BACKGROUND:Carboxylesterase 1 and inflammatory factors play a crucial role in regulating lipid metabolism and glucose homeostasis.However,the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats remain to be revealed. OBJECTIVE:To investigate the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats. METHODS:Thirty-two 8-week-old male Sprague-Dawley rats were randomly divided into normal control group(n=12)and modeling group(n=20)after 1 week of adaptive feeding.Rat models of type 2 diabetes mellitus were prepared by high-fat diet and single injection of streptozotocin.After successful modeling,the rats were randomly divided into diabetic control group(n=6),moderate-intensity exercise group(n=6)and high-intensity intermittent exercise group(n=6).The latter two groups were subjected to treadmill training at corresponding intensities,once a day,50 minutes each,and 5 days per week.Exercise intervention in each group was carried out for 6 weeks.After the intervention,ELISA was used to detect blood glucose and blood lipids of rats.The morphological changes of skeletal muscle were observed by hematoxylin-eosin staining.The mRNA expression levels of carboxylesterase 1 and inflammatory cytokines were detected by real-time quantitative PCR.The protein expression levels of carboxylesterase 1 and inflammatory cytokines were detected by western blot and immunofluorescence. RESULTS AND CONCLUSION:Compared with the normal control group,fasting blood glucose,triglyceride,low-density lipoprotein cholesterol,insulin resistance index in the diabetic control group were significantly increased(P<0.01),insulin activity was decreased(P<0.05),and the mRNA and protein levels of carboxylesterase 1,never in mitosis gene A related kinase 7(NEK7)and interleukin 18 in skeletal muscle tissue were upregulated(P<0.05).Compared with the diabetic control group,fasting blood glucose,triglyceride,low-density lipoprotein cholesterol,and insulin resistance index in the moderate-intensity exercise group and high-intensity intermittent exercise group were down-regulated(P<0.05),and insulin activity was increased(P<0.05).Moreover,compared with the diabetic control group,the mRNA level of NEK7 and the protein levels of carboxylesterase 1,NEK7 and interleukin 18 in skeletal muscle were decreased in the moderate-intensity exercise group(P<0.05),while the mRNA levels of carboxylesterase 1,NEK7,NOD-like receptor heat protein domain associated protein 3 and interleukin 18 and the protein levels of carboxylesterase 1 and interleukin 18 in skeletal muscle were downregulated in the high-intensity intermittent exercise group(P<0.05).Hematoxylin-eosin staining showed that compared with the diabetic control group,the cavities of myofibers in the moderate-intensity exercise group became smaller,the number of internal cavities was reduced,and the cellular structure tended to be more intact;the myocytes of rats in the high-intensity intermittent exercise group were loosely arranged,with irregular tissue shape and increased cavities in myofibers.To conclude,both moderate-intensity exercise and high-intensity intermittent exercise can reduce blood glucose,lipid,insulin resistance and carboxylesterase 1 levels in type 2 diabetic rats.Moderate-intensity exercise can significantly reduce the expression level of NEK7 protein in skeletal muscle,while high-intensity intermittent exercise can significantly reduce the expression level of interleukin 18 protein in skeletal muscle.In addition,the level of carboxylesterase 1 is closely related to the levels of NEK7 and interleukin 18.

OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

Objective:To investigate the current status of maternal body image during pregnancy, mother-infant attachment and postpartum depression and explore the mediating effect of mother-infant attachment on maternal body image during pregnancy and postpartum depression, in order to effectively reduce the incidence of postpartum depression and provide reference and guidance for alleviating depressive symptoms.Methods:A total of 362 pregnant women admitted to obstetric wards in Women′s Hospital of Nanjing Medical University were selected for a cross-sectional investigation by applying the Edinburgh Postnatal Depression Scale, the Body Image in Pregnancy Scale and the Maternal Postnatal Attachment Scale by convenient sampling from July to September 2022. Model 4 in the SPSS macro program PROCESS was used to test the mediating effect of maternal infant attachment between body image and postpartum depression.Results:Totally 362 valid questionnaires were retrieved including 194 individuals aged ≤30 years old and 168 individuals aged >30 years old. The scores of maternal body image during pregnancy, mother-infant attachment and postpartum depression were (89.24 ± 15.56), (71.40 ± 8.05), 7.50 (4.00, 11.00) points.Conclusions:Body image during pregnancy can not only directly predict postpartum depression, but also indirectly predict postpartum depression through the mediating effect of mother-infant attachment. In order to prevent or reduce the occurrence of postpartum depression, nursing staff should carry out intervention research based on influencing the path of postpartum depression from the perspective of positive psychology.

BACKGROUND:It has been found that vascular endothelial growth factor 165 and bone morphogenetic proteins interact with each other during hypoxia-reoxygenation and are involved in the repair process of osteoblast injury by regulating the activation of intracellular signaling pathways. OBJECTIVE:To further investigate the relationship between vascular endothelial growth factor 165/bone morphogenetic protein and hypoxic-reoxygenated osteoblast injury. METHODS:Osteoblasts were selected and the hypoxic-reoxygenated injury model was established.Vascular endothelial growth factor 165 and bone morphogenetic protein expressions at mRNA and protein levels were detected by real-time PCR and western blot before and after modeling.After modeling,osteoblasts were given different concentrations of vascular endothelial growth factor 165 and bone morphogenetic protein 2(10,20,40 ng/mL).Cell proliferation was detected by cell counting kit-8 method and apoptosis was detected by DAPI at 12,24,36,48,and 72 hours after treatment. RESULTS AND CONCLUSION:Compared with before modeling,the mRNA and protein expressions of vascular endothelial growth factor 165 and bone morphogenetic protein 2 in osteoblasts after modeling were significantly decreased(P＜0.05).The proliferation rate of osteoblasts was significantly increased with the increase of vascular endothelial growth factor 165 concentration(P＜0.05),while the apoptosis rate of osteoblasts decreased significantly with the increase of vascular endothelial growth factor 165 concentration(P＜0.05).The proliferation rate of osteoblast was significantly increased with the increase of bone morphogenetic protein 2 concentration(P＜0.05),while the apoptosis rate of osteoblast decreased significantly with the increase of bone morphogenetic protein 2 concentration(P＜0.05).To conclude,vascular endothelial growth factor 165 and bone morphogenetic protein are lowly expressed in hypoxic-reoxygenated osteoblast injury,and treatment with vascular endothelial growth factor 165 and bone morphogenetic protein can reduce the injury of hypoxic-reoxygenated osteoblast in a concentration-dependent manner,suggesting that vascular endothelial growth factor 165 and bone morphogenetic protein have a significant protective effect against the injury of hypoxic-reoxygenated osteoblasts.

； ObjectiveTo explore the effect of direct-acting antiviral treatment on renal function in patients with chronic hepatitis C. MethodsA total of 123 HCV-infected patients receiving DAAs treatment at the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2021 were included in this study. To explore the renal function in patients with chronic hepatitis C treated with direct-acting antivirals， serum creatinine values were collected before， during and after the treatment， which were used to estimate the eGFR by the MDRD equation to assess the changes in renal function. ResultsOf the 123 patients enrolled， 67.5%（n=83）were male， and the mean age of participants was （50±11） years old. The mean follow-up period was 24 weeks . Comorbidities included cirrhosis in 26.8%， and diabetes in 10.6%. Meanwhile， 11.4% of the cohort had eGFR < 60 mL/（min ·1.73 m²）， 33.3% of the cohort had eGFR 60 to 90 mL/（min ·1.73 m²）， and 55.3% had eGFR≥90 mL/（min ·1.73 m²）. No decrease in renal function was seen among all the HCV-infected patients at the end of treatment or the follow-up period after treatment. However， compared with the eGFR at the baseline， eGFR in CKD2 patients in the follow-up period was improved 【（88.65±15.52） mL/（min ·1.73 m²）vs （78.12 ±7.60） mL/（min ·1.73 m²）， P< 0.001】. And 14.6% （n=18） of patients experienced progressive deterioration of renal function. Logistic regression analysis showed that diabetes could predict the deterioration of renal function （OR=4.663， P=0.016）. ConclusionsOur study shows renal function is not impair among HCV-infected patients following DAAs treatment， and renal function in CKD2 patients have improvements. However， HCV-infected patients with diabetes mellitus are at a high risk of renal impairment and closely monitoring of renal function is still needed.

Objective:To investigate the correlation between gender, age, blood collection time, season and changes in cTnT concentration.Methods:In this study, 3548 patients (non-cardiovascular diseases) in Zhongshan Hospital of Fudan University were selected from 1 January to 31 December 2019. The basic data of the patients were collected, including gender, age, time of blood collection, medical history, clinical diagnosis, and results of cTnT testing. 1 840 males and 1 708 females were finally enrolled, with an age distribution of 65 (53, 75) years. The distribution of the data was assessed using the Kolmogorov-Smirnov (K-S) test, where non-normally distributed data were expressed as M( Q1, Q3). The Mann-Whitney U-test was used to compare cTnT concentrations between men and women, and to analyse the influence of gender on cTnT results. The Kruskal-Wallis test was used to compare cTnT levels between gender groups, to analyse the correlation between different times of blood collection, seasons, and other factors and cTnT concentrations. Result:cTnT concentrations increased with age in both males and females over the age of 60 years. cTnT levels were highest in individuals over the age of 90 years (0.028 ng/ml in males and 0.018 ng/ml in females). cTnT levels were higher in males (0.012 ng/ml) than in females (0.009 ng/ml) in all age groups ( H=6.340, P<0.01). The concentrations of cTnT varied at different time points of blood collection. In both males and females, cTnT concentrations reached a maximum at 8:00 and 13:00 (0.013 ng/ml and 0.012 ng/ml, respectively). Analysis of the physiological effect of season on cTnT secretion showed that cTnT levels were generally higher in spring and winter(0.012 ng/ml) than in summer and autumn(0.010 ng/ml). Conclusions:cTnT concentration is influenced by gender, age, time of blood collection and season. When analysing cTnT results in clinical practice, the gender and age of the individual should be taken into account, as well as the time point of blood collection and seasonal factors.

Objective:To investigate the efficacy of sacubitril/valsartan in the treatment of cancer therapy-related cardiac dysfunction(CTRCD).Methods:A comprehensive analysis of all the literature on sacubitril/valsartan therapy for CTRCD published in Pubmed,Web of Science,Cochrane Library,Medline,and Embase from the inception of the database up to March 2023 was conducted,summarizing the tim-ing of drug administration,dosage,and efficacy,and further systematically summarizing the clinical studies on the use of the drug for the prevention of CTRCD.Results:After 3-12 months of treatment with sacubitril/valsartan for CTRCD,NYHA in cancer patients improved from grade Ⅱ-Ⅳ to grade Ⅰ-Ⅱ,LVEF increased by 3.0%to 37.0%,and NT-proBNP decreased by 280.0-65 498.0 pg/mL.Conclusions:The sacu-bitril/valsartan demonstrates efficacy in managing CTRCD and holds significant clinical utility in enhancing LVEF,GLS,and other patient indic-ators,thereby enabling the continuation of anti-tumor therapy and prolonging survival for cancer patients.

Objective:To analyze clinical efficacy, failure mode and prognostic factors of nasopharyngeal carcinoma (NPC) patients undergoing intensity modulated radiation therapy (IMRT).Methods:Clinical data of 951 locally advanced NPC patients who were newly-treated with IMRT in Hunan Cancer Hospital from January 2018 to January 2019 were retrospectively analyzed. The patients' general data, overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), local recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) were analyzed. Comparison among different groups was performed by one-way ANOVA. Survival rate was calculated by Kaplan-Meier method. Survival difference was compared by log-rank test. Univariate and multivariate analyses were performed by Cox regression model.Results:The median follow-up time was 62.0 months (IQR, 58.0-65.0 months). The 5-year OS, LRFS, RRFS, LRRFS, DMFS, and PFS were 85.4%, 94.0%, 97.7%, 92.6%, 85.7% and 76.9%, respectively. According to the 8th edition staging of American Joint Committee on Cancer (AJCC), there were 10 cases (1.1%) of stage I, 76 cases (8.0%) of stage II, 445 cases (46.8%) of stage III, and 420 cases (44.2%) of stage IVA, respectively. Among them, the OS rates of stage I, II, III and IVA patients were 100%, 97.2%, 88.8% and 79.2%, respectively ( P<0.001); LRRFS rates were 100%, 90.4%, 94.7% and 90.4%, respectively( P=0.104); DMFS rates were 90.0%, 95.9%, 88.0% and 81.1%, respectively ( P<0.001); PFS rates were 90.0%, 89.1%, 80.9% and 70.1% respectively ( P<0.001). There were 183 cases of treatment failure, including 52 cases (5.5%) of local failure, 19 cases (2.0%) of regional failure, 130 cases (13.7%) of distant metastasis, 16 cases of local combined with regional failure (1.7%), 16 cases (1.7%) of local failure combined with distant metastasis, 13 cases (1.4%) of regional failure combined with distant metastasis, and 9 cases (0.9%) of local regional failure combined with distant metastasis, respectively. Multivariate regression analysis suggested that EB virus DNA copy number before treatment, T stage and N stage were the independent prognostic factors affecting OS, DMFS and PFS. Conclusions:Compared with two-dimensional radiotherapy, IMRT has improved the overall therapeutic effect for NPC, especially the local control rate. Distant metastasis is still the main failure mode. Clinical staging, prognostic risk stratification and prognostic biomarkers can be combined to deliver stratified and precise treatment, which may further improve clinical efficacy and reduce treatment-related side effects.

Objective To explore the safety and mid-term efficacy of autologous hamstring tendon implantation in the treatment of severe anterior vaginal wall prolapse.Methods We performed a prospective single arm clinical study.From May 2021,pelvic organ prolapse(POP)patients with severe anterior vaginal wall prolapse as the main cause who had symptoms and required surgical treatment were included.The patient was fully informed and voluntarily selected autologous hamstring tendon implantation and high sacral ligament suspension.Postoperative follow-ups were carried out on the Pelvic Organ Prolapse Quantification(POP-Q),Pelvic Floor Distress Inventory-Short Form 20(PFDI-20),postoperative satisfaction score,and Patient Global Impression of Improvement(PGI-I).Function of the lower limb on the tendon removal side,as well as postoperative complications and re-operations were recorded.Results The operation time of tendon removal was(19.7±8.3)min,the operation time of pelvic floor was(122.1±37.8)min,the median intraoperative bleeding volume was 70 ml(range,50-400 ml),and there was no intraoperative co-morbidity or postoperative fever.A total of 12 cases were followed up for(26.4±2.5)months.The measured values of Aa,Ba,and C were 3(-1-3),5(2-10),and 4(-1-10)before operation and-3(-3-3),-3(-3-3),and-6(-6-3)at 24 months after operation,respectively,with significant difference(P＜0.05).The PFDI-20 scores of the 12 patients before surgery and at 24 months after surgery were 88.0 points(range,16.7-204.2 points)and 8.3 points(range,0-32.3 points),respectively,with significant difference(Z=-2.803,P=0.005).The PGI-I questionnaire showed 11 patients with significant improvement in postoperative symptoms and 1 patient with improvement.The satisfaction scores at 6 and 24 months after surgery were(4.8±0.4)points and(4.6±0.7)points,respectively.One patient experienced vaginal prolapse at 12 months after surgery,with a Ⅲ degree prolapse of the anterior wall and vaginal vault,the recurrence rate being 8.3％(1/12).Two patients had pulmonary embolism at 9 d and 2 weeks after surgery,with Clavien-Dindo Ⅱ and Ⅲ grades,and recovered after outpatient and hospitalization treatment.One patient was found fascia exposure at the vagina,and had improvement with medication treatment.All the patients had good wound healing at the tendon removal site,with normal muscle strength and lower limb activity.No re-operation was required due to recurrence or complications of tendon surgery.Conclusions Autologous hamstring tendon implantation is safe in the treatment of severe anterior vaginal wall prolapse with satisfactory mid-term efficacy.Before surgery,it is necessary to educate patients on lower limb exercise to prevent complications of venous thrombosis.

Objective:To learn about the single nucleotide polymorphism (SNP) population structure and regional distribution characteristics of Yersinia pestis in the natural focus of plague in Qinghai-Tibet Plateau. Methods:A total of 319 representative strains of Yersinia pestis isolated from natural focus of plague in Qinghai-Tibet Plateau from 1954 to 2020 were selected, and 2 298 SNP loci included in the global Yersinia pestis phylogenetic tree were compared by whole genome sequencing technology. MEGA 6.0 software was used to construct phylogenetic trees of 319 strains of Yersinia pestis from Qinghai-Tibet Plateau, determine the SNP population structure of Yersinia pestis in the focus, and describe its regional distribution characteristics. Results:The 319 strains of Yersinia pestis isolated from Qinghai-Tibet Plateau natural plague foci were distributed in 5 clades, namely 1.IN, 2.ANT, 3.ANT, 0.PE and 2.MED. The 1.IN clade contained 209 strains (65.52%, 209/319), which was the dominant population of strains in Qinghai Province, accounting for 90.51% (143/158). The 2.ANT clade contained 83 strains (26.02%, 83/319), which was the dominant population in Tibet Autonomous Region, accounting for 67.24% (78/116). The 3.ANT, 0.PE, and 2.MED clades contained 12 (3.76%, 12/319), 9 (2.82%, 9/319) and 6 strains (1.88%, 6/319), respectively, which were scattered in Qinghai Province, Gansu Province, Sichuan Province, Tibet Autonomous Region, and Xinjiang Uygur Autonomous Region under the jurisdiction of Qinghai-Tibet Plateau. Conclusion:The SNP population structure of Yersinia pestis in natural focus of plague in Qinghai-Tibet Plateau is relatively rich, and the strains are distributed in 5 clades: 1.IN, 2.ANT, 3.ANT, 0.PE and 2.MED, showing the distribution characteristics of specific regions.