Poly(ADP-ribose) polymerase(PARP) is a protein-modifying and nucleotide-polymerizing enzyme. As a critical element in DNA repair, PARP can be activated by DNA strand breaks. Excessive activation of PARP, however, can deplete NAD + and ATP, leads to cell death. Cleavage of PARP by activated caspase-3 play an important role in cell apoptosis.

AIM: To study the effect of cholecystokinin octapeptide(CCK-8) on lipopolysaccharide (LPS)-stimulated pulmonary interstitial macrophage(IM) in vitro. METHODS: Pulmonary IM were isolated and cultured in the presence of LPS, CCK-8, proglumide(the antagonist of CCK receptors) and vehicle alone or together. The expression of mCD14 protein was assayed by flow cytometry, and sCD14 in the supernatant was analyzed semi-quantitatively by Western blot, and TNF-? in the supernatant was detected with ELISA. RESULTS: CCK-8, at concentrations from 10 -7 mol/L to 10 -6 mol/L inhibited significantly the expression of mCD14, the release of sCD14 and TNF-? to the supernatant up-regulated by LPS(1 mg/L). The effect of CCK-8 was inhibited by proglumide. CONCLUSION: CCK-8 modulated negatively several functions of LPS-stimulated pulmonary IM through CCK receptors, which may be one of the mechanisms for CCK-8 to alleviate the inflammation in lung tissues during endotoxemia.

Objective To evaluate clinical efficacy and safety of levornidazole in the treatment of pelvic anaerobic infections. Methods A multicenter randomized controlled clinical study was conducted to evaluate clinical efficacy and safety of levornidazole. One hundred and fourty-three patients with pelvic anaerobic bacteria infection were classified into 70 cases treated by levornidazole in study group and 73 cases treated by Ornidazole in control group. Those patients in two groups were both administered at a dose of 0. 5 g twice daily for 5 - 7 days. The rate of clinical efficacy, bacteria clearance and adverse effect were recorded and compared between two groups. Results At the endpoint, the rate of clinical efficacy were 80% (56/70) in study group and 81% (59/73) in control group, which did not reach significant difference (P＞0. 05). The rate of bacteria clearance were 97% (36/37) in study group and 92% (22/24) in control group, which also did not reach significant difference(P ＞0. 05). The rate of adverse reaction of 3% (20/70) in study group was significantly lower than 22% ( 16/73 ) in control group ( P ＜ 0. 05 ). Conclusion It is effective and safe to treat pelvic anaerobic infections with levornidazole and sodium chloride injection.

BACKGROUND:Lipoic acid, with a closed circle structure composed by sulphur and carbon atoms, exerts strong anti-oxidation, and has been extensively applied in the prevention and treatment of oxidative stress, diabetic cataract, diabetic neuropathy and cardiovascular diseases. OBJECTIVE:To investigate the protective effect of lipoic acid on peripheral nerve function during peripheral nerve ischemia/reperfusion injury. METHODS:Models of peripheral nerve ischemia/reperfusion injury were established in rabbits, and then rabbit models were then allotted to treatment and non-treatment groups. The treatment group was subdivided into experimental (injection of lippoic acid) and control groups according to the use of lipoic acid at 1, 3 and 6 hours after ischemia and before reperfusion. The ultrastructural changes of the sciatic nerve were observed under electron microscope, and the electrophysiological changes of the sciatic nerve were detected using evoked potential instrument. RESULTS AND CONCLUSION:With the ischemic time increasing, the number of vacuoles in the axon increased gradually, accompanied by axonal atrophy, and Waller's degeneration in the aggregated microfilaments. The myelin sheath thickening and dissolving were visible. All above phenomena became severest at 6 hours after ischemia. Compared with the control groups, lipoic acid reduced the number of the vacuoles in the axon and all eviated axonal atrophy, Waller's degeneration and demyelination. As the ischemic time increasing, the latency of sciatic nerve was significantly increased, and peaked at 6 hours of ischemia;while the amplitude was significantly decreased, and reached a minimum at 6 hours of ischemia. Compared with the control groups, in the experimental groups, the latency of sciatic nerve was significantly decreased, but the amplitude was significantly increased. These results suggest that lipoic acid provides neuroprotection against peripheral nerve ischemia/reperfusion injury.

[ ABSTRACT] AIM:To investigate the effects of Chaihu Shugan powder ( CSP) on lipid metabolism and the pro-teins involved in adenosine 5’-monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver tissues of the rats with non-alcoholic fatty liver disease (NAFLD).METHODS: Sprague-Dawley rats were randomly di-vided into normal control ( NC) group, with HFD ( HFD) group and CSP group.The NAFLD models were established by feeding with HFD for 16 weeks in the rats.The rats in CSP group were intragastrically administered with CSP extracts (9.6 g· kg-1 · d-1 ) , and blood and liver samples were collected 16 weeks later.Serum and liver levels of total cholesterol ( TC) and triglyceride ( TG) , and serum levels of alanine aminotransferase ( ALT) and aspartate aminotransferase ( AST) were measured using an automatic biochemical analyzer.The histological changes of liver tissues were observed with HE staining, while the lipid deposition was observed with Oil Red O staining.The ultrastructural changes of the liver tissues were observed under transmission electron microscope.Moreover, the protein levels of AMPK, phosphorylated AMPK (pAMPK), SIRT1 and uncoupling protein 2 (UCP2) in the liver were detected by Western blot.RESULTS:The results of HE staining, Oil Red O staining and electron microscopy demonstrated that NAFLD rat model was successfully estab-lished.Compared with NC group, the serum and liver levels of TC and TG, and serum level of AST in model group were markedly elevated ( P<0.01) .Moreover, the protein levels of pAMPK and SIRT1 in HFD group were markedly reduced (P<0.01), whereas UCP2 level was elevated (P<0.01).Furthermore, liver levels of TC and TG, and serum level of AST in GSP group were markedly reduced as compared with HFD group ( P<0.05 ) .The protein levels of pAMPK and SIRT1 were elevated ( P<0.05 ) , whereas the UCP2 level was reduced as compared with HFD group ( P<0.01 ) .The protein level of AMPK between the 3 groups had no significant difference.CONCLUSION: CSP attenuates hepatic lipid disorder and hepatic lipid deposition in NAFLD rats induced by feeding with HFD for 16 weeks, which is associated with the activation of AMPK/SIRT1 pathway.

To investigate the expression of microRNA-34a (miR-34a) in patients with chronic lymphocytic leukemia (CLL) in Xinjiang Uygur and Han nationalities and its prognostic significance. Our data showed that miR-34a expression in Uygur and Han CLL patients was significantly higher than that in their respective healthy controls, while miR-34a levels were similar between Uygur and Han patients. By comparing with known prognostic factors, receiver operating characteristic (ROC) curves showed that miR-34a was a good predictive factor for the prognosis of CLL (demarcation value was 3.567 6). Survival analysis was further performed according to miR-34a expression level, that low expression of miR-34a translated into poor prognosis.

OBJECTIVE: To explore the genetic basis for fetus with short limbs detected by prenatal ultrasonography. METHODS: Results of clinical imaging of the fetus was collected. Amniotic fluid sample was collected through amniocentesis for the extraction of fetal DNA. Whole exome sequencing was carried out to detect variants related to the clinical phenotypes. Candidate variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasound showed that the fetus had short limbs but no other abnormality. Whole exome sequencing has identified that the fetus carried two heterozygous pathogenic variants c.484G>T and c.1436dupA of the SLC26A2 gene, for which its mother and father were heterozygous carriers, respectively. CONCLUSION The fetus was diagnosed with atelosteogenesis type 2 by combined prenatal ultrasonography and whole exome sequencing, which may be attributed to the compound heterozygous variants of the SLC26A2 gene. Above findings provided evidence for the diagnosis of the fetus and genetic counseling.

Objective:To investigate the effect of pretreatment with butorphanol on perineal discomfort caused by intravenous injection of dexamethasone sodium phosphate.Methods:Using the method of prospective study, ninety patients undergoing elective gynecological surgery in Dalian Women And Children′s Medical Group from June to December 2021 were randomly divided into three groups: butorphanol 0.5 mg pretreatment group (group B1), butorphanol 1.0 mg pretreatment group (group B2) and normal saline control group (group C), with 30 cases in each group. Patients in groups B1 and B2 were given butorphanol 0.5 mg and 1.0 mg intravenously, respectively, prior to induction of anesthesia, while those in group C were given 0.9% sodium chloride injection. 3 minutes later, all patients in the three groups were given dexamethasone sodium phosphate injection 10 mg, and the incidence, grade and adverse reactions of their perineal discomfort symptoms were recorded.Results:The incidence of perineal discomfort and moderate perineal discomfort of patients in group B1 and group B2 was lower than that in group C: 20.00%(6/30)and 10.00%(3/30)vs. 60.00%(18/30), 3.33%(1/30)and 3.33(1/30)vs. 30.00%(10/30), with a statistically significant differences ( P<0.05). The incidence of adverse reactions such as dizziness was increased in the group B2:26.67%(8/30)and 10.00%(3/30)vs. 40.00%(12/30), with a statistically significant difference ( χ2 = 7.13, P = 0.028). Conclusions:Butorphanol 0.5 mg and 1.0 mg pretreatments are touted as effective in inhibiting perineal discomfort caused by intravenous injection of dexamethasone sodium phosphate. However, the butorphanol 0.5 mg pretreatment group have fewer adverse reactions.

OBJECTIVE To analyze the influential factors on trough concentration （cmin） and area under the drug concentration time curve （AUC） of voriconazole （VRZ） in pediatric patients with thalassemia undergoing hematopoietic stem cell transplantation （HSCT）. METHODS A total of 60 pediatric patients with thalassemia undergoing HSCT who used VRZ for prevention or treatment of invasive fungal infection were collected in our hospital from January 2021 to January 2024. The plasma concentration of VRZ was measured by high-performance liquid chromatography and the AUC was calculated. The factors affecting cmin and AUC of VRZ were analyzed using multiple linear regression. RESULTS A total of 120 cases of VRZ cmin in 60 pediatric patients was obtained and 27 cases of VRZ AUC in 26 pediatric patients were obtained. The median concentration of VRZ cmin was 0.31 mg/L； 46 cases had a cmin in 0.5-5 mg/L（ 38.33%）， 2 cases had a cmin＞5 mg/L（ 1.67%）， and 72 cases had a cmin＜0.5 mg/L. The median AUC of VRZ was 11.68 mg·h/L. The patient’s body weight， HSCT postoperative days， lymphocyte count， and combined use of phenytoin sodium， tacrolimus or cyclosporine had significant effects on VRZ cmin （P＜0.05）. Lymphocyte count and combined use of phenytoin sodium had significant effects on VRZ AUC （P＜0.05）. CONCLUSIONS The body weight， HSCT postoperative days， lymphocyte count， and combined use of phenytoin sodium， tacrolimus or cyclosporine are independent factors affecting VRZ cmin. Lymphocyte count and combined use of phenytoin sodium are independent factors affecting VRZ AUC.