[Objective] To explore the accuracy and feasibility of non-invasive prenatal diagnosis of fetal RhE genotype using cell-free fetal DNA (cff-DNA) from maternal peripheral blood. [Methods] A total of 134 pregnant women with single fetuses and RhE-negative blood group were selected from our hospital from November 2023 to August 2024. Free DNA extraction kit was used to extract free DNA from peripheral blood of pregnant women, and the RhE blood group genotype of free DNA was detected by real-time fluorescent quantitative PCR (RT-qPCR). If the qPCR amplification signal of the sample was negative, the methylated RASSF1A gene was amplified, and the positive amplification result was used as a sign of successful extraction of cff-DNA. Serological microcolumn gel method was used to detect the phenotype of RhE blood group in neonatal peripheral blood. [Results] Among the 134 maternal peripheral blood samples, the cff-DNA detection of RhE blood group phenotypes was consistent with the RhE blood group genotyping of neonatal peripheral blood in 133 cases, including 90 cases of Rhee genotype and 43 cases of RhE genotype, with diagnostic concordance rate of 99.3%, sensitivity of 97.7%, specificity of 100%, youden index of 0.977, area under ROC curve of 0.995, the Kappa value of 0.983, positive predictive value of 100%, and negative predictive value of 98.9%. The sample of 1 case failed to be detected. After the amplification of methylated RASSFIA gene, it was confirmed that the reason for the failure was that no cff-DNA was extracted from the sample. The diagnostic concordance rates of the first, second and third trimesters were 93.8% (15/16), 100% (51/51) and 100% (67/67), respectively. Fisher's exact test method was used to calculate the P value, which was P>0.05, indicating that there was no statistical significance in the difference of diagnostic concordance rate among the three pregnancy periods, and there was no difference in the detection concordance rate of this method in different pregnancy periods. [Conclusion] The use of cff-DNA in maternal peripheral blood for the detection of fetal RhE blood group genotype is an accurate and highly feasible non-invasive prenatal diagnostic method, which is helpful for the clinical diagnosis of fetal and neonatal hemolytic disease caused by anti-E antibody.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Based on the theory of qi， blood and fluids， and taking into account of the pathogenesis evolution process from constraint to phlegm， stasis and then mass in pulmonary nodules， an attempt has been made to construct a three-dimensional differentiation system for pulmonary nodules from the dimensions of time and space. The temporal progression of the early， middle， and late stages of pulmonary nodules reflects the pathological changes from constraint to phlegm and then stasis in the metabolism disorders of qi， blood and fluid. The spatial structures such as size， density， and morphology of pulmonary nodules reflect the pathological states of the duration， severity， and primary and secondary conditions of qi， blood and fluid metabolism disorders. Based on the temporal progression， the therapeutic principles have been proposed， which are dispelling pathogenic factors and promoting the use of beneficial factors to interrupt the growth momentum in the early stage， removing turbidity and dispersing phlegm to reduce the degree of nodules in the middle stage， and dispersing nodulation and eliminating abnormalities in the late stage. Based on the spatial structures， the suggested therapeutic methods are using wind herbs， employing multiple approaches to treat phlegm， and promoting blood circulation to resolve stasis， so as to provide theoretical reference for the systematic diagnosis and treatment of pulmonary nodules in traditional Chinese medicine.

This paper summarized Professor LI Yueqing's clinical experience in treating prostate cancer by stages from the perspective of deficiency and stasis. It is believed that the onset of prostate cancer is due to kidney deficiency， while blood stasis is the core pathogenesis， and dampness-heat， phlegm-turbid， and cancer toxins are the key pathological factors in the progression of the disease. The pathogenesis in the early stage of the disease is kidney qi depletion and dampness， heat and phlegm coagulation； in the middle stage， it is spleen and kidney depletion， phlegm coagulation and blood stasis； and in the late stage， the pathogenesis changes into yin deficiency and essence depletion， and stasis-turbid toxin obstruction. For treatment， the basic principle is to supplement and boost kidney qi， enrich and nourish the kidney yin. The main treatment methods are draining dampness， dissolving phlegm， dispelling stasis， clearing heat and resolving toxins， and the method of invigorating blood and dispelling stasis runs through the whole course of treatment. In the early stage， radical treatment is mainly used， and Longshe Yangquan Decoction （龙蛇羊泉汤） with modifications is supplemented to clear and drain dampness and heat. In the middle stage， androgen deprivation therapy is the basic treatment， and Bushen Tongqiao Decoction （补肾通窍汤） with modifications is used in combination to nourish the spleen and kidney， dissolve phlegm and dispel stasis. In the late stage， Dabuyin Pills and Liuwei Dihuang Pills （大补阴丸合六味地黄丸） with modifications is mainly used to enrich yin and supplement essence， resolve toxins and dissolve stasis， and prevent cancer recurrence.

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

OBJECTIVE: To observe the protective effect and mechanism of hydroxyl safflower yellow A (HSYA) from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were treated with oxygen-glucose deprivation reperfusion (OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations (1.25-160 µ mol/L) of HSYA on HUVECs after OGD/R. HSYA 80 µ mol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin (IL)-18, IL-1 β, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor α (TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3 (NLRP3), gasdermin D (GSDMD) and GSDMD-N-terminal domain (GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt (CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1 (Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot. RESULTS: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18, IL-1 β, MCP-1, TNF-α and IL-6 (P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3, Caspase-1, GSDMD and GSDMD-N proteins (P<0.01). CONCLUSIONS The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Chalcone/analogs & derivatives* ; Quinones/pharmacology* ; Pyroptosis/drug effects* ; Caspase 1/metabolism* ; Glucose ; Phosphate-Binding Proteins/metabolism* ; Signal Transduction/drug effects* ; Intracellular Signaling Peptides and Proteins/metabolism* ; Oxygen/metabolism* ; Cytokines/metabolism* ; Gasdermins

Neurodegenerative diseases are a type of disease characterized by specific types of neuronal loss and progressive progression,mainly represented by Alzheimer's disease and Parkinson's disease.This type of disease,due to its intractable and irreversible symptoms,brings great physical and psychological burden to patients,which is seriously disturbing their normal life.In terms of treatment,there is currently no specific treatment for Alzheimer's disease in clinical practice,and first-line treatment drugs for Parkinson's disease also have great limitations.In traditional Chinese medicine,kidney governs bone,generates marrow,and connects to the brain.In clinical evidence typing,premature aging,fatigue and forgetfulness,and tremor of limbs caused by kidney deficiency and medullary reduction are considered to be the main pathologies of these diseases.Di-Huang-Yin-Zi decoction which is derived from the"General Records of Holy Universal Relief",is recorded as a good formula for nourishing kidney yin and filling kidney yang.Clinical data shows that this formula has significant therapeutic effects in treating neurodegenerative diseases caused by kidney essence deficiency.Modern research results indicate that its mechanism of action involves inhibiting inflammatory reactions,regulating mitochondrial autophagy,reversing The hypothalamic-pituitary-adrenal axis abnormalities,and neuroprotection.The main effective ingredients in this formula include loganin,echinarin,and schisandrin A.This article aims to summarize and analyze the clinical efficacy,mechanism of action,and active ingredients of Di-Huang-Yin-Zi decoction in the treatment of Alzheimer's and Parkinson's disease in recent years,in order to clarify the research status of Di-Huang-Yin-Zi decoction in the neurodegenerative disease and provide reference for further research.

Objective: : Blood-blister aneurysms (BBAs) of the internal carotid artery (ICA) are challenging lesions with high morbidity and mortality rates. Although research on BBAs is well documented in different populations, the study of BBAs in the Tibetan population is extremely rare. This study aimed to evaluate the characteristics of BBAs and analyze the treatment modalities and long-term outcomes in the Tibetan population in comparison with the Han population. Methods: : The characteristics of patients with BBAs of the ICA from January 2009 to January 2021 at our institution were reviewed. The features of aneurysms, treatment modalities, complications, and follow-up outcomes were retrospectively analyzed. Results: : A total of 130 patients (41 Tibetan and 89 Han patients) with BBAs of the ICA who underwent treatment were enrolled. Compared with the Han group, the Tibetan group significantly demonstrated a high ratio of BBAs among ICAs (8.6%, 41/477 vs. 1.6%, 89/5563; p<0.05), a high ratio of vasospasm (34.1%, 14/41 vs. 6.7%, 6/89; p=0.001), a high risk of ischemic events (43.9%, 18/41 vs. 22.5%, 20/89; p<0.05), and a low ratio of good outcomes (modified Rankin scale, 0–2) at the 1-year follow-up (51.2%, 21/41 vs. 74.2%, 66/89; p<0.05). The multivariate regression model showed that ischemic events significantly contributed to the prediction of outcomes at 1 year. Further analysis revealed that microsurgery and vasospasm were associated with ischemic events. Conclusion : In comparison with Han patients, the Tibetan population had a high ratio of BBA occurrence, a high incidence of ischemic events, and a high ratio of poor outcomes. The endovascular approach showed more benefits in BBA patients.

Respiratory syncytial virus (RSV) is an enveloped, negative-sense, single-stranded RNA virus of the Orthopneumovirus  genus of the Pneumoviridae family in the order Mononegavirales. RSV can cause acute upper and lower respiratory tract infections, sometimes with extrapulmonary complications. The disease burden of RSV infection is enormous, mainly affecting infants and older adults aged 75 years or above. Currently, treatment options for RSV are largely supportive. Prevention strategies remain a critical focus, with efforts centered on vaccine development and the use of prophylactic monoclonal antibodies. To date, three RSV vaccines have been approved for active immunization among individuals aged 60 years and above. For children who are not eligible for these vaccines, passive immunization is recommended. A newly approved prophylactic monoclonal antibody, Nirsevimab, which offers enhanced neutralizing activity and an extended half-life, provides exceptional protection for high-risk infants and young children. This review provides a comprehensive and detailed exploration of RSV's virology, immunology, pathogenesis, epidemiology, clinical manifestations, treatment options, and prevention strategies.
Humans ; Respiratory Syncytial Virus Infections/prevention & control* ; Respiratory Syncytial Viruses/pathogenicity* ; Respiratory Syncytial Virus, Human/pathogenicity* ; Antiviral Agents/therapeutic use*

Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid decline in renal function. Renal ischemia-reperfusion injury (RIRI) is one of the main causes of AKI with the underlying mechanism incompletely clarified. The liver X receptors (LXRs), including LXRα and LXRβ, are members of the nuclear receptor superfamily. It has been shown that LXRs play an important role in regulating glucose and lipid metabolism, cholesterol efflux, and inflammation. The purpose of this study was to explore the role and mechanism of LXRs in RIRI. We determined the effects of LXR activation on renal function and histological changes in a mouse RIRI model and a cellular model of hypoxia/reoxygenation (H/R). In vivo results showed that LXRs agonist GW3965 significantly inhibited the increase of serum creatinine and urea nitrogen levels induced by RIRI. Both HE and PAS staining of kidney tissues revealed that GW3965 alleviated the morphological damages caused by RIRI. Immunohistochemical staining showed that GW3965 mitigated 4-HNE and GRP78 levels induced by RIRI. Furthermore, TUNEL assay indicated that GW3965 reduced RIRI-induced renal cell apoptosis. Quantitative real-time PCR (qPCR) analysis revealed that GW3965 attenuated RIRI-induced IL-6 and IL-1β mRNA expression. Compared with wild-type group, LXRα gene deficiency had little effect on RIRI-associated renal functional decline and morphological damages. Additionally, in vitro study demonstrated that GW3965 alleviated H/R-induced decrease of HK-2 human renal proximal tubule cell viability and restored the activity of superoxide dismutase (SOD) after H/R. Western blot results showed that GW3965 mitigated the increase of 4-HNE and GRP78 protein expression levels after H/R; However, knockdown of LXRβ using the small interfering RNA (siRNA) technique reduced cell viability compared to GW3965-treated group. Taken together, the LXRs agonist GW3965 significantly alleviates RIRI in mice possibly by reducing apoptosis, oxidative stress, endoplasmic reticulum stress and inflammation. These results also preliminarily confirm that the renal protective effects of LXRs agonists are dependent on LXRβ.
Animals ; Liver X Receptors/genetics* ; Reperfusion Injury/prevention & control* ; Mice ; Benzoates/pharmacology* ; Benzylamines/pharmacology* ; Male ; Endoplasmic Reticulum Chaperone BiP ; Mice, Inbred C57BL ; Apoptosis ; Acute Kidney Injury/prevention & control* ; Kidney/pathology* ; Humans