Progress in direct reprogramming of dopaminergic cell replacement therapy.

Parkinson's disease (PD) is a gradual neurodegenerative disease. While drug therapy and surgical treatments have been the primary means of addressing PD, they do not offer a cure, and the risks associated with surgical treatment are high. Recent advances in cell reprogramming have given rise to new prospects for the treatment of Parkinson's disease (PD), with induced pluripotent stem cells (iPSCs), induced dopamine neurons (iDNs), and induced neural stem cells (iNSCs) being created. These cells can potentially be used in the treatment of Parkinson's disease. On the other hand, this article emphasizes the limits of iPSCs and iNSCs in the context of Parkinson's disease treatment, as well as approaches for direct reprogramming of somatic cells into iDNs. The paper will examine the benefits and drawbacks of directly converting somatic cells into iDNs.

Interlayer adsorption of cationic dye on cationic surfactant-modified and unmodified montmorillonite.

Water pollution by toxic organic dyes is one of the most critical health and environmental problems worldwide. By means of molecular dynamics method, the present work aims to evaluate the applicability of montmorillonite (Mt) modified by hexadecyltrimethylammonium cations (HDTMA+) compared to unmodified Na-Mt for the adsorption of cationic methylene blue (MB) dye. The results showed that the adsorption energy of MB on both HDTMA-Mt and Na-Mt absorbent ranged from - 100 to - 250 kJ/mol, indicating the effectiveness of two types of adsorbents in dye water treatment. The highest adsorption energy was found at w = 50% in each adsorbent system. Adsorption mechanisms of MB depend on molecular orientations, which is influenced by the surfactant and water content. The adsorption mechanism of MB is chemisorption dominated by strong electrostatic interaction between CH3 groups of MB and oxygen atoms of Mt surfaces. Besides, physisorption also plays a minor role in MB orientations. It is found that the existence of cationic surfactants can slightly improve the adsorption capacity of MB only at higher water content through enlarging the interlayer space of Mt and reducing mobility of MB. However, there will be a negative impact on the reduction of adsorption sites for dyes especially at low water content. Our results provide a possible application for swelling clay minerals being a promising adsorbent for dyes-surfactants co-existing wastewater treatment.

The prediction and treatment of postpartum myofascial pelvic pain.

BACKGROUND: The clinical manifestations of myofascial pelvic pain (MFPP) are mainly acute or chronic muscle pain at one or more trigger points in the pelvic cavity or pelvic floor. OBJECTIVE: This study aims to explore the predictive value of pelvic floor myoelectric parameters with respect to MFPP and the effect of its clinical treatment. METHODS: Two hundred and one women followed up in the Wenzhou People's Hospital 6-12 weeks postpartum between July 2020 and July 2021. They were divided into an MFPP group (n= 90) and a non-MFPP group (n= 102), but 9 MFPP patients without a pelvic floor electromyography evaluation were not included. The general demographic data and pelvic floor electromyography evaluation parameters of the two groups were compared; the related factors of postpartum women suffering from MFPP were analyzed, and a nomogram model of the postpartum risk of suffering from MFPP was established. The 99 patients with postpartum MFPP were divided into a treatment group (n= 10) and a control group (n= 89). The difference in visual analog scale scores between the two groups initially and after three months of treatment was compared to evaluate the effective remission rate of postpartum MFPP after treatment. RESULTS: A significant difference was observed in the relaxation time at the rapid contraction stage (z= 4.369, p< 0.05) and the tension contraction stage (z= 135.645, p< 0.01) between the MFPP group and the non-MFPP group. The nomogram model for predicting postpartum MFPP was established with nine variables as potential predictors. The calibration chart and C index of 0.68 (95% CI: 0.65-0.71) proved that the model had a certain degree of discrimination. The clinical decision-making curve showed that the model could increase the net benefit rate of patients. The pain relief rate in the treatment group was significantly higher than that in the control group (p< 0.01). CONCLUSION: There is a significant correlation between postpartum MFPP and relaxation time at rapid contraction stage and tension contraction stage. The risk prediction nomogram model of postpartum MFPP established with nine potential predictors has a certain prediction capability, and clinical treatment can effectively relieve MFPP in postpartum patients.

Discovery of FtsZ inhibitors by virtual screening as antibacterial agents and study of the inhibition mechanism.

Inhibition of bacterial cell division is a novel mechanistic action in the development of new antimicrobial agents. The FtsZ protein is an important antimicrobial drug target because of its essential role in bacterial cell division. In the present study, potential inhibitors of FtsZ were identified by virtual screening followed by in vivo and in vitro bioassays. One of the candidates, Dacomitinib (S2727), shows for the first time its potent inhibitory activity against the MRSA strains. The binding mode of Dacomitinib in FtsZ was analyzed by docking, and Asp199 and Thr265 are thought to be essential residues involved in the interactions.

Primary mucosal-associated lymphoid tissue extranodal marginal zone lymphoma of the bladder from an imaging perspective: A case report.

BACKGROUND: Mucosal-associated lymphoid tissue extranodal marginal zone (MALT) lymphoma is a low-grade tumor that rarely occurs in the urinary bladder. There is currently no consensus on the common imaging findings or most appropriate treatment in MALT lymphoma in the urinary bladder due to the limited number of reports. CASE SUMMARY: A 48-year-old woman was admitted to the hospital with a 1-year history of macroscopic hematuria. Imaging showed a large homogeneous mass with an unclear boundary and an irregular morphology in the bladder. The mass had an abundant blood supply. For further diagnosis, transurethral cystoscopic biopsy and bone marrow biopsy was performed, and the patient was finally diagnosed with primary MALT lymphoma of the bladder. R-CHOP chemotherapy was carried out. After three cycles of chemotherapy, the mass disappeared and the bladder wall thickness was only 4 mm, which indicated excellent therapeutic response to the chemotherapy. To date, the patient remains asymptomatic and she visits our hospital regularly for the completion of the remaining chemotherapy cycles. CONCLUSION: Primary MALT lymphoma of the bladder is rare, and there are certain characteristics in the ultrasonographic findings. Imaging findings play an important role in evaluating the therapeutic efficacy and are critical during long-term follow-up after therapy.

Transcriptome sequencing and metabolome analysis reveal the mechanism of Shuanghua Baihe Tablet in the treatment of oral mucositis.

Oral mucositis (OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of the disease and the quality of life. Shuanghua Baihe Tablet (SBT) is a traditional Chinese medicine (TCM) formula, which is administerd to treat OM in China. It has been clinically effective for more than 30 years, but the underlying mechanism is not completely understood. With the development of multiple omics, it is possible to explore the mechanism of Chinese herbal compound prescriptions. Based on transcriptomics and metabolomics, we explored the underlying mechanism of SBT in the treatment of OM. An OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3 g·kg-1·d-1. In order to search for SBT targets and related metabolites, the dysregulated genes and metabolites were detected by transcriptomics and metabolomics. Immune related indicators such as interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) were detected by ELISA. Treg cell disorders was analyzed by flow cytometry. Our results showed that SBT significantly alleviated the symptoms of OM rats and the inflammatory infiltration of ulcer tissues. After SBT administration, inflammatory related metabolic pathways including linoleic acid metabolism, valine, leucine and isoleucine biosynthesis were significantly altered. Furthermore, the production of proinflammatory factors like IL-17 and TNF-α, were also dramatically reduced after SBT administration. Besides, the infiltration degree of Treg cells in the spleen of OM modeling rats was significantly improved by SBT administration, thus maintaining the immune balance of the body. The current study demonstrates that SBT regulates inoleic acid metabolism, glycerophospholipid metabolism and amino acid metabolism, and inhibits IL-17/TNF signal transduction to restore Treg and Th17 cell homeostasis in OM rats, thereby alleviating chemotherapy-induced OM.

Precise medication for tumor patients in the context of mental stress.

Cancer is the leading cause of disease-related death worldwide due to its late diagnosis and poor outcomes. Precision medicine plays an important role in the treatment of tumors. As found for many types of tumors, mental stress plays a vital role in the promotion and progression of tumors. In this paper, we briefly introduce the manifestation and effects of mental symptoms in tumor patients. We next specifically discuss the multiple roles of precision medicine in the tumor therapy. Finally, we also highlight the precision medicine strategy for psychiatric symptoms in tumor patients, which promises to enhance the efficacy of tumor therapy.

Rare monolocular intrahepatic biliary cystadenoma: A case report.

BACKGROUND: Intrahepatic biliary cystadenoma (IBC) is a rare benign hepatic tumor that is often misdiagnosed as other hepatic cystic diseases. Therefore, imaging examinations are required for preoperative diagnosis. Contrast-enhanced ultrasound (CEUS) has gained increasing popularity as an emerging imaging modality and it is considered the primary method for screening IBC because of its specificity of performance. We describe an unusual case of monolocular IBC and emphasize the performance of CEUS. CASE SUMMARY: A 45-year-old man complained of epigastric pain lasting 1 wk. He had no medical history of hepatitis, liver cirrhosis or parasitization. Physical examination revealed a mass of approximately 6 cm in size in the upper abdomen below the subxiphoid process. Tumor marker tests found elevated CA19-9 levels (119.3 U/mL), but other laboratory tests were unremarkable. Ultrasound and computerized tomography revealed a round thick-walled mass measuring 83 mm × 68 mm located in the left lateral lobe of the liver that lacked internal septations and manifested as a monolocular cystic structure. CEUS demonstrated that in the arterial phase, the anechoic area manifested as a peripheral ring with homogeneous enhancement. The central part presented with no enhancement. During the portal phase, the enhanced portion began to subside but was still above the surrounding liver tissue. The patient underwent left partial liver lobectomy and recovered well without tumor recurrence or metastasis. Eventually, the results of pathological examination confirmed IBC. CONCLUSION: A few IBC cases present with monolocular characteristics, and the lack of intracystic septa in imaging performance cannot exclude IBC.

Up-regulation of CTRP12 ameliorates hypoxia/re-oxygenation-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling.

C1q/TNF-related protein 12 (CTRP12) has been reported to play a key role in coronary artery disease. However, whether CTRP12 plays a role in the regulation of myocardial ischemia-reperfusion injury is not fully understood. The goals of this work were to assess the possible relationship between CTRP12 and myocardial ischemia-reperfusion injury. Here, we exposed cardiomyocytes to hypoxia/re-oxygenation (H/R) to establish an in vitro cardiomyocyte injury model of myocardial ischemia-reperfusion injury. Our results showed that H/R treatment resulted in a decrease in CTRP12 expression in cardiomyocytes. The up-regulation of CTRP12 ameliorated H/R-induced cardiomyocyte injury via the down-regulation of apoptosis, oxidative stress, and inflammation. In contrast, the knockdown of CTRP12 enhanced cardiomyocyte sensitivity to H/R-induced cardiomyocyte injury. Further investigation showed that CTRP12 enhanced the levels of nuclear Nrf2 and increased the expression of Nrf2 target genes in cardiomyocytes exposed to H/R. However, the inhibition of Nrf2 markedly diminished CTRP12-overexpression-mediated cardioprotective effects against H/R injury. Overall, these data indicate that CTRP12 protects against H/R-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling. This work suggests a potential role of CTRP12 in myocardial ischemia-reperfusion injury and proposes it as an attractive target for cardioprotection.

Dissecting the multi-omics atlas of the exosomes released by human lung adenocarcinoma stem-like cells.

Lung adenocarcinoma is heterogeneous and hierarchically organized, with a subpopulation of stem-like cells (CSCs) that reside at the apex of the hierarchy, in which exosomes act as important mediators by transporting specific molecules among different cell populations. Although there have been numerous studies on tumor exosomes, the constituents and functional properties of CSC-derived exosomes are still poorly characterized. Here we present a detail transcriptome and proteome atlas of the exosomes released by human lung adenocarcinoma stem-like cells (LSLCs). The transcriptome analysis indicates the specific patterns of exosomal constituents, including the fragmentation of transcripts and the low-level presence of circular RNAs, and identifies multiple exosomal-enriched mRNAs and lncRNAs. Integrative analysis of transcriptome and proteome data reveals the diverse functions of exosomal-enriched RNAs and proteins, many of which are associated with tumorigenesis. Importantly, several LSLC markers we identified are highly expressed in LSLC-derived exosomes and associate with poor survival, which may serve as promising liquid biopsy biomarkers for lung adenocarcinoma diagnosis. Our study provides a resource for the future elucidation of the functions of tumor-derived exosomes and their regulatory mechanisms in mediating lung cancer development.

Over-Expression and Prognostic Significance of FATP5, as a New Biomarker, in Colorectal Carcinoma.

Background: Fatty acid transporters (FATPs) family play an important role in the uptake and metabolism regulation of long-chain fatty acids, which influence the occurrence and developing of multiple tumors. Fatty acid transporter 5(FATP5), a member of FATPs family, participates in fatty acid transport and lipid metabolism and is related to tumor development, whose mechanism in colorectal cancer (CRC) remains unclear. Methods: In this study, we comprehensively utilized a range of relevant bioinformatic tools along with multiple databases to analyze the expression of FATPs family and investigate the biological function and prognostic value of FATP5 in CRC. Besides, cell proliferation and cell cycle distribution analysis, western blotting and immunohistochemistry (IHC) further validated the conclusion of bioinformatics analysis. Results: FATP5 is the only member of FATPs family which was overexpressed in CRC. In the survival analysis based on the GSE39582 databases, the low expression of FATP5 predicts poor prognosis in CRC. Similar results were also observed in GSE17536, GSE28814 and TCGA colon cohorts. The potential function of DNA methylation regulated the abnormal expression of FATP5 in CRC. In addition, enrichment analysis indicated that FATP5 also participates in the regulation of cell cycle. Furthermore, Gene Set Enrichment Analysis (GSEA) showed a strong negative correlation between FATP5 and cell growth, implying that it may participate in regulating cancer cell proliferation by the regulation of cell cycle G2/M transition. At last, we identified that FATP5 was overexpressed in colorectal carcinoma tissues through immunohistochemistry staining, and played an important role in cell cycle by cell proliferation and cell cycle distribution analysis. Conclusion: This study suggested that FATP5 was overexpression in colorectal carcinoma and predicted favorable prognosis, indicating it as a novel appealing prognostic marker for CRC.

The Influence of Venous Characteristics on Peripherally Inserted Central Catheter-Related Symptomatic Venous Thrombosis in Cancer Patients.

BACKGROUND: With increasing use, peripherally inserted central catheters (PICCs) are associated with the risk of venous thrombosis. Few studies have focused on the relationships between venous thrombosis and venous characteristics. This study aimed to identify effects of venous characteristics on symptomatic PICC-related venous thrombosis in cancer patients and explore the relationship between venous characteristics and blood flow velocity. METHODS: The data of patients who underwent placement of PICC were retrospectively studied between January 2015 and September 2017. Symptomatic PICC-related venous thrombosis was confirmed by ultrasound. Univariable, multivariable logistic regression analyses were performed to identify the risk factors associated with PICC-related venous thrombosis. In October 2017, 169 patients with PICCs were enrolled prospectively, and the relationships between blood flow velocity and venous characteristics were recorded and analyzed. RESULTS: A total of 2933 cancer patients were enrolled in this study; of these patients, 68 experienced symptomatic venous thrombosis. In the bivariate analysis, body mass index (BMI), history of venous thrombosis, triglycerides, tumor category, vessel diameter, vessel depth and arm circumference were associated with thrombosis. The multivariable analyses showed that arm circumference, vascular diameter, triglyceride level and tumor category were independent risk factors for thrombosis. Blood flow velocity was positively correlated with vessel depth and arm circumference but not with vessel diameter. CONCLUSION: Different venous characteristics can lead to different blood flow rates, which can affect the incidence of thrombosis. A vein depth of greater than 1.07cm or less than 0.57cm was associated with a higher incidence of PICC-related venous thrombosis, and the greater the arm circumference and vessel diameter, the greater the risk of venous thrombosis.

Cerebrospinal Fluid Hypovolemia and Posterior Reversible Encephalopathy Syndrome.

Posterior reversible encephalopathy syndrome (PRES) is a reversible neuroradiological syndrome characterized by reversible vasogenic edema. The pathophysiological mechanism is still unclear, but PRES may be triggered by various etiologies. To date, only a few PRES cases linked to cerebrospinal fluid (CSF) hypovolemia were reported. The association between PRES and CSF hypovolemia needs to be explored. We presented a case of PRES with CSF hypovolemia as a result of an inadvertent dural puncture and reviewed the literature to identify the clinical characterization and pathophysiological mechanism of PRES following CSF hypovolemia. A total of 31 cases of PRES-CSF hypovolemia was included for analysis. The median age was 33 years, with a notable female predominance (87.1%). Fifteen patients (48.4%) didn't have either a history of hypertension nor an episode of hypertension. The most common cause of CSF hypovolemia was epidural or lumbar puncture (n = 21), followed by CSF shunt (n = 6). The median interval between the procedure leading to CSF hypovolemia and PRES was 4 days. Seizure, altered mental state, and headache were the most frequent presenting symptom. The parietooccipital pattern was most frequent (71.0%). Conservative management remains the mainstay of treatment with excellent outcomes. Three patients had a second episode of PRES. CSF hypovolemia is a plausible cause of PRES via a unique pathophysiologic mechanism including arterial hyperperfusion and venous dysfunction. Patients with CSF hypovolemia is more susceptible to PRES, which is potentially life-threatening. Given that CSF hypovolemia is a common complication of anesthetic, neurological, and neurosurgical procedures, PRES should be early considered for prompt diagnosis and appropriate management.

Salinomycin and Sulforaphane Exerted Synergistic Antiproliferative and Proapoptotic Effects on Colorectal Cancer Cells by Inhibiting the PI3K/Akt Signaling Pathway in vitro and in vivo.

BACKGROUND: Both salinomycin (SAL) and sulforaphane (SFN) exert their antitumorigenic effects in various types of cancer We investigated whether combining salinomycin (SAL, an antibiotic ionophore) with sulforaphane (SFN, a phytochemical) exerted synergistic antiproliferative and proapoptotic activities in colorectal cancer (CRC) cells in vitro and in vivo by evaluating the proliferative and apoptotic responses of two CRC cell lines. MATERIALS AND METHODS: The combination index (CI) was calculated using the Chou-Talalay method, and the effects of the synergistic combination (CI<1) of lower doses of SAL and SFN were selected for further studies. Anti-tumor effect of the combination of SAL and SFN was tested both in vitro and in vivo. RESULTS: Cotreatment effectively inhibited proliferation, migration and invasion and enhanced apoptosis. The xenograft model also showed similar results. Furthermore, we evaluated the molecular mechanism behind SAL- and SFN-mediated CRC cell apoptosis. The combination treatment induced apoptosis in Caco-2 and CX-1 cells by inhibiting the PI3K/Akt pathway, which increased the expression of the tumor suppressor protein p53. The treatment also decreased the expression of the survival protein Bcl-2 and increased the expression of the proapoptotic protein Bax, which increased the Bax/Bcl-2 ratio, as well as enhanced poly ADP-ribose polymerase (PARP) cleavage. Upon inhibiting the PI3K/Akt pathway with LY294002 prior to cotreatment, we detected enhanced PARP cleavage compared to that in the cotreatment only group. CONCLUSION: We investigated whether the combination of SAL and SFN had antiproliferative and proapoptotic effects in CRC cells both in vitro and in vivo. Cotreatment also significantly decreased migration and invasion compared to that of the control and SAL or SFN monotherapies. This novel combination of SAL and SFN might provide a potential strategy to treat CRC.

Tissue microRNAs in non-small cell lung cancer detected with a new kind of liquid bead array detection system.

BACKGROUND: Commonly used miRNA detection methods cannot be applied for high-throughput analyses. However, this study was aimed to performed a liquid bead array detection system (LBAS) to detect tissue 6 miRNAs in non-small cell lung cancer (NSCLC). METHODS: In this study, evaluation of LBAS was performed to observe the precision, specificity, limitation and stability. Then, a total of 52 primary NSCLC patients who received resection operation without preoperative radiotherapy and chemotherapy between June 2013 and March 2014 were selected, and then the total RNA of the tissues were extracted. We prepared six NSCLC-related miRNAs for LBAS. After optimization and evaluation, LBAS was verified by detecting the relative expression levels of 6 microRNAs in the pathological tissues and corresponding normal tissues of 52 NSCLC patients. RESULTS: The results of evaluation of LBAS showed that the Mean Fluorescence Intensity (MFI) of the reaction only added with chimeric probes and beads showed no significant change after 180 days (P > 0.05). And the intra-assay Coefficient of Variation (CV) was between 1.57 and 3.5%, while the inter-assay CV was between 4.24 and 11.27%, indicating this system was ideal for diagnostic reagents. In addition, only the beads corresponding to the additional miRNAs showed high MFIs from 8426 to 18,769, whereas the fluorescence values of the other beads were under background levels (MFIs = 20 to 55) in each reaction, indicating no cross reactivity among the miRNAs. The limit of detection of miR-21, miR-210, miR-125b, miR-155, miR-375, and miR-31 were 5.27, 1.39, 1.85, 2.01, 1.34, and 2.73 amol/µL, respectively, showing that the lowest detection limit of miRNA by this system was under pM level. Then, the relative expression levels of miR-21, miR-210, miR-125b, miR-155, miR-375, and miR-31 by using this system were significantly correlated with NSCLC (P < 0.05). And the results of AUC method indicated that specific of the LBAS system was 94.2%. CONCLUSIONS: Our findings suggest that LBAS was simple, high-throughput, and freely combined with absolute quantification. Thus, this system could be applied for tumor miRNAs detection.

Postoperative Antifungal Treatment of Pulmonary Cryptococcosis in Non-HIV-Infected and Non-Transplant-Recipient Patients: A Report of 110 Cases and Literature Review.

BACKGROUND: To explore the efficacy of postoperative antifungal treatment for preventing the recurrence of pulmonary cryptococcosis (PC) and occurrence of cryptococcal meningitis (CM), a retrospective study was conducted in 112 hospitalized PC patients with or without antifungal treatment following surgery. METHODS: The treatment failure rate, PC recurrence rate, and CM incidence were compared. Additionally, the effectiveness of postoperative antifungal therapy was assessed by gathering and analyzing the published literature. RESULTS: The failure rate (P = .054) and recurrence rate (P = .178) were similar in the 2 groups, but the incidence of CM was lower in the group that received postoperative antifungal treatment (P = .039). CONCLUSIONS: This study did not show any difference in the PC recurrence rate or failure rate in the different treatment duration groups. Thus, a shorter antifungal treatment course of 2 months may be an optional treatment. In addition, upon review of the literature, no case of CM occurrence was reported among the 169 cases given postoperative antifungal treatment.

Quantitative proteomic analysis of down syndrome biomarkers in maternal serum using isobaric tags for relative and absolute quantification (iTRAQ).

Prenatal diagnosis of Down syndrome (DS) is based on calculated risk involving maternal age, biochemical and ultrasonographic markers, and, more recently, cell-free DNA (cfDNA). The present study was designed to identify Down Syndrome biomarkers in maternal serum. We quantified the changes in maternal serum protein levels between 10 non-pregnant women, 10 pregnant women with healthy fetuses, and 10 pregnant women with DS fetuses using isobaric tags for relative and absolute quantification (iTRAQ). We subsequently conducted a Gene Ontology (GO) analysis. A total of 470 proteins were identified, 11 of which had significantly different serum levels between the DS fetus group and Healthy fetuses group. Our data shows the identified proteins may be relevant to DS and constitute potential DS biomarkers.

Prevalence and causes of cesarean births among women residing at high altitude in Lhasa, Tibet: A retrospective observational study of 7365 women.

OBJECTIVE: Currently, there is paucity of data on the rate of vaginal deliveries and cesarean section among women in Tibet. In this study, we carried out an observational study of 7365 consecutive pregnant women in Lhasa, Tibet who gave birth at our tertiary care institution between 2012 and 2015. MATERIALS AND METHODS: In this retrospective study, we reviewed the hospital records for demographic data, obstetric history, and the number of vaginal and emergency cesarean section deliveries. The overall and annual rate of vaginal and cesarean section deliveries was calculated. Causes, indications or risks for cesarean section were also analyzed. RESULTS: During the review period, 7365 neonates were delivered at our hospital, including 1690 (23.0%) deliveries via cesarean section. The yearly rate of cesarean section progressively declined from 26.7% in 2012 to 18% in 2015 (P < 0.001). Furthermore, the annual rate of emergency cesarean section declined 53.9%between 2012 and 2015(P < 0.001). Fetal risk factors (39.9%) and maternal risk factors (40.3%) were the major causes of cesarean section in the women. Social factors as a cause of cesarean section fluctuated between 7.9% and 11.1%. CONCLUSION: This study has demonstrated a steady decline in the annual rate of cesarean section in women in Tibet between 2012 and 2015. A decrease in the rate of emergency cesarean section contributed substantially to this decline. Moreover, approximately 10% caesarian sections were performed without clear indications, highlighting the need for strengthening prenatal counseling for pregnant women in Tibet.

A Novel Mutant of rLj-RGD3 (rLj-112) Suppressed the Proliferation and Metastasis of B16 Cells through the EGFR Signaling Pathway.

Lj-RGD3, which contains three Arg⁻Gly⁻Asp (RGD) motifs, was first identified from the buccal glands of Lampetra japonica and has been shown to suppress the tumor progression in the previous studies. Apart from the three RGD motifs, Lj-RGD3 is also characterized by its high content of histidine in its amino acid sequence. In order to clarify whether the histidine-rich characterization of Lj-RGD3 is also associated with its anti-tumor activity, mutants were designed in which the three RGD motifs (Lj-112), or all histidines (Lj-27) or both (Lj-26) were deleted. Furthermore, a mutant (Lj-42) in which all histidines and three RGD motifs were respectively substituted with alanines and three Ala⁻Gly⁻Asp (AGD) motifs, as well as a mutant (Lj-41) in which all histidines were substituted with alanines was synthesized to avoid alterations in structure which might further cause changes in the peptides' functions. After recombination and purification, recombinant Lj-112 (rLj-112), recombinant Lj-27 (rLj-27), recombinant Lj-41 (rLj-41), and recombinant Lj-RGD3 (rLj-RGD3) exhibited anti-proliferative activity in B16 cells, respectively; while recombinant Lj-26 (rLj-26) and recombinant Lj-42 (rLj-42) did not affect the proliferation of B16 cells significantly. In addition, the anti-proliferative activity of rLj-112 in B16 cells was due to apoptosis. Typical apoptosis features were observed, including chromatin condensation, fragmented DNA, and increased levels of cleaved caspase 3/caspase 7/nuclear enzyme poly (ADP-ribose) polymerase (PARP) in B16 cells. Similar to rLj-RGD3, rLj-112 was also capable of suppressing the migration and invasion of B16 cells by disturbing the F-actin arrangement. After labeling with FITC, rLj-112 was found localized in the cytoplasm of B16 cells, which induced the internalization of epidermal growth factor receptor (EGFR), suggesting that rLj-112 might block the EGFR mediated signaling pathway. Actually, the phosphorylation level of EGFR and its downstream signal molecules including Akt, PI3K, p38, and ERK1/2 was reduced in the rLj-112 treated B16 cells. In vivo, rLj-112 also inhibited the growth, weight, and volume of the tumors in B16 xenografted C57BL/6 mice without reducing their body weight, indicating that rLj-112 might be safe and might be used as an effective anti-tumor drug in the near future.

Study of Benzofuroquinolinium Derivatives as a New Class of Potent Antibacterial Agent and the Mode of Inhibition Targeting FtsZ.

New generation of antibacterial agents are urgently needed in order to fight the emergence of multidrug-resistant bacteria. FtsZ is currently identified as a promising target for new types of antimicrobial compounds development because of its conservative characteristics and its essential role played in bacterial cell division. In the present study, the antibacterial activity of a series of benzofuroquinolinium derivatives was investigated. The results show that the compounds possess potent antibacterial activity against drug resistant pathogens including MRSA, VREF and NDM-1 Escherichia coli. Biological studies reveal that the compound is an effective inhibitor that is able to suppress FtsZ polymerization and GTPase activity and thus stopping the cell division and causing cell death. More importantly, this series of compounds shows low cytotoxicity on mammalian cells and therefore they could be new chemotypes for the development of new antibacterial agents targeting the cell-division protein FtsZ.