Chemical constituents from stems and leaves of Lonicera confusa and their anti-inflammatory activities / 中成药

AIM To study the chemical constituents and their anti-inflammatory activities of stems and leaves of Lonicera confusa DC.METHODS The 80%methanol extract from stems and leaves of L.confusa DC was isolated and purified by Diaion HP20SS,Sephadex LH-20,HSCCC and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities were evaluated by measuring NO production of LPS-stimulated RAW264.7 cells in vitro.RESULTS Thirteen compounds were isolated and identified as benzyl alcohol-O-β-D-glucopyranosyl-(1 →6)-β-D-glucopyranoside(1),sweroside(2),epi-vogeloside(3),vogeloside(4),secologanoside(5),secoxyloganin(6),secologanin dimethyl acetal(7),methyl chlorogenate(8),apigenin-7-O-β-D-glucopyranoside(9),luteolin-7-O-β-D-glucopyranoside(10),rhoifolin(11),luteolin-7-O-α-L-arabinopyranosyl(1→6)-β-D-glucopyranoside(12),and lonicerin(13).Compounds 2-8,11-13 inhibited the NO production of LPS-induced cells.CONCLUSION Compound 1 is first isolated from family Lonicera,compounds 3,5,7,9,11,and 12 are obtained from the stems and leaves of this plant for the first time.Compounds 2-8,11-13 exhibited anti-inflammatory activities.

Status quo and challenges of continuing medical education for general practitioners in China: suggestions based on the concept of people centered and integrated health care / 中华全科医师杂志

Continuing medical education for general practitioners is an important measure to upgrade the quality of primary health care services in China, which is still facing various challenges and need to be further developed and improved. This article analyzes the status quo and existing problems of continuing medical education for general practitioners in China, and proposes suggestions based on the concept of people centered and integrated health care (PCIC), including faculty development, training contents, assessment methods, and experience learning, to provide references for the improvement of continuing medical education for general practitioners.

Giant adenoma of the gallbladder misdiagnosed as gallbladder carcinoma： A case report / 临床肝胆病杂志

One patient with gallbladder mass had transient jaundice and was diagnosed with gallbladder carcinoma by abdominal ultrasonography， contrast-enhanced CT， MRCP， and PET-CT. Surgical exploration showed enlarged gallbladder and a mass in the neck of the gallbladder pressing against the hilum of the liver， with no manifestation of tumor invasion， and there were no signs of liver metastasis. Only cholecystectomy was performed for the patient. The pathological diagnosis was tubular adenoma of the gallbladder without carcinogenesis. This case is characterized by a large gallbladder tumor， without marginal infiltration on imaging or malignant transformation based on pathology.

Effects of heat exposure and vitamin C intervention on oxidative stress and blood pressure changes in treadmill rats / 中华劳动卫生职业病杂志

Objective: To investigate the effect of oxidative stress caused by heat exposure on the blood pressure increase of treadmill rats and the intervention of antioxidants. Methods: In June 2021, Twenty-four healthy SD male rats were randomly divided into four groups: normal temperature feeding, normal temperature treadmill, high temperature treadmill and high temperature treadmill supplementation with vitamin C groups, 6 rats in each group. The rats run on the platform in normal temperature or heat exposure environment for 30 min in the morning and in the afternoon daily, 6 days per week. The daily vitamin C supplement dose of high temperature treadmill supplementation with vitamin C group was 10 mg/kg. BP recordings were done at the end of the week. The rat vascular lipofuscin (LF) was detected by ELISA, the rat serum nitric oxide (NO) was detected by nitrate reductase method, the serum malondialdehyde (MDA) was detected by thibabituric acid method, the serum glutathione peroxidase (GPx) and superoxide dismutase (SOD) were detected by chemiluminescence method, and the serum catalase (CAT) was detected by ammonium molybdate method. The total antioxidant capacity (T-AOC) of serum was measured by iron reduction/antioxidant capacity method, and the content of nuclear erythroid 2-related factor 2 (Nrf2) in vascular tissue was measured by Western blot. The intra-group mean was compared by repeated measurement analysis of variance, and the inter-group mean was compared by single-factor analysis of variance and post-event LSD-t test. Results: Compared with the previous time point, the systolic BP and diastolic BP of the high temperature treadmill group were significantly increased at 7, 14 and 21 d, and decreased at 28 d which were higher than the initial level (P<0.05), and the systolic BP and diastolic BP values at each experimental time point were significantly higher than those of normal temperature treadmill group (P<0.001). The changes of thickening of the artery wall, no smoothing of the endodermis and irregular arrangement of muscle cells in high temperature treadmill group were observed. Compared with the normal temperature treadmill group, the content of MDA in serum, and LF in vascular tissue were significantly increased, the activities of SOD, CAT, T-AOC, the content of NO in serum, and the expression of Nrf2 in vascular tissue were significantly decreased in high temperature treadmill group (P<0.05). Compared with the high temperature treadmill group, the systolic BP and diastolic BP values at 7, 14, 21 and 28 d, the content of serum MDA and LF in vascular tissue were significantly decreased, the activities of CAT and T-AOC, and the expression of Nrf2 in vascular tissue significantly increased (P<0.05), the histopathological changes of the artery wall improved in high temperature treadmill supplementation with vitamin C group. Conclusion: Heat exposure has effect on oxidative stress, which may be related to the increase of BP. Vitamin C as an anti-oxidative enhancer can prevent those negative effects, which could alleviate the pathological changes of vessel intima in heat-exposed rats. And the Nrf2 may be a regulated factor to vascular protection.

A novel defined risk signature of endoplasmic reticulum stress-related genes for predicting the prognosis and immune infiltration status of ovarian cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Endoplasmic reticulum (ER) stress, as an emerging hallmark feature of cancer, has a considerable impact on cell proliferation, metastasis, invasion, and chemotherapy resistance. Ovarian cancer (OvCa) is one of the leading causes of cancer-related mortality across the world due to the late stage of disease at diagnosis. Studies have explored the influence of ER stress on OvCa in recent years, while the predictive role of ER stress-related genes in OvCa prognosis remains unexplored. Here, we enrolled 552 cases of ER stress-related genes involved in OvCa from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts for the screening of prognosis-related genes. The least absolute shrinkage and selection operator (LASSO) regression was applied to establish an ER stress-related risk signature based on the TCGA cohort. A seven-gene signature revealed a favorable predictive efficacy for the TCGA, International Cancer Genome Consortium (ICGC), and another GEO cohort (P<0.001, P<0.001, and P=0.04, respectively). Moreover, functional annotation indicated that this signature was enriched in cellular response and senescence, cytokines interaction, as well as multiple immune-associated terms. The immune infiltration profiles further delineated an immunologic unresponsive status in the high-risk group. In conclusion, ER stress-related genes are vital factors predicting the prognosis of OvCa, and possess great application potential in the clinic.

School lunch leftovers of primary and middle school students and its influencing factors in Ningbo / 中国学校卫生

Objective@#To analyze the situation and associated factors of school lunch leftovers of primary and middle school students in Ningbo, so as to provide a basis for formulating policies to improve the quality of nutritious meals and reduce the leftover meal rates.@*Methods@#During March to May of 2022, 20 primary and middle schools were selected from 10 districts in Ningbo, and 4 443 students were selected from grade 4 to 6 of primary school and grade 1 to 3 of middle school. A questionnaire was conducted among them for the students general situation and remaining meal situation.@*Results@#The total leftover rate was 62.4%, 7.9% of the students left rice every day, and 18.3% of the students left vegetables every day. The frequency of primary school students leftover food was lower than that of junior high school students ( χ 2=-2.18, P <0.05). Most of the students (68.3%) had only a little leftover food, half of the students (49.4%) had less than half leftovers, and the proportion of primary school students with large leftover food and leftovers was smaller than that of junior high school students ( χ 2=-2.05, -2.36, P <0.05). The main reason for students leftover food was "too much to eat" (accounting for 30.6%), and there was a statistical difference between primary school students and junior high school students in the composition of leftover food and leftovers ( χ 2=16.94, 14.28, P <0.05). The leftover rate of vegetables was the highest (54.5%) and the leftover rate of milk was the lowest (2.5%). Multivariate Logistic regression model showed that nutrition and food related courses during recent year, being aware the Chinese residents dietary guidelines, statisfaction with canteen food (general, more satisfied, very satisfied), reckoning school canteen food better than home food (almost, better than home) were less possibility to have leftover meals ( OR=0.79, 0.73, 0.57, 0.41, 0.26, 0.69, 0.82, P <0.05). Students chosed the meal after the teacher served the meal, the teacher divided meals and students who ate more frequently (4-6 times/week, 1 time/d, 2 times/d, ≥3 times/d) were more likely to have leftover meals ( OR=1.64, 2.23, 1.27, 1.21, 1.52, 1.44 , P < 0.05).@*Conclusion@#More than half of the students have leftovers. It should optimize the configuration of nutrition lunch, strengthen the education of nutrition knowledge and reduce the leftovers rate.

Effect of proximal fibula osteotomy on tension of lateral knee soft tissue in patients with knee osteoarthritis / 中国骨伤

OBJECTIVE@#To evaluate the short-term efficacy of proximal fibula osteotomy in the treatment of knee osteoarthritis, and to analyze the effect of osteotomy on the tension of the lateral knee soft tissue of patients and verify the reliability of the Arch string theory.@*METHODS@#A total of 71 patients with varus knee osteoarthritis from December 2019 to March 2022 were included, 3 patients dropped out, and 68 patients completed all trials, collected 27 males and 41 females, aged from 51 to 79 years old, with an average of (68.0±7.0 ) years old. The follow-up time ranged from 4 to 12 weeks, with an average of (3.76±1.94) weeks. After admission, the patient underwent Proximal fibula osteotomy, and the tension of lateral knee soft tissue, visual analogue scale (VAS) of pain, the western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and other indicators were recorded before surgery and 1 month after surgery in the weight-bearing state.@*RESULTS@#According to the VAS, the curative effect of a single index was evaluated by referring to the score before and after treatment by Bao Zongzhao. Thirty seven cases were markedly effective, 27 cases were effective, and 4 cases were ineffective. After surgery, 3 patients presented with weakness of dorsalis pedis extension and 1 presented with paresthesia of dorsalis pedis, which disappeared after symptomatic treatment . The VAS and WOMAC score at 1 month after operation were lower than those before operation, and the differences were statistically significant(P<0.001). The tension of lateral knee soft tissue 1 month after operation was lower than that before operation, and the difference had statistical significance(P<0.001).@*CONCLUSION@#Proximal fibula osteotomy is safe and effective in the treatment of varus knee osteoarthritis in the short term. One month after osteotomy, the tension of lateral knee soft tissue increases under weight-bearing state, but the long-term changes still need further observation and follow-up.

Paranasal augmentation using autologous costal cartilage as an adjunct to rhinoplasty / 中华医学美学美容杂志

Objective:To investigate the postoperative effect of paranasal concavity augment by block united with diced autologous costal cartilage.Methods:The data of 76 patients who were underwent costal cartilage rhinoplasty together with paranasal augmentation from January 2016 to December 2019 were analyzed retrospectively. The surgical technique was described in detail. Medical charts and operative records were reviewed to summary the complications. Patients′subjective satisfaction of the postoperative nasal appearance was self-evaluated with grading (1 worse, 2 no change, 3 improved, and 4 much improved). Cosmetic effects were evaluated by the measurements of the nasolabial angle and the distance between ACJ and intertragic notch preoperatively and postoperatively.Results:The postoperative follow-up duration was 6 to 34 months. Overall, functional and aesthetic outcome was satisfactory in most patients, and the mean score by the patients′self-evaluation was 3.4±0.5. Graft exposure, mobility, or significant resorption, pneumothorax or significant donor-site pain were not observed. The average nasolabial angle was changed from (78.2±13.2)° preoperatively to (89.8±10.2)° 6 months postoperative at the last follow-up ( t=152.00, P<0.01). And the distance from the alar-cheek junction to the left tragus was increased by 3.8±2.1 (2.2-6.1) mm. Conclusions:Costal cartilage rhinoplasty combined with augmentation of parasal area can improve parasal depression, with stable postoperative effect and fewer postoperative complications, and has a good effect for patients with normal occlusal relationship or mild abnormality.

Analysis of curative effect and prognosis of immune checkpoint inhibitor in the treatment of recurrent and metastatic cervical cancer / 国际肿瘤学杂志

Objective:To analyze the efficacy, safety and prognostic factors of immune checkpoint inhibitors in the treatment of recurrent and metastatic cervical cancer.Methods:A total of 87 patients with recurrent and metastatic cervical cancer admitted to the First Affiliated Hospital of Soochow University from January 2018 to June 2022 were retrospectively analyzed. They were divided into non immunotherapy group ( n=32) and immunotherapy group ( n=55) according to whether immune checkpoint inhibition was applied after recurrence and metastasis. The disease control rate (DCR), progression free survival (PFS), overall survival 1 (OS1, date of pathology diagnosis to the end of follow-up or time of death), overall survival 2 (OS2, time of first immunotherapy/non-immunotherapy to the end of follow-up or time of death), safety and prognostic factors of the two groups were analyzed and compared. Results:In 87 patients with recurrent and metastatic cervical cancer, the DCR of the non immunotherapy group and immunotherapy group were 53.1% (17/32) and 72.7% (40/55) respectively ( χ2=3.44, P=0.064). The median OS1 of the non immunotherapy group was 51.0 months, while the immunotherapy group did not reach the median OS1, with a statistically significant difference ( χ2=7.50, P=0.006). The median OS2 of the non immunotherapy group was 28.0 months, while the immunotherapy group did not reach the median OS2, with a statistically significant difference ( χ2=7.07, P=0.008). The median PFS of the non immunotherapy group and immunotherapy group were 18.0 months and 23.0 months respectively, with no significant difference ( χ2=0.01, P=0.915). In the immunotherapy group, 70.9% (39/55) of patients received immune checkpoint inhibitors as first-line treatment and 29.1% (16/55) received as second-line and above treatment. Both groups of patients did not achieve median OS2, with median PFS of 23.0 and 17.0 months respectively, and there were no statistically significant differences ( χ2=0.94, P=0.333; χ2=2.00, P=0.158) ; 38.2% (21/55) of patients received immune checkpoint inhibitor combined with local radiotherapy, 61.8% (34/55) patients did not receive radiotherapy. And neither group of patients achieved median OS2, with median PFS of 19.0 and 25.0 months respectively, with no statistically significant differences ( χ2=0.62, P=0.432; χ2=0.01, P=0.906). The incidences of grade 1-2 hematuria and hypothyroidism in the non immunotherapy group and immunotherapy group were 53.1% (17/32) vs. 27.3% (15/55, χ2=5.82, P=0.016), 3.1% (1/32) vs. 21.8% (12/55, χ2=4.19, P=0.041) respectively. The incidence of myelosuppression in the non immunotherapy group [grade 1-2: 59.4% (19/32), grade 3-4: 34.4% (11/32) ] was significantly different from that in the immunotherapy group [grade 1-2: 80.0% (44/55), grade 3-4: 3.6% (2/55) ; Z=3.50, P<0.001]. There were no statistically significant differences between creatinine increase, glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase increase, lymphocyte decrease, hypoproteinemia, proteinuria, rash, fatigue (all P>0.05). Univariate regression analysis showed that the use of immune checkpoint inhibitor was an independent protective factor affecting the prognosis of patients ( HR=0.31, 95% CI: 0.12-0.77, P=0.012) . Conclusion:Whether used as first-line or second-line or above treatment, the use of immune checkpoint inhibitors in patients with recurrent and metastatic cervical cancer prolongs their OS1, OS2, and has good safety. The application of immune checkpoint inhibitors is an independent protective factor affecting the prognosis of patients.

Molecular Biological Mechanism of Damp-Heat Syndrome Based on Intestinal Flora Related Signaling Pathway / 世界科学技术-中医药现代化

Damp-heat syndrome is one of the common syndromes of various clinical diseases.Current studies have shown that intestinal flora is closely related to damp-heat syndrome,but the specific molecular biological mechanism related to intestinal flora and damp-heat syndrome is not yet clear.In this paper,the molecular biological mechanism of damp-heat syndrome is discussed from the perspective of intestinal flora related signaling pathways,so as to provide ideas for the essence of damp-heat syndrome and clinical diagnosis and treatment.

Correlation between the levels of serum secreted frizzled-related protein 5, sputum CXC chemokine receptor 2, chemokine receptor 1 and airway inflammation in children with acute asthma / 中国小儿急救医学

Objective:To investigate the correlation between the levels of serum secreted frizzled-related protein 5 (SFRP5), sputum CXC chemokine receptor 2(CXCR2), chemokine receptor 1 (CCR1) and airway inflammation in children with acute asthma.Methods:A total of 53 cases of acute asthma (acute group), 50 cases of asthma at remission stage (stable group) and 50 cases of healthy children (control group) in our hospital from January 2017 to January 2020 were enrolled.The expression levels of serum SFRP5, CXCR2 and CCR1, as well as pulmonary function indicators (FEV1/FVC, FEV1%), fractional exhaled nitric oxide(FeNO), and airway inflammation-related cytokines[interleukin(IL-13), vascular endothelial growth factor(VEGF)] were detected, respectively.Results:The levels of serum SFRP5 was the lowest in acute group, followed by stable group, which was the highest in control group, with statistic difference ( P<0.05). The mRNA expression levels of CXCR2 and CCR1 were the highest in acute group, followed by stable group, which were the lowest in control group, with statistic difference ( P<0.05). The predicted values of FEV1/FVC and FEV1% in acute group were significantly lower than those in stable group and control group, while FeNO in acute group was significantly higher than those in stable group and control group ( P<0.05). The predicted values of FEV1/FVC and FEV1% in stable group were significantly lower than those in control group, and FeNO was significantly higher than that in control group( P<0.05). The values of FEV1/FVC and FEV1% were the lowest in acute group, followed by stable group, which were the highest in control group ( P<0.05). The values of serum IL-13 and VEGF were the highest in acute group, followed by stable group, which were the lowest in control group, with statistic difference( P<0.05). Correlation analysis showed that the level of serum SFRP5 was positively correlated with lung function index FEV1/FVC and FEV1% to the predicted value( P<0.05), and negatively correlated with the levels of inflammatory index IL-13 and FeNO ( P<0.05). The levels of sputum CXCR2 and CCR1 were negatively correlated with lung function index FEV1/FVC and FEV1% to predicted value( P<0.05), and positively correlated with inflammatory index IL-13, VEGF and FeNO( P<0.05). Conclusion:Serum SFPR5 is decreased, and septum mRNA expression levels of CCR1 and CXCR2 are elevated in asthma children, so these three indicators could be used to predict the severity of airway inflammation in asthma children, thus providing reference for clinical diagnosis and treatment.

Clinical features and prognosis of core binding factor acute myeloid leukemia children in South China: a multicenter study / 中华儿科杂志

Objective: To analyze the clinical features, efficacy and prognosis factors of core binding factor (CBF) acute myeloid leukemia (AML) children in South China. Methods: This was a retrospective cohort study. Clinical data of 584 AML patients from 9 hospitals between January 2015 to December 2020 was collected. According to fusion gene results, all patients were divided into two groups: CBF-AML group (189 cases) and non-CBF-AML group (395 cases). CBF-AML group were divided into AML1-ETO subgroup (154 cases) and CBFβ-MYH11 subgroup (35 cases). Patients in CBF-AML group chosen different induction scheme were divided into group A (fludarabine, cytarabine, granulocyte colony stimulating factor and idarubicin (FLAG-IDA) scheme, 134 cases) and group B (daunorubicin, cytarabine and etoposide (DAE) scheme, 55 cases). Age, gender, response rate, recurrence rate, mortality, molecular genetic characteristics and other clinical data were compared between groups. Kaplan-Meier method was used for survival analysis and survival curve was drawn. Cox regression model was used to analyze prognostic factors. Results: A total of 584 AML children were diagnosed, including 346 males and 238 females. And a total of 189 children with CBF-AML were included, including 117 males and 72 females. The age of diagnosis was 7.3 (4.5,10.0)years, and the white blood cell count at initial diagnosis was 21.4 (9.7, 47.7)×109/L.The complete remission rate of the first course (CR1) of induction therapy, relapse rate, and mortality of children with CBF-AML were significantly different from those in the non-CBF-AML group (91.0% (172/189) vs. 78.0% (308/395); 10.1% (19/189) vs. 18.7% (74/395); 13.2% (25/189) vs. 25.6% (101/395), all P<0.05). In children with CBF-AML, the CBFβ-MYH11 subgroup had higher initial white blood cells and lower proportion of extramedullary invasion than the AML1-ETO subgroup, with statistical significance (65.7% (23/35) vs. 14.9% (23/154), 2.9% (1/35) vs. 16.9% (26/154), both P<0.05). AML1-ETO subgroup had more additional chromosome abnormalities (75/154), especially sex chromosome loss (53/154). Compared with group B, group A had more additional chromosome abnormalities and a higher proportion of tumor reduction regimen, with statistical significance (50.0% (67/134) vs. 29.1% (16/55), 34.3% (46/134) vs. 18.2% (10/55), both P<0.05). Significant differences were found in 5-years event free survival (EFS) rate and 5-year overall survival (OS) rate between CBF-AML group and non-CBF-AML group ((77.0±6.4)%vs. (61.9±6.7)%,(83.7±9.0)%vs. (67.3±7.2)%, both P<0.05).EFS and OS rates of AML1-ETO subgroup and CBFβ-MYH11 subgroup in children with CBF-AML were not significantly different (both P>0.05). Multivariate analysis showed in the AML1-ETO subgroup, CR1 rate and high white blood cell count (≥50×109/L) were independent risk factors for EFS (HR=0.24, 95%CI 0.07-0.85,HR=1.01, 95%CI 1.00-1.02, both P<0.05) and OS (HR=0.24, 95%CI 0.06-0.87; HR=1.01, 95%CI 1.00-1.02; both P<0.05). Conclusions: In CBF-AML, AML1-ETO is more common which has a higher extramedullary involvement and additional chromosome abnormalities, especially sex chromosome loss. The prognosis of AML1-ETO was similar to that of CBFβ-MYH11. The selection of induction regimen group FLAG-IDA for high white blood cell count and additional chromosome abnormality can improve the prognosis.

Effects of co-culture of dendritic cells loaded with MAGE-A3 antigen and cytokine-induced killer cells on tumor stem cells and malignant progression of endometrial cancer / 中国临床药理学与治疗学

AIM: To explore the effects of dendritic cells (DC) and cytokine-induced killer cells (CIK) carrying melanoma-associated antigen gene A3 (MAGE-A3) on endometrial cancer tumor stem cells and malignant progression. METHODS: Human peripheral blood was collected to separate mono-nuclear cells, and DC and CIK cells were induced by cytokines, respectively. DCs were incubated with MAGE-A3 and then co-cultured with CIK, and the phenotypes of DC-CIK and MAGE-A3-DC-CIK were detected by flow cytometry; The CD133

Evidence mapping analysis of clinical research on traditional Chinese medicine in treatment of vertigo / 中国中药杂志

In this study, the evidence map system was used to sort out the clinical research evidence on traditional Chinese medicine(TCM) treatment of vertigo and understand the evidence distribution in this field. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Web of Science were searched for the clinical randomized controlled trial(RCT) and systematic reviews/Meta-analysis on TCM treatment of vertigo in recent five years, and the evidence was analyzed and presented in the form of text and charts. The Cochrane handbook for systematic reviews of interventions was used to evaluate the quality of the clinical RCT, and the AMSTAR mea-surement tool was used to evaluate the quality of the systematic reviews/Meta-analysis. A total of 382 RCTs and eight systematic reviews/Meta-analysis were included. In recent five years, the number of published articles has been on the rise. There were many intervention measures and TCM therapies for vertigo. Outcome indicators mainly included clinical efficacy, TCM syndrome score, vertigo score, occurrence of adverse reactions, and effective rate. The overall quality of clinical RCT and systematic reviews/Meta-analysis was low. Most studies have proven the potential efficacy of TCM in treating vertigo, but there was still no clear clinical evidence of efficacy. The results show that TCM has advantages in the treatment of vertigo, but there are also problems. More high-quality studies are still lacking, suggesting that more large-sample and multi-center RCT should be conducted in the future, and the quality of relevant syste-matic reviews/Meta-analysis should be improved to fully explore the advantages of TCM in the treatment of vertigo, and provide strong support for the effectiveness and safety of TCM in the treatment of vertigo.

Association between MTHFR c.677C>T variant and erectile dysfunction among males attending fertility clinic / 亚洲男科学杂志(英文版)

Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase (MTHFR) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.15-5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis.

Quercetin Attenuates Atherosclerosis via Modulating Apelin Signaling Pathway Based on Plasma Metabolomics / 中国结合医学杂志

OBJECTIVE@#To interpret the pharmacology of quercetin in treatment of atherosclerosis (AS).@*METHODS@#Fourteen apolipoprotein E-deficient (ApoE-/-) mice were divided into 2 groups by a random number table: an AS model (ApoE-/-) group and a quercetin treatment group (7 in each). Seven age-matched C57 mice were used as controls (n=7). Quercetin [20 mg/(kg·d)] was administered to the quercetin group intragastrically for 8 weeks for pharmacodynamic evaluation. Besides morphological observation, the distribution of CD11b, F4/80, sirtuin 1 (Sirt1) and P21 was assayed by immunohistochemistry and immunofluorescence to evaluate macrophage infiltration and tissue senescence. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MSC/MS) was performed to study the pharmacology of quercetin against AS. Then, simultaneous administration of an apelin receptor antagonist (ML221) with quercetin was conducted to verify the possible targets of quercetin. Key proteins in apelin signaling pathway, such as angiotensin domain type 1 receptor-associated proteins (APJ), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), tissue plasminogen activator (TPA), uncoupling protein 1 (UCP1) and angiotensin II receptor 1 (AT1R), were assayed by Western blot.@*RESULTS@#Quercetin administration decreased lipid deposition in arterial lumen and improved the morphology of ApoE-/- aortas in vivo. Quercetin decreased the densities of CD11b, F4/80 and P21 in the aorta and increased the level of serum apelin and the densities of APJ and Sirt1 in the aorta in ApoE-/- mice (all P<0.05). Plasma metabolite profiling identified 118 differential metabolites and showed that quercetin affected mainly glycerophospholipids and fatty acyls. Bioinformatics analysis suggested that the apelin signaling pathway was one of the main pathways. Quercetin treatment increased the protein expressions of APJ, AMPK, PGC-1α, TPA and UCP1, while decreased the AT1R level (all P<0.05). After the apelin pathway was blocked by ML221, the effect of quercetin was abated significantly, confirming that quercetin attenuated AS by modulating the apelin signaling pathway (all P<0.05).@*CONCLUSION@#Quercetin alleviated AS lesions by up-regulation the apelin signaling pathway.

Association between semen collection time and semen parameters: an observational study / 亚洲男科学杂志(英文版)

The process of semen collection plays a key role in the quality of semen specimens. However, the association between semen collection time and semen quality is still unclear. In this study, ejaculates by masturbation from 746 subfertile men or healthy men who underwent semen analysis were examined. The median (interquartile range) semen collection time for all participants was 7.0 (5.0-11.0) min, and the median time taken for semen collection was lower in healthy men than that in subfertile men (6.0 min vs 7.0 min). An increase in the time required to produce semen samples was associated with poorer semen quality. Among those undergoing assisted reproductive technology (ART), the miscarriage rate was positively correlated with the semen collection time. After adjusting for confounders, the highest quartile (Q4) of collection time was negatively associated with semen volume and sperm concentration. A longer time to produce semen samples (Q3 and Q4) was negatively correlated with progressive and total sperm motility. In addition, there was a significant negative linear association between the semen collection time and the sperm morphology. Higher risks of asthenozoospermia (adjusted odds ratio [OR] = 2.06, 95% confidence interval [CI]: 1.31-3.25, P = 0.002) and teratozoospermia (adjusted OR = 1.98, 95% CI: 1.10-3.55, P = 0.02) were observed in Q3 than those in Q1. Our results indicate that a higher risk of abnormal semen parameter values was associated with an increase in time for semen collection, which may be related to male fertility through its association with semen quality.

Venous thromboembolism in children with acute lymphoblastic leukemia in China: a report from the Chinese Children's Cancer Group-ALL-2015 / 医学前沿

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.

Analysis of clinical characteristics and risk factors of patients with cerebral venous sinus thrombosis in the puerperium / 中国综合临床

Objective:To investigate the risk factors of cerebral venous sinus thrombosis (CVST) during puerperal period.Methods:This study was a restrospective analysis, A total of 33 puerperal CVST patients admitted to Beijing Tiantan Hospital, Capital Medical University from January 2016 to November 2022 were selected as the observation group, and 61 puerperal healthy women who underwent postpartum follow-up at the same period in the hospital were selected as the control group. The age, body mass index (BMI), smoking history, hypertension history, diabetes history, drug use history and mode of delivery or abortion of the two groups of women were compared and collected, as well as the level of laboratory indicators. The risk factors of CVST in puerperal period were analyzed. The measurement data of normal distribution were represented by two independent samples t test for comparison between groups. The measurement data of non-normal distribution were expressed as M ( Q1, Q3), and the Wilcoxon rank sum test was used for comparison between groups. The count data is expressed as number (%), and the comparison between groups is performed using χ 2 test or Fisher exact probability method. Logistic regression model was established to analyze the risk factors of CVST in puerperal period. Results:BMI, serum LDH, α-HBDH, fasting blood glucose, HCY levels, WBC, NEU, NLR, RDW and MPV in observation group were higher than those in control group [(30.21±4.25) kg/m 2 vs (21.94±3.02) kg/m 2]. 195.15(183.10,240.98) U/L vs 165.75(154.55,184.62) U/L, 166.60(143.10,188.60) U/L vs 124.10(116.30,137.90) U/L, (4.88 ± 0.98) vs (4.25±0.41), 8.35 (7.10, 12.16) μmol/L vs 6.60 (5.30, 7.58) μmol/L, 9.26 (6.56, 11.76) × 10 9/L vs 7.25 (6.23, 8.00) × 10 9/L, and 7.18 (4.66, 8.79) × 10 9/L vs 3.93 (3.25, 4.52) × 10 9/L, 4.13 (2.27,6.55) vs 1.63 (1.16,1.97), 42.80(38.95,47.45) fL vs 40.70(38.95,42.60) fL, (9.52±0.99) fL vs 8.96±0.88 fL], LY and PDW were lower than control group [1.58(1.11,1,96)×10 9/L vs 2.50(2.04,2.91)×10 9/L, 15.60(11.65,16.20) fL vs 16.00(15.80,16.30) fL]. The differences were statistically significant ( t=4.58, P<0.001; Z=4.54, P<0.001; Z=5.56, P<0.001; t=3.38, P=0.002; Z=4.18, P<0.001; Z=3.39, P=0.001; Z=4.92, P<0.001; Z=4.92, P<0.001; Z=4.54, P<0.001; Z=5.56, P<0.001; Z=4.18, P<0.001; Z=4.92, P<0.001; Z=5.87, P<0.001; Z=2.18, P=0.029; t=2.82, P=0.006; Z=4.78, P<0.001; Z=2.52, P=0.012). Multivariate Logistic regression analysis showed that NEU, HCY and α-HBDH were risk factors for puerparal CVST (odds ratios were 3.07, 1.53 and 1.07, respectively, 95% confidence interval: 1.65~5.71, 1.09~2.15, 1.02~1.12, P values were <0.001, 0.014, 0.007, respectively). Conclusions:α-HBDH, HCY and NEU are independent risk factors for puerperal CVST.

Comparison of Exosomes Derived from Fibroblasts and Mesenchymal Stem Cells for the Treatment of Acute Wound Healing / 中山大学学报(医学科学版)

ObjectiveTo compare the therapeutical effect of exosomes derived from fibroblasts and mesenchymal stem cells on acute wound healing. MethodsPrimary human dermal fibroblasts （hDF） were isolated， cultured and identified. Human bone marrow mesenchymal stem cell exosomes （hMSC-EXO） and hDF exosomes （hDF-EXO） were extracted by ultracentrifuga tion. After 24 h of coincubation with hDF-EXO or hMSC-EXO， hDFs proliferation and migratory capacity were evaluated by cell counting kit-8 （CCK8） assay and scratch test. Full-thickness cutaneous wounds were created on 8-week-old female C57BL/6 mice， and topically applied with PBS （control）， hDF-EXO or hMSC-EXO. Wounds were measured at day 0， 2， 4， 7， and the uptake of exosomes in wound was observed at day 1. Quantitative PCR （qPCR） analysis was performed to detect the mRNA expression levels of TNF-α， IL-6， IL-1β， IL-10 in wound at day 1. HE staining was conducted to analyze the histological structure of wounds at day 7， while immunofluorescence staining was used to examine expression of PDGFR-α、α-SMA、Ki67. ResultshDF exhibited certain fibrolast-like characteristics with respect to expression of cell surface markers and specific proteins. hDF-EXO and hMSC-EXO presented exosomal morphology， size， and markers， and both concentrations were not statistically different （P>0.05）； CCK8 assay showed that both exosomes promoted hDF cell viability， compared with the negative control （P<0.01）， and hDF-EXO group had greater cell viability than hMSC-EXO group （P<0.01）. Scratch test indicated that hDF-EXO induced a significant increase in scratch healing rate versus the negative control （P<0.01）， hMSC-EXO （P<0.05）. In vivo experiments showed wound tissues took up exosomes at day 1. qPCR detected TNF-α， IL-6， IL-1β expression levels in wound at day 1 were lower in exosomes group than in the control group， and were the lowest in hMSC-EXO group （all P<0.01）. Wound areas were measured smaller at day 7 in exosomes group than in the control group （all P<0.01） and hDF-EXO group had better closure than hMSC-EXO group （P<0.05）. HE staining revealed that compared with control group， scar， incomplete epidermis and few collagen deposition remained in the hMSC-EXO group， whereas hDF-EXO group showed re-epithelialization， continuous neo-epidermis and regenerated dermis. Immunofluorescence staining suggested that the number of fibroblasts， myofibroblasts， proliferating cells was higher in both exosomes group than that in the control group， especially the highest in hDF-EXO group. ConclusionOur study shows both exosomes accelerate wound healing， whereas hDF-EXO is more effective in promoting fibroblasts proliferation， migration， transition to myofibroblasts， and hMSC-EXO may play a role in inhibiting inflammatory reaction during early stage of wound healing.