Objective To explore scientific and accurate prediction methods for the incidence of hand, foot, and mouth disease in the post-pandemic era, and to address modeling challenges caused by abnormal fluctuations in case numbers from 2020 to 2023. Methods The seasonal index was used to pre-process the data. The traditional seasonal autoregressive integrated moving average (SARIMA) model, singular spectrum analysis (SSA)-ARIMA model, ARIMA-Long short-term memory (LSTM) model, and SSA-ARIMA-LSTM model were used to fit the incidence from 2013 to 2023, and the incidence of hand, foot and mouth disease in 2024 was predicted. The real data collected in 2024 were used as the test set to compare the prediction performance of the models. Results The fitting performance of the constructed models was as follows: the ARIMA model had MAE=107.50 and RMSE=144.53, the SSA-ARIMA model showed MAE=2.84 and RMSE=4.33, the ARIMA-LSTM model achieved MAE=99.46 and RMSE=131.59, and the SSA-ARIMA-LSTM model had MAE=96.35 and RMSE=132.13. In terms of prediction performance, the ARIMA model resulted in MAE=151.64 and RMSE=146.70, the SSA-ARIMA model demonstrated MAE=41.22 and RMSE=57.01, the ARIMA-LSTM model yielded MAE=220.75 and RMSE=257.89, and the SSA-ARIMA-LSTM model recorded MAE=58.83 and RMSE=72.06. Conclusion The SSA-ARIMA model has the best fitting degree and the highest prediction accuracy, and is suitable for predicting the incidence trend of hand, foot and mouth disease.

Objective:To observe and analyze the correlation between the changes of macular microvascular structure and the level of intracocular fluid cytokines in patients with diabetic macular edema (DME).Methods:A prospective clinical study. From December 2022 to June 2024, 20 patients with 25 eyes of DME diagnosed by Department of Ophthalmology of Linyi People's Hospital were included in the study. Among them, 14 males had 17 eyes and 6 females had 8 eyes. Age was (55.08±10.34) years. Optical coherence tomography (OCT) and OCT angiography (OCTA) were used to scan the macular region at a range of 6 mm×6 mm. Central retinal thickness (CRT), blood flow density of superficial retinal capillary plexus (SCP) and area of fovea avascular zone (FAZ) were measured. The anterior aqueous humor was extracted before the first intravitreal injection of anti-vascular endothelial growth factor (VEGF), the concentrations of interleukin (IL-6), IL-8, VEGF, vascular cell adhesion molecule (VCAM), placental growth factor (PLGF) and monocyte chemotactic protein-1 (MCP-1) were detected. The correlation between macular microvascular structure and aqueous humor cytokines was analyzed by Spearman correlation analysis.Results:The CRT of the affected eyes was (617.40±167.64) μm, the SCP flow density was (39.56±1.55)%, and the FAZ area was (0.46±0.13) mm 2. The concentrations of IL-6, IL-8, VEGF, VCAM, PLGF and MCP-1 in aqueous humor were (301.36±690.52), (29.15±20.56), (71.37±29.32) and (5 621.22±7 241.06), (72.40±13.43), (464.07±163.26) pg/ml, respectively. Correlation analysis showed that there was a significant positive correlation between CRT and the concentrations of aqueous cytokines VEGF and PLGF ( r=0.460, 0.462, P<0.05). FAZ area was positively correlated with VEGF and MCP-1 concentrations ( r=0.414, 0.465; P<0.05). There was a significant negative correlation between SCP blood flow density and IL-6 ( r=0.401, P<0.05). Conclusion:There was a significant correlation between the morphological structure of macular area and the damage degree of microvessels around macular area in DME patients and the concentration of aqueous cytokines.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

In patients with Graves′ disease, repeated transition between hyperthyroidism and hypothyroidism is uncommon. This report describes a female Graves′ disease patient with persistently high levels of thyroid-stimulating hormone receptor antibodies, who experienced multiple transitions between hyperthyroidism and hypothyroidism over a 7-year follow-up period, including during pregnancy. The fluctuations may be linked to the interplay between thyroid-stimulating hormone receptor stimulating antibody(TSAb) and thyroid-stimulating hormone receptor blocking antibody(TBAb). Treatment with either antithyroid medications or levothyroxine sodium, based on the patient′s thyroid status, helped maintain normal thyroid function. Stable thyroid function may contribute to maintaining a consistent thyroid immune status and reducing thyroid function fluctuation.

Maternal high titers of thyroid stimulating hormone receptor antibody(TRAb) during pregnancy can cause fetal and neonatal thyroid dysfunction, among which hypothyroidism is relatively rare. In this case, the woman was diagnosed with Hashimoto′s hypothyroidism prior to pregnancy and was treated with levothyroxine(LT 4) to maintain normal thyroid function throughout gestation. Despite normal maternal thyroid function, TRAb levels remained persistently elevated during pregnancy. The fetus showed a normal fetal thyroid circumference and heart rate, but no secondary ossification center was observed at 37 + 6 weeks of gestation. On the 9th day after birth, the neonate was diagnosed with congenital hypothyroidism and started on LT 4 replacement therapy. By 7 months of age, thyroid function had normalized, and LT 4 was discontinued. This case highlights the importance of close monitoring of fetal growth and neonatal thyroid function in pregnant women with high TRAb titers, to ensure timely detection and management of fetal and neonatal thyroid dysfunction.

In patients with Graves′ disease, repeated transition between hyperthyroidism and hypothyroidism is uncommon. This report describes a female Graves′ disease patient with persistently high levels of thyroid-stimulating hormone receptor antibodies, who experienced multiple transitions between hyperthyroidism and hypothyroidism over a 7-year follow-up period, including during pregnancy. The fluctuations may be linked to the interplay between thyroid-stimulating hormone receptor stimulating antibody(TSAb) and thyroid-stimulating hormone receptor blocking antibody(TBAb). Treatment with either antithyroid medications or levothyroxine sodium, based on the patient′s thyroid status, helped maintain normal thyroid function. Stable thyroid function may contribute to maintaining a consistent thyroid immune status and reducing thyroid function fluctuation.

Maternal high titers of thyroid stimulating hormone receptor antibody(TRAb) during pregnancy can cause fetal and neonatal thyroid dysfunction, among which hypothyroidism is relatively rare. In this case, the woman was diagnosed with Hashimoto′s hypothyroidism prior to pregnancy and was treated with levothyroxine(LT 4) to maintain normal thyroid function throughout gestation. Despite normal maternal thyroid function, TRAb levels remained persistently elevated during pregnancy. The fetus showed a normal fetal thyroid circumference and heart rate, but no secondary ossification center was observed at 37 + 6 weeks of gestation. On the 9th day after birth, the neonate was diagnosed with congenital hypothyroidism and started on LT 4 replacement therapy. By 7 months of age, thyroid function had normalized, and LT 4 was discontinued. This case highlights the importance of close monitoring of fetal growth and neonatal thyroid function in pregnant women with high TRAb titers, to ensure timely detection and management of fetal and neonatal thyroid dysfunction.

Objective:To observe and analyze the correlation between the changes of macular microvascular structure and the level of intracocular fluid cytokines in patients with diabetic macular edema (DME).Methods:A prospective clinical study. From December 2022 to June 2024, 20 patients with 25 eyes of DME diagnosed by Department of Ophthalmology of Linyi People's Hospital were included in the study. Among them, 14 males had 17 eyes and 6 females had 8 eyes. Age was (55.08±10.34) years. Optical coherence tomography (OCT) and OCT angiography (OCTA) were used to scan the macular region at a range of 6 mm×6 mm. Central retinal thickness (CRT), blood flow density of superficial retinal capillary plexus (SCP) and area of fovea avascular zone (FAZ) were measured. The anterior aqueous humor was extracted before the first intravitreal injection of anti-vascular endothelial growth factor (VEGF), the concentrations of interleukin (IL-6), IL-8, VEGF, vascular cell adhesion molecule (VCAM), placental growth factor (PLGF) and monocyte chemotactic protein-1 (MCP-1) were detected. The correlation between macular microvascular structure and aqueous humor cytokines was analyzed by Spearman correlation analysis.Results:The CRT of the affected eyes was (617.40±167.64) μm, the SCP flow density was (39.56±1.55)%, and the FAZ area was (0.46±0.13) mm 2. The concentrations of IL-6, IL-8, VEGF, VCAM, PLGF and MCP-1 in aqueous humor were (301.36±690.52), (29.15±20.56), (71.37±29.32) and (5 621.22±7 241.06), (72.40±13.43), (464.07±163.26) pg/ml, respectively. Correlation analysis showed that there was a significant positive correlation between CRT and the concentrations of aqueous cytokines VEGF and PLGF ( r=0.460, 0.462, P<0.05). FAZ area was positively correlated with VEGF and MCP-1 concentrations ( r=0.414, 0.465; P<0.05). There was a significant negative correlation between SCP blood flow density and IL-6 ( r=0.401, P<0.05). Conclusion:There was a significant correlation between the morphological structure of macular area and the damage degree of microvessels around macular area in DME patients and the concentration of aqueous cytokines.

Objective:To evaluate the mechanical performance of customized metal prosthesis with tibia stems of varying lengths for tibial bone defects reconstruction.Methods:Morphologically matched postoperative finite element models of bone defect revision were developed, with three gradients (15 mm, 30 mm, and 45 mm) according to the degree of bone defect and were reconstructed with 3D printed tantalum metal prosthesis using three tibial stem lengths (80 mm, 120 mm, and 150 mm), respectively. Conventional static and dynamic (walking gait) loading was performed to analyze the peak tibial stress distribution and accumulated sliding distance at the prosthetic interface, and to assess the effects of the three tibial stems of different lengths on the stability of the customized tibial defect restorations and the internal tibial stress state.Results:The peak accumulated sliding distance of the dynamically loaded morphologically matched restorations ranged from 17.94 to 21.31 mm with static loading, which were 68% to 84.3% higher than those of 10.26 to 11.69 mm with static loading. The peak tibial stresses in the dynamically loaded model were greater than those in the statically loaded model, with an increase of 28%-49.2%, including 132.94-143.88 MPa in the statically loaded model and 170.41-200.14 MPa in the dynamically loaded model. The overall accumulated sliding distance of the tibia prosthetic model gradually decreased from the tibial osteotomy surface, and the accumulated peak sliding distances ranged from 10.26 to 11.69 mm for static loading, and from 17.94 to 21.31 mm for dynamic loading. The bone tissue stresses in the anterolateral and medial-posterior tibia increased gradually from top to bottom, and the maximum stress value in each section was in the posterior medial tibia (the maximum value was 200.14 MPa). The highest bone tissue stress in the lateral tibia was affected by the tibial stem length, which resulted in a different location, and it was the area most affected by stress shielding (maximum value of 170.65 MPa).Conclusion:For stability assessment of morphologically matched tantalum customized prosthesis, physiological gait dynamic loading studies are more reliable than static loading; the choice of tibial stem length depends on a combination of accumulated peak sliding distances and tibial bone stress distribution factors.

Objective:To establish a predictive model of psychological crisis based on the machine learning random forest algorithm, and to analyze the influencing factors of psychological crisis among adole scent.Methods:A total of 1 417 middle school students were surveyed using cluster sampling in two phases, in November 2020 and June 2021.Demographic data, symptom factors, protective factors were collected in the first investigation, and depression and suicide risk were measured in the second investigation. The criteria for psychological crisis were moderate to severe depression(depression score≥15) and high suicide risk(suicide risk score≥7) in the second measurement. SPSS 24.0 software was used for statistical analysis of variables, and the random forest machine learning predictive model for psychological crisis was established by using R version 4.1.1 software, and the high-estimating factors of adolescent psychological crisis were analyzed.Results:(1) The detection rate of moderate to severe depression was 10.02%(142/1 417), the detection rate of high suicide risk was 30.77%(436/1 417), and detection rate of the psychological crisis was 8.19%(116/1 417).(2) The sensitivity and specificity of psychological crisis prediction model were 0.79, 0.82, positive predictive value was 0.82, negative predictive value was 0.79, accuracy was 0.80 and area under curve was 0.88. (3) The top 10 characteristic variables of influencing factors of adolescent psychological crisis were depression, anxiety, suicidal ideation, self-harming behavior, cognitive flexibility-controllability, cognitive flexibility-selectivity, grit-persistence effort, grit-interest consistency, mother's mood and father's mood(model prediction accuracy was 0.023-0.163).Conclusions:The occurrence of adolescent psychological crisis is closely related to symptom factors, protective factors and parental emotions, and has the significance of predicting across time.The machine learning random forest algorithm can effectively identify psychological crisis individuals and identify sensitive crisis individual characteristics.