Objective To construct and assess a training program for newly appointed nurse managers.Methods According to the evaluation index system of nurse manager's post competency,a training team was set up,training experts were selected,and a training program for newly appointed nurse managers was constructed,which was based on the learning pyramid theory,and implemented in 20 newly appointed nurse managers.The scores of post competency scale,core competence scale,team assistance ability scale,and emergency management scale,and the result of practical examination were used as evaluation indexes.Results After half-year training,the mean and four dimension scores of post competency,the mean and six dimension scores of core competence,the mean and four dimension scores of team assistance ability,and the mean and four dimensions scores of emergency management in the 20 newly appointed nurses were significantly higher than those before training(all P<0.05).The mean total score of practical assessment was 92.45±1.81.Conclusion The training program for newly appointed nurse mangers on the basis of the learning pyramid theory can effectively improves the post competence,core competence and practical ability.It can provide theoretical reference for cultivating newly appointed nurse mangers.

Objective:To compare the treatment effect of endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomy plus laparoscopic cholecystectomy (ERCP/EST+ LC) and laparoscopic cholecystectomy plus laparoscopic common bile duct exploration (LC+ LCBDE) for patients with choledocholithiasis combined with gallbladder stones.Methods:Clinical data of 172 patients with choledocholithiasis combined with gallbladder stones treated in Heze Municipal Hospital from March 2018 to March 2021 were retrospectilvely analyzed, including 78 males and 94 females, aged (66.88±9.72) years. According to surgical method, patients were divided into the ERCP/EST+ LC group ( n=86) and LC+ LCBDE group ( n=86). The initial clearance rate of choledochal stones, operation time, intraoperative blood loss and postoperative complications were compared between the groups. Results:The initial clearance rate of the choledochal stones of the ERCP/EST+ LC group is 76.5%(13/17), lower than 96.3%(26/27) of LC+ LCBDE group when the diameter of stones was over 1.2 cm ( χ2=4.07, P=0.044). When the number of choledochal stones were more than 3, the initial clearance rate of the ERCP/EST+ LC group is 78.9%(15/19), lower than that of the LC+ LCBDE group [96.7%(29/30), χ2=3.99, P=0.046]. The operation time of LC+ LCBDE group was longer than that of ERCP/EST+ LC group [(129.07±19.33)min vs. (101.86±27.48)min, t=7.51, P<0.001]. The median intraoperative blood loss of LC+ LCBDE group and ERCP/EST+ LC group was 25.0 (20.0, 30.0) ml and 13.0 (10.0, 15.0) ml, respectively ( Z=916.00, P<0.001). The age, gender, maximum diameter of stones, number of stones, preoperative common bile duct diameter, surgical success rate, postoperative hospital stay, total stone clearance rate, and complication rate were comparable between the groups (all P>0.05). Conclusion:Both LC+ LCBDE and ERCP/EST+ LC are safe and feasible for choledocholithiasis combined with cholecystolithiasis. When the maximum diameter of choledochal stones is ≥1.2 cm or the number of choledochal stones is ≥3, LC+ LCBDE should be favored. When patient is in poor general condition, ERCP/EST+ LC might be more feasible.

Objective:To observe the ameliorative effects of exogenous miR-146a-5p on lipopolysaccharide (LPS)-induced embryonic resorption and fetal mouse dysplasiamice, and to preliminarily investigate its mechanism of action.Methods:1) After 36 healthy adult female mice were mated with male mice, uterine tissues were collected from females on day (D) 0 (D0/not pregnant), D0.5 (the day of embryo observed), D4.5, D7.5, D9.5 and D13.5 of gestation, and the expression levels of miR-146a-5p and its target gene TRAF6 protein in uterine tissues of mice at different gestation periods were detected by real-time fluorescent quantitative PCR (qPCR) and Western blotting. 2) The mice on D7.5 of pregnancy were treated with intraperitoneal injection of saline (control, COL group), intraperitoneal injection of 250 μg/kg LPS (named LPS250 group), LPS combined with tail vein injection of 10 nmol miR-146a-5p unrelated sequence (negative control, NC, named LPS250+NC group), or LPS combined with tail vein injection of 10 nmol miR-146a-5p agonist (miR-146a-5p agomir, named LPS250+miR-146a-5p agomir group). The total number of embryos and the number of absorbed embryos in the uterus of pregnant mice were measured and statistically analyzed on D8.5, and the expression levels of TNFα mRNA and TRAF6 protein in uterine tissues were detected by qPCR and Western blotting. 3) Then we reduced the dosage of LPS to 50 μg/kg and treated the same groups, named LPS50+NC group, LPS50+miR-146a-5p agomir group, respectively. The total number of fetal mice/embryos, the number of absorbed embryos, the number of surviving fetal mice, the weight of surviving fetal mice and the weight of the placenta were measured and statistically analyzed on D16.5. 4) Primary mouse bone marrow-derived macrophages (BMDM) were isolated and cultured. Mouse BMDM was inducted to M1 polarization by LPS stimulation, and then was transient transfected miR-146a-5p mimics or their NC fragments. The expression levels of TNFα mRNA and pSTAT1 protein were detected by qPCR and Western blotting. Results:The expression level of miR-146a-5p was significantly higher in the implantation sites of D7.5, D9.5 and D13.5 pregnant mice than in the non-implantation sites ( P=0.013, P=0.012, P=0.003), and the protein expression level of TRAF6 was significantly lower in the implantation site of D13.5 pregnant mice than in the non-implantation site ( P=0.012). After intraperitoneal injection of 250 μg/kg of LPS into D7.5 pregnant mice, the embryo absorption rate of the LPS group on D8.5 was 43.13%±3.31%, which was significantly higher than that of COL group (0%, P=0.002), while the embryo absorption rate of the LPS250+miR-146a-5p agomir group (13.50%±0.87%) was significantly lower than that of the LPS250+NC group (59.33%±4.04%, P=0.001). After intraperitoneal injection of 50 μg/kg of LPS combined with tail vein injection of NC or miR-146a-5p agomir to D7.5 pregnant mice, the fetal mouse weight [(0.29±0.09) g] and placental weight [(0.06±0.02) g] of surviving fetal mice in the LPS50+NC group on D16.5 and the LPS50+miR-146a-5p agomir group were statistically significant [(0.46±0.06) g, P<0.001; (0.07±0.02) g, P=0.021], and the differences in the number of absorbed embryos and embryo uptake rate between the two groups were not statistically significant (all P>0.05). The expression levels of both pSTAT1 protein and TNFα mRNA were significantly downregulated in BMDM transfected with miR-146a-5p mimics compared with those transfected with NC ( P=0.012, P=0.039). Conclusion:miR-146a-5p expression levels were significantly increased at the maternal-fetal interface during the late stage of mouse embryo implantation and placental development. Exogenous miR-146a-5p could effectively improve LPS-induced mouse embryo resorption and fetal mouse dysplasia. miR-146a-5p could inhibit the M1 polarization activity of mouse macrophages, suggesting that miR-146a-5p may inhibit the M1 polarization activity of mouse macrophages by suppressing M1 polarization of mouse maternal-fetal interface macrophages to safeguard the normal establishment and maintenance of pregnancy.

Objective:To observe the ameliorative effects of exogenous miR-146a-5p on lipopolysaccharide (LPS)-induced embryonic resorption and fetal mouse dysplasiamice, and to preliminarily investigate its mechanism of action.Methods:1) After 36 healthy adult female mice were mated with male mice, uterine tissues were collected from females on day (D) 0 (D0/not pregnant), D0.5 (the day of embryo observed), D4.5, D7.5, D9.5 and D13.5 of gestation, and the expression levels of miR-146a-5p and its target gene TRAF6 protein in uterine tissues of mice at different gestation periods were detected by real-time fluorescent quantitative PCR (qPCR) and Western blotting. 2) The mice on D7.5 of pregnancy were treated with intraperitoneal injection of saline (control, COL group), intraperitoneal injection of 250 μg/kg LPS (named LPS250 group), LPS combined with tail vein injection of 10 nmol miR-146a-5p unrelated sequence (negative control, NC, named LPS250+NC group), or LPS combined with tail vein injection of 10 nmol miR-146a-5p agonist (miR-146a-5p agomir, named LPS250+miR-146a-5p agomir group). The total number of embryos and the number of absorbed embryos in the uterus of pregnant mice were measured and statistically analyzed on D8.5, and the expression levels of TNFα mRNA and TRAF6 protein in uterine tissues were detected by qPCR and Western blotting. 3) Then we reduced the dosage of LPS to 50 μg/kg and treated the same groups, named LPS50+NC group, LPS50+miR-146a-5p agomir group, respectively. The total number of fetal mice/embryos, the number of absorbed embryos, the number of surviving fetal mice, the weight of surviving fetal mice and the weight of the placenta were measured and statistically analyzed on D16.5. 4) Primary mouse bone marrow-derived macrophages (BMDM) were isolated and cultured. Mouse BMDM was inducted to M1 polarization by LPS stimulation, and then was transient transfected miR-146a-5p mimics or their NC fragments. The expression levels of TNFα mRNA and pSTAT1 protein were detected by qPCR and Western blotting. Results:The expression level of miR-146a-5p was significantly higher in the implantation sites of D7.5, D9.5 and D13.5 pregnant mice than in the non-implantation sites ( P=0.013, P=0.012, P=0.003), and the protein expression level of TRAF6 was significantly lower in the implantation site of D13.5 pregnant mice than in the non-implantation site ( P=0.012). After intraperitoneal injection of 250 μg/kg of LPS into D7.5 pregnant mice, the embryo absorption rate of the LPS group on D8.5 was 43.13%±3.31%, which was significantly higher than that of COL group (0%, P=0.002), while the embryo absorption rate of the LPS250+miR-146a-5p agomir group (13.50%±0.87%) was significantly lower than that of the LPS250+NC group (59.33%±4.04%, P=0.001). After intraperitoneal injection of 50 μg/kg of LPS combined with tail vein injection of NC or miR-146a-5p agomir to D7.5 pregnant mice, the fetal mouse weight [(0.29±0.09) g] and placental weight [(0.06±0.02) g] of surviving fetal mice in the LPS50+NC group on D16.5 and the LPS50+miR-146a-5p agomir group were statistically significant [(0.46±0.06) g, P<0.001; (0.07±0.02) g, P=0.021], and the differences in the number of absorbed embryos and embryo uptake rate between the two groups were not statistically significant (all P>0.05). The expression levels of both pSTAT1 protein and TNFα mRNA were significantly downregulated in BMDM transfected with miR-146a-5p mimics compared with those transfected with NC ( P=0.012, P=0.039). Conclusion:miR-146a-5p expression levels were significantly increased at the maternal-fetal interface during the late stage of mouse embryo implantation and placental development. Exogenous miR-146a-5p could effectively improve LPS-induced mouse embryo resorption and fetal mouse dysplasia. miR-146a-5p could inhibit the M1 polarization activity of mouse macrophages, suggesting that miR-146a-5p may inhibit the M1 polarization activity of mouse macrophages by suppressing M1 polarization of mouse maternal-fetal interface macrophages to safeguard the normal establishment and maintenance of pregnancy.

Objective:To compare the treatment effect of endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomy plus laparoscopic cholecystectomy (ERCP/EST+ LC) and laparoscopic cholecystectomy plus laparoscopic common bile duct exploration (LC+ LCBDE) for patients with choledocholithiasis combined with gallbladder stones.Methods:Clinical data of 172 patients with choledocholithiasis combined with gallbladder stones treated in Heze Municipal Hospital from March 2018 to March 2021 were retrospectilvely analyzed, including 78 males and 94 females, aged (66.88±9.72) years. According to surgical method, patients were divided into the ERCP/EST+ LC group ( n=86) and LC+ LCBDE group ( n=86). The initial clearance rate of choledochal stones, operation time, intraoperative blood loss and postoperative complications were compared between the groups. Results:The initial clearance rate of the choledochal stones of the ERCP/EST+ LC group is 76.5%(13/17), lower than 96.3%(26/27) of LC+ LCBDE group when the diameter of stones was over 1.2 cm ( χ2=4.07, P=0.044). When the number of choledochal stones were more than 3, the initial clearance rate of the ERCP/EST+ LC group is 78.9%(15/19), lower than that of the LC+ LCBDE group [96.7%(29/30), χ2=3.99, P=0.046]. The operation time of LC+ LCBDE group was longer than that of ERCP/EST+ LC group [(129.07±19.33)min vs. (101.86±27.48)min, t=7.51, P<0.001]. The median intraoperative blood loss of LC+ LCBDE group and ERCP/EST+ LC group was 25.0 (20.0, 30.0) ml and 13.0 (10.0, 15.0) ml, respectively ( Z=916.00, P<0.001). The age, gender, maximum diameter of stones, number of stones, preoperative common bile duct diameter, surgical success rate, postoperative hospital stay, total stone clearance rate, and complication rate were comparable between the groups (all P>0.05). Conclusion:Both LC+ LCBDE and ERCP/EST+ LC are safe and feasible for choledocholithiasis combined with cholecystolithiasis. When the maximum diameter of choledochal stones is ≥1.2 cm or the number of choledochal stones is ≥3, LC+ LCBDE should be favored. When patient is in poor general condition, ERCP/EST+ LC might be more feasible.

Objective:To analyze the clinical characteristics of elderly-onset gouty arthritis and risk factors of tophi.Methods:A total of 1 239 gout patients were retrospective selected in the outpatient department of the Gout Clinical Medical Center of the Affiliated Hospital of Qingdao University from 2016 to 2022. According to age of onset, they were divided into the young and middle-aged group(aged<60) consisted of 826 cases, and the elderly group(aged≥60) consisted of 413 cases. Compare the clinical characteristics of elderly with Young and Middle-aged patients.Results:The systolic blood pressure, fasting blood glucose, creatinine, regular exercise, comorbidities, and tophi in the elderly group was higher than that in the middle-aged and young group. The proportion of diastolic blood pressure, serum triglycerides, eGFR, serum uric acid, alcohol consumption rate, and family history of gout was lower than that of young and middle-aged group( P<0.05); In the elderly-onset group, the initial site of arthritis was commonly observed in the first metatarsophalangeal joint. The proportion of the first attack with the upper limb joint was higher in old age group than in young and middle age group( P<0.05). Renal underexcretion type was the main subtype in the elderly group, and the proportion of overproduction type was higher than that of the young and middle-aged group( P<0.05). The logistic regression analysis showed that age, urea nitrogen, disease duration≥10 years and family history of gout were risk factors for tophi in elderly patients( P<0.05). Conclusion:The elderly-onset gout has unique clinical characteristics, characterized by a higher prevalence of tophi, a higher rate of complications. An initial site of arthritis commonly observed in the first metatarsophalangeal joint and the predominant type of uric acid excretion is renal excretion impairment. Early diagnosis and treatment, control of blood uric acid levels, smoking cessation and alcohol, regular exercise should be applied to prevent or delay the formation of tophi.

Objective:To investigate the effect and possible mechanism of the X-ray radiation-induced abscopal effects (X-RIAEs) on the ovarian reserve of mice.Methods:Totally sixteen female C57BL/6J mice aged 6-8 weeks with regular estrous cycle were randomly divided into the sham group ( n=8) and irradiation group ( n=8). After anesthesia, the mice in the irradiation group were irradiated with 8 Gy X-ray on the local area of the chest every day for 3 d, while the mice in the sham group were not irradiated. After irradiation 21 d, the estrous cycle, serum hormones, serum pro-inflammatory factors, and ovarian morphological changes were detected. Ribonucleic acid sequencing (RNA-seq) was used to detect the expression of transcriptional levels in mouse ovarian tissues. The differentially expressed genes (DEGs) were screened and analyzed by gene ontology-biological process (GO_BP). Real-time quantitative polymerase chain reaction (RT-qPCR) verified the sequencing results. The expression and localization of spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 1 (SOHLH1) and neutrophil elastase (NE) in ovarian tissues were detected by immunohistochemistry (IHC). Results:Compared with mice in the sham group, the irradiation group had a disordered estrous cycle, reduced primordial follicles[10.50 (1.25, 12.75) vs. 60.00 (30.00, 90.25), P<0.001] and growing follicles [(4.50 (2.50, 9.00) vs. 18.50 (18.00, 20.75), P<0.001], significantly increased atretic follicles [56.00 (45.25, 98.75) vs. 12.50 (5.25, 20.25), P<0.001]. The levels of serum estradiol [(70.28±5.27) pmol/L] and anti-Müllerian hormone [(104.00±6.98) μg/L] in the irradiation group were significantly lower than those in the sham group [(97.58±7.25) pmol/L, P=0.016; (129.70±8.39) μg/L, P=0.046], but the follicle-stimulating hormone (FSH) level in the irradiation group was not significantly different from that in the sham group ( P>0.05). Compared with the sham group, the serum levels of TNF-α [(488.30±36.20) μg/L vs. (31.61±12.89) μg/L, P<0.001] and IL-1β [(62.37±2.50) μg/L vs. (52.75±2.06) μg/L, P=0.018] in the irradiation group were significantly increased, and the serum level of interleukin (IL)-6 in the irradiation group was also increased compared with the sham group, but the difference was not statistically significant ( P>0.05). The results of GO_BP analysis showed that the down-regulated DGEs were mainly involved in the process of follicular development, and the up-regulated DGEs were involved in the inflammation process. The results of RT-qPCR were consistent with those of sequencing. The immunohistochemistry results showed that the positive expression area of SOHLH1 in the irradiation group [(23.18±4.00)%] was significantly lower than that of the sham group [(65.90±6.28)%, P=0.005], while the positive expression area of NE [(30.73±4.00)%] was significantly higher than that of the sham group [(14.47±2.22)%, P=0.024]. Conclusion:X-RIAEs can induce an inflammatory reaction in ovarian tissue and inhibit the growth and development of ovarian follicles in mice, which leads to a decrease in ovarian reserve.

Objective:To investigate the effect and possible mechanism of the X-ray radiation-induced abscopal effects (X-RIAEs) on the ovarian reserve of mice.Methods:Totally sixteen female C57BL/6J mice aged 6-8 weeks with regular estrous cycle were randomly divided into the sham group ( n=8) and irradiation group ( n=8). After anesthesia, the mice in the irradiation group were irradiated with 8 Gy X-ray on the local area of the chest every day for 3 d, while the mice in the sham group were not irradiated. After irradiation 21 d, the estrous cycle, serum hormones, serum pro-inflammatory factors, and ovarian morphological changes were detected. Ribonucleic acid sequencing (RNA-seq) was used to detect the expression of transcriptional levels in mouse ovarian tissues. The differentially expressed genes (DEGs) were screened and analyzed by gene ontology-biological process (GO_BP). Real-time quantitative polymerase chain reaction (RT-qPCR) verified the sequencing results. The expression and localization of spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 1 (SOHLH1) and neutrophil elastase (NE) in ovarian tissues were detected by immunohistochemistry (IHC). Results:Compared with mice in the sham group, the irradiation group had a disordered estrous cycle, reduced primordial follicles[10.50 (1.25, 12.75) vs. 60.00 (30.00, 90.25), P<0.001] and growing follicles [(4.50 (2.50, 9.00) vs. 18.50 (18.00, 20.75), P<0.001], significantly increased atretic follicles [56.00 (45.25, 98.75) vs. 12.50 (5.25, 20.25), P<0.001]. The levels of serum estradiol [(70.28±5.27) pmol/L] and anti-Müllerian hormone [(104.00±6.98) μg/L] in the irradiation group were significantly lower than those in the sham group [(97.58±7.25) pmol/L, P=0.016; (129.70±8.39) μg/L, P=0.046], but the follicle-stimulating hormone (FSH) level in the irradiation group was not significantly different from that in the sham group ( P>0.05). Compared with the sham group, the serum levels of TNF-α [(488.30±36.20) μg/L vs. (31.61±12.89) μg/L, P<0.001] and IL-1β [(62.37±2.50) μg/L vs. (52.75±2.06) μg/L, P=0.018] in the irradiation group were significantly increased, and the serum level of interleukin (IL)-6 in the irradiation group was also increased compared with the sham group, but the difference was not statistically significant ( P>0.05). The results of GO_BP analysis showed that the down-regulated DGEs were mainly involved in the process of follicular development, and the up-regulated DGEs were involved in the inflammation process. The results of RT-qPCR were consistent with those of sequencing. The immunohistochemistry results showed that the positive expression area of SOHLH1 in the irradiation group [(23.18±4.00)%] was significantly lower than that of the sham group [(65.90±6.28)%, P=0.005], while the positive expression area of NE [(30.73±4.00)%] was significantly higher than that of the sham group [(14.47±2.22)%, P=0.024]. Conclusion:X-RIAEs can induce an inflammatory reaction in ovarian tissue and inhibit the growth and development of ovarian follicles in mice, which leads to a decrease in ovarian reserve.

AIM: To evaluate the bioequivalence of the test and reference preparations of solifenacin succinate tablets administered once orally under fasting and fed conditions in Chinese healthy volunteers. METHODS: The study was designed as single-center, randomized, open, self-crossover and twenty four healthy volunteers were recruited respectively in fasting and fed conditions. Subjects were assigned to receive a single oral of the test or reference formulation per period at a dose of 10 mg. The plasma concentration of solifenacin was analyzed by LC-MS/MS. The major pharmacokinetic parameters were calculated by WinNonlin 7.0, then the bioequivalence was evaluated.RESULTS: The main pharmacokinetic parameters of a single oral solifenacin succinate under fasting condition for test and reference preparation were as follows: C