Research progress of cell membrane-coated biomimetic nanoparticle delivery systems for the treatment of lung diseases / 药学学报

Lung is susceptible to external disturbance, resulting in a variety of acute and chronic lung diseases. Functionalized nanoparticles as carriers can carry drugs through multiple biological barriers of lung into lung lesions, but there are some problems such as poor targeting and low therapeutic efficiency. As a drug carrier, membrane-coated biomimetic nanoparticles have the characteristics of immune system escape, active targeting, inflammatory chemotaxis and crossing physiological barriers due to the retention of the characteristics of the source cells. Therefore, it has been widely used in the treatment of lung diseases in recent years. In this review, the application of membrane-coated biomimetic nanoparticles in the treatment of lung diseases in the recent years was summarized and classified. Cell membrane sources include erythrocyte membrane, platelet membrane, macrophage membrane, neutrophil membrane, lung epithelial membrane, lung surfactant, endothelial membrane, cancer cell membrane, bacterial membrane, hybrid membrane and so on. The purpose of this review is to provide a new idea for treating lung diseases with membrane-coated biomimetic nanoparticles.

Diagnostic value of serum TIM-3 in patients with liver cancer / 国际肿瘤学杂志

Objective:To analyze the changes of T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) in serum of patients with liver cancer and its diagnostic value.Methods:From March 2021 to May 2021, 37 patients with viral hepatitis type B (hepatitis B group) , 44 patients with liver cirrhosis (liver cirrhosis group) and 27 patients with liver cancer (liver cancer group) were selected in the Second Affiliated Hospital of Air Force Medical University, and 35 healthy subjects who underwent physical examination during the same period were selected as the healthy control group. The serum alpha fetoprotein (AFP) , liver function indexes and TIM-3 levels were detected, and the differences among groups were analyzed. The correlations between TIM-3 and AFP and liver function indexes were analyzed by Spearman correlation. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of TIM-3 in liver cancer.Results:There was a statistically significant difference in AFP among the hepatitis B group, liver cirrhosis group and liver cancer group ( χ2=11.75, P=0.003) . There were statistically significant differences in total bilirubin ( χ2=22.85, P<0.001) , direct bilirubin ( χ2=25.90, P<0.001) , indirect bilirubin ( χ2=19.92, P<0.001) , alanine aminotransferase ( χ2=36.64, P<0.001) , aspertate aminotransferase ( χ2=26.26, P<0.001) , aspertate aminotransferase/alanine aminotransferase ( χ2=34.67, P<0.001) and total bile acid ( χ2=13.10, P<0.001) among the hepatitis B group, liver cirrhosis group and liver cancer group. The serum levels of TIM-3 in the healthy control group, hepatitis B group, liver cirrhosis group and liver cancer group were 11.1 (4.2, 14.4) ng/ml, 12.7 (4.3, 23.9) ng/ml, 11.4 (3.4, 17.0) ng/ml and 15.7 (10.5, 21.2) ng/ml, with a statistically significant difference ( χ2=11.85, P=0.008) . There were statistically significant differences between the liver cancer group and healthy control group and liver cirrhosis group (both P<0.05) . Spearman correlation analysis showed that TIM-3 had no correlation with AFP in the four groups ( r=0.05, P=0.791; r=0.18, P=0.497; r=0.03, P=0.883; r=0.24, P=0.396) . There were correlations between serum TIM-3 and total protein in the healthy control group ( r=0.36, P=0.036) , serum TIM-3 and globulin in the hepatitis B group ( r=0.35, P=0.034) , and serum TIM-3 and total bile acid in the liver cancer group ( r=0.46, P=0.017) . ROC curve analysis showed that the sensitivity of serum TIM-3 for the diagnosis of liver cancer was 48.10%, and the specificity was 91.43%, when taking healthy subjects as the control group. The sensitivity of serum TIM-3 for the diagnosis of liver cancer was 96.30%, and the specificity was 41.77%, when taking healthy subjects and liver cirrhosis patients as the control group. The sensitivity of serum TIM-3 for the diagnosis of liver cancer was 96.30%, and the specificity was 40.52%, when taking healthy subjects, hepatitis B patients and liver cirrhosis patients as the control group. Conclusion:The serum level of TIM-3 in patients with liver cancer is significantly increased, which has certain diagnostic value for liver cancer, and can be used as a diagnostic marker and potential therapeutic target for liver cancer patients.

Effect of panlong needling at Jiaji (EX-B 2) on motor dysfunction in patients with Parkinson's disease of liver and kidney deficiency: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the curative effect of panlong needling at Jiaji (EX-B 2) combined with western medication and western medication alone on motor dysfunction in patients with Parkinson's disease (PD) of liver and kidney deficiency.@*METHODS@#A total of 98 patients with PD were randomly divided into an acupuncture and medication group (49 cases, 1 case dropped off) and a western medication group (49 cases,1 case was removed). The patients in the western medication group were given oral of levodopa and benserazide hydrochloride tablets, 125 mg each time, three times a day in the 1st week, and the dose was increased according to the needs of the patients' condition from the 2nd week until 250 mg each time, three times a day, for 16 consecutive weeks. On the basis of the same western medication treatment as the western medication group, panlong needling was applied at Jiaji (EX-B 2) from C2 to L5 in the acupuncture and medication group, once a day, 20 times as a course of treatment, for 4 consecutive courses. The scores of unified Parkinson's disease rating scale (UPDRS-Ⅲ, UPDRS-Ⅳ), TCM symptoms score, and 39-item Parkinson's disease questionnaire (PDQ-39) score were evaluated before treatment, after treatment and during follow-up of 1 month after treatment, respectively. The safety of the two groups was compared.@*RESULTS@#After treatment and during follow-up, except the PDQ-39 score of the western medication group, the scores of UPDRS-Ⅲ, UPDRS-Ⅳ, TCM syndrome and PDQ-39 were lower than those before treatment in the two groups (P<0.05), and the scores of above indexes in the acupuncture and medication group were lower than those of the western medication group (P<0.05). The total incidence of adverse reactions in the acupuncture and medication group was 10.4% (5/48), which was lower than 29.2% (14/48) in the western medication group (P<0.05).@*CONCLUSION@#Panlong needling at Jiaji (EX-B 2) combined with western medication could significantly improve the motor dysfunction and clinical symptoms, improve the quality of life and has high safety, and the efficacy is superior to western medication alone.

Effects of Dasatinib on the Maturation of Monocyte-Derived Dendritic Cells Derived from Healthy Donors and Chronic Myelogenous Leukemia Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of dasatinib on the maturation of monocyte-derived dendritic cells (moDCs) derived from healthy donors (HDs) and chronic myelogenous leukemia (CML) patients.@*METHODS@#Peripheral blood mononuclear cells (PBMCs) were isolated from HDs (n=10) and CML patients (n=10) who had got the remission of MR4.5 with imatinib treatment. The generation of moDCs from PBMCs was completed after 7 days of incubation in DC I culture medium, and another 3 days of incubation in DC II culture medium with or without 25 nmol/L dasatinib. On the 10th day, cells were harvested and expression of molecules of maturation related marker were assessed by flow cytometry. The CD80+CD86+ cell population in total cells was gated as DCs in the fluorescence-activated cell storting (FACS) analyzing system, then the expression of CD83, CD40 or HLA-DR in this population was analyzed respectively.@*RESULTS@#The proportion of CD80+CD86+ cells in total cells didn't show a statistical difference between HD group and patient group (89.46%±9.70% vs 87.39%±9.34%, P=0.690). Dasatinib significantly enhanced the expression of the surface marker CD40 (P=0.008) and HLA-DR (P=0.028) on moDCs derived from HDs compared with the control group, while the expression of CD83 on moDCs didn't show a significant difference between dasatinib group and the control group (P=0.428). Meanwhile, dasatinib significantly enhanced the expression of the surface marker CD40 (P=0.023), CD83 (P=0.038) and HLA-DR (P=0.001) on moDCs derived from patients compared with the control group.@*CONCLUSION@#For CML patients, the same high proportion of moDCs as HDs can be induced in vitro, which provides a basis for the application of DC-based immunotherapy strategy. Dasatinib at the concentration of 25 nmol/L can efficiently promote the maturation of moDCs derived from HDs and CML patients in vitro. Dasatinib shows potential as a DC adjuvant to be applied in DC-based immunotherapy strategies, such as DC vaccine and DC cell-therapy.

A study on the association of postprandial hypotension with insulin and neurotensin in very old adults / 中华老年医学杂志

Objective:To investigate the association of postprandial hypotension(PPH)with insulin and neurotensin(NT)in very old adults.Methods:In this retrospective study, 22 people with PPH and 21 without non-PPH, aged ≥80, were enrolled from patients hospitalized at the First Division of the Health Department of China-Japan Friendship Hospital between September 2015 and October 2021.The levels of blood pressure, blood glucose, insulin and NT at fasting and 30, 60, 90 and 120 minutes after a meal were monitored.Changes in values of each parameter before and after a meal were compared between the two groups, and the correlation of the maximum decrease in postprandial blood pressure with the maximum increase in blood glucose, insulin and neurotensin was analyzed.Results:The maximum decrease in postprandial systolic blood pressure(SBP)in the PPH group was significantly higher than that in the non-PPH group[(35.5±13.2)mmHg(1 mmHg=0.133 kPa) vs.(16.0±8.6)mmHg, t=4.135, P<0.01)]. The maximum increase in postprandial insulin was significantly higher than that in the non-PPH group[(20.9±4.2)mU/L vs.(12.1±4.1)mU/L, t=3.949, P<0.01)]. There was no statistically significant difference between the PPH and non-PPH groups in the maximum increase in postprandial blood glucose[(3.6±1.8)mmol/L vs.(2.5±0.5)mmol/L, t=1.912, P>0.05)]or NT[65.7(22.0, 110.1)ng/L vs.112.2(47.2, 270.2)ng/L, Z=1.817, P>0.05)]. There was a significant positive correlation between the maximum decrease in postprandial systolic blood pressure and the maximum increase in insulin( r=0.907, P<0.05). There was no correlation between the maximum decrease in postprandial systolic blood pressure and the maximum increase in blood glucose( r=0.016, P>0.05). There was no correlation between the maximum decrease in postprandial systolic blood pressure and the maximum increase in NT( r=0.396, P>0.05). Conclusions:The PPH is related to abnormal increases in postprandial insulin secretion.

Clinical efficacy of 585 nm Q-switched laser treatment on inflammatory lesion and postinflammatory erythema of acne vulgaris / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the efficacy and safety of 585 nm Q-switched laser in the treatment of acne inflammatory lesions and postinflammatory erythema.@*METHODS@#A total of 25 patients with moderate facial acne, symmetrical distribution of inflammatory lesions and postinflammatory erythema on both sides of the face, were enrolled. Among the 25 patients, 22 patients completed all the treatment and evaluation, and 3 patients were lost to follow-up. 585 nm Q-switched laser was used on a randomly selected side of the face for three times of treatment at a 2 week interval. The evaluations were made before each treatment, 2 and 4 weeks after the last treatment, therefore the evaluation time points were before the treatment, weeks 2, 4, 6, and 8, respectively, for a total of 5 times. Acne severity was assessed using the investigator' s global assessment (IGA) score, and erythema severity was assessed using the investigator' s subjective erythema score and narrow-spectrum reflectance spectrophotometer at each follow-up.@*RESULTS@#After 3 times of treatment, there was statistically significant difference between the IGA score in week 8 and before treatment on both sides(Z=2.64, P < 0.01; Z=2.67, P < 0.01). There was no significant difference in IGA score between the treatment side and the control side before treatment and in week 8 (P=0.59, P=0.26). There was statistically significant difference between the investiga-tor' s subjective erythema score in week 8 and before treatment on the treatment side(Z=4.24, P < 0.01), while no significant difference was showed on the control side(Z=1.73, P=0.08). In week 8, the investigator's subjective erythema score of the treatment side was lower than that of the control side (Z=3.61, P < 0.01). The erythema index of the treatment side was significantly decreased at 5 time points (P < 0.01), and the index decreased significantly in week 8 compared with the index before treatment (P < 0.01), while the erythema index of the control side was not significantly different at 5 time points. The treatment related adverse events included erythema and edema after treatment and pain during treatment, the severity was mild to moderate, which resolved spontaneously within 1 to 3 days. Nine patients were very satisfied with the treatment, 7 patients were satisfied, and 6 patients considered average.@*CONCLUSION@#585 nm Q-switched laser has some effect in the treatment of postinflammatory erythema, and it ensures good tolerance and safety. There was no statistically significant difference between the treatment side and the control side on the improvement of acne inflammatory lesions.

Research advances on exosomes derived from adipose-derived mesenchymal stem cells in promoting diabetic wound healing / 中华烧伤杂志

Impaired healing of diabetic wounds is mainly attributed to its pathological mechanism, and refractory diabetic wounds bring heavy burdens to patients and society. Exosomes derived from stem cells possess the similar ability as stem cells in promoting tissue regeneration and more clinical advantages and are gradually playing important roles in wound healing. In recent years, researches have shown that exosomes derived from adipose-derived mesenchymal stem cells (ADSC-EXOs) can promote the healing of diabetic wounds by participating in various processes of wound healing. This article reviews the pathological mechanism leading to impaired healing of diabetic wounds, the related mechanism and the application prospect of ADSC-EXOs in promoting diabetic wound healing.

A pretest model of obstructive coronary artery disease based on machine learning: from the C-Strat study / 中华内科杂志

Objective:To develop a pretest probability model of obstructive coronary artery disease with machine learning based on multi-site Chinese population data.Methods:Chinese regiStry in early deTection and Risk strAtificaTion of coronary plaques (C-Strat) study is a prospective multi-center cohort study, in which consecutive patients with suspected obstructive coronary artery disease and ≥64 detector row coronary computed tomography angioplasty (CCTA) evaluation were included. Data from the patients were randomly split into a training set (70%) and a test set (30%). More than 50% of coronary artery stenosis by CCTA was defined as positive outcome. A boosted ensemble algorithm (XGBoost), 10-fold cross-validation and Bayesian optimization were used to establish a new prediction model-CARDIACS(pretest probability model from Chinese registry in eARly Detection and rIsk stratificAtion of Coronary plaques Study), and a logistic regression was used to establish a model-LOGISTIC in training set. The test set was used for validation and comparison among CARDIACS, LOGISTIC, UDFM (updated Diamond-Forrester Model) and DFCASS(Diamond-Forrester and CASS).Results:The study population included 29 455 patients with age of (57.0±9.7) years and 44.8% women, of whom 19.1% (5 622/29 455) had obstructive coronary artery disease. For CARDIACS, the age, the reason for visit and the body mass index (BMI) were the most important predictive variables. In the independent test set, the area under the curve (AUC) of CARDIACS was 0.72 (95% CI 0.70-0.73), which was significantly superior to that of LOGISTIC (AUC 0.69, 95% CI 0.68-0.71, P=0.015), UDFM (AUC 0.64, 95% CI 0.62-0.65, P<0.001) and DFCASS (AUC 0.66, 95% CI 0.64-0.67, P<0.001), respectively. Conclusion:Based on Chinese population, the study developed a new pretest probability model--CARDIACS, which was superior to the traditional models. CARDIACS is expected to assist in the clinical decision-making for patients with stable chest pain.

Positive role and ethical problems of artificial intelligence in ophthalmology / 国际眼科杂志(Guoji Yanke Zazhi)

@#Artificial intelligence is described as the“fourth industrial revolution”. Driven by the development of the Internet and big data, ophthalmology has become a frontier discipline in this wave, showing a good prospect of vigorous development. Artificial intelligence has been applied to the auxiliary screening, diagnosis and treatment of a variety of eye diseases, and assisted in the completion of corneal, refractive, cataract and other related operations; Help realize graded diagnosis and treatment, telemedicine and improve the training mode of ophthalmic talents, and participate in eye health management and ophthalmic education. While artificial intelligence brings benefits to mankind, it also brings a number of ethical problems, among which the contradictions related to medical ethics, such as the division of responsibility for diagnosis and treatment errors, the protection of patient information privacy, humanistic care and its fairness, the contradiction between the growing artificial intelligence and imperfect ethics and laws are particularly prominent. Artificial intelligence must be guided by the correct value and abide by the corresponding ethical norms to continue to mature and improve in clinical practice. This paper summarizes the development status and ethical dilemma of ophthalmology under the background of artificial intelligence to provide reference for promoting its healthy development in the field of ophthalmology.

Broussonetiae Fructus Protects Against APAP-induced Liver Injury in Mice by Inhibiting Endoplasmic Reticulum Stress Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Broussonetiae Fructus （BF） in preventing and treating drug-induced liver injury （DILI） induced by acetaminophen （APAP） through the endoplasmic reticulum stress pathway. MethodSixty C57BL/6N mice were randomly divided into normal group， model group， silybin group （3.4 g·kg-1）， and high-， medium- and low-dose BF groups （3.0， 1.5， 0.75 g·kg-1）， with 10 mice in each group. The DILI model was induced by intragastric administration of APAP at 800 mg·kg-1， and drugs were administered simultaneously for 10 consecutive days. The serum contents or activities of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBIL）， and direct bilirubin （DBIL） were measured. Hematoxylin-eosin（HE） staining was performed to observe the pathological changes in liver tissues. The morphological changes in liver mitochondria were observed by transmission electron microscopy. The activities or content of superoxide dismutase （SOD）， malondialdehyde （MDA）， total antioxidant capacity （T-AOC）， glutathione （GSH）， glutathione disulfide （GSSG）， glutathione peroxidase （GSH-Px）， and adenosine triphosphate （ATP） in the serum and liver tissues were detected by the colorimetric method. The expression of reactive oxygen species （ROS） in liver tissues was detected by immunofluorescence. The gene expression of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and c-Jun N-terminal kinase （JNK） in liver tissues was detected by Real-time quantitative polymerase chain reaction （PCR）. ResultCompared with the normal group， the model group showed increased serum activities or content of ALT， AST， TBIL， and DBIL （P<0.01）， increased MDA and GSSG contents （P<0.01）， decreased contents or activities of SOD， T-AOC， GSH， GSH-Px， and ATP （P<0.01）， swollen hepatocytes with inflammatory infiltration and lamellar necrosis， swollen and broken mitochondria of hepatocytes， and increased mRNA expression of GRP78， CHOP， and JNK （P<0.01）. Compared with the model group， the groups with drug intervention showed decreased serum content or activities of ALT， AST， TBIL， and DBIL （P<0.05， P<0.01）， reduced MDA and GSSG contents（P<0.05， P<0.01）， and increased contents or activities of SOD， T-AOC， GSH， GSH-Px， and ATP （P<0.05， P<0.01）， improved swollen hepatocytes， inflammatory infiltration， and lamellar necrosis， recovered bilayer membrane structure in mitochondria of hepatocytes， and decreased mRNA expression of GRP78， CHOP， and JNK （P<0.05， P<0.01）. ConclusionBF has preventive and therapeutic effects on APAP-induced DILI mice， and the mechanism may be related to the reduction of endoplasmic reticulum stress and oxidative stress level in vivo.

Effect of Wumeiwan-medicated Serum on Proliferation， Invasion， Migration， Apoptosis of Pancreatic Cancer Cells Based on PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effects of Wumeiwan-medicated serum on the proliferation， invasion， migration， and apoptosis of human pancreatic cancer SW1990 cells and explore the underlying mechanism. MethodThe Wumeiwan-medicated serum was prepared and the pancreatic cancer SW1990 cell line was cultured in vitro. The optimal time of Wumeiwan-medicated serum was selected for subsequent experiments by cell counting kit-8（CCK-8）. SW1990 cells were divided into a control group and low- （2%）， medium- （4%）， and high-dose （8%） Wumeiwan-medicated serum groups. The colony-forming， migration， and invasion abilities were detected by clonogenic assay， wound healing assay， and transwell migration assay. Flow cytometry was used to detect the effect of Wumeiwan-medicated serum on the apoptosis of pancreatic cancer SW1900 cells. Western blot was used to detect the expression levels of apoptosis-related proteins， such as B-cell lymphoma-2（Bcl-2）， Bcl-2-associated X protein （Bax）， cytochrome C （Cyt C）， cleaved cysteinyl aspartate-specific protease-3 （cleaved Caspase-3）， cleaved cysteinyl aspartate-specific protease-9 （cleaved Caspase-9）， as well as phosphatidylinositol 3-kinase（PI3K）， phosphorylated PI3K（p-PI3K）， protein kinase B （Akt）， and phosphorylated Akt（p-Akt）in PI3K/Akt pathway in SW1990 cells. ResultCompared with blank group， Wumeiwan groups showed decreased absorbance （A） 72 h after drug intervention （P<0.01）. Compared with the low-dose group， the medium- and high-dose groups showed decreased A （P<0.01）. Compared with the medium-dose group， the high-dose group showed decreased A （P<0.01）. It indicates that Wumeiwan can inhibit SW1990 cell proliferation in a dose-dependent manner after 72 h， and the optimal action time is 72 h. Compared with the blank group， the Wumeiwan groups showed weakened invasion of SW1990 cells （P<0.01）， reduced colony-forming and migration abilities （P<0.05， P<0.01） in a dose-dependent manner， and increased total apoptosis rates （P<0.01）. The inducing effect of Wumeiwan on apoptosis increased with the increase in dosage. Compared with the blank group， the Wumeiwan groups showed decreased protein expression of Bcl-2 （P<0.01）， increased protein expression of cleaved Caspase-3， cleaved Caspase-9， Cyt C， and Bax （P<0.05， P<0.01） in a certain dose-effect relationship， reduced protein expression of p-PI3K and p-Akt （P<0.05， P<0.01） with the increase in dosage， and declining p-PI3K/PI3K and p-Akt/Akt （P<0.05， P<0.01） with the increase in dosage. ConclusionWumeiwan-medicated serum can significantly inhibit the malignant biological behaviors of pancreatic cancer SW1990 cells and induce apoptosis. The mechanism may be related to the inhibition of the PI3K/Akt signaling pathway and down-regulation of protein phosphorylation level in the PI3K/Akt signaling pathway.

Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF- κ B and PI3K/AKT Signaling In Vitro and In Vivo / 中国结合医学杂志

OBJECTIVE@#To explore the influences of andrographolide (Andro) on bladder cancer cell lines and a tumor xenograft mouse model bearing 5637 cells.@*METHODS@#For in vitro experiments, T24 cells were stimulated with Andro (0-40 µmol/L) and 5637 cells were stimulated with Andro (0 to 80 µmol/L). Cell growth, migration, and infiltration were assessed using cell counting kit-8, colony formation, wound healing, and transwell assays. Apoptosis rate was examined using flow cytometry. In in vivo study, the antitumor effect of Andro (10 mg/kg) was evaluated by 5637 tumor-bearing mice, and levels of nuclear factor κ B (NF- κ B) and phosphoinositide 3-kinase/AKT related-proteins were determined by immunoblotting.@*RESULTS@#Andro suppressed growth, migration, and infiltraion of bladder cancer cells (P⩽0.05 or P⩽0.01). Additionally, Andro induced intrinsic mitochondria-dependent apoptosis in bladder cancer cell lines. Furthermore, Andro inhibited bladder cancer growth in mice (P⩽0.01). The expression of p65, p-AKT were suppressed by Andro treatment in vitro and in vivo (P⩽0.05 or P⩽0.01).@*CONCLUSIONS@#Andrographolide inhibits proliferation and promotes apoptosis in bladder cancer cells by interfering with NF- κ B and PI3K/AKT signaling in vitro and in vivo.

Clinical Analysis of Bloodstream Infection after Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics of bloodstream infection (BSI) in patients treated by hematopoietic stem cell transplantation (HSCT).@*METHODS@#The clinical characteristics, distribution of pathogenic bacteria causing BSI and drug sensitivity of 910 patients treated by HSCT in our department from January 2013 to June 2020 were retrospectively analyzed.@*RESULTS@#Among 910 HSCT patients, 111 patients were diagnosed as BSI within 100 days after transplantation, and 98 patients showed BSI during the period of agranulocytosis. Multivariate analysis showed that the usage of anti-thymocyte globulin (ATG), long duration of agranulocytosis and low infusion volume of mononuclear cell (MNC) were the independent risk factors affecting BSI after HSCT. Among 121 pathogenic bacteria isolated, 76 Gram-negative (G-) bacteria (62.8%), 40 Gram-positive (G+) bacteria (33.0%), and 5 fungi (4.1%) were detected out. The top three pathogens were Escherichia coli, Staphylococcus epidermidis and Pseudomonas aeruginosa. The drug-resistance rates of Escherichia coli and Klebsiella pneumoniae to carbapenems was 14.3% and 7.7%, respectively, and Pseudomonas aeruginosa was 66.7%. The susceptibility of G+ bacteria to vancomycin, linezolid and teicoplanin was 97.5%, 100% and 100%, respectively. The crude mortality rate of the patients with BSI at 100 days after HSCT was significantly higher than that of patients without BSI (P<0.001).@*CONCLUSION@#The usage of ATG, long duration of agranulocytosis and low infusion volume of MNC are independent risk factors for BSI after HSCT. The pathogens after HSCT are mainly G- bacteria. Pseudomonas aeruginosa is highly resistant to carbapenems. Key words　　;

Application of ultrasound-guided endoscopic retrograde appendicitis therapy in children with appendix-related chronic abdominal pain / 中国当代儿科杂志

OBJECTIVES@#To study the clinical efficacy of ultrasound-guided endoscopic retrograde appendicitis therapy in children with appendix-related chronic abdominal pain.@*METHODS@#A retrospective analysis was performed on the medical data of 30 children with the chief complaint of chronic abdominal pain who were admitted from August 2019 to May 2021. All the children were found to have inflammation of the appendix or intracavitary stool and fecalith by ultrasound and underwent ultrasound-guided endoscopic retrograde appendicitis therapy. The medical data for analysis included clinical manifestations, endoscopic findings, white blood cell count, neutrophil percentage, length of hospital stay, and cure rate.@*RESULTS@#Among the 30 children with chronic abdominal pain, there were 13 boys (43%) and 17 girls (57%), with a mean age of (9±3) years (range 3-15 years) at diagnosis. The median duration of the disease was 12 months, and the median length of hospital stay was 3 days. The children had a median white blood cell count of 6.7×109/L and a neutrophil percentage of 50%±13%. Fecalith and a large amount of feces were flushed out of the appendix cavity for 21 children (70%) during surgery. The follow-up rate was 97% (29/30), and the median follow-up time was 11 months (range 5-26 months). Of the 29 children, abdominal pain completely disappeared in 27 children (93%).@*CONCLUSIONS@#Ultrasound-guided endoscopic retrograde appendicitis therapy is effective in children with chronic abdominal pain caused by feces or fecalith in the appendix cavity.

Prevalence of gene mutations in a Chinese 46,XY disorders of sex development cohort detected by targeted next-generation sequencing / 亚洲男科学杂志(英文版)

46,XY disorders of sex development (DSD) is characterized by incomplete masculinization genitalia, with gonadal dysplasia and with/without the presence of Müllerian structures. At least 30 genes related to 46,XY DSD have been found. However, the clinical phenotypes of patients with different gene mutations overlap, and accurate diagnosis relies on gene sequencing technology. Therefore, this study aims to determine the prevalence of pathogenic mutations in a Chinese cohort with 46,XY DSD by the targeted next-generation sequencing (NGS) technology. Eighty-seven 46,XY DSD patients were enrolled from the Peking Union Medical College Hospital (Beijing, China). A total of fifty-four rare variants were identified in 60 patients with 46,XY DSD. The incidence of these rare variants was approximately 69.0% (60/87). Twenty-five novel variants and 29 reported variants were identified. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, thirty-three variants were classified as pathogenic or likely pathogenic variants and 21 variants were assessed as variants of uncertain significance. The overall diagnostic rate was about 42.5% based on the pathogenic and likely pathogenic variants. Androgen receptor (AR), steroid 5-alpha-reductase 2 (SRD5A2) and nuclear receptor subfamily 5 Group A member 1 (NR5A1) gene variants were identified in 21, 13 and 13 patients, respectively. The incidence of these three gene variants was about 78.3% (47/60) in patients with rare variants. It is concluded that targeted NGS is an effective method to detect pathogenic mutations in 46,XY DSD patients and AR, SRD5A2, and NR5A1 genes were the most common pathogenic genes in our cohort.

Observation on the efficacy of Nd:YAG laser peripheral iridotomy in the treatment of drug-uncontrollable PACG in acute attack / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To explore the effects of Nd:YAG laser peripheral iridotomy(LPI)in the treatment of drug-uncontrollable primary angle-closure glaucoma(PACG)in acute attack.<p>METHODS: A prospective study was conducted on 22 eyes of 20 patients with drug-refractory primary angle-closure glaucoma treated in the Department of Ophthalmology of Xiangyang No.1 People's Hospital from May 2019 to June 2020. All subjects underwent Nd:YAG LPI. Visual acuity, intraocular pressure, chamber angle closure range, anterior chamber angle(ACA), anterior chamber volume(ACV), central anterior chamber depth(CACD)and peripheral anterior chamber depth(PACD)were measured before and after the operation. And observe the complications of LPI.<p>RESULTS:All patients can implement LPI. All subjects' chamber angle closure range were >180° before LPI and 9 eyes(41%)were ≤180° after LPI. The intraocular pressure of 21 eyes(95%)had significantly lower than postoperative(<i>P</i><0.05). Postoperative anterior chamber parameters such as ACA, ACV and PACD were increased(<i>P</i><0.05). During the operation,15 eyes(68%)had iris cascade or silk hemorrhage and 5 eyes(23%)had corneal epithelial damage.<p>CONCLUSION: LPI has high safety and can be implemented in the acute attack stage of drug-uncontrollable PACG. It can reduce intraocular pressure effectively and relieve symptoms, which has a significant effect in the patients.

Input-output efficiency analysis for children′s diagnosis and treatment service at 27 community health service centers in China / 中华医院管理杂志

Objective:To provide strategic suggestions for optimizing children′s diagnosis and treatment services in the communities, by means of analyzing the overall efficiency of children′s diagnosis and treatment services in the sample community health service centers, and learning the current input and output of children′s diagnosis and treatment resources.Methods:In April 2020, a total of 27 community health service centers in 14 cities were selected by random sampling. Data such as the number of medical visits by children aged 0 to 18 years and the area of pediatric diagnosis and treatment departments in the sample centers in 2019 were collected by self-filling questionnaires. Excel was used for data sorting. Data envelopment analysis(DEA) was used for data processing. The data processing tool was DEAP 2.1.Results:The average comprehensive efficiency, the average technical efficiency and the average scale efficiency of the 27 sample community health service centers were 0.445, 0.865 and 0.494 respectively. There were five DEA efficient centers, 4 DEA weak inefficiency centers and 18 inefficient centers. Six out of 18 DEA inefficient centers had redundant input of healthcare professionals capable pediatrics; 12 centers were short of children visits, and 15 were short of visits by children aged 0-6 years.The centers where DEA was inefficient were concentrated in the central region, the suburbs and " centers with independent pediatric clinics but without pediatric wards" .Conclusions:The comprehensive efficiency of children′s diagnosis and treatment services in the sample community health service centers is relatively low. Currently, the sample community health service centers are faced with such problems as small and insufficient input of children′s diagnosis and treatment resources in the community, unbalanced development of children′s diagnosis and treatment services in the region among others. It is suggested that on the basis of making full use of the existing resources to create the maximum output value, we should consider appropriately expanding the scale of resource input to improve the efficiency of children′s diagnosis and treatment services at the primary level and further give play to the value of the " gatekeepers" at the primary level in children′s diagnosis and treatment.

Comparative analysis of endoscopic ligation and tissue adhesive injection for tortuous gastric varices / 中华消化内镜杂志

Objective:To evaluate the risks and benefits of endoscopic ligation and tissue adhesive injection for tortuous gastric varices.Methods:A total of 193 patients with esophagogastric varices, who underwent endoscopic variceal ligation or endoscopic tissue adhesive injection in Department of Gastroenterology of the First Affiliated Hospital of Anhui Medical University from June 2015 to June 2020, were included in the retrospective analysis. These cases were connected vessels (type Le and gf based on LDRf standard) of tortuous gastric varices (F1 in Hashizume standard). According to the treatment, the patients were divided into three groups: gastric fundus and esophageal ligation group (endoscopic ligation of gastric fundus and esophageal varices, 32 cases), tissue adhesive group (endoscopic tissue adhesive injection of gastric varices, endoscopic ligation of esophageal varices, 71 cases) and esophageal ligation group (endoscopic ligation of esophageal varices, 90 cases). The re-bleeding rate, the effectiveness rate, the significant effectiveness rate and complications of the three groups were compared.Results:The rates of re-bleeding in gastric fundus and esophageal ligation group, tissue adhesive group and esophageal ligation group were 18.75% (6/32), 12.68% (9/71) and 3.33% (3/90), respectively.There was significant difference only between gastric fundus and esophageal ligation group and esophageal ligation group ( χ2=6.110, P<0.016). The effectiveness rates of the three groups were all 100.00%. The significant effectiveness rates in gastric fundus and esophageal ligation group, tissue adhesive group and esophageal ligation group were 37.50% (12/32), 25.35% (18/71) and 14.44% (13/90), respectively. There was significant difference only between gastric fundus and esophageal ligation group and esophageal ligation group ( χ2=7.702, P<0.016). No pulmonary infection, hepatic encephalopathy, spontaneous bacterial peritonitis or perforation occurred in the three groups.The incidences of chest pain or abdominal pain in gastric fundus and esophageal ligation group, tissue adhesive group and esophageal ligation group were 18.75% (6/32), 11.27% (8/71) and 2.22% (2/90), respectively.There was significant difference only between gastric fundus and esophageal ligation group and esophageal ligation group ( χ2=10.524, P<0.016). There was no significant difference in the incidence of fever, nausea or vomiting among the three groups ( P>0.05). Conclusion:Simultaneous endoscopic ligation of gastric fundus and esophageal varices, and endoscopic tissue adhesive injection of gastric varices combined with endoscopic ligation of esophageal varices is of no benefit for patients with tortuous gastric varices, but endoscopic ligation of esophageal varices alone may yield more benefit.

Three patients with ectopic corticotropin-releasing hormone(CRH)syndrome due to medullary thyroid carcinoma and literature review / 中华内分泌代谢杂志

Objective:To investigate the pathogenesis of Cushing′s syndrome induced by medullary thyroid carcinoma.Methods:Started from April 2011 to present, three medullary thyroid carcinoma patients with Cushing′s syndrome were enrolled in this study. All patients were 40 to 50 years old, one female and two males. The blood pressure, blood glucose, thyroid function and antibodies, calcitonin, and carcinoembryonic antigen(CEA)were detected. The qualitative and localized diagnosis of Cushing′s syndrome was performed by high- and low-dose dexamethasone suppression tests as well as imaging examinations. The biopsies of all patients were taken to test the immunostaining of calcitonin, adrenocorticotropin(ACTH), and corticotropin-releasing hormone(CRH).Results:According to the clinical manifestation and function tests, three patients were diagnosed as medullary thyroid carcinoma accompanied by ACTH-dependent Cushing′s syndrome. All patients showed positive immunohistochemical staining of calcitonin and CRH, with negative immunostaining of ACTH in one and positive immunostaining of ACTH in two patients. Therefore, the diagnosis of ectopic CRH syndrome caused by medullary thyroid carcinoma was definite.Conclusions:Medullary thyroid carcinoma is a rare cause of Cushing′s syndrome. Tumor cells secrete ACTH and CRH, which in turn cause hypercorticoremia. Ectopic CRH syndrome is very rare. Early diagnosis can be made by immunohistochemical staining of biopsy tissues to guide early targeted treatment and improve the prognosis.

Correlation analysis of chronic obstructive pulmonary disease with inositol 1, 4, 5-trisphosphate 3-kinase C and phospholipase c-like 1 gene polymorphisms in elderly population / 中华老年医学杂志

Objective:To investigate the correlations of stable chronic obstructive pulmonary disease(COPD)with inositol 1, 4, 5-trisphosphate 3-kinase C(ITPKC)and phospholipase C-like 1 protein(PLCL1)single nucleotide polymorphisms(SNPs)in the Han elderly population in Ningxia.Methods:A case-control study was conducted.A total of 250 elderly patients with stable COPD were enrolled and divided into the COPD-related pulmonary hypertension(PH)group(n=103)and the COPD non-PH group(n=147). During the same period, 127 healthy elderly Han subjects were included as the control group.The ITPKC gene SNPs and the PLCL1 gene SNP were detected, and differences in alleles and genotype frequencies were compared between the groups.Results:The allele and genotype frequency distributions of rs2288450 and rs9789480 showed statistical differences between the COPD group and the control group(χ 2=6.09, 5.18, 30.14 and 32.89, P=0.048, 0.020, <0.001, <0.001). There was no difference in the allele and genotype frequency distributions of the ITPKC gene SNPs rs2290692 and rs17713068 between the control group and the COPD group(all P>0.05). The allele and genotype frequency distributions of rs9789480 showed differences between the COPD non-PH group and the COPD-PH group(χ 2=94.50 and 72.76, both P<0.001). There was no significant difference in the allele and genotype frequency distributions of rs2290692, rs17713068, rs2288450 between the COPD-PH group and the COPD non-PH group(all P>0.05). Conclusions:The ITPKC gene SNP rs2288450 CA and AA genotypes and A allele can reduce the incidence of COPD and may be a protective factor for COPD in the elderly.The PLCL1 gene SNP rs9789480 CA and AA genotypes and A allele can reduce the incidence of COPD and COPD-PH and may be a protective factor for COPD and COPD-PH in the elderly.