BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P＜0.05),and trabecular separation was elevated(P＜0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P＜0.05),and the level of osteocalcin was decreased(P＜0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P＜0.05);protein expression of β-Catenin and Frizzled9 was decreased(P＜0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P＜0.05)and a decrease in trabecular separation(P＜0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P＜0.05)and the serum level of osteocalcin was elevated(P＜0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P＜0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P＜0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P＜0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Background Air pollution is a major public health concern. Air Quality Health Index (AQHI) is a very important air quality risk communication tool. However, AQHI is usually constructed by single-pollutant model, which has obvious disadvantages. Objective To construct an AQHI based on the joint effects of multiple air pollutants (J-AQHI), and to provide a scientific tool for health risk warning and risk communication of air pollution. Methods Data on non-accidental deaths in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces from January 1, 2013 to December 31, 2018 were obtained from the corresponding provincial disease surveillance points systems (DSPS), including date of death, age, gender, and cause of death. Daily meteorological (temperature and relative humidity) and air pollution data (SO₂, NO₂, CO, PM_2.5, PM₁₀, and maximum 8 h O₃ concentrations) at the same period were respectively derived from China Meteorological Data Sharing Service System and National Urban Air Quality Real-time Publishing Platform. Lasso regression was first applied to select air pollutants, then a time-stratified case-crossover design was applied. Each case was matched to 3 or 4 control days which were selected on the same days of the week in the same calendar month. Then a distributed lag nonlinear model (DLNM) was used to estimate the exposure-response relationship between selected air pollutants and mortality, which was used to construct the AQHI. Finally, AQHI was classified into four levels according to the air pollutant guidance limit values from World Health Organization Global Air Quality Guidelines (AQG 2021), and the excess risks (ERs) were calculated to compare the AQHI based on single-pollutant model and the J-AQHI based on multi-pollutant model. Results PM_2.5, NO₂, SO₂, and O₃ were selected by Lasso regression to establish DLNM model. The ERs for an interquartile range (IQR) increase and 95% confidence intervals (CI) for PM_2.5, NO₂, SO₂ and O₃ were 0.71% (0.34%–1.09%), 2.46% (1.78%–3.15%), 1.25% (0.9%–1.6%), and 0.27% (−0.11%–0.65%) respectively. The distribution of J-AQHI was right-skewed, and it was divided into four levels, with ranges of 0-1 for low risk, 2-3 for moderate risk, 4-5 for high health risk, and ≥6 for severe risk, and the corresponding proportions were 11.25%, 64.61%, 19.33%, and 4.81%, respectively. The ER (95%CI) of mortality risk increased by 3.61% (2.93–4.29) for each IQR increase of the multi-pollutant based J-AQHI , while it was 3.39% (2.68–4.11) for the single-pollutant based AQHI . Conclusion The J-AQHI generated by multi-pollutant model demonstrates the actual exposure health risk of air pollution in the population and provides new ideas for further improvement of AQHI calculation methods.

OBJECTIVE To provide reference for the diagnosis and treatment of Stevens-Johnson syndrome caused by rebamipide， and to explore the predisposing factors of Stevens-Johnson syndrome. METHODS Clinical pharmacists analyzed the treatment process of a patient with gastrointestinal diseases and evaluated the correlation between the drug used and adverse reactions， in order to determine the suspected allergenic drug causing Stevens-Johnson syndrome. The predisposing factors of patients with Stevens-Johnson syndrome were explored. RESULTS & CONCLUSIONS The suspected allergenic drugs that caused the patient to develop Stevens-Johnson syndrome included Ilaprazole enteric-coated tablets， Rebamipide tablets and Kangfuxin liquid. In summary， the suspect drug was identified as Rebamipide tablets according to the causality evaluation method of the National Center for Adverse Drug Reaction Monitoring， Naranjo’s scoring method and the algorithm of drug causality for epidermal necrolysis scoring criteria. Hypoproteinemia， competitive binding of plasma proteins between drugs， advanced age， bacterial and viral infections were the predisposing factors of Stevens-Johnson syndrome. Therefore， before using rebamipide in clinical practice， it is necessary to inquire about the patient’s allergy history in detail. During the use process， it is necessary to strengthen the patient’s medication monitoring and be alert to the occurrence of serious adverse reactions. If any abnormalities are found， the medication should be stopped immediately and symptomatic treatment should be given as soon as possible to ensure the safety and effectiveness of the patient’s medication.

Objective:To investigate the killing effects in vitro of a new photosensitizer black titanium dioxide b-TP-700-mediated photodynamics on prostate cancer cell line PC-3 cells.Methods:The b-TP-700 was successfully prepared by using solid phase in situ thermal reduction method. PC-3 cells were treated with 31.25, 62.5, 125, 250, 500, 1 000 μg/ml b-TP-700 for 12, 24, 48 h. The cell activity was detected by using CCK-8 method, and the morphology of PC-3 cells was observed by using confocal fluorescence microscope, the toxicity of b-TP-700 to PC-3 cells was also judged. PC-3 cells were treated with different concentrations of b-TP-700 (31.25, 62.5, 125, 250, 500 μg/ml) and irradiated with laser (1 W/cm, 808 nm) for 1, 3, 5, 7 min. The cell activity was detected by using CCK-8 method. The production of reactive oxygen species in PC-3 cells cultured in 250 μg/ml b-TP-700 after laser irradiation for 5 min was detected by using confocal fluorescence microscopy. The non-laser irradiation cells were selected as the control group.Results:There were no statistically significant differences in cell activity of PC-3 cells treated with different concentrations of b-TP-700 for the same time ( F value was 1.26, 0.39 and 0.37, respectively; all P > 0.05). PC-3 cells were treated with 1 000 μg/ml b-TP-700 for 24 h, no obvious morphological changes and no obvious dead cells were observed under fluorescence microscope. When PC-3 cells were treated with the same concentration of b-TP-700, the activity of PC-3 cells was decreased with the extension of laser excitation time. Under the same laser excitation time, the activity of PC-3 cells was decreased with the increase of b-TP-700 concentration (all P < 0.05). Under laser irradiation, obvious green fluorescence could be detected in the PC-3 cells treated with 250 μg/ml b-TP-700, while almost no green fluorescence could be observed in the control group. Conclusions:A new photosensitizer b-TP-700 has the good reactive oxygen generation ability. b-TP-700-mediated photodynamics show obvious killing effects on prostate cancer PC-3 cells in vitro, which is expected to be a new method for the treatment of prostate cancer.

Background Climate change leads to frequent heavy rainfall events, and higher incidences of bacillary dysentery after heavy rainfall have been observed. The impacts of heavy rainfall and its antecedent rainfall conditions on the disease are worth paying attention to. Objective To quantitatively analyze how the relationship between heavy rainfall events and bacillary dysentery occurrence is modified by antecedent rainfall conditions in Anhui Province and explore the different moderation effects in urban and rural contexts. Methods CN05.1 meteorological data of Anhui Province and cases of bacillary dysentery of the same area were collected from January 1, 2006 to August 31, 2017. An exposure-response Poisson regression model of heavy rainfall events and the number of daily cases was constructed to explore the moderation effect of antecedent rainfall conditions on the incidence of bacillary dysentery, and further stratified by urban and rural areas. Results This study included 129 459 cases of bacillary dysentery, with a daily average of 30.39. Compared with dry antecedent conditions without heavy rainfall, dry antecedent conditions with heavy rainfall had no obvious different effect on the incidence of bacillary dysentery for the whole province (P>0.05). But wet antecedent conditions significantly increased the risk of bacillary dysentery for the whole province after heavy rainfall (wet antecedent conditions without heavy rainfall: RR=1.281, 95%CI: 1.264-1.298; wet antecedent conditions with heavy rainfall: RR=1.267, 95%CI: 1.167-1.376). After urban and rural stratification, antecedent rainfall conditions also showed a significant moderation effect on the incidence of bacillary dysentery following heavy rainfall events. Compared with dry antecedent conditions without heavy rainfall, dry antecedent conditions with heavy rainfall had no obvious effect on the incidence of bacillary dysentery for the urban and the rural populations (P > 0.05). However, wet antecedent conditions without heavy rainfall (urban: RR=1.391, 95%CI: 1.362-1.421; rural: RR=1.222, 95%CI: 1.201-1.243) and wet antecedent conditions with heavy rainfall (urban: RR=1.364, 95%CI: 1.193-1.559; rural: RR=1.218, 95%CI: 1.098-1.352) significantly increased the risk of bacillary dysentery in both rural and urban areas. Conclusion In the influence of heavy rainfall on the incidence of bacillary dysentery in Anhui Province, antecedent rainfall conditions have a certain moderation effect in the whole province and in both urban and rural areas, and the risk of bacillary dysentery is increased under wet antecedent conditions.

Objective:To analyze the risk factors of postinflammatory hyperpigmentation (PIH) after laser in the treatment of acquired bilateral nevus of Ota-like macules (ABNOM).Methods:A retrospective study was conducted to follow up 120 patients with acquired bilateral nevus of Ota-like macules in the Department of Laser and Physiotherapy, Guangzhou Institute of Dermatology between January 2011 and December 2018, which accepted 1064-nm Q-switched neodymium: yttrium-aluminum-garnet laser treatment. The difference was analyzed between different age, sex, clinical classification, Fitzpatrick skin classification, ABNOM with melasma and postinflammatory pigmentation after laser treatment. Logistic regression was used to analyze the risk factors of postinflammatory hyperpigmentation after 1064-nm Q-switched neodymium: yttrium-aluminum-garnet laser treatment of acquired bilateral nevus of Ota-like macules.Results:Fifty-three ABNOM patients (44.17%) developed PIH after laser treatment. Univariate analysis showed that age, clinical classification, Fitzpatrick skin classification and the patients with both ABNOM and melasma all affected the occurrence of PIH after laser in the treatment of ABNOM, and the difference was statistically significant ( P<0.01). Logistic regression showed that older age, more severe clinical classification and the presence of ABNOM with melasma were the risk factors of PIH after treatment of ABNOM. Conclusions:ABNOM patients should be treated as early as possible. The risk of inducing PIH is great after laser treatment in patients with more severe clinical classification and patients with both ABNOM and melasma.

Objective:To study the association between apparent temperature (AT) and the incidence of hand,foot, and mouth disease (HFMD) and its spatial heterogeneity in 46 cities in Guangdong, Anhui and Jilin provinces, and provide scientific evidence for the early warning of HFMD.Methods:The data of HFMD incidence and meteorological factors from 2009 to 2018 in Guangdong province, 2009 to 2015 in Anhui province, and 2013 to 2018 in Jilin province were collected. Distributed lag non-linear models were constructed to investigate the association between AT and the incidence of HFMD in 46 cities from three provinces in China. Meta-analysis was used to pool the city-specific estimates, and Meta-regression was applied to analyze the factors that may cause spatial heterogeneity.Results:The relationship between daily AT and the incidence of HFMD in 46 cities appeared nonlinear. The association in Guangdong was similar to that in Jilin, and the risk of HFMD increased with the increase of AT. While the risk of HFMD in Anhui first increased with the increase of AT, and peaked at 18.1 ℃ and then went down. AT on different levels showed different lag impacts and the higher AT showed greater and longer lag impact. The spatial heterogeneity of associations may have been caused by latitude, longitude, average temperature, and average sunshine hours.Conclusions:AT is a comprehensive index to evaluate the association between temperature, relative humidity and wind speed and the incidence of HFMD. Higher AT may increase the risk of HFMD. The AT and HFMD relationship across spatial heterogeneity varies depending on geographic location and meteorological conditions.

Objective:To explore the clinical characteristics, genotypes and long-term outcomes of individuals with 3-methylglutaconic aciduria.Methods:The clinical features, biochemical data, genetic test results and treatment outcomes of six children with 3-methylglutaconic aciduria admitted to the Department of Endocrinology, Genetics and Metabolism, Xinhua Hospital from February 2017 to February 2019 were retrospectively analyzed and the Gesell developmental diagnosis schedule was performed to evaluate the development of four patients.Results:Among 6 children with 3-methylglutaconic aciduria 2 were males and 4 were females.Four cases had 3-methylglutaconic aciduria type Ⅰ and 2 cases had 3-methylglutaconic aciduria with deafness,encephalopathy, and Leigh-like syndrome. Five of 6 patients were detected by newborn screening among whom 4 remained asymptomatic, and only one had a postmortem diagnosis. Among them, 4 patients remained asymptomatic, while two presented with clinical symptoms such as jaundice and dyspnea and the age of disease onset was 1 and 2 days respectively. The concentration of 3-methylglutaconic acid in urine of all affected individuals was between 22.38 and 77.09 mmol/molCr, which was above the normal value. Genetic tests were performed for all patients. Eleven variants were identified in 2 genes, of which 10 variants were novel and only c.442C>T p.(R148X) has been previously reported; Seven variants (c.656-2delA, EX5-EX6 Del, c.942+3A>G, c.373C>T p.(R125W), c.895-3C>G, c.667C>T p.(R223X) and c.894+5G>A) were in AUH gene. The others (c.548G>A p.(R138Q), c.442C>T p.(R148X), c.1339C>T p.(R447X) and c.973dupA p.(M325Nfs*5) were in SERAC1 gene. After being treated with leucine diet restriction and L-carnitine, 4 patients with AUH gene variation who were from asymptomatic phase developed normally, whereas those 2 patients with SERAC1 gene variation had a poor prognosis. During the follow-up, 2 patients exhibited varying degrees of psychomotor retardation, the rest had normal course of development.Conclusions:There are significant clinical heterogeneities among individuals with 3-methylglutaconic aciduria. The most common pathogenic variants are splicing variations, followed by nonsense, missense and frameshift mutations. Leucine-free diet and oral L-carnitine therapy are effective for some patients. Newborn screening is essential for early diagnosis and improvement of prognosis.