OBJECTIVE: To analyze the B_el subtype gene mutation and its genetic mechanism in a family line. METHODS: ABO blood groups were identified by serologic tests. ABO genotyping was performed by polymerase chain reaction with sequence-specific primer (PCR-SSP). Sanger sequencing was performed on exons 1-7 of the ABO gene, the flanking intronic region, and exon 7 of the single strand of the gene confirmed the mutation site location. Missense3D software was used to predict the protein structure alteration caused by this mutation. RESULTS: Conventional serologic tests failed to detect erythrocyte B antigen in the proband and her three family members, and only trace amounts of B antigen expression could be detected by the absorption-dispersal test. DNA analysis showed that, on the basis of the normal ABO gene, there was a G>T substitution in the position of exon 7, position 803, which resulted in the change of amino acid 268 from Gly to Val. Further single-stranded sequencing analysis showed that the mutation site was located in the B gene. CONCLUSION In this family line, the proband, her father, her son, and her daughter all have reduced B type glycosyltransferase activity due to the new point mutation (c.803G>T) in exon 7 of the B gene, and the B antigen can only be detected by the absorption-dispersal method, and the point mutation can be stably inherited by offspring.
Point Mutation ; Alleles ; ABO Blood-Group System/genetics* ; Exons ; Introns ; Genotype ; Humans ; Male ; Female ; Glycosyltransferases/genetics*

OBJECTIVE: To determine the prevalence of lumbar spondylolysis (LS) and the proportion of spondylolytic spondylolisthesis (SS) in China, and to evaluate the musculoskeletal status of patients with LS and SS. METHODS: Spine Computed Tomography (CT) images were collected from community populations aged 40 and above in a nationwide multi-center project. LS was diagnosed, and SS was graded by an experienced radiologist. Bone mineral density (BMD) and paraspinal muscle parameters were quantified based on CT images. RESULTS: One hundred and seventeen patients of a total of 3,317 individuals were diagnosed with LS, corresponding to a prevalence rate of 3.53%. 63 of the 1,214 males (5.18%) and 54 of the 2,103 females (2.57%) were diagnosed with LS. SS occurred in 64/121 vertebrae (52.89%). BMD was not associated with LS ( P = 0.341). The L5 extensor paraspinal muscle density was higher in the LS group than in the non-LS group. In the LS group, patients with SS had a smaller L5 paraspinal extensor muscle cross-sectional area than those without SS ( P = 0.003). CONCLUSION The prevalence of LS in Chinese adults was 3.53%, with prevalence rates of 5.18% in males and 2.57% in females. Patients with LS have higher muscle density, whereas those with SS have smaller muscle cross-sectional areas at the L5 level.
Humans ; Male ; Female ; Middle Aged ; China/epidemiology* ; Prevalence ; Adult ; Lumbar Vertebrae/diagnostic imaging* ; Spondylolysis/diagnostic imaging* ; Aged ; Bone Density ; Tomography, X-Ray Computed ; Aged, 80 and over ; Spondylolisthesis/epidemiology* ; East Asian People

The incidence of intrahepatic cholangiocarcinoma (ICC) continues to rise, and there are no effective drugs to treat it. The immune microenvironment plays an important role in the development of ICC and is currently a research hotspot. Icaritin (ICA) is an innovative traditional Chinese medicine for the treatment of advanced hepatocellular carcinoma. It is considered to have potential immunoregulatory and anti-tumor effects, which is potentially consistent with the understanding of "Fuzheng" in the treatment of tumor in traditional Chinese medicine. However, whether ICA can be used to treat ICC has not been reported. Therefore, in this study, sgp19/kRas, an in situ ICC mouse model with intact immune system, was selected to evaluate the efficacy of ICA in the treatment of ICC in vivo for the first time, and the effects of ICA on the tumor immune microenvironment of ICC mice were analyzed by flow cytometry. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-138). In this study, sgp19/kRas ICC mouse model was treated with oral gavage of 100 mg·kg^-1 ICA. We found that ICA significantly inhibited tumor growth and tumor cell proliferation in the sgp19/kRas ICC mouse model after 3 weeks of treatment. Flow cytometry analysis indicated that ICA treatment markedly reduced the proportion of M2 macrophages and increased the number of CD3⁺CD4⁺ T cells. In vitro experiments demonstrated that ICA promoted macrophage polarization towards the M1 phenotype while inhibiting polarization towards the M2 phenotype. Furthermore, transcriptomic analysis suggested that ICA enhanced Toll-like receptor 9 (TLR9) expression, influencing macrophage nitric oxide metabolism synthesis pathways and receptor-related activities, thereby regulating macrophage polarization. In summary, this study demonstrates that ICA treatment significantly delays tumor progression in sgp19/kRas ICC mouse models. Mechanistically, ICA may achieve its anti-ICC effects by upregulating TLR9 receptor expression levels, promoting macrophage polarization towards the M1 phenotype, and altering the tumor immune microenvironment.

Objective To observe the effects of Tianma Gouteng Decoction combined with magnesium sulfate and Labetalol on lowering blood pressure and improving hemorheology in patients with gestational hypertension.Methods Ninety patients with gestational hypertension of liver-yang hyperactivity type were randomly divided into the combination group and the control group,with 45 cases in each group.The control group was treated with magnesium sulfate combined with Labetalol,and the combination group was treated with Tianma Gouteng Decoction on the basis of treatment for the control group.The course of treatment lasted for 5 days.The changes of systolic blood pressure(SBP),diastolic blood pressure(DBP),urinary protein level,and hemorheological indicators of the two groups were observed before and after the treatment.Moreover,the adverse pregnancy outcomes,adverse reactions,and patients'satisfaction of the two groups were compared.Finally,the influencing factors of patients'adverse pregnancy outcomes were investigated by logistic regression analysis.Results(1)After treatment,the SBP,DBP and urinary protein level of patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the combination group was significantly superior to that in the control group(P＜0.01).(2)After treatment,the hemorheological indicators of plasma viscosity,whole blood viscosity and hematocrit of patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the combination group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)The total incidence of adverse pregnancy outcomes in the combination group was 11.11%(5/45),which was significantly lower and that in the control group(33.33%,15/45),the difference being statistically significant(P＜0.05).(4)The patients'satisfaction of the combination group was 97.78%(44/45),which was significantly higher than that of the control group(84.44%,38/45),and the difference was statistically significant(P＜0.05).(5)The total incidence of adverse reactions in the combination group was 13.33%(6/45)and that in the control group was 8.89%(4/45),but the intergroup comparison showed no significant difference between the two groups(P＞0.05).(6)Logistic regression analysis of influencing factors showed that no medication of Tianma Gouteng Decoction combined with Labetalol and magnesium sulfate,and poor antihypertensive effect were the independent risk factors for adverse pregnancy outcomes in patients with gestational hypertension(all OR＞1,P＜0.05).Conclusion Tianma Gouteng Decoction combined with magnesium sulfate and Labetalol in treating gestational hypertension exerts certain antihypertensive effect,and the therapy can effectively improve the hemorheological indicators and the adverse pregnancy outcomes,and enhance the patients'satisfaction.

ObjectiveThe human angiotensin converting enzyme2 （hACE2） transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus （Delta/Omicron） to angiotensin converting enzyme2 （ACE2）. Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group， SARS-CoV-2 infection group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1， with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice， detect the virus titer of the lung tissue of the mice， and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro， with median inhibitory concentration （IC₅₀） of 526.3 mg·L^-1 and 653.0 mg·L^-1， respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT， Omicron， and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died， while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1 could reduce the mortality of mice， significantly lower the virus titer in the lung tissue of mice （P<0.05）， and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However， its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.

A a novel composite ZIF-8/MWCNT was synthesized by combining zeolitic imidazolate framework-8(ZIF-8)with multi-walled carbon nanotubes(MWCNT).The composite was modified on glassy carbon electrode(GCE)to obtain ZIF-8/MWCNT/GCE,which was served as an effective electrochemical sensor for detection of Pb2+ and Cd2+.Benefiting from the high electrical conductivity of MWCNT and the synergistic effect between ZIF-8 and MWCNT,ZIF-8/MWCNT showed excellent electrocatalytic activity in individual and simultaneous detection of Cd2+ and Pb2+.Under the optimized conditions,the linear ranges were 0.03?8.00 μmol/L and 0.03?6.00 μmol/L with corresponding limits of detection(S/N=3)of 0.019 and 0.035 μmol/L for individual detection of Cd2+and Pb2+,respectively.Whereas for simultaneous detection of Cd2+and Pb2+in their mixture solutions,the linear ranges were 0.03?5.00 μmol/L and 0.03?5.00 μmol/L with corresponding limits of detection(S/N=3)of 0.022 and 0.048 μmol/L,respectively.In addition,the sensor exhibited good stability,reproducibility and anti-interference ability.Moreover,the sensor showed good feasibility and accuracy for determination of Cd2+ and Pb2+ in actual river water samples with spiking recoveries of 98.1%?104.0%and 98.3%?102.2%,respectively.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
Animals ; Neurons/physiology* ; Mice ; Brain/physiology* ; Mice, Inbred C57BL ; Somatosensory Cortex/physiology* ; Neural Pathways/physiology* ; Hippocampus/physiology* ; Mice, Transgenic ; Male ; Brain Mapping ; Nerve Net/physiology* ; Substantia Nigra/physiology* ; Tomography, Optical/methods*

Objective:To explore the mechanism of Yiqi Yangyin decoction in the treatment of thyroid cancer by means of network pharmacology and molecular docking technique.Meth-ods:the chemical constituents of 10 kinds of Yiqi Yangyin decoction were searched by HERB database,the active components were screened by PubChem and SwissADNE,and the action targets of active components were predicted by Swisstargetprediction.The disease targets after operation of thyroid cancer were obtained by searching the databases of GeneCards,OMIM,Dis-GeNET and DrugBank.The intersection target of drug and disease was obtained by Venny2.1.0 platform,the intersection target protein interaction network was constructed by String database,and the core target protein was screened by Cytoscape3.9.1,the drug-active ingredient-target network map was constructed by Cytoscape3.9.1,and the key active components were obtained;the enrichment analysis of GO and KEGG was carried out using Metascape database;and the molecular docking verification of key targets and key components was carried out.Results:157active components of Yiqi Yangyin decoction were obtained,and 507targets of active compo-nents were predicted,1817 targets of thyroid cancer-related diseases and 154targets of drug-disease intersection were obtained.The key target genes of SRC,HSP90AA1,PIK3R1,PIK3CA and AKT1 were obtained by PPI analysis.Quercetin,kaempferol and luteolin were the key active components.Molecular docking showed that the key targets and key active components had good affinity.KEGG enrichment analysis showed that cancer pathway,PI3K-Akt pathway and HIF-1 pathway were the key pathways of drug action.Conclusion:Yiqi Yangyin decoction can play a therapeutic role in anti-inflammation,anti-tumor and improving tissue microenvironment with multi-components,multi-targets and multi-pathways.

ObjectiveTo compare the effects of programmed intermittent epidural bolus （PIEB） and continuous epidural infusion （CEI） on enhanced recovery after cesarean section. MethodsTotally 120 women scheduled to undergo elective cesarean section under combined spinal and epidural anesthesia， aged 18-45 years， with single fetus， full-term pregnancy （≥37 weeks）， ASA grade II or III， were recruited， with 60 cases in each group. At the end of the surgery， after a similar epidural loading dose， patients were randomLy assigned to receive either PIEB （6 mL·h^-1 beginning 30 minutes after the loading dose） or CEI （6 mL·h^-1， beginning immediately after the loading dose） for the maintenance of analgesia with 0.1% ropivacaine. At 2， 6， 12， 24 and 36 h postoperatively， VAS score was used to evaluate the composite pain， and Bromage Score was used to evaluate the degree of lower extremity motor block. The time to first flatus， time to first ambulation and the satisfaction scores were also recorded. ResultsThe VAS scores at 12， 24 and 36 h postoperatively and the lower extremity motor block scores at 6， 12 and 24 h postoperatively in the PIEB group were significantly lower than those in the CEI group （P < 0.01）. The epidural analgesic dosage was less in the PIEB group than that of the CEI group （P=0.002）. The time to first flatus and time to first ambulation were significantly shorter than those in the CEI group （P < 0.05）. The satisfaction scores were significantly higher in the PIEB group than in the CEI group （P < 0.05）. There was no significant difference in the first urination time after urinary catheter removal and the length of hospital stay between the two groups （P > 0.05）. ConclusionCompared with CEI， PIEB provides better postoperative analgesia， less motor block scores， lower epidural analgesic dosage， shorter the time to first flatus and defecation and time to first ambulation， and greater patient satisfaction， which is more consistent with the ERAS concept of analgesia.