BACKGROUND:Disruption of biological rhythms(circadian rhythms)is a typical problem associated with aging.Maintaining the normal function of biological rhythms may be a promising anti-aging strategy.Expression of nuclear factor erthroid 2-related factor 2(Nrf2)is biologically regulated.The glycogen synthase kinase 3(GSK3)system represents a"regulatory valve"that controls subtle oscillations in Nrf2 levels.Circadian changes in the transcript levels of antioxidant genes can influence the response of organisms to oxidative stress.However,the specific molecular mechanism of GSK3/Nrf2 in regulating organismal aging is still puzzling. OBJECTIVE:To search for the general pattern of GSK3/Nrf2-regulated biological rhythms in organismal aging by reviewing the literature in this field. METHODS:The bibliographic method was used to search,review and screen the relevant literature using the keywords of"glycogen synthase kinase 3,nuclear factor erthroid 2-related factor 2,biorhythms and aging"to lay a theoretical foundation for the analysis of the whole paper.Comparative analysis method,through reading and analyzing the obtained literature,was performed to compare the similarities and differences between the literature,thereby providing reasonable theoretical support for the argument.Further comparative analysis of the literature was conducted to clarify the relationship between the relevant indicators as well as the ideas for analysis throughout the text. RESULTS AND CONCLUSION:GSK3 can indirectly regulate Nrf2 expression through the regulation of rhythm genes.GSK3 and Nrf2 are components of anti-aging programs and are associated with biological rhythms.In addition,GSK3/Nrf2 is involved in several metabolic pathways,including those associated with age-related diseases(type 2 diabetes and cancer)and neurodegenerative diseases.

Objective To explore the efficacy of repeated transcranial magnetic stimulation(rTMS)combined with flupentixol and melitracen tablets on post-stroke depression(PSD)and to evaluate the predictive value of depressive symptom dimensions on the efficacy.Methods PSD patients diagnosed and treated in the department of rehabilitation medicine of Jiaozhou Central Hospital of Qingdao from January 2021 to December 2023 were selected as the research subjects,all patients were treated with rTMS combined with flupentixol and melitracen tablets.The National Institutes of Health Stroke Scale(NIHSS),Hamilton Depression(HAMD),and Barthel Index(BI)of PSD patients before and after treatment were evaluated and compared.PSD patients were divided into the effective group and the ineffective group based on treatment effectiveness,and Logistic regression was used to explore the relationship between depression symptom dimensions and treatment outcomes.Using the receiver operating characteristic(ROC)curve to explore the predictive value of depression symptom dimensions on the efficacy of PSD patients.Results A total of 80 PSD patients were included in this study,of which 68 cases were effective in treatment and 12 cases were ineffective in treatment.Compared with before treatment,PSD patients showed a significant decrease in HAMD score,NIHSS score(P＜0.05),and BI score was significant increased(P＜0.05).The observed mood(OM)score,cognitive score,and neurological symptom(NS)score of PSD patients in the effective group were higher than those in the ineffective group,and the differences were statistically significant(P＜0.05).Logistic regression analysis showed that high-level OM score,cognitive score,and NS score were independent protective factors for effective PSD treatment.ROC analysis showed that the baseline OM score,cognitive score,and NS score for ineffective treatment were 0.744[95％CI(0.568,0.921)],0.734[95％CI(0.572,0.896)],and 0.709[95％CI 0.534,0.884)],respectively.Conclusion rTMS combined with flupentixol and melitracen tablets can significantly improve depression symptoms and neurological impairment,and improve the ability of daily living.Moreover,depressive symptom dimensions at baseline can predict the treatment effects of PSD patients.

Objective To observe the changes of abdominal oxygen saturation in very low birth weight infants (VLBWI)with feeding intolerance (FI)within 1 4 days after birth monitored by near infrared spectroscopy (NIRS).Methods VLBWI fitting entry criteria were enrolled into this study.NIRS monitoring was carried out to detect cerebral oxygen saturation (ScO2 )and abdominal oxygen saturation (SsO2 ).Data were analyzed between FI infants and feeding tolerance (FT)infants.FI was defined as follows:gastric residual of more than 50% of the previous feeding volume;emesis or abdominal distention or both;decrease,delay or discontinuation of enteral feedings. Results 93 VLBWI were enrolled.52 cases(55.91 %)presented with FI,including 29 cases(31 .1 9%)of gastric residual increasing and 23 cases(24.73%)of emesis with or without abdominal distention within 1 4 days after birth. The levels of SsO2 and SsO2 /ScO2 showed no differences in infants with FT and with FI within 24h after birth (P >0.05).The change rates of the median of SsO2 and SsO2 /ScO2 in FT infants were similar during 1 4 days (P >0.05).While both the change rates of SsO2 and SsO2 /ScO2 were markedly decreased 1 day before and the day of FI (P <0.01 ).The decreasing degree of SsO2 was similar between infants with gastric residual increasing and infants with emesis with or without abdominal distention[(1 6.2 ±5.1 )vs (1 7.4 ±3.6)%,t =0.733,P =0.476]. Conclusion Abdominal oxygen saturation measured by NIRS may be a useful method for infants adjusting the feeding plan.

Objective To investigate effects of different ventilation methods during pulmonary surfactant(PS) administration on cerebral oxygen metabolism in preterm infants with neonatal respiratory distress syndrome.Methods Newborns met the inclusion criteria were enrolled into this study,and they were randomly divided into manual group and mechanical group.During PS administration,the proximal end of the tracheal tube was connected to a bag valve mask device in the manual group or a mechanical ventilator in the mechanical group.Brain near infrared spectroscopy monitoring was carried out to detect the cerebral oxygen saturation(ScO2),and the mean arterial blood pressure (MABP) was simultaneously recorded.Results For all 49 preterm infants,PS was administered to preterm infants with severe respiratory distress syndrome treated with mechanical ventilation,including 24 cases of manual ventilation and 25 cases of mechanical ventilation.The left cerebral ScO2 and correlation coefficient of ScO2 and MABP(rScO2-MABP) showed no difference in both groups before PS administration.During administration,ScO2 dramatically increased in both groups [manual group:(85.88 ± 5.54) ％ vs.(77.31 ± 5.40) ％,t =5.521,P =0.000;mechanical group:(83.88 ± 3.18) ％ vs.(76.53 ±4.38)％,t =6.741,P =0.000],and gradually decreased after administration,the level of ScO2 didn't return to the baseline till the 2nd 5 minutes after PS administration [manual group:(79.25 ± 3.02) ％ vs.(77.31 ± 5.40) ％,t =1.560,P =0.220;mechanical group:(78.59 ± 3.45) ％ vs.(76.53 ± 4.38) ％,t =1.832,P =0.074].The same trend of ScO2 change rate was shown simultaneously in both groups.The rScO2-MABP markedly increased during administration in both groups (manual group:2.34 ±0.16 vs.1.86 ±0.21,t =9.022,P =0.000;mechanical group:2.12 ± 0.15 vs.1.87 ±0.21,t =4.810,P =0.000).The rScO2-MABt,in mechanical group rapidly decreased to baseline during the 1st5 minutes (1.84 ± 0.18 vs.1.87 ± 0.21,t =0.538,P =0.635) but went back to baseline in manual group during the 2nd 5 minutes(1.84 ±0.19 vs.1.86-0.21,t =0.350,P =0.809).Change rates of rScO2-MABP were markedly higher in manual group than those in mechanical group during the 1 st 5 minutes (1.15 ± 0.13 vs.1.00 ± 0.15,t =4.943,P =0.000).Conclusions ScO2 could be affected transiently by PS administration with different methods of ventilation.The effect on cerebral autoregulation in mechanical group is shorter than that in manual group.

OBJECTIVE:To investigate the utilization of the most used splitting drugs in the inpatients of our hospital,and to promote rational use of splitting drugs. METHODS:The medical orders of oral tablets in the inpatients of our hospital in Jan. 2016 were analyzed statistically in respects of consumption quantity,classification dosage,department dosage and the proportion of scored tablets. RESULTS & CONCLUSIONS:There were 217389 medical orders of tablets in the inpatients of our hospital in Jan. 2016. There were 12792 medical orders of splitting drugs,with utilization rate of 5.88%. The most used splitting tablet were car-diovascular drugs and drug for nervous system,accounting for 53.31% and 20.72% of total. The splitting tablets were mostly used in respiratory and critical care medicine department. Top 10 departments in the list of the number of splitting drug medical orders prescribed 8993 splitting drug medical orders,accounted for 70.30% of total. Top 20 drugs in the list of the number of splitting drugs were involved in 8971 medical orders,accounting for 70.13%of total;there were 14 kinds of scored drugs and 7506 medi-cal orders of splitting scored drugs,accounting for 83.67% of top 20 medical orders of splitting drugs. Among splitting drugs,49 types had scored-line,which were prescribed in 9265 medical orders of splitting drug,accounting for 72.43% of all medical or-ders of splitting drug. Lacking of information in most package inserts about the tablet can or can not split,it is suggested to note this information in package inserts by pharmaceutical enterprises. For commonly used splitting drugs without scored-line,it is pro-posed to produce small-size drugs or add scored-line.

The previous investigation has proved that their existed pharmacokinetic difference between the different crystal forms of the polymorphic drugs after oral administration. However, no systemic investigations have been made on the change of this pharmacokinetic difference, resulted either from the physiological or from the pathological factors. In this paper, we used polymorphic nimodipine (Nim) as a model drug and investigated the effect of age difference (2- and 9-month old) on the pharmacokinetics after oral delivery in rats. As the results shown, for L-form of Nim (L-Nim), the AUCin 2-month-old rats was 343.68±47.15 ng·h/mL, which is 23.36% higher than that in 9-month-old rats. For H-form of Nim (H-Nim), the AUCin 2-month-old rats was 140.91±19.47 ng·h/mL, which is 54.64% higher than that in 9-month-old rats. The AUCratio between H-Nim and L-Nim was 2.44 in 2-month-old rats and 3.06 in 9-month-old rats. Since age difference could result in unparallelled change of the absorption and bioavailability of the polymorphic drugs, the results in this experiment are of value for further investigation of crystal form selection in clinical trials and rational clinical application of the polymorphic drugs.

Objective To investigate the awareness of knowledge and attitude on interruption of mother-neonatal transmission of syphilis in pregnant women from different areas. Methods We extracted 900 pregnant women with pregnancy tests from a class Ⅲ grade I hospital in Beijing by means of convenience sampling with 300 for urban areas, 300 for rural areas and 300 for the transient population. The questionnaire of mother-to-neonatal transmission knowledge of syphilis was used to investigate the awareness of knowledge on basic prevention and interruption of mother-neonatal transmission of syphilis, the degree of recognition to patients with syphilis, the way of acquiring knowledge on interruption of mother-neonatal transmission of syphilis among different pregnant women.Results The overall awareness rate of mother-to-neonatal transmission knowledge of syphilis was 55.9% in 900 pregnant women. The awareness rate for the highest of 72.0% was found in pregnant women from urban areas, followed by 51. 0% from rural areas and 44. 7% from the transient population for the lowest with significant differences in awareness rates among different areas(χ2=49.820, P<0.001). In the respect of recognition degree to patients with syphilis, the highest proportion of unwillingness to have meals, shake hands with syphilis patients was found in pregnant women from urban areas with a significant difference (χ2=8.750, P=0.013). The pregnancy got the knowledge of interruption of mother-neonatal transmission of syphilis mainly via television, the network, newspapers and books. Conclusions The low awareness rate was found in knowledge on basic prevention and interruption of mother-neonatal transmission of syphilis. The awareness rate of knowledge on interruption of mother-neonatal transmission of syphilis and the degree of recognition to patients with syphilis were different among pregnant women from different areas. We should increase the publicity on the knowledge on basic prevention and interruption of mother-neonatal transmission of syphilis. Medical staff should take specific measures to propagate the knowledge of syphilis prevention for pregnant women according to different areas. Besides, the approach of knowledge transmission should be suitable for pregnant women aiming at the different ways of acquiring knowledge on interruption of mother-neonatal transmission of syphilis among pregnant women from different areas.

Objective To analyze the clinical efficacy and safety of different ways iron therapy in hemodialy -sis patients with renal anemia .Methods 68 cases of chronic renal failure patients treated with hemodialysis were randomly divided into two groups according to the digital form ,each group had 34 cases.The control group was treated with oral iron while the observation group took intravenous iron ,the clinical efficacy of the two groups was observed . Results The total effective rate of the observation group was 61.76% significantly higher than that of the control group′s 32.35%(χ2 =4.781,P=0.029);Two groups of patients′Hb,Hct,SF,TSAT were significantly improved after treatment than before(t =4.931,4.213,5.429,5.107,7.018,6.472,7.821,7.530,all P <0.05),these parameters of the observation group were significantly improved than that of the control group ( t =4.082,3.968, 4.395,4.139,all P <0.05).Conclusion Intravenous iron approach can significantly improve anemia state in patients with CRF hemodialysis , increased serum iron indicators significantly , improved erythropoiesis , and quickly replenish iron stores,correct anemia in patients with CRF .

OBJECTIVETo investigate the effects of Xinfeng Capsule (XFC) on pulmonary function and related mechanism in adjuvant-induced arthritis (AA) rats.

METHODSThe rats were randomly divided into five groups: normal control (NC), model control (MC) groups, methotrexate (MTX), tripterygium glycosides tablet (TPT) and Xinfeng capsule (XFC) treatment groups. The adjuvant-induced arthritis model was established by intracutaneous injection of 0.1 mL Freund ' s complete adjuvant in the right paw of rats; the drugs were given 19 d after model establishment. The toe swelling degree (E), arthritis index (AI), pulmonary function, peripheral blood Treg levels, pathological changes of lung tissue and expression of Foxp3, TGF-β1, Smad3, Smad7 proteins in lung tissue were measured 30 d after drug administration.

RESULTSCompared to NC group, the levels of E, AI, alveolitis score, TGF-β1 and Smad3 were significantly increased (P <0.05 or P <0.01); maximum expiratory flow 25% of vital capacity (FEF25),50% maximal expiratory vital capacity flow (FEF50), maximum expiratory flow at 75% of vital capacity (FEF75), maximum mid-expiratory flow (MMF), force peak expiratory flow (PEF), CD4+ CD25+ Treg, Foxp3 and Smad7 were significantly decreased in MC group (P <0.05 or P < 0.01). Compared to MC group,the expression of E, AI, TGF-β1 and Smad3 were reduced, while FEF50, FEF75, MMF, PEF, Treg, Foxp3 and Smad7 were elevated in XFC group (P <0.05 or P <0.01). Compared to XFC group, the level of body mass,FEF25,FEF50, FEF75, MMF and Treg were lower in MTX and TPT groups (P <0.05 or P <0.01).

CONCLUSIONThere are inflamed joints and reduced pulmonary function in rats of adjuvant-induced arthritis. XFC can inhibit paw edema degrees, reduce arthritis response, and improve pulmonary function, which is associated with up-regulating expression of Treg and Foxp3, down-regulating the expression of TGF-β1 and adjusting TGF-β1/Smads signal pathway.

Animals ; Arthritis, Experimental ; drug therapy ; metabolism ; physiopathology ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Forkhead Transcription Factors ; metabolism ; Lung ; drug effects ; pathology ; physiopathology ; Male ; Rats ; Rats, Wistar ; Smad3 Protein ; metabolism ; Smad7 Protein ; metabolism ; T-Lymphocytes, Regulatory ; metabolism ; Transforming Growth Factor beta1 ; metabolism

Both microRNA and DNA methylation are the important contents of epigenetic modification.Lots of studies have confirmed that mutual regulation of microRNA and DNA methylation involve in tumorgenesis and development of cancer.The studies of their mechanisms bring some new ideas for investigating the pathogenesis of tumors,and provide a theoretical basis for the early diagnosis and treatment.