The efficacy and safety of intravenous sucrose iron therapy for recurrent iron deficiency anemia / 中华血液学杂志

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 μg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.

Preliminary application of transesophageal echocardiography in transapical mitral valve repair with Memoclip / 中华超声影像学杂志

Objective:To explore the value of transapical catheter of mitral valve repair (MVR) with Memoclip device in the management of moderate to severe and severe mitral regurgitation (MR) guided by transesophageal echocardiography (TEE).Methods:Fifteen patients with moderate to severe and severe MR in Hefei High-tech Cardiovascular Hospital from December 2021 to October 2022 were prospectively selected. Mitral valve morphology and length, regurgitation severity, left ventricular ejection fraction and pulmonary venous Doppler spectra were carefully evaluated before MVR by TEE.Intraprocedural TEE was performed to guide the MVR including transseptal catheterization, alignment of the clip delivery system, assessment of leaflet capture, clip deployment, post-clip deployment assessment, and withdrawal of the clip delivery system. The position and coaptation length of the clips, the mitral orifice morphology, residual mitral valve regurgitation and pressure gradient were evaluated after MVR.Meanwhile, the complications were monitored throughout the procedure.Results:Among the 15 patients, 12 were implanted with 1 clip and 3 were implanted with 2 clips, respectively. No complications occurred. There were 13 patients with mild regurgitation and 2 showed to moderate mitral regurgitation 1 month later after MVR, and 13 remained mild and 2 maintained moderate regurgitation 3 months later. Significant differences were found in maximal MR area (MRA-max), maximal and mean mitral valve pressure gradient (MVPG-max, MVPG-mean) and mitral valve area (MVA) among the 5 observation time points (all P<0.05). MRA-max, MVA and MVPG-mean were significantly decreased immediately and 3 months after the procedure ( P<0.001). No significant stenosis was found in mitral valve after MVR. Conclusions:MVR with Memoclip is safe, effective, easy to operate in treating patients with moderate to severe and severe MR. TEE plays a key role in perioperative MVR with Memoclip through apical catheterization.

Effects and related mechanisms of histone deacetylase inhibitors on the proliferation of choroidal melanoma C918 cell line / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To elucidate the effect of histone deacetylase(HDAC)inhibitor suberoylanilide hydroxamic acid(SAHA)on the proliferation of choroidal melanoma(CM)cell line C918 and to explore the related mechanism.METHODS: Inverted fluorescence microscope was used to observe the effect of different concentrations of SAHA(0.625, 1.25 or 2.5 μmol/L)on the morphology of C918 cell. The cell viability was detected by cholecystokinin octapeptide(CCK-8)assay. Plate clone formation assay and EdU staining were carried out to measure the effect of SAHA on the cell proliferation. Meanwhile, the expressions of cell proliferation-related proteins including c-Myc, CyclinA2 and CDK2, and histone deacetylase 7(HDAC7)and fibroblast growth factor 18(FGF18)were detected by Western blot.RESULTS: Compared with the control group, the cell density was reduced in SAHA. SAHA could also promote cell shrinkage, and the inhibition on cell was in a concentration-dependent manner. CCK-8 assay showed that SAHA treatment decreased cell viability in a dose-dependent manner and the inhibition rate was 80% when SAHA at 2.5 μmol/L. Compared with the control group, Western blot showed that SAHA could suppress the expression of cell proliferation proteins including c-Myc, CyclinA2 and CDK2 in a dose-dependent manner. In addition, 1.25 μmol/L SAHA significantly decreased the numbers of EdU staining positive cells and cell clones. More importantly, SAHA could dose-dependently decrease the expression of HDAC7 and FGF18 compared with control group.CONCLUSION: SAHA could inhibit the proliferation of CM cell line C918 by inhibiting the HDAC7/FGF18 signaling pathway.

A Phase Ⅲ Clinical Observation of Yishen Yangxin Anshen Tablets in Treatment of Insomnia with Deficiency of Heart Blood and Insufficiency of Kidney Essence / 中国实验方剂学杂志

ObjectiveTo confirm the clinical efficacy and safety of Yishen Yangxin Anshen tablets in the treatment of insomnia （heart-blood deficiency and kidney-essence insufficiency syndrome）. MethodA randomized block， double-blind， placebo-controlled， multi-center clinical trial design method was adopted， and a total of 480 patients with insomnia due to deficiency of heart blood and insufficiency of kidney essence （treatment group-control group 3∶1） from seven hospitals （Guang'anmen Hospital， China Academy of Chinese Medical Sciences， The First Clinical Hospital， Jilin Province Academy of Traditional Chinese Medicine（TCM）， The Second Affiliated Hospital of Liaoning University of TCM， The First Affiliated Hospital of Henan University of Chinese Medicine， Henan Province Hospital of TCM， Hebei General Hospital， The First Hospital of Hunan University of Chinese Medicine） were enrolled. The treatment group was given Yishen Yangxin Anshen tablets and the control group received placebo tablets （4 tablets/time， 3 times/day， 4 weeks of administration， 4 weeks of follow-up after drug withdrawal）. The sleep dysfunction rating scale （SDRS） score， pittsburgh sleep quality index （PSQI） score， TCM， polysomnography （PSG） indicators from four hospital （Guang'anmen Hospital， China Academy of Chinese Medical Sciences， Henan Province Hospital of TCM， Hebei General Hospital， The First Hospital of Hunan University of Chinese Medicine）， and other efficacy indicators were compared between the two groups before and after treatment. Through general physical examination， laboratory examination， and observation of adverse events， the safety of the drugs was evaluated. ResultThe baseline indexes of the two groups showed no significant difference and thus the two groups were comparable. After treatment， the total score of SDRS in the treatment group was lower than that in the control group （P<0.01）. After drug withdrawal for 4 weeks， the total score of SDRS demonstrated no significant change in the treatment group as compared with that at the end of treatment， indicating that the rebound change of curative effect was not obvious. After treatment， the total score of PSQI in the treatment group decreased as compared with that in the control group （P<0.01）， and the change of total score of PSQI in the treatment group was statistically significant （P<0.05） after drug withdrawal for 4 weeks but small， indicating that the rebound change of curative effect was not obvious. After treatment， the total effective rate about the TCM symptoms in the treatment group was higher than that in the control group （χ2=137.521，P<0.01）. After treatment， the disappearance rates of single indexes in the treatment group， such as difficulty in falling asleep， easily waking up after sleeping， early awakening， short sleep time， dreamfulness， palpitation， forgetfulness， dizziness， mental fatigue， and weakness of waist and knee， increased compared with those in the control group （P<0.01）. After treatment， the treatment group demonstrated fewer awaking times （AT）， longer total sleep time （TST）， lower ATA/TST ratio， and higher sleep efficiency （%） than the control group （P<0.05）. No abnormal value or aggravation related to drugs was observed in either group. The incidence of adverse events in the treatment group and the control group was 5.57% and 8.40% respectively. No serious adverse events or adverse events leading to withdrawal happened in either group. ConclusionYishen Yangxin Anshen tablets is effective and safe for patients with insomnia of deficiency of heart-blood and insufficiency of kidney-essence.

Effective fraction from Simiao Wan prevents hepatic insulin resistant by inhibition of lipolysis via AMPK activation / 中国天然药物

Simiao Wan (SMW) is a traditional Chinese formula, including Atractylodis Rhizoma, Achyranthis Bidentatae Radix, Phellodendri Chinensis Cortex and Coicis Semen at the ratio of 1:1:2:2. It can be used to the treatment of diabetes. However, its bioactive compounds and underlying mechanism are unclear. This study aimed to screen the antilipolytic fraction from SMW and investigate its therapeutic mechanisms on hepatic insulin resistance. Different fractions of SMW were prepared by membrane separation combined with macroporous resin and their antilipolytic activities were screened in fasted mice. The effects of 60% ethanol elution (ESMW) on lipolysis were investigated in 3T3-L1 adipocytes stimulated by palmitic acid (PA) and high fat diet (HFD)-fed mice. In our study, ESMW is the bioactive fraction responsible for the antilipolytic activity of SMW and 13 compounds were characterized from ESMW by UHPLC-QTOF-MS/MS. ESMW suppressed protein kinase A (PKA)-hormone-sensitive lipase (HSL) related lipolysis and increased AMP-activated protein kinase (AMPK) phosphorylation in PA challenged 3T3-L1 adipocytes. AMPKα knockdown abolished the inhibitory effects of ESMW on IL-6 and HSL pSer-660, revealing that the antilipolytic and anti-inflammatory activities of ESMW are AMPK dependent. Furthermore, ESMW ameliorated insulin resistance and suppressed lipolysis in HFD-fed mice. It inhibited diacylglycerol accumulation in the liver and inhibited hepatic gluconeogenesis. Conditional medium collected from ESMW-treated 3T3-L1 cells ameliorated insulin action on hepatic gluconeogenesis in liver cells, demonstrating the antilipolytic activity contributed to ESMW beneficial effects on hepatic glucose production. In conclusion, ESMW, as the antilipolytic fraction of SMW, inhibited PKA-HSL related lipolysis by activating AMPK, thus inhibiting diacylglycerol (DAG) accumulation in the liver and thereby improving insulin resistance and hepatic gluconeogenesis.

Efficacy of plasma exchange in the treatment of autoimmune hemolytic anemia in children / 中国小儿急救医学

Objective:To investigate the efficacy and safety of plasma exchange(PE) in the treatment of autoimmune hemolytic anemia in children.Methods:The data from 8 hospitals in China during November 2014 to April 2017 were collected, and the clinical characteristics of PE in children with AHA were analyzed retrospectively.Results:A total of 21 children with AHA were included in the study, including 17 cases from PICU and 4 cases from pediatric kidney ward, with 11 boys and 10 girls, and the median age was 3.64(0.25, 11.10)years old, and median hospital stay was 12(4, 45)days.There were 15 cases(71.4%) with infection, 2 cases(9.5%)with autoimmune diseases, 4 cases(19.0%) with unknown.Consciousness disturbance occurred in 4 patients before replacement and recovered to normal after PE.The volume of blood decreased in two cases(9.5%) and completely relieved.There were 20 cases of anemia (95.2%), 15 cases were normal after PE, and 5 cases were improved.Jaundice occurred in 18 cases (85.7%), 12 cases were normal after PE, 6 cases were improved.Hepatosplenomegaly was found in 11 cases, 10 cases were normal after PE, 1 case was improved.After PE, the hemoglobin and red blood cell count increased, while the total bilirubin, indirect bilirubin, urea nitrogen and lactate dehydrogenase decreased, there were significant differences between pre-and post-replacement ( P<0.05). Only 1 case had allergic reaction, which was improved after symptomatic treatment, and PE was continued.After PE, 2 cases (9.5%) had complete remission, 16 cases (76.2%) had partial remission and 3 cases (14.3%) had been discharged. Conclusion:PE therapy can obviously improve the clinical symptoms and laboratory indexes of children with AHA who have failed to respond to conservative treatment.It can be used as a treatment measure for children with severe AHA and has a good safety.

Efficacy of plasma exchange in the treatment of autoimmune hemolytic anemia in children / 中国小儿急救医学

Objective:To investigate the efficacy and safety of plasma exchange(PE) in the treatment of autoimmune hemolytic anemia in children.Methods:The data from 8 hospitals in China during November 2014 to April 2017 were collected, and the clinical characteristics of PE in children with AHA were analyzed retrospectively.Results:A total of 21 children with AHA were included in the study, including 17 cases from PICU and 4 cases from pediatric kidney ward, with 11 boys and 10 girls, and the median age was 3.64(0.25, 11.10)years old, and median hospital stay was 12(4, 45)days.There were 15 cases(71.4%) with infection, 2 cases(9.5%)with autoimmune diseases, 4 cases(19.0%) with unknown.Consciousness disturbance occurred in 4 patients before replacement and recovered to normal after PE.The volume of blood decreased in two cases(9.5%) and completely relieved.There were 20 cases of anemia (95.2%), 15 cases were normal after PE, and 5 cases were improved.Jaundice occurred in 18 cases (85.7%), 12 cases were normal after PE, 6 cases were improved.Hepatosplenomegaly was found in 11 cases, 10 cases were normal after PE, 1 case was improved.After PE, the hemoglobin and red blood cell count increased, while the total bilirubin, indirect bilirubin, urea nitrogen and lactate dehydrogenase decreased, there were significant differences between pre-and post-replacement ( P<0.05). Only 1 case had allergic reaction, which was improved after symptomatic treatment, and PE was continued.After PE, 2 cases (9.5%) had complete remission, 16 cases (76.2%) had partial remission and 3 cases (14.3%) had been discharged. Conclusion:PE therapy can obviously improve the clinical symptoms and laboratory indexes of children with AHA who have failed to respond to conservative treatment.It can be used as a treatment measure for children with severe AHA and has a good safety.

A real world study on the relationship between drug resistance of targeted therapy and prognosis of HER-2-positive advanced breast cancer / 中华肿瘤杂志

Objective: To explore the effect of primary and acquired resistance to anti-human epidermal growth factor receptor 2 (HER-2) on the overall survival of patients with HER-2 positive advanced breast cancer. Methods: The clinical characteristics of HER-2 positive patients with advanced breast cancer admitted to Cancer Hospital of Chinese Academy of Medical Sciences from January 1998 to December 2018 were collected, and their neoadjuvant/adjuvant and advanced three-line chemotherapy were summarized. Among them, targeted drugs for HER-2 included trastuzumab, pertuzumab, T-DM1, RC48-ADC, lapatinib, pyrotinib, allitinib, sipatinib, seratinib. Based on the duration of benefit from anti HER-2 treatment, the patients were divided into two groups: primary anti HER-2 resistance group and acquired anti HER-2 resistance group. In this study, the overall survival (OS) was used as the main end point. Kaplan-Meier analysis and Cox proportional risk regression model were used to analyze the effects of different drug resistance mechanisms on the overall survival. Results: The whole group of 284 patients were included. The median age of recurrence and metastasis was 48 years old, 155 (54.6%) were hormone receptor (HR) positive and 129 (45.4%) were HR negative, 128 cases (45.1%) were premenopausal and 156 cases (54.9%) were postmenopausal, 277 cases (97.5%) had a score of 0-1 in ECoG PS and 7 cases (2.5%) had a score of more than 2 in the first diagnosis of relapse and metastasis. There were 103 cases (36.3%) in the primary drug resistance group and 181 cases (63.7%) in the secondary drug resistance group. The median overall survival time of the two groups was 24.9 months and 40.4 months, respectively, with statistical significance (P<0.001). Conclusion: Primary resistance to HER-2 is one of the factors of poor prognosis in HER-2 positive breast cancer, and its mechanism needs to be further explored.

Evaluation of Multidrug Resistant Loop-mediated Isothermal Amplification Assay for Detecting the Drug Resistance of / 生物医学与环境科学（英文）

Objective@#To evaluate multidrug resistant loop-mediated isothermal amplification (MDR-LAMP) assay for the early diagnosis of multidrug-resistant tuberculosis and to compare the mutation patterns associated with the @*Methods@#MDR-LAMP assay was evaluated using 100 @*Results@#The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MDR-LAMP were 85.5%, 93.6%, 96.7%, and 74.4% for the detection of resistance to isoniazid and rifampicin, respectively, and 80.5%, 92.3%, 98.6%, and 41.4% for the detection of @*Conclusion@#MDR-LAMP is a rapid and accessible assay for the laboratory identification of rifampicin and isoniazid resistance of

Update on the treatment of childhood-onset autoimmune hemolytic anemias / 国际儿科学杂志

Autoimmune hemolytic anemia is a disorder of immune function caused by various reasons, by produceing autoantibody or complement which can react with erythrocyte autoantigen, increasing the destruction of red blood cell and beyond the compensatory ability of bone marrow hematopoiesis.Children usually have acute onset and the clinical manifestations are related to the pathogenesis.As the first-line treatment of glucocorticoids, Most children respond well to glucocorticoids.Some children suffer from steroid dependence and resistance; or recurrence due to different types of antibodies, often requiring second-line treatment, such as splenectomy, immunosuppressive, etc.This article reviews the recent progress in the treatment of children with autoimmune hemolytic anemia.

Regulation of RDN on Th1/ILC1 cell imbalance in HFMD patients caused by EV71 infection / 中国天然药物

Enterovirus 71 (EV71) infection is more likely to cause hand, foot and mouth disease (HFMD) in children, which can lead to neurogenic complications and higher mortality. As a commonly used clinical medicine, Reduning injection (RDN) helps to shorten the symptoms of patients with HFMD and facilitate the early recovery of children. However, the regulatory mechanism of RDN on the HFMD immune system disorder caused by EV71 remains to be discussed. This study collected detailed treatment data of 56 children with HFMD who entered the affiliated Children's Hospital of Nanjing Medical University during 2019. Retrospective analysis of clinical data showed that the symptoms of the RDN treatment group were improved compared with the untreated group. To explore its mechanism, the relevant detection indicators were detected by flow cytometry, enzyme-linked immunosorbent assay and real-time quantitative PCR. It was found that the number and function of innate immune (ILCs) and adaptive immunity (Th1, Th2 and secreted cytokines) were reduced, suggesting that RDN plays a role by regulating cellular immunity. The in vitro differentiation inhibition test further confirmed that RDN affected Th1 differentiation by inhibiting the expression of transcription factors on the basis of Th1 cell differentiation in vitro.

Gene mutations of esophageal squamous cell carcinoma based on next-generation sequencing / 中华医学杂志(英文版)

BACKGROUND@#Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers without effective therapy. To explore potential molecular targets in ESCC, we quantified the mutation spectrum and explored the relationship between gene mutation and clinicopathological characteristics and programmed death-ligand 1 (PD-L1) expression.@*METHODS@#Between 2015 and 2019, 29 surgically resected ESCC tissues and adjacent normal tissues from the Fourth Hospital of Hebei Medical University were subjected to targeted next-generation sequencing. The expression levels of PD-L1 were detected by immunohistochemistry. Mutational signatures were extracted from the mutation count matrix by using non-negative matrix factorization. The relationship between detected genomic alterations and clinicopathological characteristics and PD-L1 expression was estimated by Spearman rank correlation analysis.@*RESULTS@#The most frequently mutated gene was TP53 (96.6%, 28/29), followed by NOTCH1 (27.6%, 8/29), EP300 (17.2%, 5/29), and KMT2C (17.2%, 5/29). The most frequently copy number amplified and deleted genes were CCND1/FGF3/FGF4/FGF19 (41.4%, 12/29) and CDKN2A/2B (10.3%, 3/29). By quantifying the contribution of the mutational signatures to the mutation spectrum, we found that the contribution of signature 1, signature 2, signature 10, signature 12, signature 13, and signature 17 was relatively high. Further analysis revealed genetic variants associated with cell cycle, chromatin modification, Notch, and Janus kinase-signal transducer and activator of transcription signaling pathways, which may be key pathways in the development and progression of ESCC. Evaluation of PD-L1 expression in samples showed that 13.8% (4/29) of samples had tumor proportion score ≥1%. 17.2% (5/29) of patients had tumor mutation burden (TMB) above 10 mut/Mb. All samples exhibited microsatellite stability. TMB was significantly associated with lymph node metastasis (r = 0.468, P = 0.010), but not significantly associated with PD-L1 expression (r = 0.246, P = 0.198). There was no significant correlation between PD-L1 expression and detected gene mutations (all P > 0.05).@*CONCLUSION@#Our research initially constructed gene mutation profile related to surgically resected ESCC in high-incidence areas to explore the mechanism underlying ESCC development and potential therapeutic targets.

Research progress of layer-by-layer self-assembly technology in drug delivery / 药学学报

In recent years, layer-by-layer self-assembly (LbL) has developed rapidly. It has been widely used in various industries such as medicine and metallurgy because of its simplicity, flexibility and controllability. In the study of drug delivery system, hollow microcapsules constructed by LbL method as drug carrier have great advantages in drug release, circulation in vivo and bioavailability, providing a technical platform for targeted drug release. In this paper, we summarize the types of film-forming materials and the driving force used in LbL technology, the way of loading drug into hollow micro capsule, and the variety of loaded drugs. We focus on the release mechanism, its evaluation and safety evaluation of self-assembled film as drug carrier in vivo and in vitro. The review shows the great application prospect of LbL technology in the field of drug delivery.

Study on literature of artichoke and properties of traditional Chinese medicine / 中国中药杂志

In this article, the foreign and domestic literature on alien plant medicine Cynara scolymus was reviewed to explore its properties and functions in traditional Chinese medicine theory, and provide theoretical basis for clinical application and reasonable compatibility. Based on the literature databases of PubMed, Web of Science, Embase, the Cochrane Library, CNKI, VIP and Sinomed, the articles with high reliability related to C. scolymus were screened out and the obtained articles were systematically classified according to clinical application, chemical compositions, pharmacological action, toxic and side effects, etc. In the analysis with traditional Chinese medicine theory, it is concluded that: C. scolymus tastes bitter and slightly cold, attributing to spleen, stomach, liver and gall meridians. It has the functions of eliminating accumulation and guiding stagnation, regulating Qi-flowing for harmonizing stomach, clearing away dampness and heat, resolving turbidity and lowering blood lipids. It can be used for the treatment of dyspepsia, diet reduction, vomiting, nausea, abdominal distention, hypochondriac pain, jaundice, hyperlipidemia, etc. Through the analysis and research of the relevant literature on C. scolymus, the properties and functions of the drug were clarified, which could provide a theoretical basis for further animal experiments and clinical research. The research model of "traditional Chinese medicine theory" for alien plant medicines can provide reference for the introduction and research of botanical drugs around the world, which can greatly enrich Chinese medicine resources and is of great significance for promoting the sustainable development of traditional Chinese medicine.

Effect of injecting mouse nerve growth factor in different ways on motor development, cerebral hemodynamics and biochemical metabolism in children with cerebral palsy / 中国针灸

OBJECTIVE@#To compare the effect of acupoint injection and intramuscular injection with mouse nerve growth factor (mNGF) on gross motor function development of children with cerebral palsy (CP), and explore the treatment mechanism.@*METHODS@#A total of 63 children with CP were randomly divided into an observation group (32 cases, 4 cases dropped off ) and a control group (31 cases, 3 cases dropped off). Based on the routine rehabilitation therapy, the control group received intramuscular injection of mNGF(18 µg/2 mL), and the observation group received acupoint injection of mNGF at Xinshu (BL 15), Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23), Sanjiaoshu (BL 22), Shenting (GV 24), Baihui (GV 20), Fengfu (GV 16), Dazhui (GV 14), etc. Of them, 5-6 acupoints alternately were selected each time, and each acupoint was given 0.3-0.5 mL, totally 18 µg/2 mL. Both treatment were carried out once every other day for six months. Before and after treatment, the children's development of brain function was assessed using gross motor function classification system (GMFCS). Before treatment (T), after 2 (T), 4 (T) and 6 (T) months of treatment, the motor function was evaluated by gross motor function measure (GMFM-88). The systolic peak velocity (Vs), mean velocity (Vm) and vascular resistance index (RI) of anterior cerebral artery (ACA) and middle cerebral artery (MCA) were measured, and the level of N-acetyl aspartate acid (NAA), choline (Cho), lactate (Lac) and creatine (Cr) from the basal ganglia, thalamus and periventricular white mater were detected by magnetic resonance spectroscopy (MRS) technology with MAGNETOM Skyra3.0T magnetic resonance imaging system before and after treatment.@*RESULTS@#Compared with before treatment, the GMFCS classification of the observation group after treatment was significantly improved (0.05), however, the observation group had a 3.142 times of feasibility for good gross motor function development by more than level 1 compared to the control group (<0.05). After 2, 4, and 6 months of treatment, the GMFM-88 scores of the two groups showed an upward trend (<0.01), and the increase of the observation group was greater than that of the control group (<0.05). Compared with before treatment, in the ACA and MCA, the Vs and Vm increased, RI decreased in both groups after treatment (<0.01), and in the brain, NAA/Cr increased, Cho/Cr and Lac/Cr decreased (<0.01), and after treatment, the Vs, Vm of ACA and MCA and NAA/Cr of brain in the observation group were higher than those in the control group (<0.05), and the RI of ACA and MCA and Cho/Cr and Lac/Cr of brain in the observation group were lower than those in the control group (<0.05).@*CONCLUSION@#The mNGF acupoint injection has a better effect on the gross motor function in the children with cerebral palsy compared with the intramuscular injection, and the mechanism may be associated with exhibiting the double effects of acupoint effect and the targeting therapy of drug, which can effectively improve the cerebral hemodynamics and the metabolism of cerebral nervous substances.

Expression of programmed cell death-ligand 1 in invasive breast cancer and its clinical significance / 肿瘤研究与临床

Objective:To explore the expression of programmed cell death-ligand 1 (PD-L1) in invasive breast cancer and its relationship with clinicopathological characteristics.Methods:A total of 651 paraffin-embedded specimens of newly diagnosed invasive breast cancer patients including 98 cases of triple-negative breast cancer (TNBC) in the Affiliated Nanjing Drum Tower Hospital of Medical School of Nanjing University from January 2018 to August 2019 were collected. The immunohistochemical EnVision method was used to detect the expression of PD-L1 protein in tumor cells of breast invasive cancer and infiltrating lymphocytes. The expression rate of PD-L1 in tumor cells of cancer section tissues and tumor interstitial lymphocytes ≥1% was positive and < 1% was negative.Results:The positive expression rate of PD-L1 expression in breast invasive carcinoma was 47.0% (306/651), among which the positive expression rate of TNBC was 69.3% (68/98). PD-L1 had a high positive expression rate in patients with high World Health Organization (WHO) grade, large tumor size, vascular invasion, advanced pathological stage, negative estrogen receptor (ER) expression, negative progesterone receptor (PR) expression, positive p53, positive CK5/6, positive epidermal growth factor receptor (EGFR), and high Ki-67 value (all P < 0.05). In TNBC, PD-L1 had a high positive expression rate in patients with high WHO grade, invaded nerves, high Ki-67 value, positive CK5/6, and positive EGFR (all P < 0.05). Multivariate analysis showed that WHO grade ( HR = 1.511, 95% CI 1.139-2.003, P = 0.004), Ki-67 value ( HR = 1.847, 95% CI 1.259-2.709, P = 0.002), p53 expression ( HR = 2.083, 95% CI 1.487-2.916, P < 0.01), and EGFR expression ( HR = 3.490, 95% CI 2.002-6.086, P < 0.01) were independent influencing factors of PD-L1 expression. Conclusions:PD-L1 is highly expressed in invasive breast cancer, especially in TNBC. It could be used as a potential treatment target for patients with invasive breast cancer.

Pregnancy-Induced Hemophagocytic Lymphohistiocytosis: A Case Report and Literature Review / 中国医学科学杂志(英文版)

Hemophagocytic lymphohistiocytosis (HLH) is a rare but devastating disease characterized by dysregulated immune response and hyperinflammation. To our knowledge, pregnancy-induced HLH has been rarely reported in the literature. A 30-year-old pregnant woman presented persistent fever for 21 days since 17 weeks of pregnancy. The possible etiologies such as infection, autoimmune disorder, and malignancy had been ruled out based on a series of exhaustive examinations. The disease progressed despite the use of broad-spectrum antibiotics and dexamethasone. The patient was diagnosed as pregnancy-induced HLH, and finally recovered completely after termination of pregnancy by caesarean and the continuous use of glucocorticoid which played a crucial part in controlling hyperinflammation. Pregnancy-induced HLH could be fatal if effective treatment was not initiated timely. Further studies are needed to improve early diagnosis and etiology identification of HLH.

Effect of antimicrobial use density on resistance rate of Stenotrophomonas maltophilia / 中国感染控制杂志

Objective To analyze the correlation between antimicrobial use density (AUD) and change in antimicrobial resistance rate of Stenotrophomonas maltophilia (SM), and explore the influencing factors of antimicrobial resistance of SM. Methods Antimicrobial resistance rate of SM and AUD of commonly used antimicrobial agents in patients in a hospital from 2012 to 2017 were summarized, correlation was analyzed with Pearson correlation method. Results A total of 23 994 strains of gram-negative bacteria were isolated, of which 1 331 strains (5.55％) were SM, mainly from sputum (54.02％) and distributed in intensive care unit (21.49％). Resistance rates of SM to ceftazidime, levofloxacin, and compound sulfamethoxazole were 21.79％, 7.66％, and 13.37％ respectively, resistance rates to levofloxacin showed an increasing trend year by year (P＜0.05). Resistance rate of SM to levofloxacin was positively correlated with the use intensity of β-lactamase inhibitors, carbapenems, fluoroquinolones, and oxazolidinones (all P＜0.05); resistance rate to compound sulfamethoxazole was positively correlated with the use intensity of macrolides (P＜0.05).Conclusion Change in resistance rates of SM to levofloxacin and compound sulfamethoxazole are positively correlated with the use intensity of some commonly used antimicrobial agents, reducing AUD is beneficial to the control and reducing of the resistance of SM.

Effect of Sanhuang Yinchi Decoction in Preventing Acute Liver Injury by HMGB1 Signaling Pathway / 中国实验方剂学杂志

Objective:To investigate the effect and mechanism of Sanhuang Yinchi decoction (SHYCD) in preventing carbon tetrachloride (CCl4)-induced acute liver injury by regulating high mobility group box1(HMGB1) signaling pathway. Method:A total of 48 KM mice were randomly divided into blank control group, model group, low, middle and high-dose SHYCD groups and positive control group. The model of acute liver injury induced by CCl4 in mice was established. The low, middle and high-dose SHYCD groups were intragastrically administered with drugs (16, 32, 48 g·kg-1·d-1) respectively, and the positive control group was given cell growth stimulating hormone (20 mg·kg-1·d-1) through intraperitoneal injection. Pathological changes of mouse liver tissue sections were observed by hematoxylin-eosin staining (HE); relevant enzyme kits were used to determine liver function indexes in mice serum-alanine aminotransferase (AST) and aspartate aminotransferase (ALT); the expression level of interleukin-6 (IL-6) in mouse serum was determined by enzyme-linked immunosorbent assay (ELISA); Western blot was used to detect the expressions of high mobility group box-1(HMGB1), cysteine aspartic acid protease(Caspase-3), apoptosis-related molecules B cell lymphoma(Bcl-2), Bcl-2 associated x protein(Bax), and Toll-like receptor 4 (TLR4). Result:Compared with the normal group, the model group significantly increased serum AST, ALT (PPPPPConclusion:SHYCD can prevent liver injury by regulating HMGB1/TLR4/NF-κB signaling pathway, reducing cellular inflammatory response and inhibiting apoptosis, so as to prevent acute liver injury in mice. This indicates that HMGB1 may become a new target to prevent acute liver injury.

Hepatotoxic Material Basis of Polygoni Multiflori Radix with Zebrafish Model / 中国实验方剂学杂志

Objective:To explore the hepatotoxic material basis of Polygoni Multiflori Radix with zebrafish model, in order to provide a theoretical basis for the study on the mechanism of Polygoni Multiflori Radix hepatotoxicity. Method:Emodin, rhein, aloe emodin, emodin-1-O-glucoside, physcion-8-O-glucoside and aloe emodin-8-O-glucoside for three days (at the concentrations of 0.000 73, 0.002 22, 0.015 05, 0.002 36, 0.198 95, 0.072 73 g·L-1) selected from the early stage of the experiment were continuously administered to zebrafish fertilized for 72 hours to establish the liver fluorescence transgenic larvae animal model. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione (GSH) and total bilirubin (TBIL) in zebrafish at 1, 2, 3 day after administration were measured respectively, and the pathological changes of zebrafish liver tissue were analyzed. Result:Emodin, rhein, emodin-1-O-glucoside and physcion-8-O-glucoside had no significant effect on the activities of ALT, AST, GSH and content of TBIL (PPO-glucoside could significantly reduce the activities of ALT, GSH, whereas increased the content of TBIL (PPConclusion:Aloe-emodin and aloe-emodin-8-O-glucoside in Polygoni Multiflori Radix have a toxic effect on zebrafish liver, suggesting that aloe-emodin and aloe-emodin-8-O-glucoside might be the hepatotoxic material basis of Polygoni Multiflori Radix.