Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

ObjectiveTo analyze the epidemiological characteristics of a local dengue fever cluster outbreak in Qingpu District of Shanghai in 2024, and to provide a reference for subsequent dengue fever prevention and control. MethodsSeven confirmed local dengue fever cases reported through the National Notifiable Infectious Diseases Surveillance System in Qingpu District of Shanghai in 2024 were selected as the research subjects. Descriptive epidemiological methods were used to conduct investigation and analysis from the aspects of onset, medical treatment and reporting, clinical symptoms, travel and contact history within 15 days before onset, and activity trajectories. ResultsA total of 7 cases were identified in this outbreak. None of the cases had a travel history to dengue-endemic areas within 15 days prior to onset, while all had shared exposure environments and mosquito bite histories, indicating a local clustered transmission pattern. The main clinical manifestations included fever (100.00%) and myalgia (42.86%). All 7 cases were positive for dengue virus serotype 2 (DENV-2) by nucleic acid testing. Genetic sequencing showed that the virus strains belonged to the Cosmopolitan genotype and were most closely related to the epidemic DENV strains circulating in southern China in recent years. ConclusionThis outbreak might be a local secondary infection caused by the short-term stay of dengue fever-infected individuals, and the possible source of importation was dengue fever endemic areas in southern China.

L-citrulline is a nonprotein amino acid that plays an important role in human health and has great market demand. Although microbial cell factories have been widely used for biosynthesis, there are still challenges such as genetic instability and low efficiency in the biosynthesis of L-citrulline. In this study, an efficient, plasmid-free, non-inducible L-citrulline-producing strain of Escherichia coli BL21(DE3) was engineered by combined strategies. Firstly, a chassis strain capable of synthesizing L-citrulline was constructed by block of L-citrulline degradation and removal of feedback inhibition, with the L-citrulline titer of 0.43 g/L. Secondly, a push-pull-restrain strategy was employed to enhance the L-citrulline biosynthesis, which realized the L-citrulline titer of 6.0 g/L. Thirdly, the NADPH synthesis and L-citrulline transport were strengthened to promote the synthesis efficiency, which achieved the L-citrulline titer of 11.6 g/L. Finally, fed-batch fermentation was performed with the engineered strain in a 3 L fermenter, in which the L-citrulline titer reached 44.9 g/L. This study lays the foundation for the industrial production of L-citrulline and provides insights for the modification of other amino acid metabolic networks.
Citrulline/biosynthesis* ; Escherichia coli/genetics* ; Metabolic Engineering/methods* ; Fermentation ; NADP/biosynthesis*

Microtubulin disease，which is rare in prenatal settings，is characterized by severe brain developmental abnormalities due to mutations in the microtuberin gene.In this article，a patient diagnosed with TUBB3-related microtubule proteinopathy during prenatal testing was reported，serving as a reference for prenatal physicians. A 33-year-old pregnant woman，who was 23 +5 weeks pregnant，visited to Peking University First Hospital Ningxia Women and Children's Hospital. During a prenatal ultrasound examination，it was discovered that the fetal brain midline was curved，the septum pellucida was twisted，the left lateral fissure had an oblique platform shape，the left lateral ventricle was enlarged，and there were left thoracic cystadenoma and right ventricular hyperechoic plaques. Whole exome sequencing was performed and revealed a mutation in the TUBB3 gene. The pregnancy was terminated at 26 +6 weeks of gestation. Prenatal ultrasound can detect some signs of microtubule protein disease，and genetic testing is recommended for prenatal diagnosis to comprehensively assess the prognosis of the fetus.

Objective:To explore the genetic characteristics of a Chinese pedigree with rare mosaic 11q partial duplication and its pathogenetic mechanisms.Methods:A pedigree which underwent prenatal diagnosis at Wenzhou Central Hospital between September 25, 2015 and November 30, 2023 was selected for the study. Clinical data were collected from the pedigree. Peripheral blood samples from the parents, amniotic fluid from the fetus, and peripheral blood sample from the neonate were obtained. Genetic testing was carried out by using G-banded chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) technology. Relevant literature was searched in the CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases to summarize the clinical phenotypes of patients with 11q partial duplication. This study was approved by the Medical Ethics Committee of Wenzhou Central Hospital (Ethics No. L2024-07-080).Results:The pregnant woman (G 3) had a history of adverse pregnancy outcomes. During her first pregnancy (G 1), prenatal ultrasound indicated intrauterine growth restriction and a Dandy-Walker variant. Follow-up at 8 years of age showed developmental delays and mild intellectual disability. During her second pregnancy (G 2), prenatal ultrasound revealed nasal bone hypoplasia, and the pregnancy was terminated at 23rd gestational week. During her third pregnancy (G 3), all prenatal tests were normal, and the neonate showed normal growth and development at 4 months of age. The karyotype of amniotic fluid of her first pregnancy was 46, X? , and the SNP-array analysis of neonatal peripheral blood showed arr[GRCh37/hg19]11q13.4q25(70432450_134607121)×2~3, with a mosaicism rate being approximately 40%. The karyotype for her second pregnancy was 46, X? , rec(11)dup(11q)inv(11)(p15q13)dmat[6]/46, X? [27], and the SNP-array result was arr[GRCh38]11q13.4q25(71406636_135067522)×2~3, with a mosaicism rate being approximately 75%. The karyotype for her third pregnancy was 46, X? , inv(11)(p15q13)mat, and the SNP-array result was arr(XN)×1, (1~22)×2. The karyotype of the woman was 46, XX, inv(11)(p15q13), and that of her husband was 46, XY. A review of 12 similar cases (including G 1) from the literature revealed that the common clinical phenotypes of 11q partial duplication included intellectual disability (12/12), developmental delay (12/12), ear abnormalities (12/12), microcephaly (10/12), seizures (8/12), hypotonia (8/12), and congenital heart malformations (7/12). Conclusion:Mosaic partial duplication of 11q may underlie the genetic etiology of this pedigree. The pregnant woman is a carrier of an inversion on chromosome 11, which might have formed the mosaic 11q partial duplication through meiotic errors and mitotic trisomy rescue mechanisms during reproduction.

Objective To explore the application effect of the dual-track nursing intervention model in the treatment process of children with lobar pneumonia.Methods A total of 186 children with lobar pneumonia were selected and randomly divided into control group and intervention group u-sing a double-blind method,with 93 cases in each group.The control group received conventional nursing intervention,while the intervention group implemented the dual-track nursing intervention model on the basis of conventional nursing.This model included the establishment and training of nurs-ing teams,personalized nursing plans,health education,and psychological support.Outside the hos-pital,it emphasized family support,regular follow-up guidance,and community-based collaborative ed-ucation.Both groups received a 3-week intervention.The improvement times of clinical symptoms,hos-pital stay,pulmonary function indicators before and after nursing,treatment compliance,and family members' satisfaction with nursing were compared and analyzed between the two groups.Results The fever resolution time[(3.89±0.96)d],cough relief time[(6.21±1.34)d],disappearance time of pulmonary rales[(7.89±1.56)d],and hospital stay duration[(9.45±1.89)d]in the intervention group were all shorter than those in the control group[(5.23±1.14),(7.45±1.67),(9.32±2.01),and(11.28±2.35)d,respectively],with statistically significant differences(P＜0.05).After nursing,the forced expiratory volume in one second(FEV1)[(1.51±0.22)L],forced vital capacity(FVC)[(1.75±0.25)L],and FEV1/FVC[(94.12±5.65)％]in the intervention group were all higher than those in the control group[(1.42±0.15)L,(1.66±0.22)L,and(85.73±8.41)％,respectively],with statistically significant differences(P＜0.05).The scores for exami-nation cooperation[(23.91±3.82)points],nursing cooperation[(24.19±4.03)points],standardized medication use[(24.26±3.94)points],and rational diet[(23.77±3.62)points]in the intervention group were higher than those in the control group[(20.16±3.53),(19.64±3.46),(23.05±3.68),and(18.85±3.41)points,respectively],with statistically significant differences(P＜0.05).The satisfaction rate of family members with nursing work in the intervention group was higher than that in the control group,with a statistically significant difference(98.92％versus 89.25％,P＜0.05).Conclusion The dual-track nursing intervention model has a signifi-cant application effect in children with lobar pneumonia.It can accelerate their recovery process,improve treatment compliance,promote pulmonary function improvement,and enhance family mem-bers' satisfaction.

Objective To explore the mechanism of Shuangshu Decoction(SSD)for inhibiting growth of gastric cancer xenografts in nude mice.Methods Network pharmacology analysis was conducted to identify the common targets of SSD and gastric cancer cell ferroptosis,and bioinformatics analysis and molecular docking were used to validate the core targets.In the cell experiment,AGS cells were treated with SSD-medicated serum,Fer-1(a ferroptosis inhibitor),or both,and the changes in cell viability,ferroptosis markers(ROS,Fe2+and GSH),expressions of P53,SLC7A11 and GPX4,and mitochondrial morphology were examined.In a nude mouse model bearing gastric cancer xenografts,the effects of gavage with SSD,intraperitoneal injection of Fer-1,or their combination on tumor volume/weight,histopathology,and expressions of P53,SLC7A11 and GPX4 levels were evaluated.Results The active components in SSD(quercetin and wogonin)showed strong binding affinities to P53.In AGS cells,SSD treatment dose-dependently inhibited cell proliferation,increased ROS and Fe2+levels,upregulated P53 expression,and downregulated the expressions of SLC7A11 and GPX4,but these effects were effectively attenuated by Fer-1 treatment.SSD also induced mitochondrial shrinkage and increased the membrane density,which were alleviated by Fer-1.In the tumor-bearing mouse models,gavage with SSD significantly reduced tumor size and weight,caused tumor cell necrosis,upregulated P53 and downregulated SLC7A11 and GPX4 expression in the tumor tissue,and these effects were obviously mitigated by Fer-1 treatment.Conclusion SSD inhibits gastric cancer growth in nude mice by inducing cell ferroptosis via the P53/SLC7A11/GPX4 axis.

OBJECTIVE: To explore the genetic characteristics of a Chinese pedigree with rare mosaic 11q partial duplication and its pathogenetic mechanisms. METHODS: A pedigree which underwent prenatal diagnosis at Wenzhou Central Hospital between September 25, 2015 and November 30, 2023 was selected for the study. Clinical data were collected from the pedigree. Peripheral blood samples from the parents, amniotic fluid from the fetus, and peripheral blood sample from the neonate were obtained. Genetic testing was carried out by using G-banded chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) technology. Relevant literature was searched in the CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases to summarize the clinical phenotypes of patients with 11q partial duplication. This study was approved by the Medical Ethics Committee of Wenzhou Central Hospital (Ethics No. L2024-07-080). RESULTS: The pregnant woman (G₃) had a history of adverse pregnancy outcomes. During her first pregnancy (G₁), prenatal ultrasound indicated intrauterine growth restriction and a Dandy-Walker variant. Follow-up at 8 years of age showed developmental delays and mild intellectual disability. During her second pregnancy (G₂), prenatal ultrasound revealed nasal bone hypoplasia, and the pregnancy was terminated at 23rd gestational week. During her third pregnancy (G₃), all prenatal tests were normal, and the neonate showed normal growth and development at 4 months of age. The karyotype of amniotic fluid of her first pregnancy was 46,X?, and the SNP-array analysis of neonatal peripheral blood showed arr[GRCh37/hg19]11q13.4q25(70432450_134607121)×2~3, with a mosaicism rate being approximately 40%. The karyotype for her second pregnancy was 46,X?,rec(11)dup(11q)inv(11)(p15q13)dmat[6]/46,X?[27], and the SNP-array result was arr[GRCh38]11q13.4q25(71406636_135067522)×2~3, with a mosaicism rate being approximately 75%. The karyotype for her third pregnancy was 46,X?,inv(11)(p15q13)mat, and the SNP-array result was arr(XN)×1,(1~22)×2. The karyotype of the woman was 46,XX,inv(11)(p15q13), and that of her husband was 46,XY. A review of 12 similar cases (including G₁) from the literature revealed that the common clinical phenotypes of 11q partial duplication included intellectual disability (12/12), developmental delay (12/12), ear abnormalities (12/12), microcephaly (10/12), seizures (8/12), hypotonia (8/12), and congenital heart malformations (7/12). CONCLUSION Mosaic partial duplication of 11q may underlie the genetic etiology of this pedigree. The pregnant woman is a carrier of an inversion on chromosome 11, which might have formed the mosaic 11q partial duplication through meiotic errors and mitotic trisomy rescue mechanisms during reproduction.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Chromosome Duplication ; Chromosomes, Human, Pair 11/genetics* ; East Asian People/genetics* ; Karyotyping ; Mosaicism ; Pedigree ; Polymorphism, Single Nucleotide ; Prenatal Diagnosis

OBJECTIVES: To explore the mechanism of Shuangshu Decoction (SSD) for inhibiting growth of gastric cancer xenografts in nude mice. METHODS: Network pharmacology analysis was conducted to identify the common targets of SSD and gastric cancer cell ferroptosis, and bioinformatics analysis and molecular docking were used to validate the core targets. In the cell experiment, AGS cells were treated with SSD-medicated serum, Fer-1 (a ferroptosis inhibitor), or both, and the changes in cell viability, ferroptosis markers (ROS, Fe²⁺ and GSH), expressions of P53, SLC7A11 and GPX4, and mitochondrial morphology were examined. In a nude mouse model bearing gastric cancer xenografts, the effects of gavage with SSD, intraperitoneal injection of Fer-1, or their combination on tumor volume/weight, histopathology, and expressions of P53, SLC7A11 and GPX4 levels were evaluated. RESULTS: The active components in SSD (quercetin and wogonin) showed strong binding affinities to P53. In AGS cells, SSD treatment dose-dependently inhibited cell proliferation, increased ROS and Fe²⁺ levels, upregulated P53 expression, and downregulated the expressions of SLC7A11 and GPX4, but these effects were effectively attenuated by Fer-1 treatment. SSD also induced mitochondrial shrinkage and increased the membrane density, which were alleviated by Fer-1. In the tumor-bearing mouse models, gavage with SSD significantly reduced tumor size and weight, caused tumor cell necrosis, upregulated P53 and downregulated SLC7A11 and GPX4 expression in the tumor tissue, and these effects were obviously mitigated by Fer-1 treatment. CONCLUSIONS SSD inhibits gastric cancer growth in nude mice by inducing cell ferroptosis via the P53/SLC7A11/GPX4 axis.
Ferroptosis/drug effects* ; Animals ; Stomach Neoplasms/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Mice, Nude ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Amino Acid Transport System y+/metabolism* ; Mice ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Xenograft Model Antitumor Assays