This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

Objective To analyze risk factors and pathogenic characteristics of intestinal colonization of carbape-nem-resistant Enterobacterales(CRE)in patients from intensive care unit(ICU).Methods A total of 392 ICU pa-tients who underwent intestinal CRE screening in a tertiary hospital in Changzhou from March to December,2023 were divided into the colonization group(n=42)and the non-colonization group(n=350)according to the screening results.Clinical data of patients,including age,gender,underlying diseases,malignant tumors,radiotherapy,chemotherapy,infection before the last screening,antimicrobial use,and invasive procedures were collected for the analysis on risk factors and pathogenicity.Results Among 42 patients with positive CRE screening results,44 CRE strains were detected,mainly Klebsiella pneumoniae(65.91％),followed by Escherichia coli(15.91％)and En-terobacter cloacae(13.64％).The average time from admission in ICU to positive screening results of intestinal CRE in the colonization group was 14 days.Long term use of carbapenem antibiotics(OR=1.47,95％CI:1.31-1.65),mechanical ventilation(OR=1.14,95％CI:1.06-1.22),and Enterobacterales infection(OR=10.10,95％CI:3.28-32.09)were independent risk factors for intestinal CRE colonization.Patients who received carbap-enem antibiotics for ≥15 days(x2=167.52,P＜0.001)and those who received mechanical ventilation for ≥15 days(x2=101.03,P＜0.001)had higher risks for intestinal CRE colonization.Conclusion In clinical practice,it is necessary to improve pathogen detection,treat Enterobacterales infection timely,choose carbapenem antibiotics carefully,shorten treatment course,actively evaluate indications for mechanical ventilation,and wean off ventilator timely.

Objective:To explore the correlation between peripheral blood B cell count and clinical features and prognosis of patients with newly diagnosed diffuse large B-cell lymphoma(DLBCL).Methods:The relationship of peripheral blood B cell count with clinical features,laboratory indexes and prognosis in 67 patients with newly diagnosed DLBCL was retrospectively analyzed.Results:Patients were divided into low B-cell count group(B cell＜0.1 × 109/L,n=34)and high B-cell count group(B cell≥0.1 × 109/L,n=33)according to the median B cell count values.Compared with the high B cell count group,the low B cell count group had a higher proportion of patients with Lugano stage Ⅲ-Ⅳ,elevated LDH,elevated β2-MG and IPI score 3-5 and increased CRP(P=0.033,0.000,0.023,0.001,0.033).The peripheral CD3+and CD4+cell counts of patients in the low B cell count group were significantly lower than those in the high B cell count group(P=0.010,0.017).After initial treatment,overall response rate(ORR)and complete remission(CR)rate in high B cell count group were significantly higher than those in low B cell count group(P=0.032,0.013).The median follow-up time of patients was 23(2-77)months,progression-free survival(PFS)and overall survival(OS)of patients in the high B cell count group were significantly better than those in the low B cell count group(P=0.001,0.002).Univariate analysis showed that pretreatment low B cell count in the peripheral blood was associated with shortened PFS and OS(HR=4.108,P=0.002;HR=8.218,P=0.006).Multivariate analysis showed that low B cell count was an independent prognostic factor for shortened PFS(HR=3.116,P=0.037).Conclusion:Decreased peripheral blood B cell count in newly diagnosed DLBCL patients is associated with high-risk clinical features and may affect the efficacy of immunochemotherapy,which is associated with poor clinical prognosis.

Objective: To explore the clinical and imaging features of acute encephalopathy with biphasic seizures and late reduced diffusion(AESD) in children. Methods: For the case series study, 21 children with AESD from Peking University First Hospital, Provincial Children's Hospital Affiliated to Anhui Medical University, Children's Hospital of Fudan University, and Shanxi Children's Hospital who were diagnosed and treated from October 2021 to July 2023 were selected. Clinical data were collected to summarize their clinical information, imaging, and laboratory tests, as well as treatment and prognostic characteristics. Descriptive statistical analysis was applicated. Results: Of the 21 cases with AESD, 11 were males and 10 were females, with the age of onset of 2 years and 6 months (1 year and 7 months, 3 years and 6 months). Of the 21 cases, 18 were typical cases with biphasic seizures. All typical cases had early seizures within 24 hours before or after fever onset. Among them, 16 cases had generalized seizures, 2 cases had focal seizures, and 7 cases reached the status epilepticus. Of the 21 cases, 3 atypical cases had late seizures in biphasic only. The late seizures in the 21 cases occurred on days 3 to 9. The types of late seizures included focal seizures in 12 cases, generalized seizures in 6 cases, and both focal and generalized seizures in 3 cases. Diffusion-weighted imaging (DWI) test on days 3 to 11 showed reduced diffusion of subcortical white matter which was named "bright tree sign" in all cases. The diffuse cerebral atrophy predominantly presented in the front-parietal-temporal lobes was found in 19 cases between day 12 and 3 months after the onset of the disease. Among 21 cases, 20 had been misdiagnosed as autoimmune encephalitis, central nervous system infection, febrile convulsions, posterior reversible encephalopathy syndrome, acute disseminated encephalomyelitis, and hemiconvulsion-hemiplegia-epilepsy syndrome. All the cases received high-dose gammaglobulin and methylprednisolone pulse therapy with poor therapeutic effect. By July 2023, 18 cases were under follow-up. Among them, 17 cases were left with varying degrees of neurologic sequelae, including 11 cases with post-encephalopathic epilepsy; 1 recovered completely. Conclusions: AESD is characterized by biphasic seizures clinically and "bright tree sign" on DWI images. Symptomatic and supportive treatments are recommended. The immunotherapy is ineffective. The prognosis of AESD is poor, with a high incidence of neurological sequelae and a low mortality.
Male ; Female ; Child ; Humans ; Infant ; Child, Preschool ; Posterior Leukoencephalopathy Syndrome/complications* ; Seizures/etiology* ; Brain Diseases/diagnostic imaging* ; Status Epilepticus ; Seizures, Febrile/diagnostic imaging*

ObjectiveThis study aimed to analyze different transcripts specifically expressed by red blood cells in RhD-positive individuals， and to explore the mechanism of alternative splicing. MethodsErythroblasts from RhD-positive individuals were isolated and cultured in an in vitro erythroblast culture system. The fragment from exon 6 to 3’untranslated coding regions of RHD gene of RhD-positive individuals was amplified by reverse transcription polymerase chain reaction （RT-PCR） method. The PCR products were then sequenced by next-generation sequencing and the mRNA transcripts were analyzed. The maximum entropy values of 5’ splice site （ss） and 3’ ss of all exons of RHD gene were analyzed using bioinformatics. ResultsThe transcripts of the RHD gene were mainly normal full-length mRNA. In addition， eight other abnormal transcripts were also identified. According to the expression frequencies （high to low）， these transcripts were exon 7 deletion， exon 9 deletion， exons 8 and 9 deletion， exons 7-9 deletion， exons 7 and 9 deletion， exons 8-9 deletion and 170 bp insertion between exon 7 and 10， full-length with 170 bp insertion between exon 7 and 8， exon 9 deletion and 170 bp insertion between exon 7 and 8. The last three transcripts were novel. Bioinformatic analysis suggested that the abnormal splicing of exon 7 and exon 9 might be due to the decreased binding ability of 5’ss or 3’ss to the spliceosome. The intron 7 was expressed in mRNA， which might be related to the sequences conserved with 5’ss and 3’ss splicing. ConclusionThe alternative splicing patterns of RHD gene are very complicated， which leads to various transcripts at the mRNA level of the RHD gene from RhD-positive individuals.

OBJECTIVE: To investigate the effects of different routes in placental mesenchymal stem cells (PMSC) on serum expression levels of IL-4, IL-17, TNF-α and IFN-γ in aplastic anemia (AA) rats. METHODS: The rat model of aplastic anemia (AA rats) was established by 5-fluorouracil combined with busulfan. The rats was divided into four groups: control, experimental, PMSC-injected into the tail vein, and PMSC-injected into the medullary cavity. The general state of rats in each group was observed in detail before and after treatment. The serum levels of interleukin-4 (IL-4) , interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) were measured by enzyme-linked immunosorbent assay (ELISA) at week 1, 3 and 5 after treatment. RESULTS: The serum levels of TNF-α, IFN-γ and IL-17 in the experimental group were significantly higher than those in the control group, while the level of IL-4 was significantly decreased (P＜0.05). The levels of TNF-α, IFN-γ and IL-17 gradually decreased after treatment while the level of IL-4 increased. By the fifth week, the above indexes were closed to the control group (P＞0.05), and the levels of TNF-α, IFN-γ and IL-17 in the group with PMSCs injected via the medullary cavity decrease more significantly than those group with PMSC injected via the tail vein, but level of IL-4 was not significantly different between two groups. CONCLUSION The level of serum hematopoietic negative regulators increase significantly, and the level of hematopoietic promoting factors decreases significantly in aplastic anemia rats. PMSC can down-regulate the level of hematopoietic negative regulators and up-regulate the level of hematopoietic promoting factors in the rats with aplastic anemia, and the inhibition of hematopoietic negative regulators by intramedullary injection is more significant than that by caudal vein injection.
Anemia, Aplastic ; Animals ; Female ; Hematopoietic Stem Cell Transplantation ; Interferon-gamma ; Mesenchymal Stem Cells ; Placenta ; Pregnancy ; Rats ; Tumor Necrosis Factor-alpha

Objective: To investigate the surgical techniques and clinical effect of Memokath transurethral spiral thermo-expandable prostatic stent (STEPS) implantation in the treatment of BPH. METHODS: From January 2017 to January 2018, 26 BPH patients underwent Memokath transurethral STEPS implantation, 9 under the flexible cystoscope and the other 17 under the rigid cystoscope. The patients were aged 62－91 years old, with a prostate volume of 32－78 ml, postvoid residual urine volume (PVR) of (67.3 ± 11.2) ml, maximum urinary flow rate (Qmax) of (6.3 ± 1.8) ml/s, and IPSS score of 26.7 ± 5.7. Eight of the patients had preoperative urinary retention, of whom, 6 received catheterization and 2 had undergone cystostomy for bladder fistula before STEPS implantation. RESULTS: The operations lasted 15－30 minutes and were successfully completed in 24 cases while stent-shedding occurred in the other 2. Twenty-two of the patients achieved spontaneous urination immediately after surgery and 2 experienced bladder clot embolism. At 3 month after surgery, 24 of the patients showed significant improvement in PVR (［21.4 ± 7.7］ ml), Qmax (［18.3 ± 4.7］ ml/s) and IPSS (8.3 ± 2.1), and 13 exhibited no statistically significant difference from the baseline in the IIEF-5 score (14.1 ± 1.1 vs 14.3 ± 1.0, P > 0.05). At 12 months, all the patients were found with markedly improved urination but no adverse events except recurrent urinary tract infection in 2 cases. CONCLUSIONS Memokath STEPS implantation, with its advantages of simple operation, high safety, definite effectiveness, non-influence on sexual function, is a new effective surgical option for the treatment of BPH.

The present study is to establish a quantitative analysis of multi-components by single marker(QAMS) for determining contents of seven compositions in Alismatis Rhizoma, alismoxide, alisol C 23-acetate, alisol A, alismol, alisol B, alisol B 23-acetate and 11-deoxy-alisol B. Six relative correction factors(RCFs) of alismoxide, alisol C 23-acetate, alisol A, alismol, alisol B and 11-deoxy-alisol B were established in the UPLC method with alisol B 23-acetate as the internal standard, which was to calculate the mass fraction of each. The mass fraction of seven effective constituents in Alismatis Rhizoma was calculated by the external standard method(ESM) at the same time. Compared with the content results determined by the ESM and QAMS, the feasibility and accuracy of QAMS method were verified. Within the linear range, the RCFs of alismoxide, alisol C 23-acetate, alisol A, alismol, alisol B, 11-deoxy-alisol B were 0.946, 4.183, 0.915, 1.039, 0.923 and 1.244, respectively, with good repeatability in different experimental conditions. There was no significant difference between the QAMS method and ESM method. Then, QAMS method was applied to determination of the different degree Alismatis Rhizoma from different areas. As a result, the concentrations of 7 components have differences in different areas, but no significant differences in different grades. The QAMS method is feasible and accurate for the determination of the seven chemical compositions, and which can be used for quality control of Alismatis Rhizoma.
Alismatales ; chemistry ; Drugs, Chinese Herbal ; analysis ; Phytochemicals ; analysis ; Rhizome ; chemistry

Near infrared spectroscopy combined with chemometrics methods was used to distinguish Ganoderma lucidum samples collected from different origins, and a prediction model was established for rapid determine polysaccharides contents in these samples. The classification accuracy for training dataset was 96.87%, while for independent dataset was 93.33%; as for the prediction model, 5-fold cross-validation was used to optimize the parameters, and different signal processing methods were also optimized to improve the prediction ability of the model. The best square of correlation coefficients for training dataset was 0.965 4, and 0.851 6 for validation dataset; while the root-mean-square deviation values for training dataset and validation dataset were 0.018 5 and 0.023 6, respectively. These results showed that combining near infrared spectroscopy with suitable chemometrics approaches could accuracy distinguish different origins of G. lucidum samples; the established prediction model could precious predict polysaccharides contents, the proposed method can help determine the activity compounds and quality evaluation of G. lucidum.
Fungal Polysaccharides ; analysis ; Geography ; Least-Squares Analysis ; Reishi ; chemistry ; Spectroscopy, Near-Infrared

We established the rapid response system for non-hospitalized patients from 2012 in order to improve the effectiveness of emergent critical care for non-hospitalized patients when emergency happened.From January 2013 to December 2016,there were 122 cases with RRS activation for non-hospitalized patients.The time to arrive was 3.16±0.41 min,and 107 cases(86.89％)were sent to the emergency department.Fifteen patients(14.02％)were classified as level 1,26(24.03％)as level Ⅱ,48(16.82％)as level Ⅲ,and 18(16.82％) as level ⅣV,and 83％ were critical patients.Rapid response system is important to cope with emergency in non-hospitalized patients.