BACKGROUND:Estrogen receptor α can act as an upstream protein to regulate the expression and phosphorylation level of adenosine monophosphate-activated protein kinase(AMPK).Activation of the estrogen receptor α-AMPK signaling pathway promotes osteogenic proliferation and differentiation.OBJECTIVE:To explore the molecular mechanism of estrogen receptor α regulating AMPK and its effect on osteoblast proliferation and differentiation at osteoblast cell line and molecular biology levels.METHODS:(1)The passaged MC3T3-E1 mouse embryonic osteoblasts were divided into three groups:blank control group,mock group(transfected with pCDNA3.1 control plasmid),and estrogen receptor α group(transfected with pCDNA3.1-estrogen receptor α overexpression plasmid),and RT-qPCR and western blot methods were used to detect the hepatic kinase B1,CaMKKβ,and AMPKα1 mRNA,protein and phosphorylation levels.(2)ChIP-qPCR was used to demonstrate that estrogen receptor α interacts with the hepatic kinase B1 promoter.Dual luciferase assay was used to demonstrate that estrogen receptorα interacts with the hepatic kinase B1 promoter region to activate its transcriptional expression.(3)The cells were divided into three groups:mock+shNC group,estrogen receptor α+shNC group,and estrogen receptor α+shLKB1 group.Changes in the expression levels of hepatic kinase B1,phosphorylated hepatic kinase B1,and phosphorylated AMPKα1 proteins in the cells were detected by western blot.(4)The cells were divided into four groups:mock group,estrogen receptor α group,estrogen receptor α+5 μmol/L Compound C(AMPK inhibitor)group,and estrogen receptor α+10 μmol/L Compound C group.The expression of proteins related to the AMPK signaling pathway and related to osteogenesis and osteoinductivity were detected by western blot method.Cells were transfected for 24 hours and then subjected to osteogenic induction for 14 days.Alkaline phosphatase staining was performed and cell viability in each group was detected.Mineralized nodule formation was detected by alizarin red staining at 21 days of osteogenic induction.(5)The cells were transfected and pretreated with different concentrations of AMPK inhibitor in corresponding groups,and cell viability was detected by cell counting kit 8.RESULTS AND CONCLUSION:(1)Estrogen receptor α activates the AMPK signaling pathway in MC3T3-E1 cells.(2)Estrogen receptor α promotes liver kinase B1 transcription and mediates AMPK signaling pathway activation.(3)Estrogen receptor α promotes the proliferation and differentiation of MC3T3-E1 cells by activating the AMPK signaling pathway,and the expression of AMPKα1,p-AMPKα,osteoprotegerin,osteopontin,and Runx2 proteins was down-regulated under the intervention of AMPK inhibitor,and the viability of osteoblasts was decreased.(4)To conclude,estrogen receptor α activates the AMPK signaling pathway by acting on liver kinase B1 promoter,promotes osteoblast proliferation and osteogenic differentiation,and prevents osteoporosis.

Villitis of unknown etiology (VUE) occurs in up to 15% of term placentas. Patients with VUE exhibit increased incidence of gestational diabetes mellitus, gestational hypertension, and preeclampsia, with demonstrated recurrence risk. VUE contributes to various adverse pregnancy outcomes. Its pathogenesis involves abnormal maternal immune responses against fetal allografts and may relate to unidentified microbial infections. Currently, VUE diagnosis relies exclusively on placental pathological examination. Clinical management remains primarily symptomatic, though immunomodulatory therapies show potential. This review summarizes recent advances in VUE epidemiology, pathogenesis, clinical significance, pathological features, and preventive strategies, aiming to enhance clinical understanding of this condition.

BACKGROUND:Estrogen receptor α can act as an upstream protein to regulate the expression and phosphorylation level of adenosine monophosphate-activated protein kinase(AMPK).Activation of the estrogen receptor α-AMPK signaling pathway promotes osteogenic proliferation and differentiation.OBJECTIVE:To explore the molecular mechanism of estrogen receptor α regulating AMPK and its effect on osteoblast proliferation and differentiation at osteoblast cell line and molecular biology levels.METHODS:(1)The passaged MC3T3-E1 mouse embryonic osteoblasts were divided into three groups:blank control group,mock group(transfected with pCDNA3.1 control plasmid),and estrogen receptor α group(transfected with pCDNA3.1-estrogen receptor α overexpression plasmid),and RT-qPCR and western blot methods were used to detect the hepatic kinase B1,CaMKKβ,and AMPKα1 mRNA,protein and phosphorylation levels.(2)ChIP-qPCR was used to demonstrate that estrogen receptor α interacts with the hepatic kinase B1 promoter.Dual luciferase assay was used to demonstrate that estrogen receptorα interacts with the hepatic kinase B1 promoter region to activate its transcriptional expression.(3)The cells were divided into three groups:mock+shNC group,estrogen receptor α+shNC group,and estrogen receptor α+shLKB1 group.Changes in the expression levels of hepatic kinase B1,phosphorylated hepatic kinase B1,and phosphorylated AMPKα1 proteins in the cells were detected by western blot.(4)The cells were divided into four groups:mock group,estrogen receptor α group,estrogen receptor α+5 μmol/L Compound C(AMPK inhibitor)group,and estrogen receptor α+10 μmol/L Compound C group.The expression of proteins related to the AMPK signaling pathway and related to osteogenesis and osteoinductivity were detected by western blot method.Cells were transfected for 24 hours and then subjected to osteogenic induction for 14 days.Alkaline phosphatase staining was performed and cell viability in each group was detected.Mineralized nodule formation was detected by alizarin red staining at 21 days of osteogenic induction.(5)The cells were transfected and pretreated with different concentrations of AMPK inhibitor in corresponding groups,and cell viability was detected by cell counting kit 8.RESULTS AND CONCLUSION:(1)Estrogen receptor α activates the AMPK signaling pathway in MC3T3-E1 cells.(2)Estrogen receptor α promotes liver kinase B1 transcription and mediates AMPK signaling pathway activation.(3)Estrogen receptor α promotes the proliferation and differentiation of MC3T3-E1 cells by activating the AMPK signaling pathway,and the expression of AMPKα1,p-AMPKα,osteoprotegerin,osteopontin,and Runx2 proteins was down-regulated under the intervention of AMPK inhibitor,and the viability of osteoblasts was decreased.(4)To conclude,estrogen receptor α activates the AMPK signaling pathway by acting on liver kinase B1 promoter,promotes osteoblast proliferation and osteogenic differentiation,and prevents osteoporosis.

Villitis of unknown etiology (VUE) occurs in up to 15% of term placentas. Patients with VUE exhibit increased incidence of gestational diabetes mellitus, gestational hypertension, and preeclampsia, with demonstrated recurrence risk. VUE contributes to various adverse pregnancy outcomes. Its pathogenesis involves abnormal maternal immune responses against fetal allografts and may relate to unidentified microbial infections. Currently, VUE diagnosis relies exclusively on placental pathological examination. Clinical management remains primarily symptomatic, though immunomodulatory therapies show potential. This review summarizes recent advances in VUE epidemiology, pathogenesis, clinical significance, pathological features, and preventive strategies, aiming to enhance clinical understanding of this condition.

Objective:To further investigate the safety and efficacy of Belimumab in the treatment of patients with systemic lupus erythematosus (SLE).Methods:All SLE patients treated with Belimumab from May 1, 2020 to February 1, 2022 in Peking Union Medical College Hospital were retrospectively collected and analyzed. The clinical manifestations, the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) score, and laboratory test such as levels of anti-dsDNA antibody, the medication before and after Belimumab treatment, adverse events were collected. Normally distributed data were tested using the t-test, otherwise the Wilcoxon paired signed rank test was used. Results:A total of 81 patients were enrolled in this study. The use of belimumab could significantly decrease the SLEDAI-2000 score [10.00(7.75, 12.00) vs. 4.00(3.75, 6.00), Z=-5.38, P<0.001], ESR of SLE patients [19.50(12.75, 32.25) mm/1 h vs. 14.00(7.75, 20.25) mm/1 h, Z=-3.71, P=0.003], anti-dsDNA titer detected by CLIFT [300.00 (117.00, 864.00) vs. 183.00(100.00, 471.00), Z=-4.15, P=0.001], meanwhile, increase the complement C3 [0.78 (0.62, 0.97)g/L vs. 0.69 (0.55, 0.84)g/L, Z=-4.68, P<0.001], and the complement C4 [0.12 (0.08, 0.19)g/L vs. 0.10 (0.05, 0.14)g/L, Z=-4.78, P<0.001]. We also observed that with the use of Belimumab, the dosage of Glucocorticoids decreased significantly, which were [10.00(7.50, 22.50) mg vs. 7.50(5.00, 10.00) mg, Z=-4.90, P<0.001]. In addition, the antibody of IgG, IgA and IgM decreased significantly. Only one patient stopped the administration of Belimumab due to the low level of immunoglobulin. Conclusion:Belimumab can alleviate disease activity of patients with SLE and help in safely tapering the daily dose of glucocorticoid with good safety.

Objective:To investigate the application value of robot-assisted parenchyma-sparing pancreatectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 54 patients who underwent robot-assisted parenchyma-sparing pancrea-tectomy in the Fujian Medical University Union Hospital from January 2017 to February 2023 were collected. There were 22 males and 32 females, aged (44±16)years. Observation indicators: (1) intraoperative conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the rank sum test. Count data were expressed as absolute numbers, and comparison between groups was performed using the Fisher exact probability. Results:(1) Intraoperative conditions. All 54 patients underwent robot-assisted parenchyma-sparing pancrea-tectomy successfully, without conversion to laparotomy. Of 54 patients, 32 cases underwent pancreatic tumor enucleation and 22 cases underwent central pancreatectomy. Of the 32 patients who underwent pancreatic tumor enucleation, 29 cases underwent conventional pancreatic tumor enucleation, and 3 cases underwent intraoperative repairing of main pancreatic duct injury. Of the 22 patients who underwent central pancreatectomy, 15 cases underwent end-to-end anastomosis, and 7 cases underwent Roux-en-Y pancreaticojejunostomy. There was no significant difference in operation time or volume of intraoperative blood loss between 29 patients undergoing conventional pancreatic tumor enucleation and 3 patients undergoing intraoperative repairing of main pancreatic duct injury ( t=-1.66, Z=-0.82, P>0.05). There were significant differences in operation time and volume of intraoperative blood loss between 15 patients undergoing end-to-end pancreatic anastomosis and 7 patients undergoing Roux-en-Y pancreaticojejunostomy ( t=-3.03, Z=-2.22, P<0.05). (2) Postoperative conditions. There were 38 of the 54 patients with postoperative complications, including 37 cases of pancreatic fistula and 1 case of delayed gastric emptying. There was no significant difference in post-operative pancreatic fistula between 29 patients undergoing conventional pancreatic tumor enuclea-tion and 3 patients undergoing intraoperative repairing of main pancreatic duct injury ( P>0.05). There was a significant difference in postoperative pancreatic fistula between 15 patients under-going end-to-end pancreatic anastomosis and 7 patients undergoing Roux-en-Y pancreaticojejunostomy ( P<0.05). (3) Follow-up. All 54 patients were followed up for 23(range, 3-76)months, and all of them survived without tumor recurrence or metastasis. None of the 32 patients undergoing enuclea-tion of pancreatic tumor experienced pancreatic endocrine or exocrine insufficiency. Of the 15 patients who underwent end-to-end pancreatic anastomosis, there were 2 cases of dilatation of the main pancreatic duct and atrophy of the distal pancreas, 1 case of pancreatic endocrine insufficiency and 1 case of exocrine insufficiency. Of the 7 patients who underwent Roux-en-Y pancreaticojejunostomy, there was 1 case of pancreatic endocrine insufficiency. Conclusion:Robot-assisted parenchyma-sparing pancreatectomy can provide intraoperative protection, repair and anastomosis of the main pancreatic duct.

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

Objective:To summarize the consultation data from the department of rheumatology and clinical immunology of Peking Union Medical College Hospital, and to describe the distribution of consultation needs of different rheumatic and immunologic diseases (RID) in each unit.Methods:To collect and analyze the data of patients who accepted the consultations of rheumatology and clinical immunology of Peking Union Medical College Hospital from January 1, 2021 to December 31, 2021.Results:A total of 1 640 consultations were executed. The ratio of male-to-female was 556∶1 084, with an average age of (44.5±16.0)years. The proportion of single consultation was 57.26% (939/1 640) while that of twice and multiple consultation was 42.74% (701/1 640). Among the consultations, 87.56% (1 436/1 640) were routine ones, especially from emergency 25.21% (362/1 436), department of infectious diseases 12.88% (185/1 436) and cardiology 12.47% (179/1 436). The other 12.44% (204/1 640) were multi-disciplinary treatment (MDT), mainly in department of general internal medicine, emergency and obstetrics. Main purposes of consultation included 52.66% (514/976) for RID condition assessment/medication adjustment and 47.34% (462/976) for etiological diagnosis in internal medicine unit; while 55.77% (58/104) for guidance for perioperative RID treatment in surgery. In Obstetrics and Gynecology, the majority purposes were RID condition assessment/medication adjustment 36.36% (12/33), perioperative treatment guidance 27.27% (9/33) and surgical risk/timing assessment 27.27% (9/33). Most consultations were focused on SLE, UCTD, SS, RA and TA.Conclusion:Requested as MDT and multiple repeat,consultation needs for department of rheumatology and clinical immunology are great, especially from emergency and infectious disease unit. It may improve the efficacy of consultation by popularizing the meaning of autoantibodies and enhancing the awarness of common RID and its complications, as well as the awareness of perioperative and prenatel periods.

Objective:To summarize the consultation data from the department of rheumatology and clinical immunology of Peking Union Medical College Hospital, and to describe the distribution of consultation needs of different rheumatic and immunologic diseases (RID) in each unit.Methods:To collect and analyze the data of patients who accepted the consultations of rheumatology and clinical immunology of Peking Union Medical College Hospital from January 1, 2021 to December 31, 2021.Results:A total of 1 640 consultations were executed. The ratio of male-to-female was 556∶1 084, with an average age of (44.5±16.0)years. The proportion of single consultation was 57.26% (939/1 640) while that of twice and multiple consultation was 42.74% (701/1 640). Among the consultations, 87.56% (1 436/1 640) were routine ones, especially from emergency 25.21% (362/1 436), department of infectious diseases 12.88% (185/1 436) and cardiology 12.47% (179/1 436). The other 12.44% (204/1 640) were multi-disciplinary treatment (MDT), mainly in department of general internal medicine, emergency and obstetrics. Main purposes of consultation included 52.66% (514/976) for RID condition assessment/medication adjustment and 47.34% (462/976) for etiological diagnosis in internal medicine unit; while 55.77% (58/104) for guidance for perioperative RID treatment in surgery. In Obstetrics and Gynecology, the majority purposes were RID condition assessment/medication adjustment 36.36% (12/33), perioperative treatment guidance 27.27% (9/33) and surgical risk/timing assessment 27.27% (9/33). Most consultations were focused on SLE, UCTD, SS, RA and TA.Conclusion:Requested as MDT and multiple repeat,consultation needs for department of rheumatology and clinical immunology are great, especially from emergency and infectious disease unit. It may improve the efficacy of consultation by popularizing the meaning of autoantibodies and enhancing the awarness of common RID and its complications, as well as the awareness of perioperative and prenatel periods.

Objective:To analyze the risk factors of patients with ankylosing spondylitis (AS) combined with premature coronary atherosclerotic heart disease (PCAD).Methods:A total of 74 patients with AS and coronary atherosclerotic heart disease (CAD) in Peking Union Medical College Hospital from January 1983 to July 2021 were enrolled. According to the age of onset of coronary heart disease, the 74 patients were divided into PCAD group and NPCAD (non-premature coronary heart disease) group. T test and Chi square test were used to analyze the data of the two groups, the risk factors for AS-PCAD were analyzed by multivariate Logistic regression. Results:① There were 37 cases in the PCAD group and 37 cases in the NPCAD group. In the PCAD group, there were 28 men and 9 women; wherease all were men in the NPCAD group. The difference was statistically significant ( χ2=10.25, P=0.001). ② Compared with the NPCAD group, the age of AS-PCAD group was younger [(23±10) years vs (29±12) years, t=-2.28, P=0.026], and the course from AS to CAD was shorter [(25±10) years vs (34±13) years, t=-3.00, P=0.004], hemoglobin (Hb) level was lower [(122±23) g/L vs(132±18) g/L, t=2.10, P=0.039], rate of anemia was higher [38.5%(14/37) vs 16.2%(6/37), χ2=4.39, P=0.037]. Proportion of increased C-reactive protein (CRP) was higher [65.5%(19/29) vs 35.5%(11/31), χ2=5.41, P=0.019]. ③ Juvenile onset AS (JoAS)[ OR(95% CI)=3.45(1.31, 9.10), P=0.012] and high levels of CRP [ OR (95% CI)=3.68 (1.44, 9.40), P=0.006] might berisk factors of AS-PCAD by multiple logisctic regression analysis. Conclusion:Patients with AS have a higher probability of PCAD, especially in those patients with JoAS, persistent inflammation and anemia. It is necessary to be alert to the risk of PCAD and early screening.