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.

Pregnancy with chronic kidney disease (CKD), particularly in stages 4-5, carries high risks of adverse outcomes including maternal renal failure, preeclampsia/eclampsia, fetal growth restriction, and preterm birth. This report described a 26-year-old woman with congenital solitary kidney, polycystic ovaries, and uterine septum due to PAX2 gene variant, complicated by CKD stage 4. Through multidisciplinary team precision management and individualized treatment strategies, including timely initiation of dialysis, the patient successfully maintained pregnancy until 34 +1 weeks and delivered a female infant via cesarean section. This case summarizes key management experiences for end-stage renal disease in pregnancy, highlighting early risk assessment, precise nutritional management, hemodialysis protocol optimization, and the crucial role of multidisciplinary collaboration, providing valuable references for managing CKD-complicated pregnancies.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

Objective To evaluate the efficacy of Compound Fipronil Spot-on Solution in repelling canine ticks.Methods A total of 140 dogs infested with ticks were randomly selected from regions in southern and northern China and assigned to four groups:southern test drug group,southern control drug group,northern test drug group,and northern control drug group.Each group comprised 35 dogs.Each dog was administered the prescribed dose.The number of ticks was counted on days 1,7,14,21,and 28 following the administration.The negative conversion and average reduction rates of the tick population were then subjected to statistical analyse.Results The mean efficacy of the test drug was 100%in both the southern and northern cohorts,28 days post-treatment.The control drug showed comparable efficacy,reaching a mean reduction of 100%in both regions by the same time point.No additional clinical manifestations or adverse events were observed across all treated dogs.Conclusions Compound Fipronil Spot-on Solutions effectively treats and prevents ticks in dogs in different regions of China.A single dose remains effective for up to 28 days,thus providing a convenient,effective solution.

Objective:To explore the impact of a three-dimensional management based on a perinatal one-day clinic on pregnancy outcomes in overweight and obese pregnant women.Methods:It was a randomized controlled trial. A simple random sampling method was used to select 460 singleton pregnant women with a pre-pregnancy body mass index≥24 kg/m2 who had regular prenatal check-ups at the Obstetrics and Gynecology Center of the Third Affiliated Hospital of Chongqing Medical University from June 1, 2018, to December 31, 2022. The women were randomly divided into an experimental group and a control group (230 cases each) using a computer-generated random number table. The control group received regular prenatal check-ups according to the pregnancy care guidelines (once every 4 weeks during mid-pregnancy, once every 2 weeks during late pregnancy, with additional frequency as needed based on the condition). The control group also received a one-time body composition analysis and dietary guidance from a nutritionist at the time of registration. In addition to the control group′s interventions, the experimental group received three-dimensional management based on a perinatal one-day clinic. It included an intensive one-day clinic session, a traditional plus internet-based re-education model (as needed based on the condition), individualized guidance from obstetrics and clinical nutrition clinics (once every 2 weeks), a free body composition test at 24 weeks of pregnancy, and weekly WeChat group push of health care knowledge during pregnancy. A total of 55 cases dropped out, leaving 200 cases in the experimental group and 205 cases in the control group for analysis. General information, pregnancy-related, and postpartum indicators were collected in the two groups. The effect of three-dimensional management based on a perinatal one-day clinic on pregnancy outcomes in overweight and obese pregnant women was analyzed using t-tests and chi-square tests. Results:There was no significant differences in baseline age, pre-pregnancy body mass index, initial blood glucose, initial glycated hemoglobin, or initial gestational age between the two groups (all P>0.05). The experimental group showed significantly lower gestational weight gain, neonatal weight, and proportion of excessive pregnancy weight gain compared to those in the control group [(11.41±5.23) vs (13.22±4.51) kg, (3 352.1±465.3) vs (3 489.5±464.0) g, 48.00% vs 73.17%] (all P<0.05). There were no significant differences in hospitalization days, gestational age at delivery, incidence of gestational diabetes, incidence of hypertensive disorders of pregnancy, incidence of premature rupture of membranes, incidence of preterm birth, incidence of macrosomia, vaginal delivery rate and rate of neonatal transfer to the pediatric department between the two groups (all P>0.05). Conclusion:Early intervention with the three-dimensional management based on the one-day perinatal clinic can effectively control gestational weight gain and neonatal weight in overweight and obese pregnant women.

Objective:To explore the impact of a three-dimensional management based on a perinatal one-day clinic on pregnancy outcomes in overweight and obese pregnant women.Methods:It was a randomized controlled trial. A simple random sampling method was used to select 460 singleton pregnant women with a pre-pregnancy body mass index≥24 kg/m2 who had regular prenatal check-ups at the Obstetrics and Gynecology Center of the Third Affiliated Hospital of Chongqing Medical University from June 1, 2018, to December 31, 2022. The women were randomly divided into an experimental group and a control group (230 cases each) using a computer-generated random number table. The control group received regular prenatal check-ups according to the pregnancy care guidelines (once every 4 weeks during mid-pregnancy, once every 2 weeks during late pregnancy, with additional frequency as needed based on the condition). The control group also received a one-time body composition analysis and dietary guidance from a nutritionist at the time of registration. In addition to the control group′s interventions, the experimental group received three-dimensional management based on a perinatal one-day clinic. It included an intensive one-day clinic session, a traditional plus internet-based re-education model (as needed based on the condition), individualized guidance from obstetrics and clinical nutrition clinics (once every 2 weeks), a free body composition test at 24 weeks of pregnancy, and weekly WeChat group push of health care knowledge during pregnancy. A total of 55 cases dropped out, leaving 200 cases in the experimental group and 205 cases in the control group for analysis. General information, pregnancy-related, and postpartum indicators were collected in the two groups. The effect of three-dimensional management based on a perinatal one-day clinic on pregnancy outcomes in overweight and obese pregnant women was analyzed using t-tests and chi-square tests. Results:There was no significant differences in baseline age, pre-pregnancy body mass index, initial blood glucose, initial glycated hemoglobin, or initial gestational age between the two groups (all P>0.05). The experimental group showed significantly lower gestational weight gain, neonatal weight, and proportion of excessive pregnancy weight gain compared to those in the control group [(11.41±5.23) vs (13.22±4.51) kg, (3 352.1±465.3) vs (3 489.5±464.0) g, 48.00% vs 73.17%] (all P<0.05). There were no significant differences in hospitalization days, gestational age at delivery, incidence of gestational diabetes, incidence of hypertensive disorders of pregnancy, incidence of premature rupture of membranes, incidence of preterm birth, incidence of macrosomia, vaginal delivery rate and rate of neonatal transfer to the pediatric department between the two groups (all P>0.05). Conclusion:Early intervention with the three-dimensional management based on the one-day perinatal clinic can effectively control gestational weight gain and neonatal weight in overweight and obese pregnant women.

Pregnancy with chronic kidney disease (CKD), particularly in stages 4-5, carries high risks of adverse outcomes including maternal renal failure, preeclampsia/eclampsia, fetal growth restriction, and preterm birth. This report described a 26-year-old woman with congenital solitary kidney, polycystic ovaries, and uterine septum due to PAX2 gene variant, complicated by CKD stage 4. Through multidisciplinary team precision management and individualized treatment strategies, including timely initiation of dialysis, the patient successfully maintained pregnancy until 34 +1 weeks and delivered a female infant via cesarean section. This case summarizes key management experiences for end-stage renal disease in pregnancy, highlighting early risk assessment, precise nutritional management, hemodialysis protocol optimization, and the crucial role of multidisciplinary collaboration, providing valuable references for managing CKD-complicated pregnancies.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

This study was aimed at understanding the Blastocystis,Enteroc ytozoon bieneusi,Cryptosporidium spp.,Gi-ardia duodenalis,and Pentatrichomonas hominis infection status in Chinese Milu deer(Elaphurus davidianus)in various prov-inces of China.A total of 81 fecal samples were collected from Beijing,Inner Mongolia,Hebei,and Hubei.PCR was used to detect the protozoans,and their subtypes and zoonoticity were determined through sequence and phylogenetic analyses.PCR re-sults indicated an infection prevalence of 40.74％,19.75％,and 8.64％for Blastocystis,E.bieneusi,and Cryptosporidium spp.,respectively,whereas G.duodenalis and P.hominis was not detected.Only one subtype of Cryptosporidium spp.(Cryptosporidium deer genotype)was detected.Four E.biene-usi genotypes were detected:HLJD-V,MWC-d1,BEB6,and CGC2.Five Blastocystis ST types were found:ST10,ST14,ST21,ST23,and ST25.Cryptosporidium spp.,E.bieneusi,and Blastocystis infections were prevalent,and zoonotic subtypes or genotypes of E.bieneusi and Blastocystis were i-dentified.The prevention and control of intestinal protozoa in Chinese Milu deer would support population health and is im-portant for public health.

This study was aimed at understanding the Blastocystis,Enteroc ytozoon bieneusi,Cryptosporidium spp.,Gi-ardia duodenalis,and Pentatrichomonas hominis infection status in Chinese Milu deer(Elaphurus davidianus)in various prov-inces of China.A total of 81 fecal samples were collected from Beijing,Inner Mongolia,Hebei,and Hubei.PCR was used to detect the protozoans,and their subtypes and zoonoticity were determined through sequence and phylogenetic analyses.PCR re-sults indicated an infection prevalence of 40.74％,19.75％,and 8.64％for Blastocystis,E.bieneusi,and Cryptosporidium spp.,respectively,whereas G.duodenalis and P.hominis was not detected.Only one subtype of Cryptosporidium spp.(Cryptosporidium deer genotype)was detected.Four E.biene-usi genotypes were detected:HLJD-V,MWC-d1,BEB6,and CGC2.Five Blastocystis ST types were found:ST10,ST14,ST21,ST23,and ST25.Cryptosporidium spp.,E.bieneusi,and Blastocystis infections were prevalent,and zoonotic subtypes or genotypes of E.bieneusi and Blastocystis were i-dentified.The prevention and control of intestinal protozoa in Chinese Milu deer would support population health and is im-portant for public health.