Objective To investigate the trends of major thyroid function indices in Chinese adolescent females at different ages and the differences from adult reference intervals.Methods A total of 791 female students from 4 junior high schools were enrolled in the study by selecting one junior high school in each of the following locations:Minhang District of Shanghai,Haimen City of Jiangsu Province,Yuhuan City of Zhejiang Province,and Deqing County of Zhejiang Province from Oct to Nov 2017 and from Jan to Mar 2019.The subjects were subjected to physical examination as well as thyroid hormone levels;and the Pubertal Developmental Events Self-Assessment Scale(PDS)was used to evaluate the staging of pubertal development.Follow-ups were conducted after 2 years,with the same survey content.Thyroid function levels were assessed in 5 age groups between 11 to 15 years old,95%CI were calculated,and mixed linear models were used to analyze the effects of age and pubertal developmental stage on hormone levels.Results The reference intervals for thyroid stimulating hormone(TSH),free triiodothyronine(FT3)and free thyroxine(FT4)in adolescent females differed significantly from those of adults,with misclassification rates ranging from 2.98%to 5.17%.Statistically significant differences were found for age,pubertal development staging,and the interaction of age and pubertal staging after correcting for BMI,waist circumference(all P<0.05).TSH levels were more affected by age before the completion of pubertal development,the level of the 12-year-old group was higher than that of the 11-year-old group(P=0.001 2)and the 13-year-old group(P<0.000 1);FT3 levels showed greater variability with age during late pubertal stage,with levels significantly higher at 13 years of age than at 11 and 12 years of age(P<0.0001),and gradually decreasing after 13 years of age(P<0.000 1).In contrast,FT4 levels were generally less affected by age between 11 and 15 years of age,with levels slightly higher at 13-15 years of age than at 11-12 years of age(P<0.000 1).Conclusion The levels of TSH,FT3,and FT4,as indicators of thyroid function in adolescent females,differ significantly from those of adults,and are differently affected by age and the stages of pubertal development;further refinement of the reference intervals for age-and pubertal-development-specific thyroid indicators is necessary.

Objective To establish an artificial intelligence(AI)diagnostic model for the histopathologic diagnosis of extramammary Paget's disease(EMPD)and to evaluate its efficiency for the diagnosis and differential diagnosis of EMPD.Methods All non-tumor skin disease patients who underwent skin tissue biopsy in Department of Dermatology of First Affiliated Hospital of Army Medical University from September 2003 to February 2023 were recruited,and their pathological data were collected,including EMPD,Bowen's disease(BD),squamous cell carcinoma(SCC),and epidermal hyperplasia and hypertrophy.With EMPD as the main research subject,the histopathological images of BD,SCC,and non-tumor skin diseases were included in the study.The histopathological data of 4 types of diseases was classified and diagnosed by ResNet101 and DenseNet121 deep learning neural networks,and the performance of these models was evaluated.Results The AUC values of the ResNet101 diagnostic model for the diagnosis of EMPD,BD,SCC and non-tumor skin diseases on the images at x20 magnification were 0.97,0.98,1.00 and 0.96,respectively,with an accuracy of 0.925±0.011,while the AUC values on the images at x40 magnification were 1.00,0.99,1.00 and 0.97,respectively,with an accuracy of 0.943±0.017.The AUC values of the DenseNet121 diagnostic model for the diagnosis of 4 diseases on the images at x20 magnification were 0.98,0.95,0.99 and 1.00,respectively,with an accuracy of 0.912±0.034,while the AUC values on the images at x40 magnification were 0.99,0.96,1.00 and 1.00,respectively,with an accuracy of 0.971±0.012.Our results indicated that the histopathologic diagnostic model could effectively differentiate EMPD from BD,SCC and non-tumor skin diseases at low power magnification.The FLPOs of ResNet101 was 786.6 M,and the parameter was 4.5 M;The FLPOs of DensNet121 was 289.7 M,and the parameter was 0.8M.Conclusion Our AI diagnostic model is of good effectiveness in the diagnosis and differential diagnosis of EMPD.DenseNet121 is recommended as the dermatopathological diagnostic model of this study.

AIM: To compare the consistency and feasibility of objective ocular torsion measured with GMPE module-based optical coherence tomography(OCT)and fundus color photography(FCP).METHODS: Patients were enrolled in our strabismus clinic from December 2020 to March 2021, and the objective ocular torsion of the eyes was measured by both GMPE module-based OCT and FCP on the same day. FCP was used to measure the fovea-disc angle(FDA)manually by using the Adobe Photoshop software, while the GMPE module-based OCT software positioned automatically the macula and the center of the optic disc to measure the FDA.RESULTS: Fifty-five patients were included, the FDA measured by OCT was -6.6°±4.5° in the right eye and -8.8°±4.7° in the left eye, respectively; The FDA measured by FCP was -6.6°±4.7° in the right eye and -8.4°±4.1° in the left eye, respectively, with no statistically significant difference between the results of the two methods(Pright eye=0.90, Pleft eye=0.08). In patients with exotropia, the FDA measured by OCT was -5.8°±4.9° in the right eye and -9.1°±4.5° in the left eye, respectively, the FDA measured by FCP was -5.7°±5.0° in the right eye and -8.6°±4.3° in the left eye, respectively,(Pright eye=0.75, Pleft eye=0.15). Similarly, the patients with esotropia, the FDA measured by OCT was -9.0°±7.3° in the right eye and -11.3°±3.5° in the left eye, respectively, while the FDA measured by FCP was -10.0°±7.0° in the right and -10.1°±2.8° in the left eye(Pright eye=0.21, Pleft eye=0.10), respectively. There were no significant differences between the two methods in patients with esotropia or exotropia(P>0.05). The results of both Pearson test and Bland-Altman analysis were highly correlated(rright eye=0.93, rleft eye=0.94, P<0.01). CONCLUSION: GMPE module-based OCT can be used for objective ocular torsion measurement with high reliability and reproducibility, and is a promising clinical alternative to the fundus color photographic method.

AIM:To investigate the correlation between corneal biomechanical parameters measured by the corneal visualization Scheimpflug Technology(Corvis ST)and corneal high-order aberrations(HOAs)in children with mild to moderate myopia.METHODS:A cross-sectional study. A total of 255 pediatric patients with myopia enrolled from April to July 2021 in Tianjin Medical University Eye Hospital were continuously collected, and all the right eyes were taken for analysis. Corneal biomechanical parameters were obtained from Corvis ST. Pentacam three-dimensional anterior segment analyzer was used to measure total corneal higher-order aberrations(RMSh), third order aberrations(RMS3)and fourth order aberrations(RMS4).RESULTS:RMS3 was positively correlated with the second applanation time(A2T)(r=0.175, P=0.009)and negatively correlated with the axis length(AL)(r=-0.155, P=0.014). RMS4 was negatively correlated with the highest concavity radius(HCR)(r=-0.165, P=0.009). RMSh was negatively correlated with HCR and AL(r=-0.152, P=0.037; r=-0.175, P=0.005).CONCLUSION:There is a correlation between corneal biomechanical parameters and HOAs in children with myopia. Cornea with higher stiffness and stronger deformation resistance has smaller RMS3, RMS4 and RMSh.

PURPOSE: Posttraumatic stress disorder (PTSD) is a significant global mental health concern, especially in the military. This study aims to estimate the efficacy of mindfulness meditation in the treatment of military-related PTSD, by synthesizing evidences from randomized controlled trials. METHODS: Five electronic databases (Pubmed, EBSCO Medline, Embase, PsychINFO and Cochrane Library) were searched for randomized controlled trials focusing on the treatment effect of mindfulness meditation on military-related PTSD. The selection of eligible studies was based on identical inclusion and exclusion criteria. Information about study characteristics, participant characteristics, intervention details, PTSD outcomes, as well as potential adverse effects was extracted from the included studies. Risk of bias of all the included studies was critically assessed using the Cochrane Collaboration's tool. R Statistical software was performed for data analysis. RESULTS: A total of 1902 records were initially identified and screened. After duplicates removal and title & abstract review, finally, 19 articles in English language with 1326 participants were included through strict inclusion and exclusion criteria. The results revealed that mindfulness meditation had a significantly larger effect on alleviating military-related PTSD symptoms compared with control conditions, such as treatment as usual, present-centered group therapy and PTSD health education (standardized mean difference (SMD) = -0.33; 95% CI [-0.45, -0.21]; p < 0.0001). Mindfulness interventions with different control conditions (active or non-active control, SMD = -0.33, 95% CI [-0.46, -0.19]; SMD = -0.49, 95% CI [-0.88, -0.10], respectively), formats of delivery (group-based or individual-based, SMD = -0.30, 95% CI [-0.42, -0.17], SMD = -0.49, 95% CI [-0.90, -0.08], respectively) and intervention durations (short-term or standard duration, SMD = -0.27, 95% CI [-0.46, -0.08], SMD = -0.40, 95% CI [-0.58, -0.21], respectively) were equally effective in improving military-related PTSD symptoms. CONCLUSION Findings from this meta-analysis consolidate the efficacy and feasibility of mindfulness meditation in the treatment of military-related PTSD. Further evidence with higher quality and more rigorous design is needed in the future.

Objective:To investigate the reference value of ultrasonography (US) image features, elastography and serum thyroid stimulating hormone (TSH) levels in preoperative diagnosis of differentiated thyroid carcinoma (DTC).Methods:Retrospective analysis was conducted to collect clinical data of patients undergoing thyroid surgery in the Fourth Affiliated Hospital of Harbin Medical University from September 2018 to January 2020. All patients underwent conventional ultrasound, elastography examination and serum TSH level measurement before surgery; patients were divided into benign group and DTC group according to the results of pathological results of the operation, and the US image features and elasticity score were analyzed by chi-square test and multivariate logistic regression to evaluate the causes of DTC; a multivariate logistic regression model was established and the receiver operating characteristic curve (ROC) was drawn with the regression model, by analyzing the area under the ROC curve (AUC), sensitivity, specificity and accuracy, the reference value of US image features, elastography and serum TSH levels in the preoperative diagnosis of DTC were judged.Results:Clinical data of 81 patients were collected, including 17 men and 64 women, aged (48.72 ± 10.58) years. In benign group, there were 37 cases, including 10 men and 27 women, with age of (53.24 ± 9.59) years; there were 44 patients in DTC group, including 7 men and 37 women, with age of (44.91 ± 9.95) years old, the age difference between benign group and DTC group was significant ( t = 3.822, P < 0.05), while the gender difference was not statistically significant (χ 2 = 1.498, P > 0.05). There were significant differences in the number, size, echo level, microcalcification, aspect ratio and elasticity score between benign group and DTC group (χ 2 = 49.000, 4.457, 32.111, 5.444, 4.457, 49.926, P < 0.05); multivariate logistic analysis showed that hypoecho, microcalcification, aspect ratio > 1 and elasticity score were risk factors for DTC ( OR = 8.042, 4.787, 4.160, 2.380, P < 0.05), the ROC curve of the multivariate logistic regression model showed that the AUC was 0.841 (95% CI = 0.743 - 0.939), sensitivity was 90.91%, specificity was 72.97%, and accuracy was 82.72%; the AUC of serum TSH level prediction of DTC showed that the AUC was 0.721 ( P < 0.05), sensitivity was 72.70%, specificity was 64.90%, accuracy was 54.30%, and TSH best cut-off value was 2.215 μU/ml. Conclusion:In the preoperative diagnosis of DTC, US image features, elastography and serum TSH levels are of important clinical reference value for diagnosis of DTC, and the establishment of multivariate logistic regression model is conducive in improving the clinicians prediction of the occurrence of DTC.

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.
Adolescent ; Adult ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Middle Aged ; Pandemics ; Pneumonia, Viral ; drug therapy ; Prospective Studies ; Young Adult

Objective: To investigate the effect of human umbilical cord mesenchymal stem cells derived exosomes (hUC-MSC-exo) on the phenotype of peripheral blood macrophages from rabbit autoimmune dry eye and the expression of related cytokines. Methods: The hUC-MSCs were isolated and characterized.Exosomes derived from hUC-MSCs were extracted by ultracentrifugation and observed directly using electronic microscopy.Specific markers of exosomes were analyzed by Western blot.Six rabbits were randomly divided into the normal control group and the dry eye group by using the random number table method, 3 rabbits for each group.Rabbit model of autoimmune dry eye was established in the dry eye group, and the lacrimal glands were collected for quantitative real-time PCR (qRT-PCR) at the 8th week.In vitro, activated peripheral blood mononuclear cells (PBMCs) from rabbit autoimmune dry eye model were incubated with hUC-MSC-exo or phosphate buffered saline (PBS). After 48 hours, cells from the hUC-MSC-exo group and the PBS control group were collected.The mRNA expression levels of related cytokine genes and subpopulation-related marker genes in macrophages were quantified by qRT-PCR.The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.This study protocol was approved by Ethic Committee of Tianjin Medical University Eye Hospital (No.TJYY20181217001). Written informed consent was obtained from each family before obtaining umbilical cord. Results: Exosomes derived from hUC-MSCs had typical morphology and specific markers.qRT-PCR results showed that, the relative expression quantity of M1 macrophages phenotypic molecular nitric oxide synthase 2 (NOS2) mRNA and inflammatory factor tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) mRNA in the lachrymal organization in the dry eye model group was significantly higher than those in the normal control group (3.06±1.00 vs. 1.00±0.03, 2.77±0.72 vs. 1.01±0.02 and 1.30±0.08 vs. 1.01±0.01, respectively), the relative expression quantity of M2 macrophages phenotypic molecular arginase 1 (Arg1), CD206 and IL-10 mRNA in the lachrymal organization in the dry eye model group was significantly lower than those in the normal control group (0.55±0.07 vs. 1.00±0.00, 0.60±0.13 vs.1.00±0.00, 0.65±0.14 vs. 1.01±0.01, respectively), with significant differences between them (all at P<0.05). In vitro, the relative expression quantity of M1 macrophages phenotypic molecular NOS2 mRNA and inflammatory factor TNF-α, IL-1β mRNA in PBMCs in the hUC-MSC-exo group was significantly lower than those in the PBS control group (0.59±0.08 vs.0.98±0.03, 0.56±0.07 vs. 1.03±0.11, 0.47±0.04 vs.1.00±0.08)(all at P<0.05); the relative expression quantity of M2 macrophages phenotypic molecular Arg1, CD206 mRNA and anti-inflammatory cytokine TGF-β, IL-10 and IL-4 mRNA in PBMCs in the hUC-MSC-exo group was significantly higher than those in the PBS control group (2.13±0.28 vs. 1.10±0.17, 1.32±0.03 vs. 1.01±0.06, 1.53±0.20 vs. 1.05±0.10, 1.47±0.08 vs.0.98±0.03, 1.51±0.16 vs. 1.01±0.03), with significant differences between them (all at P<0.05). Conclusions hUC-MSC-exo can polarize peripheral blood macrophages toward immune-suppressive M2-like phenotype, inhibit the production of pro-inflammatory cytokines TNF-α and IL-1β, and meanwhile increase the expression of anti-inflammatory factors IL-10 and TGF-β.

OBJECTIVE: This study aimed to clone and characterize the oxiranedicarboxylate hydrolase (ORCH) from Labrys sp. WH-1. METHODS: Purification by column chromatography, characterization of enzymatic properties, gene cloning by protein terminal sequencing and polymerase chain reaction (PCR), and sequence analysis by secondary structure prediction and multiple sequence alignment were performed. RESULTS: The ORCH from Labrys sp. WH-1 was purified 26-fold with a yield of 12.7%. It is a monomer with an isoelectric point (pI) of 8.57 and molecular mass of 30.2 kDa. It was stable up to 55 °C with temperature at which the activity of the enzyme decreased by 50% in 15 min (T₅₀¹⁵) of 61 °C and the half-life at 50 °C (t_{1/2, 50 °C}) of 51 min and was also stable from pH 4 to 10, with maximum activity at 55 °C and pH 8.5. It is a metal-independent enzyme and strongly inhibited by Cu²⁺, Ag⁺, and anionic surfactants. Its kinetic parameters (K_m, k_cat, and k_cat/K_m) were 18.7 mmol/L, 222.3 s^-1, and 11.9 mmol/(L·s), respectively. The ORCH gene, which contained an open reading frame (ORF) of 825 bp encoding 274 amino acid residues, was overexpressed in Escherichia coli and the enzyme activity was 33 times higher than that of the wild strain. CONCLUSIONS The catalytic efficiency and thermal stability of the ORCH from Labrys sp. WH-1 were the best among the reported ORCHs, and it provides an alternative catalyst for preparation of L(+)-2,3-dihydrobutanedioic acid.
Alphaproteobacteria/enzymology* ; Cloning, Molecular ; Dicarboxylic Acids/metabolism* ; Enzyme Stability ; Epoxide Hydrolases/metabolism*