Observation on the therapeutic efficacy and survival rate of oral Etoposide in children with disseminated medulloblastoma after the standard treatment plan / 中华实用儿科临床杂志

Objective:To explore the therapeutic efficacy and toxicity of oral Etoposide chemotherapy in children with disseminated medulloblastoma (MB) after the standard treatment plan.Methods:The clinical data of 86 children with disseminated MB admitted in the Department of Pediatrics, Beijing Shijitan Hospital of Capital Medical University from January 2016 to May 2020 were analyzed retrospectively.The median age of children was 8.8 (3.0-16.7) years old.Among them, 33 children treated with maintenance chemotherapy via oral Etoposide were included in the chemotherapy group, and 53 children without oral maintenance chemotherapy were included in the non-chemotherapy group.The gender distribution, surgical resection range, pathological type, molecular classification, postoperative mutism, M-stage and survival[progression-free survival (PFS) and overall survival (OS)] of the 2 groups were compared.The main adverse events of oral Etoposide chemotherapy were recorded. Chi- square test is used for data comparison, Kaplan-Meier method was used to plot the survival curve of disseminated MB patients, followed by the Log- rank test. Results:There were no significant differences in gender, surgical resection range, pathological type, molecular typing, postoperative mutism and M-stage between the 2 groups (all P>0.05). Of 86 patients, the median PFS and OS were 3.0 (0.2-6.3) years, and 3.6 (0.5-6.3) years, respectively.Twenty five cases (29.1%) relapsed, 13 cases (15.1%) died.The 3-year[(65.8±6.8)% vs.(82.0±7.3)%] and 5-year PFS[(56.8±7.7)% vs.(82.0±7.3)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.037). The 3-year[(81.6±5.6)% vs.100.0%] and 5-year OS[(71.2±7.7)% vs.(92.3±7.4)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.025). Among the children with the SHH subtype, the PFS of children with oral Etoposide maintenance chemotherapy after a regular treatment was significantly higher than that without oral maintenance chemotherapy (100.0% vs.57.1%)( P=0.021). The major adverse events of oral Etoposide were myelosuppression and gastrointestinal symptoms, which were mostly relieved after a symptomatic treatment.Treatment-related deaths were not reported. Conclusions:The prognosis of disseminated MB in children is relatively poor.Oral Etoposide for maintenance therapy after a standard treatment is beneficial in reducing relapse and improving the 5-year survival, which is well tolerated.

Development and validation of risk prediction model for new-onset cardiovascular diseases among breast cancer patients: Based on regional medical data of Inner Mongolia / 北京大学学报(医学版)

OBJECTIVE@#To develop and validate a three-year risk prediction model for new-onset cardiovascular diseases (CVD) among female patients with breast cancer.@*METHODS@#Based on the data from Inner Mongolia Regional Healthcare Information Platform, female breast cancer patients over 18 years old who had received anti-tumor treatments were included. The candidate predictors were selected by Lasso regression after being included according to the results of the multivariate Fine & Gray model. Cox proportional hazard model, Logistic regression model, Fine & Gray model, random forest model, and XGBoost model were trained on the training set, and the model performance was evaluated on the testing set. The discrimination was evaluated by the area under the curve (AUC) of the receiver operator characteristic curve (ROC), and the calibration was evaluated by the calibration curve.@*RESULTS@#A total of 19 325 breast cancer patients were identified, with an average age of (52.76±10.44) years. The median follow-up was 1.18 [interquartile range (IQR): 2.71] years. In the study, 7 856 patients (40.65%) developed CVD within 3 years after the diagnosis of breast cancer. The final selected variables included age at diagnosis of breast cancer, gross domestic product (GDP) of residence, tumor stage, history of hypertension, ischemic heart disease, and cerebrovascular disease, type of surgery, type of chemotherapy and radiotherapy. In terms of model discrimination, when not considering survival time, the AUC of the XGBoost model was significantly higher than that of the random forest model [0.660 (95%CI: 0.644-0.675) vs. 0.608 (95%CI: 0.591-0.624), P < 0.001] and Logistic regression model [0.609 (95%CI: 0.593-0.625), P < 0.001]. The Logistic regression model and the XGBoost model showed better calibration. When considering survival time, Cox proportional hazard model and Fine & Gray model showed no significant difference for AUC [0.600 (95%CI: 0.584-0.616) vs. 0.615 (95%CI: 0.599-0.631), P=0.188], but Fine & Gray model showed better calibration.@*CONCLUSION@#It is feasible to develop a risk prediction model for new-onset CVD of breast cancer based on regional medical data in China. When not considering survival time, the XGBoost model and the Logistic regression model both showed better performance; Fine & Gray model showed better performance in consideration of survival time.

Outcome analysis of pregnancy termination and expectant treatment in pregnant women with suspected invasive placenta accreta spectrum disorders in the second trimester / 中华妇产科杂志

Objective: To investigate the maternal and fetal outcomes of expectant treatment and early termination of pregnancy in pregnant women with suspected invasive placenta accreta spectrum disorders (PAS) in the second trimester. Methods: A retrospective cohort study was performed on 51 pregnant women with suspected invasive PAS (ultrasound score ≥10) evaluated by ultrasound with gestational age <26 weeks and confirmed as invasive PAS by intraoperative findings or postoperative pathology in Peking University Third Hospital from January 2015 to January 2022. According to the informed choice of pregnant women and their families, they were divided into expectant treatment group (37 cases) and mid-term termination group (14 cases). The general clinical data and outcome indexes of the two groups were analyzed by χ2 test, Mann-Whitney U rank sum test, logistic regression and linear regression. Results: (1) General clinical data: among 51 pregnant women who were assessed as suspected invasive PAS by ultrasonography in the second trimester, invasive PAS was finally diagnosed by intraoperative findings and postoperative pathology, among which 46 cases (90%) were placenta percreta and 5 cases (10%) were placenta increta. (2) Outcome indicators: univariate analysis showed that there were no statistically significant differences in the intraoperative blood loss (median: 2 200 vs 2 150 ml), the proportion of blood loss >1 500 ml [73% (27/37) vs 9/14], the hysterectomy rate [62% (23/37) vs 8/14], the rate of intensive care unit (ICU) admission [78% (29/37) vs 9/14] between the expectant treatment group and the mid-term termination group (all P>0.05). Multivariate analysis showed that the rate of intraoperative blood loss >1 500 ml (aOR=0.481, 95%CI: 0.017-13.958; P=0.670), hysterectomy (aOR=0.264, 95%CI: 0.011-6.569, P=0.417) and ICU admission (aOR=1.327, 95%CI: 0.048-36.882, P=0.867) between the two groups showed no statistical differences. (3) Outcome analysis: all 37 cases in the expectant treatment group had live births and no early neonatal death. Five pregnant women (14%, 5/37) in the expectant treatment group underwent emergency cesarean section in the course of expectant treatment. In the mid-term termination group, all pregnancies were terminated by operation, including 9 cases of hysterectomy and 5 cases of placental hysterectomy. There was 1 fetal survival (gestational age of termination: 27+4 weeks) and 13 fetal death in the mid-term termination group. Conclusions: Pregnant women who are diagnosed as suspected invasive PAS, especially those with placenta percreta, have the risk of uterine rupture and emergency surgery in the course of expectant treatment. However, early termination of pregnancy does not reduce the risk of intraoperative blood loss and hysterectomy.

Establishment method and significance of birthweight curve and reference in single center / 中华妇产科杂志

Objective: To establish neonatal birthweight percentile curves based on single-center cohort database using different methods, compare them with the current national birthweight curves and discuss the appropriateness and significance of single-center birthweight standard. Methods: Based on a prospective first-trimester screening cohort at Nanjing Drum Tower Hospital from January 2017 to February 2022, the generalized additive models for location, scale and shape (GAMLSS) and semi-customized method were applied to generate local birthweight percentile curves (hereinafter referred to as the local GAMLSS curves, semi-customized curves) for 3 894 cases who were at low risk of small for gestation age (SGA) and large for gestation age (LGA). Infants were categorized as SGA (birth weight<10th centile) by both semi-customized and local GAMLSS curves, semi-customized curves only, or not SGA (met neither criteria). The incidence of adverse perinatal outcome between different groups was compared. The same method was used to compare the semi-customized curves with the Chinese national birthweight curves (established by GAMLSS method as well, hereinafter referred to as the national GAMLSS curves). Results: (1) Among the 7 044 live births, 404 (5.74%, 404/7 044), 774 (10.99%, 774/7 044) and 868 (12.32%, 868/7 044) cases were diagnosed as SGA according to the national GAMLSS curves, the local GAMLSS curves and the semi-customized curves respectively. The birth weight of the 10th percentile of the semi-customized curves was higher than that of the local GAMLSS curves and the national GAMLSS curves at all gestational age. (2) When comparing semi-customized curves and the local GAMLSS curves, the incidence of admission to neonatal intensive care unit (NICU) for more than 24 hours of infants identified as SGA by semi-customized curves only (94 cases) and both semi-customized and local GAMLSS curves (774 cases) was 10.64% (10/94) and 5.68% (44/774) respectively, both significantly higher than that in non SGA group [6 176 cases, 1.34% (83/6 176); P<0.001]. The incidence of preeclampsia, pregnancy<34 weeks, and pregnancy<37 weeks of infants identified as SGA by the semi-customized curves only and both semi-customized and local GAMLSS curves was 12.77% (12/94) and 9.43% (73/774), 9.57% (9/94) and 2.71% (21/774), 24.47% (23/94) and 7.24% (56/774) respectively, which were significantly higher than those of the non SGA group [4.37% (270/6 176), 0.83% (51/6 176), 4.23% (261/6 176); all P<0.001]. (3) When comparing semi-customized curves and the national GAMLSS curves, the incidence of admission to NICU for more than 24 hours of infants identified as SGA by semi-customized curves only (464 cases) and both semi-customized and national GAMLSS curves (404 cases) was 5.60% (26/464) and 6.93% (28/404) respectively, both significantly higher than that in non SGA group [6 176 cases, 1.34% (83/6 176); all P<0.001]. The incidence of emergency cesarean section or forceps delivery for non-reassuring fetal status (NRFS) in infants identified as SGA by semi-customized curves only and both semi-customized and national GAMLSS curves was 4.96% (23/464) and 12.38% (50/404), both significantly higher than that in the non SGA group [2.57% (159/6 176); all P<0.001]. The incidence of preeclampsia, pregnancy<34 weeks, and pregnancy<37 weeks in the semi-customized curves only group and both semi-customized and national GAMLSS curves group was 8.84% (41/464) and 10.89% (44/404), 4.31% (20/464) and 2.48% (10/404), 10.56% (49/464) and 7.43% (30/404) respectively, all significantly higher than those in the non SGA group [4.37% (270/6 176), 0.83% (51/6 176), 4.23% (261/6 176); all P<0.001]. Conclusion: Compared with the national GAMLSS birthweight curves and the local GAMLSS curves, the birth weight curves established by semi-customized method based on our single center database is in line with our center' SGA screening, which is helpful to identify and strengthen the management of high-risk infants.

A case-control study on the association between a healthy lifestyle and obesity among adult twins in Shanghai / 中华流行病学杂志

Objective: To investigate the associations between the numbers of healthy lifestyles and overweight/obesity and abdominal obesity in adult twins in Shanghai. Methods: Based on the Shanghai Twin Registry System Phase Ⅱ survey data in 2017-2018, a case-control study was conducted to analyze the association between healthy lifestyles and obesity and further adjusted for confounders by a co-twin control study. Results: A total of 7 864 adult twins (3 932 pairs) were included. In the co-twin case-control analysis for monozygotic twins, compared with participants with 0 to 2 healthy lifestyles, those with 3 and 4 to 5 healthy lifestyles had a 49% (OR=0.51, 95%CI: 0.28-0.93) and 70% (OR=0.30, 95%CI: 0.13-0.69) lower risk of overweight/obesity, respectively, and a 17% (OR=0.83, 95%CI: 0.44-1.57) and 66% (OR=0.34, 95%CI: 0.14-0.80) lower risk of abdominal obesity, respectively. For each additional healthy lifestyle, the risk of developing overweight/obesity was reduced by 41% (OR=0.59, 95%CI: 0.42-0.85), and the risk of developing abdominal obesity was reduced by 37% (OR=0.63, 95%CI: 0.44-0.90). Conclusion: An increasing number of healthy lifestyles was associated with a marked decreased risk for both overweight/obesity and abdominal obesity.

Establishment of PCR assays and genetic polymorphism analysis of genes encoding Clostridium perfringens β2 toxin from different sources / 中华流行病学杂志

Objective: To establish and optimize PCR methods for the gene encoding of Clostridium perfringens β2 toxin (cpb2) and atypical-cpb2 (aty-cpb2), analyze the epidemiological characteristics and genetic polymorphism of the cpb2 of Clostridium perfringens in 9 Chinese areas from 2016 to 2021. Methods: The cpb2 of 188 Clostridium perfringens strains were examined by PCR; the cpb2 sequences were acquired by whole-genome sequencing to analyze the genetic polymorphism. Using Mega 11 and the Makeblastdb tool, a phylogenetic tree, and cpb2-library based on 110 strains carrying the cpb2 were produced. Using the Blastn technique, a comparison was made to discover sequence similarity between consensus-cpb2 (con-cpb2) and aty-cpb2. Results: The specificity of PCR assay for the cpb2 and aty-cpb2 was verified. The PCR results for cpb2 amplification were highly consistent with the whole-genome sequencing approach (Kappa=0.946, P<0.001). A total of 107 strains from nine regions in China carried cpb2, 94 types A strains carried aty-cpb2, 6 types A strains carried con-cpb2, and 7 types F strains carried aty-cpb2. The nucleotide sequence similarity between the two coding genes was 68.97%-70.97%, and the similarity between the same coding genes was 98.00%-100.00%. Conclusions: In this study, a specific PCR method for cpb2 toxin was developed, and the previous PCR method for detecting aty-cpb2 was improved. aty-cpb2 is the primary gene encoding of β2 toxin. There is a significant nucleotide sequence variance between the various cpb2 genotypes.

Study on the features of Clostridioides difficile infection among diarrhea patients in Kunming from 2018 to 2020 / 中华流行病学杂志

Objective: We analyze the characteristics of Clostridioides difficile (C. difficile) infection among diarrhea patients in Kunming from 2018 to 2020 and provide evidence for follow-up surveillance and prevention. Methods: A total of 388 fecal samples of diarrhea patients from four sentinel hospitals in Yunnan Province from 2018 to 2020 were collected. Real-time quantitative PCR was used to detect the fecal toxin genes of C. difficile. The positive fecal samples isolated the bacteria, and isolates were identified by mass spectrometry. The genomic DNA of the strains was extracted for multi-locus sequence typing (MLST). The fecal toxin, strain isolation, and clinical patient characteristics, including co-infection with other pathogens, were analyzed. Results: Among the 388 fecal samples, 47 samples with positive reference genes of C. difficile were positive, with a total positive rate of 12.11%. There were 4 (8.51%) non-toxigenic and 43 (91.49%) toxigenic ones. A total of 18 strains C. difficile were isolated from 47 positive specimens, and the isolation rate of positive specimens was 38.30%. Among them, 14 strains were positive for tcdA, tcdB, tcdC, tcdR, and tcdE. All 18 strains of C. difficile were negative for binary toxins. The MLST results showed 10 sequence types (ST), including 5 strains of ST37, accounting for 27.78%; 2 strains of ST129, ST3, ST54, and ST2, respectively; and 1 strain of ST35, ST532, ST48, ST27, and ST39, respectively. Fecal toxin gene positive (tcdB+) results were statistically associated with the patient's age group and with or without fever before the visit; positive isolates were only statistically associated with the patient's age group. In addition, some C. difficile patients have co-infection with other diarrhea-related viruses. Conclusions: The infection of C. difficile in diarrhea patients in Kunming is mostly toxigenic strains, and the high diversity of strains was identified using the MLST method. Therefore, the surveillance and prevention of C. difficile should be strengthened.

Effect of intravitreal injection of anti-vascular endothelial growth factor agents on systemic concentration of vascular endothelial growth factor / 国际眼科杂志(Guoji Yanke Zazhi)

Chorioretinal disease has become a significant problem affecting human vision. Abnormal expression of vascular endothelial growth factor(VEGF)leads to increased fundus permeability and neovascularization. Vitreous injection of anti-VEGF agents can rapidly inhibit the level of VEGF in the eye and effectively control the development of the disease. At present, anti-VEGF agents are widely administered in ophthalmology. However, studies have shown that intravitreal anti-VEGF agents can reduce plasma VEGF concentration after entering the circulatory system, and the pointless off-target effects of drugs may lead to systemic adverse reactions. For elderly patients, patients with serious comorbidities, lactating women, premature infants and other special populations, attention should be paid to systemic VEGF inhibition after multiple injections. In this paper, in order to provide reference for clinical anti-VEGF therapy, the pharmacokinetics therapy, systemic adverse reactions, contralateral eye effects, and effects of anti-VEGF on breast milk and preterm infants were discussed, and the systemic effects of vitreous injection of anti-VEGF agents were reviewed.

Effect of perioperative clinical application of enhanced recovery after surgery on elderly recipients undergoing liver transplantation / 器官移植

Objective To evaluate the application value of perioperative interventional strategy guided by enhanced recovery after surgery (ERAS) in elderly recipients undergoing liver transplantation. Methods Clinical data of 405 liver transplant recipients were retrospectively analyzed. According to age, all recipients were divided into the elderly (≥60 years, n=122) and non-elderly groups (< 60 years, n=283). All patients received perioperative interventions under the guidance of ERAS. Intraoperative and postoperative indexes, incidence of postoperative complications and discharge were analyzed between two groups. Results There were no significant differences in the duration of anesthesia, operation time, anhepatic phase, hemorrhage volume, blood transfusion volume, lactic acid level before abdominal closure, ventilator-assisted time, the length of intensive care unit (ICU) stay, Caprini score, CHIPPS score, time of gastric tube, urinary tube and drainage tube removal, time to first drinking, time to first physical activity and time to first flatus between two groups (all P > 0.05). In the elderly group, the time to first feeding was later than that in the non-elderly group (P < 0.05). There were no significant differences in the incidence of fever, ascites, pulmonary infection, delayed gastric emptying, hemorrhage and inactive venous thrombosis between two groups (all P > 0.05). No significant differences were observed in the levels of aspartate aminotransferase, total bilirubin, direct bilirubin, serum creatinine before discharge and total length of hospital stay between two groups (all P > 0.05). The alanine aminotransferase level in elderly recipients was lower than that in non-elderly counterparts, and the difference was statistically significant (P < 0.05). No unplanned reoperation was performed within postoperative 30 d in two groups. There was no significant difference in the re-hospitalization rate within 30 d after discharge (P > 0.05). Conclusions ERAS-guided interventional strategy contributes to perioperative recovery of elderly recipients undergoing liver transplantation, and yields equivalent postoperative recovery between elderly and non-elderly recipients.

Properties of new exotic traditional Chinese medicinal Vernonia amygdalina leaves:a literature research / 中国中药杂志

The leaves of Vernonia amygdalina Delile of the family Asteraceae(also known as "bitter leaf"), rich in biological activities, are used as both medicine and food for a long time in West tropical Africa. They have been introduced into Southeast Asia and Fujian and Guangdong provinces of China in recent years. However, little is known about the properties of the plant in traditional Chinese medicine(TCM), which limits its combination with other Chinese medicinal herbs. In this study, 473 articles on V. amygdalina leaves were selected from PubMed, Web of Science, CNKI, Wanfang Data and VIP to summarize their components, pharmacological effects and clinical research. V. amygdalina leaves presented anti-microbial, hypoglycemic, anti-hypertensive, lipid-lowering, anti-tumor, anti-inflammatory, antioxidant, and other pharmacological effects. On the basis of the theory of TCM properties, the leaves were inferred to be cold in property and bitter and sweet in flavor, acting on spleen, liver, stomach and large intestine and with the functions of clearing heat, drying dampness, purging fire, removing toxin, killing insects and preventing attack of malaria. They can be used to treat dampness-heat diarrhea, interior heat and diabetes, malaria, insect accumulation and eczema(5-10 g dry leaves by decoction per day and an appropriate amount of crushed fresh leaves applying to the affected area for external use). Due to the lack of TCM properties, V. amygdalina leaves are rarely used medicinally in China. The determination of medicinal properties of the leaves is conducive to the introduction of new exotic medicinal herbs and the development of new TCM resources, which facilitated further clinical application and research and development of Chinese medicinal herbs.

Mechanism of Yanghe Decoction against subcutaneous tumor in pulmonary metastasis from breast cancer through HIF-1α signaling pathway regulating glycolysis:based on network pharmacology and animal experiment / 中国中药杂志

This study aims to explore the mechanism of Yanghe Decoction(YHD) against subcutaneous tumor in pulmonary metastasis from breast cancer, which is expected to lay a basis for the treatment of breast carcinoma with YHD. The chemical components of medicinals in YHD, and the targets of the components were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The disease-related targets were searched from GeneCards and Online Mendelian Inheritance in Man(OMIM). Excel was employed to screen the common targets and plot the Venn diagram. The protein-protein interaction network was constructed. R language was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. A total of 53 female SPF Bablc/6 mice were randomized into normal group(same volume of normal saline, ig), model group(same volume of normal saline, ig), and low-dose and high-dose YHD groups(YHD, ig, 30 days), with 8 mice in normal group and 15 mice in each of the other groups. Body weight and tumor size was measured every day. Curves for body weight variation and growth of tumor in situ were plotted. In the end, the subcutaneous tumor sample was collected and observed based on hematoxylin and eosin(HE) staining. The mRNA and protein levels of hypoxia inducible factor-1α(HIF-1α), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), and glucose transporter type 1(GLUT1) were detected by PCR and Western blot. A total of 213 active components of YHD and 185 targets against the disease were screened out. The hypothesis that YHD may regulate glycolysis through HIF-1α signaling pathway to intervene in breast cancer was proposed. Animal experiment confirmed that the mRNA and protein levels of HIF-1α, PKM2, LDHA, and GLUT1 in the high-and low-dose YHD groups were lower than those in the model group. YHD has certain inhibitory effect on subcutaneous tumor in pulmonary metastasis from breast cancer in the early stage, which may intervene pulmonary metastasis from breast cancer by regulating glycolysis through HIF-1α signaling pathway.

Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways / 中国结合医学杂志

OBJECTIVE@#To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture (EA) in experimental models of Alzheimer's disease (AD) in vivo.@*METHODS@#Senescence-accelerated mouse prone 8 (SAMP8) mice were used as AD models and received EA at Yingxiang (LI 20, bilateral) and Yintang (GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin (2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier (BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid- β (Aβ), and ionized calcium-binding adapter molecule 1 (IBa-1) in mouse hippocampus (CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining. Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining.@*RESULTS@#Fibrin was time-dependently deposited in the hippocampus of SAMP8 mice and this was inhibited by EA treatment (P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice (P<0.01), which was reversed by fibrin injection (P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability (P<0.05 or P<0.01). Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8 mice, which was reversed by fibrin injection (P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1 (HMGB1)/toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nicotinamide adenine dinucleotide phosphate (NADPH) signaling pathways (P<0.01).@*CONCLUSION@#EA may potentially improve cognitive impairment in AD via inhibition of fibrin/A β deposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways.

Exploration and Practice of the "One Combination, Two Highlights, Three Combinations, Four in One" Innovative Talents Training Mode in Forensic Medicine / 法医学杂志

Talent is one of the basic and strategic supports for building a modern socialist country in all aspects. Since the 1980s, the establishment of forensic medicine major and the cultivation of innovative talents in forensic medicine have become hot topics in higher education in forensic medicine. Over the past 43 years, the forensic medicine team of Shanxi Medical University has adhered to the joint education of public security and colleges, and made collaborative innovation, forming a training mode of "One Combination, Two Highlights, Three Combinations, Four in One" for innovative talents in forensic medicine. It has carried out "5+3/X" integrated reform, and formed a relatively complete talent training innovation mode and management system in teaching, scientific research, identification, major, discipline, team, platform and cultural construction. It has made a historic contribution to China's higher forensic education, accumulated valuable experience for the construction of first-class major and first-class discipline of forensic medicine, and provided strong support for the construction of the national new forensic talent training system. The popularization of this training mode is conducive to the rapid and sustainable development of forensic science, and provides more excellent forensic talents for national building, regional social development and the discipline construction of forensic science.

Organizing Pneumonia in A Patient Double-Positive for ANCA and Anti-GBM Antibodies: A Case Report / 中国医学科学杂志(英文版)

Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.

Anti-fatigue effect of Lubian on kidney Yin deficiency and kidney Yang deficiency mice and mechanism based on PI3K-Akt pathway / 中国中药杂志

This study aimed to investigate the anti-fatigue effect and mechanism of Lubian(Cervi Penis et Testis) on kidney Yin deficiency and kidney Yang deficiency mice. After one week of adaptive feeding, 88 healthy male Kunming mice were randomly divided into a blank group, a kidney Yin deficiency model group, a kidney Yin deficiency-Panacis Quinquefolii Radix(PQR) group, kidney Yin deficiency-Lubian treatment groups, a kidney Yang deficiency model group, a kidney Yang deficiency-Ginseng Radix et Rhizoma(GR) group, and kidney Yang deficiency-Lubian treatment groups, with eight mice in each group. The kidney Yin deficiency model and kidney Yang deficiency model were prepared by daily regular oral administration of dexamethasone acetate and hydrocortisone, respectively, and meanwhile, corresponding drugs were provided. The mice in the blank group received blank reagent. The treatment lasted 14 days. The exhaustive swimming time was measured 30 min after drug administration on the 14th day. On the 15th day, blood was collected from eyeballs and the serum was separated to determine the content of lactic acid(LD), blood urea nitrogen(BUN), lactate dehydrogenase(LDH), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP). The liver was dissected to determine the content of liver glycogen and the protein expression of phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt). Compared with the kidney Yang deficiency model group, the kidney Yang deficiency-Lubian treatment groups showed increased body weight(P<0.05), relieved symptoms of Yang deficiency, decreased cGMP content(P<0.01), increased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), reduced LD(P<0.01), elevated BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K and Akt in the liver(P<0.05). Compared with the kidney Yin deficiency model group, the kidney Yin deficiency-Lubian treatment groups showed increased body weight(P<0.01), relieved symptoms of Yin deficiency, increased content of cGMP(P<0.01), decreased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), decreased LD(P<0.01), decreased BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K(P<0.05) and Akt in the liver(P<0.05). To sum up, Lubian can regulate Yin deficiency and Yang deficiency and increase glycogen synthesis by affecting the PI3K-Akt pathway, thereby exerting an anti-fatigue role.

Long-term evaluation and physical and mental effects of residual tinnitus following treatment of sudden hearing loss / 中华耳鼻咽喉头颈外科杂志

Objective: To clarify the long-term characteristics of tinnitus following treatment of sudden deafness and its long-term physical and mental effects on patients. Methods: A retrospective analysis was performed on 88 patients (46 males and 42 females; Age from 11 to 89 years) with sudden deafness treated in Department of Otoscope Surgery of Peoples's Libration Army General Hospital in Beijing from April 2020 to January 2021, and the occurrence of tinnitus and treatment effect of all patients were analyzed. Follow-up was conducted for patients with residual tinnitus after treatment for more than 1 year by the investigation and filling in the survey information collection form, Tinnitus Evaluation Questionnaire (TEQ) and Tinnitus Handicap Inventory (THI). Descriptive statistics and SPSS 22.0 software were used for statistical data analysis. Results: In this study, 93.2% (82/88) of patients with sudden deafness were accompanied by tinnitus at the onset, and the proportion of long-term tinnitus after treatment was 90.2% (74/82). After 1 year of treatment for sudden deafness, the improvement of tinnitus was significant in low-frequency sudden deafness compared with those of high-frequency, flat and total deafness sudden deafness (χ2 value was 6.801, 4.568 and 4.038, all P<0.05). In patients with residual tinnitus, 9 (12.2%) patients felt minimal loudness or even no loudness, 34 (46.0%) patients felt slight loudness, 28 (37.8%) patients felt tinnitus was relatively loud, and 3 (4.1%) patients felt tinnitus was loud or noisy. Nine (12.2%) patients's sleep was often affected, 41 (55.4%) patients's sleep was sometimes affected, 9 (12.2%) patients's sleep was rarely affected, 15 (20.3%) patients's sleep was almost not affected. Twenty-eight (37.8%) patients basically completely adapted to tinnitus and 46 (62.2%) patients did not completely adapted to residual tinnitus. Eight (10.8%) patients had no impact on life, 39 (52.7%) patients had slight impact, 22 (29.7%) patients had moderate impact, and the other 5 (6.8%) patients had greater impact. According to tinnitus evaluation questionnaire(TEQ), there were 12 cases (16.2%) of grade Ⅰ, 26 cases (35.1%) of grade Ⅱ, 28 cases (37.8%) of grade Ⅲ, 7 cases (9.5%) of grade Ⅳ and 1 case (1.4%) of grade Ⅴ. According to tinnitus handicap inventory(THI), tinnitus disability was classified into grade Ⅰ, 22 cases (29.7%), grade Ⅱ, 14 cases (18.9%), Grade Ⅲ, 27 cases (36.5%) and grade Ⅳ, 11 cases (14.9%). Conclusion: The rate of residual tinnitus following treatment of sudden deafness is high. Some of the patients can completely adapt residual tinnitus after one year, but some of them will be affected when sleep, work and study. Residual tinnitus can lead to tinnitus disability in different degrees.

Casticin Attenuates Stemness in Cervical Cancer Stem-Like Cells by Regulating Activity and Expression of DNMT1 / 中国结合医学杂志

OBJECTIVE@#To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism.@*METHODS@#Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L).@*RESULTS@#DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells.@*CONCLUSION@#CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.

Comparison of effect between internal fixation and total hip replacement in the treatment of displaced femoral neck fracture in middle age patients / 中国骨伤

OBJECTIVE@#To analyze and compare the clinical efficacy of internal fixation and total hip replacement in the treatment of displaced femoral neck fracture from 55 to 65 years.@*METHODS@#From September 2016 to August 2020, 86 patients with Garden type Ⅲ or Ⅳ femoral neck fracture were divided into two groups according to different surgical methods. Among them, 38 patients were treated with lag screws for internal fixation, there were 26 males and 12 females, aged 55 to 64 years old with an average of(60.2±3.1) years;the other 48 patients were treated with total hip replacement, including 28 males and 20 females, aged from 57 to 65 years old with an average of(61.3±3.8) years. The time from injury to operation ranged from 1 to 3 days. The reoperation rate, incidence of deep infection, Harris score of hip joint function, visual analogue scale(VAS) of pain and patients reported outcome scores(European five-dimensional Health Questionnaire, EQ-5D) were compared between two groups.@*RESULTS@#All patients were followed up for 24 to 54 months with an average of (35.8±10.3) months. There was significant difference in reoperation rate between two groups (P<0.05). There was no significant difference on the incidence of deep infection, hip Harris score and VAS between two groups(P>0.05) . The postoperative EQ-5D score of patients with internal fixation was lower than that of total hip replacement, and the difference was statistically significant(P<0.05).@*CONCLUSION@#Both the surgery of internal fixation and total hip replacement have similar effect in short-and medium term among the patients aged 55 to 65 years old. However, for the reoperation rate, the group of internal fixation was higher than that of total hip replacement. For the subjective functional score of patients, the group of internal fixation was lower than that of total hip replacement.

Traditional Chinese medicine health care from "long term taking" drugs in Shen Nong's Classic of Materia Medica / 中国中药杂志

"Taking drugs for a long term" is a qualitative expression of medication method based on the efficacy and safety of Chinese medicine, and the study on it is conducive to the full utilization of the efficacy and rational use of drugs. There are 148 drugs that can be taken for a long time recorded in Shen Nong's Classic of Materia Medica, accounting for 41% of the total drugs. This paper analyzed three-grade classification, natural qualities, four properties and five flavors, and efficacy features of the "long-term taking" drugs(LTTD), thus exploring the herbal source of traditional Chinese medicine health care and the rationality of effect accumulation by long-term taking. It was found that there were more than 110 top-grade LTTD in Shen Nong's Classic of Materia Medica, most of which were herbs, with sweet flavor, flat property, and no toxicity. The efficacies were mainly making body feel light and agile(Qingshen) and prolonging life. Eighty-three LTTD were included in the Chinese Pharmacopoeia(2020 edition). In the modern classification, tonic LTTD accounted for the most, followed by damp-draining diuretic LTTD and exterior-releasing LTTD. Twenty LTTD were included in the "List of Medicinal and Edible Products" and 21 were in the "List of Products Used for Health-care Food", involving in various modern health care effects, such as enhancing immunity, assisting in reducing blood lipids, and anti-oxidation. Shen Nong's Classic of Materia Medica is the classic source of traditional Chinese medicine health care, and its medication thought of taking drugs for a long term to accumulate effects has guiding significance for the regulation of sub-health and chronic diseases nowadays. The efficacy and safety of LTTD have been examined in practice for a long time, and some of the drugs are edible, which is unique in the whole cycle of health-care service, especially in line with the health-care needs in the aging society under the concept of Big Health. However, some records in the book are limited by the understanding of the times, which should be scientifically studied according to the Chinese Pharmacopoeia and the related regulations and technical requirements, under the attitude of eliminating falsifications and preserving the truth and keeping the right essence, so as to achieve further improvement, innovation, and development.

Epidemiological Survey of Hemoglobinopathies Based on Next-Generation Sequencing Platform in Hunan Province, China / 生物医学与环境科学（英文）

OBJECTIVE@#This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province.@*METHODS@#We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed.@*RESULTS@#The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α 3.7/αα (50.23%) and β IVS-II-654/β N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively.@*CONCLUSION@#Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.