Objective: To compare the effects of seasonal autoregressive integrated moving average (SARIMA) , seasonal autoregressive integrated moving average with exogenous regressors (SARIMAX) and long short-term memory neural network (LSTM) models in predicting the incidence of hand, foot, and mouth disease (HFMD). Methods: Monthly incidence data of HFMD in Kunming City from 2010 to 2019 were collected. SARIMA, SARIMAX and LSTM models were established using the monthly incidence of HFMD from 2010 to 2018 to predict the monthly incidence of HFMD from January to December 2019. The prediction performance of the three models was compared using mean squared error (MSE), root mean squared error (RMSE), mean absolute error (MAE) and mean absolute percentage error (MAPE). The optimal prediction model was selected based on the principle of minimizing MSE, RMSE, MAE and MAPE. Results: The HFMD cases were reported every month in Kunming City from 2010 to 2019, with the incidence fluctuating between 188.27/105 and 363.15/105. The disease exhibited a biennial high-incidence bimodal distribution. Among the four evaluation indicators for the training and testing sets, the LSTM model had the smaller values: MSE was 63.182 and 102.745, RMSE was 7.949 and 10.136, MAE was 6.535 and 7.620, and MAPE was 46.726% and 31.138%. The LSTM model performed the better, followed by the SARIMA model, while the SARIMAX model had the relatively poorest performance. Conclusion The LSTM model outperforms the SARIMA and SARIMAX models in predicting the incidence of HFMD.

Objective To analyze the relationship between changes of CD80, CD86 and Th1/Th2 cytokines and the severity of coxsackievirus A6 (CVA6) hand-foot-mouth disease (HFMD). Methods Among the 380 children with CVA6 HFMD in the 971th Hospital of the People's Liberation Army Navy and the 94th Hospital of the Joint Logistic Support Force were selected from January 2021 to January 2024. According to the disease severity, the children were divided into common group and severe group. The levels of CD80, CD86 and Th1/Th2 cytokines (interferon-γ (IFN-γ), interleukin-4 (IL-4)) were compared between the two groups. The ROC curve was used to analyze the evaluation efficiency of CD80, CD86, IFN gamma, and IL-4 levels on the severity of CVA6 HFMD. Multivariate logistic regression analysis was used to analyze the influencing factors of the severity of CVA6 HFMD. Results The levels of CD80, CD86, IFN-γ and IL-4 in the severe group were higher than those in the common group (P<0.05). The AUCs of CD80, CD86, IFN-γ, IL-4 and their combined detection in evaluating severity of CVA6 HFMD were 0.769, 0.717, 0.756, 0.864, and 0.917, respectively. The AUC value and specificity of combined detection were higher than those of single detection of each index (P<0.05). Multivariate logistic regression analysis indicated that age ≤ 3 years old was a risk factors (P<0.05), while time from onset to diagnosis ≤ 3d, duration of fever ≤ 3d, WB ≤ 12×109/L, low expression of CD80, low expression of IFN-γ, and low expression of IL-4 were protective factors (P<0.05). Conclusion CD80, CD86 and Th1/Th2 cytokines (IFN-γ, IL-4) are related to the severity of CVA6 HFMD. Early monitoring of CD80, CD86, IFN-γ and IL-4 levels in children is conducive to understanding their disease progression and guiding physician treatment.

BACKGROUND: Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage. METHODS: A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate. RESULTS: In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes ( BRCA ) mutations ( BRCA m) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs . 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs . 91.4% (32/35), P <0.001]. The 24-month progression-free survival (PFS) rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCA m, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively. CONCLUSIONS Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCA m, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.
Humans ; Female ; Ovarian Neoplasms/drug therapy* ; Piperazines/therapeutic use* ; Middle Aged ; Retrospective Studies ; Phthalazines/therapeutic use* ; Piperidines/therapeutic use* ; Indazoles/therapeutic use* ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Adult ; Aged ; China ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival

Objective To explore the effects of Atractylenolide-Ⅲ(AT-Ⅲ)on the intestinal immune barrier and kidney of rats with immunoglobulin A nephropathy(IgAN),and develop AT-Ⅲ nanoparticles to optimize its protective efficacy.Methods In this study,the zeolitic imidazolate framework(ZIF-8)loaded with AT-Ⅲ was used to prepare ZIF-8@AT-Ⅲnanoparticles.Morphological and structural characterization of the prepared samples was conducted using transmission electron microscopy and X-ray powder diffraction.48 rats were randomly divided into the normal control group,IgAN group,IgAN+AT-Ⅲ group,and IgAN+ZIF-8@AT-Ⅲ group.IgAN rats were treated with AT-Ⅲ and ZIF-8@AT-Ⅲ,and the detections of hepatic and renal function,glomerular IgA deposition,and intestinal immune barrier function were performed.Results The synthesis of ZIF-8@AT-Ⅲ nanoparticles with elevated drug loading,stability,and pH responsiveness had been successfully accomplished.The average particle size of ZIF-8@AT-Ⅲ nanoparticles was(70.62±1.07)nm,the Zeta potential was(-26.46±1.22)mV,the drug loading capacity was(19.2±1.3％),and the encapsulation efficiency was(64.0％±0.6％).Furthermore,rapid release was observed in a pH 5.5 environment,which was significantly higher than that in the pH 7.4 environment.Both AT-Ⅲ and ZIF-8@AT-Ⅲcould alleviate the destruction of intestinal wall structure and the infiltration of inflammatory cells,significantly downregulate the levels of(DAO)and(D-LA)in the serum.Moreover,there is a noteworthy upregulation in the expression of(ZO-1)and Claudin-5 in intestinal mucosal tissue,thereby substantially improving the immune barrier function and intestinal permeability in IgAN rats.This intervention also inhibited the deposition of IgA in renal glomeruli and alleviated kidney damage,and ZIF-8@AT-Ⅲ was more effective than AT-Ⅲ.Conclusion AT-Ⅲ alleviates IgAN in rats by improving intestinal immune barrier function and permeability.ZIF-8-loaded AT-Ⅲ serves as an excellent drug delivery system,enhancing the therapeutic efficacy of AT-Ⅲ in IgAN treatment.

Mammalian teeth,developing inseparable from epithelial-mesenchymal interaction,come in many shapes and the key factors governing tooth morphology deserve to be answered.By merging single-cell RNA sequencing analysis with lineage tracing models,we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1+cells within M1.These PRX1+cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell proliferation.Deeper into the mechanisms,we have discovered that Wnt5a,bestowed by mesenchymal PRX1+cells,stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling pathway.The loss of Wnt5a exhibits a defect phenotype similar to that of siPrx1.Exogenous addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth germs.These findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.

The residual pelvic floor cavity formed by laparoscopic low anterior resection for rectal cancer can result in some complications, such as spread of pelvic infection following anastomotic leakage, adhesive intestinal obstruction, and may increase the probability of radiation intestinal injury in case of postoperative radiotherapy. Reconstructing the pelvic floor can prevent the small intestine from entering the residual cavity, reduce the risk of intestinal obstruction and radiation induced intestinal injury; prevent or reduce the occurrence and severity of anastomotic leakage. Reconstructing the pelvic floor can also improve the anal function after low anterior resection to a certain extent and enhance the quality of life of patients. Direct suturing of the pelvic floor peritoneum and pedicled greater omentum flap graft transplantation are currently two commonly used pelvic floor reconstruction methods, which are relatively simple to operate, easy to promote, and worthy of routine application.

Objective Utilizing transcriptomic sequencing,this study aimed to monitor the expression alterations of GIMAP8 and SEC14L5 throughout the progression of pulmonary fibrosis,thereby providing insights into the underlying mechanisms of its pathogenesis and evolution.Methods C57BL/6 male mice were assigned in a randomized manner to either the Silica or PBS group.The Silica group underwent non-exposed endotracheal intubation on days 0 and 14 with 50 μL 100 mg/mL silica suspension,while the control group received 50 μL phosphate-buffered saline solution.On day 28,lung function was detected and the mice were sacrificed,and lung morphology,fibrosis,and mRNA levels were observed.Results When contrasted with individuals in good health,a differential expression analysis of mRNA in patients with pneumoconiosis identified a total of 584 mRNAs with significant expression differences.Among these,the expression of 242 mRNA was observed to be markedly elevated,while that of 342 mRNA was found to be considerably diminished.The enrichment analysis indicated that the primarily affected mRNAs with altered expression were associated with pathways such as p53,nuclear factor-κB,tumor necrosis factor,AMP-activated protein kinase,and other signaling pathways.In the Silica mice,the alveolar structures were compromised,characterized by the presence of collagen fiber accumulation and the formation of fibrous masses.In contrast,the PBS mice maintained a normal pulmonary architecture.GIMAP8 expression was up-regulated whereas SEC14L5 expression was down-regulated in lung tissues in the Silica mice,and mice in the Silica group had poorer lung function.Conclusions The onset and progression of pulmonary fibrosis may be significantly influenced by GIMAP8 and SEC14L5 expression in patients with pneumoconiosis and in silicosis animal models.This association could serve as a foundational molecular insight,paving the way for the development of preventative and therapeutic strategies against these conditions.

Objective:To summarize and analyze the clinical characteristics, treatment and prognosis of glycogen storage disease type Ⅱ(GSD Ⅱ) patients admitted to pediatric intensive care units(PICU), and to improve the pediatricians' understanding of children with severe GSD Ⅱ.Methods:Children with GSD Ⅱ admitted to PICU at Beijing Children's Hospital of Capital Medical University between January 2010 and December 2021 were included. Patient's data were collected through the electronic medical record system.After the patient was discharged,telephone follow-ups were conducted regularly for over a year.Results:A total of eight patients with a median age of 30.5 months were included. There were four patients with infantile GSD Ⅱ, whose median age of onset was 5.5 months. There were four patients with late-onset GSD Ⅱ, whose median age of onset was 36.0 months. Eight patients required continuous noninvasive/invasive respiratory support. Three patients with infantile GSD Ⅱ required respiratory support within one month of onset, and three patients with late onset GSD Ⅱ required respiratory support within one year of onset. A total of six patients had cardiac arrest during the course of the disease. One patient was regularly treated with enzyme replacement therapy during hospitalization but his condition did not improve significantly. Three patients were discharged following medical advice,including one patient continuing noninvasive respiratory support after discharge, and two patients requiring onging invasive respiratory support.A total of four children died,including one being an in-hospital death,and three occuring within one year after hospital discharge. A total of 14 genotypes were detected in eight patients, of which three were newly discovered gene mutations.Conclusion:The children with GSD Ⅱ admitted to PICU have severe respiratory dysfunction and need continuous respiratory support during the early stage of the disease. The incidence of cardiopulmonary arrest caused by infection and respiratory muscle weakness is high. It is recommended to closely monitor the lung function and cardiac function of such children, and actively give the prevention and treatment of infectious diseases. Whether enzyme replacement therapy can benefit patients with severe GSD Ⅱ and whether the newly identified mutations correlate with disease severity needs to be further evaluated.

Tooth number abnormality is one of the most common dental developmental diseases, which includes both tooth agenesis and supernumerary teeth. Tooth development is regulated by numerous developmental signals, such as the well-known Wnt, BMP, FGF, Shh and Eda pathways, which mediate the ongoing complex interactions between epithelium and mesenchyme. Abnormal expression of these crutial signalling during this process may eventually lead to the development of anomalies in tooth number; however, the underlying mechanisms remain elusive. In this review, we summarized the major process of tooth development, the latest progress of mechanism studies and newly reported clinical investigations of tooth number abnormality. In addition, potential treatment approaches for tooth number abnormality based on developmental biology are also discussed. This review not only provides a reference for the diagnosis and treatment of tooth number abnormality in clinical practice but also facilitates the translation of basic research to the clinical application.
Gene Expression Regulation, Developmental ; Odontogenesis ; Signal Transduction ; Tooth/metabolism* ; Humans

In growing children, growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest. Interestingly, one type of fracture injuries within the growth plate achieve amazing self-healing, however, the mechanism is unclear. Using this type of fracture mouse model, we discovered the activation of Hedgehog (Hh) signaling in the injured growth plate, which could activate chondrocytes in growth plate and promote cartilage repair. Primary cilia are the central transduction mediator of Hh signaling. Notably, ciliary Hh-Smo-Gli signaling pathways were enriched in the growth plate during development. Moreover, chondrocytes in resting and proliferating zone were dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the ciliary core gene Ift140 in cartilage disrupted cilia-mediated Hh signaling in growth plate. More importantly, activating ciliary Hh signaling by Smoothened agonist (SAG) significantly accelerated growth plate repair after injury. In sum, primary cilia mediate Hh signaling induced the activation of stem/progenitor chondrocytes and growth plate repair after fracture injury.
Mice ; Animals ; Hedgehog Proteins/genetics* ; Receptors, G-Protein-Coupled/metabolism* ; Cilia/metabolism* ; Cartilage/metabolism* ; Regeneration