Long-term outcomes of childhood steroid-sensitive nephrotic syndrome / 中华儿科杂志

Objective: To investigate the long-term outcomes and risk factors in children with steroid-sensitive nephrotic syndrome (SSNS). Methods: A retrospective cohort study was conducted on newly onset SSNS admitted to the Department of Pediatrics of the First Affiliated Hospital of Sun Yat-sen University from January 2006 to December 2010 and 105 cases with follow-up for more than 10 years were included. Clinical data including general characteristics, clinical manifestation, laboratory tests, treatment and prognosis. The primary outcome was the clinical cure, and the secondary outcomes were relapse or ongoing immunosuppressive treatment within the last 1 year of follow-up and complications at the last follow-up. According to the primary outcome, the patients were divided into clinical cured group and uncured group. Categorical variables were compared between 2 groups using the χ2 or Fisher exact test, and continuous variables by t or Mann-Whitney U test. Multiple Logistic regression models were used for multivariate analysis. Results: Of the 105 children with SSNS, the age of onset was 3.0 (2.1, 5.0) years, and 82 (78.1%) were boys, 23(21.9%) were girls. The follow-up time was (13.1±1.4) years; 38 patients (36.2%) had frequently relapsing or steroid-dependent nephrotic syndrome (FRNS or SDNS) and no death or progression to end-stage kidney disease. Eighty-eight patients (83.8%) were clinically cured. Seventeen patients (16.2%) did not reach the clinical cure criteria, and 14 patients (13.3%) had relapsed or ongoing immunosuppressive treatment within the last year of follow-up. The proportion of FRNS or SDNS (12/17 vs. 29.5% (26/88), χ2=10.39), the proportion of treatment with second-line immunosuppressive therapy (13/17 vs. 18.2% (16/88), χ2=21.39), and the level of apolipoprotein A1 at onset ((2.0±0.5) vs. (1.7±0.6) g/L, t=2.02) in the uncured group were higher than those in the clinical cured group (all P<0.05). Multivariate Logistic regression analysis showed that patients treated with immunosuppressive therapy had an increased risk of not reaching clinical cure in the long term (OR=14.63, 95%CI 4.21-50.78, P<0.001). Of the 55 clinically cured patients who had relapsed, 48 patients (87.3%) did not relapse after 12 years of age. The age at last follow-up was 16.4 (14.6, 18.9) years, and 34 patients (32.4%) were ≥18 years of age. Among the 34 patients who had reached adulthood, 5 patients (14.7%) still relapsed or ongoing immunosuppressive treatment within the last year of follow-up. At the last follow-up, among the 105 patients, 13 still had long-term complications, and 8 patients were FRNS or SDNS. The proportion of FRNS or SDNS patients with short stature, obesity, cataracts, and osteoporotic bone fracture was 10.5% (4/38), 7.9% (3/38), 5.3% (2/38), and 2.6% (1/38), respectively. Conclusions: The majority of SSNS children were clinically cured, indicating a favorable long-term prognosis. History of treatment with second-line immunosuppressive therapy was the independent risk factor for patients not reaching the clinical cure criteria in the long term. While it is not uncommon for children with SSNS to persist into adulthood. The prevention and control of long-term complications of FRNS or SDNS patients should be strengthened.

Down-regulation of SIK2 expression alleviates myocardial ischemia-reperfusion injury in rats by inhibiting autophagy through the mTOR-ULK1 signaling pathway / 南方医科大学学报

OBJECTIVE@#To explore the role of salt-inducible kinase 2 (SIK2) in myocardial ischemia-reperfusion (IR) injury in rats.@*METHODS@#Fifteen male SD rats were randomized equally into sham operation group, myocardial IR model group, and SIK2 inhibitor group (in which the rats were treated with intravenous injection of 10 mg/kg bosutinib via the left femoral vein 24 h before modeling). Ultrasound was used to detect the cardiac function of the rats, and myocardial pathologies were observed with HE staining. Transmission electron microscopy was used to observe autophagy of myocardial cells, and Western blotting was performed to detect the contents of the autophagy-related proteins SIK2, LC3B, Beclin-1, p62 and the expressions of p-mTOR, mTOR, p-ULK1, and ULK1 in myocardial tissue.@*RESULTS@#Myocardial IR injury significantly increased the number of autophagosomes (P < 0.05) and the expression of SIK2 protein (P < 0.01) in the myocardial tissues. Treatment with bosutinib before modeling obviously lowered the expression of SIK2 protein (P < 0.01), alleviated myocardial pathologies, and reduced the number of autophagosomes (P < 0.05) in the myocardial tissue. The rats with myocardial IR injury showed obviously lowered LVEF and FS values (P < 0.001), which were significantly improved by bosutinib treatment (P < 0.05); no significant difference was detected in IVSDd or LVPWDd among the 3 groups (P > 0.05). Myocardial IR injury obviously increased the expressions of LC3-II/LC3-I and Beclin-1 proteins and lowered the expression of p62 protein (P < 0.01), and these changes were significantly rescued by bosutinib treatment (P < 0.05). The rat models of myocardial IR injury showed significantly increased expression of p-ULK1 (Ser757) (P < 0.01) and lowered expression of p-mTOR protein (P < 0.0001) in the myocardium, and these changes were obviously reversed by bosutinib (P < 0.01 or 0.05); there was no significant difference in mTOR and ULK1 expressions among the 3 groups (P > 0.05).@*CONCLUSION@#SIK2 may promote autophagy through the mTOR/ULK1 signaling pathway, and inhibiting SIK2 can reduce abnormal autophagy and alleviate myocardial IR injury in rats.

Assess on rabbit conjunctival lymphatic vessels distribution in different age groups / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the distribution of conjunctival lymphatic vessels in New Zealand white rabbits and its relationship with age. METHODS: Subconjunctival trypan blue was injected in four quadrants(nasal, superior, temporal, and inferior)and recorded videos. The number of lymphatic outflow pathways arising from the blebs was counted. The difference in the number of lymphatic outflow pathways across the quadrants of each group was tested by single-factor analysis of variance. Paired <i>t</i>-test was used to compare the differences in the number of lymphatic outflow pathways in the same rabbit quadrants across different ages. RESULTS: In New Zealand white rabbits, thick annular lymphatic vessels were mainly distributed near the limbus part of the conjunctiva. The single collecting lymphatic vessels were primarily distributed in the peripheral parts. Although the lymphatic vessels of juvenile rabbits have fewer branches, the number of lymphatic vessels in the different quadrants was no significant difference in each group(all <i>P</i>>0.05)and was no difference between the two age groups(all <i>P</i> >0.05). CONCLUSION: The lymphatic vessels were abundant in rabbit conjunctiva. The number of lymphatic vessels in each quadrant and between two age groups had no significant difference.

Effect of Acyclovir on proliferation and migration of human Tenon capsule fibroblasts <i>in vitro</i> / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To explore the effect and mechanism of acyclovir(ACV)on the proliferation and apoptosis of human eye Tenon capsule fibroblasts(HTFs)<i> in vitro</i>. <p>METHODS: HTFs were divided into ACV treatment group and control group; CCK8 was used to detect cell proliferation rate under different concentration gradients, scratch assay was used to detect HTFs migration ability, and flow cytometry was used to detect HTFs apoptosis and cell cycle. <p>RESULTS: Compared with the control group, the proliferation rate of HTFs in the ACV-treated group(final concentrations were 1.125, 2.25, 3.375, 4.5mmol/L)was significantly reduced(<i>P</i><0.05)and was concentration-dependent. The scratch closure rate in the ACV-treated group(final concentrations were 4.5mmol/L)was significantly reduced(<i>P</i><0.05), the apoptosis rate was significantly increased(<i>P</i>=0.0005), the peak value of the cell cycle G0 / G1 increased(<i>P</i>=0.0011), and the S-phase decreased(<i>P</i>=0.0006). The cell cycle is blocked in the G0/G1 phase. <p>CONCLUSION: Acyclovir can promote cell apoptosis by blocking the cell cycle of HTFs, and inhibit the proliferation and migration of HTFs.

Research progress of trabecular meshwork cell oxidative stress in the pathogenesis of glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#<p>Glaucoma is a common irreversible blinding eye disease, pathological elevated intraocular pressure is the main clinical feature. The formation of intraocular pressure, related to aqueous circulation, will be pathologically elevated when the aqueous cycle is abnormal. Trabecular network, which plays a key role in maintaining normal intraocular pressure, is the main component of aqueous outflow channel. Imbalance of oxidative stress manifested as oxidation and antioxidant effects is a direct risk factor for elevated intraocular pressure in glaucoma. When it comes to the trabecular meshwork cells, a series of changes such as deposition and degeneration of extracellular matrix, autophagy and aging will eventually occur, and finally the dysfunction of trabecular meshwork cells and increased aqueous outflow resistance, causing intraocular pressure pathological elevated. In this paper, we reviewed the research progress on the relationship between oxidative stress in trabecular meshwork cells and the pathogenesis of glaucoma, in order to provide evidence for further research and reference for exploring the pathogenesis, prevention and treatment of glaucoma.

Surveillance of schistosomiasis in Xiaogan City from 2016 to 2020 / 中国血吸虫病防治杂志

Objective To analyze the surveillance data of schistosomiasis in Xiaogan City, Hubei Province from 2016 to 2020, so as to provide the scientific evidence for understanding the epidemiological changes of schistosomiasis and evaluating the schistosomiasis control strategy. Methods A total of 16 surveillance sites were selected in the schistosomiasis endemic foci of Xiaogan City from 2016 to 2020, where Schistosoma japonicum infections in humans, livestock and Oncomelania snails and the schistosomiasis transmission risk were monitored. The schistosomiasis surveillance results were descriptively analyzed. Results During the period from 2016 to 2020, there was no schistosomiasis emergency epidemic in Xiaogan City. A total of 660 sero-positive individuals were identified in Xiaogan City during the 5-year period, and the seroprevalence of S. japonicum infections reduced from 2.08% in 2016 to 0.97% in 2020. Higher seroprevalence of S. japonicum infections was detected in men than in women, and in individuals at ages of over 60 years than in those at other age groups; however, no egg-positives were detected in humans or livestock. The mean density of living snails was 0.05 to 0.06 snails/0.1 m2 during the 5-year period, and the occurrence of frames with snails increased from 2.99% in 2016 to 3.92% in 2020; however, no S. japonicum infection was found in snails. Conclusions The endemic situation of schistosomiasis remarkably decreases in Xiaogan City during the period from 2016 through 2020. Further improvements of the sensitive and effective schistosomiasis surveillance system are required with an emphasis on the monitoring of the schistosomiasis transmission risk and management of floating populations.

Recent progress in targeting degradation of FAK based on PROTAC / 药学学报

Local focal adhesion kinase (FAK) is a non-receptor intracellular tyrosine kinase that plays an important role in tumor initiation, development, metastasis and invasion, and is considered to be an important target for the development of antineoplastic drugs. It has both kinase-dependent and non-kinase-dependent scaffolding functions. However, traditional small molecular inhibitors can only inhibit its kinase-dependent activity, so it is difficult to target the kinase-independent scaffolding function. Therefore, there is an urgent need for novel strategies to enhance FAK targeting to lay the foundation for determining the druggability and discovery of FAK inhibitors. Proteolysis targeting chimera (PROTAC) is a new drug development strategy that can recruit E3 ligase to specifically ubiquitinylate target proteins for degradation through the proteasome system. The unique mechanism of action of the PROTAC system could be used to target and degrade the FAK protein, thus eliminating the scaffolding function of FAK. In this review, FAK protein, the signaling pathway, and small molecule inhibitors are briefly described, and the latest research progress in targeting the degradation of FAK using PROTAC technology is summarized.

Predicting prolonged length of intensive care unit stay via machine learning / 北京大学学报(医学版)

OBJECTIVE@#To construct length of intensive care unit (ICU) stay (LOS-ICU) prediction models for ICU patients, based on three machine learning models support vector machine (SVM), classification and regression tree (CART), and random forest (RF), and to compare the prediction perfor-mance of the three machine learning models with the customized simplified acute physiology score Ⅱ(SAPS-Ⅱ) model.@*METHODS@#We used medical information mart for intensive care (MIMIC)-Ⅲ database for model development and validation. The primary outcome was prolonged LOS-ICU(pLOS-ICU), defined as longer than the third quartile of patients' LOS-ICU in the studied dataset. The recursive feature elimination method was used to do feature selection for three machine learning models. We utilized 5-fold cross validation to evaluate model prediction performance. The Brier value, area under the receiver operation characteristic curve (AUROC), and estimated calibration index (ECI) were used as perfor-mance measures. Performances of the four models were compared, and performance differences between the models were assessed using two-sided t test. The model with the best prediction performance was employed to generate variable importance ranking, and the identified top five important predictors were pre-sented.@*RESULTS@#The final cohort in our study consisted of 40 200 eligible ICU patients, of whom 23.7% were with pLOS-ICU. The proportion of the male patients was 57.6%, and the age of all the ICU patients was (61.9±16.5) years.Results showed that the three machine learning models outperformed the customized SAPS-Ⅱ model in terms of all the performance measures with statistical significance (P < 0.01). Among the three machine learning models, the RF model achieved the best overall performance (Brier value, 0.145), discrimination (AUROC, 0.770) and calibration (ECI, 7.259). The calibration curve showed that the RF model slightly overestimated the risk of pLOS-ICU in high-risk ICU patients, but underestimated the risk of pLOS-ICU in low-risk ICU patients. Top five important predictors for pLOS-ICU identified by the RF model included age, heart rate, systolic blood pressure, body tempe-rature, and ratio of arterial oxygen tension to the fraction of inspired oxygen(PaO2/FiO2).@*CONCLUSION@#The RF algorithm-based pLOS-ICU prediction model had a best prediction performance in this study. It lays a foundation for future application of the RF-based pLOS-ICU prediction model in ICU clinical practice.

Prediction of intensive care unit readmission for critically ill patients based on ensemble learning / 北京大学学报(医学版)

OBJECTIVE@#To develop machine learning models for predicting intensive care unit (ICU) readmission using ensemble learning algorithms.@*METHODS@#A publicly accessible American ICU database, medical information mart for intensive care (MIMIC)-Ⅲ as the data source was used, and the patients were selected by the inclusion and exclusion criteria. A set of variables that had the predictive ability of outcome including demographics, vital signs, laboratory tests, and comorbidities of patients were extracted from the dataset. We built the ICU readmission prediction models based on ensemble learning methods including random forest, adaptive boosting (AdaBoost), and gradient boosting decision tree (GBDT), and compared the prediction performance of the machine learning models with a conventional Logistic regression model. Five-fold cross validation was used to train and validate the prediction models. Average sensitivity, positive prediction value, negative prediction value, false positive rate, false negative rate, area under the receiver operating characteristic curve (AUROC) and Brier score were used as performance measures. After constructing the prediction models, top 10 predictive variables based on importance ranking were identified by the model with the best discrimination.@*RESULTS@#Among these ICU readmission prediction models, GBDT (AUROC=0.858) had better performance than random forest (AUROC=0.827), and was slightly superior to AdaBoost (AUROC=0.851) in terms of AUROC. Compared with Logistic regression (AUROC=0.810), the discrimination of the three ensemble learning models was much better. The feature importance provided by GBDT showed that the top ranking variables included vital signs and laboratory tests. The patients with ICU readmission had higher mean arterial pressure, systolic blood pressure, diastolic blood pressure, and heart rate than the patients without ICU readmission. Meanwhile, the patients readmitted to ICU experienced lower urine output and higher serum creatinine. Overall, the patients having repeated admissions during their hospitalization showed worse heart function and renal function compared with the patients without ICU readmission.@*CONCLUSION@#The ensemble learning based ICU readmission prediction models had better performance than Logistic regression model. Such ensemble learning models have the potential to aid ICU physicians in identifying those patients with high risk of ICU readmission and thus help improve overall clinical outcomes.

Current situation and problems of national standards for Chinese medicinal materials / 中国中药杂志

To learn the current situation and strengthen the management of national standards for Chinese medicinal materials, we sorted out the relevant national standards. According to incomplete statistics, there are 1 185 kinds of Chinese medicinal materials, including 1 024 kinds of plant medicines, 106 kinds of animal medicines, and 54 kinds of mineral medicines, in addition to ethnic medicinal materials with different functions. The relevant standards include 819 Pharmacopoeia standards, 342 standards issued by the Ministry of Health or National Medicinal Products Administration, 7 standards for new medicinal materials, and 17 standards for imported medicinal materials. In this paper, the sources of standards as well as the distribution of families and genera and the distribution of medicinal parts of medicinal materials are analyzed. The suggestions are as follows:(1)to improve the coordination among different national standards of Chinese medicinal materials;(2)to improve the standardization and controllability of relevant standards;(3)to revise the issued standards for Chinese medicinal materials(including Tibetan, Uygur, and Mongolian medicinal materials).

Expression of BCR/ABL fusion gene in circulating endothelial cells from chronic myelogenous leukemia patients and its clinical significance / 中国实验血液学杂志

Several studies have shown that the tumor endothelial cells are different from the normal tissue endothelial cells. These tumor endothelial cells may contribute to tumor neo-vasculogenesis. This study was purposed to analyze the biologic features and determine the expression level of CD133 and BCR/ABL fusion gene in circulating endothelial cells (CEC) isolated from peripheral blood of CML patients, as well as to investigate the role of CEC in disease progression. Mononuclear cells were isolated from peripheral blood by density gradient centrifugation; CEC were sorted by MACS and harvested in the endothelial growth medium. The morphologic features of CEC were observed by microscopy, the cell growth rate was calculated by cell counting, and the cells were identified by immunofluorescence staining for the expression of CD31,CD34,VWF and CD133. The expression of BCR/ABL fusion gene was examined by FISH in 12 CML patients. The results indicated that the isolated CEC displayed the typical cobble-stone morphology. These cells could be identified by the positive immunofluorescence staining for CD31, CD34 and VWF, and showed more increased proliferative potential as compared to that of healthy donors. It was found that the positive rate of CD133 was 31.29% in CML patients, which was significantly different from that of healthy donors (P < 0.05). In 12 CML patients, CEC carried the same chromosome aberration as the leukemia cells (10.77%). Higher expression level of CD133 and BCR/ABL fusion gene positively correlated with progression of disease. It is concluded that the CEC may participate in invasion and angiogenesis in patients with CML and possibly correlate to the spreading and progression of the disease.

Clinical investigation of homoharringtonine in combination with all-transretinoic acid and arsenic trioxide for acute promyelocytic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the clinical outcome, adverse effect and treatment cost of homoharringtonine (HHT) in combination with all-trans retinoic acid (ATRA) and arsenic trioxide (AS2O3) for newly diagnosed with patients acute promyelocytic leukemia (APL).</p><p><b>METHODS</b>Clinical data of treatment of newly diagnosed patients with APL in experimental group (HHT + ATRA + AS2O3, n = 14) and control group \[Idarubicin (IDA) + ATRA + AS2O3, n = 21\] were analyzed retrospectively. The therapeutic effects, side effects and costs during induction therapy were compared between the two groups.</p><p><b>RESULTS</b>(1) The complete remission (CR) rate were 92.9% (13/14) and 95.2% (20/21) in experimental group and control group, respectively. The time to achieve CR were (28.1 ± 3.8) and (31.7 ± 4.2) days, respectively (P > 0.05). The negative rate of PML-RARα fusion gene at the time of CR were 76.9% (10/13) and 75.0% (15/20), respectively, and that in CR patient at the end of the first cycle treatment were 100.0% (13/13) and 95.0% (19/20), respectively (P > 0.05). (2) 5-year overall survival (OS) rate were (92.6 ± 0.6)% and (89.9 ± 0.5)%, respectively (P > 0.05), 5-year disease free survival (DFS) rate were 100.0% and (86.8 ± 0.6)%, respectively (P > 0.05). (3) During induction therapy, the incidence of infection in experimental and control group were 23.1% (3/13), 60.0% (12/20), respectively (P < 0.05). The amount of platelet transfusion were (54.7 ± 29.6) and (76.5 ± 25.6) units, respectively (P > 0.05), and that of fresh frozen plasma were (1157.1 ± 238.4) and (1423.5 ± 324.6) ml, respectively (P > 0.05). The total medical costs (excluding HHT and IDA) in experimental and control group were (36074.9 ± 1245.6) and (50564.5 ± 3658.4)CNY, respectively (P < 0.05).</p><p><b>CONCLUSION</b>HHT in combination with ATRA and AS2O3 regimen for newly diagnosed APL has a better efficacy, a higher long-term survival rate, and a lower costs, which is one of the reasonable choice.</p>

Expression of a tumor related gene fgfr3 mRNA in leukemic cells and its clinical significance / 中国实验血液学杂志

This study was aimed to explore fgfr3 gene expression in leukemic cells and its clinical significance. The expression levels of fgfr3 mRNA in 4 leukemic cell lines and bone marrow samples from 96 patients with leukemia and 14 controls were assayed by RT-PCR. 96 patients with leukemia included 36 cases of acute myeloid leukemia (AML), 29 cases of acute lymphoblastic leukemia (ALL), 31 cases of chronic myelogenous leukemia (CML). The results indicated that fgfr3 gene could be detected in both K562 and U937 cell lines, but not in HL-60 and SHI-1 cell lines. The positive expression rates of fgfr3 mRNA in AL and CML were 46.15% and 51.61% respectively, and were higher than that in control (14.29%, p < 0.05). The positive expression rates of fgfr3 mRNA in AML and ALL were 44.44% and 48.28% respectively, and were higher than that in control (p < 0.05). The increased level of fgfr3 mRNA had a positive correlation with high white blood cell count of > or = 20 x 10(9)/L (p < 0.05). Higher fgfr3 mRNA expression positively correlated with fuse genes of bcr/abl in ALL (r = 0.151, p < 0.05). The expression of fgfr3 gene in AL was not related with chromosome abnormality. In conclusion, the over expression of fgfr3 gene exists in AL and CML patients, it suggests that fgfr3 gene may be partially involved in leukemogenesis.