental health.Presently, pharmacological therapy remains the predominant treatment modality for elderly patients with chronic constipation; however, prolonged use can lead to drug dependence, tolerance, and adverse effects.This article systematically reviews non-pharmacological interventions for chronic constipation in elderly patients, both domestically and internationally, aiming to provide a comprehensive reference for clinical practice.

Objective To Observe the clinical characteristics and prognosis of patients with the acute macular neuroretinopathy(AMN)associated with novel coronavirus infection(COVID-19).Methods The data of 13 patients diagnosed with COVID-19-associated AMN attending the Department of Ophthalmology of the Affiliated Hospital of Yunnan University from December 2022 to February 2023,as well as 13 case reports in PubMed and Web of Science databases from 2020 to 2023 and a case series study totaling 41 patients were retrospectively selected and analyzed for their ophthalmic imaging and prognostic outcomes in clinic.Results A total of 13 cases with 25 eyes in the clinical case group were included in the study with a mean age of 30.23±6.02 years,of which 10 were females.The literature case group consisted of 41 cases and 72 eyes with a mean age of 30.12±13.24 years,including 31 female patients.(1)Duration between COVID-19 symptoms/diagnosis and ophthalmic symptoms:3(2.0,4.0)days in the clinical case group and 2(0.75,5.0)days in the literature case group.(2)Clinical characteristics:12(92.31％)of the clinical case group had the binocular onset and the literature case group,31(75.61％)had the binocular onset.The symptoms in both groups were mainly dark spots in vision,followed by decreased visual acuity.(3)Ancillary examinations:optical coherence tomography(OCT)showed the ellipsoid zone(EZ)and/or chimeric zone(IZ)breaks with strong reflections in the outer plexiform layer(OPL)and outer nuclear layer(ONL)in 13 patients in the clinical case group,and the near-infrared photography(NIR)showed the low-reflective wedge-shaped foci around the center of the macula,and some patients'optical coherence tomography angiography(OCTA)showed deep capillary lesions,and some patients'OCTA showed low reflectivity.Reduced blood flow in the deep capillary layer(DCP)and choroidal capillary layer(CC)was observed in all patients,7 patients with cotton-wool spots also had the reduced blood flow in the superficial capillary layer(SCP),and 33 patients in the case group in the literature had the visible EZ and/or IZ breaks on OCT.(4)Treatment and prognosis:11 out of 13 patients were treated with oral glucocorticoids,2 were under the observation.After year,the condition of 23 patients had been improved,1 case had visual field defects,1 case had retinal vein occlusion secondary to macular edema,and 1 case had a hyporeflective signal in the outer nuclear layer(ONL)and outer plexiform layer(OPL).Conclusion The age of onset of AMN related to COVID-19 is slightly older,with more cases involving both eyes.The main symptom is visual field scotoma,often accompanied by decreased vision.Near-infrared imaging shows low-reflective wedge-shaped lesions around the fovea,and OCT shows mainly disruption of the EZ and/or IZ.OCTA shows decreased blood flow density in the DCP and CC layers.The visual prognosis of AMN related to COVID-19 is good,but vigilance is needed for the occurrence of complications such as retinal vein occlusion.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective To investigate the utility of dual-energy CT combined with musculoskeletal ultraso-nography in differentiating between calcium pyrophosphate deposition disease and gouty arthritis.Methods A retro-spective analysis was conducted on the medical records of 102 patients diagnosed with gouty arthritis and 102 patients diagnosed with calcium pyrophosphate deposition disease.These patients were categorized into the Gout group and Calcium Deposition group,respectively,based on their respective diagnoses.All patients underwent dual-energy CT and musculoskeletal ultrasonography examinations,while joint fluid aspiration results or intra-articular crystal material served as the gold standard for diagnosis.The diagnostic efficacy of dual-energy CT and musculoskeletal ultrasonography in discriminating between calcium pyrophosphate deposition disease and gouty arthritis was evalu-ated.Results In the gout group,the proportion of male patients and serum uric acid levels were significantly higher compared to those in the calcium deposition group(P<0.05).The prevalence rates of knee joint,first metatarsopha-langeal joint,and ankle joint involvement were higher in the gout group,while knee joint,wrist joint,and shoulder joint involvement rates were higher in the calcium deposition group.The proportions of irregular bone cortex,carti-lage injury,and degenerative meniscus changes were lower in the gout group compared to the calcium deposition group(P<0.05).The proportions of double contour sign,tophus formation,hyperechoic band within ligaments or tendons,and bone erosion were higher in the gout group compared to the calcium deposition group(P<0.05),whereas cartilage calcification was lower in the gout group(P<0.05).The sensitivities for diagnosing calcium pyrophosphate deposition disease and gouty arthritis using dual-energy CT scan alone,musculoskeletal ultrasound alone,and their combined use were 86.27%,83.33%,and 94.12%respectively.The specificities for diagnosing these conditions using dual-energy CT scan alone,musculoskeletal ultrasound alone,and their combined use were 89.22%,88.24%,and 86.27%respectively.The positive predictive values were 88.89%,87.63%,and 87.27%,respectively.The negative predictive values were 86.67%,84.11%,and 93.63%,respectively.The accuracies were 87.75%,85.78%,and 90.20%respectively.The agreement Kappa values were 0.755,0.716,and 0.804 respectively.Conclusions The integration of dual-energy CT and musculoskeletal ultrasonography exhibits promising diagnostic efficacy in discriminating between calcium pyrophosphate deposition disease and gouty arthritis.This combined approach serves as a valuable adjunctive tool for the diagnosis of both conditions.