Objective To systematically evaluate the similarities between six-gene-modified pig red blood cells and human red blood cells in multiple dimensions, including cell morphology, hematological parameters, microbial safety and serological compatibility, and to verify the feasibility of using six-gene-modified pig red blood cells as an alternative for blood transfusion in cases of traumatic hemorrhage. Methods Blood samples from O-type human donor, six-gene-modified O-type pig and wild-type O-type pig were collected. The pig gene-modified phenotype was identified by flow cytometry. The morphology was observed using field emission scanning electron microscopy and the diameter was measured. Hematological tests, including blood routine, osmotic fragility test, adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) content and partial pressure of oxygen at 50% hemoglobin saturation (P50), were conducted to assess the deformability of red blood cells. Real-time fluorescent quantitative polymerase chain reaction was used to screen for zoonotic viruses, and cross-matching was performed using column gel method, condensation amine method and saline tube method. Results The six-gene-modified pig red blood cells successfully knocked out the α-Gal, Neu5Gc and Sda antigens and expressed hCD55. Wild-type pig red blood cells expressed these three antigens but did not express human complement regulatory proteins. All three types of red blood cells presented a biconcave discoid morphology. The diameter of O-type human red blood cells was larger than that of the six-gene-modified porcine red blood cells and wild-type pig red blood cells (all P < 0.05). The average red blood cell volume and average red blood cell hemoglobin of O-type humans were higher than those of the six-gene-modified pig red blood cells, and the distribution width-variable coefficient of O-type human red blood cells was lower than that of the six-gene-modified pig red blood cells (all P < 0.05). There were no statistically significant differences in the permeability fragility, ATP content, 2,3-DPG content, P50 and red blood cell deformability indicators of the three types of red blood cells (all P > 0.05). The screening for zoonotic viruses in human and animal cells of the six-gene-modified pigs and wild-type pigs was negative. The cross-matching results showed that in the column gel method and condensation amine method, the primary and secondary sides of the six-gene-modified pig red blood cells did not agglutinate with human red blood cells, while the wild-type pig red blood cells agglutinated with human red blood cells in all cross-matching methods. Conclusions The six-gene-modified pig red blood cells are highly similar to human red blood cells in terms of morphology, key hematological parameters, energy metabolism, oxygen-carrying capacity, mechanical properties, microbial safety and serological compatibility, providing an experimental basis for the clinical transformation of xenotransfusion.

Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

Objective To analyze the effect of Meleis transition theory in the intervention of family caregivers of advanced lung cancer patients.Methods From January 2022 to June 2023,94 patients with advanced lung cancer and their family caregivers treated in 4 hospitals of a tertiary A hospital in Zhejiang Province were selected by convenience sampling method,and they were divided into a control group(n=47)and an experimental group(n=47)according to random number table method.The family caregivers of the experimental group received a four-week intervention based on the Meleis transition theory on the basis of routine nursing education,including role recognition,disease knowledge,life care,psychological support,and social resource connection.Family caregivers in the control group received routine nursing education,caregiving education and guidance.The differences in the readiness,caring ability,psychological burden and patients'quality of life were compared between the 2 groups.Results There was no lost follow-up cases in the control group and experimental group.After intervention,the preparation,ability,and quality of life of family caregivers in the experimental group were better than those in the control group,and the psychological burden of caregivers was significantly lower than that in the control group(P＜0.05).Conclusion The intervention of caregiving ability of family caregivers based on Meleis transition theory can effectively improve the caregiving ability of caregivers,reduce the psychological burden of caregivers,improve the quality of care,and improve the quality of life of patients.

Objective To investigate the role of different parenting styles plays in conduct problems of 3-years-old preschool children.Methods Participants were from 148 preschools in Longhua Shenzhen,China.A structured questionnaire covering family demographic characteristics,Conners' Parent Symptom Questionnaire and Egna Minnen Betraffande Uppfostran-Parents (EMBU-P) were conducted among primary caregivers of each child.There were 9289 valid participants in the analysis and logistic regression was used to assess the relationship between three dimensions of parenting (rejection,emotional warmth and control/overprotection) and conduct problems.Results After allowing for certain confounders,parental rejection (OR =1.17,P＜0.01) and control/overprotection (OR =1.03,P＜0.01) was positively associated with conduct problems and emotional warmth was negatively related to conduct problems (OR=0.98,P＜0.01).Stratified analysis showed a significant relationship between conduct problems and both parents' rejection (OR father=1.16,P＜0.01;OR motber=1.17,P＜0.01),father's emotional warmth (OR=0.96,P＜0.01) and mother's control/overprotection (OR=1.04,P＜0.01).This relationship did not vary between boys and girls and between single and not single children.Conclusion Influence of parenting should be taken into consideration in the prevention and intervention of conduct problems.

Objective To explore the addictive tendency of internet and its influence factors among adolescents in Longhua District of Shenzhen. Methods A total of 6552 Students were selected from Longhua District of Shenzhen us?ing randomly stratified cluster sampling method. They were inquired about their gender, grade, family type, behaviors of surfing internet, risk behaviors, and internet addiction tendency with a self-report structured questionnaire and the adoles?cent pathological internet use scale (APIUS). Results The prevalence of addictive tendency of internet was 9.0%(590/6552) among adolescents in Longhua District of Shenzhen. Multiple logistic regression analysis indicated that the addic?tive tendency of internet was significantly and positively associated with male (OR=1.32, P<0.05), living in Minzhi area (OR=1.66, P<0.01), secondary school stage (OR=1.62, P<0.01), uncomplete family type (OR=1.49, P<0.01), surfing in cy?bercafé frequently (OR=2.00, P<0.01), compared with surfing 0~2 h/d, surfing 2~4 h/d (OR=1.92,P<0.01), 4~5 h/d (OR=2.97, P<0.01) or more than 6 h/d (OR=4.90, P<0.01), playing games (OR=3.27, P<0.01), chatting (OR=2.80, P<0.01) or having other kinds of entertaining (OR=2.80, P<0.01), and having risky behaviors (OR=2.39, P<0.01). Conclusion The addictive tendency of internet is affected by multiple factors among adolescents in Longhua District of Shenzhen. There?fore, comprehensive intervention measures shall be used to regulate adolescents habits of using internet and prevent them from the internet addiction.

Objective To explore the interaction between passive smoking and folic acid supplement during pregnancy on children autism spectrum disorder (ASD) behaviors.Methods Children aged about 3 years were enrolled at kindergarten entrance in Longhua district of Shenzhen in 2014.Self-administered questionnaires were completed by their primary caregivers and the information about children' s age,gender,history of preterm birth and low birth weight,parents' education level,parents' reproductive age and family income were collected.The children ASD behaviors were assessed with Autism Behavior Checklist (ABC).According to the cut point of ABC,the children were divided into normal group with score less than 31,sub-clinical group with score ranging from 31 to 61 and suspect clinical group with score no less than 62.After controlling for potential confounders,multivariate logistic regression analysis was performed to evaluate the main effects and the interaction between passive smoking and folic acid supplement during pregnancy on children ASD behaviors.Results Maternal passive smoking during pregnancy was significantly associated with children ASD behaviors (sub-clinical group:OR=1.48;suspect clinical group:OR=2.85),and maternal folic acid supplement during pregnancy was not related to children ASD behaviors (sub-clinical group:OR=1.04;suspect clinical group:OR=0.75).Stratified analysis showed that folic acid supplement during pregnancy was negatively associated with children ASD behaviors (suspect clinical group:OR=0.30) among children without mothers' passive smoking during pregnancy,and that mothers' passive smoking during pregnancy was positively associated with children ASD behaviors (sub-clinical group:OR=1.52;suspect clinical group:OR=4.45) among the children whose mothers had folic acid supplement during pregnancy.Furthermore,an interaction effect on children ASD behaviors was found between passive smoking and folic acid supplement during pregnancy (suspect clinical group:OR=5.30).Conclusion Passive smoking and folic acid supplement during pregnancy were related to children ASD behaviors and had an interaction on children ASD behaviors.

Objective:To investigate the correlation between the plasma sphingomyelin (SM ) levels and the severity of coro‐nary artery disease in patients with coronary atherosclerotic heart disease(CAD) on admission .Methods:Clinical data of 464 pa‐tients undergoing coronary angiography were retrospectively analyzed ,which included 345 male cases and 119 female cases with mean age of 62 .71 ± 0 .46 .The patients were divided into stenosis group (n=327) and normal group (n=137) according to the results of coronary angiography .The severity of coronary artery stenosis was calculated according to Gensini score .The SM levels of all patients were measured on admission .Results:SM levels in control group and stenosis group were 39 .45 ± 0 .91 mg/dL ,45 .05 ± 0 .78 mg/dL ,respectively ,and the difference between the two groups was statistically significant (P<0 .001) .SM levels were positively correlated with Gensini scores(r=0 .155 ,P=0 .001) .The Gensini scores according to their tertiles of SM levels were 6(0‐38) ,18(2‐50) ,19(0‐49) ,respectively .The differences regarding Gensini scores among the three groups were statistically significant (P=0 .035) .After multiple related risk factors had been corrected ,the multivariate linear regression analysis showed that plasma SM levels were independently associated with Gensini scores (β=0 .143 ,95% CI 0 .148~0 .654 ,P=0 .002) .Conclusions:SM level was significantly associated with coronary angiography Gensini score ,and its level might be an independent risk factor for predicting the degree of coronary stenosis .SM might provide novel therapeutic tar‐get for the treatment of CAD .

OBJECTIVE: To evaluate the value of selective arterial occlusion in the treatment of placenta percreta in late trimester of pregnancy. METHODS: Fifteen clinical patients ( gestational age ≥34 weeks), diagnosed with placenta percreta in Xiangya Hospital of Central South University from January 2003 to December 2010, were retrospectively analyzed. According to whether the selective arterial occlusion was used or not, the 15 patients were divided into 2 groups: an arterial occlusion group (n=8) and a non-arterial occlusion group (n=7). Based on the time of occlusion, the arterial occlusion group was divided into a prophylactic occlusion subgroup (n=4) and a remedial occlusion subgroup (n=4) (including 1 patient who was performed after the iliac artery balloon was taken out ). The blood loss, the rate of hysterectomy and complications were compared between the arterial occlusion group and the non-arterial occlusion group. RESULTS: In all 15 patients, the average amount of blood loss was 3813 mL, and the rate of hysterectomy was 73.3% (11/15). The recent complication rate was 20.0% (3/15, including 2 blood coagulation dysfunctions and 1 lower extremity thrombosis), and long-term complication was not found. The average amount of blood loss in the occlusion group was 2512 mL, the hysterectomy rate was 62.5%(5/8); while the average amount of bleeding was 5549 mL and the hysterectomy rate was 85.7% in the non-occlusion group (6/7). There was significant difference between the 2 groups (P<0.05). The average amount of blood loss and the rate of hysterectomy in the prophylactic occlusion subgroup were lower than those in the remedial occlusion subgroup (1350 mL vs 3600 mL, 60.0% vs 66.7%, P<0.05). CONCLUSION Patients with placenta percreta in the third trimester of pregnancy may encounter severe postpartum hemorrhage, and the rate of hysterectomy is high. The amount of blood loss and the rate of hysterectomy may be reduced by the selective arterial occlusion before or in the cesarean section, but cannot be avoided completely.
Adult ; Balloon Occlusion ; methods ; Embolization, Therapeutic ; Female ; Humans ; Hysterectomy ; statistics & numerical data ; Iliac Artery ; Placenta Accreta ; therapy ; Postpartum Hemorrhage ; prevention & control ; Pregnancy ; Pregnancy Trimester, Third ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To investigate the spatiotemporal expression of neuromedin B receptor (NMBR) in mice myometrium at different pregnant stages, as well as its mechanism and relation with parturition. METHODS: The pregnant mice were divided into no-pregnancy (NP), early pregnancy (EP), mid-pregnancy (MP), late-pregnancy (LP), parturition (PT) and postpartum (PP) groups (12 mice in each group), according to pregnant stage. The mRNA and protein expression of NMBR, HSP70 and IL-6 were detected in myometrium in pregnant mice by semi-quantitative RT-PCR and Western blot, while NF-kappaB-P65 DNA binding activity was determined by NoShift transcription factor assay kits, respectively. Their relation with parturition was analyzed. RESULTS: The mRNA expression level of NMBR in the PT group was significantly higher than that in the NP, EP, LP and PP groups (P<0.05), but this difference was not observed in the MP group (P>0.05). The NMBR protein in PT group was significantly higher than that in the other 5 groups (P<0.01). NF-kappaB-P65 DNA binding activity at PT group was remarkably higher than that in the NP, LP and PP groups (P<0.05). The expression of IL-6 mRNA was significantly higher than that in the NP, LP and PP groups (P<0.05), its protein expression in PT and LP groups was significantly higher than that in the NP and PP groups (P<0.05). The expression of HSP70 mRNA in the PT group was significantly higher than that in the NP and PP groups (P<0.05), and the protein of HSP70 was significantly up-regulated in PT and PP groups compared with in NP and LP groups (P<0.05). The DNA-binding activity of P65 was positively correlated to the mRNA expression of NMBR and IL-6 (r=0.40, P<0.01; r=0.30, P<0.05), so were positively correlated to DNA-binding activity of P65, mRNA expression of HSP70 and NMBR ( r=0.40, P<0.01; r=0.49, P<0.01). DNA-binding activity of P65 did not correlate with the mRNA expression of HSP70. CONCLUSION The mRNA and protein expressions of NMBR reach a peak at the onset of labor. NMBR may play an important role in the parturition via NF-kappaB P65-IL-6 signal transduction pathway. It may also influence the onset of labor by regulating HSP70, but this role does not rely on P65 pathway.
Animals ; Female ; Gestational Age ; HSP70 Heat-Shock Proteins ; metabolism ; Interleukin-6 ; metabolism ; Male ; Mice ; Myometrium ; metabolism ; Parturition ; metabolism ; Pregnancy ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Receptors, Bombesin ; genetics ; metabolism ; Signal Transduction ; Transcription Factor RelA ; metabolism

Aim To improve the biological activity of A-ring modified analogues of camptothecin.Methods A-ring modified camptothecins were synthesized from 10-hydroxycamptothecin or 7-ethyl-10-hydroxycamptothecin (SN-38) in three or four steps. Their cytotoxicity was evaluated using MTT assay,and their in vivo antitumor activity against mouse liver cancer H22 was tested. Results Five hexacyclic camptothecins (6a, 6b, 6c, 7a and 7b) are target compounds, and ten camptothecin derivatives are new compounds. Conclusion The modification of a 1,4-oxazine-2-one ring fused with positions 9 and 10 of Aring will reduce the antitumor activity of camptothecins.