ObjectiveThrough the correlation analysis between intestinal absorption profile and inhibition of macrophage foaming， the pharmacodynamic components of Zhuriheng dripping pills（ZRH） were explored to provide a basis for establishing its quality standard. MethodIntestinal absorption fluids with 0， 5， 10， 15， 20 times clinical equivalent doses were prepared by a rat everted gut sac（EGS）， and the oxidized low density lipoprotein（ox-LDL）-induced RAW264.7 macrophage foaming model was used to investigate the effect of intestinal absorption fluid with different doses on the accumulation of lipids in RAW264.7 cells by oil red O staining and cholesterol content determination， and to screen for the optimal dose. Ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to analyze and identify intestinal absorption fractions of ZRH intestinal absorption fluids， and partial least squares-discriminant analysis（PLS-DA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on different doses of ZRH intestinal absorption fluids using SIMCA 13.0 with peak area as the independent variable and the pharmacodynamic indicators as the dependent variables to screen the compounds with variable importance in the projection（VIP） value>1.0 as contributing components， and Pearson correlation analysis was used to determine the spectral effect relationship， determined the compounds and positive correlation with pharmacodynamic were as active ingredients. Molecular docking was used to verify the binding energy of peroxisome proliferator-activated receptor α（PPARα）， PPARγ， PPARβ， human retinoid X receptor α（RXRA） and nuclear transcription factor-κB（NF-κB） with the active ingredients in ZRH intestinal absorption fluids. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was performed to detect the mRNA levels of PPARγ， scavenger receptor A1（SRA1） and adenosine triphosphate-binding cassette transporter A1（ABCA1） in RAW264.7 cells， Westen blot was used to detect the expression level of PPARγ protein in RAW264.7 cells， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of interleukin（IL）-1β and NF-κB in RAW264.7 cells. ResultAccording to the results of oil red O staining and cholesterol content determination， the ZRH intestinal absorption fluids could significantly reduce macrophage foaming， and intestinal absorption fluids with 15， 20 times clinical equivalent doses had the best effect， the 15-fold ZRH intestinal absorption fluid was finally determined as the study subject. Spectral effect relationship showed that 52 corresponding peaks in the ZRH-containing intestinal fluid were positively correlated with the efficacy， including organic acids， phenylpropanoids， iridoids， flavonoids， bile acids， coumarins and chromones. Target validation results showed that 86.9%-96.2% of the total components processed good binding activities with the key targets of PPARα， PPARγ， PPARβ， RXRA and NF-κB， and the docking energy values were all less than -6.0 kcal·mol^-1（1 cal≈4.19 J）. The results of validation showed that， compared with the normal group， the model group showed a significant increase in the levels of SRA1 and PPARγ mRNA expression， a significant decrease in ABCA1 mRNA expression， a significant increase in the level of PPARγ protein expression， and a significant increase in the levels of IL-1β and NF-κB（P<0.01）， compared with the model group， the 15-fold intestinal absorption fluid group showed a significant decrease in the levels of SRA1 and PPARγ mRNA expression（P<0.05， P<0.01）， ABCA1 mRNA expression level was significantly up-regulated， the levels of IL-1β and NF-κB were significantly reduced（P<0.01）， and PPARγ protein expression level was significantly reduced（P<0.05）. ConclusionThis study identifies 52 components and their metabolites in ZRH intestinal absorption fluid that are positively correlated with the inhibition of macrophage foaming， which may be related to the regulation of the PPARs pathway in cells and the reduction of the levels of inflammatory factors， and can provide a reference for the quality control and clinical application of ZRH.

Objective:To investigate the role of levofloxacin combined with recombinant human granulocyte colony-stimulating factor(G-CSF)or only G-CSF supportive therapy in preventing infection in autologous hematopoietic stem cell transplantation(ASCT),and to analyze the length of hospital stay,hospitalization cost and post-transplant survival of the patients.Methods:A retrospective analysis was performed in the patients with hematological malignancies who accepted ASCT at our hospital from January 2012 to July 2022,the febrile neutropenia,the incidence of bacterial infection and the use rate of intravenous antibiotics in the levofloxacin+G-CSF group and only G-CSF support group during ASCT were observed.The length of hospital stay,total cost during hospitalization and survival after 90 days of transplantation between the two groups were compared.Results:A total of 102 cases were included in this study,including 57 cases of multiple myeloma,36 cases of acute leukaemia,7 cases of lymphoma,3 cases of myelodysplastic syndrome,1 case of light chain amyloidosis,and 1 case of POEMS syndrome.47 patients received levofloxacin+G-CSF antibacterial prophylaxis,and 55 patients received G-CSF supportive therapy.In the levofloxacin+G-CSF group,40 cases(85.11％)developed febrile neutropenia,and 13 cases(27.66％)were confirmed as bacterial infection.In the G-CSF group,44 cases(80.00％)developed febrile neutropenia,and 16 cases(29.09％)were bacterial infection.There was no statistically significant difference in the incidence of febrile neutropenia and bacterial infection between the two groups(x2=0.46,P=0.50;x2=0.03,P=0.87).The use rate of intravenous antibiotics in the levofloxacin+G-CSF group was 85.11％(40/47),which was not statistically different from 85.45％(47/55)in the G-CSF group(X2=0.04,P=0.84).The detection rates of levofloxacin-resistant bacteria in the levofloxacin+G-CSF group and G-CSF group were 8.57％(3/35)and 21.43％(6/28),respectively,with no statistical difference(x2=0.65,P＞0.05).The median length and median cost of hospitalization in the levofloxacin+G-CSF group and G-CSF group were 25 d vs 22 d and 78 216.24 yuan vs 80 724.38 yuan,with no statistically significant differences(t=3.00,P=0.09;t=0.94,P=0.09).Within 90 days after transplantation,two cases(4.26％)died in the levofloxacin+G-CSF group and one case(1.82％)died in the G-CSF group,with no statistically significant difference between the two groups(x2=0.53,P=0.47).Conclusion:Application of levofloxacin+G-CSF showed no significant benefit compared to G-CSF support for the prevention of bacterial infections during ASCT.

OBJECTIVE: To explore the clinical characteristics of nosocomial infection in newly diagnosed multiple myeloma(NDMM) patients, and establish a predictive nomogram model. METHODS: The clinical data of 164 patients with MM who were treated in Shanxi Bethune Hospital from January 2017 to December 2021 were retrospectively analyzed. The clinical characteristics of infection were analyzed. Infections were grouped as microbiologically defined infections and clinically defined infections. Univariate and multivariate regression models were used to analyze the risk factors of infection. A nomogram was established. RESULTS: 164 patients with NDMM were included in this study, and 122 patients (74.4%) were infected. The incidence of clinically defined infection was the highest (89 cases, 73.0%), followed by microbial infection (33 cases, 27.0%). Among 122 cases of infection, 89 cases (73.0%) had CTCAE grade 3 or above. The most common site of infection was lower respiratory in 52 cases (39.4%), upper respiratory tract in 45 cases (34.1%), and urinary system in 13 cases (9.8%). Bacteria(73.1%) were the main pathogens of infection. Univariate analysis showed that ECOG ≥2, ISS stage Ⅲ, C-reactive protein ≥10 mg/L, serum Creatinine ≥177 μmol/L had higher correlation with nosocomial infection in patients with NDMM. Multivariate regression analysis showed that C-reactive protein ≥10 mg/L (P＜0.001), ECOG ≥2 (P=0.011) and ISS stage Ⅲ （P=0.024） were independent risk factors for infection in patients with NDMM. The nomogram model established based on this has good accuracy and discrimination. The C-index of the nomogram was 0.779（95%CI: 0.682-0.875）. Median follow-up time was 17.5 months, the median OS of the two groups was not reached (P=0.285). CONCLUSION Patients with NDMM are prone to bacterial infection during hospitalization. C-reactive protein ≥10 mg/L, ECOG ≥2 and ISS stage Ⅲ are the risk factors of nosocomial infection in NDMM patients. The nomogram prediction model established based on this has great prediction value.
Humans ; Nomograms ; Multiple Myeloma/metabolism* ; Prognosis ; Retrospective Studies ; Cross Infection ; C-Reactive Protein

Objective: To retrospectively analyze the clinical data of different types of selective intrauterine growth restriction (sIUGR) pregnant women under expectant management, including the natural evolution, typing conversion and perinatal outcomes. Methods: The clinical data of 153 pregnant women with sIUGR under expected treatment in Women's Hospital, Zhejiang University School of Medicine from January 2014 to December 2018 were collected. Maternal characteristics including maternal age, gravidity, parity, method of conception, pregnancy complication, gestational age at delivery, indication for delivery, birth weight, the rate of intrauterine and neonatal death and neonatal outcomes were recorded. Pregnant women with sIUGR were divided into three types according to end-diastolic umbilical artery flow Doppler ultrasonography, and the differences of typing conversion and perinatal outcomes of sIUGR pregnant women based on the first diagnosis were compared. Results: (1) Clinical characteristics and pregnancy outcomes: among 153 pregnant women with sIUGR, 100 cases (65.3%) were diagnosed with type Ⅰ, 35 cases (22.9%) with type Ⅱ, and 18 cases (11.8%) with type Ⅲ. There were no significant differences in age, conception mode, pregnancy complications, first diagnosis gestational age, characteristics of umbilical cord insertion, delivery indications, fetal intrauterine mortality and neonatal mortality among three types of sIUGR pregnant women (all P>0.05). The average gestational age at delivery of type Ⅰ sIUGR was (33.5±1.9) weeks, which was significantly later than those of type Ⅱ and Ⅲ [(31.3±1.8), (31.2±1.1) weeks, P<0.001]. The percentage disordance in estimated fetal weight (EFW) of type Ⅰ sIUGR was significantly lower than those of type Ⅱ and type Ⅲ (P<0.001). The incidence rate of neonatal intensive care unit (NICU) admission, cerebral leukomalacia and respiratory complications of both fetus and necrotizing enterocolitis of large fetus in type Ⅰ were significantly lower than those in type Ⅱ and type Ⅲ (all P<0.05). (2) Typing conversion: in 100 cases of type Ⅰ sIUGR, 18 cases progressed to type Ⅱ and 10 cases progressed to type Ⅲ. Compared with 72 stable type Ⅰ sIUGR, those with progressed type Ⅰ sIUGR had higher incidence of NICU admission and lung disease in both fetuses, and cerebral leukomalacia and necrotizing enterocolitis in large fetus (all P<0.05). The proportion of inconsistent cord insertion was significantly higher in those type Ⅰ progressed to type Ⅲ (6/10) than in those with stable type Ⅰ (19.4%, 14/72) and type Ⅰ progressed to type Ⅱ sIUGR [0 (0/18), P=0.001]. Four cases of type Ⅱ sIUGR reversed to type Ⅰ and 6 cases reversed to type Ⅲ. Compared with type Ⅱ reversed to type Ⅰ sIUGR, those stable type Ⅱ and type Ⅱ reversed to type Ⅲ sIUGR had a higher incidence of NICU admission in large fetus (P<0.05). Two cases of type Ⅲ sIUGR reversed to type Ⅰ and 6 cases progressed to type Ⅱ. There were no significant differences in fetal serious complications in type Ⅲ sIUGR with or without doppler changes (all P>0.05). Conclusions: The different types of sIUGR could convert to each other. The frequency of ultrasound examinations should be increased for patients with the type Ⅰ sIUGR, especially when the percentage discordance in EFW is substantial or with discordant cord insersion.
Pregnancy ; Female ; Infant, Newborn ; Humans ; Fetal Growth Retardation/epidemiology* ; Pregnancy Outcome ; Retrospective Studies ; Enterocolitis, Necrotizing ; Twins, Monozygotic ; Umbilical Arteries/diagnostic imaging* ; Gestational Age ; Ultrasonography, Prenatal/methods* ; Pregnancy, Twin

OBJECTIVE: To explore the carrier rate, genotype and phenotype of α-thalassemia fusion gene in Huadu district of Guangzhou, Guangdong province of China, and provide data reference for the prevention and control of thalassemia. METHODS: A total of 10 769 samples who were screened for thalassemia in Maternal and Child Health Hospital of Huadu District from July 2019 to November 2020 were analyzed retrospectively. Blood cell analysis and hemoglobin (Hb) electrophoresis were performed. Thalassemia genes were analyzed by gap-PCR and PCR-reverse dot blot hybridization (PCR-RDB). RESULTS: A total of 9 cases with α-thalassemia fusion gene were detected in 10 769 samples (0.08%). There were 7 cases with fusion gene heterozygote, 1 case with compound of α-thalassemia fusion gene and Hb G-Honolulu, 1 case with compound of α-thalassemia fusion gene and Hb QS. The MCV results of 4 samples of blood cell analysis were within the reference range, the Hb A2 value of 1 case was decreased, and there were no other abnormalities found. CONCLUSION The α-thalassemia fusion gene is common in Huadu district of Guangzhou, and heterozygotes are more common, and current screening methods easily lead to misdiagnosis.
Humans ; alpha-Thalassemia/genetics* ; Retrospective Studies ; beta-Thalassemia/genetics* ; Genotype ; Phenotype ; Heterozygote ; China ; Mutation

ObjectiveTo determine the value of MRI blooming sign in differentiating benign and malignant small breast masses and investigate its radiologic-pathologic correlation. MethodsThis retrospective study included 554 small breast masses （291 malignant and 263 benign） which were ≤ 2 cm and validated by pathology analysis between June 2016 and September 2020. All 554 patients underwent breast MRI. The clinical characteristics and MR features were analyzed. Univariate and multivariate regression analysis were performed to identify the independent risk factors of breast cancer. Two diagnostic models were constructed based on independent risk factors （model 1 included blooming sign and model 2 didn’t）. ROC curve was used to evaluate the diagnostic performances of the two models. The histological changes of peritumoral tissues in all small masses were analyzed. ResultsThe blooming sign was positive in 199 cases （68.4%） of the malignant masses and 25 cases （9.5%） of the benign ones （P＜0.05）. Univariate and multivariate regression analysis showed that age， lesion diameter， margin， ADC value， time signal intensity curve type and blooming sign were independent risk factors for breast cancer. Odds ratio were 1.065， 4.515， 2.811， 0.013， 3.487 and 13.894， respectively. Their corresponding 95%CI were （1.034， 1.097）， （2.368， 8.608）， （1.954， 4.045）， （0.004， 0.049）， （2.087， 5.826） and （7.026， 27.477）， respectively. The diagnostic performance of model 1 （blooming sign included） was better than that of model 2 （blooming sign not included； AUC： 0.938 vs 0.897， P < 0.05）. Histopathological analysis showed that the blooming sign was related to peritumoral lymphocyte infiltration and vascular proliferation. ConclusionsMRI blooming sign is helpful for distinguishing breast cancer from benign masses. The correlated histopathological basis may be peritumoral lymphocyte infiltration and neovascularization.

OBJECTIVES: To study the efficacy and safety of domestic generic levetiracetam in replacement of brand-name levetiracetam in the treatment of children with epilepsy. METHODS: A retrospective analysis was performed on the medical data of 154 children with epilepsy who received domestic generic levetiracetam in the inpatient or outpatient service of Guangdong Provincial People's Hospital from May 2019 to December 2020. Domestic generic levetiracetam and brand-name levetiracetam were compared in terms of efficacy and safety. RESULTS: For these 154 children, the epilepsy control rate was 77.3% (119/154) at baseline. At 6 months after switching to domestic generic levetiracetam, the epilepsy control rate reached 83.8% (129/154), which showed a significant increase (P<0.05). There was no significant change in the frequency of seizures from baseline to 6 months after switching (P>0.05). The incidence of refractory epilepsy in children with no response after switching treatment was significantly higher than that in children with response (P<0.05). Before switching, only 1 child (0.6%) experienced somnolence, while after switching, 3 children (1.9%) experienced mild adverse drug reactions, including dizziness, somnolence, irritability, and bad temper. CONCLUSIONS Switching from brand-name to generic levetiracetam is safe and effective and holds promise for clinical application, but more prospective randomized controlled trials are required in future.
Child ; Epilepsy/drug therapy* ; Humans ; Levetiracetam ; Prospective Studies ; Retrospective Studies ; Seizures

An auxiliary isolation device of cupping therapy for cross-infection prevention is designed to reduce the disinfection steps and be against cross transmission. This device is composed of a disposable isolation unit made of fire proof plastic material and a disposable cup-mouth fixator made of elastic material. The disposable isolation unit includes two parts, the cup neck isolation unit and the inner isolation unit of fire cup. These two parts connect with the disposable cup-mouth fixator. All of those three sections of the device are center-connected ring-like structure. This device can well prevent the direct contact of fire cup with the patient's skin surface, characterized as safety protection, simple operation and saving time and manpower.
Cupping Therapy ; Humans

OBJECTIVE: To explore the genetic basis for a fetus with cerebellar dysplasia and widened lateral ventricles. METHODS: The couple have elected induced abortion after careful counseling. Skin tissue sample from the abortus and peripheral venous blood samples from both parents were collected for the extraction of genomic DNA, which was then subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasonography showed increased nuchal translucency (0.4 cm) and widened lateral ventricles. Magnetic resonance imaging revealed infratentorial brain dysplasia. By DNA sequencing, the fetus was found to carry compound heterozygous variants c.1A>G and c.1564G>A of the RARS2 gene, which were inherited from its father and mother, respectively. Among these, c.1A>G was known to be pathogenic, but the pathogenicity of c.1564G>A was unreported previously. Based on the American College of Medical Genetics and Genomics guidelines, the c.1564G>A variant of RARS2 gene was predicted to be likely pathogenic(PM2+PM3+PP3+PP4). CONCLUSION The compound heterozygous variants c.1A>G and c.1564G>A of RARS2 gene contributed to the fetus suffering from pontocerebellar hypoplasia type 6, which expanded variant spectrum of RARS2 gene.
Female ; Fetus ; Genomics ; Humans ; Mutation ; Olivopontocerebellar Atrophies ; Pregnancy ; Whole Exome Sequencing

OBJECTIVE: To analyze FOXC2 gene variant in a family affected with lymphodema-distichiasis syndrome (LDS). METHODS: Peripheral blood samples were collected for the extraction of DNA and protein. Whole-exome sequencing was carried out to detect variants in the proband. Suspected variant was validated by Sanger sequencing. Western blotting was used to detect changes in protein expression. RESULTS: The proband and his mother were both found to carry a heterozygous nonsense variant c.177C>G (p.Tyr59X) of the FOXC2 gene, which was previously unreported. Down-regulated expression of FOXC2 was detected by Western blotting. Prenatal ultrasonography of the fetus indicated increased nuchal thickness. Amniocentesis was performed at 21+1 weeks of pregnancy, genetic testing suggested that the fetus also carried the c.177C>G variant. CONCLUSION The patients' condition may be attributed to the heterozygous nonsense variant c.177C>G of the FOXC2 gene, which resulted in a significant decrease in FOXC2 expression. Increased nuchal thickness may also be related with decreased FOXC2 expression. Above finding has expanded the variant spectrum of the FOXC2 gene.
Codon, Nonsense ; Eyelashes ; abnormalities ; Female ; Forkhead Transcription Factors ; genetics ; metabolism ; Gene Expression ; Genetic Testing ; Genetic Variation ; Humans ; Lymphedema ; genetics ; Pedigree ; Pregnancy ; Prenatal Diagnosis