Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Ischemic stroke (IS), a leading cause of morbidity and mortality worldwide, primarily results from blood clot formation in cerebral vessels, leading to vessel occlusion, reduced cerebral blood flow, and subsequent tissue ischemia. While thrombolytic therapies and mechanical thrombectomy remain cornerstone treatments for restoring blood flow, their clinical efficacy is significantly limited by the narrow therapeutic window, which underscores the critical need for novel, safe, and effective therapeutic strategies. In this review, we present an intensive analysis of four pathophysiological stages of IS progression and their intervention targets, and evaluate both established and emerging therapeutic strategies with the molecular mechanisms underpinning these methods, aiming to enhance the understanding of IS intervention. Additionally, we discuss current challenges in IS therapy, emphasizing the importance of timely, stage-specific approaches to optimize therapeutic outcomes. Finally, we highlight some promising research directions and innovations to advance IS field.

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy predominantly managed via chemotherapy. Our clinical sample analysis revealed a significant correlation between elevated CD24 expression in TNBC tumor cells and patient survival rates. We developed a novel antibody-drug conjugate (ADC), named HN03, consisting of an antibody with engineered cysteines for site-specific conjugation with a low toxic nitric oxide (NO) precursor as its payload through a novel Pt(IV)-mediated bioorthogonal self-cleavable linker. HN03 specifically targets tumor cells expressing high levels of CD24, concurrently generating cisplatin and releasing NO upon activation. HN03 also exhibited potent in vitro and in vivo antitumor activity. It significantly reduced tumor growth at various doses, prevented tumor metastasis, with markedly lower toxicity than traditional chemotherapy agents. We found that a key mechanism of its action involved inducing apoptosis and endoplasmic reticulum stress, substantially decreasing the number of M2-type macrophages. Overall, HN03 stands out as a promising therapeutic option for TNBC, offering a targeted treatment with reduced side effects and the potential for improved outcomes. Furthermore, using Pt(IV) in the linker and an NO precursor as the payload enhances the versatility of the Antibody-NO donor Conjugate (ANC), offering new avenues for the design of the next generation of ADCs.

To analyze the relationship between serum non-HDL-C levels and cardiovascular disease (CVD) mortality in community populations. A retrospective cohort study was conducted using the Yuecheng District Health Information Platform in Shaoxing City, Zhejiang Province. The study cohort included individuals aged 40 years or older with no prior history of CVD who underwent physical examinations at Yuecheng District healthcare institutions between January and December 2019. A total of 39 038 participants were included, including 19 085 males (48.9%) and 19 953 females (51.1%), with a mean age of (73.64±9.10) years. The mean follow-up duration was 52.3 months. During follow-up, 1 227 CVD death events occurred. The results indicated a significant overall association between non-HDL-C levels and the risk of CVD mortality, including coronary heart disease (CHD) and stroke. Cox models indicated that, using the ideal level of non-HDL-C as the reference, the hazard ratios (HRs) for risk of CVD death in the suitable level, borderline elevated level and elevated level groups were 1.24 (95% CI: 1.08-1.42), 1.57 (95% CI: 1.34-1.85) and 2.31 (95% CI: 1.87-2.86), respectively. The corresponding HRs for CHD death were 1.39 (95% CI: 1.10-1.76), 1.69 (95% CI: 1.28-2.12) and 2.53 (95% CI: 1.76-3.64), respectively. Subgroup analysis revealed significant interaction effects between non-HDL-C and sex, smoking, alcohol consumption, and diabetes (all P interaction<0.05). Sensitivity analyses confirmed that results were consistent with the primary findings regarding the association between non-HDL-C and CVD mortality risk. In conclusion, increasing non-HDL-C levels are associated with higher risks of death from cardiovascular diseases, including stroke and CHD. The risk of CVD death associated with elevated non-HDL-C is greater among males, individuals with a history of diabetes, smokers or drinkers. In the future, attention should be paid to the monitoring of non-HDL-C in community health management, and the intensive and personalized management of blood lipids in high-risk population should be strengthened.

To analyze the relationship between serum non-HDL-C levels and cardiovascular disease (CVD) mortality in community populations. A retrospective cohort study was conducted using the Yuecheng District Health Information Platform in Shaoxing City, Zhejiang Province. The study cohort included individuals aged 40 years or older with no prior history of CVD who underwent physical examinations at Yuecheng District healthcare institutions between January and December 2019. A total of 39 038 participants were included, including 19 085 males (48.9%) and 19 953 females (51.1%), with a mean age of (73.64±9.10) years. The mean follow-up duration was 52.3 months. During follow-up, 1 227 CVD death events occurred. The results indicated a significant overall association between non-HDL-C levels and the risk of CVD mortality, including coronary heart disease (CHD) and stroke. Cox models indicated that, using the ideal level of non-HDL-C as the reference, the hazard ratios (HRs) for risk of CVD death in the suitable level, borderline elevated level and elevated level groups were 1.24 (95% CI: 1.08-1.42), 1.57 (95% CI: 1.34-1.85) and 2.31 (95% CI: 1.87-2.86), respectively. The corresponding HRs for CHD death were 1.39 (95% CI: 1.10-1.76), 1.69 (95% CI: 1.28-2.12) and 2.53 (95% CI: 1.76-3.64), respectively. Subgroup analysis revealed significant interaction effects between non-HDL-C and sex, smoking, alcohol consumption, and diabetes (all P interaction<0.05). Sensitivity analyses confirmed that results were consistent with the primary findings regarding the association between non-HDL-C and CVD mortality risk. In conclusion, increasing non-HDL-C levels are associated with higher risks of death from cardiovascular diseases, including stroke and CHD. The risk of CVD death associated with elevated non-HDL-C is greater among males, individuals with a history of diabetes, smokers or drinkers. In the future, attention should be paid to the monitoring of non-HDL-C in community health management, and the intensive and personalized management of blood lipids in high-risk population should be strengthened.

AIM: To compare the efficacy of intravitreal injection of ranibizumab(IVR)and intravitreal injection of conbercept(IVC)in children with retinopathy of prematurity(ROP).METHODS: Retrospective study. A total of 1 100 eyes with ROP treated with intravitreal anti-VEGF at our hospital from January 2015 to June 2023 were included. According to the different therapeutic drugs, the children were divided into two groups: IVR group and IVC group. According to the degree of ROP, the patients were divided into three groups: aggressive ROP(A-ROP), Zone Ⅰ type 1 ROP and Zone Ⅱ type 1 ROP. The reactivation and retreatment between the two groups were compared after propensity score matching(PSM)analysis, and they were followed-up for at least 3 mo after surgery.RESULTS: In Zone Ⅱ type 1 ROP, there was a statistically significant difference in the rates of reactivation and retreatment between the IVR and IVC groups(P<0.05); however, in A-ROP and Zone I type 1 ROP, there were no statistically significant differences in the rates of reactivation and retreatment between the two groups(P>0.05). The risk of reactivation and retreatment of Zone I type 1 ROP was higher than the Zone II type 1 ROP. Furthermore, the use of drugs and corrected gestational age of first treatment were influencing factors of lesion recurrence and retreatment.CONCLUSION: There is a significant difference in the initial cure effect between the two drugs in Zone II type 1 ROP, with the reactivation and retreatment rates of the IVC group being much lower than those of the IVR group.

BACKGROUND:In recent years,tranexamic acid has been extensively used to mitigate the substantial blood loss associated with total knee arthroplasty.However,the optimal method of topical application has not yet been established. OBJECTIVE:To evaluate the effectiveness and safety of intraoperative topical application of tranexamic acid combined with physical compression dressing in reducing perioperative blood loss in total knee arthroplasty. METHODS:A retrospective analysis was conducted on 90 patients who underwent total knee arthroplasty at the Honghui Hospital in Xi'an from January 2021 to December 2022.Based on the different topical use methods of tranexamic acid during surgery,patients were divided into three groups,with 30 cases in each group.In the compression dressing group,2 g of tranexamic acid was placed in the articular cavity,and after packing the wound with gauze and cotton pads,a bandage was used to compress the wound.In the periarticular injection group,2 g of tranexamic acid was injected into the surrounding tissue of the articular cavity.In the intra-articular injection group,2 g of tranexamic acid was injected into the articular cavity.The blood loss,operation time,coagulation indicators,inflammatory indicators,and postoperative complications of the three groups were statistically analyzed. RESULTS AND CONCLUSION:(1)In terms of total blood loss,hidden blood loss,and maximum hemoglobin drop,the periarticular injection group had the least amount,and there was no statistically significant difference between the compression dressing group and periarticular injection group(P>0.05).In terms of intraoperative blood loss,the compression dressing group had the least amount,and there were statistically significant differences compared with the periarticular injection group and intra-articular injection group(P<0.05).There was no statistically significant difference in operation time among the three groups(P>0.05).(2)There were no statistically significant differences in coagulation indicators(D-dimer and fibrinogen degradation products)and inflammation indicators(C-reactive protein and erythrocyte sedimentation rate)among the three groups preoperatively and on the first and third days after operation(P>0.05).(3)There was no statistically significant difference observed among the three groups in terms of slow blood flow in the affected limb,intramuscular venous thrombosis,soft tissue swelling,and incidence of wound complications(P>0.05).Additionally,no cases of deep vein thrombosis or pulmonary embolism were detected in any of the groups.(4)The topical application of tranexamic acid combined with compression dressing achieves the same effect as a periarticular injection in terms of simplicity of operation and reduced perioperative blood loss.This method also avoids the trauma caused by repeated punctures and does not increase the incidence of postoperative complications,making it a worthwhile option for clinical promotion.

Objective To optimize the preparation process of Jiawei Suoquan mixture and determine the quality standard.Methods The preparation technology of Jiawei Suoquan mixture was determined by orthogonal test with the yield of paste,the total amount of morroniside and loganin as indexes.The column was Diamonsil Plus 5μm C18 (250mm×4.6mm).Acetonitrile as mobile phase A,0.3％ phosphoric acid solution as mobile phase B,gradient elution;The detection wavelength was 240nm;The flow rate was 1.0ml/min.The column temperature was 35℃.Results The determined extraction process conditions were extracted twice,with 10 times of water and 8 times of water,respectively,for 1.5h and 1.0h.The established methods for the determination of morroniside and loganin were specific,reproducibility and accurate.The linear relationship of morroniside was good in the range of 0.1962 to 0.9810μg,the average recovery was 100.83％,relative standard deviation (RSD) was 1.26％,and the precision and stability met the requirements.The linear relationship of loganin in the sample size range from 0.0995 to 0.7960μg was good.The average recovery was 97.10％ and RSD was 0.84％.The precision and stability met the requirements.Conclusion The preparation process of Jiawei Suoquan mixture is simple and feasible.The content determination method is specific,accurate and reliable,and can be used for quality control of Jiawei Suoquan mixture.

BackgroundThe mental health level of the prison police is relatively low， so finding innovative ways to improve the mental health of them is of great significance for the safety of prison supervision and the implementation of peaceful China initiative. ObjectiveTo explore the relationship between perceived social support， perceived stress and psychological resilience with mental health of prison police， and to provide references for improving their mental health. MethodsIn March 2022， 424 policemen working in a male prison in a western province were selected by cluster sampling method， and investigated with the Perceived Social Support Scale （PSSS）， Chinese Perceived Stress Scale （CPSS）， Connor-Davidson Resilience Scale （CD-RISC） and General Health Questionnaire 20 （GHQ-20）， then Process 4.2 was used employed to verify the mediating role of perceived stress as well as the moderating role of psychological resilience in the relationship between perceived social support and mental health. Results①Male subjects scored higher on GHQ-20 than female subjects （t=2.095， P<0.05）. ②CPSS score was negatively correlated with PSSS and GHQ-20 scores （r=-0.670， -0.703， P<0.01）， and GHQ-20 score showed a positive correlation with PSSS and CD-RISC scores （r=0.580， 0.693， P<0.01）. ③Perceived social support positively predict mental health （β=0.154， 95% CI： 0.133~0.175， P<0.01）. ④Perceived stress played a mediating role in the relationship between perceived social support and mental health， and the mediation effect size was 0.087， accounting for 88.78% of the total effect （95% CI： 0.064~0.112， P<0.01）. ⑤Psychological resilience played a moderating role in the second half （perceived stress→mental health） of the mediating path of "perceived social support→perceived stress→mental health"（β=0.074， 95% CI： 0.046~0.102， P<0.01）. ⑥Psychological resilience also regulated the mediation effect of perceived stress on the relationship between perceived social support and mental health ［three regression coefficients tested in turn are significant： a=-0.537 （95% CI： -0.594~-0.480， P<0.01）， b1=-0.162 （95% CI： -0.197~-0.127， P<0.01）， b3=0.074 （95% CI： 0.046~0.102， P<0.01）］. ConclusionPerceived social support of prison police has an impact on their mental health both directly and indirectly through perceived stress. In addition， perceived social support of prison police has a moderated mediation effect on mental health， and it is partially moderated by psychological resilience.［ Funded by General Project of Sichuan Prison Administrative Bureau in 2022］