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Zhachong-13 pills (ZC-13), as a traditional prescription of Mongolian medicine, are often used in the clinical practice of Mongolian hospitals for the treatment of stroke and rheumatic arthritis. In this experiment, UHPLC-Q-Exactive Orbitrap MS was used to explore the chemical composition of ZC-13. The results showed that 315 compounds were identified or inferred, including 56 alkaloids, 77 2-(2-phenylethyl)chromones, 61 flavonoids, 31 tannins, 8 coumarins, 16 lignans, 21 terpenoids, 5 amino acids, 19 organic acids, and 21 other components. In addition, the pharmacological activities related to anti-cerebral ischemia of these components were summarized. This result laid a foundation for further study on the pharmacodynamic material basis of ZC-13 and provided a scientific basis for the formulation of ZC-13 quality specifications.

Background: Surgical treatment of functional single ventricle combined with atrioventricular valve regurgitation remains a clinical challenge. The outcomes of atrioventricular valve repair in patients with single ventricle are limited., Methods: A retrospective study was conducted of all 28 patients with functional single ventricle treated with single-ventricle palliation who underwent atrioventricular valve operation at the First Hospital of Tsinghua University between April 2007 and October 2022., Results: In our cohort, the female/male ratio was 7:21, with an average age of 8.7 ± 6.0 (0.75-26) years. Half of patients (50%) were right-ventricle type for single-ventricle morphology. 18 patients (64.3%) were with a common atrioventricular valve. Twenty-three patients (82.1%) were combined with heterotaxy syndrome. Pre-operatively, twenty-four patients (85.7%) were diagnosed with severe atrioventricular valve regurgitation. AVV was repaired at the Glenn ( n  = 16, 57.1%), Glenn-Fontan ( n  = 2, 7.1%) and Fontan ( n  = 10, 35.7%) stage, respectively. Valve plastic techniques included valve annulus/commissure constriction ( n  = 24), clefts repair (9 cases), edge-to-edge suturing (13 cases) and common atrioventricular valve separation (4 cases). The early mortality was 3.6% (1/28). All survival patients were observed with improved regurgitation situations. Twenty-two patients (78.5%) were observed with no more than mild regurgitation postoperatively. The mean follow-up time was 5.4 ± 2.9 years (range, 3.08-11.83 years), with late mortality of 11.1% (3/27). All these three cases were observed with a severe regurgitation by echocardiogram in the last follow-up. Besides, reoperation rate of this cohort was 3.6% (1/28)., Conclusions: AVV repair could significantly improve AVV function in SV patients combined with severe AVVR, with satisfactory mid-term results. Part of the cohort showed poor prognosis due to repeated AVVR. Regular follow-up by echocardiogram is critically important for these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Jin, Wu, Zhang, Fan, Zhang, Xue and Zhang.)

Objective: To analyze the efficacy of high-intensity focused ultrasound (HIFU) for adenomyosis and postoperative recurrence and its influencing factors., Methods: Clinical and follow-up data of 308 patients with adenomyosis who were treated with HIFU in Haifu Center, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from September 2017 to January 2022 were retrospectively analyzed. The recurrence of adenomyosis and the efficacy of HIFU at 6 months after surgery were followed up. To explore factors influencing postoperative prognosis and recurrence, the following variables were analyzed: patients' age, course of disease, gravidity and parity, size of the uterus, duration of HIFU, duration of irradiation, treatment intensity, dysmenorrhea score, time of follow-up, combined treatment of traditional Chinese medicine (TCM), western medicine adjuvant treatment, lesion location and type, and menorrhagia., Results: Among the 308 patients, 238 (77%) were followed up from 6 to 36 months, with an average follow-up time of 15.24 ± 9.97 months. The other 70 (23%) were lost to follow-up. At 6-month after surgery, efficacy rates of dysmenorrhea and menorrhagia management were 86.7% and 89.3%, respectively. Postoperative recurrence rates were 4.8% (1-12 months), 9.0% (12-24 months), and 17.0% (24-36 months) for dysmenorrhea; and 6.3% (1-12 months), 2.4% (12-24 months), and 12.2% (24-36 months) for menorrhagia. Multivariate logistic regression analyses showed that parity (P = 0.043, OR = 1.773, 95% CI 1.018-3.087), uterine size (P = 0.019, OR = 1.004, 95% CI 1.001-1.007), combined treatment of TCM (P = 0.047, OR = 1.846, 95% CI 1.008-3.381), diffuse lesion type (P = 0.013, OR = 0.464, 95% CI 0.254-0.848) and ablation rate (P = 0.015, OR = 0.481, 95%CI 0.267-0.868) were prognostic factors (P < 0.05). Age, course of disease, gravidity, duration of HIFU, duration of irradiation, treatment intensity, preoperative dysmenorrhea score, time of follow-up, western medicine adjuvant therapy, lesion location, and preoperative menstrual volume had no effect on prognosis (P > 0.05)., Conclusion: HIFU can effectively relieve dysmenorrhea and reduce menstrual volume in patients with adenomyosis. Parity, uterine size, lesion type (diffuse), and ablation rate are risk factors for symptom recurrence after HIFU, while the combination of TCM therapy is a protective factor for relapse. We, therefore, recommend TCM in the adjuvant setting after HIFU according to patient condition., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ileostomy diverts the flow of feces, which can result in malnutrition in the distal part of the intestine. The diversity of the gut microbiota consequently decreases, ultimately leading to intestinal dysbiosis and dysfunction. This condition can readily result in diversion colitis (DC). Potential treatment strategies include interventions targeting the gut microbiota. In this case study, we effectively treated a patient with severe DC by ileostomy and allogeneic fecal microbiota transplantation (FMT). A 69-year-old man presented with a perforated malignant tumor in the descending colon and an iliac abscess. He underwent laparoscopic radical sigmoid colon tumor resection and prophylactic ileostomy. Follow-up colonoscopy 3 months postoperatively revealed diffuse intestinal mucosal congestion and edema along with granular inflammatory follicular hyperplasia, leading to a diagnosis of severe DC. After two rounds of allogeneic FMT, both the intestinal mucosal bleeding and edema significantly improved, as did the diversity of the gut microbiota. The positive outcome of allogeneic FMT in this case highlights the potential advantages that this procedure can offer patients with DC. However, few studies have focused on allogeneic FMT, and more in-depth research is needed to gain a better understanding., Competing Interests: Declaration of conflicting interestYong-Ling Lv, Kai Xiong, and Zhi-Wei Jiang are employees of Maintainbiotech, Ltd. (Wuhan, China). The other authors declare no conflict of interest.

A novel in situ chemical upcycling strategy for plastic waste is proposed by the customized diphenylacetylene monomer with dual photo-response. That is, diphenylacetylene reactive monomers are in situ inserted into the macromolecular chain of polyethylene terephthalate (PET) plastics/fibers through one-pot transesterification of slight-depolymerization and re-polymerization. On the one hand, the diphenylacetylene group absorbs short-wave high-energy UV rays and then releases long-wave low-energy harmless fluorescence. On the other hand, the UV-induced photo-crosslinking reaction among diphenylacetylene groups produces extended π-conjugated structure, resulting in a red-shift (due to decreased HOMO-LUMO separation) in the UV absorption band and locked crosslink points between PET chains. Therefore, with increasing UV exposure time, the upcycled PET plastics exhibit reverse enhanced UV resistance and mechanical strength (superior to original performance), instead of serious UV-photodegradation and damaged performance. This upcycling strategy at oligomer-scale not only provides a new idea for traditional plastic recycling, but also solves the common problem of gradual degradation of polymer performance during use., (© 2023 Wiley-VCH GmbH.)

Objective: To evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) combined with the levonorgestrel intrauterine system (LNG-IUS) for adenomyosis., Methods: We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, SinoMed, Wanfang, and VIP databases from their inception to Nov 20, 2021 for relevant articles that compared HIFU combined with LNG-IUS vs. HIFU alone in patients with adenomyosis. RevMan5.4 software was used for the data analysis. The primary outcome was changes in volume of the uterine. Secondary outcomes included visual analog scale (VAS) scores for dysmenorrhea, serum CA125 level, recurrence rate, changes in volume of the adenomyotic lesion, menstrual volume scores, and adverse reactions. Data synthesis was conducted using a random-effects model with significant heterogeneity (I 2  > 50%), and using a fixed-effects model otherwise. This study is registered on the PROSPERO platform (CRD42021295214)., Results: The final analysis included 13 studies, with a total of 1861 patients. Results of analysis revealed that there was no significant difference in uterine volume reduction between the HIFU control group and the HIFU/LNG-IUS group at 3 months after procedure (MD:30.63). Compared with the HIFU control group, the HIFU/LNG-IUS group had more pronounced reduction in uterine volume at 6 (MD:29.04) and 12 months (MD:22.10) after procedure. The HIFU/LNG-IUS group has lower VAS scores for dysmenorrhea than the HIFU control group at 3 (MD:1.68), 6 (MD:1.69), and 12 months (MD:1.30) after procedure. Serum CA125 level in the HIFU/LNG-IUS group decreased more significantly than the HIFU control group at 6 (MD:18.34) and 12 months (MD:18.49) after procedure. The recurrence rate in the HIFU/LNG-IUS group was lower than that in the HIFU control group (RR:0.20)., Conclusions: Compared to HIFU control group, HIFU/LNG-IUS group for the management of adenomyosis had more advantages in alleviating symptoms and decreasing the volumes of the uterine and adenomyotic lesions. However, since the number of the included studies was too small and some of them were not RCT, this conclusion needs to be referenced with caution., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The treatment of coronary artery disease combined with severe atherosclerotic stenosis proximal to a left anterior descending artery myocardial bridge (LAD-MB) is still controversial. This study aimed to analyze the outcomes of surgical intervention in patients with severe atherosclerotic stenosis proximal to a LAD-MB., Methods: We retrospectively reviewed all patients with coronary artery disease combined with severe atherosclerotic stenosis proximal to the LAD-MB. The enrolled criteria were systolic compression of LAD more than or equal to 50% and atherosclerotic stenosis proximal to the LAD-MB more than or equal to 70%. All patients suffered from anginal symptoms refractory to medical therapy. All patients received supra-arterial myotomy and coronary artery bypass grafting (CABG) procedures. Clinical characteristics, intraoperative findings, and postoperative outcomes were evaluated., Results: Between 2004 and 2021, sixteen patients underwent supra-arterial myotomy and CABG procedure. The compression and length of LAD-MB were 63 ± 17.9% and 25.9 ± 16.3 mm, respectively. Of the 16 patients, one patient had a LAD-MB and proximal coronary stenosis, and 15 patients had LAD-MBs and multivessel lesions. All patients survived and recovered uneventfully without in-hospital mortality or severe complications. The median transfusion amount of red blood cells in the operation was 2 units, and no patients required unplanned reoperation for bleeding. The average length of intensive care unit stay was 2.74 days. Fifteen patients were followed up for 6-146.1 months (mean 45.3 ± 42.9 months). One patient had a recurrence of angina pectoris one year after surgery, and 14 patients had no symptoms of myocardial ischemia during the follow-up period. Significant improvement in symptoms and quality of life using the Seattle Angina Questionnaire assessment was observed in all five categories after surgery (p < 0.01)., Conclusions: Based on the results, supra-arterial myotomy and concomitant bypass surgery may be a better option for the treatment of LAD-MB combined with severe proximal stenosis., (© 2023. The Author(s).)

Inositol-requiring enzyme 1α (IRE1α) is the most conserved endoplasmic reticulum (ER) stress sensor with two catalytic domains, kinase and RNase, in its cytosolic portion. IRE1α inhibitors have been used to improve existing clinical treatments against various cancers. In this study we identified toxoflavin (TXF) as a new-type potent small molecule IRE1α inhibitor. We used luciferase reporter systems to screen compounds that inhibited the IRE1α-XBP1s signaling pathway. As a result, TXF was found to be the most potent IRE1α RNase inhibitor with an IC 50 value of 0.226 μM. Its inhibitory potencies on IRE1α kinase and RNase were confirmed in a series of cellular and in vitro biochemical assays. Kinetic analysis showed that TXF caused time- and reducing reagent-dependent irreversible inhibition on IRE1α, implying that ROS might participate in the inhibition process. ROS scavengers decreased the inhibition of IRE1α by TXF, confirming that ROS mediated the inhibition process. Mass spectrometry analysis revealed that the thiol groups of four conserved cysteine residues (CYS-605, CYS-630, CYS-715 and CYS-951) in IRE1α were oxidized to sulfonic groups by ROS. In molecular docking experiments we affirmed the binding of TXF with IRE1α, and predicted its binding site, suggesting that the structure of TXF itself participates in the inhibition of IRE1α. Interestingly, CYS-951 was just near the docked site. In addition, the RNase IC 50 and ROS production in vitro induced by TXF and its derivatives were negative correlated (r = -0.872). In conclusion, this study discovers a new type of IRE1α inhibitor that targets a predicted new alternative site located in the junction between RNase domain and kinase domain, and oxidizes conserved cysteine residues of IRE1α active sites to inhibit IRE1α. TXF could be used as a small molecule tool to study IRE1α's role in ER stress., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: To investigate the levels of Th9 cells and interleukin-9 (IL-9), and to assess the regulatory activity of Th9/IL-9 to anti-tumor immune response in patients with gastric cancer. Methods: Thirty-four patients with gastric cancer who received operation in the First Affiliated Hospital of Xinxiang Medical University between October 2018 and August 2019 were included. Twenty individuals who received physical examination in the same period were also enrolled. Peripheral blood was collected, and then plasma and peripheral blood mononuclear cells (PBMCs) were isolated. Tumor-infiltrating lymphocytes (TILs) and autologous gastric cancer cells were isolated from resected gastric cancer tissues. CD4(+) T cells, CD8(+) T cells, and CD4(+) CCR4(-)CCR6(-)CXCR3(-) cells were purified from PBMCs and TILs. Plasma IL-9 level was measured by enzyme linked immunosorbent assay (ELISA). The percentage of CD3(+) CD4(+) IL-9(+) Th9 cells in PBMCs and TILSs was assessed by flow cytometry. The mRNA levels of IL-9 and transcriptional factors purine-rich nucleic acid binding protein 1 (PU.1) were semi-quantified by real-time quantitative polymerase chain reaction (RT-qPCR). PBMCs and TILs from gastric cancer patients were stimulated with recombinant human IL-9. Cellular proliferation was measured by cell counting kit-8. The phosphorylation levels of signal transducer and activator of transcription 3 (STAT3) and STAT6 were investigated by western blot. Cytokine production was measured by ELISA. Purified CD8(+) T cells from TILs of gastric cancer patients were stimulated with recombinant human IL-9. CD8(+) T cells and autologous gastric cancer cells were cocultured in direct contact and indirect contact manner. The percentage of target cell death was calculated by measuring the lactate dehydrogenase (LDH) level. These cretion of γ-Interferon (γ-IFN) and tumor necrosis factor-α (TNF-α) was measured by ELISA. CD4(+) CCR4(-)CCR6(-)CXCR3(-)cells, CD8(+) T cells, and autologous gastric cancer cells were directly cocultured, and anti-IL-9 neutralizing antibody was added. The target cell death was measured. Results: The percentages of CD3(+) CD4(+) IL-9(+) Th9 cells in PBMCs of control group and PBMCs of gastric cancer group were (1.21±0.25)% and (1.14±0.19)%, respectively. The difference was not statistically significant ( P =0.280). The percentage of CD3(+) CD4(+) IL-9(+) Th9 cells in TILs of gastric cancer group was (2.30±0.55)%, which was higher than those in PBMCs of control group and PBMCs of gastric cancer group ( P <0.001). The plasma IL-9 level in control group and gastric cancer group were (5.04±1.51) and (4.93±1.25) ng/ml. The difference was not statistically significant ( P =0.787). The relative levels of IL-9 mRNA in PBMCs of control group and PBMCs of gastric cancer group were 1.33±0.39 and 1.36±0.27. The difference was not statistically significant ( P =0.691). The relative level of IL-9 mRNA in TILs of gastric cancer group was 2.90±0.75, which was higher than those in PBMCs of control group ( P <0.001) and PBMCs of gastric cancer group ( P <0.001). The relative levels of PU.1 mRNA in PBMCs of control group and PBMCs of gastric cancer group were 1.21±0.12 and 1.20±0.11. The difference was not statistically significant ( t =0.21, P =0.833). PU.1 mRNA relative level in TILs of gastric cancer group was 2.81±0.65, which was higher than those in PBMCs of control group ( P <0.001) and PBMCs of gastric cancer group ( P <0.001). Recombinant human IL-9 stimulation did not affect the proliferation of PBMCs and TILs of gastric cancer patients ( P >0.05), but elevated the phosphorylation level of STAT6 and induced the secretions of γ-IFN, IL-17, and IL-22 by TILs ( P <0.05). In direct contact culture system, IL-9 stimulation promoted tumor-infiltrating CD8(+) T cells-induced autologous gastric cancer cell death [(20.62±2.27)% vs. (16.08±2.61)%, P <0.01)]. In indirect contact culture system, IL-9 stimulation did not increase CD8(+) T cell-induced autologous gastric cancer cell death [(5.21±0.70)% vs. (5.31±1.22)%, P =0.998)]. However, the secretion levels of γ-IFN were elevated in response to IL-9 stimulation in both culture systems [direct contact culture system: (100.40±12.05) pg/ml vs. (76.45±8.56) pg/ml; indirect contact culture system: (78.00±9.98) pg/ml vs. (42.09±10.71) pg/ml; P <0.01]. The TNF-α secretion level did not significantly changed ( P >0.05). In direct contact culture system, the percentage of target cells was (22.01±3.05) % and γ-IFN secretion level was (104.5±12.84) pg/ml in CD4(+) CCR4(-)CCR6(-)CXCR3(-) cells+ CD8(+) T cells+ gastric cancer cells group, which was higher than (16.08±2.61)% and (76.45±8.56) pg/ml in CD8(+) T cells+ gastric cancer cells group ( P <0.01). However, the percentage of target cells was (14.47±3.14)% and γ-IFN secretion level was (70.45±19.43) pg/ml in CD4(+) CCR4(-)CCR6(-)CXCR3(-) cells+ CD8(+) T cells+ gastric cancer cells+ anti-IL-9 neutralizing antibody group, which were lower than those in CD4(+) CCR4(-)CCR6(-)CXCR3(-) cells+ CD8(+) T cells+ gastric cancer cells group ( P <0.01). Conclusion: Tumor-infiltrating Th9 cells and the secreting IL-9 promote the activity of CD8(+) T cells in gastric cancer patients, and enhance anti-tumor immune response.

Background: The surgical strategy among patients with malignancy and coronary artery disease (CAD) remains controversial. In this study, we present the experiences of coronary artery bypass grafting (CABG) in patients with malignancy and analyzed the treatment outcomes., Methods: From January 2011 to October 2021, eight patients combined with coronary artery disease and malignancy, six of them with three-vessel disease and two with anterior descending branch lesions on coronary angiography. The age ranged from 54 to 73 years (61.8 ± 7.7years). Four patients underwent CABG and staging for surgical oncology, and 2 patients underwent CABG and surgical oncology simultaneously. Four patients underwent CABG procedure with cardiopulmonary bypass (on-pump CABG), and the other patients underwent the procedure without cardiopulmonary bypass (off-pump CABG). All patients were followed up for 3 to 96 months (40.4 ± 31.5 months) postoperatively., Results: The mean number of grafts was 2.6 ± 1.1, there was no in-hospital death, postoperative myocardial infarction, and stroke. Among the eight patients, one patient received chemotherapy and radiation before bypass surgery, which occurred postoperatively pulmonary infection, and the rest of 7 patients had no major adverse cardiovascular events during follow-up periods., Conclusion: Based on the results of the present study, simultaneous or staged CABG and oncologic surgery according to the TNM stage of the tumor and cardiac assessment is an effective treatment for patients with severe CAD combined with malignancy., (© 2022. The Author(s).)

Objective: To investigate the pregnancy outcomes of pregnant women with cesarean scar diverticulum (CSD) and to find the relevant factors that predict the occurrence of adverse pregnancy outcomes. Methods: From January 2015 to March 2019, 501 singleton pregnant women with a history of cesarean section who underwent regular prenatal examination in early pregnancy and eventually delivered in Peking University First Hospital were prospectively collected. According to the presence or absence of CSD in the first trimester of pregnancy, the pregnant women were divided into the CSD group ( n =127, 25.3%) and the non-CSD group ( n= 374, 74.7%). According to the mode of delivery and the classification of the lower uterine segment seen during cesarean section, the CSD group was further divided into the non-rupture group (including spontaneous delivery and lower uterine segment grade Ⅰ; n =108, 85.0%) and rupture group (including lower uterine segment grade Ⅱ-Ⅳ; n =19, 15.0%). The general clinical data, pregnancy outcomes, diverticulum-related indexes [including length, width, depth (D), average diameter, volume, and residual myometrial thickness (RMT)] were compared. The predictive values of D/adjacent myometrial thickness≥50%, RMT≤2.2 mm and D/RMT>1.3 for uterine rupture in CSD pregnant women were verified. Results: (1) Comparison between CSD group and non-CSD group: the lower uterine segment thickness in the third trimester of pregnancy in the CSD group was lower than that in the non-CSD group [(1.2±0.5) vs (1.4±0.6) mm, respectively], and the incidence of uterine rupture was higher than that in the non-CSD group [15.0% (19/127) vs 8.0% (30/374), respectively], and the differences were statistically significant (both P <0.05). There were no significant differences in other clinical data and pregnancy outcomes between the two groups (all P >0.05). (2) Comparison of rupture group and non-rupture group: the lower uterine segment thickness in the third trimester of pregnancy in rupture group [(0.6±0.5) mm] was lower than that in non-rupture group [(1.2±0.6) mm], and the difference was statistically significant ( t =3.486, P =0.001). There were no significant differences in diverticulum-related indexes between the two groups (all P >0.05). (3) Relationship between high risk predictors of uterine rupture and actual uterine rupture: the sensitivity of D/adjacent muscle thickness ≥50%, RMT≤2.2 mm and D/RMT>1.3 in predicting the high risk of uterine rupture were 94.7%, 57.9% and 73.6%, the specificity were 12.0%, 40.7% and 24.1%, the positive predictive value were 15.9%, 14.7%, 14.6%, and the negative predictive value were 92.8%, 84.6%, 83.9%, respectively. Conclusions: The risk of uterine rupture in pregnant women with CSD is higher than that in those without CSD. There is no significant correlation between CSD related indexes and uterine rupture in the first trimester. Monitoring the lower uterine segment thickness in the third trimester might be helpful to predict the occurrence of adverse pregnancy outcomes.

Objective: To analyze the effects of ozone (O 3 ) concentrations measured with different approaches across different seasons on the total number of childhood asthma-related clinical visits, as well as the differentiation of such effects across different groups of patients., Methods: The outpatient data of three grade A tertiary hospitals in Lanzhou City spanning from 1 January 2014 to 31 December 2017, as well as air pollution and meteorological data during the same period were collected. Considering the nonlinear relationship between O 3 concentrations and the total number of childhood asthma-related clinical visits and meteorological factors, a generalized additive temporal sequence model was employed to analyze the short-term association between changes in O 3 concentrations and the total number of childhood asthma-related clinical visits. Taking into account of the variations in O 3 concentrations within 1 day, this study adopted different measurement approaches to address the three types of O 3 exposures, namely, the maximum 1 h daily concentration (O 3 max1h), the maximum 8 h daily concentration (O 3 8h) and the mean 24 h daily concentration (O 3 24h) as the short term exposure indicators to O 3 , followed by a model-based analysis., Results: The increase in short-term exposure levels to O 3 in summer had a significant effect on the increase in the total number of childhood asthma-related clinical visits. With lag0 for the current day, every 10 μg/m 3 increase in atmospheric concentration of O 3 max1h was associated with an increase in the total number of childhood asthma-related clinical visits by 3.351% (95% CI : 1.231%-5.516%); for every 10 μg/m 3 increase in O 3 8h concentration, the total number of childhood asthma-related clinical visits increased by 3.320% (95% CI : 0.197%-3.829%); for every 10 μg/m 3 increase in O 3 24h concentration, the total number of childhood asthma-related clinical visits in summer increased by 6.600% (95% CI : 0.914%-12.607%); moreover, an increase in exposure to O 3 max1h also led to a significant rise in the total number of childhood asthma-related clinical visits among the males., Conclusion: The increase in short-term exposure levels to O 3 in summer in Lanzhou City has a significant effect on the increase in the total number of childhood asthma-related clinical visits; O 3 max1h is more closely correlated with the increase in the total number of childhood asthma-related clinical visits.

This article reported the clinical diagnosis and treatment experience of two cases of fetal goiter in Graves' disease (GD) complicated with pregnancy. Two GD patients took antithyroid drugs regularly during pregnancy and their thyroid functions were well controlled, but the levels of thyrotropin receptor antibody (TRAb) of the two cases were still above the upper limit in the second and third trimester. Two fetuses had fetal goiter in the middle and late stages of pregnancy. After continuously controlling maternal thyroid function and closely monitoring fetal ultrasound, there was no aggravation of the fetal goiter, and the delivery went smoothly. One case had neonatal hyperthyroidism. It is suggested that although the thyroid function was well controlled during pregnancy in patients with GD, the high level of serum TRAb still needs to be alert to the occurrence of fetal goiter, and fetal ultrasound is the most direct non-invasive monitoring method.

The roles of gap junctions (GJs) and its components, connexins, in the autophagy of cervical cancer cells have been rarely investigated. Our previous study demonstrated that connexin 32 (Cx32) exerted an anti‑apoptotic effect on cervical cancer. However, as an important regulator of apoptosis, whether the autophagy is involved in the function of Cx32 on cervical cancer cells is not well defined. The present study aimed to investigate the role of Cx32 on autophagy and apoptosis inhibition in cervical cancer cells. The expression levels of Cx32 and the autophagy‑associated protein LC3‑Ⅱ in paracancerous cervical tissues (n=30) and cervical cancer (n=50) tissues were determined via western blotting. In total, 45 cervical cancer specimens were used to evaluate the clinical relevance of Cx32 and LC3‑Ⅱ. It was found that both Cx32 and LC3‑Ⅱ were upregulated in cervical cancer tissues compared with those in paracancerous cervical tissues. The effect of Cx32 on autophagy was examined by detecting the change of LC3‑Ⅱ using western blotting, transfection with enhanced green fluorescent protein‑LC3 plasmid and transmission electron microscopy analysis. Overexpression of Cx32 significantly enhanced autophagy in HeLa‑Cx32 cells, whereas knockdown of Cx32 suppressed autophagy in C‑33A cells. The flow cytometry results demonstrated that Cx32 inhibited the apoptosis of cervical cancer cells by promoting autophagy. Moreover, Cx32 triggered autophagy via the activation of the AMP‑activated protein kinase (AMPK) signalling, regardless of the presence or absence of GJs. Collectively, it was identified that Cx32 exerted its anti‑apoptotic effect by activating autophagy via the AMPK pathway in cervical cancer, which demonstrates a novel mechanism for Cx32 in human cervical cancer progression.

Necroptosis is an alternative form of programmed cell death that generally occurs under apoptosis-deficient conditions. Our previous work showed that connexin32 (Cx32) promotes the malignant progress of hepatocellular carcinoma (HCC) by enhancing the ability of resisting apoptosis in vivo and in vitro. Whether triggering necroptosis is a promising strategy to eliminate the apoptosis-resistant HCC cells with high Cx32 expression remains unknown. In this study, we found that Cx32 expression was positively correlated with the expression of necroptosis protein biomarkers in human HCC specimens, cell lines, and a xenograft model. Treatment with shikonin, a well-used necroptosis inducer, markedly caused necroptosis in HCC cells. Interestingly, overexpressed Cx32 exacerbated shikonin-induced necroptosis, but downregulation of Cx32 alleviated necroptosis in vitro and in vivo. Mechanistically, Cx32 was found to bind to Src and promote Src-mediated caspase 8 phosphorylation and inactivation, which ultimately reduced the activated caspase 8-mediated proteolysis of receptor-interacting serine-threonine protein kinase 1/3, the key molecule for necroptosis activation. In conclusion, we showed that Cx32 contributed to the activation of necroptosis in HCC cells through binding to Src and then mediating the inactivation of caspase 8. The present study suggested that necroptosis inducers could be more favorable than apoptosis inducers to eliminate HCC cells with high expression of Cx32., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objective: To analyze the proliferation potential of bone marrow-derived mesenchymal stem cells (MSC) in patients with myelodysplastic syndrome (MDS)., Methods: The MSC derived from the 24 patients with newly diagnosed MDS (MDS-MSC group) and MSC derived from 15 patients with nutritional anemia (control group) in the Affiliated Hospital of Hebei University were used as the research objects. The proliferation potential of MSC was analyzed by colony-forming unit assay, doubling time, cumulative passaging, cell number after 10 days of culture with equal amount of MSC and MTT experiment. The mechanism of abnormal proliferation was analyzed by cell cycle experiment, apoptosis experiment and p21 gene expression assay., Results: In the colony forming unit assay, the number of MDS-MSC colonies was 4.44±2.51, which was significantly lower than that of the control group (12.44±2.55)(P<0.01); the doubling time of MDS-MSC group was significantly longer than that of the control group (7.80±3.26 vs 3.63±0.85) (P<0.01); the number of MDS-MSC in 5×10 4 culture for 10 days was (39.40±14.18)×10 4 , which was significantly lower than that of the control group ［(85.30±9.49)×10 4 ］(P<0.01); the number of cumulative passages in MDS-MSC group was 5.20±1.40, which was significantly lower than that in control group (11.60±1.96)(P<0.01); MTT results showed that the proliferation capability of MSC in MDS-MSC group was lower than that in the control group. The cell proportion of G 0 /G 1 phase in MDS-MSC group was higher than that in the control group, while the cell proportion of S phase was lower (P<0.05). The percentage of early apoptotic cells in MDS-MSC group was higher than that in control group (P<0.05); the relative expression level of p21 mRNA in MDS-MSC group was significantly higher than that in control group(P<0.01)., Conclusion: The proliferative capability of MDS-MSC is significantly reduced, which relates with the arrest of cell cycle in G 0 /G 1 phase, the increase of early apoptotic cells and senescent cells of the MDS-MSC.

Emerging data have demonstrated that bone marrow mesenchymal stem cells (MSCs) play important roles in the progression of myelodysplastic syndrome (MDS). Experiments in vitro have showed that MSCs derived from MDS patients (MDS-MSC) exhibit the biological characteristics of cell senescence. Although the underlying mechanisms that regulate cell senescence need to be further elucidated, existing researches indicate that the mechanisms of MDS-MSC senescence have significant heterogeneity. Depth understanding of the underlying mechanisms involved in cell senescence of MDS-MSC are crucial to explore the potential therapeutic target of MDS. Therefore, this review summarizes research advances related with MSC senescence, such as MDS-MSC intrinsic changes in telomere shortening, DNA methylation status, oxidative stress and signal pathways regulating cell senescence in recent years.

Two novel diterpenes Enhoidin A ( 1 ) and Enhoidin B ( 2 ) featuring an unusual gibberellane skeleton were isolated from the stems and leaves of Enhalus acoroides . Their structures were elucidated on the basis of spectroscopic analysis including 1D and 2D NMR techniques and HR-ESI-MS. This is the first time that this type of lactone ring between C-18 and C-20 has been found among gibberellanes from the tropical seagrasses. Evaluation of the all compounds for cytotoxicity against four human cancer cell lines (MCF-7, HCT-116, HepG-2 and HeLa), and showed moderate cytotoxic activities.

Transcriptome differences between Hodgkin's lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), and mantle cell lymphoma (MCL), which are all derived from B cell, remained unclear. This study aimed to construct lymphoma-specific diagnostic models by screening lymphoma marker genes. Transcriptome data of HL, DLBCL, and MCL were obtained from public databases. Lymphoma marker genes were screened by comparing cases and controls as well as the intergroup differences among lymphomas. A total of 9 HL marker genes, 7 DLBCL marker genes, and 4 MCL marker genes were screened in this study. Most HL marker genes were upregulated, whereas DLBCL and MCL marker genes were downregulated compared to controls. The optimal HL-specific diagnostic model contains one marker gene (MYH2) with an AUC of 0.901. The optimal DLBCL-specific diagnostic model contains 7 marker genes (LIPF, CCDC144B, PRO2964, PHF1, SFTPA2, NTS, and HP) with an AUC of 0.951. The optimal MCL-specific diagnostic model contains 3 marker genes (IGLV3-19, IGKV4-1, and PRB3) with an AUC of 0.843. The present study reveals the transcriptome data-based differences between HL, DLBCL, and MCL, when combined with other clinical markers, may help the clinical diagnosis and prognosis.

Background: Acute liver failure (ALF) is a significant and complex hepatic insult that may rapidly progress to life-threatening conditions. Recently, menstrual blood stem cells (MenSCs) have been identified as a group of easily accessible mesenchymal stem cells with the advantages of non-invasive acquisition, low immunogenicity, a greater capacity of self-renewal and multi-lineage differentiation, making them promising candidates for stem cell-based therapy to revolutionize the treatment strategies for liver failure., Aim: To investigate the therapeutic potential of MenSCs for treating ALF in pigs and to dynamically trace the biodistribution of transplanted cells., Methods: MenSCs were labeled in vitro with PKH26, a lipophilic fluorescent dye. The treatment group received immediate transplantation of PKH26-labelled MenSCs (2.5 × 10 6 /kg) via the portal vein after D-galactosamine injection, and the control group underwent sham operation. The survival time, liver function, and hepatic pathological changes were compared between the two groups. Three major organs (liver, lungs and spleen) were extracted from animals and imaged directly with the In vivo Imaging System (IVIS) at the predetermined time points. The regions of interest were drawn to quantify the cell uptake in different organs., Results: The labelling procedure did not affect the morphology, viability or multipotential differentiation of MenSCs. Biochemical analysis showed that the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and prothrombin time (PT) measured at selected time points 24 h after transplantation were significantly decreased in the treatment group ( P < 0.05). The survival time of ALF animals was prolonged in the treatment group compared with the control group (75.75 ± 5.11 h vs 53.75 ± 2.37 h, log rank, P < 0.001). The liver pathological tissue in the MenSC treatment group showed obviously increased numbers of remaining hepatocytes and a comparatively slight necrotic degree and area. In addition, the IVIS imaging revealed that PKH26-positive MenSCs were clearly retained in the liver initially and then diffused through the systemic circulation. Interestingly, the signal intensity in the liver increased obviously at 36 h, which corresponded to the biochemical result that liver function deteriorated most rapidly at 24 - 36 h., Conclusion: Our study demonstrates the therapeutic efficacy and homing ability of transplanted MenSCs in a large animal model of ALF and suggests that MenSC transplantation could be a promising strategy for treating ALF., Competing Interests: Conflict-of-interest statement: No competing financial interests exist., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To investigate the relationship between the previous cesarean scar thickness, previous cesarean scar defect and the occurrence of uterine rupture for pregnancy women after previous cesarean section and to predict the occurrence of uterine rupture in the third trimester for pregnancy women after previous cesarean section by analyzing the lower uterine segment (LUS) situation or quantitatively measure LUS myometrium thickness. Methods: A total of 154 pregnant women who have a prior cesarean from January 2015 to March 2016 were selected, all of them regularly did the prenatal examination in the pregnancy period and finally gave birth in hospital. By the transvaginal sonograph, the LUS myometrium thickness (transverse and longitudinal thickness) and the size of the previous cesarean scar defect were measured in the first trimester, the LUS myometrium thickness (longitudinal thickness) and qualitatively analysis LUS condition were measured in the third trimester. They were divided into two groups according to the pregnancy outcome: uterine rupture group (found in the cesarean operation or during the pregnancy) and without uterine rupture group (including the vaginal delivery women and those without uterine rupture in the cesarean operation period). The sensitivity and specificity of LUS myometrium thickness in the first trimester and the qualitative analysis LUS situation, the quantitative measurement of LUS myometrium thickness in the third trimester were compared in the prediction of occurrence of uterine rupture (dehiscence or complete rupture). Results: The group without uterine rupture included 134 women (6 vaginal delivery and 128 cesarean delivery), and the group with uterine rupture included 20 women (all of them cesarean delivery). The LUS myometrium thickness in the third trimester in the group without uterine rupture was (1.6±0.5) mm, and was (1.1±0.7) mm in the uterine rupture group ( P = 0.004). There were no significant difference between two groups in the mean value of age, height, weight, the interdelivery interval, the LUS myometrium thickness (transverse and longitudinal thickness) in the first trimester. Qualitative analysis of LUS condition had higher specificity (99%), higher positive predictive value (92%), higher negative predictive value (94%) and slightly lower sensitivity (60%) than quantitative measure of LUS myometrium thickness in predicting uterine rupture. Conclusions: Measurement of the LUS myometrium thickness in the first trimester is helpful for predicting the occurrence of uterine rupture, so it is not necessary to terminate the pregnancy because of the thin LUS or the little prior cesarean scar defect in the first trimester. However it should be paid close attention to the LUS situation during the whole gestation. Qualitatively analyzing LUS situation is more meaningful than quantitatively measuring LUS myometrium thickness in predicting the uterine rupture in the third trimester.

Gap junctions (GJs) are novel molecular targets for pain therapeutics due to their pain-promoting function. INI-0602, a new GJ inhibitor, exerts a neuroprotective role, while its role in neuropathic pain is unclear. The objective was to investigate the analgesic role and mechanisms of INI-0602 in neuropathic pain induced by spared nerve injury (SNI), and whether INI-0602 attenuated pain-induced depression-like behaviors. Rats were randomly assigned to saline treatment groups (sham+NS and SNI+NS) or INI-0602 treatment groups (sham+INI-0602 and SNI+INI-0602). The von Frey test was used to assess pain behavior, and the sucrose preference test, the forced swimming test, and the tail suspension test were used to assess depression-like behaviors. Gap junction intercellular communication (GJIC) was measured by parachute assay. Western blots were used to determine the protein expression. In vitro, INI-0602 significantly suppressed GJIC by decreasing connexin43 and connexin32 expression. In vivo, INI-0602 significantly suppressed mechanical allodynia during initiation (7 days after SNI) and the maintenance phase (21 days after SNI) and simultaneously attenuated accompanying depression-like behaviors. Furthermore, INI-0602 markedly suppressed the activation of astrocytes and microglia on days 7 and 21 by reducing GJIC. Finally, INI-0602 reversed the changes in the brain-derived neurotrophic factor and Nr2b subunits of the N-methyl-D-aspartate receptor in SNI rats, suggesting that these effects of INI-0602 were related to its analgesic effect. Our findings demonstrated that blocking GJs with INI-0602 attenuated mechanical pain hypersensitivity and related depression-like behaviors in SNI rats by reducing glial activation.

Our previous study demonstrated that connexin 32 (Cx32) was upregulated and redistributed to the cytoplasm in A2780 human ovarian cancer cells with acquired resistance to cisplatin; this increased Cx32 feedback promoted cisplatin resistance. To further investigate the mechanism underlying Cx32‑mediated cisplatin resistance, alterations in drug transporters, the DNA repair system and the anti‑apoptotic signalling pathway were investigated by overexpressing or knocking down Cx32 in parental cells (A2780); cisplatin‑resistant human ovarian cancer cells (A2780/CDDP) were also acquired. Upregulation of efflux transporters [multi‑drug resistance protein 2 (MRP‑2), ATPase copper transporting α (ATP7A) and ATPase copper transporting β] and downregulation of the influx transporter copper uptake protein 1 mediated cisplatin resistance in A2780/CDDP cells. A2780/CDDP cells also exhibited increased expression of the DNA repair enzyme excision repair cross‑complementation group 1 (ERCC1) and activation of the epidermal growth factor receptor (EGFR) signalling pathway. Small interfering RNA‑mediated knockdown of Cx32 in A2780/CDDP cells decreased the expression of efflux transporters (MRP‑2 and ATP7A). Knockdown of Cx32 in A2780/CDDP cells also decreased the expression of ERCC1, inhibited the activation of the EGFR signalling pathway and enhanced the cytotoxicity of cisplatin. When Cx32 was overexpressed in A2780 cells, an opposite effect on the expression of efflux transporters (MRP‑2 and ATP7A) and the activation of the EGFR signalling pathway was observed, which resulted in insensitivity to cisplatin‑induced apoptosis. Thus, Cx32 expression may induce cisplatin resistance by modulating drug efflux transporter expression and activating the EGFR‑protein kinase B signalling pathway in ovarian cancer cells.

The pathophysiological mechanism of depression is complex and its etiology remains unclear. Metabolomics can be used to monitor multiple metabolic pathways simultaneously, thereby investigating the mechanisms of depression onset and its regulation. Therefore, we studied the metabolic profile of urine samples from a rat model of depression for identifying potential metabolic biomarkers associated with depression. The depression model of rats was induced by 14-d simulated microgravity (SMG) treatment. Principal component analysis and orthogonal partial least squares discriminate analysis were performed to classify and identify the differences of endogenous metabolites in urine between the normal and depressed rats. Multivariate statistical analysis revealed distinct separation between the urinary metabolic profiles of SMG-treated and control rats. Citric acid, oxalosuccinic acid, creatine, proline, cyclic AMP, L-dihydroxyphenylalanine (DOPA), phenylacetylglycine, 5-hydroxyindole acetaldehyde, succinylcholine, deoxyuridine, 3-hydroxyhippuric acid, glutamine, and 5-hydroxytryptophan levels were significantly reduced, whereas indole-3-acetaldehyde, xanthurenic acid, taurine, kynurenic acid, hippuric acid, 5-hydroxyindoleacetic acid, 2-phenylethanol glucuronide, 2-isopropyl-3-oxosuccinate, and adrenaline levels were elevated significantly in model group. These biochemical changes were related to tryptophan, arginine, proline, and phenylalanine metabolism, and perturbations in energy metabolism. These details of depression will be helpful to the clinical diagnosis of depression caused by space and gravity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Glioma-associated oncogene homolog-1 (Gli1)-positive resident mesenchymal stem cell-like cells are the predominant source of kidney myofibroblasts in fibrosis, but investigating Gli1-positive myofibroblast progenitor activation is hampered by the difficulty of isolating and propagating primary cultures of these cells. Using a genetic strategy with positive and negative selection, we isolated Kidney-Gli1 (KGli1) cells that maintain expression of appropriate mesenchymal stem cell-like cell markers, respond to hedgehog pathway activation, and display robust myofibroblast differentiation upon treatment with transforming growth factor-β (TGF-β). Coculture of KGli1 cells with endothelium stabilizes capillary formation. Single-cell RNA sequencing (scRNA-seq) analysis during differentiation identified autocrine ligand-receptor pair upregulation and a strong focal adhesion pathway signal. This led us to test the serum response factor inhibitor CCG-203971 that potently inhibited TGF-β-induced pericyte-to-myofibroblast transition. scRNA-seq also identified the unexpected upregulation of nerve growth factor (NGF), which we confirmed in two mouse kidney fibrosis models. The Ngf receptor Ntrk1 is expressed in tubular epithelium in vivo, suggesting a novel interstitial-to-tubule paracrine signaling axis. Thus, KGli1 cells accurately model myofibroblast activation in vitro, and the development of this cell line provides a new tool to study resident mesenchymal stem cell-like progenitors in health and disease.

Objective: To investigate a reliable clinical indication for predicting the therapeutic response of decitabine therapy in the patients with myelodysplastic syndromes (MDS)., Methods: The clinical efficacy of decitabine for 55 cases of MDS was analyzed retrospectively. According to the lymphocyte level at d28 after the first time treatment with decitabine, the patients were divided into high lymphocyte level group (H-Lym≥1.2×10 9 /L) and low lymphocyte level group (L-Lym<1.2×10 9 /L), and the overall response rate (ORR) and the progression-free survival (PFS) time in 2 groups were compared., Results: As compared with L-Lym group, the ORR and PFS time in H-Lym group were significantly enhanced ［(76.0% vs 50.0%) (P<0.05) and median time (15.7 months vs 8.5 months)(P<0.05), respectively］;the ratio of platelet level ≥100×10 9 /L in H-Lym group was very significantly higher than that in L-Lym group (72.0% vs 20.0%)(P<0.01). Multivariat analysis showed that the risk of disease progression in L-Lym group was 4.45-fold of H-Lym group (95% CI:1.58-12.59)(P<0.05)., Conclusion: The patients with lymphocyte level ≥1.2×10 9 /L at day 28 after the first time treatment with decitabine show the higher ORR and longer PFS time, therefore. the lymphocyte level at day 28 after first time treatment with decitabine can be used as an early clinical indicator for predecting the response to decitabine treatment.

Hypomethylating agents(HMA) currently are widely used in the treatment of myelodysplastic syndromes (MDS), provide a significant improvement in the treatment of MDS. However, resistance to HMA is an almost universal phenomenon. This review was focused on immune effects related to DNA methylation, and to explore the mechanism underlying HMA resistance involved in immune checkpoint pathways. However, the optimal role of checkpoint blockade therapy (CBT) and immune checkpoint pathways remain in HMA failure questionable. The better understanding of immune checkpoint pathways in resistance of HMA offers a compelling rationale to introduce CBT in patients as a novel treatment option. CBT is an established strategy in solid tumors with potential as an adjunctive therapy in hematologic malignancies, therefore, may alter the treatment landscape in MDS. The suitability and effectiveness of combining HMA with CBT need to be confirmed by the results of ongoing clinical trials, so as to find novel strategies to improve outcome after failure of HMA.

The present study identified the cytotoxic effects of etomidate on the N2a neuroblastoma cell line. Etomidate induced apoptosis in N2a cells in a concentration‑dependent manner, which was confirmed by western blotting and flow cytometry. Phase contrast microscopy was used to analyze the effect of etomidate on morphological characteristics. The number of the apoptotic cells was increased and confirmed by DAPI and PI staining, which served as a characteristic hallmark of apoptosis. Additionally, etomidate led to loss of mitochondrial membrane potential and resulted in the generation of reactive oxygen species in N2a cells. The western blot analysis revealed that N2a cells treated with etomidate had a significant modulation of pro‑apoptotic proteins, includingpoly ADP‑ribose polymerase (PARP), cleaved PARP, caspase‑9 and procaspase‑3. In conclusion, the present study determined that etomidate induced cytotoxic and apoptotic effects in N2a brain tumor cells in vitro.

Objective: To investigate the effects of absolute lymphocyte count(ALC) before start of the first cycle of consolidation chemotherapy(CC) on the relapse free survival in the patients with acute myeloid leukemia(AML), so as to explore a simple and easy method for predicting AML relapse., Methods: The clinical data of 132 patients with newly diagnosed AML (all non-acute promyelotic leukemia) from 2011 to 2017 were analyzed retrospectively. The 132 AML patients were treated with standard induction chemotherapy (IC) and consolidation chemotherapy (CC). According to lymphocyte count of patients before start of the first cycle of CC, the AML patients were divided into 2 group: high lymphocyte count group (H-Lym≥1.2×10 9 /L) and low lymphocyte count group (L-Lym<1.2×10 9 /L). The differences in ralapse rate and relapse-free survival between 2 groups were analyzed., Results: Among 132 patients with AML, patients who could be valuated and were elicible for the study accounted for 65 (49.24%). The absolute leukocyte count, age, chromosome karyotypes before IC of patients did not show statistical difference between H-Lym group (40 cases) and L-Lym group (25 cases). Unvarvate analysis showed that the Low lymphocyte count and unfavorable chromosome karyotypes were poor prognostic factors for the relapse-free survival time, and there was significant difference between 2 groups (P<0.01). The relapse risk in patients of L-Lym group increased, the hazard ratio (HR)=3.01 (95% CI=1.55-4.98) (P<0.01). In multivariate analysis containing unfavorable prognostic karyotypes, this trend still existed (HR=2.52, 95% CI 1.28-9.98)(P<0.01)., Conclusion: The AML patients with high lymphocyte count before the first CC have more long relapse free survival time suggesting that the lymphocyte count before the first CC may be prognostic factor for relapse free survival of AML patients.

Depression is a common, dysthymic, and psychiatric disorder, resulting in enormous social and economic burden. Dammarane sapogenins (DS), an active fraction from oriental ginseng, has shown antidepressant-like effects in chronic restraint rats and sleep interruption-induced mice, and the present study aimed to further confirm the antidepressant effects of DS in a model of chronic unpredictable mild stress (CUMS) and to explore the underlying mechanism. Oral administration of DS (20, 40, and 80 mg/kg) markedly improved depressant-like behaviors, increasing the sucrose intake in the sucrose preference test and reducing the latency in the novelty-suppressed feeding test, and decreasing the immobility time in both the tail suspension and forced swimming tests, compared with the CUMS mice. Biochemical analysis of brain tissue and serum showed that DS treatment restored the decreased hippocampal neurotransmitter concentrations of serotonin, dopamine, norepinephrine (noradrenaline), and gamma-aminobutyric acid, and decreased the elevated of serum hormone levels (corticotrophin releasing factor, adrenocorticotrophic hormone, and corticosterone) induced by CUMS. Our findings confirm that DS exerts an antidepressant-like effect in the CUMS model of depression in mice, and suggest it may be mediated by regulation of neurotransmitters and hypothalamic-pituitary-adrenal axis., (Copyright © 2018 John Wiley & Sons, Ltd.)

Objective: To evaluate the semen quality of the HIV/AIDS male patients after treated by the highly active antiretroviral therapy (HAART) and their potential of transmitting HIV/AIDS and provide some evidence for this cohort of males who wish for parenthood., Methods: We collected semen samples from 20 HIV/AIDS male patients who had been treated by HAART for over 6 months and wished for parenthood. We examined sperm concentration, viability and total motility and the percentage of morphologically normal sperm (MNS) using the computer-assisted semen analysis system, measured the HIV-1 RNA loads in the semen by the Cobas Amplicor Monitor test, and counted CD4+ T cells in the peripheral blood by flow cytometry., Results: The patients were aged 25－40 (30.7 ± 5.05) years. After treated by HAART for 6－26 (14.24 ± 12.26) months, the count of blood CD4+ T cells was significantly increased (341－1 058 ［535.76 ± 212.021］ /μl) in comparison with the baseline (226－965 ［422.38 ± 200.86］ /μl). Compared with the normal value, the semen volume was increased except in 1 case (≥2 ml) while total sperm motility was decreased in 13 cases (≥40%), and so were sperm concentration in 2 cases (≥15 × 106 / ml), sperm viability in 5 (58%), the percentage of progressively motile sperm in 18 (≥32%), and the percentage of MNS in 6 (≤4%). HIV-1 RNA in the peripheral blood was <20 copies/mL in all the cases and that in the seminal plasma was also <20 copies/ml in 18 cases but >20 copies/mL in the other 2 (［4.70 × 101］ and ［2.2 × 102］ copies/ml, respectively). Of the 4 couples that had sex without protective measures for over 6 months, all the 4 female partners exhibited negative HIV antibodies in regular follow-up examinations and 1 achieved spontaneous pregnancy and healthy birth, with negative HIV-1 RNA in both the mother and the baby., Conclusions: The HIV RNA level is higher in the semen than in the blood of the HIV/AIDS male patients after HAART, which indicates the potential risk of their semen transmitting HIV/AIDS to their female partners. Their sperm concentration and total sperm motility are lower than the normal value, which suggests a decreased fertility.

Paradiplozoon yunnanensis n. sp. (Monogenea, Diplozoidae) is described from the gills of Sikukia gudgeri Smith, 1931 (Cyprinidae) collected from Jinghong Basin, a tributary of the international Lancang-Mekong River. This is the first diplozoid species from S. gudgeri and its description increases the number of Paradiplozoon species recorded in China to 25. The new species is distinguished from congeners by a combination of morphological and molecular features. The anterior end of the median plate is thickened in the marginal area and a narrow rectangular trapeze spur connects to the anterior jaw through two separate anterior joining sclerites. The posterior end of the median plate sclerite is invaginated with a smooth strip-shaped posterior joining sclerite. Comparison of a newly obtained sequence of rRNA ITS2 with 18 other congeneric sequences from GenBank provides support for separation of the new species., (© L.-x. Fan et al., published by EDP Sciences, 2018.)

Background: Ground-level ozone (O 3 ) is one of the major air pollutants, which cause oxidative injury to plants. The physiological and biochemical mechanisms underlying the responses of plants to O 3 stress have been well investigated. However, there are limited reports about the molecular basis of plant responses to O 3 . In this study, a comparative transcriptomic analysis of Pak Choi (Brassica campestris ssp. chinensis) exposed to different O 3 concentrations was conducted for the first time., Results: Seedlings of Pak Choi with five leaves were exposed to non-filtered air (NF, 31 ppb) or elevated O 3 (E-O 3 , 252 ppb) for 2 days (8 h per day, from 9:00-17:00). Compared with plants in the NF, a total of 675 differentially expressed genes (DEGs) were identified in plants under E-O 3 , including 219 DEGs with decreased expressions and 456 DEGs with increased expressions. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that O 3 stress invoked multiple cellular defense pathways to mitigate the impaired cellular integrity and metabolism, including 'glutathione metabolism', 'phenylpropanoid biosynthesis', 'sulfur metabolism', 'glucosinolate biosynthesis', 'cutin, suberine and wax biosynthesis' and others. Transcription factors potentially involved in this cellular regulation were also found, such as AP2-ERF, WRKY, JAZ, MYB etc. Based on the RNA-Seq data and previous studies, a working model was proposed integrating O 3 caused reactive oxygen burst, oxidation-reduction regulation, jasmonic acid and downstream functional genes for the regulation of cellular homeostasis after acute O 3 stress., Conclusion: The present results provide a valuable insight into the molecular responses of Pak Choi to acute O 3 stress and the specific DEGs revealed in this study could be used for further functional identification of key allelic genes determining the O 3 sensitivity of Pak Choi.

To clarify the effects of Zuoguiwan containing serum on osteoblast proliferation and alkaline phosphatase(ALP) expression and its effects on the expression of β-catenin, ERK1, ERK2 mRNA and protein of osteoblast through ERK1/2, Wnt/β-catenin signaling pathway in models with osteoporosis(OP) kidney-Yang-deficiency, osteoporosis(OP) kidney-Yin-deficiency syndrome. Rat osteoporosis models were established by ovariectomy surgery, and 10 weeks after surgery, hydrocortisone was injected and thyroxine was administered by intragastric administration to establish OP kidney-Yang-deficiency rat model, and OP kidney-Yin-deficiency rat model. Osteoblasts were obtained from 24 h newborn rat skull and were identified by alkaline phosphatase and alizarin red staining. Zuoguiwan containing serum of OP, OP kidney-Yang-deficiency, and OP kidney-Yin-deficiency, as well as the blank serum were used to intervene the osteoblast, and the cells proliferation was detected by MTS. ELISA assay was used to detect ALP expression. RT-PCR assay was used to detect the mRNA expression of ERK1, ERK2, β-catenin and protein expression levels were detected by Western blot. The results showed that Zuoguiwan containing serum in OP kidney-Yin-deficiency model had stronger effect than OP kidney-Yang-deficiency in promoting osteoblast proliferation, ALP expression, osteoblast ERK1/2, Wnt/β-catenin signaling pathway related factors β-catenin, ERK1, ERK2 mRNA and protein expression levels. This was consistent with the TCM theory of "Zuoguiwan nourishes kidney Yin", providing a scientific basis for the clinical and dialectical treatment of osteoporosis. Zuoguiwan could regulate the proliferation and differentiation of bone cells by ERK1/2 and Wnt/β-catenin signaling pathway, which may be one of the mechanisms of Zuoguiwan for the prevention of osteoporosis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Autosomal dominant polycystic kidney disease (ADPKD) is driven by mutations in PKD1 and PKD2 genes. Recent work suggests that epigenetic modulation of gene expression and protein function may play a role in ADPKD pathogenesis. In this study, we identified SMYD2, a SET and MYND domain protein with lysine methyltransferase activity, as a regulator of renal cyst growth. SMYD2 was upregulated in renal epithelial cells and tissues from Pkd1-knockout mice as well as in ADPKD patients. SMYD2 deficiency delayed renal cyst growth in postnatal kidneys from Pkd1 mutant mice. Pkd1 and Smyd2 double-knockout mice lived longer than Pkd1-knockout mice. Targeting SMYD2 with its specific inhibitor, AZ505, delayed cyst growth in both early- and later-stage Pkd1 conditional knockout mouse models. SMYD2 carried out its function via methylation and activation of STAT3 and the p65 subunit of NF-κB, leading to increased cystic renal epithelial cell proliferation and survival. We further identified two positive feedback loops that integrate epigenetic regulation and renal inflammation in cyst development: SMYD2/IL-6/STAT3/SMYD2 and SMYD2/TNF-α/NF-κB/SMYD2. These pathways provide mechanisms by which SMYD2 might be induced by cyst fluid IL-6 and TNF-α in ADPKD kidneys. The SMYD2 transcriptional target gene Ptpn13 also linked SMYD2 to other PKD-associated signaling pathways, including ERK, mTOR, and Akt signaling, via PTPN13-mediated phosphorylation.

Jaundice is a common and complex clinical symptom potentially occurring in hepatology, general surgery, pediatrics, infectious diseases, gynecology, and obstetrics, and it is fairly difficult to distinguish the cause of jaundice in clinical practice, especially for general practitioners in less developed regions. With collaboration between physicians and artificial intelligence engineers, a comprehensive knowledge base relevant to jaundice was created based on demographic information, symptoms, physical signs, laboratory tests, imaging diagnosis, medical histories, and risk factors. Then a diagnostic modeling and reasoning system using the dynamic uncertain causality graph was proposed. A modularized modeling scheme was presented to reduce the complexity of model construction, providing multiple perspectives and arbitrary granularity for disease causality representations. A "chaining" inference algorithm and weighted logic operation mechanism were employed to guarantee the exactness and efficiency of diagnostic reasoning under situations of incomplete and uncertain information. Moreover, the causal interactions among diseases and symptoms intuitively demonstrated the reasoning process in a graphical manner. Verification was performed using 203 randomly pooled clinical cases, and the accuracy was 99.01% and 84.73%, respectively, with or without laboratory tests in the model. The solutions were more explicable and convincing than common methods such as Bayesian Networks, further increasing the objectivity of clinical decision-making. The promising results indicated that our model could be potentially used in intelligent diagnosis and help decrease public health expenditure.

To investigate whether the extract of Dendrobium nobile Lindl (DNL) has an antidepressant effect on chronic unpredictable mild stress (CUMS)-induced depressive mice, 72 BALB/c male mice were randomly divided into the control group, the CUMS model group, the extract of DNL groups (50, 100 and 200 mg/kg DNL, i.g.) and the paroxetine group (10 mg/kg, i.g.). The different doses of DNL or the paroxetine was administered orally once daily to CUMS mice for 8 weeks (containing two-week preventive medication before the modeling). The same volume of distilled water was given to the control group and the CUMS group. Except for the control group, the other mice were exposed to chronic stress for 35 days. Behavioral tests were performed by using the sucrose preference test (SPT), the novelty-suppressed feeding (NSF) test, the tail suspension test (TST), and the forced swim test (FST). The levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) were measured by the liquid chromatography-mass spectrometer (LC-MS)/MS. Compared with the control group, obvious behavioral changes were observed in the CUMS group after 5-week CUMS, including a decrease in the sucrose consumption, an increase in the latency to feeding in the NSF test and a prolongation of the immobility time in the TST. Compared with the CUMS group, the application of DNL resulted in a dose-dependent increase in sucrose consumption (P < 0.01) as paroxetine (10 mg/kg) did and a significant dose-dependent decrease in the latency to feeding in the NSF test (P < 0.05). In the TST, the application of paroxetine (10 mg/kg) and the high-dose DNL (200 mg/kg) obviously decreased the immobility time when compared with the CUMS group (P < 0.05). In the FST, compared with the CUMS group, all the groups had no significant differences in the immobility time (P > 0.05). In addition, in the hippocampus and cortex, the levels of 5-HT and DA were significantly decreased in the CUMS group compared with the control group (P < 0.05). In comparison with the CUMS group, paroxetine obviously increased the DA levels in the hippocampus and the cortex and the 5-HT level in the hippocampus (P < 0.05). DNL (50 and 200 mg/kg) significantly increased the DA level in cerebral cortex of the brain, and DNL (100 and 200 mg/kg) increased the DA level in the hippocampus. The 5-HT level in the 200 mg/kg DNL group was notably increased in both two brain regions (P < 0.05), but the 5-HT level in the 100 mg/kg DNL group was significantly increased only in the hippocampus (P < 0.01). These findings indicate that the extract of DNL has an antidepressant-like effect on CUMS-induced depressive mice and its mechanism may be related to the changes in DA and 5-HT in the hippocampus and cortex.

In this study, porous gelatin microspheres (GMSs) were constructed to improve the neuroprotective effect of basic fibroblast growth factor (bFGF) on spinal cord injury. GMSs were prepared by a W/O emulsion template, followed by cross-linking, washing and drying. The particle sizes and surface porosity of the blank GMSs were carefully characterized by scan electronic microscopy. The blank GMSs have a mean particle size of 35μm and theirs surface was coarse and porous. bFGF was easily encapsulated inside the bulk GMSs through diffusion along the porous channel. 200μg of bFGF was completely encapsulated in 100mg of GMSs. The bFGF-loaded GMSs displayed a continuous drug release pattern without an obvious burst release over two weeks in vitro. Moreover, the therapeutic effects of bFGF-loaded GMSs were also evaluated in spinal cord injury rat model. After implantation of bFGF-loaded GMSs, the recovery of the motor function of SCI rats were evaluated by behavioral score and foot print experiment. The motor function of SCI rats treated with bFGF-loaded GMSs was more obvious than that treated with free bFGF solution (P<0.05). At the 28th days after treatment, rats were sacrificed and the injured spinal were removed for histopathological and apoptosis examination. Compared with treatment with free bFGF solution, treatment with bFGF-loaded GMSs resulted in a less necrosis, less infiltration of leukocytes, and a reduced the cavity ratio and less apoptotic cells in injured spinal(P<0.01), indicating its better therapeutic effect. Implantable porous GMSs may be a potential carrier to deliver bFGF for therapy of spinal cord injury.

Plague is a virulent infectious disease in China. In this study, '3S' technology was used to perform spatial autocorrelation analysis and spatial interpolation analysis for Spermophilus dauricus (S. Dauricus, a species of ground squirrel) captured in Manchuria City in 2015. The results were visually inspected. During the two-month (May to July) plague surveillance in 2015, 198 S. dauricus individuals were captured in the study area in Manchuria City (48 monitoring areas) by using a day-by-day catching method. Spatial autocorrelation was conducted using the ArcGIS software, and the following significantly different results were obtained: Moran's I=0.228472, Z-score=2.889126, and P<0.05. Thus, a spatial aggregation was observed. In 2015, the distribution of S. dauricus diminished from west to east and from north to south of Manchuria. Geo Detector software was used to analyze the habitat factors affecting the spatial distribution of S. dauricus. This highly clustered species mainly exists in suburban communities, construction sites, and areas surrounding factories. In future studies, plague surveillances should be performed in areas around Manchuria and Zhalainuoer., (Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

In this study, we identified a BET bromodomain (BRD) protein, Brd4, not only as a novel epigenetic regulator of autosomal dominant polycystic kidney disease (ADPKD) but also as a novel client protein of Hsp90. We found that Brd4 was upregulated in Pkd1 mutant mouse renal epithelial cells and tissues. This upregulation of Brd4 appears to result from the chaperone activity of Hsp90 and escape proteasomal degradation. We further identify that Brd4 is an upstream regulator of the expression of c-Myc which has been upregulated in all rodent models of PKD and ADPKD patients with unknown mechanism. Inhibition of Brd4 in Pkd1 mutant renal epithelial cells with JQ1, a selective small-molecular inhibitor of BET BRD protein(s), (1) decreased the levels of c-Myc mRNA and protein; (2) increased the levels of p21 mRNA and protein, which was transcriptionally repressed by c-Myc; (3) decreased the phosphorylation of Rb; and (4) decreased cystic epithelial cell proliferation as shown by inhibition of S-phase entry. Most importantly, treatment with JQ1 strikingly delayed cyst growth and kidney enlargement, and preserved renal function in two early stage genetic mouse strains with Pkd1 mutations. This study not only provides one of the mechanisms of how c-Myc is upregulated in PKD but also suggests that targeting Brd4 with JQ1 may function as a novel epigenetic approach in ADPKD. The unraveled link between Brd4 and Hsp90 in ADPKD may also be a general mechanism for the upregulation of Brd4 in cancer cells and opens up avenues for combination therapies against ADPKD and cancer., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Hepatocellular carcinoma (HCC) was the most common primary liver cancer, and its resistance to anti-tumor drugs often caused the death of patients suffering with HCC. Matrix stiffness was reported to be closely related to tumor chemoresistance; however, the relationship between HCC drug resistance and three-dimensional (3D) matrix stiffness is still unclear at present. In this study, alginate gel (ALG) beads with controllable matrix stiffness were used to mimic tumor tissue rigidity, and the role of 3D matrix stiffness in regulating the chemoresistance of HCC cells was investigated by using these ALG beads. It was found that HCC cells in ALG beads with 105 kPa stiffness had highest resistance to paclitaxel, 5-FU, and cisplatin. Although the mechanism was still uncovered, ABC transporters and endoplasmic reticulum stress-related molecules were highly expressed in ALG bead-encapsulated HCC cells compared with two-dimensional-cultured cells, which suggested a very complex mechanism underlying HCC drug resistance in 3D culture conditions. In addition, to mimic the specific stiffness of HCC tumor tissue, or other tumor tissues in vivo, response surface methodology (RSM) was used to build up a prediction mathematical model so that ALG beads with desired matrix stiffness could be prepared by simply changing three factors: molecular weight, G content, and alginate concentration., (© 2014 International Union of Biochemistry and Molecular Biology, Inc.)

Tumor necrosis factor alpha (TNFα) is present in cyst fluid and promotes cyst growth in autosomal dominant polycystic kidney disease (ADPKD). However, the cross-talk between TNFα and PKD associated signaling pathways remains elusive. In this study, we found that stimulation of renal epithelial cells with TNFα or RANKL (receptor activator of NF-κB ligand), a member of the TNFα cytokine family, activated either the PI3K pathway, leading to AKT and mTOR mediated the increase of Id2 protein, or MAPK and Cdk2 to induce Id2 nuclear translocation. The effects of TNFα/RANKL on increasing Id2 protein and its nuclear translocation caused significantly decreased mRNA and protein levels of the Cdk inhibitor p21, allowing increased cell proliferation. TNFα levels increase in cystic kidneys in response to macrophage infiltration and thus might contribute to cyst growth and enlargement during the progression of disease. As such, this study elucidates a novel mechanism for TNFα signaling in regulating cystic renal epithelial cell proliferation in ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by renal cyst formation, inflammation, and fibrosis. Macrophages infiltrate cystic kidneys, but the role of these and other inflammatory factors in disease progression are poorly understood. Here, we identified macrophage migration inhibitory factor (MIF) as an important regulator of cyst growth in ADPKD. MIF was upregulated in cyst-lining epithelial cells in polycystin-1-deficient murine kidneys and accumulated in cyst fluid of human ADPKD kidneys. MIF promoted cystic epithelial cell proliferation by activating ERK, mTOR, and Rb/E2F pathways and by increasing glucose uptake and ATP production, which inhibited AMP-activated protein kinase signaling. MIF also regulated cystic renal epithelial cell apoptosis through p53-dependent signaling. In polycystin-1-deficient mice, MIF was required for recruitment and retention of renal macrophages, which promoted cyst expansion, and Mif deletion or pharmacologic inhibition delayed cyst growth in multiple murine ADPKD models. MIF-dependent macrophage recruitment was associated with upregulation of monocyte chemotactic protein 1 (MCP-1) and inflammatory cytokine TNF-α. TNF-α induced MIF expression, and MIF subsequently exacerbated TNF-α expression in renal epithelial cells, suggesting a positive feedback loop between TNF-α and MIF during cyst development. Our study indicates MIF is a central and upstream regulator of ADPKD pathogenesis and provides a rationale for further exploration of MIF as a therapeutic target for ADPKD.

Surface-mediated Schiff base coupling reactions between oligothiophenes equipped with an aldehyde group and aromatic diamines were investigated on highly oriented pyrolytic graphite (HOPG) by means of scanning tunneling microscopy (STM) under ambient conditions. To investigate the evolution process from monomers to resultant polymers and the mechanism of reactions, we controlled the ratio of precursors and the reactive temperature, and we obtained high-resolution STM images of different stages of the surface reaction. The results suggest that preferential adsorption of one kind of monomer has a great influence on the on-surface Schiff base reaction., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Several anti-diabetes drugs exert beneficial effects against metabolic syndrome by inhibiting mitochondrial function. Although much progress has been made toward understanding the role of mitochondrial function inhibitors in treating metabolic diseases, the potential effects of these inhibitors on mitochondrial respiratory chain complex III remain unclear., Methods: We investigated the metabolic effects of azoxystrobin (AZOX), a Qo inhibitor of complex III, in a high-fat diet-fed mouse model with insulin resistance in order to elucidate the mechanism by which AZOX improves glucose and lipid metabolism at the metabolic cellular level., Results: Acute administration of AZOX in mice increased the respiratory exchange ratio. Chronic treatment with AZOX reduced body weight and significantly improved glucose tolerance and insulin sensitivity in high-fat diet-fed mice. AZOX treatment resulted in decreased triacylglycerol accumulation and down-regulated the expression of genes involved in liver lipogenesis. AZOX increased glucose uptake in L6 myotubes and 3T3-L1 adipocytes and inhibited de novo lipogenesis in HepG2 cells. The findings indicate that AZOX-mediated alterations to lipid and glucose metabolism may depend on AMP-activated protein kinase (AMPK) signaling., Conclusions: AZOX, a Qo inhibitor of mitochondrial respiratory complex III, exerts whole-body beneficial effects on the regulation of glucose and lipid homeostasis in high-fat diet-fed mice., General Significance: These findings provide evidence that a Qo inhibitor of mitochondrial respiratory complex III could represent a novel approach for the treatment of obesity., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The influence of municipal landfill age on the characteristics of humic substances in leachate on the basis of investigating 12 different kinds of leachates from landfills in Fujian province is presented in this study. It was shown that the concentration and percentage of fulvic acid (FA) were obviously higher than those of humic acid (HA). As the landfill age increased, the concentrations of HA, FA and humic substances (HS) increased, moreover, the percentage of HA first increased and then decreased. While the percentages of FA and HS first increased and then fluctuated with the landfill age. The UV-Vis analytical results of HA and FA through E280, E300/E400 and E465/E665 revealed that HA had a relatively higher content of aromatic compounds and higher molecular weight than FA. The humification of FA had a tendency to increase as the landfill age increased, while HA had opposite result. The E300/E400 and E465/E665 of HA and FA fluctuated with increasing landfill age. A mathematical model simulating the concentration of humic substances varied with the landfill age was presented and demonstrated based on degradation kinetics. The simulated results were close to the measured values with a correlation coefficient R2 of 0.820, 0.932 and 0.946, respectively, indicating that the concentrations of HA, FA and HS could be accurately forecasted.