Type III secretory protein SINC of Chlamydia psittaci promotes host cell autophagy by activating the MAPK/ERK signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effects of SINC, a secreted protein of Chlamydia psittaci, on autophagy of host cells and the role of MAPK/ERK signaling pathway in mediating SINC-induced autophagy.@*METHODS@#RAW 264.7 cells treated with recombinant SINC were examined for changes in expression levels of LC3-II, Beclin-1, phosphorylated and total ERK1/2 using Western blotting. The expression level of LC3 in the treated cells was detected using immunofluorescence analysis, and the formation of autophagosomes and autolysosomes was observed with transmission electron microscopy (TEM). The effect of pretreatment with U0126 (a specific ERK inhibitor) on the expression levels of LC3-II and Beclin-1 in RAW 264.7 cells exposed to different concentrations of SINC was examined using Western blotting, and LC3 puncta in the cells was detected with immunofluorescence analysis.@*RESULTS@#The expression levels of LC3-II and Beclin-1 were the highest in RAW 264.7 cells treated with 2 μg/mL SINC for 12h. Immunofluorescence analysis showed exposure to SINC significantly increased the number of cells containing LC3 puncta, where the presence of autophagosomes and autolysosomes was detected. Exposure to 2 μg/mL SINC for 15 min resulted in the most significant increase of the ratios of p-ERK1/2/ERK1/2 in RAW 264.7 cells. Pretreatment of the cells with U0126 prior to SINC exposure significantly decreased the ratio of p-ERK1/2/ERK1/2, lowered the expression levels of LC3-II and Beclin-1, and decreased LC3 aggregation in the cells.@*CONCLUSIONS@#SINC exposure can induce autophagy in RAW 264.7 cells by activating the MAPK/ERK signaling pathway.

Application of scenario simulation teaching based on PBL in communication ability training of Pediatric Hematology Department / 中华医学教育探索杂志

Objective:To explore the application of scenario simulation teaching based on PBL in communication skills training of hematology students in Children's Hospital.Methods:The training of doctor-patient communication skills was conducted among trainees who had the standardized residency training at the Department of Hematology of the Children's Hospital of Soochow University. All the residents were randomized into the control group and observation group by lottery, with 24 residents in each group. The control group adopted the traditional narrative teaching method, and the observation group adopted PBL combined with scenario simulation teaching method. The Liverpool communication skills assessment scale (LCSAS) was used to compare the differences between the two groups before and after training, and the differences between the two groups after training. Then the degree of residents' recognition of these two teaching methods was investigated. Finally, the examination results were used to evaluate knowledge mastery of doctors in department of hematology. SPSS 20.0 was used for Chi-square test and t-test. Results:LCSAS scores of the two groups before training were respectively (11.61±2.21) and (11.95±2.22), with no statistically significant difference ( P >0.05). After PBL-based scenario simulation teaching and training in the observation group, the LCSAS score of the observation group (27.41±2.53) was higher than that of the control group (23.30±1.81), and the difference between the two groups was statistically significant ( P<0.05). Questionnaire survey results showed that the favorable rating rate of PBL-based scenario simulation teaching was 91.67% (22/24), higher than that of the traditional narrative teaching method [62.50% (15/24)], and the difference was statistically significant ( P<0.05). The examination of students' mastery of professional knowledge showed that after the PBL-based scenario simulation teaching and training, the trainees had a better grasp of knowledge and a higher score, with excellence rate of 91.67% (22/24）, which was higher than 66.67% (16/24) of the control group, with a statistically significant difference ( P<0.05). Conclusion:The scenario simulation teaching based on PBL could improve the communication ability and professional knowledge of trainees taking standardized residency training in the department of hematology, and the trainees are highly satisfied with this teaching method.

Automatic transfer of diversion pouches among Blood Transfusion Departments: a multicenter observation and study / 中国输血杂志

【Objective】 To explore the significance of automatic transfer of diversion pouches in blood transfusion departments on improving the standardization of quality management. 【Methods】 A total of 16 548 diversion pouches of suspended red blood cells (sRBC) were collected from Blood Transfusion Departments of ten tertiary hospitals in China. The sRBC was supplied by local blood centers from January to March 2021. The diversion pouches were randomly divided into experimental group (n=8 274, using DS-6800A automatic for transferring) and control group (n=8 274, manual transfer). The transfer duration of diversion pouches labels, whole process operation time of diversion pouches, label accuracy after transferring, table cleanliness and accurate transfer rate of diversion pouches of the two groups were recorded and compared. 【Results】 The results of experimental group and control group were as follows: transfer duration(s) of diversion pouch labels was 0.67±0.3 vs 3.67±0.6(P<0.05); whole process operation time was 16.93±0.5 vs 19.85±1 (P<0.05); label accuracy after transferring was 100% (8 274/8 274) vs 97.91% (8 101/8 274); table cleanliness was 99.19% (8 207/8 274) vs 94.39% (7 810/8 274); transfer accuracy was 100%(8 274/8 274) vs 95.85% (7 931/8 274). 【Conclusion】 Automatic transfer of diversion pouches of blood samples can improve the efficiency and quality of the sample transfer, and is conductive to the standardization of internal quality evaluation and control of blood transfusion departments.

The pathological role of hypersplenism in the course of liver cirrhosis / 中华肝胆外科杂志

Hypersplenism is an important complication of cirrhotic portal hypertension, and splenectomy is an important means to treat hypersplenism in cirrhosis. It is realized that hypersplenism played a pathological role in the course of cirrhosis. This article analyzes and compares the changes in the condition of patients with cirrhosis between splenectomy with and without hyperfunction, and comprehensively discusses the pathological role and mechanism of hypersplenism in the course of cirrhosis, in order to strengthen the clinical prevention and treatment of hypersplenism in cirrhosis and to better improve the condition and prognosis of patients with cirrhosis.

Construction and biological characterization of a Proteus mirabilis strain with modABC gene deletion / 南方医科大学学报

OBJECTIVE@#To construct a modABC gene knockout strain of Proteus mirabilis and explore the effect of modABC gene deletion on biological characteristics of Proteus mirabilis.@*METHODS@#Fusion PCR was used to obtain the fusion gene of modABC and the kanamycin-resistant gene Kn, which was ligated with the suicide vector pCVD442 and transduced into Proteus mirabilis. The modABC gene knockout strain of Proteus mirabilis was obtained after homologous recombination with the suicide vector. PCR and Sanger sequencing were used to identify genomic deletion of modABC gene in the genetically modified strain. The concentration of molybdate in the wild-type and gene knockout strains was determined using inductively coupled plasma mass spectrometry (ICP-MS), and their survival ability in LB medium was compared under both aerobic and anaerobic conditions.@*RESULTS@#PCR and sanger sequencing confirmed genomic deletion of modABC gene in the obtained Proteus mirabilis strain. The concentration of intracellular molybdenum in the modABC gene knockout strain was 1.22 mg/kg, significantly lower than that in the wild-type strain (1.46 mg/kg, P < 0.001). Under the aerobic condition, the modABC gene knockout strain grown in LB medium showed no significant changes in survival ability compared with the wild-type strain, but its proliferation rate decreased significantly under the anaerobic condition and also when cultured in nitrate-containing LB medium under anaerobic condition.@*CONCLUSION@#Homologous recombination with the suicide vector can be used for modABC gene knockout in Proteus mirabilis. modABC gene participates in molybdate uptake and is associated with anaerobic growth of Proteus mirabilis in the presence of nitrate.

Expert consensus on late stage of critical care management / 中华内科杂志

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.

Meta-analysis of efficacy and safety of Liuwei Wuling Tablets combined with conventional drugs in treatment of liver fibrosis and cirrhosis in chronic hepatitis B / 中国中药杂志

The present study evaluated the clinical efficacy and safety of Liuwei Wuling Tablets combined with conventional drugs for the treatment of liver fibrosis and cirrhosis in chronic hepatitis B. CNKI, Wanfang, VIP, CBM, PubMed, EMbase and Cochrane Library were searched for the relevant randomized controlled trials(RCTs) published from database inception to February 2021. All the retrieved papers were independently screened, extracted and evaluated by two researchers, followed by Meta-analysis by Review Manager 5.4. Finally, 18 RCTs were included, involving 2 168 patients(1 106 in the treatment group and 1 062 in the control group). The Meta-analysis results showed that compared with conventional drugs alone, Liuwei Wuling Tablets combined with conventional drugs could increase the effective rate of clinical treatment by reducing serum hyaluronic acid(HA), laminin(LN), procollagen type Ⅲ(PCⅢ), and type Ⅳ collagen(Ⅳ-C) to improve liver function, decreasing the levels of total bilirubin(TBiL), alanine amino-transferase(ALT), and aspartate aminotransferase(AST), and improving the negative conversion ratio of hepatitis B virus(HBV) DNA. In terms of safety, there were no serious adverse reactions in the treatment group and the control group. The results showed that Liuwei Wuling Tablets combined with antiviral or other conventional liver-protecting drugs could improve liver function, treat liver cirrhosis, and reduce liver fibrosis with high safety. However, due to the influence of literature quality and quantity, multi-center and high-quality RCTs with large sample size are needed for verification.

Exercise preconditioning attenuates the lipid metabolic disorder induced by chronic high fat diet feeding in mice / 生理学报

Mounting evidence has shown that exercise exerts extensive beneficial effects, including preventing and protecting against chronic diseases, through improving metabolism and other mechanisms. Recent studies have shown that exercise preconditioning affords significant cardioprotective effects. However, whether exercise preconditioning improves high fat diet (HFD)-induced obesity and lipid metabolic disorder remains unknown. The study was aimed to explore the effects of exercise preconditioning on HFD-induced obesity and lipid metabolic disorder in mice. 4-week-old C57BL/6 mice were subjected to swimming or sedentary control for 3 months, and then were fed with normal diet (ND) or HFD for 4 more months. The results showed that the blood glucose was decreased, and the glucose tolerance and grip strength were increased in exercised mice after training. Exercise preconditioning failed to improve HFD-induced body weight gain, but improved HFD-induced glucose intolerance. Exercise preconditioning showed no significant effects on both exercise capacity and physical activity in ND- and HFD-fed mice. HFD feeding increased total cholesterol and low density lipoprotein (LDL) levels in circulation, promoted subcutaneous fat and epididymal fat accumulation in mice. Exercise preconditioning increased circulating high density lipoprotein (HDL) and decreased circulating LDL, without affecting the subcutaneous fat and epididymal fat in HFD-fed mice. HFD feeding increased liver weight and hepatic total cholesterol contents, and dysregulated the expressions of several mitochondria function-related proteins in mice. These abnormalities were partially reversed by exercise preconditioning. Together, these results suggest that exercise preconditioning can partially reverse the HFD-induced lipid metabolic disorder and hepatic dysfunction, and these beneficial effects of exercise sustain for a period of time, even after exercise is discontinued.

Effect and influence factors of cardiopulmonary resuscitation in children with congenital heart disease in pediatric intensive care unit / 中华儿科杂志

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ2=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ2=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.

Diagnostic value of 18F-prostate specific membrane antigen PET/CT combined with multiparametric-MRI in identifying the grade group of prostate cancer / 中华泌尿外科杂志

Objective:To investigate the diagnostic value of the combination of 18F-prostate specific membrane antigen (PSMA) PET/CT and multiparametric magnetic resonance imaging (mpMRI) in identifying the grade group of prostate cancer, using parameters derived from the two imaging modalities. Method:Prostate cancer patients diagnosed by histopathology and received 18F-PSMA PET/CT and mpMRI during September 2018 to May 2021 in our hospital were retrospectively studied. The median age was 68(64-75), with the median PSA level of 14.74(7.75-24.19)ng/mL. All patients received mpMRI before biopsy. On biopsy, 6(12.2%) patients had International Society of Urological Pathology grade group(ISUP GG) 1 diseases, 16(32.7%) had ISUP GG 2 diseases, 12(24.5%) had ISUP GG 3 diseases, and 15(10.9%) had ISUP GG 4 or 5 diseases. Patients were then divided into high-grade group (ISUP 4-5) and low-grade group(ISUP 1-3). The median age of patients in high-grade group and low-grade group were 65(62-76) and 71(65-74), respectively. The PSA level in high-grade group and low-grade group were 15.11(6.63-42.86) ng/ml and 12.31(7.94-18.25) ng/ml, respectively. No significant differences were found in age and PSA level between the two groups ( P=0.334, P=0.448). All patients underwent 18F-PSMA PET/CT within 4 weeks after biopsy. The maximum standardized uptake value(SUV max) and the minimum apparent diffusion coefficient(ADC min)were recorded, and the ratio of SUV max/ ADC minwere calculated. The correlation between the above parameters and ISUP grade group were analyzed.The diagnostic value of the parameters was evaluated by the receiver operating characteristic (ROC) curve. Results:The data of 49 patients were analyzed. The average ADC minwas (0.57±0.16)×10 -3 mm 2/s, with the average SUV max and SUV max/ADC min of 15.30±12.54 and (29.69±23.72)×10 3, respectively. Statistical differences were found in SUV max ( P=0.012) and SUV max/ADC min ( P=0.002) between the high- and low-grade groups, while ADC min ( P=0.411) showed no statistical differences between the two groups. Significant positive correlations were found between SUV max(r=0.501, P<0.001), SUV max/ADC min (r=0.527, P<0.001) and ISUP grade group, respectively. There was a negative correlation between ADC min and ISUP grade group (r=-0.296, P=0.039). SUV max/ADC min was the best index to distinguish high-grade group from low-grade group prostate cancer with the area under the curve(AUC) of 0.749. In contrast, the AUC of SUV maxand ADC min were 0.731 and 0.615, respectively. The diagnostic sensitivity and specificity of SUV max/ADC min were 73.3% and 85.3%, respectively, with a critical value of 37.23×10 3. Conclusion:The combination use of 18F-PSMA PET/CT and mpMRI could improve the diagnostic efficiency for prostate cancer, compared to either modality alone. The ratio of SUV max/ADC min has a positive correlation with ISUP grade group, and is a promising index for distinguishing the high-grade prostate cancer from low-grade cancer.

The preliminary study about feasibility and accuracy of the frozen section during targeted prostate biopsy / 中华泌尿外科杂志

Objective:To investigate the feasibility and reliability of the frozen section during targeted prostate biopsy.Methods:The clinical and pathological information of patients who received cognitive fusion transperineal targeted plus systematic biopsy and frozen section of 1-2 core targeted biopsy were consecutively collected and retrospectively studied. The median age was 70 (ranging 64-78) years, with the median prostate-specific antigen (PSA) level of 11.00 (ranging 6.63-16.52) ng/ml and the median prostate volume of 35.72 (ranging 22.59-47.71) ml. All patients received bi-parametric magnetic resonance imaging (bp-MRI) and have Prostate Imaging Reporting and Data System (PI-RADS) 3 or higher lesions diagnosed on bp-MRI. The suspected lesions would be taken by targeted biopsy of which one or two cores would be sent to prepare for the frozen sections. Then a cognitive fusion targeted and systematic biopsy covering the above targeted zones would be routinely administered under a transperineal approach as a standard protocol. The total time used for diagnosis of the frozen sections, the pathological diagnosis and the International Society of Urological Pathology (ISUP) grade groups (GG) would be recorded. The sensitivity, the positive predictive value, and the accuracy on grade groups would be analyzed, using the pathological diagnosis based on standard sections from the same targeted lesion.Results:A total of 29 patients were included in this study. Accordingly, 29 suspected lesions were identified on bp-MRI. A total of 20 lesions were finally diagnosed of PCa on frozen section, with the detection rate of 69.0%. Of those, 9(45.0%) cases were ISUP GG 1 diseases, 5(25.0%) cases were GG 2 diseases, 1(5.0%) case was GG 3 disease, and 5(25.0%) cases were GG 4-5 diseases. A total of 22 lesions were diagnosed with PCa on standard sections of cores from the same targeted lesions, with the detection rate of 75.9%. Of those, 6(27.3%) cases were GG 1 disease, 11(50.0%) cases were GG 2 diseases, 1(4.5) case was GG 3 disease, and 4(18.2%) cases were GG 4-5 diseases. The sensitivity and the positive predictive value of frozen section were 90.9% and 100%, respectively. No false positive diagnosis was made by frozen section. Compared to diagnosis from frozen sections, the GG diagnosed from final standard sections were found to upgrade and downgrade in 2 and 2 cases, respectively. The accuracy rate on GG of frozen sections was 80%. The time used for the diagnosis of frozen sections was (11±2) minutes. The histology quality control of four specimens was dissatisfactory. Two were due to tissue loss and deformation during sampling, and the other two were due to cytoclasis during low-temperature transferring.Conclusion:It is feasible and reliable to make a pathological diagnosis from frozen section of prostate targeted biopsy.

Magnetic resonance guided focused ultrasound surgery for the treatment of low- to intermediate-risk localized prostate cancer / 中华泌尿外科杂志

Objective:To evaluate the feasibility, safety and efficacy of the magnetic resonance imaging guided focused ultrasound surgery (MRgFUS) in the treatment of localized prostate cancer (PCa).Methods:The data of 5 patients treated by MRgFUS from August 2020 to June 2021 in our institution were retrospectively analyzed. The median age was 73 (58-80) years, with the median PSA of 7.34 (5.19-8.40) ng/ml, and a median prostate volume of 27.96 (21.50-37.91) ml. The median pretreatment international prostate symptom score (IPSS) was 13(0-18). Of the 3 patients with intention of erectile function preservation, the pretreatment international index of erectile function-15 (IIEF-15) score was 12, 23 and 3, respectively. All patients had histopathology-proven PCa of grade group ≤ International Society of Urological Pathology (ISUP) 3, pre-operative PSA level <20 ng/ml, and a clinical stage ≤T 2b. A total of 6 lesions was confirmed by biopsy, with 3 of ISUP grade group 3 and 3 of ISUP grade group 1. All 5 patients underwent MRgFUS which was guided by a real-time magnetic resonance imaging (MRI). PSA, MRI and repeated biopsy were conducted to monitor recurrence. Questionnaires consisted of IPSS, IIEF-15, and the International Consultation on Incontinence-questionnaire-Short Form (ICI-Q-SF) were recorded before and after MRgFUS to evaluate the impact on functional preservation. Results:A total of 5 patients received MRgFUS. In total, 5 of the 6 lesions were treated. 1 lesion unvisible on MRI was not clinically significant and was left untreated. The median time in MRI scanner was 190 (140-355) min, and the median sonication time was 64 (35-148) min with the median sonications of 8 (5-13). The median catheter indwelling time was 1 (1-8) days. No other adverse effects were reported. The PSA level of all 5 patients decreased, with the nadir PSA of 1.196 ng/ml, 4.398 ng/ml, 4.135 ng/ml, 1.562ng/ml and 1.350ng/ml, respectively. 4 of the patients had a PSA decrease over 50%. No PCa lesion was seen on MRI at 3-month follow-up visit. As for functional preservation, the post-MRgFUS IPSS declined compared with the baseline score, and the IPSS of last follow-up was 5(0-14). Of the 3 patients with intention to preserve the erectile function, the erectile function score of IIEF-15 were 12, 30 and 9 three months after the treatment, respectively. No incontinence occurred postoperatively.Conclusions:MRgFUS is a feasible and safe way for the treatment of low- to intermediate-risk localized PCa, with satisfactory performance on functional preservation and low incidence of complications. The oncological outcomes still need to be establised with longer follow-up time and larger sample studies.

Prognostic analysis of patients with pathological positive margins after radical prostatectomy / 中华泌尿外科杂志

Objective:To analyze the prognosis of patients with positive resection margin after radical prostatectomy, as well as the prostate-specific antigen (PSA)level and risk factors for PSA progression.Methods:A retrospective analysis was performed on the data of 141 patients with pathologically diagnosed prostate cancer who underwent RP from May 2012 to August 2020 in Beijing Hospital. The mean age was (67.4±6.7)years, the preoperative median PSA was 9.6 (1.4-152.8) ng/ ml and the median follow-up time was 56 months. Postoperative pathology was T 2 stage 74 (52.5%), T 3 stage 63 (44.7%), T 4 stage 4 (2.8%). Biochemical recurrence after radical resection was defined as PSA rose to more than 0.2 ng/ml and showed an upward trend after two consecutive follow-ups. In this study, serum PSA ≥ 0.1 ng/ml without biochemical recurrence after radical operation was defined as PSA progression. The PSA level, risk factors of PSA progression and prognosis of patients with positive resection margin were analyzed. Univariate and multivariate Cox regression analysis was used to analyze the correlation between age, preoperative PSA level, pathological stage (pT), ISUP classification, surgical approach, lymph node dissection, single/multiple positive margins and PSA progression. Results:The median follow-up of 141 patients was 52 months(1-104 months). There were 69 (48.9%) patients in the PSA progression group and 72 (51.1%) patients in the non PSA progression group. In the PSA progression group, 13 (18.8%) patients did not receive treatment and 8 (61.5%) patients had biochemical recurrence. 4 (5.8%) patients received radiotherapy alone, and 2 (50.0%) patients had biochemical recurrence. 52 (75.4%) patients received endocrine therapy or endocrine therapy combined with radiotherapy, and 5 (9.6%) patients developed castration resistance. Multivariate Cox regression analysis showed preoperative PSA ( HR=1.015, 95% CI 1.005-1.025, P =0.004), ISUP grade and group ( HR=1.351, 95% CI 1.091-1.673, P =0.006), surgical method ( HR=2.233, 95% CI 1.141-4.370, P =0.019) was correlated with PSA progression. Conclusions:The incidence of surgical positive margin is high after RP. Nearly half of the patients with surgical positive margin developed a PSA progression status. Preoperative PSA, ISUP grade group, and the surgical approach are risk factors for PSA progression in patients with positive surgical margins. Patients with these risk factors should be monitored more closely and treated more aggressively.

Cranial irradiation alters dendritic spine density and morphology in the young rat hippocampus / 中华放射医学与防护杂志

Objective:To explore the changes of dendritic spine morphology and structure in dentate gyrus(DG) and CA1 areas of hippocampus of young rats, so as to provide a direct morphological basis for studying the molecular mechanism of radiation cognitive impairment.Methods:21-day-old Sprague-Dawley (SD) rats were given a single dose of 10 Gy whole brain irradiation. The changes of cognitive function, dendritic spine density and morphological changes in DG and CA1 areas of hippocampus were observed 1 and 3 months after irradiation, and the expression of postsynaptic density protein (PSD95) was detected by Western blot.Results:The cognitive impairment was observed in young rats 3 months after irradiation. The density of dendritic spines in DG area of hippocampus was decreased significantly by 39.06% and 29.27% at 1 and 3 months after irradiation ( t=14.96, 12.35, P<0.05), respectively. The density of dendritic spines in the basal dendrites of hippocampal CA1 area was decreased by 33.40% ( t=10.39, P<0.05) 1 month after irradiation, but had no significant change at 3 months after irradiation. While the density of dendritic spines in the apical dendrites of CA1 region did not change significantly at 1 and 3 months after irradiation. In addition, the morphology of dendritic spines in DG and CA1 regions of hippocampus was dynamically changed after irradiation. The expression of PSD95 protein was decreased by 24.6% and 50.5% ( t=2.97, 9.27, P<0.05) at 1 and 3 months after irradiation, respectively. Conclusions:This study reported the density and morphological changes of dendritic spines in different brain regions of hippocampus of young rats after ionizing radiation, suggesting that PSD95 may participate in the occurrence of radiation-induced cognitive impairment by affecting the structure and morphology of dendritic spines and reducing synaptic plasticity.

Protective effects of Lonicerae Japonicae Flos against acute alcoholic liver injury in rats based on network pharmacology / 中国中药杂志

This study aims to explore underlying mechanism of Lonicerae Japonicae Flos(LJF) in protecting rats against acute alcoholic liver injury(ALI) based on mitogen-activated protein kinase(MAPK) pathway. First, the targets of LJF in preventing ALI were predicted by network pharmacology and the component-target-pathway network was constructed, so that the key targets of LJF components acting on MAPK pathway were screened. Second, male SD rats were randomized into the control(KB) group, model(MX) group, positive(YX) group, and LJF high-(GJ), medium-(ZJ), and low-(DJ) dose groups. Each administration group was given(ig) corresponding drugs for 7 days and KB group and MX group received(ig) equal volume of distilled water every day. Except for KB group, rats were given Chinese spirit(56%, 3 days) for ALI modeling. The levels of aspartate transaminase(AST), alanine transaminase(ALT), interleukin-6(IL6) and tumor necrosis factor-α(TNF-α) in serum and malondialdehyde(MDA), glutathione(GSH), superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) in liver tissue of rats in each group were detected. Furthermore, we employed quantitative real-time PCR(qRT-PCR) to probe the effects of LJF on the key targets of MAPK pathway in ALI rats. A total of 28 active components of LJF were screened from TCMSP database, and 317 intersected with ALI-related targets. According to Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis, the 317 targets involved 226 pathways, which were mainly liver disease, inflammation, immunity, apoptosis and other related pathways. According to the MAPK pathway-target-active component network, the key active components of LJF, such as chlorogenic acid, hederagenol, and hyperoside, acted on 25 key targets of MAPK pathway. The results of in vivo experiments showed decreased levels of AST, ALT, and MDA in DJ, ZJ, and GJ groups(P<0.01 or P<0.05), reduced levels of IL6 in DJ and GJ groups(P<0.01 or P<0.05), and improved levels of SOD and GSH in ZJ and GJ groups(P<0.01 or P<0.05). The results of qRT-PCR demonstrated that the expression levels of mitogen-activated protein kinase kinase 4(MAPK2 K4) and mitogen-activated protein kinase 3(MAPK3) were decreased in DJ, ZJ, and GJ groups(P<0.01). The network pharmacology and experimental verification showed that the active components in LJF can reduce the inflammatory factor level and enhance the activities of SOD and GSH-Px by inhibiting the expression of key targets of MAPK pathway, thus alleviating and preventing liver damage caused by alcohol.

Rapid Internal Control Reference Recombinase-Aided Amplification Assays for EBV and CMV Detection / 生物医学与环境科学（英文）

Epstein-Barr virus (EBV) and cytomegalovirus (CMV), two of the most prevalent human herpesviruses, cause a wide spectrum of diseases and symptoms and are associated with serious health problem. In this study, we developed an internal control reference recombinase-aided amplification (ICR-RAA) assay for the rapid detection of EBV and CMV within 30 min. The assay had a sensitivity of 5 and 1 copies/test for EBV and CMV, respectively, with no cross reaction with other pathogens. In comparison with those of the commercial quantitative polymerase chain reaction (qPCR), the sensitivity of the EBV and CMV ICR-RAAs using extracted DNA was 93.33% and 84.84%, respectively; the specificity was 98.75% and 100.00%, respectively; and the Kappa values were 0.930 and 0.892 (

Diagnosis of angiostrongylus eosinophilic meningitis in infants by high-throughput sequencing: 2 cases of reports / 中华实用儿科临床杂志

Infants suffering from angiostrongylus eosinophilic meningitis (AEM) is rare, while AEM can cause severe consequences.The diagnostic value of high-throughput sequencing for AEM was studied by analyzing 2 AEM children (< 2 years old) in the Department of Neurology, Shenzhen Children′s Hospital in 2019.Case 1 mainly pre-sented intermittent fever, vomiting, mental fatigue and bregma bulge.Case 2 mainly manifested intermittent fever, cough, vomiting and convulsion.Due to hypereosinophils in patients′ peripheral blood and cerebrospinal fluid (CSF), and abundant DNA sequences from a cantonensis in CSF and positive antibody test, the patients were diagnosed with AEM.The patients were treated with albendazole to deworm, and small doses of methylprednisolone to reduce inflammation.The clinical characteristics of AEM infant are not typical, and high-throughput sequencing technology can assist the diagnosis of AEM.

Progress in strategies for positioning the epileptogenic zone in children with tuberous sclerosis complex / 中华实用儿科临床杂志

Epilepsy is one of the major clinical features of tuberous sclerosis complex, and it is drug-resistant in the majority of cases.Surgical resection is an effective way to resolve the seizures.Precise preoperative evaluation is critical to the surgical outcome.Preoperative evaluation mainly aims to determine the range of the epileptogenic zone and the functional areas that should be preserved.Because of the complexity of the epileptogenic mechanism and brain network, there isn′t a single and specific measure that can accurately position the epileptogenic zone, so it is necessary to comprehensively evaluate and localize the epileptogenic zone by using multiple methods, including collection of a detailed medical history, symptomatic analysis during the attack of seizures, magnetic resonance imaging, positronemission tomography, electroencephalogram, neuropsychological evaluation, etc.In this paper, the rational use of above-mentioned approaches and comprehensive analysis of their results were summarized, which play an essential role in contro-lling seizures in children with tuberous sclerosis complex and refractory seizures.

Role of microglial pyroptosis in hypoxic-ischemic brain damage / 中国当代儿科杂志

OBJECTIVE@#To investigate the role of microglial pyroptosis in hypoxic-ischemic brain damage.@*METHODS@#An oxygen-glucose deprivation/reoxygenation (OGD/R) model of rat microglial cells were cultured in vitro. Western blot was used to measure the expression of the pyroptosis-related proteins caspase-1, interleukin-1β (IL-1β), and N-terminal gasdermin D (GSDMD-N) at 0, 1, 3, 6, 12, and 24 hours after OGD/R. After the microglial cells were transfected with lentivirus-mediated silenced gasdermin D (GSDMD), immunofluorescence assay and Western blot were used to measure the transfection rate of GSDMD. Microglial cell lines were divided into three groups: normal control, negative control, and LV-sh_GSDMD (lentivirus-mediated GSDMD silencing). CCK-8 assay and LDH kit were used to observe the effect of GSDMD silencing on the viability and toxicity of microglial cells at 24 hours after OGD/R. Western blot was used to observe the effect of GSDMD silencing on the levels of caspase-1, GSDMD-N, and IL-1β in the microglial cells at 24 hours after OGD/R.@*RESULTS@#The expression levels of the pyroptosis-related proteins caspase-1, GSDMD-N, and IL-1β in microglial cells were upregulated since 0 hour after OGD/R and reached the peak levels at 24 hours. A microglial cell model of lentivirus-mediated GSDMD silencing was successfully constructed. At 24 hours after OGD/R, compared with the normal control group, the GSDMD silencing group had a significant increase in the cell viability and a significant reduction in the cytotoxicity (P<0.05), as well as significant reductions in the protein expression levels of caspase-1, GSDMD-N, and IL-1β in microglial cells (P<0.05).@*CONCLUSIONS@#Lentivirus silencing of the key substrate protein for pyroptosis GSDMD can alleviate hypoxic-ischemic brain damage, suggesting that microglial pyroptosis aggravates hypoxic-ischemic brain damage.

Polarization of human acute monocytic leukemia THP-1 cells-derived macprophages induced by Nippostrongylus brasiliensis proteins in vitro / 中国血吸虫病防治杂志

Objective To investigate the polarization of human acute monocytic leukemia THP-1 cells-derived macrophages induced by Nippostrongylus brasiliensis proteins in vitro, so as to provide insights into the elucidation of the mechanisms underlying host immune responses to hookworm infections. Methods The in-vitro culture of N. brasiliensis was established and maintained in the laboratory, and the third- (L3) and fifth-stage larvae (L5) were collected under a sterile condition for preparation of L3 and L5 proteins. The in-vitro culture of THP-1 cells was established, stimulated with 500 ng/mL PMA to yield M0 macrophages that were adherent to the plate wall. The LPS + IFN-γ group, IL-4 + IL-13 group, L3 protein group and L5 protein group were given stimulation with 500 ng/mL LPS plus 100 ng/mL IFN-γ, IL-4 and IL-13 (both 100 ng/mL), L3 protein (5 mg/mL) and L5 protein (5 mg/mL), respectively, while the negative control group was given no stimulation. The cell morphology was observed using microscopy, the mRNA expression of M1/M2 macrophages-specific genes was quantified using a quantitative real-time PCR (qPCR) assay, and the surface markers of M1/M2 macrophages were detected using flow cytometry, while the levels of cytokines secreted by M1/M2 macrophages were measured using enzyme-linked immunosorbent assay (ELISA) following stimulations, so as to examine the polarization of THP-1-derived macrophages induced by N. brasiliensis proteins in vitro. Results Following stimulation with PMA, THP-1 cells appeared wall-adherent M0 macrophages, and polarized to typical M1 macrophages following stimulation with LPS + IFN-γ, and typical M2 macrophages following stimulation with IL-4 + IL-13, IL-3 protein or L5 protein. There was a significant difference in the proportion of M1 macrophages among the negative control group, the LPS + IFN-γ group, the IL-4 + IL-13 group, the L3 protein group and the L5 protein group (χ2 = 3 721.00, P < 0.001), with the highest proportion detected in the LPS + IFN-γ group, and there was also a significant difference in the proportion of M2 macrophages among groups (χ2 = 105.43, P < 0.001). There were significant differences among groups in terms of the mRNA expression of CCL2 (F = 191.95, P < 0.001), TNF-α (F = 129.95, P < 0.001), IL-12b (F = 82.89, P < 0.001), PPARγ (F = 11.30, P < 0.001), IL-10 (F = 9.51, P < 0.001) and Mrc1 genes (F = 12.35, P < 0.001). In addition, there were significant differences in the proportion of positive CD86 and CD206 expression among groups (χ2 = 24 004.33 and 832.50, P < 0.001). Higher IL-1β and TNF-α levels were measured in the LPS + IFN-γ group than in the IL-4 + IL-13 group, the L3 protein group and the L5 protein group (P < 0.001), and greater TGF-β1 and IL-10 levels were seen in the IL-4 + IL-13 group, the L3 protein group and the L5 protein group than in the negative control group and the LPS + IFN-γ group (P < 0.05). Conclusions Both L3 and L5 proteins of N. brasiliensis may induce the polarization of THP-1-derived macrophages to M2 type in vitro.