Objective To evaluate the effectiveness of the integrated schistosomiasis control programme in Wuhan City from 2005 to 2023, so as to provide insights into precision control and elimination of schistosomiasis. Methods The integrated measures for schistosomiasis control implemented by health, agriculture, water resources, and forestry departments of Wuhan City, and the epidemiological data of schistosomiasis in Wuhan City were collected from 2005 to 2023, and the prevalence of human schistosomiasis, prevalence of Schistosoma japonicum infections in humans and bovines, areas of S. japonicum-infected snail habitats, areas of snail habitats in inner embankments, and actual areas of snail habitats were retrieved. In addition, the trends in prevalence of schistosomiasis in humans and livestock and snail status were evaluated in Wuhan City from 2005 to 2023 using Mann-Kendall test and a Joinpoint regression model. Results Mann-Kendall test revealed a tendency towards a decline in the prevalence of human schistosomiasis (Z = -4.41, P < 0.01), prevalence of S. japonicum infections in humans (Z = -4.89, P < 0.01) and bovines (Z = -4.50, P < 0.01), areas of S. japonicum-infected snail habitats (Z = -3.91, P < 0.01), areas of snail habitats in inner embankments (Z = -2.28, P = 0.02), and actual areas of snail habitats (Z = -5.95, P < 0.01) in Wuhan City from 2005 to 2023. Joinpoint regression analysis showed an average annual reduction of 8.58% in the prevalence of human schistosomiasis in Wuhan City from 2005 to 2023 [average annual percent change (AAPC) = -8.58%, 95% confidence interval (CI): (-10.02%, -6.65%), P < 0.01], with two joinpoints in 2013 and 2016, respectively, and the tendency towards a decline showed statistical significance during the period from 2013 through 2016 [annual percent change (APC) = -34.41%, 95% CI: (-40.36%, -20.01%), P < 0.01]. The prevalence of S. japonicum human infections appeared an average annual reduction of 51.91% in Wuhan City from 2005 to 2023 [AAPC = -51.91%, 95% CI: (-58.12%, -44.25%), P < 0.01], with two joinpoints in 2014 and 2017, respectively, and the tendency towards a decline showed statistical significance during the period from 2014 through 2017 [APC = -98.17%, 95% CI: (-99.17%, -90.87%), P < 0.01]. The prevalence of S. japonicum infections in bovines appeared an average annual reduction of 53.12% in Wuhan City from 2005 to 2023 [AAPC = -53.12%, 95% CI: (-59.65%, -42.44%), P < 0.01], with two joinpoints in 2011 and 2014, respectively, and the tendency towards a decline showed statistical significance during the period from 2014 through 2017 [APC = -98.63%, 95% CI: (-99.44%, -90.93%), P < 0.01]. The areas of S. japonicum-infected snail habitats appeared an average annual reduction of 47.09% in Wuhan City from 2005 to 2023 [AAPC = -47.09%, 95% CI: (-52.92%, -38.26%), P < 0.01], with two joinpoints in 2011 and 2014, respectively, and the tendency towards a decline showed statistical significance during the period from 2011 through 2014 [APC = -97.27%, 95% CI: (-98.65%, -88.06%), P < 0.01]. The areas of snail habitats in inner embankments appeared an average annual reduction of 4.45% in Wuhan City from 2005 to 2023 [AAPC = -4.45%, 95% CI: (-5.18%, -3.82%), P < 0.01], with three joinpoints in 2011, 2015 and 2018, respectively, and statistical significance was seen in the tendency towards a decline during the period from 2005 through 2011 [APC = -16.38%, 95% CI: (-20.15%, -14.25%), P < 0.01]. In addition, the actual areas of snail habitats appeared an average annual reduction of 2.65% in Wuhan City from 2005 to 2023 [AAPC = -2.65%, 95% CI: (-2.89%, -2.40%), P < 0.01], with a joinpoint in 2013, and the tendency towards a decline showed statistical significance during the period from 2013 through 2023 [APC = -4.06%, 95% CI: (-4.66%, -3.58%), P < 0.01]. Conclusions The integrated schistosomiasis control programme achieved significant effectiveness in Wuhan City from 2005 to 2023, with a tendency towards a decline in morbidity due to schistosomiasis in humans and livestock and snail status. The integrated schistosomiasis control strategy with emphasis on management of the source of S. japonicum infections should continue to be implemented to consolidate the schistosomiasis control achievements and achieve the goal of schistosomiasis elimination in the city.

Objective: To explore the iodine nutrition status of children in Wuhan from 2019 to 2023, and to evaluate the effect of iodine deficiency disorders control in focus groups in Wuhan, so as to provide a basis for consolidating elimination of iodine deficiency disorders. Methods: A total of 13 000 non boarding primary school students aged 8-10 were selected from 13 districts of Wuhan by stratified random sampling method.Household salt samples were collected to measure salt iodine content, random urine samples were analyzed for urinary iodine concentration. And B ultrasound was used to measure thyroid volume in students. The median of salt iodine, coverage rate of iodized salt, consumption rate of qualified iodized salt, median of urinary iodine, and the goiter rate were calculated. And Mann-Whitney U- test, Kruskal-Wallis H- test and Chi-square test were applied to compare between groups. Chi-square trend test was used to analyze the changing trends of coverage rate of iodized salt, consumption rate of qualified iodized salt and goiter rate among children in Wuhan. Results: The median of iodine content of children s household salt was 23.8 (21.7, 26.1) mg/kg, and the coverage rate of iodized salt was 98.7%, and the consumption rate of qualified iodized salt was 94.5 %. The consumption rates of qualified iodized salt showed an overall upward trend from 2019 to 2023 ( χ 2 trend =5.57， P <0.05). The median of urinary iodine of children was 220.1 (136.7, 326.0) μg/L,and boys had higher median of urinary iodine than girls [228.3(143.2, 336.0),210.2(129.1, 315.7) μg/L] ( Z =6.60, P <0.01). The median of urinary iodine of children in suburbs was higher than those in urban areas [236.3 (150.7, 342.2) , 207.1 (124.5, 309.8) μg/L]( Z =11.00, P <0.01). A total of 4 600 children were examined for thyroid volume, and the range of goiter rates were 1.1% to 3.4%, with an average goiter rate of 2.5%, which showed an overall downward trend from 2019 to 2023 ( χ 2 trend =5.11, P <0.05). Conclusions The iodine nutrition is sufficient and iodine nutrition status is good among children in Wuhan. It should continue to carry out monitoring and evaluation of children s iodine nutrition, guide the public to supplement iodine scientifically,so as to maintain the appropriate level of iodine for children.

PURPOSE: To methodically assess the effectiveness of augmentative plating (AP) and exchange nailing (EN) in managing nonunion following intramedullary nailing for long bone fractures of the lower extremity. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to gather clinical studies regarding the use of AP and EN techniques in the treatment of nonunion following intramedullary nailing of lower extremity long bones. The search was conducted up until May 2023. The original studies underwent an independent assessment of their quality, a process conducted utilizing the Newcastle-Ottawa scale. Data were retrieved from these studies, and meta-analysis was executed utilizing Review Manager 5.3. RESULTS: This meta-analysis included 8 studies involving 661 participants, with 305 in the AP group and 356 in the EN group. The results of the meta-analysis demonstrated that the AP group exhibited a higher rate of union (odds ratio: 8.61, 95% confidence intervals (CI): 4.12 - 17.99, p < 0.001), shorter union time (standardized mean difference (SMD): -1.08, 95% CI: -1.79 - -0.37, p = 0.003), reduced duration of the surgical procedure (SMD: -0.56, 95% CI: -0.93 - -0.19, p = 0.003), less bleeding (SMD: -1.5, 95% CI: -2.81 - -0.18, p = 0.03), and a lower incidence of complications (relative risk: -0.17, 95% CI: -0.27 - -0.06, p = 0.001). In the subgroup analysis, the time for union in the AP group in nonisthmal and isthmal nonunion of lower extremity long bones was shorter compared to the EN group (nonisthmal SMD: -1.94, 95% CI: -3.28 - -0.61, p < 0.001; isthmal SMD: -1.08, 95% CI: -1.64 - -0.52, p = 0.002). CONCLUSION In the treatment of nonunion in diaphyseal fractures of the long bones in the lower extremity, the AP approach is superior to EN, both intraoperatively (with reduced duration of the surgical procedure and diminished blood loss) and postoperatively (with an elevated union rate, shorter union time, and lower incidence of complications). Specifically, in the management of nonunion of lower extremity long bones with non-isthmal and isthmal intramedullary nails, AP demonstrated shorter union time in comparison to EN.
Humans ; Bone Nails/adverse effects* ; Bone Plates/adverse effects* ; Femoral Fractures/surgery* ; Fracture Fixation, Intramedullary/methods* ; Fractures, Ununited/surgery* ; Lower Extremity/injuries*

PURPOSE: We carried out the study aiming to explore and analyze the risk factors, the distribution of pathogenic bacteria, and their antibiotic-resistance characteristics influencing the occurrence of surgical site infection (SSI), to provide valuable assistance for reducing the incidence of SSI after traumatic fracture surgery. METHODS: A retrospective case-control study enrolling 3978 participants from January 2015 to December 2019 receiving surgical treatment for traumatic fractures was conducted at Tangdu Hospital of Air Force Medical University. Baseline data, demographic characteristics, lifestyles, variables related to surgical treatment, and pathogen culture were harvested and analyzed. Univariate analyses and multivariate logistic regression analyses were used to reveal the independent risk factors of SSI. A bacterial distribution histogram and drug-sensitive heat map were drawn to describe the pathogenic characteristics. RESULTS: Included 3978 patients 138 of them developed SSI with an incidence rate of 3.47% postoperatively. By logistic regression analysis, we found that variables such as gender (males) (odds ratio (OR) = 2.012, 95% confidence interval (CI): 1.235 - 3.278, p = 0.005), diabetes mellitus (OR = 5.848, 95% CI: 3.513 - 9.736, p < 0.001), hypoproteinemia (OR = 3.400, 95% CI: 1.280 - 9.031, p = 0.014), underlying disease (OR = 5.398, 95% CI: 2.343 - 12.438, p < 0.001), hormonotherapy (OR = 11.718, 95% CI: 6.269 - 21.903, p < 0.001), open fracture (OR = 29.377, 95% CI: 9.944 - 86.784, p < 0.001), and intraoperative transfusion (OR = 2.664, 95% CI: 1.572 - 4.515, p < 0.001) were independent risk factors for SSI, while, aged over 59 years (OR = 0.132, 95% CI: 0.059 - 0.296, p < 0.001), prophylactic antibiotics use (OR = 0.082, 95% CI: 0.042 - 0.164, p < 0.001) and vacuum sealing drainage use (OR = 0.036, 95% CI: 0.010 - 0.129, p < 0.001) were protective factors. Pathogens results showed that 301 strains of 38 species of bacteria were harvested, among which 178 (59.1%) strains were Gram-positive bacteria, and 123 (40.9%) strains were Gram-negative bacteria. Staphylococcus aureus (108, 60.7%) and Enterobacter cloacae (38, 30.9%) accounted for the largest proportion. The susceptibility of Gram-positive bacteria to Vancomycin and Linezolid was almost 100%. The susceptibility of Gram-negative bacteria to Imipenem, Amikacin, and Meropenem exceeded 73%. CONCLUSION Orthopedic surgeons need to develop appropriate surgical plans based on the risk factors and protective factors associated with postoperative SSI to reduce its occurrence. Meanwhile, it is recommended to strengthen blood glucose control in the early stage of admission and for surgeons to be cautious and scientific when choosing antibiotic therapy in clinical practice.
Humans ; Surgical Wound Infection/epidemiology* ; Male ; Female ; Risk Factors ; Retrospective Studies ; Middle Aged ; Adult ; Case-Control Studies ; Fractures, Bone/surgery* ; Aged ; Drug Resistance, Bacterial ; Logistic Models ; Anti-Bacterial Agents/therapeutic use* ; Incidence ; Bacteria/drug effects*

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Clinical chemotherapy for prostate cancer is still compromised by high treatment thresholds and severe off-target toxicity of drugs. Given the limited progress in improving therapeutic outcomes and reducing toxicity with the existing toolbox, efforts to broaden the chemotherapeutic window are highly desired. Here, we discover that gossypol (GSP, a natural compound) dramatically enhances the chemosensitivity of cabazitaxel (CTX), even at previously ineffective concentrations. Based on this interesting finding, we exploit a carrier-free chemotherapeutic nano-booster for prostate cancer treatment, which is molecularly co-assembled by GSP and cabazitaxel (CTX). GSP not only readily forms nanoassembly with CTX, but also functions as a chemotherapeutic enhancer that unlocks an ultra-low-dose chemotherapeutic window. Not only that, precise dual-drug nanoassembly confers CTX a significantly larger maximum tolerable dose. As expected, the nano-booster exerts striking therapeutic benefits in mouse prostate tumor xenograft models. This study advances chemotherapeutic window expansion and self-sensitized chemotherapy toward clinical applicability.

Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific Sting1 knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING-PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. In vivo, macrophage-specific Sting1 knockout reduced myocardial inflammation and injury after AMI. In vitro, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA-STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.

Background Pulmonary fibrosis currently lacks screening and diagnostic methods in the early stages and effective treatments in the later stages, so there is an urgent need to explore the mechanisms and develop targeted treatments. Objective To screen the expression of differentially expressed circular RNA (circRNA) hsa_circUCK2 under pathological conditions and to explore its effect on pulmonary fibrosis. Methods In the cell-based experiments, hsa_circUCK2 was knocked down in HPF-a cells using small interfering RNA (siRNA), and HPF-a cells were stimulated by TGF-β1. Four groups were set up: si-NC group, si-circUCK2 group, si-NC+TGF-β1-treated group, and si-circUCK2+TGF-β1-treated group. Western blot assay was used to detect the expression of fibronectin (FN1) in HPF-a cells of the four groups, scratch assay was used to detect the migration ability of HPF-a cells, and CCK-8 assay was used to detect the proliferation ability of HPF-a cells in the two groups with TGF-β1 stimulation, the si-NC+TGF-β1-treated group and the si-circUCK2+TGF-β1-treated group. In the animal experiments, forty-eighty healthy SPF-grade male C57BL/6 mice were randomly divided into four groups: saline+si-con group, saline+si-circ_0000115 group, SiO₂+si-con group, and SiO₂+si-circ_0000115 group. Mouse lung circRNA mmu_circ_0000115 (mouse homolog of hsa_circUCK2) was knocked down by tracheal drip injection of siRNA, and a mouse lung fibrosis model was constructed by tracheal drip injection of SiO₂ suspension (0.2 g·kg⁻¹, 50 mg·mL⁻¹) after 48 h. Real-time fluorescence quantitative PCR was used to detect the knockout efficiency in each organ of the mouse, Western blot was applied to detect the expression of type I collagen α2 (COL1A2) in the lung tissues, and Sirius red was used to detect collagen synthesis in the lung tissues. Results In the cell-based experiments, after the knockdown of hsa_circUCK2, the Western blot results showed that the expression level of the FN1 protein in TGF-β1-stimulated HPF-a cells was significantly down-regulated (P <0.05); the CCK-8 assay and cell scratch assay showed that the down-regulation of hsa_circUCK2 gene significantly inhibited the proliferation and migration of HPF-a cells (P<0.01). In the animal experiments, the real-time fluorescence quantitative PCR results showed that among the detected organs, mmu_circ_0000115 was significantly knocked down only in the lung tissues (P<0.0001); the Western blot results showed that knocking down mmu_circ_0000115 significantly reduced the COL1A2 protein expression level when compared with the SiO₂+si-con group (P<0.0001); the Sirius red results showed that knocking down mmu_circ_0000115 significantly reduced collagen production and deposition in lung tissues of mice in the model group. Conclusion Knockdown of hsa_circUCK2 inhibits fibroblast activation and reduces collagen deposition in lung fibrosis model mice. It is suggested that the hsa_circUCK2 is involved in the process of pulmonary fibrosis and may be a potential therapeutic target for pulmonary fibrosis.

Objective To investigate the correlation between gene polymorphisms of coagulation factor Ⅻ(FⅫ)rs1801020 and resistin rs1862513 and unexplained recurrent spontaneous abortion(URSA).Methods A total of 189 patients diagnosed with URSA and 191 healthy postpartum women during the same period were selected from the obstetric clinic of Changning Maternity and Infant Health Hospital from January 2020 to December 2022.The probe PCR was used to detect gene polymorphisms of rs1801020 and rs1862513 in peripheral blood,and the differences in genotype distribution between the groups were observed.Results The frequencies of geno-types and alleles for F Ⅻ rs1801020 in the URSA-A group were 4.9％(CC),35.7％(CT),59.5％(TT),22.7％(C),and 77.3％(T),respectively.In the control A group,the frequencies were 8.0％(CC),47.1％(CT),44.9％(TT),31.5％(C)and 68.5％(T).The frequencies of genotypes and alleles for resistin rs1862513 in the URSA-B group were 11.3％(CC),47.3％(CG),41.4％(GG),34.9％(C)and 65.1％(G).In the control B group,the frequencies were 10.2％(CC),34.1％(CG),55.7％(GG),27.3％(C)and 72.7％(G).There was no significant difference in genotype frequency of the two loci(P＞0.05),but there was a sig-nificant difference in allele frequency(P＜0.05).The distribution frequency of F Ⅻ rs1801020 T allele in the URSA group was higher than that in the control group(X2=6.32,OR=1.567,95％CI:1.100-2.238,P=0.012).The distribution frequency of resistin rs1862513 G allele in URSA group was lower than that in con-trol group(X2=4.96,OR=1.433,95％CI:1.050-1.969,P=0.026).The mutation of F Ⅻ rs1801020 C to T was a risk factor for the occurrence of URSA,while the mutation of rs1862513 C to G was a protective factor for the occurrence of URSA(P＜0.05).The combined genotype analysis showed that compared to the popu-lation carrying the rs1801020 CC+rs1862513 CC genotype combination,the population carrying the rs1801020 TT+rs1862513 CG genotype had a significantly higher risk of URSA(OR=5.684,95％CI:1.210-30.920,P=0.035).Conclusion FⅫ rs1801020 T allele may increase the risk of URSA and resistin rs1862513 G al-lele may the risk of URSA.People with rs1801020 TT+rs1862513 CG genotype combination is more likely to develop URSA than those with rs1801020 CC+rs1862513 CC genotype combination.