Objective: To compare the predictive performance of the seasonal autoregressive integrated moving average (SARIMA) model, the Prophet model, and the Bayesian structural time series (BSTS) model in forecasting the incidence of hand, foot, and mouth disease (HFMD) , so as to provide a basis for optimizing the early warning system of this disease. Methods: Weekly incidence data of HFMD in Longgang District, Shenzhen City from 2014 to 2024 were collected. The HFMD incidence data from 2014-2019 and 2023 were used as the training set to construct SARIMA, Prophet, and BSTS models, while the data from 2024 were used as the test set to compare and evaluate the predictive performance of the three models. The technique for order preference by similarity to ideal solution (TOPSIS) method was employed to calculate the C-value. This approach integrates multiple evaluation metrics, such as the mean absolute error (MAE), mean squared error (MSE), root mean squared error (RMSE), and symmetric mean absolute percentage error (SMAPE), to comprehensively assess model performance. Results: A total of 150 111 cases of HFMD were reported in Longgang District from 2014 to 2024, with an average annual incidence of 400.72/105. The weekly incidence fluctuated between 0 and 63.78/105, exhibiting a bimodal seasonal pattern characterized by a primary peak from May to July and a secondary peak from September to October. In the training set, all three models demonstrated a good fit to the bimodal epidemic trend of HFMD, with the BSTS model achieving the best fit. The BSTS model yielded performance metrics as follows: MAE=0.124, MSE=0.050, RMSE=0.223, SMAPE=0.021, and a C-value of 1.000. In the test set, all three models, including SARIMA, Prophet, and BSTS, performed well for short-term predictions (≤16 weeks), with the Prophet model showing relatively superior predictive performance. However, the prediction accuracy of all models declined as the forecast horizon extended. During the primary peak period (May-July), the Prophet model exhibited better predictive performance, whereas the BSTS model performed relatively better during the secondary peak period (September-October). Conclusions For the short-term forecasting of weekly HFMD incidence, the Prophet model outperformed both the SARIMA and BSTS models. During the primary peak period, the Prophet model demonstrated superior predictive performance, whereas the BSTS model exhibited better accuracy in forecasting the secondary peak period.

Objective To investigate the role of quercetin(QUE)in ferroptosis during intestinal ischemia-reperfusion(IR)injury and elucidate its underlying mechanisms.Methods ① Potential target genes of QUE were predicted using the TCMSP,PharmMapper,and SwissTargetPredictive databases.Target genes associated with intestinal IR injury and ferroptosis were collected from GeneCards,PharmGKB,and OMIM databases.After overlapping genes were identified and analyzed,protein-protein interaction(PPI)networks were constructed using the STRING database and then visualized with Cytoscape 3.10.0.Molecular docking was performed to validate the binding conformations between QUE and key targets.② In vivo experiments were conducted to verify QUE's protective effects against intestinal IR injury.Thirty-six SPF-grade male C57BL/6J mice(6～8 weeks old,body weight:22±2 g)were randomly divided into Sham,Sham+QUE,IR,IR+QUE,IR+QUE+erastin(IR+QUE+Era),and IR+QUE+kevetrin hydrochloride(IR+QUE+KH)groups,with 6 mice in each group.Mouse model of intestinal IR injury was induced by 45 min ischemia of the superior mesenteric artery followed by 60 min reperfusion.HE staining was used to observe histopathological changes in the intestinal tissues.ELISA was employed to the serum or intestinal contents of diamine oxidase(DAO),pro-inflammatory cytokines(TNF-α,IL-6,IL-1β),and ferroptosis markers[glutathione(GSH)and Fe2+].Western blotting was utilized to detect the protein expression of glutathione peroxidase 4(GPX4),acyl-CoA synthetase long-chain family member 4(ACSL4),and tumor protein 53(p53).Results ① Network pharmacology identified 460 QUE targets,1 552 intestinal IR injury targets,and 1 967 ferroptosis-related targets,and 92 overlapping genes were identified as potential therapeutic targets.Molecular docking revealed a strong binding affinity between QUE and p53(binding energy:-6.8 kcal/mol).② In vivo experiments demonstrated that the IR+QUE group exhibited reduced intestinal damage and lower Chiu's score(P<0.05),decreased serum DAO content but elevated intestinal DAO content(P<0.05),decreased levels of TNF-α,IL-6,and IL-1β in the serum and intestinal tissues(P<0.05),reduced Fe2+accumulation,and increased GSH content(P<0.05),and up-regulated GPX4(P<0.05)and down-regulated ACSL4 and p53 expression(P<0.05)at protein level when compared with the IR group.While,the administration of ferroptosis agonist Era,or p53 agonist KH resulted in diminished therapeutic effects of QUE(P<0.05)when compared with the IR+QUE group.Conclusion QUE alleviates intestinal IR injury by inhibiting ferroptosis,which may be associated with its down-regulating p53 expression.

Objective To investigate whether remimazolam attenuates intestinal ischemia-reperfusion(I/R)injury in mice by regulating ferroptosis through connexin-43(CX43).Methods Molecular docking was applied to predict the binding affinity of remimazolam to CX43.A total of 72 SPF-grade adult male C57BL/6J mice(6～8 weeks old,weighing 20～25 g)were subjected.Thirty of them were randomly divided into sham operation group(Sham group),I/R group 1,and I/R+10,20 and 40 mg/kg remimazolam groups(RM10,RM20 and RM40 groups),with 6 mice in each group.Another 30 mice were randomly assigned into 5 groups(n=6),I/R group 2,erastin group(E group),I/R+40 mg/kg remimazolam group 2(RM40 group 2),I/R+Fer-1 group(Fer-1 group),and erastin+40 mg/kg remimazolam group(ERM group).The left 12 mice were randomly and equally grouped into I/R+RM+oe-NC group(oe-NC group)and I/R+RM+oe-CX43 group(oe-CX43 group).The Fer-1 group was given an intraperitoneal injection of 5 mg/kg Fer-1 in 1 h prior to reperfusion,the E group was given 10 mg/kg erastin intraperitoneally 1 d before modeling,and all the remimazolam groups,the oe-NC group and the oe-CX43 group were injected intravenously with corresponding doses of remimazolam 30 min pre-modeling,while the oe-NC and oe-CX43 groups were injected with empty vector virus and overexpression of CX43 vector virus,respectively,48 h before the administration of remimazolam.A mouse intestinal I/R injury model was constructed by clamping the superior mesenteric artery for 45 min and reperfusion for 30 min.The small intestine tissues were harvested and observed for pathological changes,and the intestinal mucosal damage was assessed with Chiu's score.The contents of Fe2+,total iron,malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD)were detected by colorimetric assay;the production of reactive oxygen species(ROS)was determined by DHE probe;the expression of ferroptosis-related genes was determined by RT-qPCR;and the expression levels of CX43,GPX4,and SLC7A11 were detected by Western blotting.Results Molecular docking indicated that remimazolam had a binding energy of-6.699 kcal/mol with CX43 protein,suggesting good binding affinity between them.Compared with the Sham group,the I/R group 1 showed increases in Chiu's scores and CX43 expression(P<0.05),along with pathological damage to intestinal tissues,and elevated contents of Fe2+,total iron,ROS and MDA(P<0.05),and down-regulated GPX4 and SLC7A11(P<0.05).Compared with the I/R group 1,Chiu's score was reduced in the RM40 group,and CX43 was significantly down-regulated(P<0.05),contents of Fe2+,total iron,ROS,and MDA were decreased(P<0.05),and expression levels of GPX4 and SLC7A11 were enhanced(P<0.05),and severity of intestinal histological damage was attenuated in both the RM40 and Fer-1 groups.Compared with the E group,the ERM group had the decreases in CX43 expression level(P<0.05),Fe2+,total iron,ROS,and MDA contents(P<0.05),and increases in GPX4 and SLC7A11 expression levels(P<0.05),with the improvement in intestinal tissue.Compared with the oe-NC group,overexpression of CX43 resulted in the increased CX43 expression,elevated contents of Fe2+,total iron,ROS and MDA(P<0.05)and decreased expression of GPX4 and SLC7A11(P<0.05),leading to the exacerbated injury in intestinal tissue.Conclusion Remimazolam attenuates intestinal I/R injury by inhibiting ferroptosis through down-regulating CX43 expression.

Objective:To establish the evaluation criteria for the quality of nursing care in orthopaedic trauma specialties, and to provide a basis for scientific evaluation of the quality of nursing care in orthopaedic trauma specialties.Methods:From February to October 2023, John Hopkinson evidence-based method was used to synthesize the evidence, clinical investigation and semi-structured interview were used to draw up the "quality standard of nursing care in orthopaedic trauma specialty", and two rounds of Delphi method of expert inquiry were used to screen, demonstrate and calibrate the evaluation standard of nursing quality in orthopaedic trauma specialty.Results:The questionnaire recovery rate of 2 rounds of expert consultation was 100.00%, the coefficient of familiarity and authority of 2 rounds of expert consultation were 0.92 and 0.93. Through 2 rounds of expert letter consultation, the quality evaluation criteria of orthopaedic trauma specialist care were established, including 3 first-level indicators (structural quality, process quality and outcome quality), 22 second-level indicators and 85 third-level indicators.Conclusions:The process of constructing the evaluation standard of nursing quality in orthopaedic trauma specialty is scientific and reliable, which can provide standard guidance for clinical practice and is conducive to the development of specialized nursing.

Carcinoma-associated fibroblasts (CAFs) are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix (ECM). The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase (LOX). Small extracellular vesicles (sEVs) mediate cell-cell communication. However, the interactions between sEVs and the ECM remain unclear. Here, we demonstrated that sEVs released from oral squamous cell carcinoma (OSCC)-derived CAFs induce collagen crosslinking, thereby promoting epithelial-mesenchymal transition (EMT). CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking, and a LOX inhibitor or blocking antibody suppressed this effect. Active LOX (αLOX), but not the LOX precursor, was enriched in CAF sEVs and interacted with periostin, fibronectin, and bone morphogenetic protein-1 on the surface of sEVs. CAF sEV-associated integrin α2β1 mediated the binding of CAF sEVs to collagen I, and blocking integrin α2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I. CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway. Taken together, these findings reveal a novel role of CAF sEVs in tumor ECM remodeling, suggesting a critical mechanism for CAF-induced EMT of cancer cells.
Humans ; Paxillin/metabolism* ; Protein-Lysine 6-Oxidase/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Epithelial-Mesenchymal Transition ; Integrin alpha2beta1/metabolism* ; Mouth Neoplasms/pathology* ; Collagen/metabolism* ; Fibroblasts ; Extracellular Vesicles/metabolism* ; Cell Line, Tumor ; Tumor Microenvironment

Objectives:To investigate the relationship between visceral adipose index and glomerular filtration rate in patients with type 2 diabetes mellitus.Methods:A total of 1 036 patients with type 2 diabetes mellitus who received treatment in The Second Affiliated Hospital of Xi'an Jiaotong University from May 2017 to May 2018 were included in this study. The visceral adipose index was detected using a bioresistance assay. These patients were divided into four groups using the quartile method: Visceral adipose index < 8.10 (q1 group, n = 246), 9.60 > visceral adipose index ≥ 8.10 (q2 group, n = 64), 11.10 > visceral adipose index ≥ 9.60 (q3 group, n = 423), visceral adipose index ≥ 11.10 (q4 group, n = 233). One-way analysis of variance was performed to compare the differences among groups. Partial correlation and multiple regression were used to analyze the correlation between body mass index, waist circumference, waist-to-height ratio, waist-to-hip ratio, body fat content, visceral adipose index, and urinary microalbumin and glomerular filtration rate. Results:With the increase in the visceral adipose index, the glomerular filtration rate gradually decreased. The glomerular filtration rate in the q1, q2, q3, q4 groups was (112.19 ± 31.74) mL·min -1·1.73 m -2, (106.14 ± 28.26) mL·min -1·1.73 m -2, (104.73 ± 23.63) mL·min -1·1.73 m -2, (103.40 ± 27.51) mL·min -1·1.73 m -2, respectively. In the female group, with the increase in visceral adipose index, the glomerular filtration rate decreased gradually. After controlling for age, sex, diabetes, and hypertension, the visceral adipose index was significantly correlated with the glomerular filtration rate ( r = -0.10, P < 0.001). Multiple regression analysis showed that visceral adipose index and waist-to-height ratio were closely related to glomerular filtration rate ( F = 6.00, P < 0.001). Conclusion:With the increase of visceral adipose index, body mass index, waist circumference, waist-to-height ratio, waist-to-hip ratio, body fat content, and urinary microalbumin increased gradually. When the visceral adipose index is greater than 9.60, the glomerular filtration rate is significantly decreased. Therefore, it is suggested to adopt various methods to evaluate obesity in clinical work, and visceral fat index should be paid more attention, especially when the visceral fat index is greater than 9.60.

Objective:To observe the effect of Tuina(Chinese therapeutic massage)combined with functional training in improving clinical symptoms and balance function in patients with meniscus injury. Methods:A total of 93 patients with grade Ⅰ-Ⅱ meniscus injury were randomly divided into a functional training group,a Tuina group,and a combination group,with 31 cases in each group.The Tuina group received Tuina manipulation.The functional training group underwent functional training under the supervision of physicians.The combination group received Tuina manipulation in addition to the functional training.The treatment course of all three groups was 8 weeks.The clinical symptoms were observed before the intervention and after 4 and 8 weeks of interventions,and the changes in knee injury and osteoarthritis outcome score(KOOS)and Y-balance test(YBT)were compared. Results:There was no statistically significant difference in the total response rate among the three groups after treatment(P>0.05).The total and subscale KOOS in the three groups were significantly higher than those before treatment after 4 and 8 weeks of interventions(P<0.05).There was a statistically significant difference in the total KOOS between the combination group and the functional training group after 4 and 8 weeks of interventions(P<0.05);there was a statistically significant difference in the score of daily living ability and sports and recreation function between the two groups after 8 weeks of interventions(P<0.05).The YBT balance coefficients of the affected and non-affected knees of the three groups were significantly improved after 4 and 8 weeks of interventions(P<0.05),and there was no statistically significant difference among the groups(P>0.05). Conclusion:Tuina,functional training,and their combination can improve clinical symptoms and balance function in patients with grade Ⅰ-Ⅱ meniscus injury.Tuina combined with functional training is significantly effective in improving daily living ability and sports and recreation function.

Natamycin is a safe and efficient antimycotics which is widely used in food and medicine industry. The polyene macrolide compound, produced by several bacterial species of the genus Streptomyces, is synthesized by type Ⅰ polyketide synthases using acetyl-CoA, malonyl-CoA, and methylmalonyl-CoA as substrates. In this study, four pathways potentially responsible for the supply of the three precursors were evaluated to identify the effective precursor supply pathway which can support the overproduction of natamycin in Streptomyces gilvosporeus, a natamycin-producing wild-type strain. The results showed that over-expressing acetyl-CoA synthetase and methylmalonyl-CoA mutase increased the yield of natamycin by 44.19% and 20.51%, respectively, compared with the wild type strain under shake flask fermentation. Moreover, the yield of natamycin was increased by 66.29% compared with the wild-type strain by co-overexpression of acetyl-CoA synthetase and methylmalonyl-CoA mutase. The above findings will facilitate natamycin strain improvement as well as development of strains for producing other polyketide compounds.
Natamycin/metabolism* ; Methylmalonyl-CoA Mutase/metabolism* ; Acetyl Coenzyme A/metabolism* ; Streptomyces/genetics* ; Polyketide Synthases/metabolism*

Objective:To investigate the clinical manifestations of acquired immunodeficiency syndrome(AIDS) patients with initial-stage cytomegalovirus (CMV) retinitis (CMVR).Methods:Retrospective case series study. From July 2017 to November 2019, 21 patients with 22 eyes of AIDS combined with CMVR in the initial stage of AIDS and CMVR diagnosed in the eye examination in the study. Among them, there were 19 males with 19 eyes and 2 females with 3 eyes; the average age was 34.3±9.6 years. The average CD4 + T lymphocyte count of patients was 26.1±23.2/μl. Routine fundus screening revealed 17 cases, and the contralateral eye disease was found in 4 cases. There were 13 cases of CMVR in both eyes (61.9%, 13/21). Among them, both eyes were in the initial stage of CMVR, and the contralateral eyes were in the early stage of CMVR in 12 cases. The contralateral eye included 2 cases of human immunodeficiency virus-related retinal microangiopathy, 1 case of optic disc edema, and 5 cases of no obvious abnormality on fundus examination. All patients underwent slit lamp microscopy and ultra-wide-angle fundus photography examination. At the same time, 18 eyes underwent optical coherence tomography (OCT). Blood CMV-DNA detection was performed in 17 cases within 1 week before the first diagnosis; aqueous CMV-DNA detection was performed in 7 eyes within 1 week after the first diagnosis. Within 1 week after the fundus examination, 8 eyes of 8 cases and 8 eyes of 7 cases were received and not received systemic anti-CMV treatment; the treatment status was unknown in 6 cases and 6 eyes. After treatment, 18 eyes of 17 cases were followed up. The follow-up time was 0.5-28 months. Results:There were no obvious abnormalities in the anterior segment examination of all the affected eyes; the vitreous body was transparent. The fundus lesions were less than 1 optic disc diameter (DD), and they were white granular, clustered, with blurred edges. Among them, there were granular satellite lesions around the lesion in 18 eyes (81.8%, 18/22). The lesions were located in 19 eyes (86.4%, 19/22) in zone 2, 1 eye in zone 1 and 2 (4.5%, 1/22), and 2 eyes in zone 3 (9.1%, 2/22). In 18 eyes that underwent OCT examination, 12 eyes failed to obtain image data because the lesion was not in the conventional scanning range; the other 6 eyes showed the inner or full retina thickened or atrophy depression, structural destruction, accompanied by local vitreous punctate strong reflection. Among the 17 patients who underwent blood CMV-DNA testing, 1 (5.9%, 1/17) and 16 (94.1%, 16/17) cases were CMV-DNA negative and positive, respectively. The 7 eyes that underwent the CMV-DNA test of aqueous humor were all negative. Among the 18 eyes who were followed up, the lesions did not expand, and gradually subsided and absorbed in 4 eyes (22.2%, 4/18); the varying degrees of lesion enlargement in 14 eyes (77.8%, 14/18).Conclusion:The patients with AIDS and CMVR at the initial stage have no obvious ocular symptoms; the fundus shows white granular lesions less than 1 DD with blurred edges.

Objective:To observe the ultra-wide-angle fundus imaging characteristics of acquired immunodeficiency syndrome (AIDS) combined with cytomegalovirus retinitis (CMVR).Methods:This study was a retrospective study. From July 2017 to November 2019, 124 eyes of 86 patients diagnosed with AIDS and CMVR at the Department of Ophthalmology, Beijing You'an Hospital, Capital Medical University, were included in the study. Among them, 80 patients were males (93.0%) and 6 patients were females (7.0%) with 17-58 years old. The average age was (36.86±8.82) years old. There were 48 cases (55.8%) in one eye and 38 cases (44.2%) in both eyes. All the affected eyes underwent indirect ophthalmoscope fundus examination and Aalborg ultra-wide-angle fundus photography examination. According to the characteristics of CMVR in ultra-wide-angle fundus images, it can be divided into classic type, granular type, frost-like dendritic vasculitis and optic neuroretinitis. We observed and analyzed the type of fundus of the affected eye. According to the position of the vortex vein in the fundus image and record of the lesion as the posterior pole or peripheral part, the scope of the lesion was divided into ≤1 quadrant, >1 quadrant and ≤2 quadrants (1-2 quadrants), >2 quadrants and ≤3 quadrants (2-3 quadrants), >3 and ≤4 quadrants (3-4 quadrants). The upper and lower vascular arches or disc edges of the macula were used as boundaries to record whether the macular area or optic disc was involved. At the same time, we recorded whether the vitreous body had obvious turbidity. The comparison of CD4 + T lymphocyte count between patients of different types was performed by one-way analysis of variance, and the comparison of the positive rate of blood CMV-DNA was performed by the χ2 test; pairwise comparisons between groups were performed by the least significant difference method. Results:Among the 124 eyes, CMVR was classified into 35 eyes (28.2%) with classic type, 68 eyes with granular type (54.8%), 3 eyes with frost-like dendritic vasculitis (2.4%), and 18 eyes with optic neuroretinitis (14.5%). The lesion involved 83 eyes (66.9%) at both the posterior pole and the periphery, 22 eyes (17.7%) confined to the posterior pole, and 19 eyes (15.3%) confined to the periphery; the extent of the lesion was ≤1 quadrant in 76 eyes (61.3%), 23 eyes (18.5%) in 1-2 quadrants, 7 eyes (5.6%) in 2-3 quadrants, and 18 eyes (14.5%) in 3-4 quadrants. 54 eyes (43.5%) showed lesions involving the macular area; 52 eyes (41.9%) had lesions involving the optic disc; 33 eyes (26.6%) showed obvious vitreous inflammatory opacities. Among 86 patients, the average number of CD4 + T lymphocytes in 82 patients was 1 to 168 cells/μl, with an average of 33.60±40.02 cells/μl; the remaining 4 patients (4.7%) were unknown. There was no statistically significant difference in the positive rate of CD4 + T lymphocyte count and blood CMV-DNA load between patients in different subtypes groups ( F=0.863, 0.926; P=0.462, 0.431). Conclusion:The ultra-wide-angle fundus images of AIDS combined with CMVR have certain characteristics, which can manifest as classic, granular, frost-like dendritic vasculitis and optic neuroretinitis.