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 investigate the application value of Pelvic Inflammation No.1 formula of transdermal meridian point-targeted drug delivery therapy in the treatment of patients with chronic pelvic inflammatory disease(damp-heat stasis type).Methods:All patients with chronic pelvic inflammatory disease(damp-heat stasis type)visited Danzhou Hospital of Traditional Chinese Medi-cine from August 2017 to March 2021 and were randomly grouped,57 patients in the control group were treated with simple Western medicine,and 57 patients in the observation group were combined with Pelvic Inflammation No.1 formula transdermal meridian target-ed transdermal medication,and the therapeutic efficacies were compared after 3 months of treatment.Results:After treatment,serum matrix metalloproteinase-9(MMP-9),D dimer(D-D),IL-6 and other indexes in the observation group were lower than those in the control group,and IL-10 was higher than that in the control group,the difference was statistically significant(P<0.05).After treat-ment,the carbohydrate antigen CA125 in the observation group was lower than that in the control group,and the CD4+/CD8+and CD4+cells in the observation group were higher than those in the control group(P<0.05).After treatment,the score of summary of health status surveys(SF-36)in the observation group was higher than that in the control group,and the total score of TCM symptoms was lower than that in the control group(P<0.05).The total effective rate in the observation group was 96.49%(55/57),which was higher than 82.46%(46/57)in the control group(P<0.05).Conclusion:For patients with chronic pelvic inflammatory disease(damp-heat stagnation type),combined with Pelvic Inflammation No.1 formula transdermal via acupoints targeted drug therapy can help to regu-late inflammatory factors,regulate immune function,and improve clinical efficacy.

Objective:To evaluate the feasibility of using Patient Health Questionnaire-4 (PHQ-4) to screen for depression and anxiety in inpatients in general hospitals.Methods:Using the convenient sampling method, a total of 695 inpatients from 10 ClassⅡ Grade A and above comprehensive hospitals in Nanjing from January to June 2021 were selected as the research objects. They were investigated by PHQ-4, Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7 (GAD-7) to compare the screening results of different measuring tools for depression and anxiety. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of PHQ-4, Kappa test was used to analyze the consistency, Cronbach's α coefficient was used to evaluate the internal consistency of the scale, and Pearson correlation analysis was used to evaluate the calibration correlation validity. A total of 695 questionnaires were sent out in this study, and 672 were effectively collected, with an effective recovery rate of 96.69% (672/695) .Results:Among 672 inpatients in general hospitals, the detection rate of depression and anxiety in patients using PHQ-4 was 38.39% (258/672), while that in patients using PHQ-9 and GAD-7 was 41.82% (281/672), and the difference showed no statistical significance (χ 2=1.64, P=0.20). Cronbachs'α coefficient of PHQ-4 was 0.913, and the half reliability coefficient was 0.888. The Kappa value of the consistency test between PHQ-4, PHQ-9, and GAD-7 for depression and anxiety screening results was 0.756 ( P<0.01). The correlation coefficients between the total scores of PHQ-4, PHQ-9 and GAD-7 in 672 inpatients from general hospitals were 0.822 and 0.802, respectively (both P<0.01). The area under the ROC curve of PHQ-4 was 0.936. With a critical score of 3, the sensitivity and specificity of PHQ-4 were 81.9% and 92.8%, respectively. Conclusions:The detection rate of PHQ-4 and PHQ-9 and GAD-7 on depression and anxiety state of inpatients in general hospital is similar, and has good reliability and validity, which is suitable for the screening of depression and anxiety of inpatients in general hospital.

OBJECTIVE:To investigate the effects of blood concentration monitoring of cylosporin A(CsA) in patients with nephrotic syndrome(NS)on efficacy and safety. METHODS:The medical records of 154 NS patients receiving CsA and blood concentration monitoring in nephrology department of China-Japan Friendship Hospital during Jan. 2014-Aug. 2017 were analyzed retrospectively. The results of blood concentration monitoring in 63 adult inpatients with refractory NS receiving CsA for the first time within 6 months of initial treatment were analyzed statistically. The relationship of blood concentration monitoring with efficacy and safety was analyzed. RESULTS:The blood concentration of CsA in 154 patients were monitored for 512 times with an average of 3.32 times/person,and average blood concentration was(125.98±105.13)ng/mL. The patients with blood concentration of CsA＜100 ng/mL accounted for 44.14%. There was no statistical significance in average monitoring times or average blood concentration between male and female,average blood concentration of CsA among different age groups (P＞0.05). The blood concentration was monitored for 237 times in 63 adult inpatients with refractory NS receiving CsA for the first time within 6 months of initial treatment(induction period). Average blood concentration of effective group were significantly higher than ineffective group;the proportion of effective group with blood concentration＜100 ng/mL was significantly lower than that of ineffective group,with statistical significance (P＜0.05). Among 63 patients,17 patients suffered from ADR (the incidence of ADR was 26.98%). The average blood concentrations of ADR patients were significantly higher than those without ADR;the monitoring times of ADR patients with blood concentration＞150 ng/mL was significantly higher than those without ADR,with statistical significance(P＜0.05). There was no statistical significance in the incidence of ADR between effective group and ineffective group (P＞0.05). Among effective group,there was no statistically significance in average blood concentration between ADR patients and patients without ADR(P＞0.05);the monitoring times of ADR patients with blood concentration＞150 ng/mL was significantly higher than patients without ADR,with statistical significance(P＜0.05). With the increase of monitoring times,the incidence of ADR decreased gradually. There was no statistical significance in the incidence of ADR among patients who were monitored for different times (P＞0.05). CONCLUSIONS:The pharmacokinetics of CsA varies in different patients and many factors affect its blood concentration. The changes of blood concentration affect the efficacy and safety of CsA. It is difficult to determine the dosage of CsA based on experience in the treatment of NS with CsA. Great importance should be attached to blood concentration monitoring of CsA and the implementation of individualized dosage regimen based monitoring results so as to improve therapeutic efficacy and reduce the occurrence of ADR.

Objective To explore the detection trend of vaginal intraepithelial neoplasia(VaIN)of lower genital tract from 2013 to 2015. Methods A retrospective analysis was undertaken of colposcopy-directed biopsy of cervical, vaginal and vulvar intraepithelial neoplasia lesions include cervical intraepithelial neoplasia (CIN), VaIN and vulvar intraepithelial neoplasia (VIN) in Obstetrics and Gynecology Hospital of Fudan University from January 2013 to December 2015. Results (1) Overall data of CIN, VaIN and VIN:a total of 16732 cases were diagnosed of lower genital intraepithelial neoplasia in 3 years, accounting for 23.20% (16732/72128) of total colposcopy-directed biopsy cases. Among them, CIN, VaIN and VIN accounted for 19.48%(14053/72128), 2.67%(1923/72128), 1.05%(756/72128) of total colposcopy-directed biopsy cases of the lower genital tract, 83.99%(14053/16732), 11.49%(1923/16732), 4.52%(756/16732) of total lower genital intraepithelial neoplasia, respectively. (2) Annual data of CIN, VaIN and VIN from 2013 to 2015. The annual proportion of CIN in all intraepithelial neoplasia of lower gential tract was basically stable, consisting of 86.02%(3955/4598),83.25%(4795/5760) and 83.20%(5303/6374), respectively. The annual proportion of VaIN was gradually increasing, consisting of 8.09% (372/4598), 12.45%(717/5760) and 13.08%(834/6374), respectively. The annual proportion of VIN was gradually decreasing, consisting of 5.89% (271/4598), 4.31% (248/5760) and 3.72% (237/6374), respectively. Conclusion The increasing detection of VaIN from 2013 to 2015 might correlate with the increasing attention to inspection of the entire vaginal wall.

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 explore the sensitivity and specificity of colposcopy directed biopsy (CDB) and the value of loop electrosurgical excision procedure (LEEP) for the diagnosis and treatment of microinvasive cervical cancer (MCC). Methods One hundred and thirty five patients with MCC were diagnosed with LEEP in Obstetrics and Gynecology Hospital, Fudan University from April 2008 to November 2010, and were retrospectively analyzed on CDB diagnoses and following treatment after LEEP. According to patient′s desire for preservation of fertility and cone margin status, following strategies after LEEP included follow-up, second LEEP, hysterectomy, modified radical hysterectomy and radical hysterectomy. Single and multiple factors related to residual lesions after LEEP were analysed with Pearson Chi-square test and logistic regression model, respectively. Results CDB diagnosed MCC with a sensitivity of 4.4%(6/135), specificity of 100.0%(4 680/4 680), and false negative rate of 95.6%(129/135). Among the 135 patients, 29 did not receive further treatment in our hospital and lost contact. One hundred and six patients had secondary treatment or follow-up in our hospital, 4 of among which were closely followed up;one hundred and two received further treatment, which included 6 cases with second LEEP (3 received extrafascial hysterectomy after repeat LEEP), 59 cases hysterectomy, 14 cases modified radical hysterectomy and 26 cases radical hysterectomy. For factors related to residual lesions after LEEP, single factor analysis showed that the ratio of residual lesion in patients aged 27-39, 40-49 and 50-65 years were respectively 19.0%(11/58), 15.4%(10/65) and 5/12 (χ2=4.505, P=0.105). Residual lesions occurred in 24.7%(23/93) of patients with positive LEEP margins, which was more than that 7.1%(3/42) of patients with negative LEEP margins (χ2=5.756, P=0.016). The ratio of residual lesions in patients with positive endocervical, ectocervical and deep stromal margins were respectively 29.6%(8/27), 17.1%(7/41)and 30.6%(11/36;χ2=2.275, P=0.321). Residual lesions in patients with or without lymph vascular space invasion (LVSI) were 2/7 and 18.8%(24/128), respectively (χ2=0.412, P=0.521). The ratio of residual lesions in patients with invasion depth of<1 mm was 17.1%(7/41), 1-<3 mm was 19.0%(16/84), and 3-5 mm was 3/10, with no significant difference among three groups (χ2=0.870, P=0.647). Logistic regression analysis showed positive cone margin (OR=5.069, P=0.014) and age (OR=1.080, P=0.024) were the independent risk factors of residual lesions after LEEP conization. Conclusions CDB alone is not adequate for the diagnosis of MCC. For young patients who desire to preserve fertility with a negative cone margin, close follow-up is acceptable. Cone margin status and age are two independent risk factors for residual lesions after LEEP.

Objective To explore the function of extended nursing combined with PDSA circle and based on positivepsychology in improving self-efficacy of patients with colostomy. Methods A total of 80 patients with colostomy match the inclusion and exclusion standard from December 2014 to December 2015, were divided into the control group and the intervention group according to the order of discharge date.Patients in the control group received conventional extended nursing, while patients in the intervention group received extended nursing combined with PDSA circle and based on positivepsychology, and interventions were conducted a week, a month, two months, three months after discharge. Patients were evaluated by stoma related self-efficacy questionnaire before the intervention, after the fourth intervention and 3 months after intervention ( T0 , T1 ,T2 ) . Results There were significant differences in the dimensions, independent items and total scores of stoma related self-efficacy between two groups at different time after intervention except the item of confidence in sexual life (P<0.05), and they also had interactive effect (P<0.05).There was significant difference in the main effect of intervention time for the single item “confidence in sexual life” (P<0.05). In the intervention group, the scores of dimensions, independent items and total scores of stoma related self-efficiency after intervention and three months after intervention were significantly higher than those before intervention. Conclusions The extended nursing combined with PDSA circle and based on positivepsychology can improve the self-efficacy of patients with colostomy.

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.

OBJECTIVETo study the association of methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation and plasma homocysteine (Hcy) levels with hyperlipidemia.

METHODSBlood samples were collected from 1591 adults for detecting MTHFR gene C677T polymorphism with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), plasma Hcy levels with enzymatic cycling method, and blood lipid levels as well. The patients were divided according to the lipid levels into hyperlipidemia group (n=694) and healthy control group (n=897) and the differences in MTHFR gene C677T polymorphisms and plasma Hcy levels were compared.

RESULTSThe hyperlipidemia group and healthy control group showed no significant differences in CC, CT, or TT genotype frequencies or C and T allele frequencies of MTHFR C677T gene, and had comparable plasma Hcy levels (P>0.05). Patients with 3 different MTHFR C677T genotypes had significant differences in plasma Hcy levels (P<0.01) but not in blood lipid levels (P>0.05). Pairwise comparison indicated a significantly higher plasma Hcy level in TT genotype than in CC and CT genotypes (P<0.01), and the latter two genotypes showed no significant difference (P>0.05).

CONCLUSIONMTHFR C677T polymorphisms and plasma Hcy levels are closely related but neither of them is associated with hyperlipidemia. The TT genotype is associated with a significantly higher plasma Hcy level than CC and CT genotypes.

Adult ; Gene Frequency ; Genotype ; Homocysteine ; blood ; Humans ; Hyperlipidemias ; blood ; genetics ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Mutation ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length