Objective:To explore the correlation between intrahepatic cholestasis of pregnancy(ICP)and ad-verse pregnancy outcomes.Methods:A total of 511 singleton pregnant women with ICP treated at The Third Affili-ated Hospital of Guangzhou Medical University from August 2017 to January 2024 were selected as the study sub-jects.Among them,patients were divided into the adverse pregnancy outcome group(n=49)and the control group without adverse pregnancy outcomes(n=462).The general and clinical data of the two groups were com-pared and analyzed.Results:①General situation:The number of pregnancies and deliveries,ICU transfer rate,total hospital stay,and total hospitalization costs were significantly higher in the adverse pregnancy outcome group compared to the control group(P<0.05).The number of prenatal check-ups,diagnostic gestational weeks,and gestational weeks at delivery were significantly lower compared to the control group(P<0.05).②Clinical symp-toms:The incidence of itching in the adverse pregnancy outcome group was lower compared to the control group(10.2%vs.26.6%,P<0.05),while other symptoms such as rash,fatigue,jaundice,and gastrointestinal symp-toms showed no significant difference between the two groups(P>0.05).③Laboratory examinations:Compared with the control group,patients in the adverse pregnancy outcome group had significantly the increased levels of alanine aminotransferase,aspartate aminotransferase,uric acid,urea nitrogen,and triglycerides,and significantly the decreased levels of alkaline phosphatase and fasting blood glucose,with statistical significance(P<0.05).Other biochemical indicators showed no significant difference between the two groups(P>0.05).④ICP grading and complications:The proportion of early-onset ICP,severe and very severe ICP in the adverse pregnancy out-come group was significantly higher compared to the control group(P<0.001);the proportion of adverse preg-nancy outcome group with pregnancy-induced hypertension was significantly higher compared to the control group;the incidence of preterm birth,fetal growth restriction,meconium-stained amniotic fluid,and fetal distress in the adverse pregnancy outcome group was significantly higher compared to the control group(P<0.001).⑤Neo-natal outcomes:The neonatal Apgar scores(1 min,5 min,10 min)and neonatal weight in the adverse pregnancy outcome group were lower compared to the control group(P<0.001),and the incidence of mild neonatal asphyx-ia was significantly higher,with a statistically significant difference(P<0.001).Conclusions:The severity of ICP is closely related to the occurrence of adverse pregnancy outcomes.Therefore,it is clinically necessary to pay at-tention to the grading of ICP,closely monitor the levels of total bile acids and liver enzymes,and try to avoid ad-verse pregnancy outcomes,especially intrauterine fetal death.

Objective:To explore the correlation between intrahepatic cholestasis of pregnancy(ICP)and ad-verse pregnancy outcomes.Methods:A total of 511 singleton pregnant women with ICP treated at The Third Affili-ated Hospital of Guangzhou Medical University from August 2017 to January 2024 were selected as the study sub-jects.Among them,patients were divided into the adverse pregnancy outcome group(n=49)and the control group without adverse pregnancy outcomes(n=462).The general and clinical data of the two groups were com-pared and analyzed.Results:①General situation:The number of pregnancies and deliveries,ICU transfer rate,total hospital stay,and total hospitalization costs were significantly higher in the adverse pregnancy outcome group compared to the control group(P<0.05).The number of prenatal check-ups,diagnostic gestational weeks,and gestational weeks at delivery were significantly lower compared to the control group(P<0.05).②Clinical symp-toms:The incidence of itching in the adverse pregnancy outcome group was lower compared to the control group(10.2%vs.26.6%,P<0.05),while other symptoms such as rash,fatigue,jaundice,and gastrointestinal symp-toms showed no significant difference between the two groups(P>0.05).③Laboratory examinations:Compared with the control group,patients in the adverse pregnancy outcome group had significantly the increased levels of alanine aminotransferase,aspartate aminotransferase,uric acid,urea nitrogen,and triglycerides,and significantly the decreased levels of alkaline phosphatase and fasting blood glucose,with statistical significance(P<0.05).Other biochemical indicators showed no significant difference between the two groups(P>0.05).④ICP grading and complications:The proportion of early-onset ICP,severe and very severe ICP in the adverse pregnancy out-come group was significantly higher compared to the control group(P<0.001);the proportion of adverse preg-nancy outcome group with pregnancy-induced hypertension was significantly higher compared to the control group;the incidence of preterm birth,fetal growth restriction,meconium-stained amniotic fluid,and fetal distress in the adverse pregnancy outcome group was significantly higher compared to the control group(P<0.001).⑤Neo-natal outcomes:The neonatal Apgar scores(1 min,5 min,10 min)and neonatal weight in the adverse pregnancy outcome group were lower compared to the control group(P<0.001),and the incidence of mild neonatal asphyx-ia was significantly higher,with a statistically significant difference(P<0.001).Conclusions:The severity of ICP is closely related to the occurrence of adverse pregnancy outcomes.Therefore,it is clinically necessary to pay at-tention to the grading of ICP,closely monitor the levels of total bile acids and liver enzymes,and try to avoid ad-verse pregnancy outcomes,especially intrauterine fetal death.

Objective:To explore the mechanism of zoledronic acid (ZOL) affects osteogenic differentiation and bone formation through the regulation of sirtuin 3 (SIRT3) / P53 expression.Methods:Bone marrow mesenchymal stem cells (BMSCs) were induced to differentiate into osteogenic cells, the expression of SIRT3 in the cells was detected, and the targeting regulation relationship between SIRT3 and P53 was analyzed. The intracellular expressions of SIRT3 and P53 were intervened and ZOL was used to treat the cells. MTT method, Western blot method and kit were used to detect cell viability, osteogenesis-related genes Osteoprotegerin (OPG), runt-related transcription factor 2 (Runx2) expression, alkaline phosphatase (ALP) activity and alizarin red S (ARS) staining, respectively. Ovariectomy (OVX) was used to construct a rat model and explore the effect of ZOL on the progression of osteoporosis (OP) in vivo.Results:ZOL promoted osteogenic differentiation of BMSCs. The expression of SIRT3 was down-regulated in the serum of OP patients (0.78±0.23) compared with that of healthy subjects (1.00±0.26 vs. 0.78±0.23. t=3.85, P<0.001). During the osteogenic differentiation of BMSCs, the expression level of SIRT3 gradually increased with the prolonged induction of osteogenesis. Compared with the p53 protein expression and BMSCs activity in the control group, SIRT3 knockout could increase the expression level of p53 protein (0.59±0.05 vs. 1.01±0.11. t=6.02, P=0.004) but inhibited the activity of BMSCs (100.00±8.41 vs. 51.26±5.59. t=8.36, P=0.001). After ZOL treatment, the inhibitory effect of SIRT3 on cell viability (49.61±5.11 vs. 87.61±7.31. t=7.38, P=0.002) and osteogenesis was relieved, and the level of P53 was inhibited (1.10±0.10 vs. 0.69±0.04. t=6.59, P=0.003). P53 overexpression partially offseted the effects of ZOL on cell viability (84.61±6.52 vs. 66.54±5.47. t=3.68, P=0.021) and osteogenesis. Compared with the sham surgery group, the OVX group showed inhibition of osteogenesis in rats, and ZOL treatment significantly improved osteogenic inhibition. ZOL treatment increased the expression level of SIRT3 protein in bone tissue of OVX rats, but inhibited the expression level of P53. Conclusion:ZOL promoted osteogenic differentiation and bone formation of BMSCs by promoting the ubiquitination and degradation of P53 by SIRT3.

Background In recent years,rare diseases have become a major public health issue.There is an urgent need to improve the diagnosis and treatment for these diseases,and the training for doctors engaged in rare diseases is an important part of it.Methods This study conducted a questionnaire survey on the doctors engaged in rare diseases in Peking Union Medical College Hospital to better understand their characteristics and evaluate their psychological and working status.Results A total of 95 questionnaires from doctors engaged in rare diseases were collected in this study,among which the female:male ratio was 1.6∶1,and 63.2％of them were in the 40-54 age group.Their main reason for choosing rare diseases was the enjoyment in the process of studying rare diseases(64.2％).Compared with the 108 doctors not engaged in rare diseases surveyed during the same period,those working on rare diseases reported higher patient recognition based on self-evaluation(P＜0.001).In terms of the time-consuming work,in addition to routine medical work,teaching and research,34.7％of doctors engaged in rare diseases chose doctor-patient communication and 31.6％chose medical man-agement communication.Conclusions This study proposes some suggestions on the talent training for rare dis-eases,the establishment of continuing education platforms,and the technology and policy support needed through the analysis of the questionnaire survey results of doctors engaged in rare diseases.

Objective To investigate the relationship between the expression level of miRNA Let-7 and the deletion of DNA mismatch repair(dMMR)proteins in endometrial carcinoma(EC).Methods A total of 74 patients with EC who underwent radical surgery at Lianyungang Maternal and Child Health Hospital in Jiangsu Province from May 2016 to December 2022 were selected.Immunohistochemistry was used to detect the expression of dMMR proteins(including MLH1,PMS2,MSH2,and MSH6),while real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was performed to measure the relative expression levelof miRNA Let-7.According to the expression of dMMR proteins,EC patients were divided into the complete expression group(n=43)and the absent expression group(n=31).Logistic multivariate regression analysis was conducted to identify risk factors associated with dMMR protein deficiency,and receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of relevant factors.Results In 74 cases of EC,the expression level of miRNA Let-7 was higher in the myographic infiltration＜1/2 group than in the myographic infiltration ≥ 1/2 group,and the difference was significant(t=1.79,P=0.04).The deletion rate of dMMR protein expression was 41.89％,the deletion rate in patients aged＜55 years and miRNA Let-7 low expression group(＜0.715)were higher than those in ≥ 55 years and miRNA Let-7 high expression group(≥ 0.715),with significant differences(x2=3.92,4.50,all P＜0.05).Logistic regression analysis revealed that miRNA Let-7 expression level was an independent risk factor for dMMR expression deletion(P=0.012).Spearman correlation analysis demonstrated a negative correlation between miRNA Let-7 expression level and dMMR protein deletion(r=-0.247,P=0.034).ROC curve analysis indicated that the expression level of miRNA Let-7 had a certain predictive value for dMMR protein deletion in EC patients,with an AUC of 0.737,an optimal critical value of 0.77,a sensitivity and a specificity of 0.651 and 0.806,respectively.Conclusion The expression level of miRNA Let-7 was correlated with the deletion of dMMR proteins in patients diagnosed with EC.Moreover,it served as a potential risk factor for dMMR protein deficiency.It may offer valuable insights into predicting dMMR expression deletion.

In recent years,with the development of gene testing and new drug research,the diagnosis and treatment of inherited diseases have made rapid progress,corresponding to higher requirements for genetics education.As a teacher of medical genetics,the author joined the course remodeling during last 10 years from a web-based study of genetic disorders to a"case-based learning"supported by flipped classroom in order to optimize teaching effects and learning outcomes.The result of this remodeling project proposes a new strategy to guide perspectives course de-sign in future.

Objective:To investigate the correlation of illness uncertainty with anxiety and depression in perioperative patients with early gastric cancer.Methods:A cross-sectional survey was conducted among 107 patients with early gastric cancer who were admitted in Department of Gastroenterology of a Class A tertiary hospital in Beijing from April 2020 to August 2021. The demographic data questionnaire was used for survey, and the psychological status of patients was evaluated with Mishel′s Uncertainties in Illness Scales (MUIS), self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Spearman correlation analysis was used to explore the correlation of disease uncertainty with anxiety and depression in patients with early gastric cancer.Results:The illness uncertainty in patients with early gastric cancer was at a moderate level (93.2±14.0). The total scores on the SAS and SDS were (46.5±9.7) and (47.7±10.2), respectively. And the incidence rate of anxiety and depression was 34.6% (37/107) and 31.8% (34/107) respectively. The illness uncertainty of patients with early gastric cancer was positively correlated with anxiety and depression ( r=0.40,0.31,all P<0.05). Conclusion:Some patients with early gastric cancer have illness uncertainty, anxiety and depression, and the illness uncertainty is related to anxiety and depression.

OBJECTIVE To carry out qualitative and quantitative analysis of volatile components of Olibanum, Olibanum prepared with vinegar and Olibanum stir-fried with Rush by GC-MS, and the quantitative study of the surface color by RGB model, provide auxiliary reference for the subjective evaluation indexes of Olibanum and its products. METHODS The volatile oil of Olibanum, Olibanum prepared with vinegar and Olibanum stir-fried with Rush were extracted. Explored the difference of volatile components by GC-MS in combination with principal component analysis and orthogonal partial least-squares discriminant analysis make a comprehensive analysis. Collected the image information of Olibanum, Olibanum prepared with vinegar and Olibanum stir-fried with Rush, then measured the surface color of them by RGB color model, and counted three color differences. RESULTS The differences of odor among oils might be related to the contents and types of terpenoids and alcohols, especially linalool and 1-octanol. According to surface color determination results, Olibanum stir-fried with Rush was R*76.86%-85.49%, G*61.96%-70.59%, B*38.04%-45.88%; Olibanum prepared with vinegar was R*56.86%-61.57%, G*38.04%-41.96%, B*27.45%-30.59%; Olibanum was R*69.41%-74.51%, G*56.86%-62.35%, B*40.78%-47.06%. By t test, there were significant differences among the three color measurement results, which were consistent with the differences recorded in the corresponding standards for "yellow white" Olibanum, "yellow brown" Olibanum prepared with vinegar, and "golden yellow" Olibanum stir-fried with Rush, indicating that the model was accurate and reliable. CONCLUSION The differences of volatile components and surface color of Olibanum, Olibanum prepared with vinegar and Olibanum stir-fried with Rush are studied to provide reference for character description of Olibanum and its processed products, and to avoid errors caused by traditional subjective evaluation.

Objective::The aim of this study was to investigate the efficacy and safety of tolvaptan, as well as the impact of its treatment dose and duration in heart failure patients with congestive signs.Methods::The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched to collect data from all randomized controlled trials (RCT) examining the efficacy and safety of tolvaptan in heart failure patients with congestive signs compared with placebo or blank control until March 4, 2021. Urine volume, change in body weight, improvement in dyspnea, and reduction of edema were evaluated as efficacy indicators. All-cause mortality, worsening heart failure, and adverse events were considered safety indicators. The quality of eligible publications was assessed using the Cochrane risk of bias for RCTs.Results::Ten RCTs with 5,980 patients were included in this analysis. Compared with control, tolvaptan significantly reduced weight in the short term (day 1, 7 RCTs, weighted mean difference (WMD): -1.09, 95% confidence interval (CI): -1.27 to -0.91; day 2, 2 RCTs, WMD: -1.67, 95% CI: -3.00 to -0.33; day 7, 4 RCTs, WMD: -0.95, 95% CI: -1.25 to -0.66), increased urine volume (WMD: 1,825.72, 95% CI: 1,438.38-2,213.07), and relieved dyspnea (risk ratio (RR): 1.12, 95% CI: 1.05-1.19) without increasing the mortality rate (RR: 0.96, 95% CI: 0.87-1.06). Furthermore, the weight loss and increase in urine volume were not dose-dependent effects, and prolonged medication did not lead to sustained weight loss. In addition, there seemed to be more adverse events (RR: 1.17, 95% CI: 1.03-1.32) after treatment with tolvaptan. Further analysis revealed that patients treated with tolvaptan were more likely to report thirst (RR: 6.09, 95% CI: 3.37-11.00) and dry mouth (RR: 6.36, 95% CI: 4.09-9.90), as well as develop hypernatremia (RR: 12.76, 95% CI: 3.52-46.32).Conclusions::The meta-analysis shows that tolvaptan can improve congestion with no increase in mortality rate, but should be used to guard against adverse events. Deserve to be mentioned, the number of RCTs included was limited, suggesting that the observed results should be interpreted with caution. Additional robust clinical studies are warranted to validate the present findings.

Objective::The aim of this study was to investigate the efficacy and safety of tolvaptan, as well as the impact of its treatment dose and duration in heart failure patients with congestive signs.Methods::The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched to collect data from all randomized controlled trials (RCT) examining the efficacy and safety of tolvaptan in heart failure patients with congestive signs compared with placebo or blank control until March 4, 2021. Urine volume, change in body weight, improvement in dyspnea, and reduction of edema were evaluated as efficacy indicators. All-cause mortality, worsening heart failure, and adverse events were considered safety indicators. The quality of eligible publications was assessed using the Cochrane risk of bias for RCTs.Results::Ten RCTs with 5,980 patients were included in this analysis. Compared with control, tolvaptan significantly reduced weight in the short term (day 1, 7 RCTs, weighted mean difference (WMD): -1.09, 95% confidence interval (CI): -1.27 to -0.91; day 2, 2 RCTs, WMD: -1.67, 95% CI: -3.00 to -0.33; day 7, 4 RCTs, WMD: -0.95, 95% CI: -1.25 to -0.66), increased urine volume (WMD: 1,825.72, 95% CI: 1,438.38-2,213.07), and relieved dyspnea (risk ratio (RR): 1.12, 95% CI: 1.05-1.19) without increasing the mortality rate (RR: 0.96, 95% CI: 0.87-1.06). Furthermore, the weight loss and increase in urine volume were not dose-dependent effects, and prolonged medication did not lead to sustained weight loss. In addition, there seemed to be more adverse events (RR: 1.17, 95% CI: 1.03-1.32) after treatment with tolvaptan. Further analysis revealed that patients treated with tolvaptan were more likely to report thirst (RR: 6.09, 95% CI: 3.37-11.00) and dry mouth (RR: 6.36, 95% CI: 4.09-9.90), as well as develop hypernatremia (RR: 12.76, 95% CI: 3.52-46.32).Conclusions::The meta-analysis shows that tolvaptan can improve congestion with no increase in mortality rate, but should be used to guard against adverse events. Deserve to be mentioned, the number of RCTs included was limited, suggesting that the observed results should be interpreted with caution. Additional robust clinical studies are warranted to validate the present findings.