B cell subsets-related biomarkers and molecular pathways for systemic lupus erythematosus by transcriptomics analyses.

BACKGROUND: Systemic lupus erythematosus (SLE), an autoimmune disease, is characterised by B-cell abnormalities and a loss of tolerance that can produce autoantibody. However, the imperative genes and molecular pathways involved in the change of B cell populations remain unclear. METHODS: The expression of B cell subsets between SLE and healthy controls (HCs) was detected based on micro-array transcriptome data. The Weighted Gene Co-Expression Network Analysis (WGCNA) further revealed the co-expression modules of naïve and memory B cells. Whereafter, we performed the functional enrichment analysis, Protein-protein interaction (PPI) networks construction and feature selection to screen hub genes. Ultimately, we recruited SLE patients and HCs from the Second Hospital of Shanxi Medical University and further verified these genes in transcriptome sequencing samples. RESULTS: Total of 1087 SLE patients and 86 HCs constituted in the study. Compared to HCs, the levels of peripheral naïve B cells of SLE patients decreased, while memory B cells increased. WGCNA identified two modules with the highest correlation for the subsequent analysis. The purple module was primarily in connection with naïve B cells, and the GO analysis indicated that these genes were mainly abundant in B cell activation. The blue module relevant to memory B cells was most significantly enriched in the "defence response to virus" correlation pathway. Then we screened six hub genes by PPI and feature selection. Finally, four biomarkers (IFI27, IFITM1, MX2, IRF7) were identified by transcriptome sequencing verification. CONCLUSION: Our study identified hub genes and key pathways associated with the naïve and memory B cells respectively, which may offer novel insights into the behaviours of B cells and the pathogenesis of SLE.

A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation.

BACKGROUND: Compound kushen injection (CKI), a Chinese patent drug, is widely used in the treatment of various cancers, especially neoplasms of the digestive system. However, the underlying mechanism of CKI in pancreatic cancer (PC) treatment has not been totally elucidated. METHODS: Here, to overcome the limitation of conventional network pharmacology methods with a weak combination with clinical information, this study proposes a network pharmacology approach of integrated bioinformatics that applies a weighted gene co-expression network analysis (WGCNA) to conventional network pharmacology, and then integrates molecular docking technology and biological experiments to verify the results of this network pharmacology analysis. RESULTS: The WGCNA analysis revealed 2 gene modules closely associated with classification, staging and survival status of PC. Further CytoHubba analysis revealed 10 hub genes (NCAPG, BUB1, CDK1, TPX2, DLGAP5, INAVA, MST1R, TMPRSS4, TMEM92 and SFN) associated with the development of PC, and survival analysis found 5 genes (TSPOAP1, ADGRG6, GPR87, FAM111B and MMP28) associated with the prognosis and survival of PC. By integrating these results into the conventional network pharmacology study of CKI treating PC, we found that the mechanism of CKI for PC treatment was related to cell cycle, JAK-STAT, ErbB, PI3K-Akt and mTOR signalling pathways. Finally, we found that CDK1, JAK1, EGFR, MAPK1 and MAPK3 served as core genes regulated by CKI in PC treatment, and were further verified by molecular docking, cell proliferation assay, RT-qPCR and western blot analysis. CONCLUSIONS: Overall, this study suggests that the optimized network pharmacology approach is suitable to explore the molecular mechanism of CKI in the treatment of PC, which provides a reference for further investigating biomarkers for diagnosis and prognosis of PC and even the clinical rational application of CKI.

[Effects of moisture and heat coupling on xylem growth of Pinus tabuliformis in Shenyang, China]. / 水热耦合对沈阳地区油松木质部生长的影响.

Based on the micro-core technology, we can accurately examine the tree cambium phenology and the radial growth at the cellular scale, and reveal the relationship between tree growth and climate. Pinus tabuliformis is one of the constructive species in forests of northern China. We investigated the growth pattern of P. tabuliformis in Shenyang and the changes in cambium and xylem cells throughout the growing season (April to November) in 2020. Results showed that the dividing activity in cambium started in early April and ended at the end of September. Xylem began to grow from the appearance of enlargement cells (mid April) to the end of the disappearance of lignified cells (late October), with a growth trajectory of 'S' shape curve. Approximately 53 xylem cells per row in radical direction were produced in 2020. The maximum growth rate (0.55 ind/row/day) occurred at the end of May, while the change of earlywood and latewood cells occurred at the end of July. When the minimum temperature above 0 ℃ in Shenyang, the cambium began to divide. The minimum critical temperature that affected the beginning and ending of xylem growth was 2-3 ℃. Precipitation promoted the growth in the growing season. The high temperature and insufficient water supply at the end of July were the main factors driving the differentiation of xylem cells to form earlywood and latewood.

Mesenchymal stem cell treatment for peripheral nerve injury: a narrative review.

Peripheral nerve injuries occur as the result of sudden trauma and lead to reduced quality of life. The peripheral nervous system has an inherent capability to regenerate axons. However, peripheral nerve regeneration following injury is generally slow and incomplete that results in poor functional outcomes such as muscle atrophy. Although conventional surgical procedures for peripheral nerve injuries present many benefits, there are still several limitations including scarring, difficult accessibility to donor nerve, neuroma formation and a need to sacrifice the autologous nerve. For many years, other therapeutic approaches for peripheral nerve injuries have been explored, the most notable being the replacement of Schwann cells, the glial cells responsible for clearing out debris from the site of injury. Introducing cultured Schwann cells to the injured sites showed great benefits in promoting axonal regeneration and functional recovery. However, there are limited sources of Schwann cells for extraction and difficulties in culturing Schwann cells in vitro. Therefore, novel therapeutic avenues that offer maximum benefits for the treatment of peripheral nerve injuries should be investigated. This review focused on strategies using mesenchymal stem cells to promote peripheral nerve regeneration including exosomes of mesenchymal stem cells, nerve engineering using the nerve guidance conduits containing mesenchymal stem cells, and genetically engineered mesenchymal stem cells. We present the current progress of mesenchymal stem cell treatment of peripheral nerve injuries.

α-γ-Type [Mo8O26]4--Containing Metal-Organic Complex Possessing Efficient Catalytic Activity toward the Oxidation of Thioether Derivatives.

In this work, a new α-γ-type [Mo8O26]4- anion was first synthesized and characterized by single-crystal X-ray diffraction analysis and was obtained by introducing molybdate to the synthesis of metal-organic complex (MOC) under hydrothermal conditions. An octamolybdate-based MOC, namely, {[Cu8(H2O)6](dpyh)4(α-γ-Mo8O26) }·(ß-Mo8O26)·8.5H2O (H2dpyh = N,N-bis(3-pyrazolamide)-1,2-hexahydrobenzene), was obtained. The α-γ-type [Mo8O26]4- anion was composed of four MoO6 octahedra and four MoO5 trigonal bipyramids by sharing their edges and corners. The title complex exhibited a 1D structure in which an α-γ-type [Mo8O26]4- anion was connected with [Cu4(dpyh)2] units in a staggered manner. Under optimized conditions, complex 1 as the catalyst can achieve a highly efficient conversion (more than 99%) of thioanisole within 30 min and above 99% selectivity toward sulfoxide. Furthermore, efficient catalytic oxidation of thioether derivatives was also performed with 1 as the catalyst. In addition, the stable electrochemical sensing performance and adsorption capacity toward organic dyes were tested.

Ventral tegmental area GABAergic neurons induce anxiety-like behaviors and promote palatable food intake.

The obesity epidemic is a global problem and a great challenge for public health. Overconsumption of food, especially palatable food, is the leading cause of obesity. The precise neural circuits underlying food overconsumption remain unclear and require further characterization. In the present study, we showed that Ca2+ signals of GABAergic neurons within the ventral tegmental area (VTA) increased after the onset of food intake, especially high-fat or high-sugar chow. Optogenetic activation of VTA GABAergic neurons evoked immediate eating of palatable food and significantly increased palatable food intake in satiated mice. Photoinhibition of VTA GABAergic neurons suppressed palatable food intake. Surprisingly, photoactivation of VTA GABAergic neurons suppressed the intake of standard chow in fasted mice, but did not reduce the duration of eating of standard chow. Moreover, we found that photoactivation of these neurons drove a series of anxiety-like behaviors in the open field, elevated plus maze, and marble-burying test. Additionally, we found that VTA GABAergic neurons sent abundant projections to the lateral hypothalamus and photoactivation of GABAergic VTA terminals in the lateral hypothalamus induced overconsumption of palatable food, but not anxiety-like behaviors. Taken together, our results illustrate that GABAergic VTA neurons are a key node in the neural circuitry underlying anxiety-like behavior and over-feeding of palatable food, and that over-excitation of GABAergic VTA neurons may underlie clinical diseases related to anxiety and obesity.

The mechanism of formation of thin-walled cystic lung cancer.

Thin-wall cystic lung cancer is becoming of increasing interest in the study of pulmonary medicine. Consequently, more and more different images and pathologic manifestations have been found. The purpose of this article is to find pathologic characteristics and try to explain the formation mechanism of thin-walled cystic lung cancer.Sixty-five patients with this special lung cancer were analyzed retrospectively based on the review of medical records, radiologic findings, and pathologic changes.We found 3 pathologic types: adenocarcinoma, squamous cell carcinoma, and lymphoma. There were 60 cases of adenocarcinoma, 4 cases were squamous cell carcinoma, and only 1 lymphoma. Tumor cells, pulmonary vessels, fibrous tissues, and residual bronchi are the pathologic basis of different image findings.Thin-walled cystic lung cancers are mostly adenocarcinoma, but other pathologic types can also appear, such as squamous cell carcinoma and lymphoma. We can see that a large amount of fibrous tissues were generated by tumors around the bronchus, resulting in airway stenosis and degeneration. Tumor cells also can invade the bronchial wall and cause structural damage. All these lesions are similar to 1-way valves which can cause gas accumulation in the tumor area and result in thin-walled cystic lung cancer.

APLNR promotes the progression of osteosarcoma by stimulating cell proliferation and invasion.

Osteosarcoma is the most common type of bone malignancies with a poor prognosis. In recent years, targeted therapy has shown great potential in the treatment of osteosarcoma, and more effective therapeutic targets for this disease need to be developed. APLNR is a seven transmembrane G-protein-coupled receptor expressed widely in multiple tissues. As has been reported, APLNR is involved in various physiological and pathological processes. Although APLNR plays a role in the development and progression of multiple tumors, the potential role of APLNR in osteosarcoma, a highly malignant tumor, remains unclear. Here, we reported that APLNR expression was correlated positively with clinical features including tumor size and stage of osteosarcoma. We found that APLNR knockdown inhibited the proliferation and invasion of osteosarcoma cells in vitro. In addition, APLNR could promote the progression and metastasis of osteosarcoma in mice. Collectively, this study showed the potential link between APLNR and osteosarcoma and suggested APLNR as a novel therapeutic target for osteosarcoma.

MUC1 overexpression predicts worse survival in patients with non-small cell lung cancer: evidence from an updated meta-analysis.

BACKGROUND: Previous studies on the prognostic role of MUC1 expression in non-small cell lung cancer (NSCLC) remain controversial. We conducted a meta-analysis to appraise the clinicopathological and prognostic effect of MUC1 in NSCLC patients. MATERIALS AND METHODS: Searches of PubMed, EMBASE and CNKI (Chinese National Knowledge Infrastructure) were conducted and relevant studies were extracted. The pooled hazard ratio (HR) or odds ratio (OR) with 95% confidence intervals (CIs) were used to estimate effects. Heterogeneity among studies and publication bias were also evaluated. RESULTS: A total of 15 studies with 1,682 patients were included in this meta-analysis. The pooled HRs indicated that elevated MUC1 expression was associated with poorer overall survival (HR = 2.12, 95% CI: 1.47-3.05; P < 0.001) and progression-free survival (HR = 2.00, 95% CI: 1.53-2.62; P < 0.001) in patients with NSCLC. Significant associations were also found in patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) (HR = 3.16, 95% CI: 2.21-4.52, P < 0.001) and with a platinum-based regimen (HR = 4.35, 95% CI: 2.45-7.72, P < 0.001). Additionally, MUC1 overexpression was significantly associated with performance status (OR = 2.32, 95% CI: 1.13-4.73, P = 0.021). CONCLUSIONS: MUC1 could be a valuable biomarker of the prognoses of NSCLC patients.

Dog-transmitted Rabies in Beijing, China.

Rabies remains a continuous threat to public health in Beijing. In this study, a total of 224 brain tissues were collected from suspected infected stray dogs within Beijing between January 2015 and December 2016. Among them, total of 67 samples were diagnosed positive for rabies. In the phylogenetic analysis, rabies in Beijing is currently a relatively independent public health issue originating from local rabid dogs apart from the imported cases from elsewhere in the country. Because vaccination of unregistered dogs against rabies is still neglected in Beijing and other regions of China, national and local authorities should play central roles in all related aspects, such as development of policies, engagement of stakeholders for public and professional education, entire vaccination process, and animal management.

Anti-tumor activity of SL4 against breast cancer cells: induction of G2/M arrest through modulation of the MAPK-dependent p21 signaling pathway.

SL4, a chalcone-based compound, has been shown to retard tumor invasion and angiogenesis by suppressing HIF1 activity and to induce apoptosis by promoting ROS release. Here, we report that SL4 is able to inhibit the proliferation of different types of breast cancer cell in vitro and in vivo by inducing G2/M cell cycle arrest. Our results showed that SL4 exhibited strong anti-proliferative activity in several human breast cancer cell lines, with IC50 values lower than 1.3 µM. Further studies indicated that SL4 induced G2/M arrest in these cell lines. Mechanistically, SL4 reduces the expression of cyclin A2 and cdc25C and decreases the activity of the cdc2/cyclin B1 complex. Notably, SL4 treatment resulted in an obvious increase in p21 mRNA and protein levels through activation of MAPK signaling pathways, but not the TGF-ß pathway. SP600125 and PD98059, specific inhibitors of JNK kinase and ERK kinase, significantly blocked the SL4-induced G2/M phase arrest and upregulation of p21. Furthermore, SL4 suppressed the growth of established breast tumors in nude mice through upregulation of p21 and downregulation of cdc25C, and displayed a good safety profile. Taken together, these findings demonstrate the potential value of SL4 as a novel multi-target anti-tumor drug candidate.

Prognostic value of endocan expression in cancers: evidence from meta-analysis.

Endocan is a 50 kDa dermatan sulfate proteoglycan. Numerous previous studies have indicated that endocan might be an attractive prognostic tumor biomarker. However, the results of different studies are inconsistent. We conducted a meta-analysis to explore the association between endocan expression and cancer prognosis. A systematic, comprehensive search of the PubMed, Embase, and China National Knowledge Infrastructure databases was performed. Expression of endocan and its association with overall survival were evaluated by pooled hazard ratios (HRs) and their 95% confidence intervals (CIs). In total, 15 eligible studies of 1,464 patients were finally included in this meta-analysis. A significant association was found between elevated endocan expression and poorer overall survival (pooled HR: 2.48, 95% CI: 2.12-2.90, P<0.001). In the cancer-type subgroup, significant associations were detected for gastrointestinal (HR: 2.27, 95% CI: 1.77-2.91, P<0.001) and hepatocellular (HR: 2.61, 95% CI: 1.96-3.48, P<0.001) carcinoma. Our results demonstrate that endocan could be useful to exploit as a novel prognostic biomarker for patients with cancer.

A novel method for right one-lung ventilation modeling in rabbits.

There is no standard method by which to establish a right one-lung ventilation (OLV) model in rabbits. In the present study, a novel method is proposed to compare with two other methods. After 0.5 h of baseline two-lung ventilation (TLV), 40 rabbits were randomly divided into sham group (TLV for 3 h as a contrast) and three right-OLV groups (right OLV for 3 h with different methods): Deep intubation group, clamp group and blocker group (deeply intubate the self-made bronchial blocker into the left main bronchus, the novel method). These three methods were compared using a number of variables: Circulation by heart rate (HR), mean arterial pressure (MAP); oxygenation by arterial blood gas analysis; airway pressure; lung injury by histopathology; and time, blood loss, success rate of modeling. Following OLV, compared with the sham group, arterial partial pressure of oxygen and arterial hemoglobin oxygen saturation decreased, peak pressure increased and lung injury scores were higher in three OLV groups at 3 h of OLV. All these indexes showed no differences between the three OLV groups. During right-OLV modeling, less time was spent in the blocker group (6±2 min), compared with the other two OLV groups (13±4 min in deep intubation group, P<0.05; 33±9 min in clamp group, P<0.001); more blood loss was observed in clamp group (11.7±2.8 ml), compared with the other two OLV groups (2.3±0.5 ml in deep intubation group, P<0.001; 2.1±0.6 ml in blocker group, P<0.001). The first-time and final success rate of modeling showed no differences among the three OLV groups. Deep intubation of the self-made bronchial blocker into the left main bronchus is an easy, effective and reliable method to establish a right-OLV model in rabbits.

[Biological characteristics of drug induced tumor cells and its medicine prevention and treatment].

Recently, the incidence and mortality of cancer has raised. More and more cytotoxic drugs and molecular targeted medicines have been used in clinic. However, most drugs just display a short-term anti- tumor effect. If patients received treatment for a long time, it would arise resistance to chemotherapy frequently. One of its important reasons is the accumulation of drug induced cancer cells. Thus, this paper emphasizes on biological character of drug induced cells, including cell biological phenotype, the change of gene and protein, variation of metabolism, dynamic change of signal transduction pathway and so on. Meanwhile, according to the characteristics of drug induced cells, we propose some strategies to inhibit drug induced cells, which would provide the foundation of clinical therapy and novel anti-tumor drug research and development.

167.75-nm vacuum-ultraviolet ps laser by eighth-harmonic generation of a 1342-nm Nd:YVO4 amplifier in KBBF.

We demonstrate a ps 167.75-nm vacuum-ultraviolet (VUV) laser by cascaded second-harmonic generation (SHG). The VUV laser is produced by eighth-harmonic generation (EHG) of a mode-locked ps 1342-nm Nd:YVO4 amplifier through three stages cascaded SHG with two LiB3O5 crystals and one KBe2BO3F2 crystal, successively. The 167.75-nm laser provides up to 65-µW output power, and the corresponding photon flux and photon flux density are 5.5×10(13) s(-1) and 1.6×10(18) s(-1)·cm(-2), respectively.

Comparison between two types of confocal laser endomicroscopy in gastrointestinal tract.

OBJECTIVES: Confocal laser endomicroscopy (CLE) consists of endoscope-based CLE (eCLE) and probe-based CLE (pCLE). This study aimed to compare eCLE and pCLE in their diagnostic yield in different parts of the gastrointestinal (GI) tract. METHODS: Consecutive patients were scheduled for CLE examination due to GI symptoms. All patients were randomly assigned to eCLE or pCLE group and underwent a programmed procedure using one type of CLE. Differences in procedure time, complication rate, CLE image quality and image acquisition feasibility between these two types of CLE for esophagogastroduodenoscopy (EGD) and colonoscopy were calculated. RESULTS: Altogether 513 CLE procedures were performed, including 324 EGD and 189 colonoscopy. The procedure time of pCLE was significantly shorter than that of eCLE both in EGD and colonoscopy (16.78 min vs 18.13 min for EGD, P = 0.027; 32.48 min vs 39.89 min for colonoscopy, P < 0.001). No significant difference was found between these two types of CLE in diagnostic utility, including the detection and prediction of histopathological results of the lesions. The CLE image quality of both eCLE and pCLE were comparable in the stomach and colon, but eCLE seemed to be superior to pCLE in examining the esophagus. Colonoscopy using pCLE had a higher complete rate than that of eCLE, although the difference was not statistically significant (P = 0.065). CONCLUSIONS: pCLE is more flexible in diagnosing GI diseases with a shorter procedure time than eCLE regardless of comparable diagnostic yields, except the diagnosis of esophageal diseases in which eCLE provides better image quality.

Comparison of laser induced thermal fracture between polycrystalline ceramic and crystal Nd:YAG.

Continuous wave 808 nm pump laser-induced thermal damage of polycrystalline transparent ceramic and crystalline Nd:YAG materials was investigated both experimentally and theoretically. The measured temperature agrees well with the theoretical simulation, and the maximum hoop stresses occur on the incident facet of the end-pumped rod at about √2 times of the pump beam radius w0, where the temperature gradient is the highest and the damage occurs first at this location. The fracture-limited laser intensity of ceramics was experimentally measured to be 6.4±0.6 kW/cm2, nearly 64% higher than that of the crystals (3.9±0.3 kW/cm2). The deduced thermal fracture stress for ceramic was 386±50 MPa, which is 64% higher than that of the crystals (235±16 MPa).

Stent-assisted coiling of cerebral aneurysms using the Enterprise and the Solitaire devices.

OBJECTIVE: To evaluate the technical feasibility, peri- and post-procedural morbidity and mortality as well as clinical and angiographic follow-up using the Enterprise and the Solitaire stent currently available to be used for stent-assisted coiling of broad-based cerebral aneurysms. MATERIAL AND METHODS: We conducted a retrospective study to investigate differences in aneurysms stented with the Enterprise (n  =  58) and Solitaire stents (n  =  19). Angiographic follow-up (mean: 8.25 onths) was available in 82.6% of patients treated with stent-assisted coiling. RESULTS: All stents were successfully deployed. There is a higher acute in-stent thrombosis complication in Solitaire stent placement (P  =  0.012). However, we observed no significant differences in peri-procedural morbidity and mortality rate (P  =  0.253), angiographic results (P  =  0.411), recurrence rate (P  =  1.000), or long-term neurological deficit (P  =  0.435). CONCLUSION: Both stents exhibited similar immediate and mid-term results with major neurological morbidities and mortality rate being low. More thrombogenic complications overall were found in Solitaire group.

Multiple transmissible genes encoding fluoroquinolone and third-generation cephalosporin resistance co-located in non-typhoidal Salmonella isolated from food-producing animals in China.

The aim of this study was to identify genes conferring resistance to fluoroquinolones and extended-spectrum ß-lactams in non-typhoidal Salmonella (NTS) from food-producing animals in China. In total, 31 non-duplicate NTS were obtained from food-producing animals that were sick. Isolates were identified and serotyped and the genetic relatedness of the isolates was determined by pulsed-field gel electrophoresis of XbaI-digested chromosomal DNA. Antimicrobial susceptibility was determined using Clinical and Laboratory Standards Institute methodology. The presence of extended-spectrum ß-lactamase (ESBL) and fluoroquinolone resistance genes was established by PCR and sequencing. Genes encoded on transmissible elements were identified by conjugation and transformation. Plasmids were typed by PCR-based replicon typing. The occurrence and diversity of numerous different transmissible genes conferring fluoroquinolone resistance [qnrA, qnrD, oqxA and aac(6')-Ib-cr] and ESBLs (CTX-M-27 and CTX-M-14), and which co-resided in different isolates and serovars of Salmonella, were much higher than in European countries. Furthermore, different plasmids encoded fluoroquinolone resistance (ca. 6 kb) and ß-lactam resistance (ca. 63 kb) and these co-resided in isolates with mutations in topoisomerase genes (gyrA and parC) giving very resistant Salmonella. The presence of multidrug-resistant bacteria in food-producing animals in countries that export foodstuffs suggests that global transfer of antibiotic resistances from country to country on food is possible.

High efficiency and high peak power picosecond mid-infrared optical parametric amplifier based on BaGa4Se7 crystal.

A high efficiency and high peak power picosecond (ps) mid-infrared optical parametric amplifier with a new nonlinear crystal BaGa(4)Se(7) pumped by a 30 ps 1064 nm Nd:YAG laser is demonstrated for the first time. The maximum photon conversion efficiency of 56% from 1064 nm to 3.9 µm idler has been achieved at the pump energy of ~1.8 mJ. A maximum idler output of 830 µJ at 3.9 µm with peak power of ~27 MW was obtained at pump energy of ~9.1 mJ. Moreover, a 3-5 µm idler tuning range was demonstrated, with output energies of ~300 µJ at 5 µm and up to 1 mJ at 3 µm at ~8.2 mJ pump energy.