Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase (HO-1) signaling pathway in the attenuation of endotoxin-induced acute lung injury (ALI) by hydromorphone and the relationship with Golgi apparatus stress (GA stress) in mice.Methods:Eighteen SPF wild-type (WT) and 18 Nrf2 knockout (Nrf2 KO) male C57BL/6J mice, aged 6-8 weeks, weighing 18-20 g, were divided into 3 groups ( n=6 each) using a random number table method: control groups (WT+ Con group, Nrf2 KO+ Con group), ALI groups (WT+ ALI group, Nrf2 KO+ ALI group) and ALI+ hydromorphone groups (WT+ ALI+ HM group, Nrf2 KO+ ALI+ HM group). ALI was induced by injecting lipopolysaccharide (LPS) 15 mg/kg via the tail vein in anesthetized animals. Hydromorphone 120 μg was intraperitoneally injected at 15 min before LPS injection in WT+ ALI+ HM group and Nrf2 KO+ ALI+ HM group, and the equal volume of normal saline was given instead in control groups. The animals were sacrificed after anesthesia at 12 h after LPS injection, and lung tissues were obtained for examination of the pathological changes which were scored and Golgi ultrastructure (with a transmission electron microscope) and for determination of the content of malondialdehyde (MDA), activity of superoxide dismutase (SOD), and expression of Nrf2, HO-1 and Golgi stress-related markers (Golgi matrix protein 130 [GM130], Golgi autoantigen 97 kDa [Golgin-97], ATPase secretory pathway Ca 2+ Transporting 1 [ATP2C1], Golgi phosphoprotein 3 [GOLPH3]) (by Western blot). Results:Compared with WT+ Con group and Nrf2 KO+ Con group, the lung injury scores and content of MDA were significantly increased, the activity of SOD was decreased, the expression of GM130, Golgin-97 and ATP2C1 was down-regulated, the expression of GOLPH3 was up-regulated ( P<0.05), no significant changes were found in the expression of Nrf2 and HO-1 ( P>0.05), and the damage to the Golgi apparatus was aggravated in WT+ ALI group and Nrf2 KO+ ALI group. Compared with WT+ ALI group, the lung injury scores and content of MDA were significantly decreased, the activity of SOD was increased, the expression of Nrf2, HO-1, GM130, Golgin-97 and ATP2C1 was up-regulated, the expression of GOLPH3 was down-regulated ( P<0.05), and the damage to the Golgi apparatus was significantly attenuated in WT+ ALI+ HM group. Compared with Nrf2 KO+ ALI group, the lung injury scores were significantly decreased, and the activity of SOD was increased ( P<0.05), no significant changes were found in the content of MDA and expression of Nrf2, HO-1, GM130, Golgin-97, ATP2C1 and GOLPH3 ( P>0.05), and no significant reduction in the damage to the Golgi apparatus was found in Nrf2 KO+ ALI+ HM group. Compared with WT+ ALI+ HM group, the lung injury scores and content of MDA were significantly increased, the activity of SOD was decreased, the expression of Nrf2, HO-1, GM130, Golgin-97 and ATP2C1 was down-regulated, the expression of GOLPH3 was up-regulated ( P<0.05), and the damage to the Golgi apparatus was aggravated in Nrf2 KO+ ALI+ HM group. Conclusions:Nrf2/HO-1 signaling pathway is involved in the attenuation of endotoxin-induced ALI by hydromorphone, and it is associated with the inhibition of Golgi stress.

Objective:To evaluate the clinical efficacy of TCM acupoint application combined with Fuyang cupping in the treatment of chronic bronchitis with lung and kidney yin deficiency syndrome.Methods:A randomized controlled trial study was conducted. From July 2022 to July 2024, 96 patients with chronic bronchitis in our hospital were selected as the observation subjects and divided into two groups using a random number table method, with 48 cases in each group. The control group received treatment with Fuyang cupping, while the study group received treatment with Fuyang cupping and acupoint application. Both groups were treated continuously for 14 days. TCM syndrome scores were performed before and after treatment, and serum TNF-α, CRP, and procalcitonin (PCT) levels were detected using ELISA. Arterial oxygen partial pressure (PaO 2) and carbon dioxide partial pressure (PaCO 2) were measured using a blood gas analyzer. FVC, FEV1, and FEV1 percentage of predicted values (FEV1% predicted value) and maximum expiratory flow (PEF) were measured using a pulmonary function analyzer. The relief time of clinical symptoms such as cough, sputum production, and wheezing during the treatment period were observed and recorded, and the clinical efficacy was evaluated. Results:The total effective rate of the research group was 95.83% (46/48), while that of the control group was 79.16% (38/48), with statistical significance ( χ2=6.10, P=0.013). After treatment, the scores of cough, sputum, wheezing, wheezing, and dry throat and mouth in the study group were lower than those in the control group ( t values were 4.86, 5.89, 5.23, 4.10, 5.49, respectively, P<0.01); PaO 2 level [(95.63 ± 6.45) mmHg vs. (88.44 ± 5.76) mmHg, t=5.76] was higher than of the control group ( P<0.01), and the PaCO 2 level [(40.12 ± 4.28) mmHg vs. (45.63 ± 4.36) mmHg, t=6.25] was lower than of the control group ( P<0.01); the levels of FEV1 [(2.64 ± 0.69) L vs. (1.97 ± 0.74) L, t=4.59], FEV1% predicted value (79.25 ± 11.27 vs. 62.55 ± 10.56, t=7.49), FVC [(3.05 ± 1.04) L vs. (2.06 ± 0.96) L, t=4.85], and PEF [(241.54 ± 19.85) L/min vs. (221.36 ± 19.65) L/min, t=5.01] were higher than those in the control group ( P<0.01); the levels of TNF-α, CRP and PCT in the serum were lower than those in the control group ( t values were 4.39, 6.51 and 18.59, respectively, P<0.001). Conclusion:TCM acupoint application combined with Fuyang cupping can effectively improve the TCM syndrome score and lung function, inhibit inflammatory factor levels, and improve clinical efficacy in chronic bronchitis patients with lung and kidney yin deficiency syndrome.

Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase (HO-1) signaling pathway in the attenuation of endotoxin-induced acute lung injury (ALI) by hydromorphone and the relationship with Golgi apparatus stress (GA stress) in mice.Methods:Eighteen SPF wild-type (WT) and 18 Nrf2 knockout (Nrf2 KO) male C57BL/6J mice, aged 6-8 weeks, weighing 18-20 g, were divided into 3 groups ( n=6 each) using a random number table method: control groups (WT+ Con group, Nrf2 KO+ Con group), ALI groups (WT+ ALI group, Nrf2 KO+ ALI group) and ALI+ hydromorphone groups (WT+ ALI+ HM group, Nrf2 KO+ ALI+ HM group). ALI was induced by injecting lipopolysaccharide (LPS) 15 mg/kg via the tail vein in anesthetized animals. Hydromorphone 120 μg was intraperitoneally injected at 15 min before LPS injection in WT+ ALI+ HM group and Nrf2 KO+ ALI+ HM group, and the equal volume of normal saline was given instead in control groups. The animals were sacrificed after anesthesia at 12 h after LPS injection, and lung tissues were obtained for examination of the pathological changes which were scored and Golgi ultrastructure (with a transmission electron microscope) and for determination of the content of malondialdehyde (MDA), activity of superoxide dismutase (SOD), and expression of Nrf2, HO-1 and Golgi stress-related markers (Golgi matrix protein 130 [GM130], Golgi autoantigen 97 kDa [Golgin-97], ATPase secretory pathway Ca 2+ Transporting 1 [ATP2C1], Golgi phosphoprotein 3 [GOLPH3]) (by Western blot). Results:Compared with WT+ Con group and Nrf2 KO+ Con group, the lung injury scores and content of MDA were significantly increased, the activity of SOD was decreased, the expression of GM130, Golgin-97 and ATP2C1 was down-regulated, the expression of GOLPH3 was up-regulated ( P<0.05), no significant changes were found in the expression of Nrf2 and HO-1 ( P>0.05), and the damage to the Golgi apparatus was aggravated in WT+ ALI group and Nrf2 KO+ ALI group. Compared with WT+ ALI group, the lung injury scores and content of MDA were significantly decreased, the activity of SOD was increased, the expression of Nrf2, HO-1, GM130, Golgin-97 and ATP2C1 was up-regulated, the expression of GOLPH3 was down-regulated ( P<0.05), and the damage to the Golgi apparatus was significantly attenuated in WT+ ALI+ HM group. Compared with Nrf2 KO+ ALI group, the lung injury scores were significantly decreased, and the activity of SOD was increased ( P<0.05), no significant changes were found in the content of MDA and expression of Nrf2, HO-1, GM130, Golgin-97, ATP2C1 and GOLPH3 ( P>0.05), and no significant reduction in the damage to the Golgi apparatus was found in Nrf2 KO+ ALI+ HM group. Compared with WT+ ALI+ HM group, the lung injury scores and content of MDA were significantly increased, the activity of SOD was decreased, the expression of Nrf2, HO-1, GM130, Golgin-97 and ATP2C1 was down-regulated, the expression of GOLPH3 was up-regulated ( P<0.05), and the damage to the Golgi apparatus was aggravated in Nrf2 KO+ ALI+ HM group. Conclusions:Nrf2/HO-1 signaling pathway is involved in the attenuation of endotoxin-induced ALI by hydromorphone, and it is associated with the inhibition of Golgi stress.

Objective To evaluate effect of dexmedetomidine on mitochondrion-dependent apoptosis during hypoxia-reoxygenation (H/R) injury to hippocampal neurons of rats.Methods The primarily cultured hippocampal neurons of Sprague-Dawley rats were divided into 4 groups (n =40 each) using a random number table method:control group (C group),vehicle group (V group),H/R group and dexmedetomidine group (D group).Hippocampal neurons were subjected to oxygen-glucose deprivation followed by restoration of oxygen supply to establish the model of H/R injury.Dexmedetomidine 1 μmol/L was added at 6 h of reoxygenation in D group.The viability of neurons was measured by methyl thiazolyl tetrazolium assay at 20 h of reoxygenation.The ultrastructure of mitochondria was observed by transmission electron microscopy.The expression of cytochrome c (Cyt c),caspase-3,Fis1 and Drp1 was detected by Western blot.The neuronal apoptosis was detected by flow cytometry,and apoptosis rate was calculated.Results Compared with C group,no significant change was found in the viability of neurons in group V (P＞0.05),and the viability of neurons was significantly decreased,the apoptosis rate was increased,the expression of Cyt c,caspase-3,Fis1 and Drp1 was up-regulated (P＜0.05),and the damage to mitochondrial ultrastructure was accentuated in H/R and D groups.Compared with H/R group,the viability of neurons was significantly increased,the apoptosis rate was decreased,the expression of Cyt c,caspase-3,Fis1 and Drp1 was down-regulated (P＜0.05),and the damage to mitochondrial ultrastructure was significantly attenuated in D group.Conclusion The nechanism by which dexmedetomidine reduces the H/R injury to hippocampal neurons is related to inhibiting mitochondrion-dependent apoptosis in rats.

Objective To retrospectively analyze the efficacy and toxicity of intensity?modulated radiotherapy ( IMRT) alone and IMRT with concurrent chemotherapy ( CRT) in the treatment of early?stage nasopharyngeal carcinoma ( NPC) using pairwise group comparison. Methods A total of 98 patients with stage T1?2N1M0 NPC were treated with IMRT alone or CRT from 2009 to 2010, and 39 pairs out of them were selected for comparison of efficacy and toxicity. The survival rates were calculated using the Kaplan?Meier method and analyzed using the log?rank test. Results The 3?year follow?up rate was 95%. There were no significant differences in the 3?year overall survival ( OS ) , progression?free survival ( PFS ) , local recurrence?free survival ( LRFS ) , and distant metastasis?free survival ( DMFS ) rates between the IMRT alone group and the CRT group ( 97% vs. 95%, P=0?411;97% vs. 92%, P=0?301;97% vs. 97%, P=0?606;100% vs. 92%, P=0?082) . The incidence rates of leucopenia, anemia, and thrombocytopenia were significantly higher in the CRT group than in the IMRT alone group ( P=0?000;P=0?000;P=0?000 ) . There were no significant differences in the incidence rates of grade 3 oral mucositis and hearing loss between the IMRT alone group and the CRT group ( 26% vs. 23%, P= 0?093;41% vs. 62%, P= 0?100 ) . Conclusions CRT fails to increase the OS, PFS, and LRFS rates and reduce the DMFS rate in patients with stage T1?2 N1 NPC. Moreover, CRT results in higher incidence rates of hematotoxicity, grade 3 mucositis, and hearing loss than IMRT alone.

Objective To investigate the FECH gene mutation in a Chinese family with erythropoietic protoporphyria, to explore the relationship between gene mutation and clinical manifestations so as to estab-lish a basis for the genetic diagnosis and treatment of erythropoietic protoporphyria. Methods Clinical data on a Chinese family with typical EPP was collected. Peripheral blood was obtained from patients, unaffected individuals in the family and 50 unrelated human controls. Genomic DNA was extracted and PCR was per-formed to amplify the whole coding regions (exons 1 to 11) of FECH gene and their flanking intron sequences followed by direct sequencing to detect possible mutations. Results Based on clinical symptom and por-phyrin levels, a diagnosis of erythropoietic protoporphyria was made in 3 family members. DNA fragments of expected size were amplified by PCR. Gene sequencing revealed a heterozygons mutation (IVS1 + 1G >C) in intron 1 of FECH gene in the proband, his sister and father, but not in unaffected family members or unrelated human controls. Also, an IVS1-23C/T polymorphism associated with low expression alleles was observed in intron 1 of FECH gene of the proband, his sister and mother. Conclusions A novel mutation in the donor splice site of intron 1 of FECH gene is first reported in a Chinese family with EPP; this muta-tion may lead to a deficiency of FECH gene and serve as a molecular basis of development of erythropoietic protoporphyria.

BACKGROUND:Erythromycin spreads widely in the body with a short period of effective concentrations and has a lot of adverse effects.Therefore,it is necessary to make erythromycin as targeted medicine.OBJECTIVE:To optimize the preparation conditions of erythromycin gelatin microspheres.DESIGN,TIME AND SETTING:An orthogonal controlled test was performed in the Department of Pharmacy,Guangdong Pharmaceutical University from June to December in 2005.MATERIALS:Erythromycin and gelatin.METHODS:According to the emulsion principle,erythromycin dispersed in the gelatin solution.In the process of preparing microspheres,the gelatin solution and oil should form W/O emulsion and then it turned into spheres by solidification.The formation and quality of microspheres were influenced by four factors,namely the concentration of gelatin,dosage of emulsifier,the solidification time and the speed of mixing.The arithmetic mean diameter of microspheres,the drug loading efficiency and the encapsulation efficiency were targets for the survey in this study on the basis of pretests.The best preparation conditions were optimized in accordance with the results of L9 (34) orthogonal tests.The optimized preparation conditions were obtained according to the results of orthogonal tests.MAIN OUTCOME MEASURES:The mean diameter of microspheres,the drug loading efficiency,the encapsulation efficiency,and the orthogonal tests were examined.RESULTS:The optimized preparation conditions of erythromycin gelatin microspheres included 15% gelatin,3.0 mL emulsifier,0.5 hour solidification and mixing at 1 000 r/rain.The erythromycin gelatin microspheres were regular in their morphology.Drug was enveloped in microspheres.The average particle size was (14.15±0.20) μm;the drug loading efficiency and the encapsulation efficiency were (5.83±0.38)% and (65.70±0.56)%,respectively.Over 90.16% of the microspheres was in the range of 7-25 μm;The reappearance of pharmaceutical technology was good.CONCLUSION:The optimized preparation conditions of erythromycin gelatin microspheres are obtained using L9 (34)orthogonal tests.The microspheres prepared meet the requirement of the size for lung targeting.

Background and purpose:To investigate the induction of apoptosis by epigallocatechin-3-gallate(EGCG) in xenograft nude mice with human gastric cancer cells and its molecular mechanism. Methods:Human gastric cancer cells were planted into nude mice in order to establish the cancer model, the different dosages of EGCG were injected intraperitoneally in the nude mice. After treatment, flow cytometry (FCM) was used to detect the apoptosis of implanted tumor cells. Immunohistochemical staining was used to detect the expression of apoptosis-related genes like Bal-2 and Bax in implanted tumor.Results:EGCG significantly inhibited tumor growth after being injecting intraperitoneally in the nude mice. The apoptotic cells in implanted tumor could be detected by flow cytometry with PI staining. The expressions of Bax、Caspase-3 were upregulated and Bcl-2 expression was downregulated in implanted tumor.Conclusions:EGCG could significantly inhibit tumor growth in xenograft nude mice with human gastric cancer cells through inducing apoptosis. The down-regulation of Bcl-2 expression and up-regulation of Bax expression observed could result in the activation of Caspase-3, the pathway might account for the induction of apoptosis.