Nanosized copper particles induced mesangial cell toxicity via the autophagy pathway

Nanosized copper particles (nano Cu) have been incorporated into products in multiple industries, although studies have demonstrated that these particles are nephrotoxic. We investigated the cytotoxicity of nanosized copper particles on rat mesangial cells and measured rates of apoptosis, the expression of caspase-3, and generation of reactive oxygen species. We also measured autophagy through the acridine orange (AO) staining and expression of Beclin-1, microtubule-associated protein 1 light chain 3, and p62 to screen the underlying mechanism of toxicity. Nanosized copper particles inhibited mesangial cell viability, up-regulated the activity of caspase-3, and increased the rates of apoptosis and the generation of reactive oxygen species in a concentration-dependent manner. Exposure to nano Cu increased the formation of acidic vesicular organelles and the expression of Beclin-1, microtubule-associated protein 1 light chain 3, and p62, and treatment with an autophagy inhibitor reduced nephrotoxicity. This indicated that the autophagy pathway is involved in the toxicity induced by nanosized copper particles to mesangial cells. This finding can contribute to the development of safety guidelines for the evaluation of nanomaterials in the future.

Comparison of physical fitness and physiological function of children and adolescents with different nutritional status in Beijing Tianjin Hebei Region / 中国学校卫生

Objective@#To understand physical fitness and physiological function level of children and adolescents with different nutritional status in Beijing Tianjin Hebei Region, and to provide reference for physical health promotion and intervention of children and adolescents.@*Methods@#From September to December 2019, 4 424 children and adolescents aged 7-18 years old in Beijing Tianjin Hebei Region were tested for different nutritional status, physical fitness and physiological function by using stratified cluster sampling method.@*Results@#The detection rates of malnutrition, normal, overweight and obesity were 7.93%, 67.36% and 24.71%, respectively.There were differences in heart rate, systolic blood pressure, diastolic blood pressure, vital capacity body mass index, grip strength body mass index, oblique pull up/pull up, standing long jump, 50 m running, 1 000 m running, and BMI in boys with different nutritional status statistical significance ( Z =9.6, 55.2, 118.6, 332.5, 122.8, 15.6, 49.5, 47.5, 12.6, 113.5, P <0.01); There were differences in heart rate, systolic blood pressure, diastolic blood pressure, vital capacity body mass index, grip strength body mass index, sit up for 1 minute, standing long jump, 50 m running, 800 m running and physical fitness index in girls with different nutritional status statistical significance ( Z =33.9, 24.5, 46.5, 262.5, 102.6, 32.5, 27.5, 33.6, 27.6, 51.6, P <0.01). Correlation analysis showed that the nutritional status of boys was positively correlated with systolic blood pressure, diastolic blood pressure, 50 m running, and 1 000 m running ( r =0.27, 0.31, 0.14, 0.16, P <0.05), and was correlated with heart rate, vital capacity, body mass index, grip strength body mass index, oblique pull up/pull up, standing long jump, and BMI were negatively correlated ( r =-0.07, -0.62, -0.41, -0.21, -0.35, -0.29, P ＜0.05); nutritional status of girls it was positively correlated with systolic blood pressure, diastolic blood pressure, and 800 m running ( r =0.21, 0.27, 0.22, P <0.05), and negatively correlated with heart rate, vital capacity BMI, grip strength BMI, and BMI ( r =-0.12, -0.49, -0.32, -0.18, P <0.05).@*Conclusion@#The nutritional status of children and adolescents in Beijing Tianjin Hebei Region is related to physical fitness and physiological function. Overweight and obese child have lower physical fitness and physiological function. In the future, childhood overweight and obesity should be effectively controlled to better promote the development of physical fitness and physiological function.

Perioperative rehabilitation clinical pathway of acetabular fracture in light of the integration of orthopedics and rehabilitation: a prospective randomized control trial / 中国康复理论与实践

ObjectiveTo evaluate the efficacy and safety of a perioperative rehabilitation clinical pathway of acetabular fracture in light of orthopedics rehabilitation team approach. MethodsA prospective randomized control trial was conducted in 82 patients with acetabular fractures who had been admitted from the Emergency Department of Orthopaedic Trauma, Beijing Jishuitan Hospital from June, 2019 to January, 2021. The patients were randomly divided into control group (n = 41) and intervention group (n = 41). The control group was managed routinely, while the intervention group received the rehabilitation clinical pathway, for 24 weeks. The Visual Analogue Score (VAS) of pain, the Barthel Index (BI) and Majeed Pelvic Score were compared. ResultsFinally, 76 patients completed the trial. There was no statistical difference in VAS score between two groups in all periods (|Z| < 1.926, P > 0.05). The BI score was higher in the intervention group than in the control group at discharge, two weeks, six weeks and twelve weeks after operation (|Z| > 2.121, P < 0.05); and no significant difference was found before operation and 24 weeks after operation (|Z| < 1.862, P > 0.05). Majeed Pelvic Score was higher in the intervention group than in the control group two weeks, six weeks, twelve weeks and 24 weeks after operation (|Z| > 2.428, P < 0.05). Six, twelve and 24 weeks after operation, the excellent rate of Majeed Pelvic Score was higher in the intervention group than in the control group (χ2 > 6.136, P < 0.05). ConclusionIn comparison with traditional protocol in acetabular fracture, the perioperative rehabilitation clinical pathway was proved effective and of great safety in the light of the integration of orthopedics and rehabilitation mode for improving the function and activities of daily living of patients.

Influencing factors for occupational stress among frontline employees in a chemical fiber manufacturing enterprise / 预防医学

Objective @#To investigate the status of occupational stress and analyze its influencing factors among frontline employees working in a chemical fiber manufacturing enterprise, so as to provide insights into the development of occupational stress interventions. @*Methods @#The frontline employees working in a chemical fiber manufacturing enterprise were selected as the study subjects using a cluster sampling method in October 2018. The status of occupational stress was investigated using the Chinese version of the effort-reward imbalance ( ERI ) questionnaire. The influencing factors for occupational stress were identified using a multivariable logistic regression model. @*Results @#A total of 1 780 questionnaires were sent out, and 1 115 valid ones ( 62.64% ) were recovered. Among the 1 115 respondents, there were 427 men ( 38.30% ) and 688 women ( 61.70% ), and 71.22% were at ages of 21 to 39 years. There were 561 respondents with < 1 year of service ( 50.31% ), and the longest length of service was 11 years. In addition, there were 1 069 respondents ( 95.87% ) exposed to high noise, and 346 respondents ( 31.03% ) were diagnosed at a high occupational-stress state and 769 ( 68.97% ) at a low state. Multivariable logistic regression analysis identified 5 years or longer of service ( OR=1.540, 95%CI: 1.057-2.245 ) and exposure to high noise ( OR=1.917, 95%CI: 1.004-3.659 ) as risk factors for occupational stress among frontline employees in the chemical fiber manufacturing enterprise. @*Conclusions @#There are 31.03% of frontline employees at a high occupational-stress state in the chemical fiber manufacturing enterprise, and a high occupational-stress state is associated with exposure to high noise and 5 years or longer of service.

Functional outcomes of 100 patients with adenocarcinoma of the esophagogastric junction undergoing Cheng's GIRAFFE(®) reconstruction after proximal gastrectomy / 中华胃肠外科杂志

Objective: To investigate the functional outcomes and postoperative complications of Cheng's GIRAFFE reconstruction after proximal gastrectomy. Methods: A descriptive case series study was conducted. Clinical data of 100 patients with adenocarcinoma of the esophagogastric junction who underwent Cheng's GIRAFFE reconstruction after proximal gastrectomy in Cancer Hospital of University of Chinese Academy of Sciences (64 cases), Zhejiang Provincial Hospital of Chinese Medicine (24 cases), Lishui Central Hospital (10 cases), Huzhou Central Hospital (1 case) and Ningbo Lihuili Hospital (1 case) from September 2017 to June 2021 were retrospectively analyzed. Of 100 patients, 64 were males and 36 were females; the mean age was (61.3 ± 11.1) years and the BMI was (22.7±11.1) kg/m(2). For TNM stage, 68 patients were stage IA, 24 were stage IIA and 8 were stage IIB. Postoperative functional results and postoperative complications of radical gastrectomy with Giraffe reconstruction were analyzed and summarized. Gastroesophageal reflux disease questionnaire (RDQ) score and postoperative endoscopy were used to evaluate the occurrence of reflux esophagitis and its grade (grade N, grade A, grade B, grade C, and grade D from mild to severe reflux). The continuous data conforming to normal distribution were expressed as (mean ± standard deviation), and those with skewed distribution were presented as median (Q1, Q3). Results: All the 100 patients successfully completed R0 resection, including 77 patients undergoing laparoscopic surgery and 23 patients undergoing laparotomy. The Giraffe anastomosis time was (38.6±14.0) min; the blood loss was (73.0±18.4) ml; the postoperative hospital stay was 9.5 (8.2, 13.0) d; the hospitalization cost was (6.0±0.3) ten thousand yuan. Fourteen cases developed perioperative complications (14.0%), including 7 cases of pleural effusion or pneumonia, 3 cases of anastomotic leakage, 2 cases of gastric emptying disorder, 1 case of gastrointestinal hemorrhage and 1 case of anastomotic stenosis, who were all improved and discharged after symptomatic management. Patients were followed up for (33.3±1.6) months. Eight patients were found to have reflux symptoms by RDQ scale six months after surgery, and 11 patients (11/100,11.0%) were found to have reflux esophagitis by gastroscopy, including 6 in grade A, 3 in grade B, and 2 in grade C. All the patients could control their reflux symptoms with behavioral guidance or oral PPIs. Conclusion: Cheng's GIRAFFE reconstruction has good anti-reflux efficacy and gastric emptying function; it can be one of the choices of reconstruction methods after proximal gastrectomy.

Pretreatment evaluation of 18F-FDG PET-CT in extranodal NK/T-cell lymphoma / 中华肿瘤杂志

Objective: To investigate the clinical value of pretreatment 18F-fluorodeoxy glucose positron emission tomography/computed tomography (18F-FDG PET-CT) in extranodal NK/T-cell lymphoma. Methods: Eighty-one patients with pathologically confirmed extranodal NK/T-cell lymphoma and pretreatment with PET-CT scan in Cancer Hospital, Chinese Academy of Medical Sciences from August 2006 to December 2017 were enrolled in the study. The clinical, follow-up and imaging data were analyzed retrospectively. The relationship between maximum standard uptake value (SUVmax) and prognosis were evaluated by Mann-Whitney U test and Spearman rank correlation analysis. Results: Among the 81 patients, 98.8% (80/81) were upper aerodigestive tract (UAT) involved. Lesions at extra-UAT sites were detected in 7 cases, involving parotid gland (n=1), breast (n=1), spleen (n=1), pancreas (n=1), skin and subcutaneous soft tissue (n=1), muscle (n=1), lung (n=2) and bone (n=3). Lymph node involvement were demonstrated in 33 cases. All of the lesions had increased uptake of PET, the median SUVmax was 8.6. PET-CT changed staging in 15 cases, and 12 cases were adjusted treatment methods. 21 cases were changed radiotherapy target because of PET-CT. The 1-, 2-year progression-free survival (PFS) rates were 88.7% and 80.3% while 1-, 2-year overall survival (OS) rates were 97.2% and 94.4% respectively. The median SUVmax of patients with local lymph nodes involvement was significantly higher than those without local lymph nodes involvement (P=0.007). The SUVmax was positively associated with Ann Arbor stage (r=0.366, P=0.001), lactate dehydrogenase (r=0.308, P=0.005) and Ki-67 level (r=0.270, P=0.017). The SUVmax was inversely associated with lymphocyte count (r=-0.324, P=0.003) and hemoglobin content (r=-0.225, P=0.043). Conclusions: Extranodal NK/T-cell lymphoma predominantly occurs in extra-nodal organs, mainly in the upper respiratory and gastrointestinal tracts, with marked FDG-addiction. Compared with conventional imaging, 18F-FDG PET-CT is sensitive and comprehensive in detecting extra-nodal NK/T-cell lymphoma involvement, assisting in accurate clinical staging and treatment planning. Pretreatment SUVmax is potential for prognosis evaluation since it is correlated with prognostic factors.

Relationship between physical activity screen time and sleep duration and overweight and obesity among children and adolescents in Beijing Tianjin Hebei region / 中国学校卫生

Objective@#To investigate the relationship among physical activity, sleep duration and screen time and overweight and obesity among children and adolescents in Beijing Tianjin Hebei region, and to provide reference for children and adolescents in Beijing Tianjin Hebei region to maintain healthy physique.@*Methods@#In November 2019, 4 262 primary and secondary school students in Beijing Tianjin Hebei region were surveyed on physical activity, sleep status and screen time according to the physical activity guidelines for children and adolescents, and the relationship between overweight and obesity was analyzed by Logistic regression.@*Results@#The prevalence of overweight and obesity among children and adolescents in Beijing Tianjin Hebei region was 22.03%. The positive rate of overweight was 12.01% and obesity was 10.02%. The prevalence of overweight and obesity in male students (26.09%) was higher than that in female students (17.88%), the difference was statistically significant ( χ 2=41.77, P < 0.01 ). The prevalence of overweight and obesity in urban children (24.09%) and Han children (22.74%) was significantly higher than that in rural areas (21.05%) and ethnic minorities (17.70%) ( χ 2=5.00, 7.63, P <0.05). The proportion of children who met physical activity, screen time and sleep duration guideline was 24.85%, 38.69% and 57.09%, respectively. A total of 21.68% of children and adolescents did not meet the guideline of physical activity, screen time and sleep duration, among which 42.80% and 28.77% met the guideline for one or two out of three behaviors, respectively. Only 6.76% of children and adolescents met the guideline of all three behaviors. Logistic regression analysis showed that the risk of overweight and obesity was negatively correlated with sleep duration ( OR=0.72, 95%CI =0.52-0.98). The risk of overweight and obesity was lower in patients with 2 criteria than in those with less sleep duration and less screen time ( OR=0.57, 95%CI =0.36-0.87).@*Conclusion@#Percentage of sufficient physical activity among children and adolescents in Beijing Tianjin Hebei region is low, and ensuring sufficient sleep duration is helpful for overweight and obesity prevention. The impact of sleep duration and screen time on overweight and obesity in children and adolescents should be considered in childhood obesity prevention and control.

Efficacy and safety of umbilical cord mesenchymal stem cells for the treatment of patients with COVID-19

OBJECTIVES: The coronavirus disease (COVID-19) outbreak has catastrophically threatened public health worldwide and presented great challenges for clinicians. To date, no specific drugs are available against severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) appear to be a promising cell therapy owing to their potent modulatory effects on reducing and healing inflammation-induced lung and other tissue injuries. The present pilot study aimed to explore the therapeutic potential and safety of MSCs isolated from healthy cord tissues in the treatment of patients with COVID-19. METHODS: Twelve patients with COVID-19 treated with MSCs plus conventional therapy and 13 treated with conventional therapy alone (control) were included. The efficacy of MSC infusion was evaluated by changes in oxygenation index, clinical chemistry and hematology tests, immunoglobulin (Ig) levels, and pulmonary computerized tomography (CT) imaging. The safety of MSC infusion was evaluated based on the occurrence of allergic reactions and serious adverse events. RESULTS: The MSC-treated group demonstrated significantly improved oxygenation index. The area of pulmonary inflammation decreased significantly, and the CT number in the inflammatory area tended to be restored. Decreased IgM levels were also observed after MSC therapy. Laboratory biomarker levels at baseline and after therapy showed no significant changes in either the MSC-treated or control group. CONCLUSION: Intravenous infusion of MSCs in patients with COVID-19 was effective and well tolerated. Further studies involving a large cohort or randomized controlled trials are warranted.

Effects of neutrophilic granule protein on nitric oxide production in lipopolysaccharide-induced macrophages / 中华危重病急救医学

Objective:To explore the influences of neutrophilic granule protein (NGP) on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced macrophages and the regulatory mechanism.Methods:NGP highexpression RAW264.7 cells (NGP/RAW) and negative control empty vector cells (NC/RAW), NGP knockout RAW264.7 cells (NGP KO/RAW) and wild-type cells (WT/RAW) were cultured in vitro. Cells in logarithmic phase were stimulated with 10 mg/L LPS (LPS group) or phosphate buffered saline (PBS group) respectively. The content of NO in the supernatant was detected by Griess method. The mRNA expression of inducible nitric oxide synthase (iNOS) was detected by quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The protein expressions of iNOS and phosphorylated signal transducer and activator of transcription 1 (p-STAT1) were detected by Western blotting.Results:Compared with PBS group, iNOS mRNA and NO expression were significantly increased at different time after LPS stimulation, the mRNA expression of iNOS peaked at 12 hours after LPS stimulation (2 -ΔΔCt: 38.45±1.34 vs. 1.00±0.00 in NC/RAW cells, 56.24±2.41 vs. 1.45±0.30 in NGP/RAW cells, 37.84±1.52 vs. 1.00±0.00 in WT/RAW cells, 5.47±0.62 vs. 0.98±0.40 in NGP KO/RAW cells, all P < 0.05), and the production of NO peaked at 24 hours after LPS stimulation (μmol/L: 24.15±1.26 vs. 0.15±0.04 in NC/RAW cells, 58.80±2.11 vs. 0.18±0.02 in NGP/RAW cells, 25.04±1.80 vs. 0.16±0.02 in WT/RAW cells, 2.42±0.38 vs. 0.12±0.03 in NGP KO/RAW cells, all P < 0.05). After being stimulated by LPS, the expression of iNOS mRNA and NO in NGP/RAW cells were increased significantly compared with NC/RAW cells [iNOS mRNA (2 -ΔΔCt): 8.42±0.59 vs. 4.63±0.37 at 2 hours, 27.16±1.60 vs. 14.25±1.02 at 6 hours, 56.24±2.41 vs. 38.45±1.34 at 12 hours; NO (μmol/L): 4.12±0.25 vs. 2.23±0.17 at 6 hours, 16.50±1.52 vs. 6.35±0.39 at 12 hours, 58.80±2.11 vs. 24.15±1.26 at 24 hours, all P < 0.05]. At the same time, the protein expressions of p-STAT1 and iNOS were also significantly enhanced (p-STAT1/GAPDH: 4.26±1.84 vs. 1.00±0.32 at 0 hours, 20.59±4.97 vs. 0.93±0.21 at 2 hours, 141.99±10.99 vs. 11.17±2.11 at 6 hours; iNOS/GAPDH: 1.27±0.86 vs. 1.00±0.22 at 0 hours, 7.94±1.94 vs. 2.01±0.92 at 2 hours, 24.24±4.88 vs. 3.72±1.11 at 6 hours, all P < 0.05), indicating that NGP might increase the expression of iNOS by promoting the phosphorylation of the signal transducer and activator of transcription 1 (STAT1) pathway, thereby increasing the production of NO. After being stimulated by LPS, the expression of iNOS mRNA and NO in NGP KO/RAW cells were significantly lower than that of WT/RAW cells [iNOS mRNA (2 -ΔΔCt): 2.46±0.31 vs. 4.22±0.18 at 2 hours, 3.61±0.44 vs. 13.02±1.34 at 6 hours, 5.47±0.62 vs. 37.84±1.52 at 12 hours; NO (μmol/L): 1.22±0.19 vs. 2.01±0.12 at 6 hours, 1.60±0.44 vs. 5.15±0.62 at 12 hours, 2.42±0.38 vs. 25.04±1.80 at 24 hours, all P < 0.05]. It showed that iNOS activation was reduced after NGP knockout, which in turn reduced NO production. Conclusion:NGP can positively regulate NO production in activated macrophages by activating the STAT1/iNOS pathway.

Perioperative rehabilitation approaches based on the concept of Enhanced Recovery After Surgery for pelvic fractures: a prospective randomized control trial / 中华创伤骨科杂志

Objective:To evaluate the efficacy and safety of perioperative rehabilitation approaches based on the concept of Enhanced Recovery After Surgery (ERAS) for pelvic fractures.Methods:A prospective randomized control trial was conducted to include 114 emergency patients who had been admitted to Department of Orthopaedic Trauma, Beijing Jishuitan Hospital for surgical treatment of pelvic fractures from June 2019 to December 2020. Of them, 57 were assigned into an intervention group according to a random digits table. They were 42 males and 15 females, aged from 18 to 77 years and subjected to management of pelvic fractures with tentative perioperative ERAS approaches which were adjusted at different stages. The other random 57 patients were assigned into a control group. They were 40 males and 17 females, aged from 17 to 70 years and subjected to management of pelvic fractures with conventional rehabilitation approaches which included postoperative in-hospital consultation and guidance by rehabilitation physicians. The 2 groups were compared in terms of Majeed pelvis scores and Barthel indexes at postoperative 2, 6, 12 and 24 weeks, and visual analogue scale (VAS) pain scores and SF36 scores at postoperative 12 and 24 weeks.Results:A total of 105 patients (55 in the intervention group and 50 in the control group) were completely followed up for 151 to 254 d (mean, 177 d). The 2 groups were comparable due to no significant difference between them in the preoperative general data ( P>0.05). The Majeed scores (44±13, 67±16, 86±14 and 98±7) and Barthel indexes (57±13, 79±16, 95±8 and 100±2) at postoperative 2, 6, 12 and 24 weeks in the intervention group were significantly higher than those in the control group [(35±16, 51±16, 73±14 and 91±12) and (45±19, 67±18, 86±12 and 98±4)] (all P<0.05). At postoperative 12 and 24 weeks, the SF-36 scores (129±15 and 141±6) in the intervention group were significantly higher than those in the control group (114±15 and 131±12) ( P<0.05). There was no significant difference in the pain degree between the 2 groups ( P>0.05). Conclusion:In management of pelvic fractures, compared with conventional perioperative rehabilitation approaches, the perioperative ERAS rehabilitation approaches may improve early functional outcomes and thus help the patients restore their activities of daily living earlier.

Modified posterior tibialis muscle transfer for treatment of foot drop and varus deformity after common peroneal nerve injury / 中华创伤杂志

Objective:To investigate the early effect of modified posterior tibialis muscle transfer in treating foot drop and varus deformity caused by common peroneal nerve injury.Methods:A retrospective case series study was conducted to analyze the clinical data of 6 patients with foot drop of common peroneal nerve palsy and varus deformity admitted to Beijing Jishuitan Hospital from December 2017 to October 2019, including 4 males and 2 females, aged 33-48 years [(39.5±6.0)years]. The left side was involved in 4 patients and the right side in 2 patients. All patients underwent posterior tibial muscle transfer. The insertion of posterior tibial muscle was reconstructed in the fourth metatarsal with the tendon allograft to correct foot drop and varus deformity. The range of motion of active ankle dorsiflexion and plantar flexion and range of motion of varus and valgus of foot were measured before operation and at the last follow-up. The isokinetic torque peak value of ankle dorsiflexion and plantar flexion at 60°/s angular velocity and peak isokinetic torque of foot varus and valgus at 60°/s angular velocity were measured before operation and at the last follow-up. The postoperative foot imaging evaluation was performed at the last follow-up, including Meary angle, calcaneal projection and diameter of the fourth metatarsal. The American Orthopaedic Foot & Ankle Association (AOFAS) ankle-hindfoot score was used to evaluate the ankle function.Results:All patients were followed up for 6-17 months [10(6, 15)months]. At the last follow-up, the range of motion of dorsiflexion of the ankle [6(0, 10)°] and foot valgus [3(0, 5)°] were significantly improved compared with the preoperative level [-31(-33, -28)°, -10(-12, -8)°] ( P<0.05); the ankle dorsiflexion torque [(7.7±0.8)Nm] and foot valgus torque [(7.2±0.7)Nm] were significantly improved compared with the preoperative level [(0.0±0.0)Nm, (2.1±0.6)Nm]at 60°/s angular velocity ( P<0.01). Imaging examination showed no acquired flat foot deformity and deformation of the fourth metatarsal insertion. The AOFAS ankle-hindfoot score increased from 50-73 points [(61.3±8.4)points] before operation to 75-97 points [(86.8±7.2)points] at the last follow-up ( P<0.01). Conclusion:For foot drop and varus caused by common peroneal nerve injury, modified posterior tibialis muscle transfer can increase the torque of ankle dorsiflexion and valgus, improve the ankle range of motion, and accelerate the ankle function recovery.

Effect of pregnancy malaria on T cells in immune organ of offspring mice / 中华地方病学杂志

Objective:To observe the influence of pregnant mice having malaria on T cell function of offspring mice, and to study the changes of cellular immune response in offspring mice exposed to malaria infection in uterus.Methods:Adult Kunming mice of clean grade were selected after mating, on the 14th day of pregnancy, pregnant mice were randomize assigned into experimental group ( n = 5) and control group ( n = 5) according to the method of random number table. Each mouse in the experimental group was intraperitoneally inoculated with 1 × 10 6 red blood cells infected with Plasmodium berghei ( P.b), and same volume of normal saline was given to control group. After birth, the changes of CD4/CD8 T cell subsets in their thymuses and spleens of the two group neonatal mice were analyzed by flow cytometry at day 0, 1, 3, 5 and 4-week-old. Then the 4-weeks-old neonatal mice were intraperitoneally inoculated with 1 × 10 6P.b. On the third day, the changes of CD4/CD8 T cells subsets in their thymuses and spleens were observed, respectively, and the immune response of spleen cells stimulated by P.b antigen or mitogen [concanavalin A (Con A)] was detected. Results:Compared with the control group, the proportions of CD3 +CD4 +CD8 - T cells in thymus and spleen of the offspring of the experimental group (0, 1, 3, 5 days) were higher ( P < 0.05), while the proportions of CD3 +CD4 -CD8 + T cells in thymus were lower ( P < 0.05). For 4-week-old offspring and after infection of P.b, the proportions of CD3 +CD4 +CD8 - T cells in thymus and spleen of the experimental group were both significantly higher than those of control group ( P < 0.05), in contrast, the proportions of CD3 +CD4 -CD8 + T cells in thymus and spleen were both significantly lower than those of control group ( P < 0.05). The spleen cells of 4-week-old mice were stimulated by P.b antigen or mitogen ConA in vitro, compared with the control group, there were no significant differences in the proportions of CD3 +CD4 +CD8 - T cells and CD3 +CD4 -CD8 + T cells in the experimental group ( P > 0.05). Conclusion:During pregnancy, the maternal infection of P.b could significantly affect the ratio of CD4/CD8 T cell subsets in thymus and spleen of offspring mice; and could change the cellular immune response of offspring to P.b infection.

Deep learning applied to two-dimensional color Doppler flow imaging ultrasound images significantly improves diagnostic performance in the classification of breast masses: a multicenter study / 中华医学杂志(英文版)

BACKGROUND@#The current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images.@*METHODS@#Taking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR-), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists.@*RESULTS@#The accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87-0.91, 0.89-0.92, 0.87-0.91, and 0.86-0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%).@*CONCLUSIONS@#The CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.

Berberine exerts antidepressant-like effects via regulating miR-34a-synaptotagmin1/Bcl-2 axis / 中草药·英文版

Objective: Berberine, a cationic alkaloid first isolated in 1917, has been approved by the China Drug Administration for decades. Accumulating evidence demonstrated its antidepressant-like activities in vivo. Our previous study has shown that chronic stress leads to the upregulation of miR-34a in the hippocampus of mice. This study aims to evaluate the underlying miR-34a mediated mechanism of berberine in chronic stress-induced depression in mice. Methods: In the present study, mice were administered with berberine during chronic stress. Levels of miR-34a, dendritic density, mitochondrial morphology, and neurogenesis were assessed in the hippocampus. Subsequently, miR-34a agomir was used as a pharmacological intervention for the investigation of berberine. Results: The results showed that berberine reversed the decrease in sucrose preference and the increase in latency to feed without altering total food consumption. Furthermore, chronic stress-induced overexpression of miR-34a decreased synaptotagmin-1 and Bcl-2 levels, thereby impairing spinal morphology, mitochondria and neurogenesis. Berberine inhibited miR-34a expression, in turn restored synaptotagmin-1 and Bcl-2 levels, and thus improved spinal morphology, mitochondria and neurogenesis in the hippocampus. However, the improvements induced by berberine were totally blocked by the pretreatment of miR-34a agomir, which caused the elevation of miR-34a levels in the hippocampus. Conclusion: This finding demonstrated that miR-34a downregulation was involved in the antidepressant-like effects of berberine in mice exposed to chronic stress.

Identification of activated pathways in lung adenocarcinoma based on network strategy

Background: Lung adenocarcinoma has increased incidence over the past years and is the cause for almost 50% of deaths attributable to lung cancer. The objective of this paper is to identify activated pathways associated with lung adenocarcinoma based on gene co-expression network analysis. Materials and Methods: Kyoto Encyclopedia of Genes and Genomes pathway analysis of dysregulated genes was performed based on Expression Analysis Systematic Explorer test to illuminate the biological pathways. Co-expression networks of lung adenocarcinoma in different tumor Stages (IA, IB, IIA, IIB, IIIA, IIIB, and IV) were constructed by Empirical Bayes approach to reweight gene pair scores. Pathway activity analysis was conducted to compute the distribution of pathways in different stages and to identify “activated” pathways in lung adenocarcinoma. Results: We evaluated 211 dysregulated genes between lung adenocarcinoma patients and normal controls. Pathway activity analysis was performed and P values of pathways, which obtained from co-expression networks (Stage IA, IB, IIA, IIB, IIIA, IIIB, and IV), were calculated. Cell cycle, progesterone-mediated oocyte maturation, and oocyte meiosis were activated during all stages in lung adenocarcinoma. Conclusions: We successfully identified three activated pathways (cell cycle, progesterone-mediated oocyte maturation, and oocyte meiosis) in different Stages (IA, IB, IIA, IIB, IIIA, IIIB, and IV) of lung adenocarcinoma

Resveratrol protects H9c2 cells against hypoxia-induced apoptosis through miR-30d-5p/SIRT1/NF-κB axis

Previous studies have demonstrated the cardioprotective role of resveratrol (Res). However, the underlyingmolecular mechanisms involved in the protective role of Res are still largely unknown. H9c2 cells weredistributed into five groups: normal condition (Control), DMSO, 20 mMRes (dissolved with DMSO), hypoxia(Hyp), and Res?Hyp. Cell apoptosis was evaluated using flow cytometry and protein analysis of cleavedcaspase 3 (cle-caspase 3). qRT-PCR assay was performed to measure the expression of microRNA-30d-5p(miR-30d-5p). MTT assay was performed to evaluate the cell proliferation. The relationship between miR-30d5p and silent information regulator 1 (SIRT1) was confirmed by luciferase reporter, RNA immunoprecipitation(RIP), and western blot assays. Western blot was performed to analyze NF-jB/p65 and I-jBa expressions. Ourdata showed that hypoxia enhanced apoptosis and NF-jB signaling pathway, which was alleviated by Restreatment. Hypoxia increased the expression of miR-30d-5p while decreased the SIRT1expression, which wasalso attenuated by Res treatment. Furthermore, miR-30d-5p depletion inhibited the proliferation, reducedapoptosis and decreased the expression of cle-caspase 3 in H9c2 cells with hypoxia treatment. Luciferasereporter, RIP, and western blot assays further confirmed that miR-30d-5p negatively regulated the expression ofSIRT1. Interestingly, the rescue-of-function experiments further indicated that knockdown of SIRT1 attenuatedthe effect of miR-30d-5p depletion on proliferation, apoptosis NF-jB signaling pathway inH9c2 cells withhypoxia treatment. In addition, the suppression of NF-jB signaling pathway increased cell viability whiledecreased cell apoptosis in hypoxia-mediatedH9c2 cells. Our data suggested Res mayprotectH9c2 cells againsthypoxia-induced apoptosis through miR-30d-5p/SIRT1/NF-jB axis

The value of growth differentiation factor-15 and extravascular lung water index in severity grading of acute respiratory distress syndrome patients and their prognosis prediction / 中华危重病急救医学

Objective:To investigate the value of growth differentiation factor-15 (GDF-15) and extravascular lung water index (EVLWI) in severity grading and prognosis prediction of patients with acute respiratory distress syndrome (ARDS).Methods:Patients with ARDS aged 18-75 years admitted to the department of respiratory intensive care unit (RICU) of Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2019 to February 2020 were enrolled. All patients were treated with conventional therapies such as mechanical ventilation, anti-infection, stabilization of water, electrolytes and acid-base environment, blood purification and nutritional support according to their conditions. Besides, the pulse-indicated continuous cardiac output (PiCCO) was performed after admission to the department, and EVLWI before treatment and at 24, 48 and 72 hours of treatment were recorded. Serum GDF-15 level was measured by enzyme linked immunosorbent assay (ELISA) during the same period. Patients were classified as mild, moderate, and severe degree according to the 2012 Berlin Definition of ARDS, and EVLWI and GDF-15 levels in patients with different disease levels before and after treatment were compared. In addition, the length of intensive care unit (ICU) stay, ICU mortality, and 28-day mortality of patients with different GDF-15 or EVLWI levels were analyzed comparatively, with the GDF-15 3 458 ng/L and EVLWI 15 mL/kg as the cut point.Results:A total of 82 patients with ARDS were enrolled, including 22 patients with mild ARDS, 28 patients with moderate ARDS, and 32 patients with severe ARDS. The GDF-15 and EVLWI levels in patients with moderate and severe ARDS at each time point before and after treatment were higher than those in patients with mild ARDS. Both GDF-15 and EVLWI levels in patients with severe ARDS were higher than those in the patients with moderate ARDS. The differences were statistically significant at all the time points except for the difference of GDF-15 levels at 24 hours after treatment (ng/L: 3 900.41±546.43 vs. 3 695.66±604.73, P > 0.05). [GDF-15 (ng/L): 3 786.11±441.45 vs. 3 106.83±605.09 before treatment, 3 895.48±558.96 vs. 3 333.29±559.66 at 48 hours, 3 397.33±539.56 vs. 3 047.53±499.57 at 72 hours; EVLWI (mL/kg): 19.06±1.91 vs. 14.31±1.50 before treatment, 18.56±2.23 vs. 13.26±1.69 at 24 hours, 17.23±1.76 vs. 12.45±1.36 at 48 hours, 15.47±1.81 vs. 11.13±2.19 at 72 hours, all P < 0.05]. According to the cut-off value, there were 23 patients with GDF-15 ≥ 3 458 ng/L and GDF-15 < 3 458 ng/L respectively and there were 23 patients with EVLWI ≥ 15 mL/kg and EVLWI < 15 mL/kg respectively. The length of ICU stay and 28-day mortality in patients with high GDF-15 were significantly higher than those in patients with low GDF-15 [length of ICU stay (days): 21.22±2.69 vs. 15.37±3.14, 28-day mortality: 56.5% vs. 21.7%, both P < 0.05]. The length of ICU stay and 28-day mortality in patients with high EVLWI were also significantly higher than those in patients with low EVLWI [length of ICU stay (days): 18.45±2.61 vs. 14.98±2.75, 28-day mortality: 47.8% vs. 17.4%, both P < 0.05]. Conclusion:To some extent, GDF-15 and EVLWI levels reflect the severity of patients with ARDS, and high GDF-15 and EVLWI levels are significantly associated with poor prognosis in patients with ARDS.

Influencing factors for hospitalization of pneumoconiosis patients / 预防医学

Objective@#To analyze the influencing factors for hospitalization of pneumoconiosis patients, so as to provide reference for improving the timeliness of treatment and quality of life in these patients. @*Methods@#The pneumoconiosis patients in Changshan, Wenling and Changxing ( having mining industry ) of Zhejiang Province were selected by stratified and typical sampling methods. Their demographic features, prevalence of pneumoconiosis and hospitalization status were collected by a questionnaire survey. Logistic regression analysis was conducted to analyze the influencing factors for hospitalization. @*Results@#Among 166 pneumoconiosis patients, 122 ( 73.49% ) chose to be hospitalized. The multivariate logistic regression analysis revealed that the patients who scored higher in ED-5Q ( OR=65.821, 95%CI: 3.831-1130.781 )and who would communicate with other pneumoconiosis patients ( OR=3.744, 95%CI: 1.261-11.115 ) were more likely to be hospitalized; the patients who were under the medical insurance for urban employees were more likely to be hospitalized than those who were under the new rural cooperative medical care system ( OR=0.033, 95%CI: 0.007-0.154 ) and others ( OR=0.038, 95%CI: 0.002-0.960 ) . @*Conclusion@#The quality of life, communication with other pneumoconiosis patients and type of medical insurance were the influencing factors for hospitalization of pneumoconiosis patients.

Addition and Subtraction Therapy of Zhishi Xiebai Guizhitang and Lizhongtang for Stable Angina and Effect on Inflammatory Factors and Endothelial Function / 中国实验方剂学杂志

Objective:To discuss the efficacy of addition and subtraction therapy of Zhishi Xiebai Guizhitang and Lizhongtang for stable angina (SAP) with syndrome of Yin-cold stagnation and investigate its effects on inflammatory factors and endothelial function. Method:One hundred and thirty- eight patients were randomly divided into control group (69 cases) and observation group (69 cases) by random number table. During the study period, there were 3 drop-out cases, 3 excluded cases, and 63 completed cases in the control group. There were 3 drop-out cases, 1 excluded case, and 65 completed cases in the observation group. Basic therapy was given in both groups. Patients in both groups got metoprolol tartrate tablets, 50 mg/time, 2 times/days. Aspirin enteric-coated tablets, 100 mg/time, 1 time/day. Trimetazidine dihydrochloride tablets, 1 tablet/time, 3 times/days In case of angina pectoris attacks, nitroglycerin tablets under the tongue, 0.25-0.5 mg, for every 5 minutes until the angina is relieved. And they also got treatment to control blood glucose, lipids and blood pressure. Based on the above treatment, the patients in control group additionally received Guanxin Suhe pills, chewed for administration, 1 pill/time, twice a day. The patients in observation group additionally received addition and subtraction therapy of Zhishi Xiebai Guizhitang and Lizhongtang, 1 dose/day. The course of treatment was 12 weeks in both groups. One week before treatment and one week after treatment, the number of times and duration of anginal attacks and dosage of nitroglycerin were recorded. Before treatment and after treatment, electrocardiogram was checked, and scores of Seattle Angina Questionnaire (SAQ) and syndrome of Yin-cold stagnation were graded; levels of serum phospholipase A2 (Lp-PLA2), homocysteine (Hcy), D-dimer (D-D), hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nitric oxide (NO) and endothelin (ET-1) were detected. Result:The number of times of angina attacks and Nitroglycerin consumption in observation group were less than those in control group (P<0.01), and the duration of angina attacks was shorter than that in control group (P<0.01). Score of syndrome of Yin-cold stagnation in observation group was lower than that in control group (P<0.01), and score of SAQ was higher than that in control group (P<0.01). Levels of Lp-PLA2, D-D, Hcy, IL-6, hs-CRP, TNF-α and ET-1 in observation group were lower than those in control group (P<0.01), and level of NO was higher than that in control group (P<0.01). The efficacy shown in electrocardiogram was also better than that in control group (Z=2.043, P<0.05； Z=2.003, P<0.05). Conclusion:On the basis of routine treatment of western medicine, addition and subtraction therapy of Zhishi Xiebai Guizhitang and Lizhongtang can further alleviate symptoms, reduce ischemic attack, improve the quality of life in patients with SAP and syndrome of Yin-cold stagnation. It has anti-inflammatory effect and can improve the function of blood vessels and stabilize plaque, showing better clinical effects and electrocardiographic results than Western medicine alone.

Effect of Addition and Subtraction Therapy of Xuanbitang on Acute Inflammation Caused by Knee Osteoarthritis of Rheumatic Fever Arthralgia Type at Attack Stage / 中国实验方剂学杂志

Objective:To observe the controlling effect of addition and subtraction therapy of Xuanbi tang on knee osteoarthritis of rheumatic fever arthralgia type (KOA) at attack stage and to investigate the influence to acute inflammation factors. Method:One hundred and twenty-eight patients were randomly divided into control group and observation group (1∶1) by random number table with SAS software. The patients in both groups got celecoxib capsules, 0.2 g/time, 1 time/day, glucosamine hydrochloride capsule, 1 grain/time, 2 times/day. Patients in control group addiiontally got Simiaowan, 6 g/time, 2 times/day. Patients in observation group got addition and subtraction therapy of Xuanbitang, 1 dose/day, with a treatment course of 2 weeks in both groups. Visual analogue scale of pain (VAS) was used to discuss pain degree of knee joint, and the VAS scores during activity and resting state were recorded every day, and the time to pain relief and time to pain disappearance were also recorded. Before and after treatment, the scores of osteoarthritis index visual scale of Western Ontario and McMaster University (WOMAC), scores of swelling degree and scores of rheumatism heat arthralgia syndrome were graded. The levels of high sensitive C-reactive protein (hs CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and serum matrix metalloproteinase-3 (MMP-3) were detected before and after treatment. In addition, safety was evaluated and discussed. Result:The comprehensive total effective rate in observation group was 95.00% (57/60), higher than 83.05% (49/59) in control group (P<0.05). At the third, seventh, tenth, fourteenth day after treatment, scores of knee joint pain degree in observation group were lower than those in control group (P<0.01). Time to pain relief and time to pain disappearance were shorter than those in control group (P<0.01). Scores of WOMAC, swelling degree and rheumatism heat arthralgia syndrome were all lower than those in control group (P<0.01). Levels of hs-CRP, IL-1β, IL-6, TNF-α and MMP-3 were lower than those in control group (P<0.01). In addition, there was no adverse reaction related to Xuanbitang. Conclusion:Addition and subtraction therapy of Xuanbitang can relieve pain, swelling and other symptoms, improve knee joint function, shorten the course of disease, and control the acute inflammatory reaction, with significant clinical efficacy and safety.