Statistical methods of unmeasured confounder control based on negative control theory / 中华流行病学杂志

Controlling unmeasured confounders in non-randomized controlled studies is challenging. Negative control theory is based on the theoretical concept that the test result of negative controls must be negative. Setting appropriate negative control incorporates the specificity of association into population studies for the identification and control of unmeasured confounders. This paper explains the principles to control unmeasured confounders using negative control theory from a statistical perspective. A detailed introduction of derived methods based on negative control theory is also introduced, including adjusted standardized mortality ratio method, calibrating P-value method, generalized difference-in-difference model and double negative control method. The reasonable application of those derived methods is also comprehensively summarized based on representative case studies. Negative control is an important statistical design to identify, revise and control unmeasured confounders and a valuable method for comparative effectiveness research based on real-world data.

Clinicopathological features and prognosis of kidney injury in patients after hematopoietic stem cell transplantation / 中华预防医学杂志

To summarize the clinicopathological features and prognosis of kidney injury after hematopoietic stem cell transplantation (HSCT), to provide basis for preventing its occurrence and development. By using a retrospective cohort study method, we collected the clinical and renal biopsy pathological data of all the patients who hospitalized in the Department of Nephrology of Peking University First Hospital from June 2011 to June 2021 with renal injury after HSCT and underwent renal biopsy, and prognosis was followed up by telephone. The clinical laboratory characteristics, renal pathology and prognosis, and their association were analyzed. The results showed that the most common clinical phenotype was chronic kidney disease (CKD,69.2%, 18/26), in this term 13/18 patients received stem cells from haploidentical donors, and 11/18 patients experienced with extrarenal graft-versus-host disease (GVHD). The most common pathologic phenotype was thrombotic microangiopathy (TMA, 61.5%, 16/26). Renal function returned to baseline level in 6 patients, and the kidney survival at 2 years and 5 years were 95.7% (22/23) and 87.5% (14/16), respectively. In conclusion, the clinical phenotype of renal injury after HSCT were mainly CKD, and the most common pathologic phenotype was TMA, the long-term prognosis was favourable.

Prediction and analysis of Q-markers of Elephantopus scaber based on its UPLC fingerprint, content determination of components, and in vitro a nti-tumor activity / 中国中药杂志

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.

Value of fractional flow reserve derived from coronary computed tomographic angiography and plaque quantitative analysis in predicting adverse outcomes of non-obstructive coronary heart disease / 中华危重病急救医学

OBJECTIVE@#To investigate the value of coronary computed tomographic angiography (CCTA)-based fractional flow reserve (CT-FFR) and plaque quantitative analysis in predicting adverse outcomes in patients with non-obstructive coronary heart disease (CAD).@*METHODS@#Clinical data of patients with non-obstructive CAD who underwent CCTA at the Affiliated Hospital of Jiangnan University from March 2014 to March 2018 were retrospectively analyzed and followed up, and the occurrence of major adverse cardiovascular event (MACE) was recorded. The patients were divided into MACE and non-MACE groups according to the occurrence of MACE. The clinical data, CCTA plaque characteristics including plaque length, stenosis degree, minimum lumen area, total plaque volume, non-calcified plaque volume, calcified plaque volume, plaque burden (PB) and remodelling index (RI), and CT-FFR were compared between the two groups. Multivaritate Cox proportional risk model was used to evaluate the relationship between clinical factors, CCTA parameters and MACE. The receiver operator characteristic curve (ROC curve) was used to assess the predictive power of outcome prediction model based on different CCTA parameters.@*RESULTS@#Finally 217 patients were included, of which 43 (19.8%) had MACE and 174 (80.2%) did not. The median follow-up interval was 24 (16, 30) months. The CCTA showed that patients in the MACE group had more severe stenosis than that in the non-MACE group [(44.3±3.8)% vs. (39.5±2.5)%], larger total plaque volume and non-calcified plaque volume [total plaque volume (mm3): 275.1 (197.1, 376.9), non-calcified plaque volume (mm3): 161.5 (114.5, 307.8) vs. 117.9 (77.7, 185.5)], PB and RI were larger [PB: 50.2% (42.1%, 54.8%) vs. 45.1% (38.2%, 51.7%), RI: 1.19 (0.93, 1.29) vs. 1.03 (0.90, 1.22)], CT-FFR value was lower [0.85 (0.80, 0.88) vs. 0.92 (0.87, 0.97)], and the differences were statistically significant (all P < 0.05). Cox regression analysis showed that non-calcified plaques volume [hazard ratio (HR) = 1.005. 95% confidence interval (95%CI) was 1.025-4.866], PB ≥ 50% (HR = 3.146, 95%CI was 1.443-6.906), RI ≥ 1.10 (HR = 2.223, 95%CI was 1.002-1.009) and CT-FFR ≤ 0.87 (HR = 2.615, 95%CI was 1.016-6.732) were independent predictors of MACE (all P < 0.05). The model based on CCTA stenosis degree+CT-FFR+quantitative plaque characteristics (including non-calcified plaque volume, RI, PB) [area under the ROC curve (AUC) = 0.91, 95%CI was 0.87-0.95] had significantly better predictive efficacy for adverse outcomes than the model based on CCTA stenosis degree (AUC = 0.63, 95%CI was 0.54-0.71) and the model based on CCTA stenosis degree+CT-FFR (AUC = 0.71, 95%CI was 0.63-0.79; both P < 0.01).@*CONCLUSIONS@#CT-FFR and plaque quantitative analysis based on CCTA are helpful in predicting adverse outcomes in patients with non-obstructive CAD. Non-calcified plaque volume, RI, PB and CT-FFR are important predictors of MACE. Compared with the prediction model based on stenosis degree and CT-FFR, the combined plaque quantitative index can significantly improve the prediction efficiency of adverse outcomes in patients with non-obstructive CAD.

Pancreatic glucagonoma with metastasis followed up for 15 years: A case report / 中华内分泌代谢杂志

To explore the clinical characteristics, diagnosis, and management of pancreatic glucagonoma, a retrospective analysis of the clinical data and diagnostic algorithm of a patient with pancreatic glucagonoma was conducted, along with literature review. Pancreatic glucagonoma is a rare neuroendocrine tumor that originates from the pancreatic alpha cells. The main manifestations of glucagonoma syndrome(GS) include necrolytic migratory erythema, diabetes, anemia, and other systemic involvement. Early diagnosis of GS is challenging and crucial. Early identification and recognition of skin lesions contribute to timely diagnosis and treatment of the disease. Surgical resection is an effective treatment modality for glucagonoma.

Mechanism of scutellarein inhibiting foaming of macrophages by promoting cholesterol efflux pathway / 中国药理学通报

Aim To investigate the effects of scutellarein on the macrophage foam cell formation and cholesterol efflux, and the underlying mechanism. Methods THP-1 cells were differentiated with PMA, and the cell viability was detected by MTT assays. The effects of scutellarein on the cholesterol efflux and macrophage foam cell formation were evaluated by using NBD-la-beled cholesterol and the cholesterol detection kit. The effects of scutellarein on the activation of PPARγ-LXRα-ABCA1 signaling pathway were determined by molecular docking, ELISA, dual-luciferase reporter and Western blot. The effects of PPARγ knowdown on scutellarein-induced cholesterol efflux and inhibiting macrophage foaming were analyzed by siRNA interference. Results Scutellarein dose-dependently inhibited oxLDL-induced cholesterol accumulation, accelerated cholesterol efflux and significantly increased the protein expression of LXRα and ABCA1. At the same time, scutellarein could bind PPARγ and initiate its downstream LXRa-ABCAl signaling pathway. In addition, gene silencing of PPARγ not only significantly inhibited scutellarein-induced LXRα-ABCA1 signaling pathway and cholesterol efflux, but also reversed the inhibitory effect of scutellarein on macrophage foaming. Conclusions Scutellarein could promote the cholesterol efflux by activating PPARγ and initiating the downstream LXR-ABCA1 signaling pathway, thereby prevent the macrophage foam cell formation.

Flare and change in disease activity among patients with stable rheumatoid arthritis following coronavirus disease 2019 vaccination: A prospective Chinese cohort study / 中华医学杂志(英文版)

BACKGROUND@#Vaccination has been shown effective in controlling the global coronavirus disease 2019 (COVID-19) pandemic and reducing severe cases. This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis (RA).@*METHODS@#A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status. Each of them was examined every 3 to 6 months. In the vaccination group, disease activity was compared before and after vaccination. The rates of flare defined as disease activity scores based on 28-joint count (DAS28) >3.2 with ΔDAS28 ≥0.6 were compared between vaccination and non-vaccination groups.@*RESULTS@#A total of 202 eligible RA patients were enrolled. Of these, 98 patients received no vaccine shot (non-vaccination group), and 104 patients received two doses of vaccine (vaccination group). The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days, respectively. The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar. At enrollment, gender, RA disease course, seropositivity, and disease activity were comparable across the two groups. Flare was observed in five (4.8%) of the vaccination group patients and nine (9.2%) of the non-vaccination group patients at post-vaccination assessment ( P  = 0.221). In terms of safety, 29 (27.9%) patients experienced adverse events (AEs) after vaccination. No serious AEs occurred.@*CONCLUSIONS@#COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity. Patients with stable RA should be encouraged to receive the COVID-19 vaccination.

Comparison of panoramic radiography and cone-beam computed tomography images for detecting external root resorption of mandibular second molar associated with third molar impaction / 口腔医学

Objective@# To compare the diagnostic performance between panoramic radiography(PR)and cone beam computed tomography(CBCT)in the assessment of external root resorption(ERR)of mandibular second molars associated with impacted third molars. @*Methods@# A total number of 832 patients with 1 074 mesially and horizontally impacted mandibular third molars treated at our institution from January 2019 to December 2020 were retrospectively analyzed. Presence of ERR on the adjacent second molar was investigated with PR and CBCT. Factors affecting the diagnostic accuracy of PR were determined. @*Results@# The overall incidence of ERR in second molars was 33.15%(356/1 074)as detected by CBCT images. The accuracy of PR was 66.39%. Multivariate Logistic regression analyses further revealed that middle and Class Ⅲ impaction, crown contact or overlap with the root of adjacent tooth were risk factors for inaccurate diagnosis of PR(P<0.05). @*Conclusion@#The accuracy of detection on ERR of mandibular second molar associated with impacted third molar using panoramic radiography is lower. CBCT is recommended for this clinical scenario.

Association of community built environment with obesity among elderly residents / 环境与职业医学

Background In the context of improving urban environment for healthy aging, it is necessary to rationally plan and provide community living space and public service facilities suitable for the elderly, and constantly optimize the built environment towards an age-friendly city. Objective To understand the relationship between community built environment and obesity in the elderly in Longgang City, and to provide a reference basis for improving the health of the elderly. Methods Elderly adults aged 60-90 years (n=6527) who completed a physical examination during the period from October 2020 to January 2021 in Longgang City were surveyed, and data on height and weight, waist circumference (WC), and other sociological demographic characteristics were obtained. Overweight was determined by 24 kg·m−2 ≤ body mass index (BMI) < 28 kg·m−2 and obesity by BMI ≥ 28 kg·m−2. Men with WC ≥ 85 cm and women with WC ≥ 80 cm were considered central obesity. Based on the participants' residential addresses, geocoding was performed using a geographic information system, and built environment indicators such as restaurants, convenience stores, and basic medical facilities were obtained using Gaode Map. A binary logistic regression model with adjusted individual-level covariates was used to evaluate the relationship between obesity and built environment indicators among elderly adults by gender and age. Results Among the 6527 community elderly, 46.93% were male and 53.07% were female, with a mean age of (73.69±0.07) years, a mean BMI of (24.32±2.84) kg·m−2, and 51.92% of the elderly were overweight or obese. The regression results showed that for elderly men, the more convenience stores and the higher mixed land use in residential areas, the higher risk of central obesity; however, the increases in street connectivity and accessibility to parks and recreational areas were associated a decreased risk of central obesity. The prevalence of overweight/obesity was higher among elderly women with more convenience stores in residential areas, while increased street connectivity was associated with a lower prevalence of central obesity among elderly women. Accessibility to primary health care facilities was negatively associated with the risk of central obesity among the 60- to 70-year-olds. For elderly residents aged 71−80 years, higher mixed land use and better accessibility to transit stations were associated with a higher prevalence of overweight/obesity, while street connectivity was negatively associated with the central obesity. Proximity to parks and recreational areas was associated with a reduced risk of overweight/obesity among the 81- to 90-year-olds. Conclusion Among the variables of a 500-m neighborhood built environment, the number of convenience stores, mixed land use, street connectivity, accessibility to primary health care facilities, accessibility to public transit stations, and accessibility to parks and recreational areas are correlated with obesity among elderly residents, and the degree of influence varies by gender and age.

Research progress on the relationship between ciliary muscle and myopia / 国际眼科杂志(Guoji Yanke Zazhi)

As a key ocular structure, ciliary muscle has a major role in accommodating both eye and aqueous humor drainage. Recent studies have found that the position and shape of ciliary muscles in myopia are significantly different from those in emmetropia or hyperopia, and the differences of ciliary muscle may affect the progress of myopia by altering ocular accommodation, choroidal tension and intraocular pressure. The present evidence indicating that the thickening of posterior ciliary muscle was associated with the development of myopia, but the mechanism has not been clearly confirmed. This paper summarizes the relationship between the differences of ciliary muscle and myopia, and the possible mechanism of myopia changes affected by ciliary muscle, so as to provide reference for follow-up research.

Image-guided Strategy of Intensity-modulated Radiotherapy in Helical Tomography for Nasopharyngeal Carcinoma / 中山大学学报(医学科学版)

ObjectiveThis study aimed to analyze the difference in setup error before and after correction of systematic error. To determine the most appropriate image-guided strategy during HT treatment， we use different scanning ranges and image-guidance frequencies in patients with nasopharyngeal carcinoma （NPC） treated with helical tomotherapy （HT）. MethodsFifteen patients with NPC who received HT treatment in Sun Yat-sen University Cancer Center from October 2019 to February 2020 were selected. Megavoltage computed tomography （MVCT） scanning was performed before each treatment. After five times of radiotherapy， system-error correction was performed to adjust the setup center. The setup errors before and after the correction of systematic errors， as well as the setup errors of different scanning ranges and different scanning frequencies， were collected for analysis and comparison. ResultsWhen comparing the setup errors before and after the correction of systematic error， the differences in setup errors in the left–right （LR）， superior–inferior （SI）， and anterior–posterior （AP） directions were statistically significant （P<0.05）.The different scanning ranges of "nasopharynx + neck" and "nasopharynx" were compared， and a statistically significant difference was found in yaw rotational errors （P<0.05）. In the comparison of daily and weekly scan frequency after system-error correction， a significant difference was found in AP direction （P<0.05）. ConclusionDuring radiotherapy for NPC， the systematic error can be corrected according to the first five setup errors， and then small-scale scanning was selected for image-guided radiotherapy every day.

Will male semen quality improve with environmental quality? / 亚洲男科学杂志(英文版)

Wenzhou has improved its environmental quality because of comprehensive environmental remediation; nevertheless, the semen quality of infertile males remains unclear. This study determined whether better environmental quality improved semen quality in this region. We recorded semen quality data from 22 962 infertile males from January 2014 to November 2019 at the Center for Reproductive Health of The First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China). Patients were predominantly 30-35 years old (33.1%) and workers (82.0%), with high school education or lower (77.6%); more than a half of the patients (52.6%) were Wenzhou household registration; and most patients (77.5%) had abnormal semen quality. Patients who were older than 40 years and workers, and those with Wenzhou household registration, had significantly worse semen quality (all P < 0.05). From 2014 to 2019, progressive sperm motility, total sperm motility, and semen volume showed increasing linear trends in all patients (P = 0.021, 0.030, and 0.005, respectively), yet normal sperm morphology showed a linearly decreasing trend (P = 0.046). Sensitivity analyses for subgroups yielded similar results. In conclusion, the improvement of environmental quality and better function of the accessory glands are associated with progressive sperm motility, total sperm motility, and semen volume. Normal sperm morphology is influenced by occupational exposures and personal lifestyle and does not improve with environmental quality.

Synergistic antitumor effect of Andrographolide and cisplatin through ROS-mediated ER stress and STAT3 inhibition in colon cancer.

Colon cancer is one of the most leading death-causing cancers in the world. Cisplatin has been widely used as the first-line treatment of cancer. However, its clinical application is limited by the side effects or acquired drug resistance. Hence, it is of vital clinical significance to develop novel agents that synergize with cisplatin and decrease its side effects. The aim of this study was to investigate whether Andrographolide (AP) synergistically potentiates the anti-tumor effect of cisplatin on colon cancer cells. Here, we found that AP synergizes with cisplatin in exerting anticancer activity in colon cancer cells. Further studies showed that AP potentiates cisplatin-induced endoplasmic reticulum stress and STAT3 inhibition through increasing intracellular ROS. Notably, pre-treatment of NAC, a ROS scavenger, reversed apoptosis induced by combined treatment of AP and cisplatin, while relieving the activation of endoplasmic reticulum stress as well as STAT3 inhibition. These findings indicated that ROS plays a pivotal role in mediating synergistic anticancer effects of AP and cisplatin on colon cancer cells. Overall, this study presents a potential new therapeutic strategy for the treatment of colon cancer.

A novel prognostic index for sporadic Burkitt lymphoma in adult patients: a real-word multicenter study.

BACKGROUND: Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. METHODS: We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan-Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm. RESULTS AND CONCLUSIONS: Univariate and multivariate analyses revealed that platelets< 254 × 109/L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell's concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.

The inhibition mechanism of ZST93 on proliferation of K562 through regulating cell cycle and apoptosis induced by autophagy / 中国药理学通报

Aim To evaluate the effect of ZST93 on the proliferation in human chronic myeloid leukemia(CML)cells(K562)and explore the possible mechanism.Methods MTT assay, cell growth curve and inverted microscope were used to investigate the effect of ZST93 on proliferation of K562 cells.Cell transfection and Western blot were performed to detect the autophagy, while PI staining, Annexin V-FITC/PI and flow cytometry were conducted to determine cell apoptosis and its anticancer mechanism.Results ZST93 could significantly inhibit the proliferation of K562(IC50=2.59 μmol·L-1)and induce cell cycle arrest at G1-phase in a dose- and time-dependent manner.Also, through leading to accumulation of GFP-LC3, transition into LC3- II from LC3- 1 , and decrease of p62 expression, ZST93 induced autophagy initiation and autophagic flux.Furthermore, ZST93 induced extrinsic apoptotic pathway by activating caspase-8, and further promoted the cleavage of apoptosis related proteins including caspase-9, caspase-3 and PAR P.Moreover, Z-DEYD-FMK, the specific inhibitor of caspase-3 , could dramatically reduce the apoptosis induced by ZST93.Taken together, ZST93 could effec tively inhibit CML cells, arrest eell cycle at G,-phase, induce cell apoptosis anrl initiate autophagy.Conclusions The potential mechanism may he related to the regulation of autophagy intiation/caspase-8/caspase-3 signaling pathway, which provides a new idea and theoretical basis for the treatment of CML.

Ginsenoside Rgl regulates autophagy through AMPK/mTOR signaling pathway and delays brain aging in mice / 中国药理学通报

Aim To investigate the mechanism by which ginsenoside Rgl regulates autophagy anrl delays brain aging in mice through AMPK/mTOR signaling pathway.Methods C57BL/6J male mice were ran¬domly divided into four groups, namely brain aging model group ,control group, Rgl anti-aging group,auto¬phagy activator Rapamycin anti-aging group.After the modeling was completed, the test of each experimental index would be carried out on the next day.Morris wa¬ter maze experiment was used to detect the learning and memory ability of mice.Paraffin sections of the hippocampus were prepared, HE , Nissl and immunohis- tochemical staining were used to observe the morpholo¬gy of hippocampal neurons, the number of neurons and Nissl bodies was counted, and autophagy-related proteins p62 , ATG5 , ULK1 were detected.Brain tissue homogenates were prepared to detect the aetivity of brain tissue acetylcholinesterase ( AChE ).Western blot was userl to detect brain tissue autophagy-related proteins LC3II, P62, beclinl, P-AMPK/AMPK, P- mTOR/mTOR and apoptosis protein P53.Results Water maze test showed that Rgl and Hap significantly improved the learning and memory abilities of brain-ag¬ing mice.HE and Nissl staining showed that Rgl and Rap decreased necrotic cells and increased the number of Nissl bodies in the hippocampus of brain-aging mice.Immunohistochemistry staining showed that Rgl and Rap decreased the expression of neuronal autoph- agv protein P62 in hippocampus and increased the ex-pression of ATG5 and ULK1.Rgl and Rap decreased the activity of AhcE in brain-aging mice.Western blot showed that Rgl and Rap increased autophagy-related proteins LC3II, Beclinl , P-AMPK/AMPK, but de¬creased the expression of P-mTOR/mTOR, P62, P53.Conclusions Ginsenoside Rgl can effectively antago¬nize the aging effect of D-gal on mouse brain.The pos¬sible mechanism is related to the regulation of autoph- agv by Rgl through AMPK/mTOR signaling pathway.

Design and Verification of Human Metabolic Measurement System Based on STM32 / 中国医疗器械杂志

A high-precision human metabolic measurement system is designed. The system uses STM32F103 as the main control chip to acquire oxygen, carbon dioxide and flow signals to calculate four quantitative indicators: oxygen consumption(VO2), carbon dioxide production(VCO2), respiratory entropy(RQ) and resting energy metabolism(REE), and finally uses an upper computer to display the calculation results.In this paper, the signal acquisition circuit design was carried out for the oxygen sensor, carbon dioxide sensor and flow sensor, and the validity of the device was verified with the American machine MGCDiagnositcs using Bland-Altman analysis method, and the results showed that the four parameters of VO2,VCO2, RQ and REE of both devices fell in the agreement interval of more than 95%. The device thus provides accurate metabolic measurements and offers an effective tool for the field of general health and clinical nutrition support in China.

Effects and mechanism of hydrogen peroxide pretreatment with low molarity on oxidative stress induced apoptosis of mouse bone marrow mesenchymal stem cells / 中华烧伤杂志

Objective: To investigate the effects and mechanism of hydrogen peroxide (HP) pretreatment with low molarity on oxidative stress induced apoptosis of mouse bone marrow mesenchymal stem cells (BMSCs). Methods: The experimental research methods were used. BMSCs were isolated and cultured from two 2-week-old male BALB/c mice by the whole bone marrow culture method. The 3rd-7th passages of cells in logarithmic growth phase were used for the experiments after identification. According to the random number table (the same grouping method below), the cells were divided into 0 μmol/L HP group (without HP, the same below), 25 μmol/L HP group, 50 μmol/L HP group, 100 μmol/L HP group, 150 μmol/L HP group, 200 μmol/L HP group, 250 μmol/L HP group, and 300 μmol/L HP group in which cells were treated by the corresponding final molarity of HP, respectively. The apoptosis rate was detected by flow cytometry (n=4) after 24 hours of culture. The cells were divided into 0 μmol/L HP group, 25 μmol/L HP group, 50 μmol/L HP group, and 100 μmol/L HP group in which cells were treated by the corresponding final molarity of HP, respeclively. After 24 hours of culture, the protein expressions of B-lymphoma-2 (Bcl-2) and Bcl-2-related X protein (Bax) were detected by Western blotting, and the Bcl-2/Bax ratio was calculated (n=3). The cells were divided into 0 μmol/L HP group, 25 μmol/L HP group, 50 μmol/L HP group, 100 μmol/L HP group, 200 μmol/L HP group, and 300 μmol/L HP group in which cells were treated by the corresponding final molarity of HP, respectively. After 24 hours of culture, the protein expressions of glycogen synthase kinase-3β (GSK-3β) and phosphorylated GSK-3β (p-GSK-3β) were detected by Western blotting (n=3). The cells were divided into 0 μmol/L HP group, 50 μmol/L HP group, and 300 μmol/L HP group in which cells were treated by the corresponding final molarity of HP, respeclively, and HP pretreatment group with 50 μmol/L HP being added in advance for 12 h and then 300 μmol/L HP being added. After 24 hours of culture, the morphology and growth of cells were observed by inverted fluorescence microscopy (non-fluorescent condition) and immunofluorescence method, the apoptosis rate was detected by flow cytometry, the protein expressions of Bcl-2, Bax, cysteine aspartic acid specific protease-3 (caspase-3), caspase-9, cleavage caspase-3, cleavage caspase-9, GSK-3β, and p-GSK-3β were detected by Western blotting, and the Bcl-2/Bax ratio was calculated, with all the number of samples being 3. Data were statistically analyzed with one-way analysis of variance and Bonferroni test. Results: After 24 hours of culture, compared with that in 0 μmol/L HP group, the apoptosis rate of cells did not change significantly in 25 μmol/L HP group, 50 μmol/L HP group, or 100 μmol/L HP group (P>0.05) but increased significantly in 150 μmol/L HP group, 200 μmol/L HP group, 250 μmol/L HP group, and 300 μmol/L HP group (P<0.01). After 24 hours of culture, compared with that in 0 μmol/L HP group, the Bcl-2/Bax ratio of cells increased significantly in 25 μmol/L HP group and 50 μmol/L HP group (P<0.05 or P<0.01) but decreased significantly in 100 µmol/L HP group (P<0.05). After 24 hours of culture, compared with those in 0 μmol/L HP group, the protein expression of GSK-3β in cells showed no significant change in 25 μmol/L HP group and 50 μmol/L HP group (P>0.05), the protein expressions of p-GSK-3β in cells significantly increased in 25 μmol/L HP group and 50 μmol/L HP group (P<0.01), the protein expressions of GSK-3β and p-GSK-3β in cells in 100 μmol/L HP group showed no significant change (P>0.05), the protein expressions of GSK-3β in cells in 200 μmol/L HP group and 300 μmol/L HP group were significantly increased (P<0.05). but the protein expression of p-GSK-3β in cells in 200 μmol/L HP group and 300 μmol/L HP group was significantly decreased (P<0.05). After 24 hours of culture, the morphology and growth of cells in 0 μmol/L HP group and 50 μmol/L HP group were similar and normal; in contrast, the cells in 300 µmol/L HP group became smaller and round, with the cell protrusions being shorter or disappeared, the nucleus being cavitated, and the cell abscission being increased significantly; the morphology of most cells in HP pretreatment group was normal, with the shedding of cells being less than that in 300 µmol/L HP group, and the morphology of nucleus being normal. After 24 hours of culture, the protein expression of caspase-9 was similar among the four groups (P>0.05). Compared with that in 0 μmol/L HP group, the apoptosis rate and the protein expressions of cleavage caspase-9, caspase-3, and cleavage caspase-3 of cells in 50 μmol/L HP group showed no significant changes (P>0.05), the Bcl-2/Bax ratio of cells in 50 μmol/L HP group increased significantly (P<0.05), the apoptosis rate and the protein expressions of cleavage caspase-9, caspase-3, and cleavage caspase-3 of cells in 300 μmol/L HP group were significantly increased (P<0.01), while the Bcl-2/Bax ratio of cells in 300 μmol/L HP group was significantly decreased (P<0.05). Compared with those in 300 μmol/L HP group, the apoptosis rate and the protein expressions of cleavage caspase-9, caspase-3, and cleavage caspase-3 of cells were significantly decreased in HP pretreatment group (P<0.05 or P<0.01), while the Bcl-2/Bax ratio of cells was significantly increased in HP pretreatment group (P<0.01). After 24 hours of culture, the protein expressions of GSK-3β and p-GSK-3β of cells in 0 μmol/L HP group, 50 μmol/L HP group, 300 μmol/L HP group, and HP pretreatment group were 1.09±0.14, 0.62±0.17, 1.35±0.21, 0.74±0.34, 0.68±0.03, 0.85±0.08, 0.38±0.10, and 0.54±0.09, respectively. Compared with those in 0 μmol/L HP group, the protein expression of p-GSK-3β of cells was significantly increased in 50 μmol/L HP group (P<0.05) but significantly decreased in 300 μmol/L HP group (P<0.01), while the protein expression of GSK-3β of cells was significantly increased in 300 μmol/L HP group (P<0.05). Compared with those in 300 μmol/L HP group, the protein expression of GSK-3β of cells was significantly decreased in HP pretreatment group (P<0.01), while the protein expression of p-GSK-3β of cells was significantly increased in HP pretreatment group (P<0.01). Conclusions: The molarity of 50 μmol/L may be the optimal molarity of HP to pretreat mouse BMSCs, and 50 μmol/L HP pretreatment can antagonize mitochondrial pathway of oxidative stress induced apoptosis by inhibiting the activity of GSK-3β.

Epidemiological characteristics of Yersinia enterocolitica in patients with diarrhea from 2013 to 2019 in Pudong New Area, Shanghai / 中华预防医学杂志

Objective: To investigate the epidemiological characteristics of Yersinia enterocolitica in patients with diarrhea in Pudong New Area, Shanghai. Methods: Active surveillance of diarrhea was conducted in 14 sentinel hospitals (three tertiary-level hospitals, nine secondary-level hospitals, and two primary-level hospitals) from January 2013 to December 2019 in Pudong New Area of Shanghai, China base on their location, catchment area, and patient volume. Cold enrichment method was used to isolate Y. enterocolitica and further detection of bioserotype, virulence genes and antimicrobial susceptibility of the isolates were conducted. The difference of rates was determined using chi-square test or Fisher's exact test. Results: A total of 12 941 diarrhea cases were included, and 0.7% (88/12 941) cases were confirmed with Yersinia enterocolitica infection. 67.0% (59/88) cases were single infection, 33.0% (29/88) cases were mixed infections. Detection rates of Y. enterocolitica increased annually (0.3%-1.2%) and were highest in children<5 years of age (1.1%, 37/3 218) and in spring (1.1%, 32/2 998) (χ2 were 18.64 and 9.76, respectively, P<0.05). 58.0% (51/88) cases had watery diarrhea, 15.9% (14/88) had fever and 14.8% (13/88) had vomiting. The predominant bioserotypes were 3/O:3 (53.4%, 47/88), followed by 1A/O:8 (15.9%, 14/88) and 1A/O:5(6.8%, 6/88), respectively. Bioserotype 3/O:3 counted for the highest proportions (89.2%, 33/37) in children <5 years of age. All the strains of bioserotype 3/O:3 harbored ail, ystA, yadA and virF genes, which encoded pathogenic Y. enterocolitica. 11/14 strain of 1A/O:8 and 4/6 strains of 1A/O:5 harbored ystB gene. Most strains were resistant to ampicillin (80.7%,71/88) and amoxicillin/clavulanic acid (71.6%,63/88), and 63.8% (56/88) strains were multidrug resistance (MDR). The difference of antimicrobial resistance rates between 3/O:3 and non 3/O:3 was statistically significant in ampicillin, cefoxitin, nalidixic acid, tetracycline and ampicillin/sulbactam (χ2 was 14.68, 43.80, 41.86, 30.54 and 5.07, respectively, P<0.05). Conclusion: The detection rate of Yersinia enterocolitica was higher in children than in adults in Pudong New Area , Shanghai. The predominant bioserotype was pathogenic 3/O:3 with multidrug resistance.

Ineffectiveness of Skin Tests in Predicting Allergic Reactions Induced by Chinese Herbal Injections / 中国结合医学杂志

OBJECTIVE@#To evaluate whether skin tests are suitable to predict the allergy reactions induced by Chinese herbal injections (CHIs).@*METHODS@#The skin tests including skin prick tests (SPT), intradermal tests (IDT) and provocation tests including subcutaneous tests and intravenous tests were administered to 249 healthy subjects and 180 allergic patients for 3 CHIs, including ginkgolide injection, diterpene ginkgolide meglumine injection and Salvianolate lyophilized injection. The results of the provocation tests were used as the "gold standard" to determine the sensitivity and specificity of the skin tests.@*RESULTS@#The results did not show any significant differences between the healthy and allergy groups in both skin tests and provocation tests (P>0.05). The specificities of SPT and IDT were 0.976 and 0.797, respectively, and the sensitivities of both SPT and IDT were 0.@*CONCLUSION@#Skin tests are insufficient to predict the likelihood of allergic reactions resulting from CHIs. (ChiCTR-CPC-15006921).