Construction of micropapillary lung adenocarcinoma organoids and screening of targeted drugs / 天津医药

Objective To establish a culture method for micropapillary lung adenocarcinoma organoids and conduct targeted drug screening.Methods Organoids were extracted and cultured from a surgical tissue sample of a patient diagnosed with micropapillary lung adenocarcinoma,and the growth of lung cancer organoids was observed and recorded dynamically.The morphological and gene expression characteristics of tumor cells between lung cancer organoids and parental tissue were compared using hematoxylin eosin(HE)staining and immunohistochemical methods.Real time fluorescence quantitative polynucleotide chain reaction(qRT-PCR)method was used to detect gene mutations in lung cancer parental tissue and organoids.Finally,based on results of genetic testing,targeted drugs were selected and their therapeutic effects were verified.Results We have successfully cultured spherical organoids from micropapillary lung adenocarcinoma tissue,which can be passaged for at least 3 generations.HE staining results showed that the morphology of tumor cells in organoids was roughly consistent with that of parental tissue.The immunohistochemical results showed that the protein expression levels of various genes in lung cancer organoids and parental tissue were roughly the same.Results of gene mutation analysis showed that the mutated genes in lung cancer parental tissue and organoids were consistent,both reflecting RET fusion.The screening results of targeted drugs based on lung cancer organoids showed that vandertinib had the best anti-tumor effect in vitro.Conclusion Drug screening experiments based on micropapillary lung adenocarcinoma organoids can screen highly efficient targeted drugs in a short period of time,which may benefit patients with micropapillary lung adenocarcinoma.

Analysis of osteoporosis-related biomarker levels in patients with subclinical hypothyroidism complicated with type 2 diabetes mellitus / 中华健康管理学杂志

Objective:To investigate the levels of osteoporosis-related biomarkers in individuals with subclinical hypothyroidism complicated by type 2 diabetes mellitus.Methods:A cross-sectional study. From January 2021 to June 2022, 40 patients with subclinical hypothyroidism, 40 patients with type 2 diabetes, 40 patients with type 2 diabetes complicated with subclinical hypothyroidism, and 40 individuals receiving physical examination in Shanxi Bethune Hospital were selected as subjects in this study. The glucose and lipid metabolism indexes and bone metabolism indexes of the subjects were detected, and the differences and correlations of the metabolic indexes among the groups were analyzed by t-tests, nonparametric tests or correlation analysis. Results:Compared with healthy group, beta C-terminal cross-linked telopeptides of type Ⅰ collagen (β-CTX) level in type 2 diabetes group was higher [(344.60±125.61) vs (227.56±68.33) pg/ml] ( t=-5.176, P<0.001), osteocalcin (OC) and total procollagen type 1 aminoterminal peptide (t-PINP) were both lower [(15.76±4.70) vs (28.02±5.83)ng/ml, (43.49±13.63) vs (59.58±15.80) ng/ml] ( t=10.352, t=4.874, P<0.001). The β-CTX level in type 2 diabetes patients complicated with hypothyroidism was higher than that in patients with simple subclinical hypothyroidism [(380.51±122.22) vs (212.41±44.17) pg/ml] ( t=-8.180 ,P<0.001), but the levels of OC and t-PINP were both lower [(13.67±4.06) vs (26.12±4.55) ng/ml, (38.76±9.53) vs (61.50±12.31) ng/ml] ( t=12.897, P<0.001); but there was no significant difference in the three biomarkers between patients with type 2 diabetes mellitus complicated by subclinical hypothyroidism and those with type 2 diabetes mellitus alone. [β-CTX: (380.51±122.22) vs (344.60±125.61) pg/ml, OC: (13.67±4.06) vs (15.76±4.70) ng/ml, t-PINP: (38.76±9.53) vs (43.49±13.63) ng/ml] ( t=1.296,1.890,-1.799 ,all P>0.05). In the patients with type 2 diabetes mellitus complicated by subclinical hypothyroidism, the β-CTX was positively correlated with fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c)( r=0.293,0.487,all P<0.05), while OC and t-PINP were negatively correlated with FBG and HbA1c ( r=-0.560,-0.502,-0.289,-0.326, P<0.05). Conclusion:Changes of serum osteoporosis-related biomarkers in subclinical hypothyroidism patients with type 2 diabetes indicate the increased risk of osteoporosis in those patients.

Expression of miR-182-5p in patients with chronic heart failure and its correlation with left ventricular remodeling and prognosis / 中华老年心脑血管病杂志

Objective To investigate the serum expression level of miR-182-5p in patients with chronic heart failure(CHF),and analyze its correlation with left ventricular remodeling and prog-nosis.Methods A total of 138 CHF patients admitted to Liaocheng People's Hospital from Janu-ary 2019 to December 2021 were enrolled as CHF group,and another 120 healthy volunteers who took physical examinations at the same time served as the healthy group.The expression level of miR-182-5p in serum was detected in the two groups.Pearson analysis was used to analyze the correlation between its expression level and left ventricular remodeling.ROC curve was plotted to analyze the diagnostic value of miR-182-5p expression level.During 1 year of follow-up,their sur-vival status was collected and analyzed in the CHF patients.The prognostic value of miR-182-5p expression level was evaluated by Kaplan-Meier survival curve.Results The CHF patients had significantly lower LVEF value,but higher left ventricular remodeling index(LVRI)and miR-182-5p expression level than the healthy group(P＜0.05,P＜0.01).The expression level of miR-182-5p was negatively correlated with LVEF(r=-0.496,P=0.000)and positively with LVRI(r=0.460,P=0.000).The AUC value of miR-182-5p expression level in diagnosing CHF was 0.964,the cutoff value was 0.905,the sensitivity was 91.3％,and the specificity was 86.7％.Kaplan-Meier survival curve analysis showed that the high expression level of miR-182-5p could predict the overall survival of CHF patients(P=0.039).Conclusion The expression level of miR-182-5p is higher in CHF patients than healthy people,and the patients with higher level indi-cate more serious left ventricular remodeling.Detecting the expression level of miR-182-5p is help-ful for the diagnosis and poorgnosis prediction of CHF patients.

Methimazole-induced agranulocytosis and other hematologic damages: Bone marrow characteristics and literature review / 中华内分泌代谢杂志

Objective:To retrospectively analyze the bone marrow characteristics of methimazole-induced agranulocytosis and other hematologic damage, and to explore its correlation with clinical features and prognosis.Methods:The bone marrow and clinical parameters of 20 patients of Graves′ disease diagnosed with methimazole-induced agranulocytosis at the First Affiliated Hospital of Xi′an Jiaotong University from January 2000 to December 2022 were collected. The intergroup differences in bone marrow characteristics and granulocyte recovery time were analyzed. Differences in peripheral blood and bone marrow characteristics between patients with single agranulocytosis and pancytopenia were compared. Besides, literature review of the bone marrow characteristics of methimazole-induced hematologic diseases was conducted.Results:Compared to patients with bone marrow characteristics of granulocyte and precursor maturation disorders(Type Ⅱ), patients with aplastic marrow(Type Ⅰ) had significant decreases in the proportions of granulocytes in all phases( P<0.05). Patients with bone marrow characteristics of Type Ⅰ had a significant increase in the proportion of the lymphocyte system [51.00%(41.50%, 75.50%) vs 22.00%(14.00%, 35.00%), P=0.002], and got a longer to recovery time [(6.58±1.68)d vs(3.71±1.60)d, P=0.003]; Correlation analysis suggested the granulocyte to erythrocyte ratio was negatively correlated with the granulocyte recovery time( r=-0.520, P=0.023), and the proportion of the bone marrow lymphocyte was positively correlated with granulocyte recovery time( r=0.622, P=0.004). Compared to patients with single agranulocytosis, patients with pancytopenia had a markedly longer hospital stay duration [(27.14±5.27)d vs(14.15±7.36)d, P=0.001]. Literature review suggestsed that methimazole may cause various degrees of damage to blood system and bone marrow. Conclusion:Methimazole can induce a variety of hematologic damages. Analysis of bone marrow characteristics can aid in further prognosis assessment. Clinicians should be vigilant about potential hematologic adverse reactions when using methimazole and promptly diagnose and treat them to prevent serious consequences.

Therapeutic effect of low-carbohydrate diet and lifestyle intervention on patients with lean nonalcoholic fatty liver disease / 临床肝胆病杂志

ObjectiveTo investigate the therapeutic effect of low-carbohydrate diet and online lifestyle intervention on patients with lean nonalcoholic fatty liver disease （NAFLD）. MethodsThis study was conducted among 53 patients with lean NAFLD who attended Department of Infectious Diseases in Peking University Shenzhen Hospital and Shenzhen Qianhai Shekou Free Trade Zone Hospital from December 2019 to March 2021， and the patients were given low-carbohydrate diet for calorie restriction ［total calorie intake was calculated based on basal metabolic rate （BMR） and physical activity level （PAL） and was restricted within （BMR×95%×PAL-1 000） kcal to （BMR×95%×PAL-500） kcal， and carbohydrate ratio fluctuated between 10% and 55%］ and lifestyle interventions for 8 weeks. An online software was used for supervision and follow-up， and the patients were observed in terms of treatment outcome and safety. The patients were compared in terms of controlled attenuation parameter （CAP）， liver stiffness measurement （LSM）， Anthropometric parameters， blood biochemistry， urinary protein， and urine ketone body before and after intervention. The patients were followed up after 1 year to measure body weight and body mass index （BMI）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the paired-sample Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous； the chi-square test was used for comparison of categorical data between groups. ResultsAfter 8 weeks of intervention， CAP decreased from 304.47±31.91 db/m to 242.43±26.74 db/m， LSM decreased from 7.43±2.41 kPa to 6.36±1.79 kPa， and body weight decreased from 64.29±7.37 kg to 60.24±7.08 kg （t=11.25，3.72， and 14.07， all P<0.001）. Of all patients， 25 （47.2%） had disappearance of fatty liver， and abnormal LSM in 12 patients （63.2%） returned to normal； 52 patients （98.1%） had a mean reduction of 4.05±2.32 kg in body weight. The degree of reduction in CAP increased with the degree of reduction in body weight. After intervention， there were significant reductions in BMI， waist circumference， hip circumference， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， gamma-glutamyl transpeptidase （GGT）， uric acid， fasting blood glucose， triglyceride （TG）， total cholesterol （TC）， and low-density lipoprotein （LDL） and a significant increase in high-density lipoprotein （t=12.85， 13.77， 10.28， 7.64， 6.21， 8.35， 6.83， 6.31， 7.4， 4.97， 5.95， and -2.21， all P<0.05）. The patients with abnormal ALT， AST， GGT， uric acid， fasting blood glucose， TG， TC， and LDL at baseline which returned to normal after intervention accounted for 75%， 100%， 81.8%， 57.1%， 100%， 66.7%， 73.5%， and 85.3%， respectively. There were no significant changes in blood urea nitrogen， serum creatinine， urine protein， and urine ketone body （all P>0.05）. There was no rebound in body weight and BMI after 1 year of follow-up （P>0.05）. There were no gastrointestinal reactions during intervention or follow-up. ConclusionLow-carbohydrate diet and lifestyle intervention can improve liver fat content， liver function， and blood lipid parameters in patients with lean NAFLD， with good safety.

Effect of safflower yellow on learning and memory ability of APP/PS1 at different months based on TLR4/NF-KB signaling pathway / 中国药理学通报

Aim To investigate the effect of safflower yellow (SY) on learning and memory ability of APP/ PS1 mice at different disease stages, and to explore the mechanism of SY anti- Alzheimer's disease by using 3-,6- and 9-month-old APP/PS 1 transgenic mice as experimental animal models. Methods Behavioral experiments were conducted to observe the effects of SY on learning and memory of APP/PS1 mice of different months. ELISA was used to detect the effect of SY on the expression of inflammatory factors in cortex of mice of different months. Western blot was used to detect the microglia activation marker protein, and its mechanism of action was further analyzed. Results SY could enhance the learning and memory ability of mice aged 3, 6 and 9 months, reduce the content of IL-6 and increase the content of TGF-β1 in brain tissue, up-regulate the expression levels of arginase-1 (arg-1) and triggering receptor expressed on myeloid cells 2 (tREM2) in brain tissue of mice of different months, and down-regulate the expression levels of inducible nitric oxide synthase (iNOS), Toll-like receptors 4 (tlr4) and nuclear factor-kappa B (nf-KB). Conclusions Compared with 3- and 9-month-old mice, SY is the most effective in improving learning memory in 6-month-old APP/PS1 mice. SY inhibits TLR4/NF-KB pathway activation by inducing TREM2 expression in brain tissue of APP/PS 1 transgenic mice, promotes microglia phenotype shift to anti-inflammatory phenotype, reduces chronic neuroinflammatory response, and improves learning memory in APP/PS1 mice at all months of age.

Research progress on metabolic function in patients with polycystic ovary syndrome / 公共卫生与预防医学

The incidence of infertility disorders is increasing year by year, affecting about 12-15% of women of reproductive age worldwide. Polycystic ovary syndrome (PCOS) is one of the common causes of infertility. In recent years, the incidence rate of PCOS has increased year by year, but the improvement of endocrine and metabolic dysfunction and pregnancy outcomes in patients with PCOS are not satisfactory. There is a consensus both domestically and internationally that improving metabolic function and endocrine abnormalities in PCOS patients can increase their pregnancy rate. Therefore, it is important to explore the improvement of metabolic function in patients with PCOS. This article reviews the progress of basic research on improving metabolic function in patients with PCOS.

Effects of Xiaoyao San on exercise capacity and liver mitochondrial metabolomics in rat depression model / 中草药·英文版

OBJECTIVE@#This study aimed to investigate the therapeutic effects of Xiaoyao San (XYS), a herbal medicine formula, on exercise capacity and liver mitochondrial metabolomics in a rat model of depression induced by chronic unpredictable mild stress (CUMS).@*METHODS@#A total of 24 male SD rats were randomly divided into four groups: control group (C), CUMS control group (M), Venlafaxine positive treatment group (V), and XYS treatment group (X). Depressive behaviour and exercise capacity of rats were assessed by body weight, sugar-water preference test, open field test, pole test, and rotarod test. The liver mitochondria metabolomics were analyzed by using liquid chromatography-mass spectrometry (LC-MS) method. TCMSP database and GeneCards database were used to screen XYS for potential targets for depression, and GO and KEGG enrichment analyses were performed.@*RESULTS@#Compared with C group, rats in M group showed significantly lower body weight, sugar water preference rate, number of crossing and rearing in the open field test, climbing down time in the pole test, and retention time on the rotarod test (P < 0.01). The above behaviors and exercise capacity indices were significantly modulated in rats in V and X groups compared with M group (P < 0.05, 0.01). Compared with C group, a total of 18 different metabolites were changed in the liver mitochondria of rats in M group. Nine different metabolites and six metabolic pathways were regulated in the liver mitochondria of rats in X group compared with M group. The results of network pharmacology showed that 88 intersecting targets for depression and XYS were obtained, among which 15 key targets such as IL-1β, IL-6, and TNF were predicted to be the main differential targets for the treatment of depression. Additionally, a total of 1 553 GO signaling pathways and 181 KEGG signaling pathways were identified, and the main biological pathways were AGE-RAGE signaling pathway, HIF-1 signaling pathway, and calcium signaling pathway.@*CONCLUSION@#XYS treatment could improve depressive symptoms, enhance exercise capacity, positively regulate the changes of mitochondrial metabolites and improve energy metabolism in the liver of depressed rats. These findings suggest that XYS exerts antidepressant effects through multi-target and multi-pathway.

Evaluation of the clinical relevant effect of hospital-wide blood glucose management in perioperative cholelithiasis patients with type 2 diabetes / 中华临床营养杂志

Objective:To evaluate the clinical relevant effect of hospital-wide blood glucose management in perioperative cholelithiasis patients with type 2 diabetes.Methods:The subjects of the study were patients with type 2 diabetes mellitus complicated with cholelithiasis who were treated at the Baiqiu'en Hospital in Shanxi from September 2022 to October 2023. The patients were divided into hospital-wide blood sugar management group and conventional treatment group, according to different blood glucose management they received. The differences in preoperative blood glucose control, length of stay, postoperative complications, and hospitalization expenses between the two groups were compared.Results:Compare based on the median (quartiles) of the observed indicators, patients with cholelithiasis who underwent hospital-wide blood glucose management based on insulin pumps had a higher proportion of time in range [72.00(70.21, 82.90)% vs. 64.80 (61.55,70.50)%, P<0.001)], lower average blood glucose level [9.00 (8.55, 10.44) mmol/L vs. 11.50 (10.50, 12.50) mmol/L, P<0.001], and shorter hospital stay [8.00 (7.00,13.00) days vs. 10.00 (8.00, 12.00) ) days, P<0.05]. Moreover, the incidence of postoperative complications was lower [5(11.11)% vs. 15(33.33)%, P<0.05], and hospitalization expenses were lower [16 535.34 (14 271.44, 29 569.23) yuan vs. 18 633.85 (17 482.66) yuan , 22 855.02) yuan, P<0.05] in patients who received hospital-wide blood glucose management. Conclusion:Hospital-wide blood glucose management based on insulin pumps showed favorable effects in the perioperative clinical application in cholelithiasis patients with type 2 diabetes, and could contribute to shortening the average length of stay, reducing hospitalization costs, and reducing postoperative complications.

Investigation on the signaling pathways in the mechanism of hyperoxia-induced acute lung injury based on transcriptomics sequencing / 中华危重病急救医学

Objective:To observe and verify the changes of transcriptome in hyperoxia-induced acute lung injury (HALI), and to further clarify the changes of pathways in HALI.Methods:Twelve healthy male C57BL/6J mice were randomly divided into normoxia group and HALI group according to the random number table, with 6 mice in each group. The mice in the normoxia group were fed normally in the room, and the mice in the HALI group was exposed to 95% oxygen to reproduce the HALI animal model. After 72 hours of hyperoxia exposure, the lung tissues were taken for transcriptome sequencing, and then Kyoto Encyclopedia of Genes and Genomes database (KEGG) pathway enrichment analysis was performed. The pathological changes of lung tissue were observed under light microscope after hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to verify the key molecules in the signal pathways closely related to HALI identified by transcriptomics analysis.Results:Transcriptomic analysis showed that hyperoxia induced 537 differentially expressed genes in lung tissue of mice as compared with the normoxia group including 239 up-regulated genes and 298 down-regulated genes. Further KEGG pathway enrichment analysis identified 20 most significantly enriched pathway entries, and the top three pathways were ferroptosis signaling pathway, p53 signaling pathway and glutathione (GSH) metabolism signaling pathway. The related genes in the ferroptosis signaling pathway included the up-regulated gene heme oxygenase-1 (HO-1) and the down-regulated gene solute carrier family 7 member 11 (SLC7A11). The related genes in the p53 signaling pathway included the up-regulated gene tumor suppressor gene p53 and the down-regulated gene murine double minute 2 (MDM2). The related gene in the GSH metabolic signaling pathway was up-regulated gene glutaredoxin 1 (Grx1). The light microscope showed that the pulmonary alveolar structure of the normoxia group was normal. In the HALI group, the pulmonary alveolar septum widened and thickened, and the alveolar cavity shrank or disappeared. RT-RCR and Western blotting confirmed that compared with the normoxia group, the mRNA and protein expressions of HO-1 and p53 in lung tissue of the HALI group were significantly increased [HO-1 mRNA (2 -ΔΔCt): 2.16±0.17 vs. 1.00±0.00, HO-1 protein (HO-1/β-actin): 1.05±0.01 vs. 0.79±0.01, p53 mRNA (2 -ΔΔCt): 2.52±0.13 vs. 1.00±0.00, p53 protein (p53/β-actin): 1.12±0.02 vs. 0.58±0.03, all P < 0.05], and the mRNA and protein expressions of Grx1, MDM2, SLC7A11 were significantly decreased [Grx1 mRNA (2 -ΔΔCt): 0.53±0.05 vs. 1.00±0.00, Grx1 protein (Grx1/β-actin): 0.54±0.03 vs. 0.93±0.01, MDM2 mRNA (2 -ΔΔCt): 0.48±0.03 vs. 1.00±0.00, MDM2 protein (MDM2/β-actin): 0.57±0.02 vs. 1.05±0.01, SLC7A11 mRNA (2 -ΔΔCt): 0.50±0.06 vs. 1.00±0.00, SLC7A11 protein (SLC7A11/β-actin): 0.72±0.03 vs. 0.98±0.01, all P < 0.05]. Conclusions:HALI is closely related to ferroptosis, p53 and GSH metabolism signaling pathways. Targeting the key targets in ferroptosis, p53 and GSH metabolism signaling pathways may be an important strategy for the prevention and treatment of HALI.

Effects of electroacupuncture on NLRP3/Caspase-1/GSDMD axis and neurological function in rats with cerebral ischemic reperfusion / 中国针灸

OBJECTIVE@#To investigate the neuroprotective effect of electroacupuncture (EA) at "Quchi" (LI 11) and "Zusanli" (ST 36) in the rats with cerebral ischemic reperfusion and the potential mechanism of microglia pyroptosis.@*METHODS@#Sixty SD rats were randomly divided into a sham-operation group, a model group and an EA group, with 20 rats in each group. The Zea Longa method was employed to establish the rat model of the middle cerebral artery occlusion and reperfusion (MACO/R) in the left brain. In the EA group, since the 2nd day of modeling, EA was given at "Quchi" (LI 11) and "Zusanli" (ST 36) of right side with disperse-dense wave, 4 Hz/20 Hz in frequency and 0.2 mA in current intensity, 30 min each time, once a day for lasting 7 consecutive days. The reduction rate of cerebral blood flow was measured with laser Doppler flowmetry during operation. The neurological function of rats was observed using Zea Longa neurobehavioral score. The cerebral infarction volume was detected by TTC staining method. The microglia positive expression in the ischemic side of the cortex was detected with the immunofluorescence method. Under transmission electron microscope, the ultrastructure of cell in the ischemic cortex was observed. The mRNA expression levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cysteinyl aspartate specific proteinase-1 (Caspase-1) and gasdermin D (GSDMD) in the ischemic cortex were detected using real-time PCR.@*RESULTS@#Compared with the sham-operation group, in the model group, the reduction rate of cerebral blood flow was increased during operation (P<0.001); Zea Longa neurobehavional score and the percentage of cerebral infarction volume were increased (P<0.001), the numbers of M1-type microglia marked by CD68+ and M2-type microglia marked by TMEM119+ were elevated in the ischemic cortex (P<0.001), the mRNA expression of NLRP3, ASC, Caspase-1 and GSDMD was increased (P<0.001, P<0.01); the cytomembrane structure was destroyed, with more cell membrane pores formed in the ischemic cortex. Compared with the model group, after intervention, Zea Longa neurobehavioral score and the percentage of cerebral infarction volume were reduced (P<0.05), the number of M1-type microglia marked by CD68+ was reduced (P<0.05) and the number of M2-type microglia marked by TMEM119+ was increased (P<0.05); and the mRNA expression of NLRP3, ASC, Caspase-1 and GSDMD was decreased (P<0.01, P<0.05) in the EA group. Even though the cytomembrane structure was incomplete, there were less membrane pores presented in the ischemic cortex in the EA group after intervention.@*CONCLUSION@#The intervention with EA attenuates the neurological dysfunction and reduces the volume of cerebral infarction in the rats with cerebral ischemic reperfusion. The underlying mechanism is related to the inhibition of microglia pyroptosis through modulating NLRP3/Caspase-1/GSDMD axis.

Scientific basis of acupuncture on mesenchymal stem cells for treating ischemic stroke / 中国针灸

The scientific basis of acupuncture on mesenchymal stem cells (MSCs) for treating ischemic stroke (IS) is discussed. MSCs transplantation has great potential for the treatment of tissue damage caused by early stage inflammatory cascade reactions of IS, but its actual transformation is limited by various factors. How to improve the homing efficiency of MSCs is the primary issue to enhance its efficacy. As such, the possible mechanisms of acupuncture and MSCs transplantation in inhibiting inflammatory cascade reactions induced by IS are explored by reviewing literature, and a hypothesis that acupuncture could promote the secretion of stromal cell-derived factor-1α (SDF-1α) from ischemic foci to regulate SDF-1α/CXC chemokine receptor 4 (CXCR4) axis, thereby improving the homing efficiency of MSCs transplantation, exerting its neuroprotective function, and improving the bed transformation ability, is proposed.

The short-term outcomes of non-contact low frequency ultrasonic debridement in treating periprosthetic joint infections:a prospective single-arm clinical study / 中华外科杂志

Objective: To evaluate the short-term outcomes of non-contact low-frequency ultrasonic debridement in treating periprosthetic joint infections(PJI). Methods: The clinical data of patients with PJI who met the eligibility criteria and were treated with non-contact low-frequency ultrasonic debridement from August 2021 to January 2022 at the Department of Orthopaedics,the First Affiliated Hospital of Xinjiang Medical University were prospectively analyzed. PJI was defined according to the modified Musculoskeletal Infection Society criteria in 2016. After mechanical debridement,an 8-mm handheld non-contact low-frequency ultrasound probe was used for ultrasonic debridement in the whole surgical area at a frequency of (25±5)kHz and power of 90% for 5 minutes. Each ultrasound lasted 10 seconds with 3-second intervals. The probe was repeatedly sonicated among all soft tissue,bone interface and metal prosthesis surface(patients underwent debridement,antibiotics and implant retention (DAIR)) in the surgical area. The femoral canal of the hip joint,the distal femoral canal and the posterior capsule of the knee were fully sonicated with a special right-angle probe. Before and after ultrasonic debridement,20 ml of liquid was extracted from each operation area and injected into aerobic and anaerobic culture bottles,respectively,for pathogen culture. Harris hip score and Hospital for Special Surgery (HSS) score were used to evaluate clinical function. Treatment failure was defined as the recurrence of infection in the same joint. The patients were routinely followed up in the outpatient clinic at 1,3,and 6 months postoperatively and then annually with a deadline of August 2022. The paired t-test,rank sum,Mann-Whitney U or χ2 test was used to compare the observed data,and rates among multiple groups were compared using the Bonferroni approach. Results: A total of 45 patients were included in the study,including 21 men and 24 women with age of (65.8±15.2)years(range: 20 to 80 years) and body mass index of (29.3±4.2)kg/m2(range: 20.2 to 38.5 kg/m2). Twenty-eight patients (18 hips and 10 knees) underwent one-stage revision,and 17 cases (5 hips and 12 knees) underwent DAIR. Three of the patients (6.7%) had recurrent infections during follow-up. There were no intraoperative complications related to ultrasonic debridement (neurovascular and muscle injury,poor wound healing and fat liquefaction). Seventeen patients who received DAIR were followed for a median(M(IQR)) of 9(3) months,and two relapsed 3 weeks and 3 months post-operation,respectively. In addition,28 patients who underwent one-stage revision were followed for a median of 9(2) months,and one of the patients (3.6%,1/28) had a recurrence 6 months post-operation. The culture-positive rate of preoperative aspiration was 47.6% (20/42). The data of intraoperative soft tissue culture was 86.7% (39/45). The culture-positive rate of wound liquid before ultrasonic debridement was 46.7% (21/45). And the culture-positive rate after ultrasonic debridement was (75.6% (34/45)). After sonication,the culture-positive rate of explanted prostheses was 88.9% (40/45). There was a significant difference in culture-positive rates among all five cultures (χ2=35.483,P<0.01). Further pairwise comparison showed that the culture-positive rate of wound liquid after ultrasonic debridement was higher than that before ultrasonic debridement (χ2=7.901,P=0.005) but was not significantly different from the positive rates of other cultures (all P>0.05). The median number of colonies 24 hours after ultrasonic debridement(2 240 (1 310) CFU/ml,range: 310 to 3 140 CFU/ml) was significantly higher than that before debridement(450 (550) CFU/ml,range: 10 to 910 CFU/ml) (U=43, P=0.017). The post-operative Harris ((78.6±4.2)points,range:70.5 to 85.3 points) and HSS scores((76.4±4.8)points,range: 68.5 to 84.3 points) were significantly higher than the preoperative scores((46.0±9.8)points,range: 27.5 to 64.3 points;and (45.5±10.3)points,range: 27.6 to 63.1 points) (t=-14.6,t=-12.7;both P<0.01). Conclusions: Non-contact low-frequency ultrasonic debridement can increase the culture-positive rate and lead to a favorable short-term outcome. In addition,no complications are associated with using this new technique to treat PJI.

The directionality of measurement bias: a directed acyclic graph-based structural perspective / 中华流行病学杂志

Measurement bias (MB) has been described in causal structures but is still not entirely clear. In practice, the correctness of substitution estimate (SE) of effect is a prerequisite for causal inference, usually based on a bidirectionally non-differential misclassification between the measured exposure and the measured outcome. Based on a directed acyclic graph (DAG), this paper proposes a structure for the single-variable measure, where its MB is derived from the choice of an imperfect, "input/output device-like" measurement system. The MB of the SE is influenced both by the measurement system itself and by factors outside the measurement system: while the independence or dependence mechanism of the measurement system still ensures that the MB of the SE is bidirectionally non-differential; however, the misclassification can be bidirectionally non-differential, unidirectionally differential, or bidirectionally differential resulted from the factors outside the measurement system. In addition, reverse causality should be defined at the level of measurement, where measured exposures can influence measured outcomes and vice versa. Combined with temporal relationships, DAGs help elucidate MB's structures, mechanisms, and directionality.

Association between gestational diabetes mellitus and preterm birth subtypes / 中华流行病学杂志

Objective: To investigate the association between gestational diabetes mellitus (GDM) and preterm birth subtypes. Methods: Based on the cohort of pregnant women in Anqing Prefectural Hospital, the pregnant women who received prenatal screening in the first or second trimesters were recruited into baseline cohorts; and followed up for them was conducted until delivery, and the information about their pregnancy status and outcomes were obtained through electronic medical record system and questionnaire surveys. The log-binomial regression model was used to explore the association between GDM and preterm birth [iatrogenic preterm birth, spontaneous preterm birth (preterm premature rupture of membranes and preterm labor)]. For multiple confounding factors, the propensity score correction model was used to compute the adjusted association. Results: Among the 2 031 pregnant women with a singleton delivery, the incidence of GDM and preterm birth were 10.0% (204 cases) and 4.4% (90 cases) respectively. The proportions of iatrogenic preterm birth and spontaneous preterm birth in the GDM group (n=204) were 1.5% and 5.9% respectively, while the proportions in non-GDM group (n=1 827) were 0.9% and 3.2% respectively, and the difference in the proportion of spontaneous preterm birth between the two groups was significant (P=0.048). Subtypes of spontaneous preterm were further analyzed, and the results showed that the proportions of preterm premature rupture of membranes and preterm labor in the GDM group were 4.9% and 1.0% respectively, while the proportions in the non-GDM group were 2.1% and 1.1% respectively. It showed that the risk of preterm premature rupture of membranes in GDM pregnant women was 2.34 times (aRR=2.34, 95%CI: 1.16-4.69) higher than that in non-GDM pregnant women. Conclusions: Our results showed that GDM might increase the risk of preterm premature rupture of membranes. No significant increase in the proportion of preterm labor in pregnant women with GDM was found.

Analysis of healthy life expectancy and related socioeconomic influencing factors among the middle-aged and elderly in China, the United States, and the European Union / 中华流行病学杂志

Objective: To calculate and compare the healthy life expectancy (HLE) of the middle-aged and elderly in China, the United States, and developing and developed countries in the European Union(EU) and analyze the impact of socioeconomic factors on HLE in different countries or regions. Methods: Four surveys from 2010 to 2019 were brought into the research. The data were collected from the China Health and Retirement Longitudinal Study, Health and Retirement Study, and the Survey of Health, Ageing and Retirement in Europe. Developed and developing countries in the EU were divided into two groups for calculation. Education level, total family wealth, and work retirement status were selected to measure socioeconomic status, and activities of daily living were used as health status indicators. We used the multi-state life cycle table method to calculate the transition probability between different health states and estimate life expectancy and HLE. Results: A total of 69 544 samples were included in the study. In terms of age, the middle-aged and elderly in the United States and developed countries of the EU have higher HLE in all age groups. In terms of gender, only Chinese women have lower HLE than men. Regarding socioeconomic factors, the middle-aged and elderly with higher education levels and total family wealth level have higher HLE. In China, working seniors have higher HLE, while for USA women and developed countries of the EU, retired or unemployed seniors have higher HLE. Conclusions: Demographic and socioeconomic factors impact HLE in different countries or regions. China should pay more attention to the health of women and the middle-aged and elderly retired with lower education and less total family wealth.

Clinical characteristics of acute occupational poisoning caused by carbon dioxide leakage from a cargo ship / 中华劳动卫生职业病杂志

Carbon dioxide is a simple asphyxial gas, with low concentrations having an excitatory effect on the respiratory center, while high concentrations have an inhibitory effect on the respiratory center. Simple carbon dioxide poisoning is rarely seen clinically. This article reviews and analyzes the treatment process of 9 cases of acute inhalation carbon dioxide poisoning in a cargo ship carbon dioxide leakage accident in May 2019, summarizes clinical treatment experience, and provides timely and effective treatment for acute pulmonary edema caused by acute inhalation carbon dioxide poisoning. In particular, the application of hormones has a good prognosis, improving clinicians' understanding of the disease.

Therapeutic effect and prognosis of PKP in patients with diabetes mellitus complicated with osteoporotic thoracolumbar compression fractures / 中华内分泌外科杂志

Objective:To investigate the therapeutic effect and prognosis of percutaneous balloon kyphoplasty (PKP) for diabetic patients with osteoporotic thoracolumbar compression fractures.Methods:A total of 105 patients with diabetes mellitus complicated with osteoporotic thoracolumbar compression fractures who received diagnosis and treatment in our hospital from May. 2017 to Feb. 2020, who were followed up to Mar. 2022 were selected as the research subjects, and all were treated with PKP. Time, intraoperative blood loss, hospital stay, incidence of secondary vertebral fracture, anterior height of injured vertebral body, Sagittal kyphosis Cobb angle, VAS score, and ODI index were investigated. The patients were divided into good prognosis group ( n=82) and poor prognosis group ( n=23) according to the presence or absence of secondary vertebral fractures during the follow-up period. Binary Logistic regression model was used to analyze the risk factors affecting the prognosis. Results:After PKP treatment, the efficiency of all 105 patients was 87.62% and the incidence of secondary vertebral fracture was 21.90%. The operative time was (83.52±16.85) min, the intraoperative blood loss was (32.11±1.52) ml, and the length of hospital stay was (10.62±1.65) d. The height of the anterior edge of the injured vertebra was (24.62±5.16) mm and (24.67±5.03) mm at the last follow-up and 3 months after surgery, respectively, higher than that before surgery ( t=15.21, 15.63, P=0.000). The Cobb angle of sagittal kyphosis was (10.03±1.27) ° and (10.10±1.25) °, respectively, and the VAS score was (3.11±0.52) and (1.00±0.11) points, respectively, 3 months after surgery and at the last follow-up. The ODI indexes were (11.25±2.85) % and (5.32±1.01) %, respectively, lower than those before surgery ( t3 months after surgery=28.84, 18.17, 29.21, tlast follow-up=25.68, 27.49, 42.78, P=0.000). There were significant differences in age, BMD, bone cement leakage, bone cement distribution and use of anti-osteoporosis drugs between the good prognosis group and the poor prognosis group ( t=4.03, 5.22, χ2=12.50, 22.694, 26.22, P=0.000). Logistic regression analysis showed that age ( OR=1.309, 95%CI=1.134-1.511, P=0.000), BMD ( OR=126.660, 95%CI=13.376-1199.376, P=0.000), bone cement leakage ( OR=4.698, 95%CI=1.306-16.902, P=0.018), dense distribution of bone cement ( OR=9.697, 95%CI=2.679-34.869, P=0.001), no use of anti-osteoporosis drugs ( OR=7.586, 95%CI=2.197-26.193, P=0.001) was an independent risk factor for the prognosis of patients with diabetes complicated with osteoporotic thoracolumbar compression fracture. Conclusion:PKP has a high rate of excellence in the treatment of diabetes mellitus complicated with osteoporotic thoracolumbar compression fractures, but factors such as age, BMD, bone cement leakage, bone cement dense distribution, and no postoperative use of anti-osteoporotic drugs will increase risks of secondary fractures, which in turn affects their prognosis.

SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity / 药物分析学报

Small ubiquitin-related modifier(SUMOylation)is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload.However,the function of SUMOylation after myocardial infarction(MI)and the molecular details of heart cell responses to SUMO1 deficiency have not been determined.In this study,we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI.However,SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury.Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells.Among cardiomyocytes,SUMO1 deletion increased the Nppa+Nppb+Ankrd1+cardiomyocyte subcluster pro-portion after MI.In addition,the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice.Importantly,SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes.Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium.Mice preinjected with cardiomyocyte-specific AAV-SUMO1,but not the endothelial cell-specific form,and exhibited ameliorated cardiac remodeling following MI.Collectively,our results identified the role of SUMO1 in cardiomyocytes,fibroblasts,and endothelial cells after Ml.These findings provide new insights into SUMO1 involvement in the patho-genesis of MI and reveal novel therapeutic targets.

Clinical study of radiation exposure from atrial fibrillation catheter ablation guided by magnetic navigation system and cryoballoon / 中华放射医学与防护杂志

Objective:To identify the method to reduce X-ray exposure during ablation of atrial fibrillation (AF) by comparing the cryoballoon (CRYO) ablation and remote magnetic navigation (RMN) ablation.Methods:A retrospective analysis was conducted on 144 patients undergoing CRYO ablation (CRYO group) and 121 patients undergoing RMN ablation (RMN group) in our hospital. Entrance surface doses at reference points online, exposure time during procedure and outcomes were analyzed for different types of patients.Results:Compared with the RMN group, the procedure time for the CRYO group significantly decreased [(165.0±23.6), (97.8±18.4) min, t=26.05, P<0.001]. However, the entrance surface dose value [(232.3±130.7), (669.0±387.5) mGy, Z=-12.29, P<0.001] and X-ray exposure time [(8.1±3.1), (23.4±6.2) min, t=-24.57, P<0.001] increased significantly for the CRYO group. No significant difference was found between the two groups in the proportion of maintaining sinus rhythm during follow-up of patients (71.9%, 75.7%, P=0.618). Multiple regression analysis showed that obese patients, patients with non-paroxysmal AF and patients with variant pulmonary veins were associated with an increase in entrance surface dose values in the CRYO group ( t=5.47, 2.23, 3.39, P<0.05). The X-ray exposure time for the three types patients above in the CRYO group also increased ( t=2.87, 3.86, 3.25, P<0.05) in the CRYO group. However, only obese patients in the RMN group had an increase in entrance surface dose value ( Z=-4.15, P<0.001) and no increase in exposure time. For the three types of patients above, there was no significant difference in proportion of maintaining sinus rhythm between the CRYO group and the RMN group during follow-up ( P>0.05). Conclusions:Compared with RMN ablation, the radiation exposure of CRYO AF ablation significantly increased, especially in obese patients, patients with non-paroxysmal AF and patients with pulmonary veins variation. The use of RMN for these types of patients may reduce the radiation exposure without affecting the procedure outcomes.