An outbreak of epidemic keratoconjunctivitis caused by human adenovirus type 8 in primary school, southwest China.

BACKGROUND: Two outbreaks of epidemic keratoconjunctivitis (EKC) occurred successively with an interval of 5 days in two primary boarding schools in Weixi Lisu Autonomous County, Diqing, and Tibetan Autonomous Prefecture, Yunnan. The aims of this study were to determine the intensity and characteristics of the outbreaks, as well as the clinical manifestations in the patients, the risk factors for infection and the pathogen responsible for the two outbreaks. METHODS: An outbreak investigation was conducted in two primary schools, and a case-control study including patients from the Weixi County Ethnic Primary School was performed. Relevant specimens were collected according to the case definition, and next-generation sequencing was employed to identify the pathogen. An epidemiological investigation method was used to analyse the related epidemiological characteristics, such as risk factors. The phylogenetic tree was constructed by MEGA 7.0. RESULTS: A total of 331 acute conjunctivitis cases, including probable cases of EKC, were reported in the two schools, and the attack rates were 30.59% (171/559, 95%CI: 26.76-34.42) and 20.41% (160/784, 95%CI: 17.58-23.24), respectively. Cases occurred in all grades and classes in both schools, and only one staff member in each school presented illness. The epidemics lasted for 54 days and 45 days, respectively. The patients had typical manifestations of EKC, such as acute onset, follicular hyperplasia, pseudomembrane formation, preauricular lymphadenopathy, corneal involvement and blurred vision, and a relatively long disease course (average 9.40 days, longest 23 days and shortest 7 days). The risk factor for infection was close contact with a patient or personal items contaminated by a patient. The pathogen responsible for the outbreaks was HAdV-8. The virus was highly similar to the 2016 HAdV-8 strain from Tibet, China. CONCLUSIONS: This study strongly suggests that HAdV-8 could lead to serious consequences. This is the second report of a HAdV-8-associated EKC outbreak in mainland China. Tibetan HAdV-8 might be circulating in southwest China; therefore, it is necessary to monitor the pathogens causing acute conjunctivitis in this area.

Ghrelin attenuates ultraviolet B radiation-induced impairment in capacities of epidermal stem cells.

Persistent exposure to solar ultraviolet radiation (UVR) causes continuous damages to skin, including progressive impairment of epidermal stem cells (ESCs) capacities. Ghrelin is the only known endogenous orexigenic hormone, which has displayed its various pharmacological functions. In the current study, we found that the specific receptor of ghrelin, growth hormone secretagogue receptor (GHS-R), is expressed in ESCs. Interestingly, GHS-R expression is significantly upregulated in response to ultraviolet B (UVB) radiation. We also found that ghrelin treatment prevented UVB radiation-induced reduction in cell viability and the release of lactate dehydrogenase (LDH). Additionally, ghrelin reduced UVB radiation-induced generation of reactive oxygen species (ROS) and restored the intracellular level of reduced glutathione (GSH). UVB radiation significantly suppressed the expressions of integrin ß1 and Krt19, the two major ESC markers, which were restored by ghrelin. Notably, knockdown of GHS-R abolished the effects of ghrelin on the expressions of integrin ß1 and Krt19, suggesting the involvement of GHS-R. Also, we found that ghrelin treatment inhibited UVB radiation- induced reduction of Wnt1, Wnt3a, Myc, and cyclin D1 at both the mRNA levels and the protein levels. Taken together, our findings identify a novel function of ghrelin on maintaining the capacities of ESCs against UVB radiation.

[Long-term results of personalized treatment in 72 breast cancer patients who failed chemotherapy].

OBJECTIVE: To evaluate the efficacy and prognostic factors of personalized treatment for breast cancer patients who failed chemotherapy. METHODS: Seventy-two patients with breast cancer who failed chemotherapy were treated at the Tumor Hospital of Harbin Medical University from January 2001 to January 2012. Among them, 42 cases received 5.6 cycles (range, 4-8 cycles) of postoperative adjuvant chemotherapy, and 30 cases received 12.2 cycles (range, 6-22 cycles), both postoperative adjuvant and salvage chemotherapy. All of the 72 patients of stage IV were given personalized treatment. Under guidance of the principle that multidisciplinary treatment improves control rate but does not or less damage the normal tissues and host immune function, precise radiotherapy combined with Chinese herbal medicine (CHM), biological agent and others were chosen for the patients. RESULTS: The median survival time was 20 months. Univariate analysis showed that non-invasive ductal carcinoma, less metastasized organs, without brain, liver and lung metastasis, Karnofsky performance scores ≥ 80, not combined with chemotherapy, and multiple courses of Chinese herbal medicine and biolojical agent treatment had significant impact on survival (P < 0.05). Multivariate analysis showed that no brain metastasis, non-invasive ductal carcinoma, and Chinese herbal medicine and biological agent treatment ≥ 7 courses and not combined with chemotherapy had obvious significance (P < 0.05). The rate of grade 3 and 4 treatment-related hematological toxicity was 8.3% (6/72) and 5.6% (4/72), respectively. All the patients with grade 4 hematological toxicity were the cases of grade 3 at hospital admission. No grade 3 and 4 acute radiation damages of the lung and liver were noticed. CONCLUSION: Chinese herbal medicine combined with biological agents and others prolongs survival time in breast cancer patients who failed chemotherapy, and provides an alternative treatment modality for them.

Mechanism of glutamate receptor for excitation of medial vestibular nucleus induced by acute hypotension.

In the vestibular nuclei, acute hypotension induces excitation of electrical activity and expression of c-Fos protein and phosphorylated extracellular signal-regulated kinase (pERK). Expression of c-Fos protein and pERK is mediated by the excitatory neurotransmitter, glutamate. We investigated the signaling pathway of glutamate and its receptors in the vestibular nuclei following acute hypotension in conscious rats. Glutamate release and the expression of c-Fos protein in the medial vestibular nuclei (MVN) were measured by microdialysis and immunohistochemical analysis, respectively. We compared the responses of rats with unilateral labyrinthectomy to unaltered controls. Acute hypotension was induced by infusing sodium nitroprusside (SNP) into the femoral vein. In the control group, glutamate release and the expression of c-Fos protein increased in the bilateral MVN following acute hypotension. In the unilateral labyrinthectomy group, glutamate release and the expression of c-Fos protein increased in the MVN contralateral to the lesion, but did not change in the ipsilateral MVN following acute hypotension. Microinjection of NMDA or AMPA into the lateral ventricle increased the expression of c-Fos protein in the bilateral MVN of conscious intact labyrinthine rats. However, after intracerebroventricular microinjection of MK-801 or CNQX little c-Fos protein was expressed in the bilateral MVN of these rats following acute hypotension. These results suggest that in response to acute hypotension, excitatory afferent signals from the peripheral vestibular receptors release glutamate into postsynaptic neurons in the vestibular nuclei. These excitatory signals are transmitted through the NMDA receptors and AMPA receptors of glutamate in the vestibular system.

cAMP produced by pituitary adenylate cyclase-activating polypeptide 27 inhibits atrial natriuretic peptide secretion in rabbit beating atria.

The aim of the present study was to determine the effects of increased cAMP levels in response to pituitary adenylate cyclase-activating polypeptide 27 (PACAP27) on atrial atrial natriuretic peptide (ANP) secretion in rabbit atria. A perfused beating atrial model was used in the present study and cAMP efflux and ANP levels in atrial perfusates were measured by radioimmnoassay. At 100 nmol/L, PACAP27 increased cAMP production, which resulted in subsequent inhibition of ANP secretion. Nicardipine (1.0 micromol/L), an L-type Ca2+ channel blocker, attenuated inhibition of ANP secretion by PACAP27. Staurosporine (1.0 micromol/L), a non-specific protein kinase inhibitor, and H-89 (1.0 micromol/L), a cAMP-dependent protein kinase A (PKA) inhibitor, completely blocked the inhibition of ANP secretion in response to PACAP27 but had no effect on PACAP27-induced increases in cAMP. In conclusion, the results suggest that increased cAMP levels in response to PACAP27 negatively regulate ANP secretion via the adenylate cyclase-cAMP-PKA signalling pathway in rabbit atria and that L-type Ca2+ channels may be involved, in part, in the regulation of ANP secretion by cAMP.

[Effects of purinergic analogues on spontaneous contraction and electrical activities of gastric antral circular muscle in guinea-pig].

In order to investigate the role of non-adrenergic non-cholinergic nerves in regulating mechanical and electrical activity of gastric circular smooth muscle, the effects of ATP and its analogues on gastric motility and electrical activities were observed in guinea-pig. In organ bath system, isometric force of the circular smooth muscle of guinea-pig gastric antrum was measured. Electrical activity of the muscle was recorded by using intracellular microelectrode. Electrical and mechanical activities were recorded by chart recorder. ATP and 2-MeSATP potentiated the mechanical activity but did not affect electrical activity in gastric circular smooth muscle. ATP and 2-MeSATP-induced contraction was effectively blocked by nonselective P2y-purinoceptor antagonist, reactive-blue-2 and suramin, but ATP-induced contraction was not blocked by alpha,beta-MeATP-induced desensitization of P2x-purinoceptors. However, alpha,beta-MeATP, P2x-purinoceptor agonist, attenuated slow waves with membrane hyperpolarization and inhibited contraction. The relaxation by beta,gamma-MeATP was blocked by alpha,beta-MeATP-induced desensitization of P2x-purinoceptors. ATP-induced contraction was blocked by external calcium-free, but not by nicardipine, a L-type calcium channel blocker. Indomethacin, a nonselective cyclooxygenase inhibitor, did not block ATP-induced contraction. The results suggest that: (1) ATP- and analogues-induced contraction is mediated by P2y-purinoceptor, whereas alpha,beta-MeATP-induced relaxation by P2x-purinoceptor in guinea-pig gastric antral circular smooth muscle. (2) ATP-induced contraction is dependent on extracellular calcium, but Ca2+ entry is not mediated by L-type calcium channel. (3) Prostaglandins are not involved in ATP- and analogue-induced contraction of gastric circular smooth muscle in guinea-pigs, and alpha,beta-MeATP-induced relaxation is related to membrane hyperpolarization.