Stroke is the leading cause of death and disability among adults in China， and its common complications include digestive system abnormalities， cognitive impairment， depression， stroke-associated pneumonia， and hemiplegia. The combination of traditional Chinese and Western medicine has great potential in treating post-stroke complications. Xinglou Chengqitang （XLCQT） is a representative prescription of alleviating the disease in the upper part by treating the lower part. It has definite therapeutic effect and high safety. Clinically， XLCQT is often used to treat stroke and its complications. However， the quantity and quality of clinical trials of XLCQT in treating post-stroke complications need to be improved. Additionally， since the basic research is weak， the material basis and multi-target mechanism for the efficacy of this prescription are unknown. This article reviews XLCQT in terms of the pharmacodynamic basis， medicinal properties， safety evaluation， and progress in clinical research and mechanisms in treating post-stroke complications. This article summarizes 22 key active ingredients of XLCQT in treating acute stroke complicated with syndrome of phlegm heat and fu-organ excess. Among these key active ingredients， resveratrol， kaempferol， luteolin， chrysoeriol， apigenin， （+）-catechin， and adenosine have good pharmacokinetic properties and high bioavailability. The mechanisms of XLCQT in treating post-stroke complications are complex， including inflammatory response， brain-gut axis， hypothalamic-pituitary-adrenal （HPA） axis， intestinal flora， neurotrophic factors， autophagy， oxidative stress， and free radical damage. This review helps to deeply understand the pharmacodynamic basis and mechanisms of XLCQT in treating post-stroke complications and provides a theoretical basis for the clinical application of XLCQT against post-stroke complications and the development of drugs.

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.

With the increasing severity of bacterial antibiotic resistance， finding new ways to overcome this global challenge has become an urgent task. Chinese medicine， with abundant resources， offers potential for discovering diverse bioactive ingredients to enhance antibiotic efficacy and alleviate the crisis of bacterial antibiotic resistance. This review summarizes bacterial resistance mechanisms， prevention strategies， and the roles and mechanisms of Chinese medicine and its active ingredients in enhancing the efficacy of existing antibiotics. Two major resistance mechanisms—bacterial obstruction of antibiotic uptake and weakening of intracellular antibiotic activity—are introduced， with corresponding prevention and control strategies outlined. Based on the regulatory effects of active ingredients from Chinese medicine on bacteria， their mechanisms for enhancing antibiotic efficacy are categorized into two types， including improving the bacterial uptake of antibiotics and reducing the bacterial resistance to antibiotics. The former mainly enhances extracellular antibiotic uptake by regulating membrane permeability， biofilm formation， and metabolic pathways. The latter weakens intracellular antibiotic resistance by inhibiting efflux pumps and bacterial resistance targets. Furthermore， compound formulas of Chinese medicine， characterized by multi-component， multi-target， and multi-pathway interventions， exert similar antimicrobial effects and mechanisms with active ingredients， offering rich resources for developing antibiotic-enhancing applications. Finally， the review highlights the challenges such as insufficient structural research on active ingredients and potential druggability issues in their application for antibiotic enhancement. This will provide insights for advancing the research on Chinese active ingredients in antibiotic therapy and offers novel strategies to combat bacterial antibiotic resistance.

With the increasing severity of bacterial antibiotic resistance， finding new ways to overcome this global challenge has become an urgent task. Chinese medicine， with abundant resources， offers potential for discovering diverse bioactive ingredients to enhance antibiotic efficacy and alleviate the crisis of bacterial antibiotic resistance. This review summarizes bacterial resistance mechanisms， prevention strategies， and the roles and mechanisms of Chinese medicine and its active ingredients in enhancing the efficacy of existing antibiotics. Two major resistance mechanisms—bacterial obstruction of antibiotic uptake and weakening of intracellular antibiotic activity—are introduced， with corresponding prevention and control strategies outlined. Based on the regulatory effects of active ingredients from Chinese medicine on bacteria， their mechanisms for enhancing antibiotic efficacy are categorized into two types， including improving the bacterial uptake of antibiotics and reducing the bacterial resistance to antibiotics. The former mainly enhances extracellular antibiotic uptake by regulating membrane permeability， biofilm formation， and metabolic pathways. The latter weakens intracellular antibiotic resistance by inhibiting efflux pumps and bacterial resistance targets. Furthermore， compound formulas of Chinese medicine， characterized by multi-component， multi-target， and multi-pathway interventions， exert similar antimicrobial effects and mechanisms with active ingredients， offering rich resources for developing antibiotic-enhancing applications. Finally， the review highlights the challenges such as insufficient structural research on active ingredients and potential druggability issues in their application for antibiotic enhancement. This will provide insights for advancing the research on Chinese active ingredients in antibiotic therapy and offers novel strategies to combat bacterial antibiotic resistance.

Objective To investigate the epidemiological characteristics and control measures of dengue fever in Zhongshan City in 2024, so as to provide insights into optimization of dengue fever control strategies in the city. Methods Data pertaining to dengue fever cases in Zhongshan City in 2024 were collected from the Infectious Disease Reporting System of China Disease Prevention and Control Information System, and the epidemiological characteristics of the cases were analyzed using a descriptive statistical method. The density of Aedes albopictus mosquito was monitored across all 23 townships (subdistricts) using Breteau index (BI) and mosquito ovitrap index (MOI) at midmonth each month from March to December 2024. In addition, the climatic characteristics, case reporting patterns, and corresponding control measures were analyzed during different phases of dengue fever epidemics in Zhongshan in 2024. Furthermore, real-time quantitative reverse transcription PCR (RT-qPCR) assay was employed to serotype the dengue virus among local dengue fever cases with unknown sources of infections. The dengue virus envelope (E) gene was sequenced using Sanger sequencing among dengue fever cases without apparent epidemiological links. A phylogenetic tree was constructed using the neighbor-joining method to infer major transmission chains during the dengue fever epi demics. Results A total of 952 dengue fever cases were reported in Zhongshan City in 2024, including 879 local cases, 57 domestically imported cases from other regions, and 16 overseas imported cases, representing the largest outbreak in nearly two decades. The first local dengue fever case was reported on July 5, and the last one was detected on December 19, with all townships and subdistricts affected. Mosquito monitoring data indicated that both MOI and BI rose rapidly from March to May, and then remained at high levels with fluctuations, and began to decline in October. The dengue fever epidemic was categorized into five distinct phases in Zhongshan, including non-epidemic, pre-epidemic, early-epidemic, peak, and receding stages. During the pre-epidemic and early-epidemic phases, key measures included enhancing sensitivity of case detection, implementing isolation and treatment of hospitalized cases, and carrying out standardized vector control measures in affected communities. In the peak phase, the strategy shifted towards targeted mosquito control in key communities and clinical rescue and treatment emphasized on “preventing severe cases and deaths”. Among 481 local cases with unknown sources of infections, RT-qPCR assay revealed that 68.8% (331/481) were infected with dengue virus type I and 31.2% (150/481) with type II among local dengue fever cases in Zhongshan City in 2024. Phylogenetic analysis revealed two major transmission chains: one originating from imported cases within Guangdong Province around Zhongshan City, and another from cases imported from Malaysia. Late detection of local dengue fever cases contributed to widespread community outbreaks. Conclusions The 2024 dengue fever epidemic in Zhongshan City was of considerable scale, which was primarily driven by imported cases from overseas and surrounding regions, leading to local community outbreaks. The epidemic began in early July, increased rapidly during August and September, peaked in October, and subsequently declined, with a trend consistent with the average pattern observed in previous high-incidence years. By implementing differentiated control measures tailored to each phase of the epidemic, the local transmission of dengue fever was successfully contained in Zhongshan City in 2024.

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

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*

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

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.