Objective To analyze the risk factors of postpartum mild uterine prolapse and to investigate the effects of Buzhong Yiqi Decoction on serum transforming growth factor β1(TGF-β1),matrix metalloproteinase 2(MMP-2),and microRNA-30d(miRNA-30d).Methods By blinded and controlled methods and through convenience sampling,80 postpartum patients with mild uterine prolapse were retrospectively collected from Tangshan Maternal and Children Health Hospital from January 2020 to January 2022,and they served as the uterine prolapse group.In addition,80 postpartum patients without uterine prolapse from the same department of the hospital in the same period served as the healthy group.Questionnaire investigation was performed for collecting the basic information such as delivery manner,age,parity,gestational weeks,neonatal weight and body mass index(BMI).The risk factors of postpartum uterine prolapse were investigated by univariate analysis and multivariate logistic regression analysis.The patients in the uterine prolapse group were then divided into the observation group and the control group according to the medication of Buzhong Yiqi Decoction or not,with 40 cases in each group.The control group was treated with electromyographic biofeedback therapy(EBT),while the observation group was treated with Buzhong Yiqi Decoction combined with EBT,and the course of treatment for the two groups covered one month.The changes of pelvic floor function and levels of serum TGF-β1,MMP-2,miRNA-30d in the patients of the two groups were observed before and after treatment.After treatment,the clinical efficacy of patients in the two groups was evaluated.Results(1)The results of univariate analysis showed that compared with the healthy group,the patients in the uterine prolapse group were elder,usually had given two childbirths or more by vaginal delivery,and accounted for a high percentage of overweight/obesity(BMI≥24.0 kg/m2)and perineal laceration,the difference being statistically significant(P<0.05 or P<0.01).(2)The results of multivariate logistic regression analysis showed that age,delivery manner,parity,laceration of perineum,and BMI were risk factors for postpartum uterine prolapse(P<0.01).(3)After one month of treatment,the total effective rate of Buzhong Yiqi Decoction in the observation group was 95.00%(38/40),while that in the control group was 77.50%(31/40),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P<0.05).(4)The observation of effects of Buzhong Yiqi Decoction on pelvic floor function showed that after treatment,the distance between the cervix and the hymenal edge,the maximum intravaginal pressure,the voltage of vaginal muscles,the contraction time of pelvic floor muscles of typeⅠand Ⅱmuscle fibers in the two groups of patients were significantly improved compared with those before treatment(P<0.05),and the improvement in the observation group was significantly superior to that in the control group(P<0.01).(5)The observation of effects of Buzhong Yiqi Decoction on serological indicators showed the post-treatment serum TGF-β1 levels in the two groups were increased compared with those before treatment(P<0.05),and the serum levels of MMP-2 and miRNA-30d were decreased compared with those before treatment(P<0.05),and the increase of serum TGF-β1 level and the decrease of serum MMP-2 and miRNA-30d levels in the observation group were both significantly superior to those in the control group(P<0.01).Conclusion The incidence of postpartum uterine prolapse is related to age,delivery manner,parity,laceration of perineum,BMI,etc.The treatment of Buzhong Yiqi Decoction on the basis of EBT can improve the pelvic floor function of the patients and regulate the expression of serum TGF-β1,MMP-2,and miRNA-30d,and the clinical efficacy is remarkable.

Objective:The association between air pollutants and the risk of sudden cardiac death (SCD) remains controversial. This study aimed to investigate the relationship between five air pollutants—PM 2.5, PM 2.5–10, PM 10, NO 2, and NO?—and the risk of SCD. Methods:We analyzed data from 460 862 participants in the UK Biobank cohort, all enrolled between 2006 and 2010, with no baseline SCD. Follow-up continued until the study endpoint. Annual average concentrations of the five pollutants were assessed. Associations between pollutants and SCD were evaluated using Cox proportional hazards models, followed by Mendelian randomization (MR) to assess causality.Results:Over a mean follow-up of 12.4 years, 2 662 SCD cases were recorded. After adjusting for confounders, no significant associations were found between air pollutants and SCD risk: PM 2.5 ( HR 1.03, 95% CI 0.99–1.07, P = 0.14), PM 2.5–10 ( HR 1.04, 95% CI 1.00–1.08, P = 0.08), PM 10 ( HR 1.01, 95% CI 0.99–1.03, P = 0.26), NO? ( HR 1.00, 95% CI 0.99–1.00, P = 0.26), and NO x ( HR 1.00, 95% CI 1.00–1.01, P = 0.19). MR analysis further supported the absence of causal relationships: PM 2.5 ( β = -0.149, P = 0.90), PM 2.5–10 ( β = 0.387, P = 0.62), PM 10 ( β = -0.994, P = 0.62), NO? ( β = –0.005, P = 0.99), and NO 2 ( β = –0.827, P = 0.25). Conclusions:This study found no evidence linking PM 2.5, PM 2.5–10, PM 10, NO?, or NO 2 to an increased risk of SCD. Mendelian randomization confirmed the lack of causal associations between these pollutants and SCD.

AIM:Bone morphogenetic protein 7(BMP7)reduces the expression of Yes-related protein 1(YAP1)by down-regulating Ajuba level and decreasing extracellular matrix(ECM)deposition.This study aimed to inves-tigate the influence of these factors on modifying the degree of renal fibrosis in rats with diabetic nephropathy.METH-ODS:Eighteen Sprague-Dawley(SD)rats were randomly divided into three groups:the normal control(NC)group,the diabetes mellitus(DM)group,and the DM group treated with BMP7 overexpressing adeno-associated virus(DM+rAAV-BMP7).Each group consisted of six rats.Diabetic kidney disease(DKD)was established in the DM and DM+rAAV-BMP7 groups by injecting 55 mg/kg streptozotocin(STZ)via the tail vein.NRK-52E cells were divided into three groups:the normal glucose(NG)group,the high glucose(HG)group,and the high glucose group treated with recombinant hu-man BMP7(HG+rhBMP7)group.Pathological changes in renal tissues were observed using hematoxylin and eosin(HE)and Sirius red staining.Immunohistochemical staining was performed to examine the expression sites of Ajuba and YAP1 in the renal cortex.Western blot analysis was conducted to determine the expression levels of BMP7,Ajuba,YAP1,colla-gen type Ⅲ(Col-Ⅲ),and fibronectin(FN)in the rat renal cortex and NRK-52E cells.RT-qPCR was used to measure the mRNA levels of Ajuba and YAP1 in the rat renal cortex.RESULTS:Biochemical indices revealed significantly ele-vated levels of blood glucose,serum creatinine,triglycerides,total cholesterol,and 24-hour urinary protein in the DM group compared to the NC group(P<0.05).In the DM+rAAV-BMP7 group,the levels of serum creatinine,24-hour uri-nary protein,triglycerides,and total cholesterol were lower than those in the DM group(P<0.05).Pathological staining demonstrated that the renal interstitium of the DM group exhibited inflammatory cell infiltration,fibrous tissue,collagen fi-ber deposition,disordered renal tubule arrangement,atrophy,and vacuolar degeneration,which were ameliorated in the DM+rAAV-BMP7 group.Immunohistochemistry revealed that Ajuba and YAP1 were mainly expressed in the cytoplasm and nucleus,with high expression in the cytoplasm of the DM group,which was significantly decreased in the DM+rAAV-BMP7 group.Western blot results indicated that the protein levels of FN,Col-Ⅲ,Ajuba,and YAP1 were up-regulated in the DM and the HG groups(P<0.05),but significantly down-regulated in the DM+rAAV-BMP7 group(P<0.05).RT-qP-CR results demonstrated that the mRNA levels of Ajuba and YAP1 were higher in the DM group and significantly lower in the DM+rAAV-BMP7 group(P<0.05).CONCLUSION:The overexpression of BMP7 can ameliorate renal fibrosis in rats with DKD.This effect is likely mediated by the down-regulation of Ajuba,reduction of YAP1 expression,and subse-quent inhibition of ECM deposition.

This article reviews the concept and significance of death literacy, assessment tools, current status domestically and internationally, influencing factors, and intervention measures. The aim is to provide insights for effective strategies to enhance residents' death literacy, thereby offering a new perspective for improving palliative care practices and research in China and ensuring quality of death.

CUDC-101, an effective and multi-target inhibitor of epidermal growth factor receptor (EGFR), histone deacetylase (HDAC), and human epidermal growth factor receptor 2 (HER2), has been reported to inhibit many kinds of cancers, such as acute promyelocytic leukemia and non-Hodgkin's lymphoma. However, no studies have yet investigated whether CUDC-101 is effective against myeloma. Herein, we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma (MM) cell lines and induces cell apoptosis in a time- and dose-dependent manner. Moreover, CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase (PI3K) and HDAC, and regulated the cell cycle G2/M arrest. Moreover, we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug. Bortezomib is one of the important drugs in MM treatment, and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib. The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade. Collectively, our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib, which provides insights into exploring new strategies for MM treatment.
Humans ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; Bortezomib/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; ErbB Receptors/antagonists & inhibitors* ; G2 Phase Cell Cycle Checkpoints ; Histone Deacetylase Inhibitors/pharmacology* ; Histone Deacetylases/metabolism* ; M Cells ; Multiple Myeloma/drug therapy*

Objective: To buildSERPING1-knockout porcine fetal fibroblasts(PFFs) based on CRISPR/Cas9 technology and provide cell experimental materials for the construction of hereditary angioedema models. Methods: Firstly, protein structure prediction software was used to analyze the amino acid homology between human and pigSERPING1. Secondly, the eighth exon was selected as the knockout target by screening the effective coding region of the pigSERPING1gene. A single guide RNA targeting pigSERPING1was designed, synthesized and linked to pX330 vector containing Cas9 endonuclease. G418 was used to obtain the positive monoclonal cells after transfection into PFFs. Finally, the circumstance of CRISPR/Cas9 mediated knockout was assessed by the T7 EN1 enzyme digestion assay and the genotypes of monoclonal cells were identified by sequencing analysis Results: Bioinformatic analysis revealed that theSERPING1protein of human and pig had high homology, amino acid sequence identity reached 65.87%. A vector targetingSERPING1was constructed successfully and transfected into cells. Monoclonal cells with knockoutSERPING1gene were obtained through drug screening. Sequencing confirmed the mutant genotype. Conclusion The human and pigSERPING1sequences and their protein structures are highly homologous, and it is suitable for the construction of disease model. CRISPR/Cas9 expression vectors were constructed to achieve theSERPING1gene targeting in PFFs.SERPING1-knockout monoclonal cells were obtained, which could contribute to the construction of theSERPING1knockout miniature pig model.

OBJECTIVE: To analyze and compare the effects of leukapheresis on hemostatic function in patients with hyperleukocytic leukemia. METHODS: A total of 139 patients with AML, ALL and CML who underwent leukapheresis from June 2009 to February 2020 and did coagulation test before and after operation were included in this study. The clearance efficiency of each group and the difference among three groups were evaluated, as well as hemostatic function including platelet counts, coagulation indicators, CDSS score and incidence of adverse events. The difference of hemostatic function caused by leukapheresis in different leukemia patients were compared. RESULTS: After leukapheresis, the WBC counts were decreased significantly in the three groups of patients (P<0.001), and the clearance efficiency was highest in ALL patients. However, the platelet counts also were decreased significantly (AML:P＜0.001, ALL: P＜0.001, CML: P＜0.01) in the three groups of patients, particularly for acute leukemia patients with a positive correlation with WBC clearance efficiency(r=0.284). After leukapheresis, fibrinogen decreased, PT and APTT prolonged. For acute leukemia patients, higher CDSS score was related to an elevated incidence of bleeding events (P<0.05). CONCLUSION Leukapheresis is an effective method to decrease the leukemic burden, but it is necessary to monitor the impact on hemostatic function. It is recommended to assess the CDSS socre for acute leukemia patients, in order to identify the predictive value for bleedings.
Acute Disease ; Blood Coagulation ; Blood Coagulation Tests ; Hemorrhage ; Hemostatics ; Humans ; Leukapheresis/methods* ; Leukemia, Myeloid, Acute/therapy*

High mobility group box 1 (HMGB1) has been reported to play an important role in experimental autoimmune encephalomyelitis (EAE). Astrocytes are important components of neurovascular units and tightly appose the endothelial cells of microvessels by their perivascular endfeet and directly regulate the functions of the blood-brain barrier. Astrocytes express more HMGB1 during EAE while the exact roles of astrocytic HMGB1 in EAE have not been well elucidated. Here, using conditional-knockout mice, we found that astrocytic HMGB1 depletion decreased morbidity, delayed the onset time, and reduced the disease score and demyelination of EAE. Meanwhile, there were fewer immune cells, especially pathogenic T cells infiltration in the central nervous system of astrocytic HMGB1 conditional-knockout EAE mice, accompanied by up-regulated expression of the tight-junction protein Claudin5 and down-regulated expression of the cell adhesion molecules ICAM1 and VCAM1 in vivo. In vitro, HMGB1 released from astrocytes decreased Claudin5 while increased ICAM1 and VCAM1 expressed by brain microvascular endothelial cells (BMECs) through TLR4 or RAGE. Taken together, our results demonstrate that HMGB1 derived from astrocytes aggravates EAE by directly influencing the immune cell infiltration-associated functions of BMECs.
Mice ; Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; HMGB1 Protein/metabolism* ; Endothelial Cells/metabolism* ; Mice, Inbred C57BL ; Mice, Knockout ; Blood-Brain Barrier/metabolism*

To explore the mode of"one-day outpatient"based continuous management and examine its feasibility and preliminary effects for improving menopausal syndrome and mood among menopausal women.Clinical intervention study was conducted in Obstetrics and Gynecology Center of the Third Affiliated Hospital of Chongqing Medical University from May 2020 to May 2021.The continuous management mode of "one-day outpatient service" for menopause was constructed in terms of multidisciplinary resources, including offline "one-day outpatient" health education, online 7-week group continuous intervention on "healthy lifestyle" and offline half-day focus group interview. Pre-and post-scores of the modified Kupperman scale and the positive/negative emotional scale (PANAS) were measured to compare the status of menopausal syndrome and emotional experience of Seventy-eight female participants (40-60 years old), meanwhile, before and after comparison of the blood lipid and body composition indexes of participants were also performed. Paired t test or Wilcoxon signed rank test were used.Results show that the pre-and post Kupperman scores were 14.65±8.51 vs 10.26±5.83 ( t=-5.59, P<0.01), and the positive emotional scores (pre- 28.53±5.85 vs post- 30.13±6.30) were improved ( t=2.59, P=0.012) and negative emotional scores [pre- 20.5(10) vs post- 17.0(7)] were decreased ( Z=-5.09, P<0.01). The triglyceride level of participants declined from (1.27±0.54) mmol/L to (1.09±0.38) mmol/L ( t=-2.45, P<0.05). In addition, the body mass index(pre- 22.52±2.34 vs post- 22.06±2.22), percentage of body fat (pre- 31.72±6.22 vs post- 30.91±6.52)and Visceral fat area(pre- 83.96±30.26 vs post- 79.66±29.71) were all improved ( t=-3.58, t=-2.57, t=-2.59, P<0.05). Therefore,the mode of"one-day outpatient"based continuous management can effectively improve menopausal syndrome and adverse mood, reduce patients′ blood lipid, improve the body composition, and maybe contribute to the prevention of long-term chronic diseases.

AIM: To investigate the effect of ezetimibe combined with statins on residual lipoprotein-cholesterol (RLP-C) levels and major cardiovascular adverse events (MACE) in patients with acute coronary syndrome (ACS) after emergency intervention (PCI). METHODS: A total of 90 hospitalized patients with ACS and undergoing emergency PCI were randomly divided into two groups: 48 patients in the control group received atorvastatin, and 42 patients in the study group were additionally treated with ezetimibe. RLP-C level before and after treatment was detected. The occurrence of MACE events and adverse drug events during the treatment were obtained through regular follow-up. RESULTS: Compared with the control group, the level of RLP-C in the study group was significantly decreased (P<0.05), the incidence of MACE were significantly decreased (P<0.05), and adverse drug events were not increased. CONCLUSION: The combination therapy of ezedemibe and statins can reduce RLP-C level and MACE in ACS patients undergoing emergency PCI with less adverse reactions, which is worthy of promotion and application.