The medicinal materials of Bawei Chenxiang Pills(BCPs) were extracted via three methods: reflux extraction by water, reflux extraction by 70% ethanol, and extraction by pure water following reflux extraction by 70% ethanol, yielding three extracts of ST, CT, and CST. The efficacy of ST(760 mg·kg~(-1)), CT(620 mg·kg~(-1)), and CST(1 040 mg·kg~(-1)) were evaluated by acute myocardial ischemia(AMI) and p-chlorophenylalanine(PCPA)-induced insomnia in mice, respectively. Western blot was further utilized to investigate their hypnosis mechanisms. The main chemical components of different extracts were identified by the UPLC-Q-Exactive-MS technique. The results showed that CT and CST significantly increased the ejection fraction(EF) and fractional shortening(FS) of myocardial infarction mice, reduced left ventricular internal dimension at end-diastole(LVIDd) and left ventricular internal dimension at end-systole(LVIDs). In contrast, ST did not exhibit significant effects on these parameters. In the insomnia model, CT significantly reduced sleep latency and prolonged sleep duration, whereas ST only prolonged sleep duration without shortening sleep latency. CST showed no significant effects on either sleep latency or sleep duration. Additionally, both CT and ST upregulated glutamic acid decarboxylase 67(GAD67) protein expression in brain tissue. A total of 15 main chemical components were identified from CT, including 2-(2-phenylethyl) chromone and 6-methoxy-2-(2-phenylethyl) chromone. Six chemical components including chebulidic acid were identified from ST. The results suggested that chromones and terpenes were potential anti-myocardial ischemia drugs of BCPs, and tannin and phenolic acids were potential hypnosis drugs. This study enriches the pharmacological and chemical research of BCPs, providing a basis and reference for their secondary development, quality standard improvement, and clinical application.
Animals ; Drugs, Chinese Herbal/isolation & purification* ; Mice ; Male ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Humans ; Myocardial Infarction/drug therapy* ; Myocardial Ischemia/drug therapy*

To evaluate the effectiveness and safety of implantable D-shant atrial shunt device in patients with severe pulmonary arterial hypertension(PAH)and right heart failure.A 53-year-old female patient diagnosed with severe idiopathic PAH and right heart failure,her WHO FC grade was Ⅳ.The right heart catheter and implantation of D-shant atrial shunt device were performed under local anesthesia on November 30,2021.A 6 mm×4 cm peripheral artery balloon was selected to dilate the atrial septum and a D-shant atrial shunt device with a fixed 4 mm diameter orifice was implanted into the heart.The clinical symptoms and hemodynamics of the patient was improved after the intervention.Implantation of atrial shunt device as a palliative therapy to established a right to left shunt is another strategy for treating patients with severe PAH in late period,which has good effectiveness and safety.It could be the last replacement therapy to improve symptoms and prolonged lives to drug resistant and severe PAH patients.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective:To explore the diagnostic value of 18F-FDG PET/CT imaging in etiology of patients with hemophagocytic lymphohistiocytosis (HLH). Methods:Retrospective analysis was performed on 49 patients newly diagnosed as HLH (32 males, 17 females; age 19-61 years) who received 18F-FDG PET/CT imaging in Affiliated Hospital of Jining Medical University from January 2017 to January 2023. PET/CT images and clinical parameters were observed and recorded. Based on the pathological examination and clinical follow-up results, diagnostic efficacies for HLH etiology of PET/CT, PET and CT imaging were calculated. χ2 test, independent-sample t test and Mann-Whitney U test were used to compare the differences between hematologic tumors associated HLH and non-hematologic tumor associated HLH. Multivariate logistic regression was used to analyze the predictors of secondary HLH in hematologic tumors. ROC curve analysis was used to calculate AUCs and optimal threshold of lymph node SUV max and soluble CD25 (sCD25) to predict secondary HLH in patients with hematologic tumors. Results:The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of PET/CT, PET and CT in the etiological diagnosis of HLH were 85.7%(30/35), 8/10, 84.4%(38/45), 93.8%(30/32), 8/13; 77.1%(27/35), 6/10, 73.3%(33/45), 87.1%(27/31), 6/14; 62.9%(22/35), 5/10, 60.0%(27/45), 81.5%(22/27), 5/18, respectively. There were differences in lymph node distribution and boundary, liver and spleen and bone lesions, SUV max of lymph node and liver and spleen and bone, gender, age, WBC, neutrophil (ANC), PLT, lactate dehydrogenase (LDH), total bilirubin (TBIL), C-reactive protein (CRP) and sCD25 between different etiology groups ( χ2 values: 3.91-9.66, t values: 3.75-7.90, z values: 3.82-4.01, all P<0.05). SUV max of lymph nodes and sCD25 were predictive factors for secondary HLH of hematological tumors (odds ratio ( OR): 1.28 (95% CI: 1.09-1.72), 1.56 (95% CI: 1.17-2.49), P values: 0.004, 0.013). The optimal thresholds were 12.6 and 40 028 ng/L, with the AUC of 0.87 and 0.76, with the sensitivity and specificity of 88.6%(31/35) and 8/10, 65.7%(23/35) and 7/10, respectively. The combined AUC was 0.83 and the sensitivity and specificity were 74.3% (26/35) and 9/10. Conclusions:18F-FDG PET/CT imaging is of high value for the diagnosis of the cause of HLH. SUV max of lymph node and sCD25 are predictive factors for secondary HLH of hematologic tumors.

Objective:To describe the clinical features and prognosis of congenital anomalous origin of coronary artery(AOCA) in children to increase our understanding of the disease.Methods:This retrospective study included children diagnosed with AOCA using computed tomography coronary angiography(CTCA) admitted to the Department of Cardiology, Beijing Children′s Hospital, Capital Medical University, from January 1, 2014 to December 31, 2019.The clinical presentations, laboratory results, imaging analyses, treatments, and prognoses of these patients were analyzed.Results:A total of 208 children, including 105 boys and 103 girls, we evaluated the ages(9.03±4.18)years old with AOCA.Of these, 157 cases(75.5%) presented with cardiac symptoms, such as chest tightness, palpitations, dizziness, syncope, fatigue, and decreased endurance.Three cases(1.4%) had atypical symptoms of paroxysmal crying, dyspnoea and cyanosis, and 48 cases(23.1%) were asymptomatic.Levels of serological markers of myocardial injury were elevated in 59 cases(28.4%), and 140 cases(67.3%) had predominant ST-T abnormalities on electrocardiograms.Transthoracic echocardiography identified 27 cases (13%) with cardiac enlargement and ten cases(4.8%) with left ventricular systolic dysfunction.There were 126 cases(60.6%) with the anomalous origin of the left coronary artery revealed by CTCA, 50 cases(24.0%) with the anomalous origin of the right coronary artery and 32 cases(15.4%) with bilateral coronary arteries of anomalous origin.Five children underwent surgical treatment, and the remaining 203 children were treated conservatively with drugs.The whole group was successfully treated, and no death case was recorded during the follow-up period.Conclusion:AOCA may cause different degrees of myocardial ischemia.Diverse clinical presentations and diagnostic limitations of transthoracic echocardiography often lead to missed diagnosis or misdiagnosis.In contrast, CTCA has high diagnostic accuracy and can be used to identify the location and course of the coronary ostia.Hence, the management of AOCA should be tailored on a case-to-case basis, taking into consideration of the specific type of coronary origin, with surgical intervention being warranted if necessary.

Abstract: Objective To explore the threshold of ALT for initiating antiviral therapy in HBV infected patients, and to provide a basis for initiating antiviral therapy in chronic HBV-infected patients. Methods This retrospective cohort study recruited 707 consecutive treatment-naïve chronic hepatitis B (CHB) patients undergoing diagnostic liver biopsy in the department of infectious diseases of the Affiliated Hospital of Yan′an University from October 2013 to August 2018. Liver biopsy specimens were obtained under ultrasound guidance using Menghini 16G disposable needles. The METAVIR scoring system, which is commonly used internationally, was used to divide the patients into the group with mild liver tissue injury and the group with significant liver tissue injury, and the alanine aminotransferase (ALT) levels were measured separately. Receiver operating characteristic (ROC) curve and Mann-Whitney U test were used to evaluate the diagnostic value of ALT for significant liver tissue injury under different demographic characteristics. Results Of 707 patients, 292 (41.30%) had significant liver tissue injury confirmed by liver biopsy (METAVIR ≥A2 and/or F2). When the ULN of ALT was set to NICE criteria (30 U/L for males, 19 U/L for females), AASLD criteria (35 U/L for males, 25 U/L for females) and EASL or APASL criteria (40 U/L for males and females), CHB patients with 30 years olds, 22 U/L for HBeAg negative and 31 U/L for HBeAg positive patients. Conclusions The threshold of ALT for initiating antiviral therapy in chronic HBV patients should be individualized, especially should be down-regulated for the females, olders and HBeAg-negative patients.

Microbial transformation is an efficient enzymatic approach for the structural modification of exogenous compounds to obtain derivatives. Compared with traditional chemical synthesis, the microbial transformation has in fact the undoubtable advantages of strong region-and stereo-selectivity, and a low environmental and economic impact on the production process, which can achieve the reactions challenging to chemical synthesis. Because microbes are equipped with a broad-spectrum of enzymes and therefore can metabolize various substrates, they are not only a significant route for obtaining novel active derivatives, but also an effective tool for mimicking mammal metabolism in vitro. Artemisinin, a sesquiterpene with a peroxy-bridged structure serving as the main active functional group, is a famous antimalarial agent discovered from Artemisia annua L. Some sesquiterpenoids, such as dihydroartemisinin, artemether, and arteether, have been developed on the basis of artemisinin, which have been successfully marketed and become the first-line antimalarial drugs recommended by WHO. As revealed by pharmacological studies, artemisinin and its derivatives have exhibited extensive biological activities, including antimalarial, antitumor, antiviral, anti-inflammatory, and immunomodulatory. As an efficient approach for structural modification, microbial transformation of artemisinin and its derivatives is an increasingly popular strategy that attracts considerable attention recently, and numerous novel derivatives have been discovered. Herein, this paper reviewed the microbial transformation of artemisinin and its artemisinin, including microbial strains, culture conditions, product isolation and yield, and biological activities, and summarized the advances in microbial transformation in obtaining active derivatives of artemisinin and the simulation of in vivo metabolism of drugs.
Animals ; Antimalarials/pharmacology* ; Antiviral Agents ; Artemether ; Artemisinins ; Mammals

OBJECTIVE: To explore the clinical features and genetic etiology of two children with intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia (MICPCH). METHODS: Two children with MICPCH who were presented at the Henan Provincial People's Hospital between April 2019 and December 2021 were selected as the study subjects. Clinical data of the two children were collected, along with peripheral venous blood samples of them and their parents, and amniotic fluid sample of the mother of child 1. Whole exome sequencing (WES), array-comparative genomic hybridization (aCGH) and real-time quantitative PCR (qPCR) were carried out for the children, their parents and the fetus. The pathogenicity of candidate variants were evaluated. RESULTS: Child 1 was a 6-year-old girl featuring motor and language delay, whilst child 2 was a 4.5-year-old girl mainly featuring microcephaly and mental retardation. WES revealed that child 2 has harbored a 158.7 kb duplication in Xp11.4 (chrX: 41446160_41604854), which has encompassed exons 4~14 of the CASK gene. The same duplication was not found in either of her parents. aCGH revealed that child 1 has harbored a 29 kb deletion at Xp11.4 (chrX: 41637892_41666665), which encompassed exon 3 of the CASK gene. The same deletion was not found in either of her parents and the fetus. The above results were confirmed by qPCR assay. Above deletion and duplication were not found in the ExAC, 1000 Genomes and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PS2+PM2_Supporting). CONCLUSION The deletion of exon 3 and duplication of exons 4~14 of the CASK gene probably underlay the pathogenesis of MICPCH in these two children, respectively.
Humans ; Child ; Female ; Child, Preschool ; Microcephaly/genetics* ; Developmental Disabilities/genetics* ; Intellectual Disability/complications* ; Comparative Genomic Hybridization ; Mutation

OBJECTIVE: To explore the genetic basis for fetus with bilateral lateral ventriculomegaly. METHODS: Fetus umbilical cord blood and peripheral blood samples of its parents were collected. The fetus was subjected to chromosomal karyotyping, whilst the fetus and its parents were subjected to array comparative genomic hybridization (aCGH). The candidate copy number variation (CNV) were verified by qPCR, Application goldeneye DNA identification system was used to confirm the parental relationship. RESULTS: The fetus was found to have a normal karyotype. aCGH analysis indicated that it has carried a 1.16 Mb deletion at 17p13.3, which partially overlapped with the critical region of Miller-Dieker syndrome (MDS), in addition with a 1.33 Mb deletion at 17p12 region, which is associated with hereditary stress-susceptible peripheral neuropathy (HNPP). Its mother was also found to harbor the 1.33 Mb deletion at 17p12. qPCR analysis confirmed that the expression levels of genes from the 17p13.3 and 17p12 regions were about the half of that in the normal control, as well as the maternal peripheral blood sample. Parental relationship was confirmed between the fetus and its parents. Following genetic counseling, the parents has chosen to continue with the pregnancy. CONCLUSION The fetus was diagnosed with Miller-Dieker syndrome due to the de novo deletion at 17p13.3. Ventriculomegaly may be an important indicator for prenatal ultrasonography in fetuses with MDS.
Pregnancy ; Female ; Humans ; Classical Lissencephalies and Subcortical Band Heterotopias ; Comparative Genomic Hybridization ; DNA Copy Number Variations ; Fetus ; Hydrocephalus ; Prenatal Diagnosis ; Chromosome Deletion