Baihe Wuyaotang Ameliorates NAFLD by Enhancing mTOR-mediated Liver Autophagy / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang （BWT） on non-alcoholic fatty liver disease （NAFLD） and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups： normal control， model， positive drug （pioglitazone hydrochloride 1.95×10-3 g·kg-1）， and low-， medium-， and high-dose BWT （1.3，2.5 and 5.1 g·kg-1）. Following a 12-week high-fat diet （HFD） inducement， the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week， glucose tolerance （GTT） and insulin tolerance （ITT） tests were conducted. Subsequently， the mice were euthanized for the collection of liver tissue and serum， and the subcutaneous adipose tissue （iWAT） and epididymal adipose tissue （eWAT） were weighed. Serum levels of total triglycerides （TG） and liver function indicators，such as alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， were determined. Histological examinations， including oil red O staining， hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy， were performed to evaluate hepatic lipid deposition， pathological morphology， and ultrastructural changes， respectively. Meanwhile， Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to analyze alterations， at both gene and protein levels， the insulin signaling pathway molecules， including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 （IRS1/2/Akt/FoxO1）， glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase （Pepck） and glucose-6-phosphatase （G6Pase）， lipid metabolism-related genes stearoyl-coA desaturase-1 （SCD-1） and carnitine palmitoyltransferase-1 （CPT-1）， fibrosis-associated molecules α-smooth muscle actin （α-SMA）， type Ⅰ collagen （CollagenⅠ）， and the fibrosis canonical signaling pathway transforming growth factor-β1/drosophila mothers against decapentaplegic protein2/3（TGF-β1/p-Smad/Smad2/3）， inflammatory factors such as interleukin（IL）-6， IL-8， IL-11， and IL-1β， autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1， and the expression of mammalian target of rapamycin （mTOR）. ResultCompared with the model group， BWT reduced the body weight and liver weight of NAFLD mice（P<0.05， P<0.01）， inhibited liver lipid accumulation， and reduced the weight of white fat： it reduced the weight of eWAT and iWAT（P<0.05， P<0.01） as well as the serum TG content（P<0.05， P<0.01）. BWT improved the liver function as reflected by the reduced ALT and AST content（P<0.05， P<0.01）. It improved liver insulin resistance by upregulating IRS2， p-Akt/Akt， p-FoxO1/FoxO1 expressions（P<0.05）. Besides， it improved glucose and lipid metabolism disorders： it reduced fasting blood glucose and postprandial blood glucose（P<0.05， P<0.01）， improved GTT and ITT（P<0.05， P<0.01）， reduced the expression of Pepck， G6Pase， and SCD-1（P<0.01）， and increased the expression of CPT-1（P<0.01）. The expressions of α-SMA， Collagen1， and TGF-β1 proteins were down-regulated（P<0.05， P<0.01）， while the expression of p-Smad/Smad2/3 was downregulated（P<0.05）， suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6， IL-8， IL-11 and IL-1β（P<0.01） and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression（P<0.05）while downregulating the expression of p62/SQSTM1 and mTOR（P<0.05）. ConclusionBWT ameliorates NAFLD by multifaceted improvements， including improving IR and glucose and lipid metabolism， anti-inflammation， anti-fibrosis， and enhancing autophagy. In particular， BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.

Effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism / 环境与职业医学

Background Long-term exposure to noise during sleep may has adverse effects on metabolic system, and liver lipid metabolism is closely related to circadian clock genes. Objective To investigate the effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism in mice and its related mechanism. Methods Twenty C57BL/6J male mice were randomly divided into two groups: a noise exposure group and a control group with 10 mice in each group. The mice in the noise exposure group were exposed to white noise at 90 dB sound pressure level (SPL) for 30 consecutive days, 8 h a day, from 9:00 to 17:00. The mice in the control group were exposed to background noise ≤40 dB SPL. After noise exposure, the animals were neutralized at 14:00 (ZT6) and 2:00 (ZT18), 5 animals at each time spot, and the liver tissues were collected. Total cholesterol and triglyceride in liver were determined by cholesterol oxidase method and glycerol phosphate oxidase method respectively. The expressions of circadian clock genes (Clock, Bmal1, Rev-erbα, and Rev-erbβ) and lipid metabolism genes (Srebp1c, Hmgcr, Fasn, Lxrα, Acc1, and Chrebp) in liver were detected by quantitative real-time PCR. Results Compared with the control group, the content of total cholesterol in liver in the noise exposure group increased by 48% (P<0.05) and the content of liver triglyceride increased by 61% (P<0.05) at ZT18. The mRNA expression levels of circadian clock genes Clock and Bmal1 in the noise exposure group was significantly increased at ZT18 and decreased at ZT6 (P<0.05). The mRNA expression level of Rev-erbα decreased at both ZT6 and ZT18 (P<0.05). The mRNA expression level of Rev-erbβ had no significant change at ZT6 and ZT18. The mRNA expression levels of liver lipid metabolism related genes Srebp1c, Hmgcr, Chrebp, and Lxrα in the noise exposure group were higher than those in the control group at ZT18 (P<0.05). The mRNA expression levels of Acc1 and Fasn showed no significant change at ZT6, then an upward trend at ZT18, but no significant difference between the two time spots (P>0.05). Conclusion Long-term noise exposure during sleep can cause circadian clock and lipid metabolism disorders in mice. Among them, suppression of key circadian clock genes may be associated with Rev-erbα-mediated upregulation of the nuclear receptors Srebp1c and Chrebp for lipid synthesis and deposition in the liver, resulting in lipid metabolism disorder.

Exploring the mechanism of Xihuang Pill's anti-hyperplasia of mammary glands effect based on UPLC-Q-orbitrap-MS technology / 药学学报

Based on UPLC-Q-orbitrap-MS and biological network analysis tools, the mechanism of Xihuang Pill in improving hyperplasia of mammary glands was systematically analyzed. The rat model of hyperplasia of mammary glands was established by intramuscular injection of estradiol benzoate and progesterone. LC-MS tissue metabolomics was used to explore the key metabolites and metabolic pathways of Xihuang Pill in improving hyperplasia of mammary glands in rat. The network analysis of the key metabolites regulated by Xihuang Pill was carried out by integrating biological network analysis tools, focusing on the key metabolic pathways, and exploring the potential targets of Xihuang Pill to improve hyperplasia of mammary glands. Compared with the control group, there were significant differences in the content of 49 differential metabolites in the tissues of the model group (P < 0.05). Xihuang Pills could significantly call back 17 metabolites such as L-alanine, threonine, indole-3-carboxylic aldehyde, lysine, arginine, alanylleucine, glycyltyrosine, γ-glutamyl leucine, vitamin B3, serine leucine, threonine leucine, isoleucine glutamic acid, γ-glutamyl tyrosine, decanoyl-L-carnitine, uric acid, leucylleucine, S-adenosyl-methionine. Further network analysis and literature research on the key metabolites regulated by Xihuang Pills showed that the AGE-RAGE signaling pathway may be one of the important pathways for Xihuang Pills to improve hyperplasia of mammary glands. STAT3, MAPK1, EGFR, CASP3, CASP8, PRKCA and JUN in the AGE-RAGE signaling pathway may be potential targets for Xihuang Pills to improve hyperplasia of mammary glands. The animal experiment operations involved in this paper follow the provisions of the Animal Ethics Committee of Gansu University of Traditional Chinese Medicine and pass the ethical review of animal experiments (approval number: 2022-705).

Lung transplantation after paraquat poisoning in an adolescent: one case report and literature review / 器官移植

Objective To summarize the effect of the timing of lung transplantation and related treatment measures on clinical prognosis of patients with paraquat poisoning. Methods Clinical data of a patient with paraquat poisoning undergoing bilateral lung transplantation were retrospectively analyzed. Clinical manifestations, auxiliary examination, diagnosis and treatment of this patient were summarized and analyzed. Results A 17-year-old adolescent was admitted to hospital due to nausea, vomiting, cough and systemic fatigue after oral intake of 20-30 mL of 25% paraquat. After symptomatic support treatment, the oxygen saturation was not improved, and pulmonary fibrosis continued to progress. Therefore, sequential bilateral lung transplantation was performed under extracorporeal membrane oxygenation (ECMO). After postoperative rehabilitation and active prevention and treatment for postoperative complications, the patient was discharged at postoperative 50 d. Conclusions The timing of lung transplantation after paraquat poisoning may be selected when the liver and kidney function start to recover. Active and targeted prevention of potential pathogen infection in perioperative period and early rehabilitation training contribute to improving clinical prognosis of lung transplant recipients.

Effect and Mechanism of Total Saponins from Panax Japonicus on White Adipose Tissue Browning/Brown Adipose Tissue Activation in High-fat Diet-induced Mice / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of total saponins from Panax japonicus （TSPJ） on white adipose tissue （WAT） browning/brown adipose tissue （BAT） activation in C57BL6/J male mice fed on a high-fat diet （HFD）. MethodThirty-two C57BL6/J male mice （8-week-old） were randomly divided into a normal group， a model group， a low-dose TSPJ group， and a high-dose TSPJ group. The mice in the low-dose and high-dose TSPJ groups were given TSPJ for four months by gavage at 25， 75 mg·kg-1·d-1， respectively， and those in the other groups were given 0.5% sodium carboxymethyl cellulose （CMC-Na） accordingly. After four months of feeding， all mice were placed at 4 ℃ for acute cold exposure， and the core body temperature was monitored. Subsequently， all mice were sacrificed， and BAT and inguinal WAT （iWAT） were separated rapidly to detect the corresponding indexes. Hematoxylin-eosin （HE） staining was used to observe the morphological changes in each group. The effect of TSPJ on the mRNA expression of uncoupling protein 1 （UCP1）， fatty acid-binding protein 4 （FABP4）， cytochrome C （CytC）， PR domain-containing protein 16 （PRDM16）， elongation of very long chain fatty acids protein 3 （ELOVL3）， peroxisome proliferator-activated receptor γ （PPARγ）， and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） in iWAT and BAT was detected by Real-time polymerase chain reaction （Real-time PCR）. Western blot was also used to detect the protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in BAT and iWAT of each group. The effect of TSPJ on UCP1 expression in BAT and iWAT was detected by immunohistochemistry. Result① Compared with the model group， TSPJ could decrease the body weight and proportions of iWAT and BAT in the HFD-induced mice （P<0.05， P<0.01）. ② The body temperature of mice in the model group decreased compared with that in the normal group in the acute cold exposure tolerance test （P<0.05）. The body temperature in the high-dose TSPJ group increased compared with that in the model group （P<0.01）. ③ Compared with the normal group， the model group showed increased adipocyte diameter in iWAT and BAT and decreased number of adipocytes per unit area. Compared with the model group， the TSPJ groups showed significantly reduced cell diameter and increased number of cells per unit area， especially in the high-dose TSPJ group. ④ Compared with the normal group， the model group showed decreased mRNA expression of FABP4， UCP1， CytC， PRDM16， ELOVL3， PGC-1α， and PPARγ in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the mRNA expression was significantly up-regulated （P<0.05， P<0.01）. ⑤ Compared with the normal group， the model group showed decreased protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the protein expression increased significantly （P<0.05， P<0.01）. ConclusionTSPJ could induce the browning of iWAT/BAT activation and enhance adaptive thermogenesis in obese mice induced by HFD. The underlying mechanism may be attributed to the activation of the PPARγ/PGC-1α signaling pathway.

Noninvasive Diagnostic Technique for Nonalcoholic Fatty Liver Disease Based on Features of Tongue Images / 中国结合医学杂志

OBJECTIVE@#To investigate a new noninvasive diagnostic model for nonalcoholic fatty liver disease (NAFLD) based on features of tongue images.@*METHODS@#Healthy controls and volunteers confirmed to have NAFLD by liver ultrasound were recruited from China-Japan Friendship Hospital between September 2018 and May 2019, then the anthropometric indexes and sampled tongue images were measured. The tongue images were labeled by features, based on a brief protocol, without knowing any other clinical data, after a series of corrections and data cleaning. The algorithm was trained on images using labels and several anthropometric indexes for inputs, utilizing machine learning technology. Finally, a logistic regression algorithm and a decision tree model were constructed as 2 diagnostic models for NAFLD.@*RESULTS@#A total of 720 subjects were enrolled in this study, including 432 patients with NAFLD and 288 healthy volunteers. Of them, 482 were randomly allocated into the training set and 238 into the validation set. The diagnostic model based on logistic regression exhibited excellent performance: in validation set, it achieved an accuracy of 86.98%, sensitivity of 91.43%, and specificity of 80.61%; with an area under the curve (AUC) of 0.93 [95% confidence interval (CI) 0.68-0.98]. The decision tree model achieved an accuracy of 81.09%, sensitivity of 91.43%, and specificity of 66.33%; with an AUC of 0.89 (95% CI 0.66-0.92) in validation set.@*CONCLUSIONS@#The features of tongue images were associated with NAFLD. Both the 2 diagnostic models, which would be convenient, noninvasive, lightweight, rapid, and inexpensive technical references for early screening, can accurately distinguish NAFLD and are worth further study.

Association between exposure patterns of adverse childhood experiences and anxiety symptom trajectories in medical college students / 中华预防医学杂志

Objective: To analyze the association between exposure patterns of adverse childhood experiences (ACEs) and anxiety symptom trajectories in medical college students. Methods: A survey was conducted on first-year students from Anhui Medical College and Anqing Medical College, using the Childhood Abuse Questionnaire, Family Disability Questionnaire, Childhood Adverse Social Experience Item, and Anxiety Self Rating Scale. The baseline survey was conducted from November to December 2019, and two follow-up visits were conducted once every six months until November to December 2020. The latent class analysis (LCA) was used to analyze the exposure patterns of ACEs. The latent class growth analysis (LCGA) was used to analyze the development trajectory of anxiety symptoms. The multiple logistic regression model was used to analyze the correlation between different exposure patterns of ACEs and the trajectory of anxiety symptom trajectories. Results: A total of 3 662 college students aged (19.2±1.0) were surveyed. The LCA showed that the exposure patterns of ACEs could be divided into the "high ACEs" group (13.4%), "high neglect/emotional abuse" group (25.7%), "high family dysfunction" group (6.9%), "high neglect" group (27.1%), and "low ACEs" group (26.3%). The LCGA divided anxiety trajectories into four groups: "high anxiety decline" (7.1%),"anxiety increase "(4.1%), "moderate anxiety"(52.9%), and "low anxiety"(35.9%). Using the low ACEs group as a reference group, compared with the low anxiety trajectory, the high ACEs group, high neglect/emotional abuse group, high family dysfunction group, high neglect group, and medium to high-level anxiety trajectory were all associated with an increased risk (P<0.05). Conclusion: There is heterogeneity in ACEs exposure patterns among medical college students, and ACEs exposure patterns are important influencing factors for anxiety symptom trajectories.

Construction of predictive model for pregnancy-related anxiety risk in pregnant women based on LASSO regression / 环境与职业医学

Background Pregnancy-related anxiety has a negative impact on the physical and mental health of pregnant women and the normal growth and development of the fetus. Establishing prediction models for pregnancy-related anxiety to screen associated predictive factors may provide important opportunities for prenatal intervention. Objective To establish a prediction model of pregnancy-related anxiety risk of pregnant women. Methods From January to July 2021, a questionnaire survey on pregnancy-related anxiety and predictors was conducted among pregnant women having routine prenatal check-ups provided by an obstetrics clinic of a tertiary grade A hospital in Ningxia. The socio-demographic characteristics of the subjects were collected, and the pregnant women were evaluated by the Life Event Scale (LES), Perceived Social Support Scale (PSSS), Family APGAR Index (APGAR), and Pregnancy-related Anxiety Questionnaire (PAQ). R 4.2.0 software was used to fit all selected variables by least absolute shrinkage and selection operator (LASSO) regression to identify predictors of pregnancy-related anxiety in the second and third trimesters. On the basis of logistic regression analysis, prediction models of pregnancy-related anxiety in the second and third trimesters were constructed, and the model nomogram and receiver operating characteristic curve (ROC) were drawn. The prediction effect of the model was evaluated by area under the curve (AUC). A calibration chart was drawn to evaluate the calibration of the model. Results A total of 1500 questionnaires were distributed, and 1448 valid questionnaires were recovered, with an effective rate of 96.53%. Among the 1448 pregnant women, the overall positive rate of pregnancy-related anxiety was 28.80% (417/1448), and the positive rates in the second and third trimesters were 29.21% (276/935) and 27.49% (141/513), respectively. The predictors entering the the second trimester model were age of marriage, family care, social support, family expectations for the fetus, physical condition during pregnancy, and whether experiencing life stressful events during pregnancy. The predictors entering the the third trimester model were pregnancy intention, physical discomfort, and whether experiencing life stress during pregnancy. A risk prediction model of pregnancy-related anxiety for the second trimester was established: risk of pregnancy-related anxiety=−0.07× marriage age +0.12× family care −0.03× social support −0.65× family expectation of fetal sex +0.42× physical condition during pregnancy +0.47× whether experiencing life stressful events during pregnancy. A risk prediction model of pregnancy-related anxiety for the third trimester was established: risk of pregnancy-related anxiety=−5.69+0.82× pregnancy intention +1.06× physical discomfort +0.94× whether experiencing life stressful events during pregnancy. The ROC curves of the two models were drawn. The AUC of the second trimester model was 0.71, and the AUC of related validation model was 0.68. The AUC of the third trimester model was 0.72, and the AUC of related validation model was 0.66. Conclusion The risk prediction models of pregnancy-related anxiety constructed based on LASSO regression and logistic regression have good prediction ability, and they suggest that pregnant women in the second trimester with short marriage age, high family care, low social support, family expectations for fetal sex, average physical condition, and experiencing life stress during pregnancy, and pregnant women in the third trimester with spontaneous pregnant intention, unintended pregnancy, physical discomfort, and experiencing life stress during pregnancy are high-risk groups for pregnancy-related anxiety.

Treatment of paclitaxel and doxorubicin changes the immune microenvironment of breast cancer and inhibits the growth of tumor cells in mice / 细胞与分子免疫学杂志

Objective To investigate the effects of paclitaxel and doxorubicin on the immune microenvironment of breast cancer in mice. Methods The CTR-DB database, a database for analysis of gene expression profiles and drug resistance characteristics related to tumor drug response, was used to analyze the effect of chemotherapeutic drugs on the immune microenvironment of breast cancer. Mouse models with breast cancer were established by in situ injection with 4T1 cells, a triple-negative breast cancer (TNBC) cells. Then they were treated with doxorubicin and paclitaxel, respectively. The sizes of tumor were recorded and analyzed by growth curve. The number of different types of immune cells was analyzed using flow cytometry. The expressions of Ki67, S100 calcium binding protein A9 (S100A9) and matrix metalloproteinase 9 (MMP9) were detected by immunohistochemistry. The cell cycles of 4T1 cells in paclitaxel group and doxorubicin group were analyzed by flow cytometry. Results The results of CTR_Microarray_75 analysis showed that the immune scores, and the number of cytotoxic lymphocytes, B lineages, CD8+ T cells, dendritic cells (DCs), monocytic lineages and natural killer (NK) cells in chemotherapy-sensitive breast cancer were higher than those in chemotherapy-insensitive breast cancer. Through growth curve analysis in mice with breast cancer, we found that both paclitaxel and doxorubicin could inhibit the increase of the tumor sizes, and the paclitaxel showed a higher inhibitory effect. The results of cytometry displayed that both paclitaxel and doxorubicin could restrain the expression of Ki67 and increase the number of breast cancer cells in G2/M phase, and in the paclitaxel group, the expression of Ki67 was lower and the number of breast cancer cells in G2/M phase was larger. Paclitaxel and doxorubicin enhanced the infiltration of CD45+ immune cells but decreased the infiltration of neutrophils. Additionally, paclitaxel promoted the infiltration of CD3+CD4+ T helper cells, CD3+CD8+ cytotoxic T cells and CD45+CD19+B cells, while doxorubicin increased the infiltration of CD4+CD25+ regulatory T cells (Tregs). The results of immunohistochemistry displayed that the paclitaxel significantly inhibited the expression of S100A9, while the doxorubicin significantly restrained the expression of MMP9. Conclusion Paclitaxel and doxorubicin can effectively inhibit the growth of breast cancer cells and change immune microenvironment of TNBC by regulating the different patterns of cell infiltration and the expression of different extracellular matrix components.

Retrospective analysis of cell-free fetal DNA prenatal testing of maternal peripheral blood / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of non-invasive prenatal testing (NIPT) for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, chromosomal microdeletions and microduplications using cell-free fetal DNA from peripheral blood samples of pregnant women.@*METHODS@#A total of 15 237 pregnant women who had undergone NIPT testing at the Maternity and Child Health Care Hospital of Zaozhuang from February 2015 to December 2021 were enrolled in this study. For those with a high risk by NIPT, amniotic fluid samples were collected for G-banding chromosomal karyotyping analysis and chromosomal microarray analysis to verify the consistency of NIPT with results of prenatal diagnosis. All of the women were followed up by telephone for pregnancy outcomes.@*RESULTS@#Among the 15 237 pregnant women, 266 (1.75%) were detected with a high risk for fetal chromosomal abnormality were detected. Among these, 79 (29.7%) were at a high risk for T21, 26 (9.77%) were at a high risk for T18, 9 (3.38%) were at a high risk for T13, 74 (27.82%) were at a high risk for sex chromosome aneuploidies, 12 (4.51%) were at a high risk for other autosomal aneuploidies, and 66 (24.81%) were at a high risk for chromosomal microdeletions or microduplications. 217 women had accepted invasive prenatal diagnosis and respectively 50, 13, 1, 25, 1 and 18 were confirmed with T21, T18, T13, sex chromosome aneuploidies, autosomal aneuploidies and microdeletions/microduplications, and the positive predictive values were 75.76%, 68.42%, 11.11%, 40.32%, 10% and 35.29%, respectively. For 13 042 women (85.59%), the outcome of pregnancy were successfully followed up. During the follow-up, one false negative case of T21 was discovered. No false positive cases for T13 and T18 were found.@*CONCLUSION@#NIPT has a sound performance for screening T13, T18 and T21, and is also valuable for screening other autosomal aneuploidies, sex chromosome aneuploidies and chromosomal microdeletions/microduplications.

Prenatal diagnosis of two fetuses with Xp22.31 microdeletion syndrome indicated by non-invasive prenatal testing / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of non-invasive prenatal testing (NIPT) for detecting fetal chromosomal microdeletion/microduplication syndromes by carrying out prenatal diagnoses for two fetuses with Xp22.31 microdeletion indicated by NIPT.@*METHODS@#Two pregnant women suspected for fetal Xp22.31 microdeletion syndrome who presented at Zaozhuang Maternal and Child Health Care Hospital on December 5, 2017 and October 15, 2020 were selected as the study subjects. Clinical data of the two women were collected, and peripheral venous blood samples were collected for NIPT testing. Amniotic fluid samples were taken for G-banding chromosomal karyotyping analysis and copy number variation sequencing (CNV-seq) for fetus 1, while G-banding chromosomal karyotyping and single nucleotide polymorphism microarray analysis (SNP array) were carried out for fetus 2. Peripheral venous blood samples of couple 1 were collected for CNV-seq to verify the origin of copy number variation .@*RESULTS@#NIPT indicated that fetus 1 had harbored a 1.3 Mb deletion in the Xp22.31 region, while G-banding chromosomal karyotyping had found no abnormality. CNV-seq analysis verified the fetus to be seg[GRCh37]del(X)(p22.31)chrX:g.6800001_7940000del, with a 1.14 Mb deletion at Xp22.31, which was derived from its mother. NIPT indicated that fetus 2 had harbored a 1.54 Mb deletion in the Xp22.31 region, while G-banding chromosomal karyotyping had found no abnormality. SNP array analysis indicated arr[GRCh37]Xp22.31(6458940_8003247)×0, with a 1.54 Mb deletion in Xp22.31 region.@*CONCLUSION@#NIPT not only has a good performance for detecting fetal trisomies 21, 18 and 13, but also has the potential for detecting chromosomal microdeletion/microduplications. For high risk fetuses indicated by NIPT, prenatal diagnosis needs to be carry out to verify the chromosomal abnormalities.

Augmenting locking plate with autologous bone graft for the treatment of nonunion of long bone fracture in the lower extremity with retaining of the original intramedullary nail / 中国骨伤

OBJECTIVE@#To explore clinical effect of attaching locking plate with bone grafting based on retaining the original intramedullary nail in treating non-union after intramedullary nail fixation of long shaft fractures of lower limbs.@*METHODS@#A retrospective study was conducted on 20 patients treated with non-union fractures after intramedullary nailing of long shaft fractures of lower limbs from June 2015 to June 2020. All patients were treated with the original intramedullary nailing and bone grafting from the iliac bone, and were underwent open reduction plate internal fixation and bone grafting for old fractures. Among them, 14 were males and 6 were females, aged from 35 to 56 years old with an average of (42.2±9.6) years old. Nine patients were femoral shaft fracture and 11 patients were tibial shaft fracture. According to characteristics of fracture end nonunion, 6 patients were stable/atrophic, 9 patients were unstable/large, and 5 patients were unstable/atrophic. The nonunion time ranged from 8 to 12 months with an average of(9.8±2.0) months after the initial surgery. Visual analogue scale (VAS), knee range of motion, bone healing time, complications and fracture-end healing were recorded before and at the latest follow-up.@*RESULTS@#All patients were followed up for 18 to 48 months with an average of (36.3±10.5) months. The incision of all patients were healed at stageⅠwithout complications such as infection or internal fixation ruptur. Healing time of femur and tibia was (8.5±2.6) months and (9.5±2.2) months. Knee joint motion increased from preoperative (101.05±8.98) ° to postoperative (139.35±8.78) ° at the latest follow-up (t=-12.845, P<0.001). VAS decreased from preoperative (5.15±1.72) to postoperative (0.75±0.96) at the latest follow-up (t=11.186, P<0.001).@*CONCLUSION@#On the basis of retaining the original intramedullary nail, the addition of locking plate internal fixation and autogenous iliac bone grafting have advantages of simple operation, less trauma, fewer complications and high fracture healing rate. It is one of the effective surgical schemes for the treatment of nonunion after intramedullary nail fixation of long bone fracture of lower extremity.

Hemilateral bone longitudinal transport technique for the treatment of hemilateral defects of long bones of lower limbs / 中国骨伤

OBJECTIVE@#To explore clinical efficacy of Ilizarov hemilateral bone longitudinal transport technique in treating hemilateral bone defects associated with chronic osteomyelitis of lower extremity long bones.@*METHODS@#Clinical data of 13 patients with hemilateral bone defects caused by chronic osteomyelitis of lower extremity long bones and treated by Ilizarov hemilateral bone longitudinal transport technique were retrospective analyzed, including 10 males and 3 female, aged from 14 to 55 years old;4 patients occurred femoral and 9 patients occurred tibial;10 patients were diagnosed as traumatic osteomyelitis and 3 patients as hematogenous osteomyelitis. The anatomical classification of Cierny-Mader in 13 patients was type Ⅲ. Bone and wound healing, postopertaive complication, and bony and functional results were observed by Paley evaluation standard.@*RESULTS@#After removing external fixator, all patients were followed up from 6 to 70 months. Transporting time ranged from 54 to 158 d. And the time in external fixation ranged from 6.8 to 19.5 months. External fixation index (EFI) ranged from 1.23 to 1.6 months/cm. According to Paley's evaluation criteria, bony results were excellent in 13 patients;functional results showed excellent in 12 patients and good in 1 patient. Two patients occurred poor union on the docking sites and healed with autogenous iliac bone graft. The callus at the extended area was poorly mineralized and improved significantly when treated with low-intensity pulsed ultrasound in one patient. All patients had good wound healing without recurrence of osteomyelitis and refracture. There was no vascular and nerve injury and axial deviation in all patients and they were satisfied with the appearance and function of lower limbs. The range of motion of knee and ankle joint before operation was 120 ° to 150 ° and 35 °to 80 ° respectively, and at the latest follow-up was 110 ° to 140 ° and 30 ° to 75 ° .@*CONCLUSION@#Ilizarov hemilateral bone longitudinal transport technique is effective in treating infective hemilateral bone defects of lower extremity long bones, which could not only simplify architecture of external fixation, but also reduce the number of fixation pins, shorten the time in external fixator and decrease the incidence of pin tract infection. However, this technique is highly demanding, and the growth of callus in extended region and healing of bone apposition should be noticed.

Prognostic Prediction Value and Biological Functions of Non-Apoptotic Regulated Cell Death Genes in Lung Adenocarcinoma / 中国医学科学杂志(英文版)

Objective To explore the potential biological functions and prognostic prediction values of non-apoptotic regulated cell death genes (NARCDs) in lung adenocarcinoma.Methods Transcriptome data of lung adenocarcinoma were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. We identified differentially expressed NARCDs between lung adenocarcinoma tissues and normal tissues with R software. NARCDs signature was constructed with univariate Cox regression analysis and the least absolute shrinkage and selection operator Cox regression. The prognostic predictive capacity of NARCDs signature was assessed by Kaplan-Meier survival curve, receiver operating characteristic curve, and univariate and multivariate Cox regression analyses. Functional enrichment of NARCDs signature was analyzed with gene set variation analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. In addition, differences in tumor mutational burden, tumor microenvironment, tumor immune dysfunction and exclusion score, and chemotherapeutic drug sensitivity were analyzed between the high and low NARCDs score groups. Finally, a protein-protein interaction network of NARCDs and immune-related genes was constructed by STRING and Cytoscape software. Results We identified 34 differentially expressed NARCDs associated with the prognosis, of which 16 genes (ATIC, AURKA, CA9, ITGB4, DDIT4, CDK5R1, CAV1, RRM2, GAPDH, SRXN1, NLRC4, GLS2, ADRB2, CX3CL1, GDF15, and ADRA1A) were selected to construct a NARCDs signature. NARCDs signature was identified as an independent prognostic factor (P < 0.001). Functional analysis showed that there were significant differences in mismatch repair, p53 signaling pathway, and cell cycle between the high NARCDs score group and low NARCDs score group (all P < 0.05). The NARCDs low score group had lower tumor mutational burden, higher immune score, higher tumor immune dysfunction and exclusion score, and lower drug sensitivity (all P < 0.05). In addition, the 10 hub genes (CXCL5, TLR4, JUN, IL6, CCL2, CXCL2, ILA, IFNG, IL33, and GAPDH) in protein-protein interaction network of NARCDs and immune-related genes were all immune-related genes. Conclusion The NARCDs prognostic signature based on the above 16 genes is an independent prognostic factor, which can effectively predict the clinical prognosis of patients of lung adenocarcinoma and provide help for clinical treatment.

Mechanism of anti-hyperplasia of mammary glands of Xihuang Pills blood-entering component based on UPLC-Q-TOF-MS and network pharmacology / 中国中药杂志

In this study, based on network pharmacology and molecular docking method, the mechanism of anti-hyperplasia of mammary glands of Xihuang Pills blood-entering components was explored, and the efficacy and key targets of Xihuang Pills blood-entering components were experimentally verified by MCF-10A proliferation model of human mammary epithelial cells. In order to clarify the material basis and mechanism of Xihuang Pills in realizing anti-hyperplasia of mammary glands, the blood-entering components of Xihuang Pills were qualitatively analyzed by UPLC-Q-TOF-MS, and 22 blood-entering components were identified. By taking the blood-entering components as the research object, the network pharmacology prediction and molecular docking verification were carried out, and finally, three key targets were screened out, namely JAK1, SRC, and CDK1. In vitro experiments show that Xihuang Pills can inhibit the proliferation of MCF-10A cells, promote the apoptosis of MCF-10A cells, and reduce the expression of JAK1, SRC, and CDK1 targets in cells. To sum up, Xihuang Pills can promote the apoptosis of mammary epithelial cells by regulating the expression of JAK1, SRC, and CDK1 and then play an anti-hyperplasia role, which provides an experimental basis for clarifying the material basis of Xihuang Pills for anti-hyperplasia effect.

PK/PD model of Chuanxiong gel plaster in treatment of rheumatoid arthritis / 中国中药杂志

In this experiment, the PK/PD fitting model of Chuanxiong(Chuanxiong Rhizoma) in the treatment of rheumatoid arthritis was established in the form of acupoint combined with external application gel paste. Firstly, the rheumatoid arthritis model was induced by ovalbumin, and the articular fluid of rabbits was extracted by microdialysis. The pharmacokinetic process of Chuanxiong in rabbit articular fluid was analyzed by UPLC-MS/MS, and the pharmacokinetic model was established. The pharmacodynamic effects of Chuanxiong on inflammatory factors IL-1β, TNF-α, and IL-6 were analyzed by enzyme-linked immunosorbent assay(ELISA). The pharmacodynamic model was established, and the PK/PD model was obtained by fitting the data of pharmacokinetics and pharmacodynamics. The results of pharmacokinetics showed that the concentration of ligustrolide A in the articular cavity by drug administration on classical acupoint Zusanli(ST 36) was higher than that by Yanglingquan(GB 34), which reflected the advantage of typical acupoint, while ligustrazine concentration was higher after administration through Yanglingquan than through Zusanli, which was different from the traditional acupoint theory. The results of pharmacodynamics showed that the drug had lag effect. The PK/PD model was constructed by fitting the data. When IL-1β was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=115.28C_e/(3 316.72+C_e), E=108.73C_e/(2 993.47+C_e), and E=101.34C_e/(3 028.51+C_e). When TNF-α was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=68.31C_e/(3 285.16+C_e), E=59.27C_e/(2 919.86+C_e), and E=53.61C_e/(2 862.87+C_e). When IL-6 was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=59.92C_e/(3 461.17+C_e), E=58.34C_e/(2 723.51+C_e), and E=49.17C_e/(2 862.76+C_e). The parameters showed that there were significant differences in E_(max), EC_(e50) and k_(eo). The analysis of data found that the PK/PD fitting effect of Zusanli, a typical acupoint, was the best, which proved that it was still the best site for drug administration. To sum up, it shows that there may be bidirectional selectivity between drugs and acupoints.

Urine metabolomics study of intervention of Xihuang Pills in rats with hyperplasia of mammary gland / 中国中药杂志

This study aimed to investigate the mechanism of Xihuang Pills in improving hyperplasia of mammary gland(HMG) in rats based on urine metabolomics using ultra-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry(UPLC-Q-Orbitrap-MS). The HMG rat model was established by intramuscular injection of estradiol benzoate solution(0.5 mg·kg~(-1), 25 days) followed by progesterone injection(5 mg·kg~(-1), 5 days). UPLC-Q-Orbitrap-MS technology was used to establish the endogenous small-molecule metabolic profiles in urine samples of rats in the blank group, the HMG model group, and Xihuang Pills group. Multivariate statistical analysis was performed for pattern recognition, t test and variable importance in the projection(VIP) were used to screen potential biomarkers. The significantly changed differential metabolites were identified using the online database Human Metabolome Database(HMDB). Metabolic pathway enrichment analysis was conducted using the MetaboAnalyst 5.0 database. The results showed that 90 differential metabolites with significant changes(P<0.05) were identified between the blank group and the HMG model group using the HMDB. Among them, 48 metabolites significantly reverted(P<0.05) after administration of Xihuang Pills, which may be related to the regulatory effect of Xihuang Pills. Thirteen metabolic pathways significantly associated with HMG were identified when the differential metabolites were imported into the MetaboAnalyst 5.0 database, and Xihuang Pills could modulate seven of these pathways. These metabolic pathways mainly involved histidine metabolism, arginine and proline metabolism, β-alanine metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, pyrimidine metabolism, and amino sugar and nucleotide sugar metabolism. This study utilized UPLC-Q-Orbitrap-MS and urine metabolomics technology to analyze the mechanism of Xihuang Pills in improving HMG, laying the foundation for further in-depth research.

Recent advances in nanocarrier-based drug delivery systems in treatment of rheumatoid arthritis / 中国中药杂志

Rheumatoid arthritis(RA) is a widely prevalent autoimmune inflammatory disease that severely affects patients' quality of life. Currently, conventional formulations against RA have several limitations, such as nonspecificity, poor efficacy, large drug dosages, frequent administration, and systemic side effects. Nanotechnology-based drug delivery systems have emerged as a promising stra-tegy for the diagnosis and treatment of RA since nanotechnology can overcome the limitations of traditional treatments and simplify the complexity of the disease. These systems enable targeted delivery of anti-inflammatory drugs to the inflamed areas through active and passive targeting, achieving specificity to the joints, overcoming the need for increased dosage and administration frequency, and reducing associated adverse reactions. This article aimed to review nanocarrier-based drug delivery systems in the field of RA and elucidate how nanosystems can be utilized to deliver therapeutic drugs to inflamed joints for controlling RA progression. By discussing the current issues and challenges faced by nanodrug delivery systems and highlighting the urgent need for solutions, this article offers theoretical support for further research on nanotechnology-based co-delivery systems in the future.

Mediating role of psychological resilience between family intimacy and adaptability and experiential avoidance among undergraduate nursing students / 中国职业医学

Objective: To investigate the mediating role of psychological resilience in the relationship between family intimacy and adaptability and experiential avoidance among undergraduate nursing students (hereafter referred as nursing undergraduates). Methods: A total of 725 nursing undergraduates from six colleges in Guangdong Province were selected as the research subjects using convenience sampling method. The Acceptance Action Questionnaire-2nd Edition, Conner-Davidson Resilience Scale and Family Intimacy and Adaptability Scale were used to evaluate the experiential avoidance, psychological resilience, and family intimacy and adaptability, respectively. Results: The mean scores of experiential avoidance, psychological resilience and family intimacy and adaptability among nursing undergraduates were (23.4±7.7), (58.8±8.9) and (99.7±20.3), respectively. The results of the mediation analysis indicated that the total effect of family intimacy and adaptability on experiential avoidance was -0.16 (P<0.01), with a direct effect of -0.05 (P>0.05). Psychological resilience played a significant mediating role in the relationship between family intimacy and adaptability and experiential avoidance among nursing undergraduates (P<0.01). The standardized mediation effect was -0.11, accounting for 68.8% of the total effect. Conclusion: Resilience plays a mediating role between family intimacy and adaptability and experiential avoidance among nursing undergraduates.

Relationship between father s emotional symptoms and emotional and behavioral problems in preschool children / 中国学校卫生

Objective@#To explore the relationship between father s emotional symptoms with offspring s emotional and behavioral problems, so as to provide reference for the prevention and intervention of emotional and behavioral problems in preschool children.@*Methods@#Using the method of multi stage sampling, two kindergartens from each of the two counties, two districts and two development zones were selected from Hefei during February to April 2023. A total of 3 672 children aged 3 to 6 years old and their fathers were selected from 12 kindergartens. Fathers filled out the Depression Anxiety and Stress Scale (DASS-21) and mothers filled out the Strength and Difficulty Questionnaire (SDQ). Multivariate Logistic regression model was established to analyze the relationship between father s emotional symptoms and preschool children s emotional and behavioral problems.@*Results@#The detection rate of emotional and behavioral problems in preschool children was 18.65%, and the detection rates of stress, anxiety and depression in fathers were 4.82%, 10.05% and 6.64%, respectively. Multivariate Logistic regression model analysis showed when fathers had negative emotions of stress, anxiety and depression, the detection rate of emotional and behavioral problems in their offspring was higher than children with father without negative emotion group ( OR =1.77-2.13, P <0.01). Father s stress symptoms were associated with increased risk of emotional and behavioral problems in boys, while father s anxiety and depressive symptoms were associated with increased risk of emotional and behavioral problems in boys and girls ( OR =1.45-2.69, P <0.05). Father s stress symptoms were associated with increased risk of emotional and behavioral problems in the first child, while father s anxiety and depressive symptoms were associated with increased risk of emotional and behavioral problems in the first child, second child and above ( OR =1.81-2.49, P <0.05).@*Conclusions@#Father s negative emotional symptoms are important factors affecting preschool children s emotional and behavioral problems. Early detection and targeted intervention of father s negative emotional symptoms are beneficial to the prevention and control of preschool children s emotional and behavioral problems.