Objective: To assess the outcomes and toxic effects of 5-day actinomycin D (Act-D) salvage therapy and to explore the predictors of Act-D resistance in patients with low-risk gestational trophoblastic neoplasia (GTN)who failed 5-day methotrexate (MTX) chemotherapy. Methods: This retrospective study analyzed patients with low-risk GTN administered Act-D salvage therapy after failing MTX chemotherapy at Women's Hospital, School of Medicine Zhejiang University between January 2000 and December 2015. The clinical parameters of these patients were collected and analyzed. Results: The final analysis included 89 cases. Of these, 73 cases (82.02%) responded to salvage Act-D. The remaining 16 resistant cases were switched to etoposide, MTX, Act-D/ cyclophosphamide, and vincristine chemotherapy and achieved complete remission. Serum human chorionic gonadotrophin levels before Act-D salvage therapy (hCG Act-D )in the Act-Dresistant cases were significantly higher than those in the Act-D responders (median 605 vs.103 IU/L, p=0.009). However, the range of hCGAct-D values in Act-D responders was wider than that in Act-D-resistant cases (5.76–16,664 IU/L vs. 11.43–6,732 IU/L). Thus, assigning a general cut-off value was difficult considering the individual setting. Except for 2 cases requiring other salvage regimens due to Act-D toxicity, 97.80% of cases (89/91) tolerated the toxicity. During at least 1-year follow-up, the survival rate was 100.00% and no case developed recurrence. Conclusion Based on the good therapeutic effect and tolerable toxicity, we recommend Act-D salvage therapy for all patients with low-risk GTN who fail primary MTX chemotherapy.The higher serum hCG levels before Act-D salvage therapy may be associated with resistance to this treatment.

Objective To evaluate etoposide,methotrexate and dactinomycin (EMA)/ cyclophosphamide and vincristine (CO) regimen for treatment of ultra high-risk gestational trophoblastic neoplasia (GTN).Methods A total of twenty-four ultra high-risk patients who had International Federation of Gynecology and Obstetrics (FIGO) prognostic scores greater or equal to 12 with liver,brain,or extensive metastases did poorly when treated with primary chemotherapy admitted in Women's Hospital,School of Medicine,Zhejiang University from January 2001 to December 2015.All of the patients were treated by EMA/CO regimen and followed up to death or December 2017.The clinical data of patients were analyzed retrospectively and the efficacy and toxicity of EMA/CO were evaluated.Results All of the cases with ultra high-risk GTN had FIGO prognostic scores ≥12 (ranged 12-18,median 13.0).Twenty patients (83％,20/24) received EMA/CO regimen as primary treatment and 4 patients (17％,4/24) had a history of failed chemotherapy.Seven patients (29％,7/24) had metastasis of liver or brain and 17 patients (71％,20/24)had no metastasis of liver and brain.Twenty-four patients received totally 167 courses of EMA/CO regimen (average 7.0 courses).Sixteen patients achieved complete remission and 8 patients showed drug-resistant.The complete remission rate was 67％ (16/24) and the resistance rate was 33％ (8/24).Of the 16 patients who got complete remission,6 cases were treated with EMA/CO regimen alone,and 10 cases were treated by chemotherapy combined with surgery.For the 8 patients who showed drug-resistant to EMA/CO,5 cases of them received EMA/etoposide and cisplatin (EP) regimen and 3 cases got remission,1 case received methotrexate,dactinomycin and cyclophosphamide (MAC) regimen and got remission,2 cases gave up treatment because of economic factors.The side effects of EMA/CO mainly included Ⅲ-Ⅳ degree neutropenia,anemia and alopecia.The incidence of Ⅲ-Ⅳ degree neutropenia during the treatment of EMA/CO was 21.6％ (36/167),the incidence of anemia was 96.4％ (161/167),and the incidence of alopecia was 60.5％ (101/167).In these 24 ultra high-risk GTN patients,4 patients died during follow-up.In the 20 patients who got complete remission,no recurrence or secondary tumor by chemotherapy were occurred.Conclusion EMA/CO is an effective regimen with manageable toxicity for patients with ultra high-risk GTN.

Objective:To study the risk factors of necrotizing enterocolitis (NEC) after surgery for intestinal atresia.Method:From August 2013 to June 2020, children with intestinal atresia receiving surgery in our hospital were retrospectively reviewed. The patients were assigned into NEC group and non-NEC group according to the occurrence of postoperative NEC. Demographic data and clinical characteristics were summarized and the risk factors for postoperative NEC were analyzed using Logistic regression analysis method.Result:A total of 96 infants were enrolled and NEC occurred in 13 patients (13.5%) after surgery for intestinal atresia. Compared with the non-NEC group, the NEC group were diagnosed of intestinal atresia [4.0(1.5,6.0)d vs. 1.4(0,2.0)d, P<0.001] and received surgery [4.8(2.0,7.0)d vs. 3.1(1.0,4.0)d, P=0.034] at later ages. The incidences of complex intestinal atresia [76.9%(10/13) vs. 44.6%(37/83), P=0.030] and blood transfusion [46.2%(6/13) vs. 13.3%(11/83), P=0.007] in the NEC group were higher than the non-NEC group. Logistic regression analysis showed that the age of initial diagnosis of intestinal atresia ( OR=3.346, 95% CI 1.493~7.500, P=0.003), complex intestinal atresia ( OR=9.052, 95% CI 1.119~73.209, P=0.039) and blood transfusion ( OR=6.835, 95% CI 1.399~33.380, P=0.018) were independent risk factors for postoperative NEC. Conclusion:Patients with delayed diagnosis of intestinal atresia, complex intestinal atresia and blood transfusion within 48 hours after surgery should be monitored for the occurrence of postoperative NEC.

OBJECTIVE To study the improvement effects of arbutin on myocardial fibrosis （MF） model rats and its mechanism. METHODS The network pharmacology was used to predict the potential target of arbutin in improving MF and molecular docking was used to validated. Totally 50 SD rats were given isoprenaline subcutaneously （5 mg/kg， once a day， for 14 consecutive days） to induce the MF model. Modeled rats were randomly divided into model group， captopril group （9 mg/kg）， arbutin low-dose， medium-dose and high-dose groups （50， 100， 200 mg/kg）， with 10 rats in each group. Another 10 healthy rats were included as normal group. Each group was given the corresponding drugs， once a day， for 28 consecutive days. Twenty-four hours after the final administration， electrocardiograms and heart-related indexes [heart weight index （HWI）， left ventricular weight index （LVWI）] of rats were detected； the levels of creatine kinase （CK）， lactate dehydrogenase （LDH）， N-terminal pro-brain natriuretic peptide （NT-proBNP） and type Ⅰ collagen （Col Ⅰ） and Col Ⅲ were detected in myocardial tissue of rats； the pathological changes of myocardial tissue were observed， and protein and mRNA expressions of adenosine deaminase （ADA） and adenosine kinase （ADK） were detected in the myocardial tissue of rats. RESULTS The results of network pharmacology showed that the main targets of arbutin improving MF were ADA and ADK. The results of molecular docking showed that arbutin bind stably with ADA and ADK. The results of experimental verification showed that compared with model group， the amplitude of ST and T waves in electrocardiogram were improved in administration groups， and the symptoms of atrial flutter were alleviated； HWI （except for arbutin medium-dose group）， LVWI， the levels of CK， LDH， NT-proBNP， Col Ⅰ and Col Ⅲ in the myocardial tissue of rats were decreased significantly （P＜0.05）； the degree of myocardial fibrosis in rats decreased； protein and mRNA expressions of ADA and ADK in the myocardial tissue were significantly increased （P＜0.05）. CONCLUSIONS Arbutin can improve cardiac fibrosis and cardiac function of MF model rats， the mechanism of which may be associated with up-regulating protein and mRNA expressions of ADA and ADK，influencing the nucleotide metabolism and collagen generation. zhangminghao@hactcm.edu.cn

ObjectiveTo explore the brain mechanism of repetitive transcranial magnetic stimulation (rTMS) on dysfunction after stroke using functional magnetic resonance imaging (fMRI). MethodsLiteratures about the functional magnetic resonance imaging study about repetitive transcranial magnetic stimulation for dysfunction after stroke were retrieved in PubMed, Web of Science, CNKI and Wanfang data from establishment to June 1st, 2021. The quality of the literature was evaluated with Physiotherapy Evidence Database (PEDro) scale. Literature screening, and data extraction were performed by two researchers. ResultsA total of 14 randomized controlled trials were finally enrolled. They were of high or very high quality. They mainly involved the therapeutic effect and imaging mechanisms of rTMS on dysfunction after stroke. ConclusionrTMS could change the excitability of the cerebral cortex and the effective connections between brain regions after stroke, promote the reorganization of brain function, and achieve the recovery of post-stroke dysfunction.

OBJECTIVE To establish a quantitative fingerprint analysis method for sugar components in Yuanhu Zhitong oral liquid using high performance liquid chromatography-charged aerosol detection(HPLC-CAD). METHODS Chromatographic column was NH2P-50 4E(4.6 mm×250 mm, 5 μm) column. Water(A) and acetonitrile(B) were used as the mobile phase in the gradient elute mode. The column temperature was 30 ℃. The injection volume was 10 μL. The flow rate was 0.6 mL·min−1. The evaporation temperature of CAD was 35 ℃. The acquisition frequency was 10 Hz. The power function value was 1.0. RESULTS The linear relationship of the quantitative component was good within the quantitative range, with R2>0.999. The relative standard deviations(RSDs) of instrument precision, intermediate precision and method repeatability were all <3%. The test solution was stable within 24 h. The average recoveries at low, medium and high concentration levels ranged 97.15%−101.13%. There were 5 common peaks in the fingerprint. The RSDs of instrument precision, method repeatability and sample stability were all <4%. CONCLUSION The established analytical method is stable, accurate and reproducible. It can be used to detect sugar excipients in the preparations.

OBJECTIVE To investigate the mechanism of Pangshi antai zhixue decoction in the improvement of spontaneous abortion with heat syndrome by regulating the NOD-like receptor protein 3 （NLRP3） inflammasome. METHODS The binding activities of 13 main components in Pangshi antai zhixue decoction with NLRP3， apoptosis-associated speck-like protein ， containing a CARD （ASC）， and caspase-1 precursor （pro- No.20-21ZY1053） caspase-1） were predicted by molecular docking. Sixty 1-day-old pregnant rats were randomly divided into normal group， model group， dexamethasone group （0.002 g/kg）， and Pangshi antai zhixue decoction low-， medium-， and high-dose groups （11.025， 22.05， 44.10 g/kg）， with 10 rats in each group. Each group was given distilled water/corresponding medicinal solution intragastrically， once a day， for 12 consecutive days. Except for normal group， other groups were given traditional Chinese medicine for warming yang and mifepristone to establish a model of spontaneous abortion with heat syndrome. 24 h after the last medication， serum levels of triiodothyronine （T3）， thyroxine （T4）， interleukin-2 （IL-2）， IL-4， IL-6， IL-10， and interferon-γ （IFN-γ） were all detected； the abortion rate and uterine coefficient were calculated； the pathological morphology of the pregnant uterus was observed； protein expressions of NLRP3， ASC and caspase-1 were detected. RESULTS The molecular docking results showed that the binding energies of 13 main components of Pangshi antai zhixue decoction with NLRP3， ASC， and pro-caspase-1 were all less than －5 kJ/moL. The animal experiment results showed that compared with normal group， the uterine coefficient and serum levels of IL-4， IL-6 and IL-10 were decreased significantly in model group （P＜0.05）； the abortion rate and serum levels of T3， T4， IL-2 and IFN-γ as well as protein expressions of NLRP3， ASC and caspase-1 were increased significantly （P＜0.05）； there were abortion lesions in the pregnant endometrium. Compared with the model group， most of the quantitative indicators mentioned above were significantly reversed in Pangshi antai zhixue decoction groups （P＜0.05）， and the endometrial miscarriage lesions in pregnancy were improved to varying degrees. CONCLUSIONS Pangshi antai zhixue decoction influences the immune balance between mother and fetus by regulating the formation of NLRP3 inflammasome， down-regulating pro-inflammatory cytokines such as IFN-γ and IL-2， and up-regulating anti-inflammatory cytokines such as IL-4， IL-6 and IL-10， thereby improving spontaneous abortion with heat syndrome.