Objective: To analyze the disease burden of chronic obstructive pulmonary disease (COPD) and changes in its risk factors among residents in Zhejiang Province from 1990 to 2021, so as to identify key priorities for COPD prevention and control. Methods: Data on COPD mortality and disability-adjusted life years (DALY) for residents in Zhejiang Province from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. Standardized mortality and standardized DALY rate were calculated using the GBD 2021 world population standard structure. Premature mortality was computed via the life table method. The average annual percent change (AAPC) was applied to analyze trends in COPD mortality, DALY rate, and premature mortality. Changes in deaths of COPD risk factors were evaluated using population attributable fraction (PAF). Results: From 1990 to 2021, the standardized COPD mortality in Zhejiang Province decreased from 272.40/100 000 to 70.56/100 000 (AAPC=-4.395%), and the standardized DALY rate declined from 4 167.37/100 000 to 1 071.89/100 000 (AAPC=-4.396%). Similar downward trends were observed in both males (AAPC=-3.933%, -4.173%) and females (AAPC=-4.785%, -4.480%), all P<0.05. Crude mortality and DALY rates increased with age, and the crude mortality and DALY rates of various age groups in Zhejiang Province showed decreasing trends from 1990 to 2021 (all P<0.05). The premature mortality declined from 4.37% to 0.60% from 1990 to 2021 (AAPC=- 6.206%), with consistent trends across males and females (AAPC=- 6.144%, - 6.379%, all P<0.05). From 1990 to 2021, particulate matter pollution showed the largest reduction in PAF (- 56.76%), while ambient ozone pollution had the largest increase (103.07%) in Zhejiang Province. By 2021, smoking became the leading risk factor for deaths of COPD (PAF=43.32%). Conclusions The standardized mortality, standardized DALY rate, and premature mortality for COPD show consistent declining trends in Zhejiang Province from 1990 to 2021. However, risk factors such as smoking and ambient ozone pollution require intensified focus to further reduce disease burden of COPD.

AIM:To observe the effect of the plus power ring zone(PPRZ)area and distribution on myopia progression.METHODS:This retrospective study enrolled 137 pre-teens aged 8-12 at Taiyuan Aier Eye Hospital between 2019 and 2021. They were fitted with Ortho-K lenses for the first time due to refractive error, with a one-year follow-up period. To indicate the peripheral plus ring zone overlapping with the pupil zone(PPROPZ)accompanying PPRZ, participants were divided based on the PPROPZ to PPRZ ratio. The experimental group had 103 eyes with a PPROPZ to PPRZ ratio of ≥0.2, and the control group had 103 eyes with a ratio of <0.2. Participants had a spherical diopter in the range of -6.00 D to -0.75 D, against-the-rule astigmatism less than 1.00 D, with-the-rule astigmatism less than 1.50 D, and corneal curvatures of 39.00 D to 46.00 D. They had a stable best corrected visual acuity of 0.10 LogMAR(20/25)or better when wearing orthokeratology(Ortho-K)lenses. PPRZ and PPROPZ were measured using ImageJ; corneal topography assessed corneal-related parameters, and an optical biometer measured the axial length of the eyes pre and post-one years of lens wear.RESULTS: Changes in axial length elongation were found to decrease when either the PPRZ(P<0.01)or PPROPZ(P<0.001)was increased significantly. The axial length growth was faster in the control group(0.37±0.2 mm)than in the experimental group(0.21±0.11 mm). Furthermore, we found that a larger horizontal visible iris diameter(HVID)corresponded to slower axial growth of the eye. In contrast, axial length growth showed no correlation with surface regularity index(SRI), surface asymmetry index(SAI), flat keratometry value(Kf), steep keratometry value(Ks).CONCLUSION:For orthokeratology, wearers with larger PPROPZ to PPRZ ratio usually experiences a reduction in axial length growth. The PPRZ and PPROPZ are negatively correlated with the axial length. Our findings provide a recommendation and methods for studying the myopia control mechanism through Ortho-K lenses.

OBJECTIVE: To observe the clinical effect of acupuncture and moxibustion combined with umbilical therapy on anxiety and depression in patients with neurogenic bladder (NB) after spinal cord injury (SCI). METHODS: Thirty cases of NB after SCI with anxiety and depression were selected and treated with acupuncture and moxibustion combined with umbilical therapy. Acupuncture was applied at Baihui (GV20), Yintang (GV24⁺), Sanyinjiao (SP6), Shenmen (HT7), Hegu (LI4), Taichong (LR3), once a day, continuous treatment for 4 weeks. Ginger moxibustion was applied at the bladder meridian of foot taiyang and governor vessel, once a day, continuous treatment for 4 weeks. In treatment of umbilical therapy, Chaihu (Radix Bupleuri), Yujin (Radix Curcumae), Rougui (Cortex Cinnamomi) were ground and mixed with the same amount of honey, put into the application, and the application was placed on the navel after filling the navel with fine salt, once a day for 4 weeks. Hamilton anxiety scale (HAMA) score, Hamilton depression scale (HAMD) score, urodynamic indexes (maximum urinary flow rate [Qmax], maximum detrusor pressure [Pdet-max], residual urine volume [RUV]), neurogenic bladder symptom score (NBSS), urinary symptom distress scale (USDS) score were compared before and after treatment, and the clinical efficacy was evaluated. RESULTS: After treatment, the scores of HAMA, HAMD, NBSS, USDS and RUVwere lower than those before treatment (P<0.05), and Qmax and Pdet-max were higher than those before treatment (P<0.05). The total effective rate was 93.3 (28/30). CONCLUSION Acupuncture and moxibustion combined with umbilical therapy can effectively relieve anxiety and depression symptoms, improve urination disorders in patients with NB after SCI.
Humans ; Moxibustion ; Male ; Female ; Adult ; Middle Aged ; Acupuncture Therapy ; Spinal Cord Injuries/psychology* ; Depression/etiology* ; Anxiety/etiology* ; Urinary Bladder, Neurogenic/etiology* ; Young Adult ; Aged ; Combined Modality Therapy ; Acupuncture Points

Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.

Tongue squamous cell carcinoma (TSCC) is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion. Accurate diagnosis and effective treatment are essential for enhancing the quality of life and the survival rates of TSCC patients. The current treatment modalities for TSCC frequently suffer from a lack of specificity and efficacy. Nanoparticles with diagnostic and photothermal therapeutic properties may offer a new approach for the targeted therapy of TSCC. However, inadequate accumulation of photosensitizers at the tumor site diminishes the efficacy of photothermal therapy (PTT). This study modified gold nanodots (AuNDs) with the TSCC-targeting peptide HN-1 to improve the selectivity and therapeutic effects of PTT. The Au-HN-1 nanosystem effectively targeted the TSCC cells and was rapidly delivered to the tumor tissues compared to the AuNDs. The enhanced accumulation of photosensitizing agents at tumor sites achieved significant PTT effects in a mouse model of TSCC. Moreover, owing to its stable long-term fluorescence and high X-ray attenuation coefficient, the Au-HN-1 nanosystem can be used for fluorescence and computed tomography imaging of TSCC, rendering it useful for early tumor detection and accurate delineation of surgical margins. In conclusion, Au-HN-1 represents a promising nanomedicine for imaging-based diagnosis and targeted PTT of TSCC.
Tongue Neoplasms/diagnostic imaging* ; Carcinoma, Squamous Cell/diagnostic imaging* ; Animals ; Gold/chemistry* ; Mice ; Photothermal Therapy/methods* ; Tomography, X-Ray Computed ; Photosensitizing Agents ; Metal Nanoparticles ; Humans ; Cell Line, Tumor

Vein graft (VG) failure (VGF) is associated with VG intimal hyperplasia, which is characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs). Most neointimal VSMCs are derived from pre-existing VSMCs via a process of VSMC phenotypic transition, also known as dedifferentiation. There is increasing evidence to suggest that ginger or its bioactive ingredients may block VSMC dedifferentiation, exerting vasoprotective functions; however, the precise mechanisms have not been fully characterized. Therefore, we investigated the effect of ginger on VSMC phenotypic transition in VG remodeling after transplantation. Ginger significantly inhibited neointimal hyperplasia and promoted lumen (L) opening in a 3-month VG, which was primarily achieved by reducing ferroptotic stress. Ferroptotic stress is a pro-ferroptotic state. Contractile VSMCs did not die but instead gained a proliferative capacity and switched to the secretory type, forming neointima (NI) after vein transplantation. Ginger and its two main vasoprotective ingredients (6-gingerol and 6-shogaol) inhibit VSMC dedifferentiation by reducing ferroptotic stress. Network pharmacology analysis revealed that 6-gingerol inhibits ferroptotic stress by targeting P53, while 6-shogaol inhibits ferroptotic stress by targeting 5-lipoxygenase (Alox5), both promoting ferroptosis. Furthermore, both ingredients co-target peroxisome proliferator-activated receptor gamma (PPARγ), decreasing PPARγ-mediated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1) expression. Nox1 promotes intracellular reactive oxygen species (ROS) production and directly induces VSMC dedifferentiation. In addition, Nox1 is a ferroptosis-promoting gene that encourages ferroptotic stress production, indirectly leading to VSMC dedifferentiation. Ginger, a natural multi-targeted ferroptotic stress inhibitor, finely and effectively prevents VSMC phenotypic transition and protects against venous injury remodeling.

Hydroxyectoine, a vital compatible solute, is widely utilized in cosmetics, food, pharmaceutical industries, and biologics. However, the current microbial fermentation methods for hydroxyectoine production face challenges including insufficient precursor supply and low yields. Therefore, developing engineering microbial strains capable of efficiently synthesizing hydroxyectoine is of great significance. In this study, we first constructed a high-yield ectoine-producing strain ECT04 by multi-copy integration of the ectoine synthesis genes ectABC into the pseudogene loci of Escherichia coli MG1655(DE3), achieving an ectoine titer of 6.03 g/L. Subsequently, we employed plasmids with varying copy numbers to express ectD from Chromohalobacter salexigens to enable the conversion for hydroxyectoine production. We further investigated the effects of promoter, co-substrate ɑ-ketoglutarate, Fe²⁺ concentration, and dissolved oxygen on hydroxyectoine synthesis. Through fed-batch fermentation in a 7-L bioreactor, we significantly enhanced the hydroxyectoine production efficiency, attaining a final titer of 8.58 g/L and a productivity of 0.24 g/(L·h). This work successfully achieved the de novo synthesis of hydroxyectoine in E. coli, laying a foundation for the efficient bioproduction of this compound.
Escherichia coli/genetics* ; Fermentation ; Amino Acids, Diamino/biosynthesis* ; Bioreactors/microbiology* ; Metabolic Engineering/methods* ; Chromohalobacter/genetics* ; Plasmids/genetics*

Objective To induce an NLRP3-/- mouse model of ulcerative colitis(UC)using different concentrations of dextran sulfate sodium(DSS)and different administration times,and to analyze and evaluate the advantages and disadvantages of the preparations to provide a more suitable animal model for the study of UC pathogenesis in humans and the development of therapeutic drugs.Methods Forty-eight male NLRP3-/- specific-pathogen-free mice were divided randomly into blank,2.5％7 d,3％7 d,and 3％5 d groups(n=12 mice per group).UC mouse models were induced using combinations of different concentrations and administration times of DSS.Body weight,DAI(disease activity index)score,hematoxylin and eosin(HE)staining,colon length,and related indicators(interleukin IL-6,tumor necrosis factor(TNF)-α,and tight junction protein(ZO-1))were observed and evaluated.Results(1)UC membrane type was induced in each group with different concentrations and administration times.(2)Mouse body weight decreased,the fecal occult blood became more positive,the DAI score increased,and more mice died with increasing DSS concentration and administration time.(3)Longer administration time and higher concentration of DSS were also associated with more severe damage to the intestinal mucosa,as shown by HE staining.(4)Immunohistochemistry showed that the inflammatory factors TNF-α and IL-6 were increased in the model group compared with the blank control group,while expression of ZO-1 was decreased compared with the blank group.Conclusions(1)Administration of 2.5％or 3％DSS for 7 days or 3％DSS for 5 days can induce UC in NLRP3-/- mice.(2)The combination of DAI score,HE staining,the detection of related indicators,and mouse survival rate indicated that NLRP3-/- mice treated with 3％DSS for 5 days produced the most suitable UC model to study the clinical manifestations and drug treatment of UC.

Objective: To analyze the disease burden and risk factors of colorectal cancer in Zhejiang Province from 1990 to 2019, so as to provide the basis for prevention and control of colorectal cancer. Methods: Based on data of 2019 Global Burden of Disease (GDB 2019), disease burden and risk factors of colorectal cancer in Zhejiang Province from 1990 to 2019 was assessed using years of life lost (YLL), years lived with disability (YLD), disability-adjusted life years (DALY). Results: In 2019, the YLL rate, YLD rate and DALY rate caused by colorectal cancer in Zhejiang Province were 496.15/105, 31.81/105 and 527.96/105, respectively. From 1990 to 2019, the YLL rate, YLD rate and DALY rate caused by colorectal cancer in Zhejiang Province increased by 114.90%, 482.60% and 123.38%, respectively, showing increasing trends (average annual percent change values were =2.663, 6.283 and 2.800, respectively,all P<0.05). From 1990 to 2019, the YLL rate, YLD rate and DALY rate in the age groups of 15 to 49 years, 50 to 69 years and 70 years and older showed increasing trends (all P<0.05). In 1990, the top ten risk factors for colorectal cancer in Zhejiang Province were diet low in calcium, diet low in milk, diet low in whole grains, smoking, alcohol use, low physical activity, high fasting plasma glucose, diet high in red meat, diet low in fiber and high body mass index. In 2019, the top ten risk factors for colorectal cancer in Zhejiang Province were diet low in milk, diet low in whole grains, diet low in calcium, alcohol use, diet high in red meat, high body mass index, high fasting plasma glucose, low physical activity, diet low in fiber and diet high in processed meat. Conclusions The disease burden of colorectal cancer in Zhejiang Province showed an upward trend from 1990 to 2019. The top ten risk factors for colorectal cancer remained between 1990 and 2019, while there was a slight change in ranking.

Objective:To explore the value of conventional magnetic resonance imaging (MRI), diffusion weighted imaging (DWI), diffusion kurtosis imaging (DKI) sequence and pathological examination in predicting the efficacy of neoadjuvant chemotherapy (NAC) in advanced breast cancer.Methods:The clinical data of 65 cases of advanced breast cancer with NAC confirmed by pathology in the Affiliated Hospital of Jining Medical University from March 2022 to May 2023 were retrospectively analyzed, including 20 cases in the pathological complete remission (pCR) group and 45 cases in the non pCR group; All patients underwent routine MRI, DWI, DKI examinations and pathological analysis. The clinical pathological data, routine MRI features, apparent diffusion coefficient (ADC) values, mean kurtosis coefficient (MK), and mean diffusion coefficient (MD) between the two groups were analyzed; We compared the differences in various parameters between two groups and plotted receiver operating characteristic (ROC) curves to compare their diagnostic efficacy of NAC in breast cancer.Results:There were significant differences in molecular typing, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and Ki-67 between pCR group and non pCR group (all P<0.05). In pCR group, Her-2 overexpression type and triple negative breast cancer (TNBC) type breast cancer were more common. ER and PR were mostly negative, Her-2 was mostly positive, and Ki 67 was mainly positive. The difference in tumor T2WI signal between the pCR group and the non pCR group was statistically significant ( P<0.05), with the pCR group showing mostly moderate/low T2WI signal. The ADC and MD values of the pCR group were lower than those of the non pCR group, while the MK value of the pCR group was higher than that of the non pCR group, and the differences were statistically significant (all P<0.001). The area under the ROC curve (AUC) for predicting the efficacy of NAC using a clinical pathological model was 0.829, which was higher than the AUC of molecular subtypes, ER, PR, Her-2, and Ki-67 ( Z=3.008, 2.697, 2.815, 2.131, 2.376, all P<0.05); The AUC of the DKI+ DWI predicting the efficacy of NAC was 0.934, which was higher than that of the DWI single sequence model, and the difference in type was statistically significant ( Z=2.396, P=0.017). The diagnostic efficacy of the DKI+ DWI model was higher than that of the single parameter ADC, MD, and MK, and the differences were statistically significant ( Z=2.396, 2.219, 2.161, all P<0.05); The AUC of the combined imaging and pathology model was 0.983, and its diagnostic efficacy was higher than that of the conventional MRI feature model, pathology model, DWI model, and DKI model, with statistically significant differences ( Z=5.877, 2.961, 3.240, 2.264, all P<0.05). Conclusions:The results of pathology, conventional MRI, DWI and DKI parameters of pCR and non pCR breast cancer patients are significantly different, and the combined model is better than the single model in predicting the efficacy of NAC.