Unique totipotency of embryonic stem cell make it great value.Embryonic stem cells have received extensive attention from the discovery,research to application.This paper outlined the discovery of embryonic stem cell and the challenges faced in the progress of the study and research process,focusing on the ethical issues.Meanwhile,this paper analyzed the attitude of various governments,the status of the relevant laws and regulations in order to discuss the prospects of stem cell re

Immune-checkpoint blockers(ICBs)have been well received in a variety of tumors,and the quality of patient life has improved significantly.However,the reasons why not all patients treated with ICBs benefit from lesion control,symptom improvement,and survival time.Many patients are resistant to the first time when they have been using ICBs for a period of time.This is a clinical challenge.This review lists possible causes of primary drug resistance and acquired resistance to ICBs.The primary resistance is associated with several mechanisms,including tumor microenvironment,cancer cells themselves and other related factors.The acquired resistance includes nonclassical immunoprecipitation molecules secondary overexpression,abnormalities of antigen presenting signal pathway and dysfunction of T cell activation killer.Finally,we have described a variety of possible new combination of treatment,including combined radiotherapy and chemotherapy,and combined targeted therapy with other measures.

ObjectiveTo observe the effect of acetylcholine (ACh) on lipopolysaccharide (LPS) induced inflammatory model of rat alveolar macrophages, and to observe the effect of the acetylcholinesterase inhibitor physostigmine (Phy) on the anti-inflammatory effect of ACh.Methods The rat alveolar macrophages NR8383 were cultured in vitro, which were divided into five groups: blank control group, LPS group (stimulated with 1 mg/L LPS for 12 hours), LPS+ ACh group (0.01, 0.1, 1, 10, 100μmol/L of ACh were added for 5 minutes before LPS stimulation), LPS+ Phy group (1 mmol/L Phy was added for 5 minutes before LPS stimulation), and LPS+ ACh+ Phy group (1 mmol/L Phy and 10μmol/L ACh were added for 5 minutes before LPS stimulation). The supernatants were collected in each group, the enzyme-linked immunosorbent assay (ELISA) was used to assay the contents of tumor necrosis factor-α (TNF-α), interleukins (IL-1β, and IL-6). The activity of acetylcholine esterase (AChE ) in the supernatant was also determined.Results① The contents of TNF-α (ng/L: 605.09±57.13 vs. 34.07±8.62), IL-1β (ng/L: 377.09±28.55 vs. 32.33±10.62) and IL-6 (ng/L: 558.04±77.45 vs. 42.62±11.21) in the LPS group were significantly higher than those in the blank control group (allP< 0.05). These results indicated that the inflammatory model of rat alveolar macrophages was constructed successfully.② ACh with the final concentrations of 0.01, 0.1, and 1μmol/L had less influence on the production of TNF-α, IL-1β and IL-6 in the culture supernatants of alveolar macrophages stimulated with LPS compared with LPS group (allP> 0.05). Nevertheless, 10μmol/L and 100μmol/L ACh notably reduced the production of TNF-α (ng/L: 451.19±30.67, 332.19±32.19 vs. 604.96±22.56), IL-1β(ng/L: 261.08±24.78, 143.98±28.39 vs. 367.06±10.44) and IL-6 (ng/L: 342.75±54.60, 235.48±29.75 vs. 562.69±63.34) in the culture supernatants compared with the LPS group (allP< 0.05).③ The activity of AChE in the LPS group was significantly higher than that in the blank control group (kU/L: 5.21±0.63 vs. 3.09±0.10,P< 0.05). The activity of AChE was successfully inhibited by 1 mmol/L acetylcholinesterase inhibitor Phy pretreatment compared with that in the LPS group (1.51±0.12 vs. 5.21±0.63,P< 0.05).④ The level of TNF-α (ng/L: 183.17±35.44 vs. 451.19±30.67), IL-1β (ng/L: 91.49±12.27 vs. 261.08±24.78) and IL-6 (ng/L: 108.17±22.82 vs. 342.75±54.60) in the culture supernatants of LPS+ ACh+ Phy group was significantly decreased as compared with LPS+ ACh group (allP< 0.05).Conclusions ACh with the final concentrations of 10μmol/L and 100μmol/L can inhibit the LPS induced inflammatory reaction in alveolar macrophages. The acetylcholinesterase inhibitor Phy can reinforce the ACh-mediated anti-inflammatory effect on alveolar macrophages inflammatory model.

AIM:To investigate the role of microRNA-132 (miR-132) on alveolar macrophage inflammation. METHODS: Rat alveolar macrophage cell line NR8383 was transfected with miR-132 mimic, mimic negative control ( NC) , miR-132 inhibitor, or inhibitor NC.The cells were divided into transfection group, transfection +lipopolysaccha-ride ( LPS) group, and transfection +LPS +acetylcholine ( ACh) group.The mRNA expression of acetylcholinesterase ( AChE) was detected by real-time PCR.The protein levels of AChE, signal transducer and activator of transcription 3 (STAT3) and phosphorylated STAT3 (p-STAT3) in the cells, and nuclear factor-κB (NF-κB) in the cytoplasm and nu-cleus were analyzed by Western blot.The activity of AChE in the culture supernatant was measured by AChE activity assay kit.The nuclear translocation of NF-κB was detected by immunofluorescence assay.RESULTS: Up-regulation or down-regulation of miR-132 had no effect on the mRNA expression of AChE.However, up-regulation of miR-132 decreased the protein level of AChE compared with mimic NC group (P<0.05).Transfection with miR-132 inhibitor increased the pro-tein expression of AChE compared with inhibitor NC group ( P<0.05 ) .In the alveolar macrophages treated with LPS+ACh, the inhibition of nuclear translocation of NF-κB p65 in miR-132 mimic group was more effective than that in mimic NC group ( P<0.05) .The inhibitory effect in miR-132 inhibitor group was weaker than that in inhibitor NC group ( P<0.05 ) .The inhibitory effect of miR-132 mimic on the protein levels of STAT3 and p-STAT3 was stronger than that of mimic NC (P<0.05).CONCLUSION:miR-132 in LPS-stimulated alveolar macrophages reinforced ACh-mediated anti-inflam-matory reaction by targeting AChE to suppress ACh hydrolyzation, which was related to the suppression of NF-κB and STAT3 activation.

OBJECTIVE: To analyze the clinical phenotype and genetic variant in a Chinese pedigree affected with benign familial neonatal convulsion (BFNC). METHODS: Clinical data and peripheral blood samples of the pedigree were obtained with informed consent. Whole exome sequencing (WES) was carried out for the proband. Candidate variants were verified by Sanger sequencing. RESULTS: The pedigree comprised 9 individuals, among whom 4 were affected, including 3 males and 1 female. All patients had developed seizures during the neonatal period, which had ceased in 4 to 6 months. One patient had recurrence in between 1 and 2 years old. Genetic testing has identified a novel nonsense c.810G>A (p.W270X) variant in exon 5 of the KCNQ2 gene, which has co-separated with the BFNC phenotype in the pedigree. CONCLUSION The patients from this pedigree have conformed to the diagnosis of BFNC with good prognosis, which was in keeping with previously reported cases. The heterozygous c.810G>A (p.W270X) nonsense variant of the KCNQ2 gene probably underlay the pathogenesis of BFNC in this pedigree, which has expanded the mutational spectrum of the disease.
Asians/genetics* ; Child, Preschool ; China ; Epilepsy, Benign Neonatal/genetics* ; Female ; Genetic Testing ; Humans ; Infant ; Male ; Mutation ; Pedigree

OBJECTIVETo detect the influence of compatibility of rhubarb with different traditional Chinese medicines (TCM) on extracted quantities of AQs, and to provide scientific basis for the clinical code for rhubarb preparation.

METHODThe influence of compatibility of rhubarb with different traditional Chinese medicines (saponin, alkaloids, flavonoids TCMs, animal medicines and mineral medicines) on decocting volume of anthraquinone substance was detected using ultra performance liquid chromatography.

RESULTIn comparable conditions, more AQs were extracted from mixed decoction of rhubarb and saponin medicinal materials (Astragali Radix, Notoginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Polygalae Radix, Ginseng Radix et Rhizoma) than single decocting of rhubarb. The mixed decoction of rhubarb and alkaloid medicinal materials (Coptidis Rhizoma, Sophorae Flavescentis Radix, Prepared Aconiti Lateralis Radix Praeparata, Phellodendri Chinensis Cortex, Aconiti Lateralis Radix) caused a remarkable decrease in extracted quantities of AQs. And the mixed decoction of rhubarb and mineral medicines (Natrii Sulfas, Gypsum Fibrosum, Ostreae Concha, Alumen) also resulted in less extracted quantities of AQs to varying degrees. Besides, more rhubarb AQs were extracted from mixed decoction with Curcuma than single decoction. But less rhubarb AQs were observed in mixed decoction with Lonicerae Flos, Rehmanniae, Artemisiae Herb and Forsythiae Fructus than single decoction to varying degrees. In the study, the maximum extracted quantities of AQs is 2. 3-fold higher than the minimum, the largest difference existed in the extracted quantity of physcion which was 13.5 times.

CONCLUSIONIn compatibility between rhubarb and different TMCs, mixed decoction and single decoction show different influences on extracted quantity of rhubarb AQs. It is proved that more AQs may be extracted from mixed decoction between rhubarb and saponin medicinal materials, whereas less AQs may be observed in mixed decoction between rhubarb and alkaloid medicinal materials.

Alkaloids ; chemistry ; Animals ; Anthraquinones ; analysis ; isolation & purification ; Chromatography, High Pressure Liquid ; methods ; Drug Compounding ; methods ; standards ; Flavonoids ; chemistry ; Humans ; Medicine, Chinese Traditional ; methods ; standards ; Plants, Medicinal ; chemistry ; Reference Standards ; Reproducibility of Results ; Rheum ; chemistry ; Saponins ; chemistry

Objective:To explore the value of low-dose CT in pregnancy with COVID-19.Methods:A retrospective analysis was performed on the clinical characteristics, laboratory tests, and chest CT findings of 12 pregnant women with COVID-19 diagnosed by nucleic acid testing in the Renmin Hospital of Wuhan University from January 20, 2020 to February 16, 2020. Two radiologists blinded to the reconstruction algorithm independently scored subjective image quality on a 5-point Likert scale. Image quality score ≥ 3 was acceptable in clinics. The CT radiation doses were recorded, including CT volume dose index (CTDI vol), dose length product (DLP), and effective radiation dose ( E). Two radiologists observed the distribution, shape, density, and other characteristics of lung lesions, and they also decided whether hilar, mediastinal lymphadenopathy, and pleural changed. Results:A total of 12 pregnant women with COVID-19, 8 had cough, 4 had fever, 2 had chest tightness, and 1 had dyspnea and diarrhea each. The CT image quality score of all patients was 3-4, with an average of 3.46, which fully met the clinical diagnosis requirements. The CTDI vol value was 1.13-4.31 mGy, with an average of 3.02 mGy. The DLP value was 34.48-75.29 mGy·cm, with an average of 55.48 mGy·cm. The Evalue was 0.48-1.05 mSv, with an average of 0.78 mSv. In all cases, chest CT examination showed abnormal manifestations after clinical symptoms, including unilateral lung lesions in 5 cases and bilateral lung lesions in 7 cases, 1 case of ground-glass opacity, 1 case of solidification, 7 cases of ground-glass and consolidation, 1 case of strip opacity, ground-glass, and consolidation and strip cable shadow coexisted in 2 cases. Conclusions:The application of low-dose CT scan in pregnant women with COVID-19 is completely feasible. CT mainly manifested as bilateral lung patchy and flaky ground-glass opacity with consolidation. Active and effective treatment can help recover and improve prognosis.

Objective To study the effects of mirabilite stuck on umbilical region combined with early enteral nutrition (EEN) on gastrointestinal function and serum inflammatory mediators in patients with mechanical ventilation. Methods Sixty-four patients with mechanical ventilation admitted to the Department of Intensive Care Unit of the Second Affiliated Hospital of Zhejiang Traditional Chinese Medical University from January to December 2016 were enrolled, and they were divided into an observation group and a control group by random number table, 32 cases in each group. The control group was treated with routine western medicine+ EEN, and the observation group was treated additionally with mirabilite stuck onto umbilical region on the basis of the treatment of the control group. The clinical effect was observed after 7 days of treatment. The differences in gastrointestinal function scores and the levels of serum inflammatory mediators were compared between the two groups before and after treatment.Results After treatment, gastrointestinal function scores of the diarrhea, bowel sound, abdominal distension and the levels of white blood cell count (WBC), serum procalcitonin (PCT), serum C-reactive protein (CRP) were decreased significantly in both groups compared with those before treatment, and the degrees of decreasing in above index levels after treatment in the observation group were more obvious than those in the control group [diarrhea: 0.72±0.03 vs. 1.59±0.21, bowel sounds: 0.87±0.05 vs. 1.54±0.18, abdominal distension: 0.77±0.04 vs. 1.63±0.09, WBC (×109/L): 9.87±1.25 vs. 12.46±2.04, PCT (μg/L): 5.43±1.02 vs. 9.65±1.63, CRP (mg/L): 56.87±4.52 vs. 89.43±8.24, allP < 0.05].Conclusion Applying mirabilite stuck on umbilical region combined with EEN can effectively promote the recovery of gastrointestinal function and significantly decrease the levels of serum inflammatory mediators in patients with mechanical ventilation.

OBJECTIVE: To investigate the individual external dose level of medical radiation staffs in Guangzhou City.METHODS: The medical radiation staffs of Guangzhou City who conducted individual dose monitoring at Guangdong Province Hospital Center for Occupational Diseases Prevention and Treatment from 2008 to 2014 were selected as study subjects by convenient sampling method.Their individual dosage monitoring data were analyzed.RESULTS: A total of 17 754 person-times were monitored in 7 years.The annual collective effective dose was 10 621.1 person·mSv and the median per capita annual effective dose was 0.21 mSv/a.The per capita annual effective dose in 2008-2012 showed an increasing trend each year( P < 0.05),peaked in 2012,and then decreased in 2013 and 2014( P < 0.05).The per capita annual effective dose of radiology staffs in level Ⅱ medical institutions was higher than that of level Ⅲ medical institutions,level Ⅰ medical institutions and those below level Ⅰ( P < 0.01).The per capita annual effective dose of radiation staffs in level Ⅲ medical institutions was higher than level Ⅰ medical institutions and those below level Ⅰ( P <0.01).The effective monitoring rates of radiation staffs monitored for 4 cycles every year increased with time from 2008 to 2014( P < 0.01).The effective monitoring rate increased with the hospital level( P < 0.01).The per capita annual effective dose of the staffs in radiological diagnosis department was lower than that of clinical nuclear medicine,radiotherapy and interventional radiology( P < 0.01).CONCLUSION: The radiation dose of medical radiation staffs in Guangzhou City was within the national standard limit.Protection should be focused on the the staffs in secondary hospitals,clinical nuclear medicine,radiotherapy and interventional radiology.

Objective To observe the effect of early enteral nutrition (EEN) on nutritional indicators and clinical outcomes in patients with severe heart failure undergoing mechanical ventilation. Methods Thirty-four patients with severe heart failure (grade Ⅲ-Ⅳ of cardiac function) and pulmonary infections undergoing mechanical ventilation admitted to intensive care unit (ICU) of Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from May 2017 to April 2018 were enrolled. They were randomly divided into EEN group and delayed enteral nutrition (DEN) group. Both groups were given routine treatment, including mechanical ventilation, improvement of cardiac function, anti-infection, protection of vital organ function, regulation of blood sugar and adjustment of electrolyte and acid-base balance. The patients in EEN group received enteral nutrition (EN) within 48 hours after ICU admission, and in DEN group, EN was started after the patients had spent the early stage of stress and had stable vital signs (48 hours after ICU admission). The changes in serum B-type natriuretic peptide (BNP), C-reactive protein (CRP), nutritional indicators and liver function indicators at ICU admission and 7 days after treatment were compared between the two groups. The time needed for patients to reach EN target, duration of mechanical ventilation, length of ICU stay, and the 28-day mortality were recorded, and complications were observed. Results There was no significant difference in serum BNP, CRP, nutritional indicators or liver function indicators at ICU admission between the two groups. After treatment for 7 days, BNP and CRP in both groups were decreased significantly as compared with those at ICU admission [BNP (ng/L): 592.1±370.9 vs. 2 517.7±1 163.4 in EEN group, 621.9±418.8 vs. 2 251.5±1 006.8 in DEN group; CRP (mg/L): 46.0±19.6 vs. 59.8±22.5 in EEN group, 40.5±18.8 vs. 61.2±24.6 in DEN group, all P < 0.05], pre-albumin (PA) and transferrin (TF) were significantly increased [PA (g/L): 0.18±0.05 vs. 0.15±0.06 in EEN group, 0.17±0.04 vs. 0.12±0.06 in DEN group; TF (g/L): 1.6±0.4 vs. 1.5±0.4 in EEN group, 1.7±0.5 vs. 1.4±0.5 in DEN group, all P < 0.05]. However, there was no significant difference in the above indicators after treatment between the two groups (all P > 0.05). There was no significant change in liver function after treatment in both groups. The EN treatment was successfully completed in both groups. Some patients developed abdominal distension and diarrhea in varying degrees, which were alleviated by slowing down the infusion rate, supplemented by gastrointestinal motility drugs and intestinal flora adjustment drugs. The time needed to reach EN target in EEN group was significantly earlier than that in DEN group (hours: 42.4±10.2 vs. 53.8±17.1, P < 0.05), the duration of mechanical ventilation (days: 14.2±8.7 vs. 13.4±7.9), the length of ICU stay (days: 17.8±6.7 vs. 18.3±5.6) and 28-day mortality [5.9% (1/17) vs. 11.8% (2/17)] showed no significant difference as compared with those in DEN group (all P > 0.05), and it did not increase the incidence of aspiration pneumonia [23.5% (4/17) vs. 17.7% (3/17), P > 0.05]. Conclusion EEN could help to achieve nutritional goals as soon as possible, improve the nutritional status of the body, and provide conditions and basis for further treatment of severe heart failure patients.