Objective To explore the clinico-pathological features, immunophenotype, treatment and prognosis of urologic primary primitive neuroectodermal tumor (PNET). Methods The clinical data of 3 patients with urologic PNET were analyzed retrospectively. All patients were male, aged 29, 32 and 75 years respectively. Two of the lesions were located in the kidney, and the third was located in the bladder. The sizes of renal tumors were 7.7 cm×6.2 cm and 12.6 cm×9.4 cm respectively. Imaging examinations revealed a well-defined mass with inhomogeneous echo inside. The size of bladder tumor was 10.0 cm×10.0 cm. CT scan demonstrated irregular thickening of the bladder wall, and the density of the wall was inhomogeneous. In the 2 cases of renal PNET radical surgery was performed, while an emergency palliative surgery to remove a blood clot and biopsy were performed in the bladder PNET case. Results In light microscope, the tumors were characterized by uniform small round or oval cells and nest-like or dense sheet structures surrounded by sparse fibrovascular stroma. Homer-Wright rosettes or pseudorosettes were observed, as well as mitoses. Immunohistochemical study revealed that all cases showed positive staining for CD99, synaptophysin and vimentin. One of the renal tumor cells showed positive for CD56, and the other renal tumor and urocystic tumor cells were focally positive for chromogranin A. Additionally, in 1 of the cases of renal tumor there was a high positive rate of 80% for Ki67 staining while the other case showed less than 5%. All 3 cases were eventually diagnosed as PNET. The first renal tumor case was not treated with radiotherapy and chemotherapy postoperatively, and the patient died of recurrence 14 months after surgery. Both the second renal tumor case and the bladder tumor case underwent chemotherapy postoperatively, and they died 4 and 6 months after surgery respectively. Conclusions The urologic primary PNET is a very rare, highly malignant soft tissue tumor, and the diagnosis must be based on pathologic findings and immunohistochemical phenotypes. The multimodal treatment for urologic primary PNET consists of surgery, chemotherapy and radiotherapy.

Objective To analyze and summarize the clinical-pathological features,immunophenotype and prognosis of the lymphoepithelioma-like gastric carcinoma (LELGC).Methods The clinical,radiographic and histological data of four patients with LELGC were retrospectively analyzed.The expression of cytokeratin (CK),CD20,CD3,CD4,CD8,E-cadherin,β-catenin,bcl-2,p16,p53,p63,c-erbB-2,cyclin D1,Ki67 and DNA methyl-transferase 1 (DNMT1) in tumor was detected by Epstein-Barr virus-encoded small RNA (EBER) in situ hybridization and immunohistochemical methods.Results The size of four tumor was 1.8 cm× 1.6 cm,1.5 cm× 2.0 cm,2.5 cm× 2.0 cm and 4.0 cm× 2.5 cm.Under light microscope,tumor cells appeared like cords,small lumps or scattered single infiltration with vacuolized nucleus; clear nucleoli and obvious interstitial lymphocytic infiltration.The results of immunohistochemical examination indicated that in four tumors CK was positive in membrane of all the tumor cells,while EBER was positive in all cell nucleus.The number of lymphocytes with CD3 positive was over those with CD20 positive,which was mainly CD8 positive lymphocytes.The percentage of E cadherin and β-catenin positive in the cell membrane of four tumors was between 10 ％ and 90 ％,and two cases with β-catenin positive in cytoplasm.The expressions of DNMT1,cyclin D1 and bcl-2 were all positive,while p16 and c-erbB-2 were all negative.The expression of p63 was positive in only one case,and p53 was negative in one case.The percentage of Ki67 positive was 40％,15％,60％ and 40％,respectively.Conclusions LELGC is a rare neoplasm with better prognosis.The features of clinical pathology and immunohistology may help to make a correct diagnosis.

Objective To compare clinical effect of gonadotropin releasing hormone agonist(GnRH-a) alone and GnRH-a combined with low-dose dydrogesteronea and estradiol valerate on sex hormone, hypoestrogenic symptoms, quality of life and bone mineral density (BMD)in treatment of endometriosis.Methods Seventy patients with moderate or severe endometriosis, who were diagnosed by laparotomy or laparoscopic surgery within two months, were randomly assigned into two groups.35 patients in GnRH-a group were treated by goserelin (3.6 mg)for three months, and 35 patients in add-back group were treated by goserelin (3.6 mg)combined with estradiol valerate 0.5 mg and dydrogesteronea 5 mg daily.Before and after the treatment, clinical parameters were recorded and analyzed, including visual analog scale (VAS), medical outcomes survey short form 36 (SF-36), Kupperman menopausal index(KMI), BMD, the serum level of follicle stimulating hormone (FSH), estradiol (E_2) and bone gla-protein (BGP) .The first menstruation and VAS were also followed up after treatment.Results Every 3 cases in two groups lost follow-up.(1)Reproductive hormone: the level of E_2 in add-back group [(94 ± 71) pmol/L]was significantly higher than (54±52) pmol/L in GnRH-a group(P <0.01).The level of FSH in add-back group [(3.0 ± 1.9) U/L]was significantly lower than (5.7 ± 2.9) U/L in GnRH-a group (P < 0.05).(2) VAS: after treatment, VAS in both group decreased significantly when compared with that before treatment(P < 0.05), and remained until menstruated.(3) KMI: KMI in add back-group (10 ± 8) was significantly lower than (14 ± 6) in GnRH-a group (P < 0.05).(4) BMD: compared with that before treatment, BMD decreased significantly after treatment in GnRH-a group (P < 0.05), no remarkable difference of BMD was observed before and after treatment in add-back group.Before treatment, serum BGP in both groups did not show statistical difference.After treatment, the level of BGP in GnRH-a group [(7932±5206) ng/L]was significantly higher than (5419±2917) ng/L in add-back group (P <0.05).Conclusions GnRH-a combined with estrogen-progesterone regimen could relieve pain from endometriosis as effectively as GnRH-a alone and reduce hypoestrogenic symptoms and bone loss.Therefore,it is a safe and effective treatment.

Objective To establish the reference ranges of the spatial angles among cardiac chambers and great vessels in second and third trimester fetuses measured by spatiotemporal image correlation (STIC).Methods Volume images of 352 normal fetuses from 20 to 38 weeks of gestation were recruited in the study.An off-line analysis of acquired volume datasets was carried out with multiplanar mode.Parameters measured included angles between:(1) the 4-chamber view and the left ventricular long axis view; (2) the left ventricular long axis view and main pulmonary artery; and (3) the ductal arch and aortic arch.The relationships between above-mentioned angles and gestational age were assessed by correlation and regression analysis.Results The angle between the 4-chamber view and the left ventricular long axis view (range:55.7° - 35.7°,mean:45.7° ± 5.12°) was uncorrelated with gestational age (r = 0.03,P = 0.51).In contrast,the angle between the left ventricular long axis view and main pulmonary artery,and the angle between the ductal arch and aortic arch were correlated with gestational age (P ＜ 0.001),and the correlation coefficient was - 0.53 and 0.57 respectively.The best-fit exponential curve regression equations of the angle between the left ventricular long axis view and main pulmonary artery was:Y = 154- 4.24X +0.05X2 ,and the angle between the ductal arch and aortic arch was:Y = - 20.8 + 2.65X - 0.37X2.Conclusions The angles among cardiac chambers and great arteries of fetuses from 20 to 38 weeks of gestation can be quantitatively measured by STIC.The reference ranges provide a reliable quantitative standard to estimate the spatial relationships of the cardiac large arteries of fetuses,which may be clinically useful in prenatal screening congenital heart disease.

Objective To evaluate the effectiveness of spatio-temporal image correlation with M-mode display ( STIC-M ) in monitoring fetal left ventricular systolic function in fetuses with congenital heart disease(CHD) . Methods Five hundred and thirty-six normal fetuses and 34 fetuses with CHD( 29 without hydrops and 5 with hydrops) were involved in the study . Left ventricular fractional shortening ( LVFS) was measured using STIC-M . The data of normal fetuses was used to construct reference ranges of LVFS for assessment of fetuses with CHD . Results The LVFS of the normal fetuses [ range :26 .8％ - 42 .9％ , mean :( 34 .9 ± 4 .1) ％ ] was negatively correlated with gestational age ( r = - 0 .16 , P < 0 .001) . Compared with the normal controls ,LVFS was significantly decreased in CHD fetuses with hydrops ( P < 0 .001) . However ,there was no significant difference in LVFS between normal controls and CHD fetuses without hydrops ( P > 0 .05) . Conclusions STIC-M is a new method that can be used to measure LVFS to evaluate fetal ventricular systolic function . The fetal ventricular contractile function of CHD fetuses without hydrops may not be damaged or is in compensation stage . The fetuses with cardiac hydrops generally become lower .

Glutamate serves as a major excitatory neurotransmitter in the mammalian central nervous system and is stored in synaptic deft by an uptake system that is dependent on the high-affinity glutamate transporters (ETTAs),which locate in the plasma membrane of glial cells and neurons.ETTAs can rapidly terminate the action of glutamate and maintain its normal physiological functions.If the content or function of glutamate transporters is abnormal,it can result in many physiological dysfunctions.Studies have demonstrated that high-affinity glutamate transporters play an important role in the development of chronic pain,which might be a new therapeutic target for the pain.

Objective To investigate the density seasonal fluctuation and insecticide resistance of Anopheles sinensis in the Taibai Lake area and to provide a scientific basis for formulation of Anopheles sinensis control strategy.Methods The surveillance was carried out from June to October in 2013-2016.The adult mosquito density was monitored using human bait trapping method.WHO bioassay method was used to measure the sensibility of mosquitoes to insecticides.Results In 2013-2016,totally 2 318 Anopheles sinensis were captured,the Anopheles sinensis peaked in late July till early August,which were 67-127,317-386,77-89,107-139,respectively.Anopheles sinensis showed high resistance to dichlorodiphenyltrichloroethane,malathion,and initial resistance to propoxur and deltamethrin (mortality ratio:38.10％,41.82％,86.11％,83.02％).Conclusions The Taibai Lake area has a diverse Anopheles sinensis population,its seasonal fluctuations and insecticide resistance monitoring can provide effective guidance for malaria control.In order to prevent the development of resistance to the insecticides,integrated management measures should be adopted in the future.

SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further and studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.

BACKGROUND: The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear. METHODS: A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization. RESULTS: There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not. CONCLUSIONS In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.
Camptothecin/therapeutic use* ; Glucuronosyltransferase/genetics* ; Humans ; Lung Neoplasms/drug therapy* ; Mutation ; Polymorphism, Genetic ; Retrospective Studies