Pregnancy complicated by aortic root aneurysm in patients with Marfan syndrome is one of the main causes of termination of pregnancy or even death in pregnant women. A very small number of pregnant women require cardiac surgery to preserve pregnancy under extracorporeal circulation, and all surgeries use aortic root replacement. We reported a 30-year-old patient with severe aortic regurgitation combined with giant aortic root aneurysm and Marfan syndrome in mid-pregnancy. Valve-sparing root replacement using reimplantation technology was performed via a multidisciplinary cooperation model. This not only achieved the patient’s desire to continue pregnancy but also avoided the anticoagulation and bleeding complications brought by mechanical valve replacement, reduced pregnancy risks and improved long-term quality of life. Postoperative echocardiography showed a small amount of aortic valve regurgitation, aortic valve coaptation height of 0.6 cm, effective height of 1.1 cm, maximum aortic flow velocity of 1.4 m/s, mean transvalvular pressure gradient of 4.4 mm Hg, and satisfactory clinical results.

ObjectiveTo investigate the effects of Scutellariae Radix combined with epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） on cell proliferation， apoptosis， cancer stem cell （CSC） marker expression， and metabolism in non-small cell lung cancer （NSCLC） cells. MethodsThe anti-tumor effects of Scutellariae Radix and EGFR-TKIs （gefitinib or osimertinib） in NSCLC cells were evaluated using the cell counting kit-8 （CCK-8） and Annexin V-FITC/propidium iodide （PI） double staining apoptosis assay. The activity of Scutellariae Radix and EGFR-TKIs in three-dimensional （3D） cultures of NSCLC cells was assessed using the CellTiter-Glo® 3D cell viability assay. The mRNA and protein expression levels of CSC markers， sex determining region y box protein 2 （SOX2） and aldehyde dehydrogenase 1 family member A1 （ALDH1A1）， were detected by quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot， respectively. Changes in intracellular reactive oxygen species （ROS） levels were detected by ROS staining， and the redox ratio was detected by femtosecond laser labeling free imaging （FLI）. ResultsUnder both two-dimensional （2D） and 3D culture conditions， compared with the blank group and EGFR-TKI group， the combination group showed significantly reduced cell viability and increased apoptosis rate （P<0.05）. Compared with the EGFR-TKI group， the mRNA and protein levels of CSC markers were significantly downregulated in the combination group （P<0.05）. Additionally， the redox ratio was significantly elevated （P<0.05）， and ROS levels were also increased in the combination group compared with the EGFR-TKI group. ConclusionIn NSCLC cells， Scutellariae Radix enhances the redox ratio and increases ROS levels， thereby inhibiting the expression of CSC markers and strengthening the anti-tumor effects of EGFR-TKIs. This provides a novel molecular mechanism by which Scutellariae Radix may enhance the sensitivity of targeted therapies.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective To investigate the protective effect of cardamomine(CAR)on anthracycline-induced cardiotoxicity in rats by regulating the pyroptosis mediated by Notch/nuclear factor-κB(NF-κB)signal pathway.Methods The rat model of cardiotoxicity was established by intraperitoneal injection of doxorubicin(DOX).The model rats were randomly divided into DOX group,CAR-L group,CAR-H group and Jagged1 group.Another 10 rats were taken as the control group.The control group and the DOX group were given the same amount of 0.9％NaCl.The CAR-L group and CAR-H group were given 40 and 80 mg·kg-1 CAR by gavage,respectively.The Jagged1 group was given 80 mg·kg-1 CAR+and 25 ng·kg-1 Jagged1 by gavage once a day for 4 weeks.Myocardial injury markers creatine kinase isoenzyme(CK-MB)and troponin Ⅰ(cTn Ⅰ)were detected by kit.The expression of pyroptosis protein Nod-like receptor protein 3(NLRP3)and desquamate D(GSDM-D)were observed by immunohistochemistry.The expression of Notch1 and phosphorylated NF-κB p65(p-NF-κB p65)protein in myocardial tissue was detected by Western blotting.Results The levels of CK-MB in control group,DOX group,CAR-L group,CAR-H group and Jagged1 group were(48.51±5.39),(175.93±13.27),(106.83±9.73),(83.71±8.39)and(126.08±9.74)U·L-1;the levels of cTn Ⅰ were(1.95±0.18),(12.46±1.83),(7.15±0.64),(4.13±0.38)and(8.01±0.78)ng·mL-1;the average optical density of NLRP3 protein were 0.19±0.07,0.36±0.05,0.25±0.05,0.21±0.03 and 0.31±0.06;the average optical density of GSDM-D were 0.18±0.04,0.43±0.06,0.24±0.03,0.19±0.04 and 0.32±0.05.There were significant differences in the above indexes between DOX group and control group(all P＜0.05).There were significant differences in the above indexes between CAR-L group,CAR-H group and DOX group(all P＜0.05),and there were significant differences between CAR-L group and CAR-H group(all P＜0.05).The above indexes in Jagged1 group were significantly different from those in CAR-H group(all P＜0.05).Conclusion CAR can improve myocardial injury in DOX cardiotoxic rats,reduce oxidative stress,inflammatory reaction and pyroptosis,and its mechanism may be related to the inhibition of Notch/NF-κB pathway.

Objective To observe the effect and safety of menatetrenone combined with percutaneous kyphoplasty(PKP)in the treatment of osteoporotic vertebral compression fracture(OVCF).Methods Patients with OVCF were divided into treatment group and control group by random number table method.The control group was treated with PKP and conventional anti-osteoporosis treatment,and the treatment group was treated with menatetrenone 15 mg,tid,on the basis of control group.The two groups were compared on the changes in T value of bone mineral density,Oswestry disability index(ODI)scores,visual analogue scale(VAS)and bone metabolism indicators[osteocalcin(OC),alkaline phosphatase(ALP),C-telopeptide of type Ⅰ collagen(CTX-Ⅰ)and 25-hydroxyvitamin D(25(OH)D)].The incidence rates of refracture and adverse reactions were recorded.Results There were 40 cases in treatment group and 40 cases in control group.After treatment,T values of bone mineral density of lumbar spine(L2-4)in treatment group and control group were-1.79±0.24 and-2.16±0.28;T values of bone mineral density of femoral neck were-1.44±0.16 and-2.01±0.22;T values of bone mineral density of femoral great trochanter were-1.76±0.18 and-1.97±0.23,all with significant difference(all P＜0.05).Three months after operation,ODI scores in treatment group and control group were 34.12±3.56 and 37.67±3.89;six months after operation,ODI scores were 17.85±1.84 and 26.75±2.78;three months after operation,VAS were 2.61±0.28 and 2.84±0.31;six months after operation,VAS were 0.85±0.11 and 1.23±0.16,all with significant difference(all P＜0.05).After treatment,OC levels in treatment group and control group were(9.08±0.95)and(7.64±0.79)μg·L-1;ALP levels were(86.27±8.79)and(91.33±9.25)U·L-1;CTX-Ⅰ levels were(0.21±0.04)and(0.25±0.03)ng·mL-1;the above indexes were significantly different between control group and treatment group(all P＜0.05).The incidence of refracture in treatment group and control group were 10.00％and 2.50％,and the incidence of adverse drug reactions were 10.00％and 17.50％,without statistically significant difference between the two groups(all P＞0.05).Conclusion Menatetrenone combined with PKP can significantly increase bone mineral density of patients with OVCF,improve bone metabolism indicators and reduce lumbar dysfunction and pain,without increasing the risks of refracture and adverse drug reactions.

Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (-)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (-)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

OBJECTIVE To explore the impact of placental polypeptide on the Runt-related transcription factor 3 （RUNX3）/ Notch signaling pathway in rats with cyclophosphamide-induced premature ovarian failure （POF）， and its effects on ovarian function and oxidative stress. METHODS A POF rat model was induced by intraperitoneal injection of cyclophosphamide. Sixty POF rats of the model were randomly assigned to model group， low-dose （1 mg/kg） and high-dose （2 mg/kg） placental polypeptide groups， placental polypeptide plus empty vector group [placental polypeptide （2 mg/kg）， empty vector （1 μg）]， and placental polypeptide plus RUNX3 silencing group [placental polypeptide （2 mg/kg）， RUNX3 small interfering RNA （1 μg）]， with 12 rats in each group. Additionally， 12 healthy rats were selected as a control group. The intervention lasted for 4 weeks for all groups. After the final administration， the levels of sex hormones [estradiol （E2）， anti-Müllerian hormone （AMH）， follicle- stimulating hormone （FSH）] in rat serum and oxidative stress indicators [malondialdehyde （MDA）， superoxide dismutase （SOD）， catalase （CAT）， reactive oxygen species （ROS）] in ovarian tissue were measured. The pathology of rat ovarian tissue and apoptosis of ovarian granulosa cells were examined； the expression of apoptosis-related proteins [caspase-3， cleaved-caspase-3， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）and RUNX3/Notch signaling pathway-related proteins in rat ovarian tissue were detected. RESULTS Compared with the model group， the low and high doses of placental polypeptide groups showed an increase in the number of normal follicles and a marked decrease in the number of atretic follicles， with significant increases in the serum levels of E2 and AMH， the ovarian tissue levels of SOD and CAT， as well as the expression levels of Bcl-2， RUNX3 and Notch1 proteins， and significant decreases in the serum FSH levels， the ovarian granulosa cell apoptosis rate， and the ovarian tissue levels of MDA and ROS， as well as the expression levels of cleaved-caspase-3， caspase-3 and Bax proteins （P＜0.05）； the changes in the high-dose group were significantly more pronounced （P＜0.05）. Compared with the high-dose placental polypeptide group and the placental polypeptide plus empty vector group， the placental polypeptide plus RUNX3 silencing group showed a decrease in the number of normal follicles and a significant reversal of the above indicators （P＜0.05）. CONCLUSIONS Placental polypeptide may alleviate the symptoms of rats with POF by upregulating the RUNX3/Notch signaling pathway， improving sex hormone secretion， oxidative stress， ovarian granulosa cell apoptosis and ovarian function.

Objective To observe the influence of Qishen Yiqi Guttate Pills(mainly composed of Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Notoginseng Radix et Rhizoma,and Dalbergiae Odoriferae Lignum)on the clinical efficacy of patients with acute myocardial infarction after percutaneous coronary intervention(PCI).Methods Sixty post-PCI patients with acute myocardial infarction of qi deficiency and blood stasis type who met the inclusion criteria were randomly divided into a treatment group and a control group,with 30 patients in each group.The control group was treated with conventional western medicine,and the treatment group was treated with Qishen Yiqi Guttate Pills on the basis of treatment for the control group.The course of treatment for the two groups lasted for 3 months.The changes of cardiac function indicators and serum levels of hypersensitive C-reactive protein(hs-CRP)and N-terminal B-type natriuretic peptide precursor(NT-pro BNP)were observed before and after the treatment in the two groups,and the incidence of cardiovascular adverse events during the treatment in the two groups were also compared.Results(1)After treatment,the serum hs-CRP and NT-pro BNP levels of patients in the two groups were significantly decreased(P＜0.05)and the left ventricular ejection fraction(LVEF)was significantly increased(P＜0.05)compared with those before treatment.And the effects on lowering the levels of serum hs-CRP and NT-pro BNP and on increasing LVEF of the treatment group were significantly superior to those of the control group,the differences being statistically significant(P＜0.05).(2)During the treatment period,the incidence of cardiovascular adverse events in the treatment group was 6.67%(2/30),which was significantly lower than 26.67%(8/30)of the control group,and the difference was statistically significant when comparing the two groups(P＜0.05).Conclusion Qishen Yiqi Guttate Pills can effectively improve cardiac function,decrease serum hs-CRP and NT-pro BNP levels,and reduce the occurrence of adverse cardiovascular events in post-PCI patients with acute myocardial infarction of qi deficiency and blood stasis type.

Objective To evaluate the patient-reported outcome(PRO)of patients with breast cancer who underwent autologous breast reconstruction and implant breast reconstruction.Methods Patients who underwent breast reconstruction in Shanghai Cancer Center,Fudan University from Jan 2020 to Jun 2021 were selected,including 111 patients who underwent autologous breast reconstruction and 108 patients who underwent implant breast reconstruction.Chinese version Breast-Q2.0 scale,breast cancer specificity scale QLQ-BR23 and EORTC quality of life scale QLQ-C30 were used to investigate the PRO of the two groups 18 months after operation.Results The rate of stage Ⅲ breast cancer in the self-weight construction group was higher than that in the implant reconstruction group(64.9%vs.44.4%,P<0.001).The preoperative neoadjuvant therapy and postoperative radiotherapy in the autologous reconstruction group were higher than those in the implant reconstruction group(P<0.001).Postoperative chemotherapy and endocrine therapy in the autologous reconstruction group were lower than those in the implant reconstruction group(P<0.001).The study based on Breast-Q scale showed that the breast satisfaction of autologous reconstruction group was higher than that of implant reconstruction(59.28±17.20 vs.54.94±14.48,P<0.05).The study based on QLQ-BR23 showed that the self-weight construction group was higher than the implant reconstruction group in the field of arm symptoms(20.02±20.80 vs.12.65±16.18,P<0.05).The study based on QLQ-C30 scale showed that there was no significant difference in all functional areas and symptom areas of patients.There was no significant difference in the number and time of social regression between the two groups.Conclusion Breast reconstruction can improve the PRO of breast cancer patients,and oncology factors will affect the choice of breast reconstruction.Patients with autologous breast reconstruction are more satisfied with breast appearance,but upper limb symptoms such as swelling and pain are more obvious than implant reconstruction,which is related to the higher proportion of axillary lymph node dissection in patients with autologous reconstruction.There is no significant difference in quality of life and social regression between the two groups.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.