ObjectiveThis paper aims to analyze the clinical characteristics and medication rationality of liver injury related to Epimedii Folium preparation （EP） and explore the possible risk factors of liver injury， so as to provide a reference for the safe clinical application of Epimedii Folium （EF）. MethodA retrospective analysis was conducted on liver injury cases related to EP from 2012 to 2016. ResultThe number of reported liver injury cases and the proportion of severe cases related to the use of EP show an increasing trend， indicating the objective existence of liver injury caused by EP. There are more cases of liver injury related to EP in women than in men， with an onset age range of 15-91 years old and a median onset age of 60 years old （median onset ages for men and women are 59 and 60 years old， respectively）. The time span from taking EP alone to the occurrence of liver injury is 1-386 days， with a median of 38 days. The time span from taking both EP and Western medicine to the occurrence of liver injury is 1-794 days， with a median of 34 days. EF-related liver injury preparations are mostly composed of traditional Chinese medicines that promote immunity and tonify the liver and kidney， indicating that immune stress in the body may be the mechanism of liver injury caused by the use of EP alone or in combination. There is no increasing trend of toxicity with time or dose in the liver injury caused by EP. By further exploring its risk factors， it is found that patients have unreasonable medication methods such as excessive dosage， repeated use， and multi-drug combination， which may also be one of the important risk factors for EF-related liver injury. ConclusionEP has a certain risk of liver injury and should be emphasized in clinical diagnosis and treatment. Immune stress may be the mechanism of liver injury caused by EP， and in clinical use， it is necessary to be vigilant about the risk of liver injury caused by unreasonable use and combined use with Western medicine.

Atherosclerosis caused by disorders of lipid metabolism is the main pathological basis of atherosclerotic cardiovascular disease.Statins are the cornerstone of lipid-modulating therapy for this type of disease,but in practice there are still some patients with suboptimal lipid management.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors have been gradually applied as a new class of lipid-modulating drugs for the treatment in patients with this type of disease,and recent studies have shown that in addition to regulating lipid metabolism,PCSK9 inhibitors also have potential anti-inflammatory and anti-platelet activation effects.This article sorts out the multiple pharmacological mechanisms of action of PCSK9 inhibitors and the current status of clinical research of PCSK9 inhibitors.Besides,it discusses the factors that may affect the efficacy of PCSK9 inhibitors,in order to provide a reference for the safe and rational medication of PCSK9 inhibitors.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

In order to study the analgesic effect of Shaoyao Gancao Decoction, this paper discussed material basis and mechanism from the perspective of macromolecules in traditional Chinese medicine. Inspired by the phenomenon of turbidity after boiling Chinese medicine, this experiment took Shaoyao Gancao Decoction as the research object to study the formation process of precipitation during boiling. The results showed that aggregates with a certain shape were formed in the solvent during the boiling process, and the precipitate was obtained by standing and centrifuging. Analysis found that the precipitation was mainly composed of small molecules such as paeoniflorin, albiflorin, liquiritin, glycyrrhizic acid, isoliquiritin and gallic acid, and macromolecules such as protein and polysaccharide. The composition of precipitate was consistent with that of Shaoyao Gancao Decoction, but the analgesic effect of Shaoyao Gancao Decoction after removing the precipitate was significantly reduced. Based on these results, we isolated small molecular compounds, polysaccharides and protein from Shaoyao Gancao Decoction and their contents are 60.4, 700.7 and 207.2 mg·g^-1 respectively. We get the ratio, polysaccharide: small molecule = 11.6∶1, protein: small molecule = 3.4∶1, the precipitate is prepared in the state of boiling. The characterization results showed that the particle size of the precipitate will change significantly after co-heating, and the content determination results showed that the content of the six small molecular compounds which was free in solvent was significantly reduced after the formation of the precipitate. The acetic acid writhing experiment proved that the precipitate has a good analgesic effect, and effectively reduced the levels of inflammatory factors prostaglandin E2 and nitric oxide, and increased the level of anti-inflammatory factor interleukin-10. These results proved that the precipitate in Shaoyao Gancao Decoction is an important material basis for analgesic effect, and macromolecules such as protein and polysaccharide are the main components of the precipitate. The study of macromolecules in the precipitate of Shaoyao Gancao Decoction not only provides new ideas and methods for elucidating the pharmacodynamic material basis of Shaoyao Gancao Decoction, but also provides a reference for analyzing the scientificity of traditional decoction.

BACKGROUND: Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood. METHODS: Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5. RESULTS: In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development. CONCLUSIONS CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.

Objective: To establish and optimize PCR methods for the gene encoding of Clostridium perfringens β₂ toxin (cpb₂) and atypical-cpb₂ (aty-cpb₂), analyze the epidemiological characteristics and genetic polymorphism of the cpb₂ of Clostridium perfringens in 9 Chinese areas from 2016 to 2021. Methods: The cpb₂ of 188 Clostridium perfringens strains were examined by PCR; the cpb₂ sequences were acquired by whole-genome sequencing to analyze the genetic polymorphism. Using Mega 11 and the Makeblastdb tool, a phylogenetic tree, and cpb₂-library based on 110 strains carrying the cpb₂ were produced. Using the Blastn technique, a comparison was made to discover sequence similarity between consensus-cpb₂ (con-cpb₂) and aty-cpb₂. Results: The specificity of PCR assay for the cpb₂ and aty-cpb₂ was verified. The PCR results for cpb₂ amplification were highly consistent with the whole-genome sequencing approach (Kappa=0.946, P<0.001). A total of 107 strains from nine regions in China carried cpb₂, 94 types A strains carried aty-cpb₂, 6 types A strains carried con-cpb₂, and 7 types F strains carried aty-cpb₂. The nucleotide sequence similarity between the two coding genes was 68.97%-70.97%, and the similarity between the same coding genes was 98.00%-100.00%. Conclusions: In this study, a specific PCR method for cpb₂ toxin was developed, and the previous PCR method for detecting aty-cpb₂ was improved. aty-cpb₂ is the primary gene encoding of β₂ toxin. There is a significant nucleotide sequence variance between the various cpb₂ genotypes.
Humans ; Clostridium perfringens/genetics* ; Clostridium Infections ; Bacterial Toxins/genetics* ; Phylogeny ; Polymerase Chain Reaction ; Polymorphism, Genetic

【Objective:】 To explore the correlation between hospital ethics atmosphere and work engagement of nurses in emergency department, and provide a basis for reasonably solving ethical issues and improving nurses’ work engagement. 【Methods:】 From May 2019 to May 2021, the convenient sampling method was used to select 350 nurses from emergency departments of four tertiary or above hospitals in Xi’an as the research subjects. The Ethical Climate Cognitive Scale and the Work Engagement Scale were used to evaluate the hospital ethical atmosphere and work engagement of nurse, and analyze their correlation. The univariate factor analysis and multiple factor analysis were used to explore the influencing factors. 【Results:】 The work engagement score of emergency department nurses was (51.69±11.09) points, and the ethical atmosphere score was (72.78±11.45) points. The results of univariate analysis showed that there were statistically significant differences in the work engagement scores among emergency department nurses with different educational backgrounds, hospital grades, hospital employment methods, and whether they had received ethics training (P<0.05). The results of multiple factor analysis indicated that the cognition of hospital ethical atmosphere, hospital employment methods, and whether they had received ethics education and training were all factors that affected work engagement (P<0.05). 【Conclusion:】 The hospital ethical atmosphere is positively correlated with the work engagement of emergency department nurse. The ethical atmosphere and work engagement of nurses are both at a moderate level, with significant room for improvement. Therefore, it is necessary to continue to strengthen the management support of emergency nursing work and improve the perceived level of recognition and respect among emergency department nurses in the organization.

Objective: To investigate the influence of autologous adipose stem cell matrix gel on wound healing and scar hyperplasia of full-thickness skin defects in rabbit ears, and to analyze the related mechanism. Methods: Experimental research methods were adopted. The complete fat pads on the back of 42 male New Zealand white rabbits aged 2 to 3 months were cut to prepare adipose stem cell matrix gel, and a full-thickness skin defect wound was established on the ventral side of each ear of each rabbit. The left ear wounds were included in adipose stem cell matrix gel group (hereinafter referred to as matrix gel group), and the right ear wounds were included in phosphate buffer solution (PBS) group, which were injected with autologous adipose stem cell matrix gel and PBS, respectively. The wound healing rate was calculated on post injury day (PID) 7, 14, and 21, and the Vancouver scar scale (VSS) scoring of scar tissue formed on the wound (hereinafter referred to as scar tissue) was performed in post wound healing month (PWHM) 1, 2, 3, and 4. Hematoxylin-eosin staining was performed to observe and measure the histopathological changes of wound on PID 7, 14, and 21 and the dermal thickness of scar tissue in PWHM 1, 2, 3, and 4. Masson staining was performed to observe the collagen distribution in wound tissue on PID 7, 14, and 21 and scar tissue in PWHM 1, 2, 3, and 4, and the collagen volume fraction (CVF) was calculated. The microvessel count (MVC) in wound tissue on PID 7, 14, and 21 and the expressions of transforming growth factor β₁ (TGF-β₁) and α smooth muscle actin (α-SMA) in scar tissue in PWHM 1, 2, 3, and 4 were detected by immunohistochemical method, and the correlation between the expression of α-SMA and that of TGF-β₁ in scar tissue in matrix gel group was analyzed. The expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) in wound tissue were detected by enzyme-linked immunosorbent assay on PID 7, 14, and 21. The number of samples at each time point in each group was 6. Data were statistically analyzed with analysis of variance for repeated measurement, analysis of variance for factorial design, paired sample t test, least significant difference test, and Pearson correlation analysis. Results: On PID 7, the wound healing rate in matrix gel group was (10.3±1.7)%, which was close to (8.5±2.1)% in PBS group (P>0.05). On PID 14 and 21, the wound healing rates in matrix gel group were (75.5±7.0)% and (98.7±0.8)%, respectively, which were significantly higher than (52.7±6.7)% and (90.5±1.7)% in PBS group (with t values of 5.79 and 10.37, respectively, P<0.05). In PWHM 1, 2, 3, and 4, the VSS score of scar tissue in matrix gel group was significantly lower than that in PBS group (with t values of -5.00, -2.86, -3.31, and -4.45, respectively, P<0.05). Compared with the previous time point within the group, the VSS score of scar tissue at each time point after wound healing in the two groups was significantly increased (P<0.05), except for PWHM 4 in matrix gel group (P>0.05). On PID 7, the granulation tissue regeneration and epithelialization degree of the wounds between the two groups were similar. On PID 14 and 21, the numbers of fibroblasts, capillaries, and epithelial cell layers in wound tissue of matrix gel group were significantly more than those in PBS group. In PWHM 1, 2, 3, and 4, the dermal thickness of scar tissue in matrix gel group was significantly thinner than that in PBS group (with t values of -4.08, -5.52, -6.18, and -6.30, respectively, P<0.05). Compared with the previous time point within the group, the dermal thickness of scar tissue in the two groups thickened significantly at each time point after wound healing (P<0.05). Compared with those in PBS group, the collagen distribution in wound tissue in matrix gel group was more regular and the CVF was significantly increased on PID 14 and 21 (with t values of 3.98 and 3.19, respectively, P<0.05), and the collagen distribution in scar tissue was also more regular in PWHM 1, 2, 3, and 4, but the CVF was significantly decreased (with t values of -7.38, -4.20, -4.10, and -4.65, respectively, P<0.05). Compared with the previous time point within the group, the CVFs in wound tissue at each time point after injury and scar tissue at each time point after wound healing in the two groups were significantly increased (P<0.05), except for PWHM 1 in matrix gel group (P>0.05). On PID 14 and 21, the MVC in wound tissue in matrix gel group was significantly higher than that in PBS group (with t values of 4.33 and 10.10, respectively, P<0.05). Compared with the previous time point within the group, the MVC of wound at each time point after injury in the two groups was increased significantly (P<0.05), except for PID 21 in PBS group (P>0.05). In PWHM 1, 2, 3, and 4, the expressions of TGF-β₁ and α-SMA in scar tissue in matrix gel group were significantly lower than those in PBS group (with t values of -2.83, -5.46, -5.61, -8.63, -10.11, -5.79, -8.08, and -11.96, respectively, P<0.05). Compared with the previous time point within the group, the expressions of TGF-β₁ and α-SMA in scar tissue in the two groups were increased significantly at each time point after wound healing (P<0.05), except for the α-SMA expression in matrix gel group in PWHM 4 (P>0.05). There was a significantly positive correlation between the expression of α-SMA and that of TGF-β₁ in scar tissue in matrix gel group (r=0.92, P<0.05). On PID 14 and 21, the expressions of VEGF (with t values of 6.14 and 6.75, respectively, P<0.05) and EGF (with t values of 8.17 and 5.85, respectively, P<0.05) in wound tissue in matrix gel group were significantly higher than those in PBS group. Compared with the previous time point within the group, the expression of VEGF of wound at each time point after injury in the two groups was increased significantly (P<0.05), and the expression of EGF was decreased significantly (P<0.05). Conclusions: Adipose stem cell matrix gel may significantly promote the wound healing of full-thickness skin defects in rabbit ears by promoting collagen deposition and expressions of VEGF and EGF in wound tissue, and may further inhibit the scar hyperplasia after wound healing by inhibiting collagen deposition and expressions of TGF-β₁ and α-SMA in scar tissue.
Male ; Rabbits ; Animals ; Cicatrix ; Vascular Endothelial Growth Factor A ; Epidermal Growth Factor ; Hyperplasia ; Wound Healing ; Stem Cells ; Transforming Growth Factor beta

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVE: To evaluate the clinical characteristics, treatment and prognosis of systemic anaplastic large cell lymphoma(sALCL). METHODS: The clinical data of 90 cases with sALCL treated in the Department of Hematology of the Affiliated Xijing Hospital of Air Force Medical University from November 2018 to October 2021 were retrospectively analyzed. The clinical features, treatment and prognosis were summarized and the prognostic factors were investigated. RESULTS: There were 58 males and 32 females, with a median age of 32 (12-73) years old. 69 (76.7%) patients had Ann Arbor stage Ⅲ-Ⅳ disease and half of the patients had extranodal infiltration. The median age was 27(12-72) years of the 60 ALK⁺ patients while 53(15-73) years of the 30 ALK^- patients, and it was significantly different in the age of onset between the two group(P<0.01). 88 patients received first line chemotherapy, and 50(568%) cases achieved complete remission(CR). IPI score≥3 was an independent risk factor for CR. The median progressive free survival(PFS) and overall survival(OS) of the patients were not reached. Multivariate analysis showed that no achievement of CR after first-line therapy was a significant prognostic factor influencing PFS and OS. CONCLUSION sALCL mainly occurs in males and most patients were in advanced stage. Half of the patients had extranodal involvement. The CR rate after first-line chemotherapy was 568%, and IPI score≥3 was a significant prognostic factor for CR. No achievement of CR after first-line therapy is poorly prognostic for PFS and OS.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child ; Disease-Free Survival ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic/diagnosis* ; Male ; Middle Aged ; Prognosis ; Receptor Protein-Tyrosine Kinases ; Retrospective Studies ; Young Adult