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Reconsideration of the third-generation non-steroidal aromatase inhibitors in pediatrics
J Zhejiang Univ (Med Sci), 2020, 49(3): 275-282.   https://doi.org/10.3785/j.issn.1008-9292.2020.04.01
Abstract( 1303 )   HTML( 49 )     PDF(1066KB)( 406 )

Aromatase is the rate-limiting enzyme in estrogen biosynthesis. The third generation aromatase inhibitors (AIs), represented by letrozoleand and anastrozole, can combine with aromatase, effectively reducing the estrogen level in the body. Because of its high efficiency, selectivity and reversibility, it has been used in the treatment of McCune-Albright syndrome, familial male-limited precocious puberty, gynecomastia, and adolescent boy with short stature. The good efficacy and safety of AIs have been observed. However, so far the drug instructions of AIs usually do not show indications for children; there are risks of adverse reactions involving liver and kidney function, lipid metabolism, hyperandrogenemia and bone metabolism; especially the long-term effects on reproductive system and bone metabolism are still not clear. Therefore, it is necessary to prescribe it carefully and follow up closely. It was not recommended that AIs be routinely used to improve adult height of adolescent boy with short stature. And more clinical evidences are needed for the safety and effectiveness of AIs prescribed in pediatrics.

Aromatase inhibitors combined with growth hormone in treatment of adolescent boys with short stature
KONG Yuanmei,CHEN Hong,LIANG Li,ZHENG Maoni,FANG Yanlan,WANG Chunlin
J Zhejiang Univ (Med Sci), 2020, 49(3): 283-290.   https://doi.org/10.3785/j.issn.1008-9292.2020.04.06
Abstract( 1070 )   HTML( 28 )     PDF(1058KB)( 562 )

Objective: To assess the efficacy and safety of aromatase inhibitors (AIs) combined growth hormone in treatment of adolescent boys with short stature. Methods: One hundred and fifty-one short stature pubertal boys with age of 10-14 years and bone age of 13-15 years, who were admitted to the Department of Pediatrics, the First Affiliated Hospital, Zhejiang University School of Medicine, were included in this trial. According to their own or parents' intention, the children were divided into recombinant human growth hormone (rhGH)+AI group (n=108) and rhGH group (n=43). All children were injected subcutaneously with rhGH 0.15-0.2 IU·kg-1·d-1, and those in rhGH+AI group were additionally given 2.5 mg/d letrozole or 1 mg/d anastrozole, orally for 12 months or longer. The children were followed-up every 3 months. During the follow-up visit, the predicted adult height (PAH), sex hormone level, glucose and lipid metabolism, and other indicators were measured, and adverse reactions were monitored. Results: After intervention, there were significant differences in ΔBA(bone age)/ΔCA(chronological age), ΔHtSDSBA(height standard deviation score based on bone age)and ΔPAH between rhGH+AI group and the rhGH group(P < 0.05 or P < 0.01). During follow-up, 63.9%of the children in the rhGH+AI group had elevated uric acid and 51.9%had decreased high-density lipoprotein (HDL); 25.9%showed severe acne, excitement, hyperactivity and irritability, 11.1%had knee pain; 4.6%had fracture; 2.8%had mild renal dysfunction; 1.9%had inactivity, drowsiness, memory loss and performance decline; 1.9%showed mild abnormal liver function; 0.9%showed impaired fasting glucose; 0.9%showed granulocytopenia. In the rhGH group, 11.6%of the children presented with knee pain and 2.3%with impaired fasting glucose. Conclusions: AI combined with rhGH can delay the growth of BA and effectively improve the PAH of adolescent boys with larger bone age. However, the occurrence of adverse reactions of AI should be closely monitored during treatment.

Efficacy and safety of letrozole in treatment of McCune-Albright syndrome girls with peripheral precocious puberty
XU De,LU Wenli,WANG Xueqing,WANG Junqi,XIE Yiwen,DONG Zhiya,WANG Wei
J Zhejiang Univ (Med Sci), 2020, 49(3): 291-296.   https://doi.org/10.3785/j.issn.1008-9292.2020.04.03
Abstract( 591 )   HTML( 11 )     PDF(1026KB)( 424 )

Objective: To evaluate the efficacy and safety of the third-generation aromatase inhibitor letrozole in the treatment of McCune-Albright syndrome (MAS) girls with peripheral precocious puberty. Methods: Twenty-one MAS girls with peripheral precocious puberty treated in Pediatrics Department of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from March 2012 to June 2017 were enrolled in the study. Patients presented with repeated vaginal bleeding, premature breast enlargement, café-au-lait spots or dysplasia of bone fibers, and low levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH); and the congenital adrenal hyperplasia, estrogen-producing tumors, and exogenous estrogen intake were excluded. Letrozole were administrated at a dose of 0.5-2 mg·m-2·d-1 for 6 to 12 months. The patients were observed for changes in breast staging, vaginal bleeding, sex hormone levels, liver function and bone age changes, and changes in uterine and ovarian volume. Results: After treatment, bone age/chronological age (BA/CA)was decreased from 1.23±0.30 to 1.11±0.18 (P < 0.01); the predicted adult height (PAH) increased from (156.2±5.9)cm to (158.4±2.1)cm after treatment (P < 0.05); the vaginal bleeding was reduced and the estradiol level decreased, while the teststosterone level and the uterus showed no significant increase, and no adverse reactions such as ovarian torsion and abnormal liver function were observed. Conclusion: Precocious puberty is one of the most common endocrine manifestations in MAS. Our findings suggest that letrozole may be an effective and safe therapy to precocious puberty in girls with McCune-Albright Syndrome.

Efficacy and safety of letrozole in treatment of male children with disorders of sex development
YU Bingqing,NIE Min,WU Xueyan,MAO Jiangfeng,WANG Xi,MA Wanlu,JI Wen,HUANG Qibin,ZHANG Rui
J Zhejiang Univ (Med Sci), 2020, 49(3): 297-301.   https://doi.org/10.3785/j.issn.1008-9292.2020.04.02
Abstract( 596 )   HTML( 8 )     PDF(1014KB)( 199 )

Objective: To investigate the efficacy and safety of aromatase inhibitor letrozole in treatment of male children with disorders of sex development (DSD). Methods: Clinical data of 12 male DSD children with a mean age of 14.6±2.5 years admitted to Peking Union Medical College Hospital from January 2014 to January 2016 were retrospectively analyzed. The patients were treated with letrozole (1.25-2.5 mg, once a day) for 3 months or longer, and followed up for 0.5-2.5 years. Clinical manifestation and laboratory test findings were documented, and the efficacy and safety were evaluated. Results: After half-year treatment, the blood luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels of patients increased (all P < 0.05), and estrogen levels decreased from baseline (P < 0.05). After 1 year of treatment, the blood testosterone level was significantly higher (P < 0.05); the LH and FSH levels tended to increase and the estrogen level tended to decrease, but there was no significant statistical difference (P>0.05). Semen was routinely detected in 8 patients, and sperms were detected in semen of 3 patients with hypospadias. There were no significant changes in biochemical results after treatment, and no significant adverse event was observed during the treatment. Conclusion: Letrozole can effectively increase testosterone levels in patients with disorders of sex development and promote spermatogenesis, it has no significant adverse effects in short-term administration.

Efficacy of letrozole in treatment of children with congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency
WANG Qian,ZHANG Shule,MA Xue,LI Guimei,WANG Zengmin,WANG Fengxue
J Zhejiang Univ (Med Sci), 2020, 49(3): 302-307.   https://doi.org/10.3785/j.issn.1008-9292.2020.04.04
Abstract( 531 )   HTML( 7 )     PDF(1030KB)( 310 )

Objective: To assess the efficacy of letrozole in treatment of children with congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency (21-OHD). Methods: Twenty eight children, including 19 boys and 9 girls aged 4-10y, with CAH due to 21-OHD were enrolled in the study. At the first six months of study, all children received conventional treatment with hydrocortisone or fludrocortisone, then letrozole was added to original regimen. The height velocity (HV), difference between bone age and chronological age (BA-CA), height standard diviation score based on bone age (HtSDSBA), predicted adult height (PAH), Tanner phase, sex hormone, and possible adverse reaction were evaluated and compared between those before and after letrozole treatment. Results: After 6 months of letrozole treatment, there was significant deceleration of HV, but it would recover soon. There was significant increase of HtSDSBA after 12 months of letrozole treatment (P < 0.05 or P < 0.01), and significant changes in BA-CA after 18 months of letrozole treatment (P < 0.05). PAH of female children was significantly increased during letrozole treatment (P < 0.05), whereas PAH of male children was significantly increased 18 months after letrozole treatment (P < 0.05). Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were significantly increased, but did not meet the diagnostic criteria of central precocious puberty. Estradiol was significantly decreased (P < 0.01), but no changes in testosterone level was observed. During 24 months letrozole treatment, no hirsutism, severe acne, headache, bone pain, obesity, hypertension, rash and other adverse reactions were observed. Conclusions: Letrozole can delay bone maturation and improve PAH, which can be used with conventional treatment for children with CAH due to 21-OHD, especially for those with high BA and low PAH.

Efficacy of letrozole in treatment of male adolescents with idiopathic short stature
LI Yanhong,DU Minlian,MA Huamei,CHEN Qiuli,CHEN Hongshan,ZHANG Jun
J Zhejiang Univ (Med Sci), 2020, 49(3): 308-314.   https://doi.org/10.3785/j.issn.1008-9292.2020.04.05
Abstract( 1029 )   HTML( 20 )     PDF(1045KB)( 382 )

Objective: To evaluate the efficacy and safety of aromatase inhibitor letrozole in treatment of male adolescents with idiopathic short stature (ISS). Method: Seventy five boys with height less than 2 standard deviation (SD) below the mean who had entered puberty were enrolled in our study from 2004 to 2017, in the Pediatric Department of the First Affiliated Hospital, Sun Yat-Sen University. Among 75 patients, 28 in letrozole group received letrozole and spironolactone, 30 in gonadotrophin releasing hormone analogue (GnRHa) group received GnRHa injection and 17 had no intervention. Height velocity (HV), increment of bone age/chronological age (ΔBA/ΔCA), the final adult height (FAH) were compared among groups and the safety of letrozole treatment was evaluated. Results: HV maintained faster during letrozole treatment when compared with other groups. HV during GnRHa treatment showed slightly decline in the first 6 months, but decreased remarkably after 6 months, and was significantly lower than that in letrozole group (P < 0.05). The maturation of BA slowed down in both letrozole and GnRHa groups. But the ΔBA/ΔCA in letrozole group during the first and the second year of treatment were significantly higher (0.67±0.09, 0.50±0.15, respectively) when compared with GnRHa group (0.59±0.16, 0.44±0.13, respectively) (t=2.78 and 2.20, all P < 0.05). FAH in letrozole group and GnRHa group were (170±4) cm and (170±6)cm, there was no significant differences between the two groups (P>0.05), and both were higher than that in no intervention group (162±4 cm, P < 0.01). After 6 months of letrozole treatment, testicular volumes and serum testerone levels increased; 39.2% (11/28) boys had clinical manifestations of hyperandrogenemia, and 82.1% (23/28) boys had decreased serum high-density lipoprotein (HDL) levels. Serum levels of HDL and testerone returned normal and the hyperandrogenemia disappeared after the cessation of letrozole treatment. No significant changes in serum triglyceride, serum low-density lipoprotein (LDL), fating serum levels of insulin and glucose, HOMA-IR were observed. No abnormal liver function, myalgia, scoliosis or aggravations of scoliosis was found. Conclusions: Long term letrozole therapy during puberty in boys with ISS can delay bone maturation without significant decrease of linear growth, and thus can improve the final adult height. No severe adverse reactions were found.

Comparative analysis of structural characteristics and epitopes in S proteins between SARS-CoV-2 and SARS-CoV
LUN Yongzhi,LIU Ben,DONG Wen,SUN Jie,PAN Linghong
J Zhejiang Univ (Med Sci), 2020, 49(3): 315-323.   https://doi.org/10.3785/j.issn.1008-9292.2020.05.01
Abstract( 699 )   HTML( 12 )     PDF(15104KB)( 316 )

Objective: To provide data support for the study of pathogenic mechanism of SARS-CoV-2 at the molecular level, and provide suitable candidate targets for vaccine, antibody and drug research and development through comparative analysis for structural characteristics and epitopes of S protein of SARS-CoV-2 and SARS-CoV. Methods: Based on the reference sequences of S protein, physical and chemical properties, hydrophobicity, signal peptide, transmembrane region, domain, secondary structure, tertiary structure analysis and antigenic epitopes prediction were carried out. Meanwhile, the tissue expression, related pathways and reactome pathways of angiotensis Ⅰ converting enzyme 2 (ACE2) and C-type lectin domain family 4 member M (CLEC4M) receptors were analyzed. Results: The amino acid sequence of S protein of SARS-CoV-2 and SARS-CoV has a 75.80% consistency. The structural characteristics of the two coronaviruses are highly consistent, but the secondary structure and tertiary structure of SARS-CoV-2 is not as obvious as SARS-CoV. ACE2 and CLEC4M are expressed in alimentary system, heart, kidney, lung and placenta. The main related the pathways of renin-angiotensin system, protein digestion and absorption pathway, and the reactome pathways of metabolism of angiotensinogen to angiotensins, GPCR ligand binding, are related to typical symptoms of coronavirus disease 2019 induced by SARS-CoV-2. Three pairs of highly or completely homologous epitopes of S protein were obtained. The 600-605, 695-703 and 888-896 amino acid residues in SARS-CoV-2 were highly homologous with 586-591, 677-685 and 870-878 amino acid residues in SARS-CoV, respectively. Conclusions: The similarity of S protein of SARS-CoV-2 and SARS-CoV determines that they have similar infection patterns and clinical manifestations. The candidate epitopes with high reliability can provide reference for virus diagnosis and vaccine development.

Replication and transmission mechanisms of highly pathogenic human coronavirus
HE Yeyan,ZHENG Chanying
J Zhejiang Univ (Med Sci), 2020, 49(3): 324-339.   https://doi.org/10.3785/j.issn.1008-9292.2020.03.16
Abstract( 1125 )   HTML( 29 )     PDF(9898KB)( 435 )

The three known highly pathogenic human coronaviruses are severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human highly pathogenic coronaviruses are composed of non-structural proteins, structural proteins, accessory proteins and ribonucleic acid. Viral particles recognize host receptors via spike glycoprotein (S protein), enter host cells by membrane fusion, replicate in host cells through large replication-transcription complexes, and promote proliferation by interfering with and suppressing the host's immune response. Highly pathogenic human coronaviruses are hosted by humans and vertebrates. Viral particles are transmitted through droplets, contact and aerosols or likely through digestive tract, urine, eyes and other routes. This review discusses the mechanisms of replication and transmission of highly pathogenic human coronaviruses providing basis for future studies on interrupting the transmission and pathogenicity of these pathogenic viruses.

Coagulation dysfunction in COVID-19
XU Yiming,LYU Dandan,YING Kejing
J Zhejiang Univ (Med Sci), 2020, 49(3): 340-346.   https://doi.org/10.3785/j.issn.1008-9292.2020.05.02
Abstract( 747 )   HTML( 15 )     PDF(1035KB)( 479 )

In addition to common clinical features, patients with coronavirus disease 2019 (COVID-19) have varying degree of coagulation dysfunction with the risk of thrombosis and/or bleeding. COVID-19 related coagulation dysfunction is a dynamic process, which may be accompanied by the formation of disseminated intravascular coagulation and is related to the severity of the disease. The imbalance of the body's immune and inflammatory response caused by coronavirus infection is an important cause of coagulation dysfunction. Dynamic monitoring as well as early prevention and treatment are of great significance for improving the prognosis of patients. This article reviews the research progress of COVID-19 related coagulation dysfunction, to provide reference for clinical research and management.

Nutritional support for critically ill patients with COVID-19
HU Yan,LI Xiaofeng,GONG Weiyue
J Zhejiang Univ (Med Sci), 2020, 49(3): 347-355.   https://doi.org/10.3785/j.issn.1008-9292.2020.06.01
Abstract( 530 )   HTML( 4 )     PDF(1069KB)( 305 )

Nutritional support is an indispensable part in the treatment of critically ill patients with coronavirus disease 2019 (COVID-19). Critically ill COVID-19 patients are often in a state of high inflammation, high stress, high catabolism, and their energy consumption increases significantly. All critically ill patients with COVID-19 should be screened for nutritional risk with NRS-2002 or Nutric tool in the early stage. If there is a risk of malnutrition, subjective global assessment (SGA) or Global Leadership Initiative on Malnutrition (GLIM) are further used for malnutrition assessment. After assessment, the daily energy, protein, electrolyte and liquid quantity needed by the patients should be determined according to the actual condition. Then, according to the degree of gastrointestinal function impairment in patients, the oral nutrition supplement, enteral nutrition, parenteral nutrition or their combination are selected for nutritional support. For patients with normal gastrointestinal function who require prone position ventilation or receive extracorporeal membrane oxygenation (ECMO) treatment, enteral nutrition is recommended as the first choice. In addition, in the process of nutrition implementation, it is necessary to closely monitor the adverse reactions such as abdominal distention, diarrhea, regurgitation, phlebitis and liver function damage, timely adjust the nutrition program to ensure the smooth implementation of nutritional support. Based on the metabolic characteristics of critically ill patients with COVID-19, this paper makes a summary and suggestion on the following perspectives such as nutritional risk screening and assessment, target amount of nutritional treatment, nutritional intervention and treatment, nutritional support of special populations, and common adverse reactions in nutritional support treatment, so as to provide reference for individualized nutritional support therapy of critically ill patients with COVID-19.

Quantitative determination and optimun extraction technique of nine compounds of Paeoniae Radix Alba
FENG Yihan,YIN Lei,LIU Yuanrong,CAO Lujing,ZHENG Ning,LI Mingjuan,ZHAN Shuyu
J Zhejiang Univ (Med Sci), 2020, 49(3): 356-363.   https://doi.org/10.3785/j.issn.1008-9292.2020.06.02
Abstract( 441 )   HTML( 5 )     PDF(1369KB)( 194 )

Objective: To establish the optimum extraction technique and high performance liquid chromatographic (HPLC) method to simultaneously quantify nine compounds of gallic acid, hydroxy-paeoniflorin, catechin, albiflorin, paeoniflorin, pentagalloylglucose, benzoic acid, benzoylpaeoniflorin and paeonol in Paeoniae Radix Alba. Methods: Linear gradient elution was applied using water containing 0.1%phosphoric acid and acetonitrile as the mobile phase with a flow rate of 0.8 mL/min, column temperature of 30℃ and wavelength of 230 nm. The method of ultrasound extraction was used. Methanol and ethanol were used as extraction solvents, and three factors and three levels of orthogonal experiments was designed using L9(34) table to investigate the effects of solvent concentration, ratio of liquid to material and extraction time on the total content of nine components of Paeoniae Radix Alba. Results: HPLC method was verified to have high specificity, sensitivity and accuracy through methodological validation, and it could be used for simultaneous quantitative analysis of nine components of Paeoniae Radix Alba. The results showed that the optimum extraction technology of nine components of Paeoniae Radix Alba was using 70%ethanol as extraction solvent, ratio of liquid to material was 200 mL/g and ultrasound extraction time was 30 min. Conclusion: HPLC method for the simultaneous determination of nine components of Paeoniae Radix Alba is established, and the optimum extraction technology is confirmed.

Synthesis of folate modified chitosan-based nanomicelles and its in vitro anti-tumor activity
LIU Lu,HUANG Guojun,BAI Hongzhen,TANG Guping
J Zhejiang Univ (Med Sci), 2020, 49(3): 364-374.   https://doi.org/10.3785/j.issn.1008-9292.2020.06.03
Abstract( 656 )   HTML( 13 )     PDF(16027KB)( 234 )

Objective: To design and synthesize folate-modified pH-responsive chitosan-based nanomicelles and investigate the in vitro anti-tumor activity of the drug-loaded micelles. Methods: CHI-DMA was obtained by reductive amination reaction of aldehyde-based chitosan and hydrophilic amine compounds, and CHI-DMA-LA was obtained by condensation reaction with lauric acid; FA-CHI-DMA-LA was obtained after modification with folic acid (FA). The drug-loaded nanomicelles FA-CHI-DMA-LA/DOX were assembled by solvent change method. The physicochemical properties of polymers were characterized by hydrogen nuclear magnetic resonance and transmission electron microscope. The particle size and surface potential were determined by dynamic light scattering method. Folic acid access rate, doxorubicin (DOX) loading rate and entrapped efficiency were measured by UV-vis spectrophotometer. The drug release properties of DOX-loaded micelles in vitro were monitored by fluorescence spectrophotometer at different pHs (7.4, 6.5, 5.0). The cytotoxicity against human oral cancer KB cells was detected by MTT assay. Fluorescence microscope and flow cytometry were applied to investigate the phagocytosis of DOX-loaded micelles on KB cells. Results: FA-CHI-DMA-LA was synthesized. The particle sizes of FA-CHI-DMA-LA-1 and FA-CHI-DMA-LA-2 micelles which used for the subsequent experiments were (73±14) nm and (106±15) nm, zeta potential were (15.59±1.98) mV and (21.20±2.35) mV, respectively. The drug loading rates of drug-loaded micelles FA-CHI-DMA-LA-1/DOX and FA-CHI-DMA-LA-2/DOX are (4.08±1.12)%and (4.12±0.44)%, respectively. In vitro drug release is pH-responsive, with cumulative release of DOX up to 37%and 36%at pH 5.0, which is about 1.5 times higher than that of pH 7.4. For FA-CHI-DMA-LA micelles with 1.25 to 125 μg/mL concentration, the survival rate of KB cells is more than 70%after incubation for 24 hours. The cell uptake of FA-CHI-DMA-LA/DOX micelles was enhanced compared to CHI-DMA-LA/DOX, and the cell uptake was higher in incubation without FA medium than that with FA. Compared with free DOX or CHI-DMA-LA/DOX, FA-CHI-DMA-LA/DOX nanomicelles showed higher cyctoxicity to KB cells, especially the FA-CHI-DMA-LA-2/DOX nanomicelles, the cell survival rate was about 17% after incubation for 24 hours. Conclusion: FA-modified chitosan-based nanomicelle with good biocompatibility was successfully prepared, which exhibits tumor microenvironmental pH responsive drug release and tumor targeting.

Prediction model of mid-term fatality risk after radical resection in patients with hepatocellular carcinoma based on ALBI-grade
WANG Xiaobo,ZHANG Zhaohui,WU Zhangqiang,SUN Yuezong,ZHANG Yili,GONG Ming,JI Feng
J Zhejiang Univ (Med Sci), 2020, 49(3): 375-382.   https://doi.org/10.3785/j.issn.1008-9292.2020.06.04
Abstract( 618 )   HTML( 5 )     PDF(1779KB)( 420 )

Objective: To establish a clinical prediction model of the mid-term fatality risk after radical resection in patients with primary hepatocellular carcinoma (HCC) based on the albumin-bilirubin (ALBI) grade and to assess its prediction value. Methods: Clinical data of 533 patients who received HCC radical resection in Jinhua Hospital of Zhejiang University, Jinhua People's Hospital, Jinhua Hospital of Traditional Chinese Medicine and Jinhua Guangfu Hospital from January 2010 to August 2016 were retrospectively reviewed. In the training group (n=407), Cox model was used to screen the clinical risk factors of postoperative death, and a predictive model based on ALBI grade was established and then examined in the validation group (n=126). The value of the prediction model was assessed by ROC curve and calibration curve; the prediction results of the model were visualized by the nomogram for the convenience of clinical use. Results: Cox model showed that ALT ≥ 80 U/L, tumor maximum diameter ≥ 5 cm, portal vein tumor thrombus and ALBI grade 2 were independent risk factors for the prognosis of patients with HCC radical resection. The prognosis index (PI) was 0.550×ALT+0.512×ALBI grade+0.872×maximum tumor diameter+1.377×portal vein tumor thrombus. The AUCs for predicting the risk of death in 12, 36 and 60 months were 0.872, 0.814 and 0.810, respectively (all P < 0.01), and the goodness of fit (r2) of the established model were 0.953, 0.976 and 0.994. AUC of the established model for predicting risk of death in 36 months after resection was 0.814, which was higher than those of ALBI (AUC=0.683), BCLC (AUC=0.713), CLIP (AUC=0.689), Child-Pugh (AUC=0.645), TNM (AUC=0.612) (P < 0.05 or P < 0.01). Conclusion: ALT ≥ 80 U/L, maximum tumor diameter ≥ 5 cm, portal vein tumor thrombus and ALBI grade 2 are independent risk factors of patients after HCC resection, and ALBI grade-based prediction model is satisfactory in prediction of mid-term death risk of the patients.

Preliminary result of stents implantation for spontaneous isolated dissection of the superior mesenteric artery: a prospective single-arm study
SUN Jinhong,QIU Chenyang,WU Ziheng,ZHANG Hongkun
J Zhejiang Univ (Med Sci), 2020, 49(3): 383-388.   https://doi.org/10.3785/j.issn.1008-9292.2020.06.05
Abstract( 506 )   HTML( 4 )     PDF(4944KB)( 220 )

Objective: To access the efficacy of stents for spontaneous isolated dissection of the superior mesenteric artery (SIDSMA). Method: The study is a prospective single-arm study which has been registered on Clinical Trials (NCT03916965). Clinical data and follow-up information of the SIDSMA patients who received stent implantation in the First Affiliated Hospital of Zhejiang University during April 1, 2019 and September 30, 2019 were collected. The patients were recommended to be followed up at 1, 3, 6 and 12 months. Results: A total of 34 patients were enrolled. Their mean age was (54±8) years. Abdominal pain was the most common symptom. Patients received (2.1±0.6) stents on the average. Post-operation hospital stay was (2.7±1.6) days, and the patients were followed up for (2.3±1.9) months (CT angiography) and (5.5±1.7) months (clinical visit/phone call). There was no recurrence of abdominal pain. The CT angiography showed complete remodeling and incomplete remodeling took place in 23 and 9 patients (69.7% and 27.3%), respectively. Two patients (6.1%) had mild in-stent stenosis. No stent rupture or migration was reported. Conclusion: This study demonstrated a satisfactory short-term result of stents implantation for SIDSMA, which indicated the endovascular treatment could be the first-line therapy for SIDSMA.

Relationship of group B streptococcus colonization in late pregnancy with perinatal outcomes
YANG Lindong,BAO Fang,WU Yuanzhe,SUN Lizhou
J Zhejiang Univ (Med Sci), 2020, 49(3): 389-396.   https://doi.org/10.3785/j.issn.1008-9292.2020.04.12
Abstract( 518 )   HTML( 5 )     PDF(1091KB)( 336 )

Objective: To investigate the relationship of group B streptococcus (GBS) colonization in late pregnancy with perinatal outcome. Methods: Pregnant women who underwent antenatal check-up at General Hospital of PLA Eastern Theater Command and the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2018 were enrolled in the study. The vaginal and rectal swab samples were collected for GBS culture at 35-37 weeks of pregnancy. The perinatal outcomes of positive and negative GBS groups were compared. The GBS-positive group samples were tested for antibiotic susceptibility. In GBS positive group the maternal and child perinatal outcomes were compared between pregnant women with antibiotics treatment and those without antibiotics. Results: A total of 13 000 pregnant women were enrolled, and the overall colonization rate of GBS was 3.65%(475/13 000). The colonization rate of GBS in the vagina was 2.33%(303/13 000), and the colonization rate in the rectum was 1.75%(227/13 000). Through the collection and detection of rectal specimens, the positive rate of GBS increased by 56.77%(172/303). The monthly colonization rate of GBS showed significant fluctuations with the highest in March and October (all P < 0.05). The sensitivity of 475 GBS-positive specimens to ceftriaxone, vancomycin and linezolid were 100%, and the sensitivity to ampicillin and penicillin were 97.26%and 93.47%, respectively. The resistance rates of the strains to levofloxacin, clindamycin, erythromycin and tetracycline were 30.11%, 48.00%, 52.21%and 88.63%. The incidence of premature rupture of membranes, postpartum hemorrhage, puerperal infection, neonatal pneumonia and sepsis in GBS positive group were significantly higher than those in GBS negative group (all P < 0.01). In pregnant women with positive GBS, the incidence of puerperal infection, neonatal infection and admission to the NICU in the antibiotic group were significantly lower than those in the non-antibiotic group (P < 0.05 or P < 0.01). Conclusions: The total colonization rate of GBS is low. The detection of GBS can be significantly improved by supplementing rectal examination. Ceftriaxone, ampicillin and penicillin are currently the drugs of choice for the prevention and treatment of GBS-related diseases. GBS infection can increase the incidence of maternal and child complications. The use of antibiotics during labor can improve the outcome of mothers and infants.

Efficacy of black cohosh extracts for improving low estrogen status induced by postoperative GnRHa treatment in patients with endometriosis: a systematic review
PENG Jie,XU Wenfei,LI Xuhui,WU Qiaoai
J Zhejiang Univ (Med Sci), 2020, 49(3): 397-405.   https://doi.org/10.3785/j.issn.1008-9292.2020.06.06
Abstract( 437 )   HTML( 6 )     PDF(2185KB)( 240 )

Objective: To evaluate the efficacy of black cohosh extracts (BCE) in improving the low estrogen status induced by postoperative gonadotropin-releasing hormone agonist (GnRHa) in patients with endometriosis. Methods: Randomized clinical controlled trial about the improvement of low estrogen status caused by GnRHa with the treatment of BCE in patients with endometriosis after laparoscopic surgery were retrieved from Medline (Ovid), PubMed, Cochrane Library, CNKI, CBMdisc, Wanfang and VIP databases before January 2020, and meta-analysis of included studies was performed by Revman 5.3 software. Results: Seven randomized controlled trials involving 745 patients were included in this study. Meta-analysis results showed that the addition of BCE did not alter hormone levels of patients, including serum estradiol levels [MD=1.24, 95% CI(-4.58, 7.08), P>0.05] and luteinizing hormone levels [MD=-0.02, 95% CI(-0.15, 0.11), P>0.05]. BCE effectively improved the perimenopausal symptoms induced by low estrogen status:improving hectic fever and sweating [OR=0.1, 95% CI(0.02, 0.47), P < 0.01], reducing the occurrence of insomnia symptoms [OR=0.23, 95% CI(0.13, 0.39), P < 0.01], improving fatigue [OR=0.09, 95% CI(0.04, 0.20), P < 0.01], reducing the occurrence of vaginal dryness [OR=0.04, 95% CI(0.01, 0.30), P < 0.01]. BCE affected Kupperman's menopausal index (KMI) score 12 weeks after the surgery [MD=-11.50, 95% CI(-20.09, -2.90), P < 0.01] and KMI score 24 weeks after the surgery [MD=-23.68, 95% CI(-39.66, -7.69), P < 0.01]. Conclusion: The limited evidence so far indicates that BCE could efficiently improve perimenopausal symptoms cause by low estrogen status of the patients recieved GnRHa treatment after surgery for endometriosis, but does not alter hormone levels of patients.

A case of Gilbert syndrome caused by UGT1A1 gene compound heterozygous mutations
OU Weijie,LIN Su,WU Yilong,ZHU Yueyong
J Zhejiang Univ (Med Sci), 2020, 49(3): 406-409.   https://doi.org/10.3785/j.issn.1008-9292.2020.04.13
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A case of Gilbert syndrome (GS) with a heterozygous mutation in the UGT1A1 gene is reported. The patient had no symptoms except for recurrent sclera icterus since childhood. Laboratory examinations revealed an elevated unconjugated bilirubin. Biliary obstruction, hemolysis and other diseases that might cause jaundice were excluded. UGT1A1*28 and c.211G>A heterozygous mutations in UGT1A1 gene were found, which may be another type of mutation causing GS in Chinese population.

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