DHX9/DNA-tandem repeat-dependent downregulation of ciRNA-Fmn1 in the dorsal horn is required for neuropathic pain.

Circular RNAs (ciRNAs) are emerging as new players in the regulation of gene expression. However, how ciRNAs are involved in neuropathic pain is poorly understood. Here, we identify the nervous-tissue-specific ciRNA-Fmn1 and report that changes in ciRNA-Fmn1 expression in spinal cord dorsal horn neurons play a key role in neuropathic pain after nerve injury. ciRNA-Fmn1 was significantly downregulated in ipsilateral dorsal horn neurons after peripheral nerve injury, at least in part because of a decrease in DNA helicase 9 (DHX9), which regulates production of ciRNA-Fmn1 by binding to DNA-tandem repeats. Blocking ciRNA-Fmn1 downregulation reversed nerve-injury-induced reductions in both the binding of ciRNA-Fmn1 to the ubiquitin ligase UBR5 and the level of ubiquitination of albumin (ALB), thereby abrogating the nerve-injury-induced increase of ALB expression in the dorsal horn and attenuating the associated pain hypersensitivities. Conversely, mimicking downregulation of ciRNA-Fmn1 in naïve mice reduced the UBR5-controlled ubiquitination of ALB, leading to increased expression of ALB in the dorsal horn and induction of neuropathic-pain-like behaviors in naïve mice. Thus, ciRNA-Fmn1 downregulation caused by changes in binding of DHX9 to DNA-tandem repeats contributes to the genesis of neuropathic pain by negatively modulating UBR5-controlled ALB expression in the dorsal horn.

Clinicopathologic Features and Treatment Characteristics of Congenital Corneal Opacity Infants and Children Aged 3 Years or Less: A Retrospective Single Institution Analysis.

OBJECTIVE: In this retrospective single institution study, we investigated the clinicopathologic features and treatment characteristics of 90 patients with congenital corneal opacities (CCO) (117 eyes) who were 3 years and younger and treated at our hospital. SUBJECT AND METHODS: We reviewed the clinical data of patients with CCO who presented for the first time for treatment at our hospital between January 1, 2017, and December 31, 2017. CCO were classified using the "STUMPED" (Sclerocornea, Tears in Descement's membrane, Metabolic, Peters, Endothelial dystrophy and Dermoid) method and confirmed by pathological examination. -Results: Seventy percent of the patients had unilateral CCO. Iridocorneal adhesions (61 eyes, 52.1%) and cataracts (22 eyes, 18.8%) were the 2 most common ocular abnormalities. Systemic abnormalities were present in 5 patients (5.6%), including growth retardation (4 patients) and congenital brain defects (1 patient). Eighty-five eyes (72.6%) underwent penetrating keratoplasty (PK), and lamellar keratoplasty (LK) was performed in 30 (25.6%) eyes. Forty-seven (95.9%) eyes with Peters anomaly and all 16 eyes with sclerocornea received PK, and all 24 eyes with dermoids were treated with LK. CONCLUSION: Our study demonstrates that CCO has varied manifestations in infants and young children in China. A thorough medical history, careful clinical examination, and the use of accessory examinations such as ultrasound biomicroscopy are critical for the accurate diagnosis and classification of CCO and to provide guidance on therapeutic choices.

Downregulation of miR-219 enhances brain-derived neurotrophic factor production in mouse dorsal root ganglia to mediate morphine analgesic tolerance by upregulating CaMKIIγ.

BACKGROUND: Increasing evidence suggests that microRNAs are functionally involved in the initiation and maintenance of pain hypersensitivity, including chronic morphine analgesic tolerance, through the posttranscriptional regulation of pain-related genes. We have previously demonstrated that miR-219 regulates inflammatory pain in the spinal cord by targeting calcium/calmodulin-dependent protein kinase II gamma (CaMKIIγ). However, whether miR-219 regulates CaMKIIγ expression in the dorsal root ganglia to mediate morphine tolerance remains unclear. RESULTS: MiR-219 expression was downregulated and CaMKIIγ expression was upregulated in mouse dorsal root ganglia following chronic morphine treatment. The changes in miR-219 and CaMKIIγ expression closely correlated with the development of morphine tolerance, which was measured using the reduction of percentage of maximum potential efficiency to thermal stimuli. Morphine tolerance was markedly delayed by upregulating miR-219 expression using miR-219 mimics or downregulating CaMKIIγ expression using CaMKIIγ small interfering RNA. The protein and mRNA expression of brain-derived neurotrophic factor were also induced in dorsal root ganglia by prolonged morphine exposure in a time-dependent manner, which were transcriptionally regulated by miR-219 and CaMKIIγ. Scavenging brain-derived neurotrophic factor via tyrosine receptor kinase B-Fc partially attenuated morphine tolerance. Moreover, functional inhibition of miR-219 via miR-219-sponge in naive mice elicited thermal hyperalgesia and spinal neuronal sensitization, which were both suppressed by CaMKIIγ small interfering RNA or tyrosine receptor kinase B-Fc. CONCLUSIONS: These results demonstrate that miR-219 contributes to the development of chronic tolerance to morphine analgesia in mouse dorsal root ganglia by targeting CaMKIIγ and enhancing CaMKIIγ-dependent brain-derived neurotrophic factor expression.

[Effect of Osthole on Adrenocortical Function in Y1 Mouse Adrenocortical Tumor Cells].

OBJECTIVE: To study the effect of osthole (Ost) on adrenocortical function in Y1 mouse adrenocortical tumor cells. METHODS: Y1 mouse adrenocortical tumor cells were taken as subjects in this experiment. In 10.0%, 1.0%, and 0.1% serum DMEM-F12 medium, Y1 cells were treated with 1, 10, 25, 50, 100, and 200 micromol/L Ost for 24 and 48 h. 0.1% Dimethyl Sulfoxide (DMSO) was taken as negative control group and 1 mmol/L (Bu) 2cAMP as positive control group. Cell growth morphology was observed under inverted microscope. Contents of corticosterone were tested by ELISA. Expression levels of steroids synthase such as Star, Cyp11a1, Cyp21a1, Hsd3b2, Cyp11b1, Cyp11b2, Cyp17a1, and Hsd17b3 mRNA were detected by Real time quantitative PCR (RT-qPCR). RESULTS: Y1 cell proliferation was obviously inhibited by 100 and 200 micromol/L Ost, and its inhibitory effect was more significant in 0.1% serum medium. Compared with the negative control group, gene expressions of Star, Cyp11a1 , Cyp21a1, Hsd3b2, Cyp11b1, Cyp17a1, and Hsd17b3 were significantly enhanced in the posi- tive control group (P < 0.05). Y1 cell corticosterone levels significantly increased in 50 micromol/L Ost treatment group after 24-and 48-h intervention (P < 0.05). Contents of corticosterone increased more obviously in 25 and 50 +/- mol/L Ost treatment groups after 48-h intervention, as compared with 24-h intervention (P < 0.01). After 24-h intervention, expression levels of Star, Cyp21a1, and Hsd3b2 genes were significantly up-regulated in 25 and 50 lLmol/L Ost groups (P < 0.05). Star gene expression was further enhanced after 48-h intervention (P < 0.05). However, Ost showed no effect on Cyp11a1 (P > 0.05). Additionally, gene expressions of Cyp11b1 and Cyp17a1 were significantly enhanced by 10, 25, and 50 pLmolIL Ost after treatment for 24 and 48 h (P < 0.05). Ost showed no obvious effect on Cyp11b2 and Hsd17b3 expressions. CONCLUSION: Ost could regulate adrenal cortex function and promote corticosterone synthesis and secretion through strengthening gene expressions of steroidogenic enzymes.

[The field radiometric calibration and validation of ZY-3 multispectral sensor].

A field calibration campaign of ZY-3 multispectral sensor (MUS) was performed by the China Center for Resources Satellite Data and Application at the Dunhuang site. The reflectance-based method with two-point sites was used to obtain MUS absolute calibration coefficients in 2013. Compared to the calibration results in 2012, the calibration coefficients in 2013 changed by about 1%-8.5% in different bands. The results were also validated by intercalibration method using the Landsat 8 Operational Land Imager (OLI) data. It shows largely good consistency between field calibration and intercalibration. It was concluded that the absolute calibration coefficients were highly reliable.

Kv3.1 Interaction with UBR5 Is Required for Chronic Inflammatory Pain.

Chronic inflammatory pain caused by neuronal hyperactivity is a common and refractory disease. Kv3.1, a member of the Kv3 family of voltage-dependent K+ channels, is a major determinant of the ability of neurons to generate high-frequency action potentials. However, little is known about its role in chronic inflammatory pain. Here, we show that although Kv3.1 mRNA expression was unchanged, Kv3.1 protein expression was decreased in the dorsal spinal horn of mice after plantar injection of complete Freund's adjuvant (CFA), a mouse model of inflammatory pain. Upregulating Kv3.1 expression alleviated CFA-induced mechanical allodynia and heat hyperalgesia, whereas downregulating Kv3.1 induced nociception-like behaviors. Additionally, we found that ubiquitin protein ligase E3 component n-recognin 5 (UBR5), a key factor in the initiation of chronic pain, binds directly to Kv3.1 to drive its ubiquitin degradation. Intrathecal injection of the peptide TP-CH-401, a Kv3.1 ubiquitination motif sequence, rescued the decrease in Kv3.1 expression and Kv currents through competitive binding to UBR5, and consequently attenuated mechanical and thermal hypersensitivity. These findings demonstrate a previously unrecognized pathway of Kv3.1 abrogation by UBR5 and indicate that Kv3.1 is critically involved in the regulation of nociceptive behavior. Kv3.1 is thus a promising new target for treating inflammatory pain.

Branched-Chain Amino Acids Deficiency Promotes Diabetic Neuropathic Pain Through Upregulating LAT1 and Inhibiting Kv1.2 Channel.

Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences  is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.

[Research on the atmospheric correction for ZY-3 MUX image].

The resolution of the ZY-3 MUX data is 5.8 meter, which is used to the subject classification. It is very difficult to use the dark target method for the atmosphere correction due to the lack of near infrared band in ZY-3 MUX data. The present paper uses the atmospheric correction coefficient look-up table (LUT) constructed by the radiation transmission model 6S based on the aerosol optical depth retrieved from the MODIS data for the atmospheric correction of ZY-3 image. To validate the results, the paper compares the surface spectral curves of the gypsum mine and Gobi and the NDVI values from the corrected and TOA reflectance, the relative error of the atmosphere corrected and the ground-based surface reflectance is less than 6%; the atmospheric correction increases the difference between vegetation NDVI and other features NDVI, highlights vegetation monitoring application ability.

[Recent advances in dry eye: etiology, pathogenesis and management].

Dry eye is one of the most common and multifactorial disease of the ocular surface that results in ocular discomfort, blurred vision, reduced quality of life, and decreased productivity. Recent advances in our knowledge of the causation of dry eye open opportunities for improving diagnosis , and disease management and for developing new, more effective therapies to manage this widely prevalent and debilitating disease state. In light of the above knowledge, the present article reviews the newer theories and reports on etiology , pathogenesis and management of dry eye.

[Transplantation of autologous labial salivary glands for severe dry eye].

OBJECTIVE: Autologous labial salivary gland transplantation has been a promising alternative for the treatment of severe dry eye. In this article, we describe the results of the ocular surface changes after labial salivary gland transplantation and investigate the feasibility of this treatment. METHODS: The results of this technique in 8 patients (eyes) who suffered from severe dry eye were prospectively analyzed after surgery (follow-up of 6 months). The best-corrected visual acuity, Schirmer I test, degree of discomfort, usage of pharmaceutical tear substitutes, tear interferometry and slit lamp examination were investigated at different time before and after surgery. RESULTS: All grafts remained viable and the survival rate is 100%. All patients showed significant increase in the Schirmer's test and they expressed great improvement in their ocular discomfort. The use of artificial tear substitutes was reduced because of the increased ocular surface lubrication. CONCLUSION: Although the authors' long-term experience still is limited, we believe that the procedure is a promising alternative approach for severe dry eye.

Microglial P2Y12 Signaling Contributes to Cisplatin-induced Pain Hypersensitivity via IL-18-mediated Central Sensitization in the Spinal Cord.

Administration of cisplatin and other chemotherapy drugs is crucial for treating tumors. However, cisplatin-induced pain hypersensitivity is still a critical clinical issue, and the underlying molecular mechanisms have remained unresolved to date. In this study, we found that repeated cisplatin treatments remarkedly upregulated the P2Y12 expression in the spinal cord. Expression of P2Y12 was predominant in the microglia. Pharmacological inhibition of P2Y12 expression markedly attenuated the cisplatin-induced pain hypersensitivity. Meanwhile, blocking the P2Y12 signal also suppressed cisplatin-induced microglia hyperactivity. Furthermore, the microglia Src family kinase/p38 pathway is required for P2Y12-mediated cisplatin-induced pain hypersensitivity via the proinflammatory cytokine IL-18 production in the spinal cord. Blocking the P2Y12/IL-18 signaling pathway reversed cisplatin-induced pain hypersensitivity, as well as activation of N-methyl-D-aspartate receptor and subsequent Ca2+-dependent signals. Collectively, our data suggest that microglia P2Y12-SFK-p38 signaling contributes to cisplatin-induced pain hypersensitivity via IL-18-mediated central sensitization in the spinal, and P2Y12 could be a potential target for intervention to prevent chemotherapy-induced pain hypersensitivity. PERSPECTIVE: Our work identified that P2Y12/IL-18 played a critical role in cisplatin-induced pain hypersensitivity. This work suggests that P2Y12/IL-18 signaling may be a useful strategy for the treatment of chemotherapy-induced pain hypersensitivity.

[Analysis of the dynamic changes of blood hormone levels in H22 liver cancer mice of poisonous pathogenic factors syndromes to different degrees].

OBJECTIVE: To study the dynamic changes of blood hormone levels in H22 liver cancer mice of poisonous pathogenic factors syndromes (PPFS) to different degrees. METHODS: Two hundred and twenty mice were injected with H22 tumor cells from their armpits. On the ninth day after inoculation the mice of severe poisonous pathogenic factors syndrome (SPPFS) and of mild poisonous pathogenic factors syndrome (MPPFS) were screened. Besides, another normal control group consisting of 30 mice was set up. The mice were killed on the tenth and eleventh day after inoculation (as the 1st and 2nd time window). The weight of the tumor, the wet weight of the thymus and the spleen were weighed. The plasma adrenocorticotropic hormone (ACTH), corticosterone, aldosterone, thyroid hormone T3 and T4, testosterone, TNF-alpha, and IFN-gamma were detected by ELISA. All the aforesaid laboratory parameters were analyzed. RESULTS: The tumor weight was obviously larger in mice of the SPPFS group than in those of the MPPFS group at the same time window (P < or = 0.05). Compared with the normal control group, the thymus was obviously atrophied (P < or = 0.05), the spleen was significantly enlarged (P < or = 0.05), the plasma ACTH significantly increased (P < or = 0.05) in the SPPFS group at the two time windows. But the increment of ACTH was less in the MPPFS group. The plasma corticosterone showed similar tendency as that of ACTH. At the 1st time window the plasma testosterone significantly increased in the two groups (P < or = 0.05). The plasma testosterone and T4 showed a decreasing tendency in the SPPFS group. The plasma TNF-alpha and IFN-gamma levels showed an increasing trend in the two groups. Correlation study showed that the degree of PPFS was negatively correlated with qi deficiency (r = -0.766, P < or = 0.05) and T4 (r = -0.738, P < or = 0.05). The degrees of PPFS was positively correlated with the plasma ACTH level (r = 0.635, P < or = 0.05). The degree of qi deficiency was positively correlated with yang heat syndrome (r = 0.632, P < or = 0.05). The plasma ACTH was negatively correlated with T4 (r = -0.504, P < or = 0.05). The plasma testosterone was positively correlated with TNF-alpha (r = 0.619, P < or = 0.05). CONCLUSIONS: PPFS occurs naturally and shows difference to different degrees in the development of H22 liver cancer. The disorders of neuroendocrine hormones and the suppression of the immune function show dynamic changing trends.

[The correlation between adrenal corticosteroids and cytokines expressions in mice of different syndromes].

OBJECTIVE: To study the cytokines expressions in the adrenal gland and its correlation with serum adrenal corticosteroids in mice of different syndromes. METHODS: Using the quantitative four diagnosis and syndrome differentiation methods, 60 normal mice and 190 H22 liver cancer bearing mice were syndrome typed. Serum corticosterone and aldosterone were tested by ELISA, and mRNA expressions of cytokines in the adrenal gland were detected using Real-time PCR. RESULTS: Mice of different syndromes were obtained, such as normal mice of no syndrome, normal mice of vigorous qi syndrome, normal mice of qi deficiency syndrome, liver cancer bearing mice of excessive evil toxic syndrome, liver cancer bearing mice of evil lying in the middle syndrome, liver cancer bearing mice of weak evil toxic syndrome, and liver cancer bearing mice of poisonous pathogenic factors and qi deficiency syndrome. The serum corticosteroids were significantly higher in the liver cancer bearing mice than in the normal mice (P < 0.05). The cortex hormones increased most significantly in the liver cancer bearing mice of excessive evil toxic syndrome (P < 0.05). Compared with the normal mice, IL-1beta, IL-2, IL-6, IL-10, IL-12alpha, IL-12beta, and TNF-alpha gene expressions increased in the liver cancer bearing mice, while only expressions of IL-1alpha and IL-5 decreased. But the expressions of IL-13 and transforming growth factor beta1 (TGF-beta1) showed no regularity. The expressions of IL-4 and INF-alpha were not detected in all mice. It is notable that the more severe degree of poisonous pathogenic factors, the higher the expressions of serum corticosterone and aldosterone levels as well as IL-6, the lower expressions of IL-1beta, IL-2, IL-5, IL-12alpha, IL-12beta, and TNF-alpha. CONCLUSIONS: The increased serum corticosteroid level in liver cancer bearing mice could possibly be induced by chronic tumor stress, partial cytokines were involved in the synthesis and secretion of the adrenal hormone. Of them, IL-6 might positively regulate the secretion of corticosteroids, while IL-1beta, IL-2, IL-5, IL-12alpha, IL-12beta, and TNF-alpha might negatively regulate their secretions.

[Clinical study of type â ¢ prostatitis treated with "warming and promoting technique" of acupuncture combined with extracorporeal shock wave].

OBJECTIVE: To observe the clinical curative effect of wentongzhenfa (warming and promoting technique of acupuncture) combined with extracorporeal shock wave in treatment of type Ⅲ prostatitis. METHODS: A total of 96 patients with type Ⅲ prostatitis were randomly divided into an observation group (48 cases) and a control group (48 cases). In the control group, the extracorporeal shock wave was combined with even-needling technique of acupuncture at Guanyuan (CV4), Mingmen (GV4), Zhongji (CV3), Zusanli (ST36), etc. In the observation group, the extracorporeal shock wave was combined with "warming and promoting technique" of acupuncture at the same acupoints as the control group. The treatment lasted 30 min each time, once daily in either group. There were 2 days of interval after consecutive treatment for 5 days. Totally, the duration of treatment was 1 month in two groups. The clinical curative effect was assessed after treatment. Before and after treatment, the changes in the concentrations of tumor nerosis factor-α (TNF-α), interleukin-1ß(IL-1ß) and IL-6 in prostatic fluid were determined; and the symptoms were scored, i.e. frequent, urgent and burning painful urine, difficulty in urination, dribbling urine, distending pain in perineum, bitter taste and dry mouth, and scrotal dampness. The changes in the scores of National Institute of Health chronic prostatitis symptom index (NIH-CPSI), international index of erectile function (IIEF), visual analogue scale (VAS) were evaluated befroe and after treatment. Successively, before treatment, after treatment, as well as 1 and 3 months after treatment, the quality of life was evaluated by Karnofsky in the patients of two groups. RESULTS: After treatment, the total effective rate was 89.6% (43/48) in the observation group, higher than 70.8% (34/48) in the control group (P<0.05). Compared with those before treatment, the concentrations of TNF-α and IL-1ß in the prostatic fluid were all decreased (P<0.05) and the concentration of IL-6 was increased (P<0.05), the scores of symptoms, NIH-CPSI, IIEF and VAS were all reduced (P<0.05) in two groups. The changes of the above indexes were more obvious in the observation group than those in the control group (P<0.05). After treatment and 1 and 3 months after treatment, Karnofsky scores all increased (P<0.05) in two groups，and the increases were more significant in the observation group (P<0.05). CONCLUSION: "Warming and promoting technique" of acupuncture combined with extracorporeal shock wave promotes the elimination of local inflammatory factors, relieves clinical symptoms, improves the quality of life, as well as has a satisfactory short-term and medium-term curative effect on type Ⅲ prostatitis.

Changes in corneal nerve morphology and function in patients with dry eyes having type 2 diabetes.

BACKGROUND: Dry eye syndrome (DES) is a common disease with various clinical manifestations. DES had a significant association with diabetes. Blink reflex (BR) is also known as trigeminal nerve facial reflex. The stimulation of corneal nerves is one of the origins of BR stimulation. The parasympathetic fibers sent out through the facial nerve are the outlet of tear reflexes. BR can be used to assess the function of the corneal nerve closed-loop; however, whether the BR changes in these patients is unclear. AIM: To understand the morphology and function of the corneal nerve in patients with dry eyes having diabetes or not. METHODS: This study enrolled 131 patients who visited the inpatient and outpatient services of ophthalmology and endocrinology departments between January 2019 to August 2020 with subjective symptoms of dry eyes and non-dry eye reasons, as well as volunteers such as colleagues. The patients were divided into four groups: DEwDM, with dry eyes having type 2 diabetes mellitus (T2DM); DMnDE, with T2DM not having dry eyes; DEnDM, with dry eyes not having diabetes; and nDMnDE, with neither dry eyes nor diabetes. The tear film break-up time, Schirmer I test, in vivo confocal microscopy, and BR were performed. RESULTS: The DEwDM, DMnDE, DEnDM, and nDMnDE groups included 56, 22, 33, and 20 patients, respectively. Sex and age were not statistically different among the four groups. The nerve fiber length (NFL) of patients in the DEwDM, DEnDM, and DMnDE groups reduced (P < 0.001, P = 0.014, and P = 0.001, respectively). No significant difference in corneal nerve fiber density (NFD) (P = 0.083) and corneal nerve branch density (NBD) (P = 0.195) was found among the four groups. The R1 Latency of blink reflexes increased only in the DEwDM group (P = 0.008, P = 0.001, P < 0.001, compared with the DMnDE, DEnDM, and nDMnDE groups, respectively). The NBD and R1 Latency were different between DEwDM and DEnDM groups in patients with moderate and severe dry eyes. CONCLUSION: The corneal nerve morphology changed in patients with dry eyes or diabetes, or with both, while the function of corneal nerve closed-loop reduced only in those with dry eyes and diabetes.

Targeted delivery of maytansine to liver cancer cells via galactose-modified supramolecular two-dimensional glycomaterial.

A two-dimensional (2D) glycomaterial for targeted delivery of maytansine to liver cancer cells was developed. Host-guest interaction between a galactosyl dye and human serum albumin (HSA) produces supramolecular galactoside-HSA conjugates, which are then used to coat 2D MoS2. The 2D glycomaterial was shown to be capable of the targeted delivery of maytansine to a liver cancer cell line that highly expresses a galactose receptor, resulting in greater cytotoxicity than maytansine alone.

[Characteristics of gene expression of adrenal cortical steroid synthetase and its regulatory factor in mice with H22 liver cancer of different patterns].

OBJECTIVE: To study the characteristics of gene expression of adrenal cortical steroid synthetase and its regulatory factor in mice with H22 liver cancer of different patterns. METHODS: Syndromes revealed in mice with H22 tumor were differentiated by quantified four diagnostic methods and syndrome differentiation, and mice with commonly encountered patterns (A: evil-toxin accumulation pattern, B: qi-deficiency pattern, C: yang-qi deficiency pattern and D: qi-yin-yang deficiency pattern) were screened out for subjecting to the study. Two batches of GeneChip Mouse Exon 1.0 ST Array detection were performed in the selected mice for detecting the gene expressions of adrenal cortical steroid synthetase and its regulatory factor, with the analysis performed put stress on the differential expressions in mice of various syndrome patterns. RESULTS: Data obtained from the two batches detection showed well repeatability, in which similar genes of high or low expression emerged. The adrenal cortical steroid synthetase genes, such as Cyp11a1, Star, Cyp11b2, Cyp21a1, Hsd3b and Hsd17b were highly expressed, with few difference among the four patterns. However, Cyp11a1 was down-regulated and Cyp1b2 up-regulated in all patterns; Hsd3b1 and Cyp21a1 down-regulated in pattern A and B, but up-regulated in pattern C and D. As for the expressions of the relative regulatory factors, Cyb5b and Wnt4 were down-regulated but Fdx1, Fdxr, Hsd11b1, Por, Agt and Nr 0b1 were up-regulated in all patterns; Nr5al down-regulated in pattern A but up-regulated in other three patterns; Nr4al and Nr4a2 up-regulated in pattern A and down-regulated in the others. CONCLUSIONS: The adrenal cortical steroid synthetase genes are rather conservative and stable in mice bearing H22 liver cancer, part of the expression might be correlated to the condition of disease and essence of syndromes, embodying the differences among different patterns in the same disease.

[Emphasis on the T regulatory cells in stabilizing immunology of the eye].

T regulatory cells (Tregs) have been recognized as the hotspot in recent immunology research. Because of the capability of immune suppression, they play an important role in regulating many immune associated diseases. It has been reported that they are involved in stabilizing local immune microenvironment of the eye and regulating many eye diseases such as corneal transplantation immune rejection, uveitis, allergic conjunctivitis, infectious keratitis and dry eye. Treatment with Tregs may provide novel method for immune related eye diseases.

Topical Steroids and Antibiotics for Adult Blepharokeratoconjunctivitis (BKC): A Meta-Analysis of Randomized Clinical Trials.

PURPOSE: A meta-analysis was conducted to evaluate the efficacy and safety of topical treatments (including steroids and antibiotics) for adults with blepharokeratoconjunctivitis (BKC). METHODS: The following databases were searched for relevant randomised controlled trials (RCTs): China National Knowledge Infrastructure (CNKI), Web of Science, MEDLINE, PubMed, Embase, and Cochrane Central Register of Controlled Trials database (CENTRAL). Two reviewers selected studies and analyzed the risk of bias independently. The treatments were loteprednol 0.5%/tobramycin 0.3% (LE/T) and dexamethasone 0.1%/tobramycin 0.3% (DM/T). The efficacy outcome measures were change from baseline (CFB) in composite scores of ocular symptoms and signs; the CFB in the signs composite scores for blepharitis, conjunctivitis, and keratitis at each visit; the total ocular adverse event incidence (AEs); and the incidence of intraocular pressure (IOP) increase after treatment. Prepost mean differences (MDs) were compared for continuous outcome variables, and incidences were analyzed for dichotomous data. The pooled effect sizes were analyzed using 95% confidence intervals (CIs) in a fixed-effect model. Heterogeneity was evaluated using the Q-test and I 2 statistic. RESULTS: The CFB to final visit in ocular symptoms and signs of BKC was not statistically different between the two treatments (95% CI, -0.33 to 1.50; MD = 0.58; P=0.21). The CFB in signs composite scores for blepharitis (95% CI, -0.16 to 0.48; MD = 0.16; P=0.32), conjunctivitis (95% CI, -0.55 to 1.76; MD = 0.61; P=0.30), and keratitis (95% CI, 0.00-0.28; MD = 0.14; P=0.05) was also similar with the two treatments. LE/T was a safer intervention than DM/T, with fewer overall adverse events (95% CI, 0.34-0.80; RR = 0.52; P=0.003) and significantly less elevation of intraocular pressure (IOP) (95% CI, 0.32-0.70; RR = 0.47; P=0.0002). CONCLUSIONS: DM/T and LE/T are both effective treatments for BKC, but LE/T may be a safer intervention.

Adenovirus-mediated RNA interference against herpes simplex virus infection in vitro.

INTRODUCTION: Herpetic keratitis caused by the herpes simplex virus (HSV) is the most common form of ocular herpes that causes corneal blindness. Although treatments for herpes keratitis have improved in recent years. there is still considerable room for new treatments against viral infection that shows great promise. The aim of the study was to evaluate the effect of RNA interference on HSV Type 1 (HSV1) infection in vitro, first prophylactically then therapeutically. MATERIAL AND METHODS: The highly conserved glycoproteins D (gD) and E (gE) were chosen as targets for this study. Different small interfering RNA (siRNA) duplexes that target gD and gE were designed and chemically synthesized. The recombinant adenovirus type 5 was developed and used as the vehicle with which we delivered the siRNA into the Vero cells infected with the HSV1 KOS strain. Evaluation of the efficacy of siRNA-mediated inhibition was performed either before virus inoculation (prophylactically) or after virus inoculation at the first appearance of lesions (therapeutically). The expression of messenger RNA encoding gD and gE was detected using a real-time polymerase chain reaction (qPCR). We analyzed HSV replication in Vero cells, cytotoxicity of HSV, and cell viability. RESULTS: When used prophylactically, the siRNA-targeting gD and gE created a more marked decrease in viral titer than when used therapeutically. The transfection of cells with recombinant adenovirus containing the siRNA expression cassette was associated with very low cytotoxicity. CONCLUSIONS: Adenovirus-mediated siRNA-targeting gD and gE genes effectively inhibit the replication of the HSV in Vero cells. In addition, these findings indicate that the prophylactic use of siRNA is far more effective at inhibiting HSV replication than the therapeutic use.