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Sleep apnea presents as recurrent respiratory arrests or shallow breathing during sleep, resulting in decreased oxygen saturation and sleep disruption. Among its various types, obstructive sleep apnea is the most common. Over the past few decades, the prevalence of sleep apnea has been on the rise, drawing increasing attention, particularly with the growing obesity and aging population. Prolonged exposure to a hypoxic environment due to sleep apnea not only damages multiple systems throughout the body but may also pose a threat to vision. Examining the relationship between sleep apnea and ocular diseases, along with exploring its pathogenesis, has become a prominent research topic in recent years. This article provides a comprehensive review of the existing literature concerning the correlation between sleep apnea and ocular diseases such as glaucoma, optic nerve diseases, retinal and choroidal diseases, and anterior eye segment diseases. In clinical practice, prioritizing early screening and treatment for sleep apnea is crucial to prevent the worsening of associated ophthalmic conditions.

A series of dihydrotriazine derivatives bearing 5-aryloxypyrazole moieties were designed, and their anticancer activities against three human cancer cell lines (SGC-7901, HepG-2 and MCF-7) and one non-cancer cell line (LO2) were explored using the MTT assay in vitro. Most of the compounds exhibited potent antiproliferative activities against the three cancer cell lines, with compound 10e (IC 50  = 2.12 µM) exhibiting the most potent antiproliferative activity against HepG-2 cells. Interestingly, autophagy was observed in the 10e-treated HepG-2 cells. Compound 10e also increased reactive oxygen species (ROS) levels and resulted in marked HepG-2 cells apoptosis. Further studies revealed that compound 10e could enhance the expression of Cl-PARP, Cl-caspase-3, and Cl-caspase-9. In addition, 10e triggered the formation of autophagosomes by promoting LC3-II and Beclin-1 expression. These results might be useful for exploring and developing dihydrotriazine derivatives as novel anticancer agents., (Copyright © 2022. Published by Elsevier Inc.)

Background and Objective: Asthma is one of the most common chronic inflammatory diseases of the respiratory tract. Previous studies have shown that the reduction of regulatory B cells (Bregs) can increase inflammation of the body and promote the formation of chronic airway inflammation in asthma, but the detailed mechanisms have not been fully elucidated. The intestinal flora Clostridium leptum (CL) has been reported to modulate immune regulatory cells in the body, but the specific mechanisms are not clear. This study aimed to investigate the effects of CL on the differentiation of interleukin (IL)- 10 + Bregs and the regulation of the asthmatic inflammation-associated immune network., Methods: The abundances of CL and the frequencies of blood Bregs from asthmatic patients and healthy controls were compared. The house dust mite (HDM)-induced asthma model was established in mice. The effects of CL exposure and B cell infusion on Breg differentiation, T cell cytokine production, and inflammatory cell infiltration in mouse lungs were examined. Bregs were cocultured with regulatory T cells (Tregs) and CD4 + non-Tregs to evaluate their roles on Foxp3 expression and T cell differentiation, respectively., Results: Compared with healthy controls, asthmatic patients had significantly reduced frequencies of blood Bregs and abundances of fecal CL, and these two parameters were positively correlated. In the asthma model, the frequencies of Bregs in lungs were significantly reduced; while the infusion of Bregs isolated from CL- supplemented mice significantly reduced airway inflammation and hyperresponsiveness. In addition, Bregs inhibited the differentiation of cocultured non-Tregs into multiple effector cells and enhanced Foxp3 expression in cocultured Tregs., Conclusion: Bregs contribute to the alleviation of airway inflammation, which provides insight on implementing CL-based microbial induction of Bregs in asthma therapy., (Copyright © 2022. Published by Elsevier Ltd.)

In order to discover novel anti-inflammatory agents, three series of compounds obtained by appending 1,2,3-triazole moieties on ursolic acid were designed and synthesized. All compounds have been screened for their anti-inflammatory activity by using an ear edema model. The potent anti-inflammatory compound was subjected to in vitro cyclooxygenase COX-1/COX-2 inhibition assays. In general, the derivatives were found to be potent anti-inflammatory activity. Especially, the compound 11b exhibited the strongest activity of all of the compounds prepared, with 82.81% inhibition after intraperitoneal administration, which was better than celecoxib as a positive control. Molecular docking results unclose the rationale for the interaction of the compound 11b with COX-2 enzyme. Further studies revealed that compound 11b exhibited effective COX-2 inhibitory activity, with half-maximal inhibitor concentration (IC 50 ) value of 1.16 µM and selectivity index (SI = 64.66) value close to that of celecoxib (IC 50  = 0.93 µM, SI = 65.47). Taken together, these results could suggest a promising chemotype for development of new COX-2-targeting anti-inflammatory agent., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Here, two series of novel ursolic acid-based 1,2,4-triazolo[1,5-a]pyrimidines derivatives were synthesized and screened for their anti-inflammatory activity by evaluating their inhibition effect of using LPS-induced inflammatory response in RAW 264.7 macrophages in vitro; the effects of different concentrations of the compounds on the secretion of nitric oxide (NO) and inflammatory cytokines including TNF-α and IL-6 were evaluated. Their toxicity was also assessed in vitro. Results showed that the most prominent compound 3 could significantly decrease production of the above inflammatory factors. Docking study was performed for the representative compounds 3, UA, and Celecoxib to explain their interaction with cyclooxygenase-2 (COX-2) receptor active site. In vitro enzyme study implied that compound 3 exerted its anti-inflammatory activity through COX-2 inhibition., (© 2020. Springer Nature Switzerland AG.)

In the present investigation, a series of dihydrotriazine derivatives-bearing 5-aryloxypyrazole moieties were synthesized and their structures were confirmed by different spectral tools. The biological evaluation in vitro revealed that some of the target compounds exerted good antibacterial and antifungal activity in comparison with the reference drugs. Among these novel hybrids, compound 10d showed the most potent activity with minimum inhibitory concentration values (MIC) of 0.5 µg/mL against S. aureus 4220, MRSA 3506 and E. coli 1924 strain. The cytotoxic activity of the compounds 6d, 6m, 10d and 10g was assessed in MCF-7 and HeLa cells. Growth kinetics study showed significant inhibition of bacterial growth when treated with different conc. of 10d. In vitro enzyme study implied that compound 10d exerted its antibacterial activity through DHFR inhibition. Moreover, significant inhibition of biofilm formation was observed in bacterial cells treated with MIC conc. of 10d as visualized by SEM micrographs. Twenty-nine target compounds were designed, synthesized and evaluated in terms of their antibacterial and antifungal activities.

Trigeminal neuropathic pain (TNP) is a significant health problem but the involved mechanism has not been completely elucidated. Toll-like receptors (TLRs) have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain. Here, we show that TLR8 was persistently increased in the trigeminal ganglion (TG) neurons in model of TNP induced by partial infraorbital nerve ligation (pIONL). In addition, deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia, reduced the activation of ERK and p38-MAPK, and decreased the expression of pro-inflammatory cytokines in the TG. Furthermore, intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity. VTX-2337 also increased the intracellular Ca 2+ concentration, induced the activation of ERK and p38, and increased the expression of pro-inflammatory cytokines in the TG. These data indicate that TLR8 contributes to the maintenance of TNP through increasing MAPK-mediated neuroinflammation. Targeting TLR8 signaling may be effective for the treatment of TNP.

The present work describes the in vitro antibacterial evaluation of some new pyrimidine derivatives. Twenty-two target compounds were designed, synthesized and preliminarily explored for their antimicrobial activities. The antimicrobial assay revealed that some target compounds exhibited significantly inhibitory efficiencies toward bacteria and fungal including drug-resistant pathogens. Compound 7c presented the most potent inhibitory activities against Gram-positive bacteria (e.g., Staphylococcus aureus 4220), Gram-negative bacteria (e.g., Escherichia coli 1924) and the fungus Candida albicans 7535, with an MIC of 2.4 μmol/L. Compound 7c was also the most potent, with MICs of 2.4 or 4.8 μmol/L against four multidrug-resistant, Gram-positive bacterial strains. The toxicity evaluation of the compounds 7c, 10a, 19d and 26b was assessed in human normal liver cells (L02 cells). Molecular docking simulation and analysis suggested that compound 7c has a good interaction with the active cavities of dihydrofolate reductase (DHFR). In vitro enzyme study implied that compound 7c also displayed DHFR inhibition.

Aim: To study the change of torsion in both eyes after unilateral inferior oblique (IO) weakening on children with congenital superior oblique palsy (SOP)., Methods: This retrospective study enrolled all patients diagnosed with unilateral congenital superior oblique palsy (UCSOP) accompanied by inferior oblique overaction (IOOA). A total of 120 eyes of 60 patients were divided into group 1 (more extorted paretic eye) and group 2 (more extorted nonparetic eye). The degree of fundus torsion was evaluated before and 1mo after the IO weakening procedure. The torsion of the fundus was recorded by measuring the disk-foveal angle (DFA) using fundus photography., Results: Group 1 included 26 cases and group 2 included 34 cases, thus the rate of extorsion was insignificantly higher in the nonparetic eye ( P =0.10). The preoperative DFA in the paretic and nonparetic eyes was 13.21±5.95, 7.97±4.25 in group 1, and 4.65±3.79, 13.16±5.35 in group 2 (both P <0.001). The postoperative DFA in the paretic and nonparetic eyes was 8.57±4.87, 7.32±4.27 in group 1 ( P =0.24), and 3.85±6.00 and 9.94±5.45 in group 2 ( P <0.001). The amount of postoperative reduction of the DFA in the paretic and nonparetic eyes was 4.64±3.90, 0.65±0.76 in group 1 ( P =0.002), and 0.80±0.81, 3.21±5.50 in group 2 ( P =0.01). The difference in the amount of reduction of DFA in the more extorted eye in group 1 (paretic eye) vs group 2 (nonparetic eye) was insignificant ( P =0.30)., Conclusion: Excyclotorsion in the nonparetic eye has a similar probability in the paretic eye in UCSOP children, and weakening of the ipsilateral IO has a more obvious effect on the decrement of extorsion in the more extorted eye regardless of which eye is paretic., (International Journal of Ophthalmology Press.)

Twenty benzothiazole derivatives bearing a 1,3,4-oxadiazole moiety were synthesized and evaluated for their anti-oxidant and anti-inflammatory activities. Among these compounds, 8h and 8l were appeared to have high radical scavenging efficacies as 0.05 ± 0.02 and 0.07 ± 0.03 mmol/L of IC 50 values in ABTS + bioassay, respectively. In anti-inflammatory tests, compound 8h displayed good activity with 57.35% inhibition after intraperitoneal administration, which was more potent than the reference drug (indomethacin). Molecular modeling studies were performed to investigate the binding mode of the representative compound 8h into COX-2 enzyme. In vitro enzyme study implied that compound 8h exerted its anti-inflammatory activity through COX-2 inhibition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The changes and distribution of non-structural carbohydrate (NSC, including soluble sugar and starch) content in different organs of one-year-old Caryopteris mongolica seedlings were investigated under suitable water condition (CK), slow-dying drought stress, and fast-dying drought stress. There was no significant difference in soluble sugar content of all organs between slow-dying drought stress and CK. With the extended duration of drought, the soluble sugar content in stem increased firstly and then decreased, while starch and NSC contents decreased. The soluble sugar content in coarse roots decreased, while starch and NSC contents increased. The soluble sugar content in leaves increased, while starch and NSC contents of leaves decreased. The NSC content of leaves, stems, coarse roots and fine roots were 6.2%, 7.8%, 8.3% and 7.4% at the death time (80 days), respectively. Under fast-dying drought stress, soluble sugar content in all organs was higher than that in CK, while starch and NSC contents were lower than that in CK. With the increasing time, soluble sugar content of roots decreased, while starch and NSC contents increased. The soluble sugar, starch and NSC contents in stems increased. The soluble sugar content of leaves increased, while starch and NSC contents decreased. The NSC content of leaves, stems, coarse roots and fine roots were 5.9%, 6.6%, 8.9% and 7.7% at lethal time (30 days), respectively. Under different drought stress, non-structural carbohydrates among different organs of C. mongolica seedlings showed different dynamics. Under slow-dying drought stress, NSC gave priority to allocate energy for maintaining physiological metabolism of organs. Under fast-dying drought stress, NSC mainly maintained plant metabolism in the form of soluble sugar, regulated osmotic potential, promoted water absorption, and coped with drastic drought stress.

Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule that plays important roles in the cardiovascular system. In our previous studies, we demonstrated that H2S regulates lipid metabolism. In the present study, we aimed to explore the mechanisms through which H2S regulates lipid metabolism in HepG2 cells in vitro. Treatment of the HepG2 cells with H2S inhibited the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) and increased the level of low‑density lipoprotein receptor (LDLR) in a time‑ and dose‑dependent manner. The knockdown of PCSK9 by siRNA effectively increased the levels of LDLR and 1,1'‑dioctadecyl‑3,3,3',3'‑tetramethyl‑indocarbocyanine perchlorate‑labeled LDL (DiI‑LDL) uptake in the H2S‑treated HepG2 cells. Furthermore, the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt)‑sterol regulatory element binding proteins 2 (SREBP‑2) signaling pathway was confirmed to be involved in H2S‑regulated PCSK9 expression. Notably, the HepG2 cells were incubated with 30% serum and DiI‑LDL for 24 h, and the results revealed that H2S increased lipid uptake, but caused no increase in lipid accumulation. On the whole, the findings of this study demonstrate that H2S is involved in the regulation of lipid metabolism in HepG2 cells through the regulation of the expression of PCSK9 via the PI3K/Akt‑SREBP‑2 signaling pathway. To the very best of our knowledge, this study is the first to report that H2S can regulate the expression of PCSK9.

Toll-like receptors (TLRs) are nucleic acid-sensing receptors and have been implicated in mediating pain and itch. Here we report that Tlr8 -/- mice show normal itch behaviors, but have defects in neuropathic pain induced by spinal nerve ligation (SNL) in mice. SNL increased TLR8 expression in small-diameter IB4 + DRG neurons. Inhibition of TLR8 in the DRG attenuated SNL-induced pain hypersensitivity. Conversely, intrathecal or intradermal injection of TLR8 agonist, VTX-2337, induced TLR8-dependent pain hypersensitivity. Mechanistically, TLR8, localizing in the endosomes and lysosomes, mediated ERK activation, inflammatory mediators' production, and neuronal hyperexcitability after SNL. Notably, miR-21 was increased in DRG neurons after SNL. Intrathecal injection of miR-21 showed the similar effects as VTX-2337 and inhibition of miR-21 in the DRG attenuated neuropathic pain. The present study reveals a previously unknown role of TLR8 in the maintenance of neuropathic pain, suggesting that miR-21-TLR8 signaling may be potential new targets for drug development against this type of chronic pain., (© 2018 Zhang et al.)

In this Letter, we demonstrate a whispering-gallery-mode (WGM) microsphere resonator. The device is fabricated by fusion splicing a section of no-core fiber with multimode fiber (MMF) and single-mode fiber at its two ends. The open end of the MMF is etched to create an arc-shaped cavity, with a microsphere glued at its bottom. When the arc of the cavity bottom and microsphere surface are tangent, part of the incident light is coupled into the microsphere and travels exactly one circle before being directed back to the MMF core along the tangent line and exciting the WGM. The device has a Q-factor of 1.21×10 4 , and is robust in structure and low in cost.

Objective: To investigate the clinical characteristics, surgical approaches and postoperative effects associated with congenital fibrovascular pupillary membranes. Methods: A retrospective study design was used. Thirteen children (13 eyes) with congenital fibrovascular pupillary membranes, treated in Beijing Children's Hospital from January 2014 to December 2017 were included. The morphology of the membrane and the anterior chamber was evaluated using a digital wide-area fundus imaging system. The ophthalmic signs, examination results, operation methods, intraocular pressure and ocular position were analyzed. Results: There were 13 children (13 eyes) were enrolled, including 9 males and 4 females. The age at surgery ranged from 2.0 months to 34.5 months, with an median of 5.1 months. According to the degree of obstruction of the pupil and the intraocular pressure, the eyes were divided into three groups. In the 5 eyes of group A, the pupil membrane did not completely cover the pupil, and the depth of the anterior chamber was normal. Among them, 4 eyes had normal intraocular pressure (9-12 mmHg) (1 mmHg=0.133kPa), and 1 eye had elevated intraocular pressure (18 mmHg). In the 5 eyes of group B, the pupillary membrane completely covered the pupil into a pinhole, the anterior chamber was normal or slightly shallow, and the intraocular pressure was normal (6-16 mmHg). In the 3 eyes of group C, the pupillary membrane completely covered the pupil, the anterior chamber was shallow or disappeared, and the intraocular pressure was high (24-45 mmHg). Membranectomy and pupilloplasty were performed in group A, and trabeculectomy was combined when there was glaucoma; postoperative intraocular pressure was normal (4-10 mmHg). Membranectomy, pupilloplasty and iridectomy were performed in group B; postoperative intraocular pressure was normal (7-13 mmHg). Membranectomy, pupilloplasty, iridectomy and goniosychialysis were performed in group C; after surgery, intraocular pressure was normal in 2 eyes (10 mmHg and 13 mmHg) and 25 mmHg in 1 eye. All eyes were orthophoric before and after operation in group A. In group B, 1 eye was esotropic, 2 eyes were exotropic (worse after surgery in 1 eye), and 2 eyes were orthophoric before surgery. In group C, one eye was esotropic, one eye was exotropic, and one eye was orthophoric before surgery, and all eyes were exotropic after operation. Conclusions: Congenital fibrovascular pupillary membranes are unilaterally a continuation of the iris covering the pupil at different degrees, with or without glaucoma. Surgical treatment should be performed promptly when there is obscuring of the visual axis or incorporating of glaucoma. The main surgical procedures are membranectomy and pupilloplasty and iridectomy. Postoperative intraocular pressure can be well controlled, and strabismus has no improvement. (Chin J Ophthalmol, 2018, 54:849-854) .

Atherosclerosis is characterized by chronic inflammation and lipid accumulation in arterial walls, resulting in several vascular events. Proprotein convertase subtilisin kexin 9 (PCSK9), a serine protease, has a pivotal role in the degradation of hepatic low-density lipoprotein receptor (LDLR). It can increase plasma concentrations of low-density lipoprotein cholesterol and affect lipid metabolism. Recently, PCSK9 has been found to accelerate atherosclerosis via mechanisms apart from that involving the degradation of LDLR, with an emerging role in regulating the inflammatory response in atherosclerosis. Apolipoprotein E receptor 2 (apoER2), one of the LDLR family members expressed in macrophages, can bind to its ligand apolipoprotein E (apoE), exhibiting an anti-inflammatory role in atherosclerosis. Evidence suggests that apoER2 is a target of PCSK9. This review aims to discuss PCSK9 as a potential regulator of apoE/apoER2 against inflammation in atherosclerosis., (Copyright © 2018. Published by Elsevier B.V.)

Objective: To explore whether the iliac wing influences L5 pedicle screw (PS) fixation and to propose methods to reduce such influence., Methods: A total of 100 computed tomography scans (from 50 male and 50 female patients) of the lower lumbar region and pelvis were obtained and 3-dimensionally reconstructed. Cylinders with 6.5-mm diameters were drawn to simulate the different trajectories of L5 PS. The maximum lengths and lateral angles of trajectories, and the vertical distances from the inner edge of the iliac wing to these trajectories, were measured., Results: The maximum lengths and lateral angles differed significantly among trajectories; the maximum length, but not the lateral angle, differed significantly between male and female subjects. The influence of the iliac wing was more significant in male than in female subjects. The iliac wing had a greater effect on screws implanted along the pedicle axis than on screws for which the trajectories commenced at Du's entry point and passed through the center of the pedicle., Conclusions: This study elucidates the influence of the iliac wing on L5 PS fixation. Careful attention is required when implanting PSs, especially in male patients. The combined use of Du's technique and a percutaneous method for PS implantation effectively reduces the influence of the iliac wing. To minimize the complications of PS fixation further, preoperative simulation of fixation for each patient is very important., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis (ACD). CXCR3 in the spinal cord also contributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3 -/- mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund's adjuvant-induced chronic inflammatory pain were reduced in Cxcr3 -/- mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water (AEW). Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Furthermore, touch-elicited itch (alloknesis) after compound 48/80 or AEW treatment was suppressed in Cxcr3 -/- mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3 -/- mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.

Chemokines-mediated neuroinflammation in the spinal cord plays a critical role in the pathogenesis of neuropathic pain. Chemokine CXCL9, CXCL10, and CXCL11 have been identified as a same subfamily chemokine which bind to CXC chemokine receptor 3 to exert functions. Our recent work found that CXCL10 is upregulated in spinal astrocytes after spinal nerve ligation (SNL) and acts on chemokine receptor CXCR3 on neurons to contribute to central sensitization and neuropathic pain, but less is known about CXCL9 and CXCL11 in the maintenance of neuropathic pain. Here, we report that CXCL9 and CXCL11, same as CXCL10, were increased in spinal astrocytes after SNL. Surprisingly, inhibition of CXCL9 or CXCL11 by spinal injection of shRNA lentivirus did not attenuate SNL-induced neuropathic pain. In addition, intrathecal injection of CXCL9 and CXCL11 did not produce hyperalgesia or allodynia behaviors, and neither of them induced ERK activation, a marker of central sensitization. Whole-cell patch clamp recording on spinal neurons showed that CXCL9 and CXCL11 enhanced both excitatory synaptic transmission and inhibitory synaptic transmission, whereas CXCL10 only produced an increase in excitatory synaptic transmission. These results suggest that, although the expression of CXCL9 and CXCL11 are increased after SNL, they may not contribute to the maintenance of neuropathic pain.

Recent data demonstrated that chemokine CXCL13 mediates neuroinflammation and contributes to the maintenance of neuropathic pain after nerve injury in the spinal cord. Pro-nociceptive chemokines activate mitogen-activated protein kinases (MAPKs) which are potential signaling pathways contributing to the nociceptive behavior in inflammatory or neuropathic pain. However, whether activation of p38 and JNK MAPK signaling pathway in the trigeminal ganglion (TG) are involved in CXCL13 and its receptor CXCR5-mediated orofacial pain has not yet been clarified. Here, we show that the unilateral partial infraorbital nerve ligation (pIONL) induced a profound orofacial pain in wild-type (WT) mice. Western blot results showed that pIONL induced p38 but not JNK activation in the TG of WT mice. However, the orofacial pain induced by pIONL was alleviated in Cxcr5 -/- mice, and the activation of p38 was also abrogated in Cxcr5 -/- mice. Furthermore, intra-TG injection of CXCL13 evoked mechanical hypersensitivity and increased p-p38 expression in WT mice. But CXCL13 had no effect on pain behavior or p-p38 expression in Cxcr5 -/- mice. Finally, pretreatment with p38 inhibitor, SB203580, attenuated the pIONL-induced mechanical allodynia and decreased the mRNA expression of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the TG. Taken together, our data suggest that CXCL13 acts on CXCR5 to increase p38 activation and further contributes to the pathogenesis of orofacial neuropathic pain.

Background: Hyperlipidemia is a risk factor for neurodegenerative diseases. Proprotein convertase subtilisin / Kexin type 9 (PCSK9) degrades hepatic low-density lipoprotein receptor (LDLR) to regulate lipid metabolism. It is unclear if PCSK9 plays a role in neurodegenerative diseases., Objective: This study was designed to determine whether PCSK9 is crucial between hyperlipidemia and Alzheimer's disease. The interrelationship between PCSK9 and neuronal apoptosis was explored in PC12 cells in response to treatment with oxidized low-density lipoprotein (oxLDL)., Methods: Cultured PC12 cells were serum-starved and incubated with different concentrations of oxLDL for 24 h. Intracytoplasmic lipid droplets were observed by oil red O staining. Morphological assessment of apoptotic cells was performed using Hoechst 33258 staining and flow cytometry analysis. The expression of mRNA and protein was detected by reverse-transcription polymerase chain reaction (RT-PCR) and western blot analyses, respectively. Transfection of small interfering RNA (siRNA) into PC12 cells was conducted using HiperFect Transfection Reagent. Concentrations of Aβ40 and Aβ42 were detected by enzyme-linked immunosorbent assay (ELISA) kit., Results: Intracellular lipid content, the number of apoptotic cells, and PCSK9 expression were increased in PC12 cells after oxLDL treatment. Transfection with PCSK9 siRNA reduced the oxLDL-induced apoptosis of PC12 cells. We further confirmed the involvement of Bcl-2/Bax-Caspase (9, 3) signaling pathway in the regulation of PC12 cells apoptosis.β-Secretase 1, another target gene of PCSK9, was downregulated in PC12 cells in response to oxLDL treatment. Aβ40 and Aβ42 contents were also decreased., Conclusion: PCSK9 promotes oxLDL-induced PC12 cell apoptosis through the Bcl-2/Bax-Caspase 9/3 signaling pathway.

This study was aimed to investigate the mRNA and protein expression of CTGF, CYR61, VEGF-C and VEGFR-2 in bone marrow of patients with leukemia, and to analyze the role and clinical significance of these 4 factors in genesis and development of leukemia, infiltration and metastasis of leukemic cells. A total of 100 cases of newly diagnosed leukemia, 26 cases of acute leukemia in complete remission and 30 controls were enrolled in this study. The mononuclear cells of bone marrow were collected, the mRNA and protein expression levels of CTGF, CYR61, VEGF-C, VEGFR-2 in leukemia patients and controls were detected by real time PCR and Western blot, respectively. The results showed that the mRNA and protein expression levels of above mentioned 4 factors were significantly higher than those in control (P < 0.05), only CTGF mRNA expression in AL patients after complete remission showed statistical difference as compared with control (P < 0.05), but the expression of CTGF mRNA showed statistical significance in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF protein showed difference in different chromosome karyotypes of leukemia (P < 0.05). The expression levels of CYR61 and VEGF-C proteins showed statistical difference in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF, CYR61, VEGF-C mRNA and protein in CML group were higher than that in control group. The expression levels of CTGF and CYR61 protein were higher than that in control. The mRNA and protein expression levels of above-mentioned 4 factors in sex and infiltration lf leukemic cells did not show statistical significance(P < 0.05). In correlative analysis, the mRNA expressions of above mentioned 4 factors were positively correlated with bone marrow blast count(P < 0.05), the protein expression of CTGF, CYR61 and VEGF-C were positively correlated with bone marrow blast count. It is concluded that the CTGF, CYR61, VEGF-C and VEGFR-2 mRNA and protein play a role in acute leukemia. In acute leukemia (AML/ALL), the expression of above mentioned factor was high, but except VEGFR-2. Most of them were positively correlated with bone marrow blast count. Joint block of these angiogenesis-related factors is likely to play an important role in targeting treatment of leukemia.

In order to improve the protection system to reduce the damage of biodiversity and protect broad-leaved Korean pine mixed forest, 64 forest farms from 6 Forestry Bureaus around Changbai Mountains Nature Reserve were investigated and analyzed. A total of 41 plants were selected as key protected plants, and felling area, cropland, mining area, highway, railway and residential area were considered as the disturbance factors. GAP and GIS spatial analysis were used to draw the indicator plant and disturbance intensity distribution maps. The results showed that the indicator species distribution was uneven. The indicator plant enrichment regions were located on the north western and southern slopes centered with Shengli and Lenggouzi forest farms of Quanyang County, respectively, and single distributions of the endemic plants were found in Baoshan, Henshan, Lenggouzi and Heishan forest farms. The different disturbance severities were observed in the different forest farms, among which the north part in Lushuihe and Baihe forest farms were severely disrupted. Two ecologically critical areas, Quanyang-Lushuihe-Baihe on the north slope of Changbai Mountains and the east part of Changbai County on the south slope, were determined based on the comprehensive analysis.

The purpose of this study was to compare the in vitro release and the in vivo pharmacokinetics of bilayer tablets with the conventional dispersible tablets of nimesulide. The tablets were administered to beagle dogs and the plasma levels of nimesulide were determined by high-performance liquid chromatography-MS/MS. The pharmacokinetic parameters were calculated using a noncompartmental model. The bilayer tablets showed a biphasic in vitro release pattern with initial burst release and sustained release following the quasi-Fickian diffusion-based release mechanism. The C(max), t(max), mean residence time (MRT), and area under the curve from 0 to 36 h were 10.8 ± 4.2 μg/mL, 2.3 ± 1.0 h, 6.7 ± 2.1 h, 81.5 ± 26.7 μg·h/mL for the bilayer tablets and 14.8 ± 5.8 μg/mL, 2.7 ± 0.8 h, 5.6 ± 0.9 h, 95.4 ± 44.2 μg·h/mL for the dispersible tablets. Compared with the dispersible tablets, the bilayer tablets have lower C(max), similar t(max), and longer MRT. The aforementioned pharmacokinetic parameters, especially the MRT demonstrated to be valuable for evaluating the biphasic characteristics. This study provides a promising in vivo evaluation method for the bilayer tablets with biphasic release pattern.

In the title compound, [Mn(C(19)H(12)N(5))(2)], each Mn(II) atom lies on a position of site symmetry 222 and has a distorted octa-hedral coordination geometry made up from six N atoms of two tridentate 2-[6-(1H-benzimidazol-2-yl)-2-pyrid-yl]benz-imidazolate ligands. The complex mol-ecules are linked into layers parallel to (001) by N-H⋯N hydrogen bonds, with the H atoms disordered over four symmetry-equivalent non-coordinated N atoms.

Objective: To analyze the types, distribution characteristics and in vitro susceptibility of antibiotic agents of ocular non-viral microbial isolates in children., Methods: Experimental research.785 specimens obtained from children below the age of 14 in Beijing Tongren Hospital during 1999 to 2004 were cultured and identified for bacterium, fungus and Acanthamoeba respectively at Beijing Institute of Ophthalmology. Microbial culture-positive rate, susceptibility patterns and the organisms distribution of positive cultures were retrospectively analyzed. The results were statistical analyzed by chi(2)., Results: Of the 785 specimens, 211 were culture positive. The percentage of positive culture was 26.88%. Of those positive cultures, 176 (83.41%) had pure bacterial infections, 32 (15.17%) had pure fungal infections, and 3 (1.42%) had pure cultures of Acanthamoeba. Of the 176 bacterial positive cultures, polymicrobial infection was present in 38 cases (33 bacterial, 5 fungal and bacterial). Of 214 bacterial isolates, the most common isolate was Neisseria gonorrhoeae (39/214, 18.22%), followed by Staphylococcus epidermidis (37/214, 17.29%), and Corynebacterium spp. (36/214, 16.82%). The most common fungal pathogen isolated was Fusarium spp. representing 25.00% (8/32) of all positive fungal cultures, followed by Aspergillus spp. (15.63%, 5/32). The sensitivity of tobramycin, norfloxacin, gentamicin, amikacin, ciprofloxacin, ofloxacin, rifampicin and levofloxacin of bacteria was 62.57%, 64.94%, 70.06%, 70.87%, 71.19%, 73.89%, 85.80% and 87.50%. Gram-positive isolates were susceptible to levofloxacin. Gram-negative isolates showed high susceptible to ciprofloxacin, ofloxacin and levofloxacin. The fungal isolates were most susceptible to natamycin, followed by terbinafine, but resistant to fluconazole., Conclusions: Bacteria are the most common pathogens in non-viral microbial eye infection in children. Neisseria gonorrhoeae, Staphylococcus epidermidis, and Corynebacterium spp. are the most common bacterial pathogens, which are highly susceptible to levofloxacin and rifampicin. Fusarium spp. and Aspergillus spp. are the most common fungal pathogens, which are highly susceptible to natamycin but resistant to fluconazole.

Objective: To assess the in vitro susceptibilities of ocular bacterial isolates to Gatifloxacin and other fluoroquinolones which are often used in ophthalmic treatment., Methods: Non-randomized, non-comparative, retrospective study. Ocular bacterial isolates (n = 619) from Beijing Institute of Ophthalmology were tested for their susceptibilities to gatifloxacin, ciprofloxacin, ofloxacin and levofloxacin in vitro by the Kirby-Bauer disk diffusion method., Results: The total number of ocular bacterial isolates was 619 from January, 2005 to December, 2006 including gram-positive cocci 372(60.1%), gram-negative cocci 7 (1.1%), gram-positive bacilli 60 (9.7%), gram-negative bacilli 177 (28.6%), other 3 (0.5%). The percentage of susceptibility in total ocular bacterial isolates to gatifloxacin, ciprofloxacin, ofloxacin and levofloxacin was 88.4%, 72.1%, 64.8% and 54.4%. The susceptibility of Staphylococcus species to gatifloxacin (89.9%) was significantly higher than ciprofloxacin (38.8%), ofloxacin (48.2%) and levofloxacin (61.6%). Streptococcus species showed significantly higher susceptibility to gatifloxacin (93.2%), levofloxacin (89.2%) and ofloxacin (87.8%) than ciprofloxacin (62.2%). The susceptibility of gram-positive bacilli to gatifloxacin (86.7%) was significantly higher than ciprofloxacin (58.3%); All above differences are significant (P < 0.0083). Gram-negative cocci, enteric bacilli family and Pseudomonas species have the equivalent susceptibility to gatifloxacin, ciprofloxacin, ofloxacin and levofloxacin (P > 0.05)., Conclusions: Most of ocular bacterial are susceptible to gatifloxacin in vitro, especially gram-positive bacteria including Staphylococcus species, Streptococcus species and gram-positive bacilli.

RNAi technique has been proved as a powerful tool for plant breeding. In this paper, the coat protein of tobacco mosaic virus (TMV) was used for constructing the RNAi interference vector. The tobacco varieties K326 and Longjiang 911 were transformed via Agrobacterium tumefaciens-mediated transformation, and transgenic plants were generated. The expression analysis with real-time PCR indicated that TMV RNA had been degraded varied in different transgenic lines. Field assay revealed that 83% and 90 % transgenic plants showed immunity resistance to TMV in K326 and Longjiang 911 respectively.

Increased calcium intake may reduce body weight and fat in non-growing individuals. This study explored the long-term effects of high versus low calcium intake on body weight, body fat, BMC, BMD and bone size in growing male and female rats. Ninety male and 90 female Sprague-Dawley rats were randomly assigned either to a high calcium (1%) or low calcium (0.25%) diet from age 3 weeks until 40 weeks. Half of the animals were fed ad libitum, and half of the animals were on an adjusted feeding schedule (the food intake of the low calcium animals was reduced to maintain equal body weight with high calcium animals of the same gender). DXA and radiographic measurements (femur and skull length and width) were collected at the age of 4, 13 and 34 weeks. Growing male rats fed the low calcium diet ad libitum gained more weight and more fat than rats on a high calcium diet. When food intake was controlled, male rats on the low calcium diet still had a greater fat mass (despite their similar body weight) and smaller skeletal measurements than the high calcium animals. Growing female rats initially responded like the males: when fed ad libitum low calcium animals had an increased body weight and fat mass; when food intake was controlled the low calcium animals had a greater fat mass and smaller skeletal measurements. However, these differences were found at 13 weeks and not at 34 weeks, suggesting a transient effect with no long-term differences between high and low calcium intake in the growing female rats.

WRKY family proteins are a class of plant specific transcription factors that involve in many stress response pathways. It has been shown that one Arabidopsis WRKY protein, AtWRKY29/22, is activated by MAP kinase signaling cascade and confers resistance to both bacterial and fungal pathogens. However, little is known about the biological roles of WRKY proteins in rice. In this study, we investigated the expression patterns of rice AtWRKY29/22 homolog, OsWRKY03, under different conditions, and also its possible role involved in plant defense. Our results showed that OsWRKY03 was up-regulated by several defense signaling molecules or different treatments. Further analysis revealed that the expression of OsWRKY03 was light dependent. Transcriptional activation activity of OsWRKY03 was also demonstrated by yeast functional assay. Transient expression of OsWRKY03-GFP fusion protein in onion epidermis cells showed that OsWRKY03 was a nuclear localized protein. OsNPR1 as well as several other pathogenesis-related genes, such as OsPR1b, phenylalanine ammonia-lyase (ZB8) and peroxidase (POX22.3), were induced in OsWRKY03-overexpressing transgenic plants. These results indicated that OsWRKY03 is located upstream of OsNPR1 as a transcriptional activator in salicylic acid (SA)-dependent or jasmonic acid (JA)-dependent defense signaling cascades.

Objective: This study was conducted to detect the expression of laminin (LN) and laminin receptor (LN-R) in the specimens of hydatidiform mole (HM), invasive mole (IM) and choriocarcinoma(CC), respectively., Methods: The immunohistological staining method was used., Results: It was found that the level of the laminin expression was higher in the specimens of choriocarcinoma at more advanced stage., Conclusion: The results suggest that there may be relations between the invasion and metastasis of choriocacinoma cell and the malignant degree of this disease, chemotherapy has some effect on the expression of LN and LN-R in gestational trophablastic tumor (GTT), and that LN and LN-R may be of potential value in GTT treatment. However, referring whether LN and LN-R could be used as clinical prognosticators, further studies will be needed.

Objective: To study the changes of the dental occlusion and the maxillofacial region after treatment with FR-III for crossbite in children in deciduous and mixed dentition phases., Methods: Sixty-four children with crossbite in deciduous and mixed dentition phases were included in this study. Tooth models and Schuller's position and lateral head X-rays were measured before and after treatment with FR-III to study the changes in the three-dimensional structures of the dental occlusion and maxillofacial region., Result: The width of dental arch exhibited little changes after the treatment whereas the length of the maxillary dental arch was increased. The upper incisors grew in labial inclination and the condyle withdrew to its natural position. The relationship of maxillary and mandibular base bone was obviously improved after the treatment, which also promoted the lingual inclination of the lower incisiors and the decrease of the genial angle. The lower and posterior facial height was increased., Conclusion: FR-III readjusts the muscle function of oral and maxillofacial system and promotes normal development of the dental arch and jaw.

Objective: To study the surgical management of metastatic disease in the conjunctive area between the neck and thorax and its efficacy., Methods: Fourteen cases with metastatic node disease in the area between neck and thorax were collected and analysed. Eleven tumors were from the thyroid cancer, and the other three were from the hypopharyngeal cancer, esophagual cancer and malignant pheochromocytoma, respectively. The clavicle was displaced or resected, and the upper half of the manubrium might also be resected when necessary. The recurrent laryngeal nerve and phrenic nerve were exposed and protected. The metastatic disease was completely removed with the internal jugular and/or the brachiocephalic vein resected or spared, depending on the disease condition., Results: In 10 cases with metastases from the thyroid, no local recurrence was found within the follow-up period from 2 to 5 years. In contrast, no patient with metastatic disease from hypopharyngeal or esophageal cancer survived more than 11 months. No serious complications were found in this group., Conclusions: The surgical treatment of node metastases in the conjunctive area between neck and thorax from the well-developed thyroid cancer has promising effect and is comparatively safe.

To explore the clinical features, risk factors an d treatment of retinoic acid syndrome (RAS) in patients with acute promyelocytic leukemia (APL) treated with retinoic acid, the clinical and laboratory data of 11 APL patients with RAS were retrospectively analysed. The results showed that earlier and more common symptoms of RAS were successively dyspnea (11/11), fever (10/11) and hydrothorax (6/11). Higher WBC count (> or = 15.0 x 10(9)/L) in the course of treatment of all-trans retinoic acid susceptible to develop RAS (9/11). The RAS patients were treated with dexamethasone without discontinuing the treatment of retinoic acid, complete remission was achieved in 10 cases and one patient died from disseminated intravascular coagulation. It is concluded that the identification and dexamethasone treatment of RAS in earlier period are extremely important for obtaining better clinical curative effect, and it does not influence therapeutic effect of continuing application of retinoic acid.

We have succeeded in growing the HTLV-IIIB strain of human immunodeficiency virus type 1 (HIV-1) in cultured human thymic epithelial (TE) cells. Expression of the HIV-1 proteins p17 and p24 was detected by immunofluorescence and reached a peak at 3 days after infection. Antigen capture and reverse transcriptase assays were used to detect HIV-1 in culture fluids, with positive results also being realized. The infection was cytolytic; cellular disarrangement, increased numbers of Hassall's corpuscles, and giant cells first appeared in monolayers of TE cells at 2 days after inoculation. By 4 days these changes were increased, and by 7 days, retraction and involution of TE cells were evident. The infection of TE cells by HIV-1 was blocked by preincubation with monoclonal OKT4A antibodies directed against CD4 target molecules.

A tissue culture system for the growth of human fetal and infantile thymic epithelial (TE) cells has been established and characterized. We have investigated the effects of infection of these cells by human cytomegalovirus (CMV), measles virus, and human immunodeficiency virus type-1 (HIV-1). In the case of CMV, morphological changes were apparent by 2-4 days after viral inoculation of infantile TE cells. CMV-related antigens were detected by immunofluorescence after 12 days, and progeny infectious CMV was recovered from culture media after 18 days. Following infection by measles virus, distinctive, multinucleated giant TE cells appeared in both cultures of fetal and infantile TE cells. Measles virus-inoculated TE cells displayed an altered phenotype, as revealed by reaction with monoclonal antibodies with specificity for a variety of TE markers. Finally, infection of TE cells by HIV-1 resulted in cellular disarrangement, increased numbers of Hassall's corpuscles, and multinucleated giant cells. An increase in the number of cells reactive with monoclonal antibodies, specific for Hassall's corpuscles, was observed in the case of cells infected by either measles virus or HIV-1. These findings suggest that a variety of different viruses can successfully infect thymic epithelial tissue. Because of the important role of the thymus in development of the immune system, it is reasonable to conclude that viral infection of thymic tissue might play an important role in virus-mediated suppression of immune responsiveness.