Objective To investigate the outcome of endovascular aortic repair under digital subtraction angiography (DSA) in the treatment of Stanford type B aortic dissection (TBAD). Methods A total of 104 TBAD patients admitted to our hospital from October 2019 to October 2022 were selected,of which 52 patients treated with best medication treat (BMT) were included into the BMT group,and 52 patients who underwent endovascular aortic repair under DSA on the basis of BMT were included into the combination group. The acute physiological and chronic health evaluation Ⅱ (APACHE Ⅱ) score,serum inflammatory indicators,liver and kidney function indicators,and coagulation function indicators before and after treatment,and hospital stay were compared between the two groups. Results The APACHE Ⅱ score,liver and kidney function indicators and inflammatory factors after treatment in the combination group were lower than those before treatment and in the BMT group (P<0.05). The combination group had more significant changes of coagulation function indicators after treatment than those before treatment and in the BMT group (P<0.05). The hospital stay of the combination group was shorter than that of the BMT group (P<0.05). Conclusion Endovascular aortic repair under DSA for TBAD can reduce inflammatory response,improve liver and kidney functions and coagulation function,and shorten the hospital stay,which has a better therapeutic effect than conservative drug treatment.

Objective To explore the influencing factors of acute kidney injury in severe burn patients,and to construct a visual risk nomogram model.Methods A total of 390 patients with severe burn admitted to the Institute of Burn Frostbite and Tissue Function Reconstruction of Chinese People's Armed Police Force Specialty Medical Center from January 2018 to January 2022 were collected as an internal training data set,and 50 patients with severe burn admitted from February to December 2022 were collected as an external validation data set.The 390 patients of the internal training data set were divided into the acute kidney injury group and the non-acute kidney injury group according to the occurrence of acute kidney injury,and the baseline data of patients in the two groups were compared.Univariate and multivariate Logistic regression were used to analyze the risk factors of acute kidney injury in severe burn patients of the internal training data set,and a nomogram model was drawn.Subsequently,the model was verified both internally and externally.Kaplan-Meier analysis and Log-rank test were used to compare the 90-day survival rate of patients between the acute kidney injury group and the non-acute kidney injury group.Results The burn area(OR=1.18,95%CI:1.06 to 2.36,P=0.004),sequential organ failure assessment(SOFA)score(OR=1.81,95%CI:1.21 to 5.92,P<0.001),inhalation injury(OR=3.21,95%CI:1.23 to 6.35,P<0.001),neutrophil to lymphocyte ratio(NLR)(OR=1.22,95%CI:1.05 to 3.65,P<0.001)and albumin(ALB)(OR=0.78,95%CI:0.57 to 0.92,P=0.011)were the independent risk factors for the development of acute kidney injury in severe burn patients.The nomogram model was established by the above factors.The area under the receiver operating characteristic curve(AUC)of the internal training data set was 0.833(95%CI:0.752 to 0.935),the sensitivity was 81.2%,and the specificity was 83.2%.The AUC of the external validation data set was 0.842(95%CI:0.762 to 0.912),the sensitivity 87.2%,and the specificity was 78.7%.The 90-day survival rate of patients in the acute kidney injury group after burns was significantly lower than that in the non-acute kidney injury group(P<0.001).Conclusion Larger burn area,higher SOFA score,combined inhalation injury,increased NLR,and decreased ALB level are the risk factors for the occurrence of acute kidney injury in severe burn patients,which are related to the 90-day survival rate of patients after burns.The nomogram model based on the risk factors can provide certain reference for clinical individualized prevention and treatment of acute kidney injury in severe burn patients.

Mesenchymal stem cells(MSCs)induces fusion of multiple monocyte macrophages by secre-ting key cytokines such as receptor activator for nuclear factor-κB ligand(RANKL)and macrophage CSF(M-CSF)to form multinucleated macrophages thereby SUMO-specific protease 3(SENP3)modifies pro-teins by de-SUMOylation,which in turn affects the stability,localization and activity of substrate pro-teins.Based on the previous work in our laboratory,we found that the number of osteoclasts increased in mice with SENP3 knockdown in MSC(***P＜0.001).To further explore the mechanism,using immuno-fluorescence as well as Western blotting assay,we found that knockdown of the Hedgehog(Hh)signaling pathway by SENP3 increased the transcription factor glioma-associated oncogene homolog 2(Gli2),which is the most important transcription factor for the production of osteoclasts.CHIP-qPCR results showed that Gli2 promoted COX2 transcription by binding to cyclooxygenase-2(COX2)promoter regions-1 235～-1 249 and-1 158～-1 172(*P＜0.05);meanwhile,the main secretion product of COX2,pep-tide,was detected by ELISA(*P＜0.05).The level of prostaglandin E2(PGE2),the main secretory product of COX2,was increased in the supernatant of the culture medium of MSC with knockdown of SENP3 by ELISA(***P＜0.001).PGE2 is known to mediate cell migration and osteoclastogenesis through E-type prostanoid receptor 2(EP2)and E-type prostanoid receptor 4(EP4).In the study,the expression of EP4 receptor was found to be elevated in differentiated osteoclasts(**P＜0.01).The inhib-itors of the EP4 receptor significantly reduced the expression of nuclear factor-activated T cell 1(NFATc1),Cathepsin K(Ctsk),and tartrate resistant acid phosphatase(TRAP)genes(*P＜0.05)and decreased osteoclastogenesis(***P＜0.001),suggesting that EP4 receptors play a critical role in PGE2-mediated osteoclast differentiation.In conclusion,SENP3 deletion in mouse MSCs promotes COX2 transcription and PGE2 secretion through activation of the Hh signaling pathway thereby promoting osteo-clast formation.

Mesenchymal stem cells(MSCs)induces fusion of multiple monocyte macrophages by secre-ting key cytokines such as receptor activator for nuclear factor-κB ligand(RANKL)and macrophage CSF(M-CSF)to form multinucleated macrophages thereby SUMO-specific protease 3(SENP3)modifies pro-teins by de-SUMOylation,which in turn affects the stability,localization and activity of substrate pro-teins.Based on the previous work in our laboratory,we found that the number of osteoclasts increased in mice with SENP3 knockdown in MSC(***P＜0.001).To further explore the mechanism,using immuno-fluorescence as well as Western blotting assay,we found that knockdown of the Hedgehog(Hh)signaling pathway by SENP3 increased the transcription factor glioma-associated oncogene homolog 2(Gli2),which is the most important transcription factor for the production of osteoclasts.CHIP-qPCR results showed that Gli2 promoted COX2 transcription by binding to cyclooxygenase-2(COX2)promoter regions-1 235～-1 249 and-1 158～-1 172(*P＜0.05);meanwhile,the main secretion product of COX2,pep-tide,was detected by ELISA(*P＜0.05).The level of prostaglandin E2(PGE2),the main secretory product of COX2,was increased in the supernatant of the culture medium of MSC with knockdown of SENP3 by ELISA(***P＜0.001).PGE2 is known to mediate cell migration and osteoclastogenesis through E-type prostanoid receptor 2(EP2)and E-type prostanoid receptor 4(EP4).In the study,the expression of EP4 receptor was found to be elevated in differentiated osteoclasts(**P＜0.01).The inhib-itors of the EP4 receptor significantly reduced the expression of nuclear factor-activated T cell 1(NFATc1),Cathepsin K(Ctsk),and tartrate resistant acid phosphatase(TRAP)genes(*P＜0.05)and decreased osteoclastogenesis(***P＜0.001),suggesting that EP4 receptors play a critical role in PGE2-mediated osteoclast differentiation.In conclusion,SENP3 deletion in mouse MSCs promotes COX2 transcription and PGE2 secretion through activation of the Hh signaling pathway thereby promoting osteo-clast formation.

Three taraxerane nortriterpenoids were isolated from mastic by using various modern chromatographic separation techniques. They were identified as(5R,8R,9R,10S,11S,12R,13S,17R,18R)-28-norlupa-11,12-epoxy-14-taraxerene-3,16-dione(1),(5R,8R,9R,10S,11S,12R,13S,17S,18S)-17-hydroxy-28-norlupa-11,12-epoxy-14-taraxerene-3-one(2), and(5R,8R,9R,10R,11S,12R,13R,14S,17S,18S)-14,17-epoxy-28-norlupa-11,12-oxidotaraxerone(3) through the high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), infrared(IR), ultraviolet(UV), nuclear magnetic resonance(NMR), and single-crystal X-ray diffraction techniques as well as comparison with literature data. Compounds 1-3 were C-28 nortriterpenoids and isolated from mastic for the first time, and compounds 1-2 were new ones. In the model for RAW264.7 cell anti-inflammation induced by lipopolysaccharide(LPS), compound 1 demonstrates an inhibitory effect on nitric oxide(NO) [IC_(50)=(13.38±0.68) μmol·L~(-1)], comparable to the activity of the positive control dexamethasone [IC_(50)=(14.59±1.49) μmol·L~(-1)]. Compounds 2 and 3 exhibit weaker inhibitory effects, with IC_(50) values of(24.17±2.56) and(22.25±2.84) μmol·L~(-1), respectively.
Animals ; Mice ; Triterpenes/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Mastic Resin/chemistry* ; Nitric Oxide ; Molecular Structure ; Macrophages/immunology* ; RAW 264.7 Cells

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Objective To explore the influencing factors of acute kidney injury in severe burn patients,and to construct a visual risk nomogram model.Methods A total of 390 patients with severe burn admitted to the Institute of Burn Frostbite and Tissue Function Reconstruction of Chinese People's Armed Police Force Specialty Medical Center from January 2018 to January 2022 were collected as an internal training data set,and 50 patients with severe burn admitted from February to December 2022 were collected as an external validation data set.The 390 patients of the internal training data set were divided into the acute kidney injury group and the non-acute kidney injury group according to the occurrence of acute kidney injury,and the baseline data of patients in the two groups were compared.Univariate and multivariate Logistic regression were used to analyze the risk factors of acute kidney injury in severe burn patients of the internal training data set,and a nomogram model was drawn.Subsequently,the model was verified both internally and externally.Kaplan-Meier analysis and Log-rank test were used to compare the 90-day survival rate of patients between the acute kidney injury group and the non-acute kidney injury group.Results The burn area(OR=1.18,95%CI:1.06 to 2.36,P=0.004),sequential organ failure assessment(SOFA)score(OR=1.81,95%CI:1.21 to 5.92,P<0.001),inhalation injury(OR=3.21,95%CI:1.23 to 6.35,P<0.001),neutrophil to lymphocyte ratio(NLR)(OR=1.22,95%CI:1.05 to 3.65,P<0.001)and albumin(ALB)(OR=0.78,95%CI:0.57 to 0.92,P=0.011)were the independent risk factors for the development of acute kidney injury in severe burn patients.The nomogram model was established by the above factors.The area under the receiver operating characteristic curve(AUC)of the internal training data set was 0.833(95%CI:0.752 to 0.935),the sensitivity was 81.2%,and the specificity was 83.2%.The AUC of the external validation data set was 0.842(95%CI:0.762 to 0.912),the sensitivity 87.2%,and the specificity was 78.7%.The 90-day survival rate of patients in the acute kidney injury group after burns was significantly lower than that in the non-acute kidney injury group(P<0.001).Conclusion Larger burn area,higher SOFA score,combined inhalation injury,increased NLR,and decreased ALB level are the risk factors for the occurrence of acute kidney injury in severe burn patients,which are related to the 90-day survival rate of patients after burns.The nomogram model based on the risk factors can provide certain reference for clinical individualized prevention and treatment of acute kidney injury in severe burn patients.

Objective To investigate the outcome of endovascular aortic repair under digital subtraction angiography (DSA) in the treatment of Stanford type B aortic dissection (TBAD). Methods A total of 104 TBAD patients admitted to our hospital from October 2019 to October 2022 were selected,of which 52 patients treated with best medication treat (BMT) were included into the BMT group,and 52 patients who underwent endovascular aortic repair under DSA on the basis of BMT were included into the combination group. The acute physiological and chronic health evaluation Ⅱ (APACHE Ⅱ) score,serum inflammatory indicators,liver and kidney function indicators,and coagulation function indicators before and after treatment,and hospital stay were compared between the two groups. Results The APACHE Ⅱ score,liver and kidney function indicators and inflammatory factors after treatment in the combination group were lower than those before treatment and in the BMT group (P<0.05). The combination group had more significant changes of coagulation function indicators after treatment than those before treatment and in the BMT group (P<0.05). The hospital stay of the combination group was shorter than that of the BMT group (P<0.05). Conclusion Endovascular aortic repair under DSA for TBAD can reduce inflammatory response,improve liver and kidney functions and coagulation function,and shorten the hospital stay,which has a better therapeutic effect than conservative drug treatment.

Objective To investigate the efficacy and safety of Chinese herbal compound modified Huanglian Wendan Decoction in the treatment of hypertension complicated with sleep disorders of phlegm-heat harassing the interior type.Methods A total of 70 patients with hypertension complicated with sleep disorders of phlegm-heat harassing the interior type were randomly divided into a control group and an observation group,35 cases in each group.The patients in the control group were treated with conventional western medicine,and the patients in the observation group were treated with modified Huanglian Wendan Decoction on the basis of treatment for the control group.The course of treatment covered four weeks.The Clinical Global Impression(CGI)score,traditional Chinese medicine(TCM)syndrome score,Pittsburgh Sleep Quality Index(PSQI)score,blood pressure,and serum levels of homocysteine(Hey),interleukin 6(IL-6),interleukin 10(IL-10)and interleukin 8(IL-8)levels in the two groups were observed before and after treatment.Moreover,the safety of medication was evaluated in the two groups.Results(1)After four weeks of treatment,the CGI score of the observation group was(1.63±0.60)points,which was significantly lower than that of the control group[(2.74±0.82)points],and the difference was statistically significant(P＜0.01).(2)After treatment,the TCM syndrome score,systolic blood pressure,diastolic blood pressure and PSQI score of the two groups were significantly decreased compared with those before treatment(P＜0.01),and the decrease of TCM syndrome score,systolic blood pressure,diastolic blood pressure and PSQI score in the observation group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)After treatment,the levels of serum Hcy,IL-6 and IL-8 in the two groups were significantly decreased compared with those before treatment(P＜0.01),and the serum IL-10 level was significantly increased compared with that before treatment(P＜0.01).The decrease of serum Hcy,IL-6 and IL-8 levels and the increase of serum IL-10 level in the observation group were significantly superior to those in the control group(P＜0.01).(4)During the treatment,no treatment-related adverse reactions or complications occurred in the two groups.Conclusion Modified Huanglian Wendan Decoction has certain efficacy on patients with hypertension complicated with sleep disorders of phlegm-heat harassing the interior type.The decoction can not only reduce the blood pressure and serum Hcy level of the patients,but also regulate the level of inflammatory factors with high safety.