ObjectiveTo evaluate the public health governance capacity in Jiangsu Province and provide an optimized pathway for the construction of a “strong, rich, beautiful, and high-quality” new Jiangsu. MethodsA total of 806 policy documents, 658 public information reports, and 148 research literatures related to public health governance capacity in Jiangsu Province from January 1995 to December 2023 were collected. The status of current public health goverance was assessed based on the evaluation criteria suitable for public health systems, and the strengths and the weaknesses of the system were identified. ResultsThe public health governance capability of Jiangsu Province was scored at 738.3 points, ranking 3rd nationally. Maternal health care and emergency response capacities achieved leading positions nationwide, both ranking 2nd. Jiangsu had exhibited a standardized guidance in the strategic level, a well-established management mechanism, an extensive coverage in information collection, and a scientifically established health targets setting. However, bottlenecks remained, including an unclear division of responsibilities across organizational departments, an insufficient public-health workforce, the absence of a stable growth mechanism for government funding investment, and difficulties in promptly identifying public needs. ConclusionJiangsu’s public-health system demonstrates leading nationally, yet several components remain underdeveloped. Future efforts should consolidate advantages while addressing weaknesses, further diversify content and forms, establish a stable funding increase mechanism, and clarify departmental functions, thereby providing solid health support for realizing the developmental goals of a “strong, rich, beautiful and high-quality” new Jiangsu.

This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified＿f＿Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Lung/metabolism* ; Mice, Inbred C57BL ; Capsules ; Orthomyxoviridae Infections/virology* ; Gastrointestinal Microbiome/drug effects* ; Male ; Humans ; Female ; Influenza A virus/physiology* ; Influenza, Human/virology*

OBJECTIVE: To compare the efficacy and safety of intravenous colistin sulfate combined with nebulized inhalation versus intravenous monotherapy for pulmonary infections caused by carbapenem-resistant organism (CRO). METHODS: A multicenter retrospective cohort study was conducted. Clinical data were collected from patients admitted to the intensive care unit (ICU) of 10 tertiary class-A hospitals in Henan Province between July 2021 and May 2023, who received colistin sulfate for CRO pulmonary infections. Data included baseline characteristics, inflammatory markers [white blood cell count (WBC), neutrophil count (NEU), procalcitonin (PCT), C-reactive protein (CRP)], renal function indicators [serum creatinine (SCr), blood urea nitrogen (BUN)], life support measures, anti-infection regimens, clinical efficacy, microbiological clearance rate, and prognostic outcomes. Patients were divided into two groups: intravenous group (colistin sulfate monotherapy via intravenous infusion) and combination group ((intravenous infusion combined with nebulized inhalation of colistin sulfate). Changes in parameters before and after treatment were analyzed. RESULTS: A total of 137 patients with CRO pulmonary infections were enrolled, including 89 in the intravenous group and 48 in the combination group. Baseline characteristics, life support measures, daily colistin dose, and combination regimens (most commonly colistin sulfate plus carbapenems in both groups) showed no significant differences between two groups. The combination group exhibited higher clinical efficacy [77.1% (37/48) vs. 59.6% (52/89)] and microbiological clearance rate [60.4% (29/48) vs. 39.3% (35/89)], both P < 0.05. Pre-treatment inflammatory and renal parameters showed no significant differences between two groups. Post-treatment, the combination group showed significantly lower WBC and CRP [WBC (×10⁹/L): 8.2±0.5 vs. 10.9±0.6, CRP (mg/L): 14.0 (5.7, 26.6) vs. 52.1 (24.4, 109.6), both P < 0.05], whereas NEU, PCT, SCr, and BUN levels showed no significant between two groups. ICU length of stay was shorter in the combination group [days: 16 (10, 25) vs. 21 (14, 29), P < 0.05], although mechanical ventilation duration and total hospitalization showed no significant differences between two groups. CONCLUSIONS Intravenous colistin sulfate combined with nebulized inhalation improved clinical efficacy and microbiological clearance in CRO pulmonary infections with an acceptable safety profile.
Humans ; Colistin/therapeutic use* ; Retrospective Studies ; Administration, Inhalation ; Anti-Bacterial Agents/therapeutic use* ; Carbapenems/pharmacology* ; Male ; Female ; Middle Aged ; Gram-Negative Bacteria/drug effects* ; Aged ; Treatment Outcome ; Respiratory Tract Infections/drug therapy*

Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority. Our previous research demonstrated the efficacy of artesunate (ART) in alleviating liver fibrosis by eliminating activated hepatic stellate cells (HSCs). However, the underlying mechanism remains unclear despite these findings. Notably, endocytic adaptor protein (NUMB) has significant implications for treating hepatic diseases, but current research primarily focuses on liver regeneration and hepatocellular carcinoma. The precise function of NUMB in liver fibrosis, particularly its ability to regulate HSCs, requires further investigation. This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs. We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs, exhibiting a negative correlation with the progression of liver fibrosis. Additionally, ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor (P53) axis. We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate. This research examines the specific target of ART in eliminating activated HSCs, providing both theoretical and experimental evidence for the treatment of liver fibrosis.
Hepatic Stellate Cells/cytology* ; Liver Cirrhosis/genetics* ; Artesunate/pharmacology* ; Cellular Senescence/drug effects* ; Membrane Proteins/genetics* ; Animals ; Humans ; Nerve Tissue Proteins/genetics* ; Tumor Suppressor Protein p53/genetics* ; Male ; Mice

O-acetyl-L-homoserine (OAH) is a promising platform compound for the production of L-methionine and other valuable compounds, while its low yield and low conversion rate limit the industrial application. To solve these problems, we constructed a strain for high OAH production with the previously constructed L-homoserine producer Escherichia coli HS33 as the chassis by systematic metabolic engineering. Firstly, PEP accumulation, pyruvate utilization, and OAH synthesis pathway (overexpressing aspB, aspA, and thrA^C1034T) were enhanced to obtain an initial strain accumulating 13.37 g/L OAH. Subsequently, the co-factor synthesis genes were integrated to supply reducing power and energy, which increased the yield to 15.79 g/L. The OAH yield of the engineered strain OAH28 was further increased to 17.49 g/L by strengthening the acetic acid reuse pathway, improving the supply of acetyl-CoA, and regulating the expression of MetX from different sources. Finally, in a 5 L fermenter, OAH28 achieved an OAH titer of 47.12 g/L, with a glucose conversion rate of 32% and productivity of 0.59 g/(L·h). The results lay a foundation for increasing the OAH production by metabolic engineering and give insights into the industrial production of OAH.
Metabolic Engineering/methods* ; Escherichia coli/genetics* ; Homoserine/biosynthesis* ; Fermentation

Objective:To investigate the preventive and therapeutic effects of iridoid glycosides from Boschniakia rossica(IGBR)on precancerous lesions of liver cancer in rats,and to clarify its possible mechanism.Methods:Thirty Wistar rats were selected and the precancerous liver lesion model was established using the modified Solt-Faber method.The rats were randomly divided into sham operation group,model group,and IGBR group,and there were 10 rats in each group.The morphology of liver tissue of the rats in various groups were observed;the liver weights,liver indexes and liver regeneration degrees of the rats in various groups were measured;HE staining was used to observe the pathomorphology of liver tissue of the rats in various groups;immunohistochemistry method was used to detect the expression of glutathione-S-transferase(GST)-Pi protein in liver tissue of the rats in various groups;colorimetric method was used to detect the activities of γ-glutamyl transpeptidase(γ-GT),catalase(CAT),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and glutathione S-transferase(GST),and the level of malondialdehyde(MDA)in liver tissue and mitochondria of the rats in various groups;Western blotting method was used to detect the expression levels of α-smooth muscle actin(α-SMA),collagen type Ⅰ alpha 1 chain(ColⅠα1),matrix metalloproteinase(MMP)13,MMP2,tissue inhibitor of metalloproteinase(TIMP)1,TIMP2,transforming growth factor β1(TGF-β1),TGF-β1 receptor(TβR),mothers against decapentaplegic homolog(Smad)2/3,Smad4,and Smad7 proteins in liver tissue of the rats in various groups.Results:Compared with sham operation group,the liver weight,liver index and degree of liver regeneration of the rats in model group were increased(P<0.05);compared with model group,the liver weight and liver index of the rats in IGBR group showed a decreasing trend,but the difference was not statistically significant(P>0.05).The HE staining results showed that the liver lobule structure in sham operation group was intact and clear,with large hepatocytes,abundant eosinophilic cytoplasm,and hepatocytes arranged in single cords radiating from the central vein;there were irregular hepatic sinusoids between plates,with only a small amount of collagen fibers and inflammatory cell infiltration in the portal area,and no degeneration or necrosis of hepatocytes.In model group,the normal arrangement of hepatocytes disappeared,the liver lobule structure was disrupted,small cell hyperplasia(mainly oval cells)was observed in the portal area,with massive collagen deposition and significant fibrous tissue hyperplasia in the fibrous septum;hepatocytes showed extensive degenerative edema,hydropic degeneration or even ballooning degeneration and focal necrosis;basophilic hepatocytes formed proliferative areas with clear cytoplasm,centrally located nuclei and 1-2 prominent nucleoli;glassy hepatocytes with enlarged nuclei and pale transparent cytoplasm were also observed.In IGBR group,the liver lobule structure was basically preserved,with reduced inflammatory lesions,mild edema,and scattered spotty or focal necrosis;nuclear atypia and pathological mitotic figures or binucleation were observed.The immunohistochemistry results showed GST-Pi protein positive foci with brown-yellow cytoplasmic staining in round or oval nodules.The GST-Pi protein positive foci were observed in liver tissue of the rats in model group,indicating successful establishment of precancerous liver lesion model.The scattered GST-Pi protein positive foci were observed in IGBR group,which were significantly reduced compared with model group.Compared with sham operation group,the activity of γ-GT in liver tissue of the rats in model group was increased(P<0.05);compared with model group,the activity of γ-GT in liver tissue of the rats in IGBR group was decreased(P<0.05).Compared with sham operation group,the GST activity and MDA level in liver tissue and liver mitochondria of the rats in model group were increased(P<0.05),while the activities of SOD,CAT,and GSH-Px were decreased(P<0.05);compared with model group,the GST activity and MDA level in liver tissue and liver mitochondria of the rats in IGBR group were decreased(P<0.05),while the activities of SOD,CAT,and GSH-PX were increased(P<0.05).The Western blotting results showed that compared with sham operation group,the expression levels of α-SMA,ColⅠα1,TIMP1,and TIMP2 proteins in liver tissue of the rats in model group were increased(P<0.05),while the expression levels of MMP13 and MMP2 proteins were decreased(P<0.05),and the ratios of TIMP1/MMP13 and TIMP2/MMP2 were increased(P<0.05);compared with model group,the expression levels of α-SMA,ColⅠα1,and TIMP2 proteins in liver tissue of the rats in IGBR group were decreased(P<0.05),while the expression levels of MMP13 and MMP2 proteins were increased(P<0.05),and the ratios of TIMP1/MMP13 and TIMP2/MMP2 were decreased(P<0.05).Compared with sham operation group,the expression levels of TGF-β1 and Smad2/3 proteins in liver tissue of the rats in model group were increased(P<0.05);compared with model group,the expression levels of TGF-β1,Smad2/3 and Smad 4 proteins in liver tissue of the rats in IGBR group were decreased(P<0.05).Conclusion:IGBR can inhibit precancerous liver lesions and liver fibrosis in rats,and its mechanism may be related to enhancing the antioxidant capacity of liver tissue,inhibiting TGF-β/Smad signaling pathway and regulating TIMP/MMP balance.

Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*