Objective:To investigate the diagnostic value of machine learning model based on 18F-FDG PET/CT for polymyalgia rheumatica (PMR). Methods:From November 2014 to December 2022, 177 patients (119 males, 58 females; age: 67.0 ( 61.0, 72.0) years) admitted to the Department of Rheumatology and Immunology, the First People′s Hospital of Changzhou, with suspected PMR and undergoing 18F-FDG PET/CT examination were retrospectively analyzed. Patients were randomly divided into training set and validation set at the ratio of 7∶3. Three machine learning models, including classification and regression tree (CART), the least absolute shrinkage and selection operator (LASSO) algorithm, and logistic regression, were established based on the PET/CT imaging features to aid in the diagnosis of PMR. The diagnostic efficacy of each model was evaluated by ROC curve analysis and differences among AUCs were analyzed by Delong test. Results:There were 78(44.1%, 78/177) PMR patients and 99(55.9%, 99/177) non-PMR patients, and 124 patients in the training set and 53 patients in the validation set. The logistic regression model (training set: AUC=0.961; validation set: AUC=0.930) was superior to the CART (training set: AUC=0.902, z=2.96, P=0.003; validation set: AUC=0.844, z=2.46, P=0.014) in diagnosing PMR, and was similar to LASSO algorithm (training set: AUC=0.957, z=0.95, P=0.340; validation set: AUC=0.930, z=0.00, P=1.000), but with fewer sites evaluated. The simplified PMR-Logit score had the AUC of 0.951 in the overall population, with the sensitivity of 89.74%(70/78) and the specificity of 90.91%(90/99). Conclusion:Machine learning models based on 18F-FDG PET/CT imaging features are expected to be an effective diagnostic tool for PMR.

Objective To evaluate the bioequivalence of test product and reference product in a single dose of amoxicillin clavulanate potassium tablet under fasting and fed conditions in healthy volunteers.Methods An open label,randomized,single dose,four-period,crossover bioequivalence study was designed.Fasting and postprandial tests were randomly divided into 2 administration sequence groups according to 1:1 ratio,amoxicillin clavulanate potassium tablet test product or reference product 375 mg,oral administration separately,liquid chromatography tanden mass spectrometry was applied to determine the concentration of amoxicillin and clavulanate potassium in plasma of healthy subjects after fasting or fed administration,while Phoenix WinNonlin 8.2 software were used for pharmacokinetics(PK)parameters calculation and bioequivalence analysis.Results Healthy subjects took the test product and the reference product under fasting condition,the main PK parameters of amoxicillin are as follows:Cmax were(5 075.57±1 483.37)and(5 119.86±1 466.73)ng·mL-1,AUC0_twere(1.32 × 104±2 163.76)and(1.30 × 104±1 925.11)ng·mL-1,AUC0-∞were(1.32 × 104±2 175.40)and(1.31 ×104±1 935.86)ng·mL-1;the main PK parameters of clavulanic acid are as follows:Cmax were(3 298.27±1 315.23)and(3 264.06±1 492.82)ng·mL-1,AUC0-twere(7 690.06±3 053.40)and(7 538.39±3 155.89)ng·mL-1,AUC0-∞were(7 834.81±3 082.61)and(7 671.67±3 189.31)ng·mL-1;the 90％confidence intervals of Cmax,AUC0-tand AUC0-∞ after logarithmic conversion of amoxicillin and clavulanate potassium of the two products were all within 80.00％-125.00％.Healthy subjects took the test and reference product under fed condition,the main PK parameters of amoxicillin are as follows:Cmax were(4 514.08±1 324.18)and(4 602.82±1 366.48)ng·mL-1,AUC0-twere(1.15 × 104±1 637.95)and(1.15 × 104±1 665.69)ng·mL-1,AUC0-∞ were(1.16 × 104±1 646.26)and(1.15 × 104±1 607.20)ng·mL-1;the main PK parameters of clavulanic acid are as follows:Cmax were(2 654.75±1 358.29)and(2 850.51±1 526.31)ng·mL-1,AUC0-twere(5 882.82±2 930.06)and(6 161.28±3 263.20)ng·mL-1,AUC0-∞ were(6 022.70±2 965.05)and(6 298.31±3 287.63)ng·mL-1;the 90％confidence intervals of Cmax,AUC0-t and AUC0-∞ after logarithmic conversion of amoxicillin and clavulanate potassium of the two products were all within 80.00％-125.00％.Conclusion The two formulations were bioequivalent to healthy adult volunteers under fasting and fed conditions.

The study identified the blood-entering components of Sijunzi Decoction after gavage administration in rats by UPLC-Q-TOF-MS/MS, and investigated the mechanism of Sijunzi Decoction in treating Alzheimer's disease by virtue of network pharmacology, molecular docking, and experimental verification. The blood-entering components of Sijunzi Decoction were identified based on the mass spectra and data from literature and databases. The potential targets of the above-mentioned blood-entering components in the treatment of Alzheimer's disease were searched against PharmMapper, OMIM, DisGeNET, GeneCards, and TTD. Next, STRING was employed to establish a protein-protein interaction(PPI) network. DAVID was used to perform the Gene Ontology(GO) annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape 3.9.0 was used to carry out visual analysis. AutoDock Vina and PyMOL were used for molecular docking of the blood-entering components with the potential targets. Finally, the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway enriched by the KEGG analysis was selected for validation by animal experiments. The results showed that 17 blood-entering components were detected in the serum samples after administration. Among them, poricoic acid B, liquiritigenin, atractylenolide Ⅱ, atractylenolide Ⅲ, ginsenoside Rb_1, and glycyrrhizic acid were the key components of Sijunzi Decoction in treating Alzheimer's disease. HSP90AA1, PPARA, SRC, AR, and ESR1 were the main targets for Sijunzi Decoction to treat Alzheimer's disease. Molecular docking showed that the components bound well with the targets. Therefore, we hypothesized that the mechanism of Sijunzi Decoction in treating Alzheimer's disease may be associated with the PI3K/Akt, cancer treatment, and mitogen-activated protein kinase(MAPK) signaling pathways. The results of animal experiments showed that Sijunzi Decoction significantly attenuated the neuronal damage in the hippocampal dentate gyrus area, increased the neurons, and raised the ratios of p-Akt/Akt and p-PI3K/PI3K in the hippocampus of mice. In conclusion, Sijunzi Decoction may treat Alzheimer's disease by activating the PI3K/Akt signaling pathway. The findings of this study provide a reference for further studies about the mechanism of action and clinical application of Sijunzi Decoction.
Animals ; Mice ; Rats ; Proto-Oncogene Proteins c-akt ; Network Pharmacology ; Alzheimer Disease/drug therapy* ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases/genetics* ; Tandem Mass Spectrometry ; Drugs, Chinese Herbal/pharmacology*

Objective:To investigate the regulation and possible mechanism of hyperthermia (HT) on the ferroptosis of squamous cell carcinoma of the tongue cell line CAL-27.Methods:Half maximal inhibitory concentration (IC 50) of Fer-1, an inhibitor of ferroptosis, was detected by CCK-8 assay and used for subsequent experiments. CAL-27 cells were divided into the HT, control, Fer-1 and HT+ Fer-1 groups according to experimental design. Reactive oxygen species (ROS) levels and iron ion concentration were determined by corresponding detection kits. The p53 and TfR1 mRNA levels were detected by real-time reverse transcription PCR. Cell migration was detected by cell scratch test and cell apoptosis was detected by flow cytometry. Results:HT significantly up-regulated the ROS levels ( P<0.01) and iron ion concentration ( P<0.001), and significantly increased the expression levels of p53 and TfR1 mRNA (both P<0.01). The cell migration ability was decreased ( P<0.001), whereas cell apoptosis rate was increased by HT ( P<0.01). In the HT+Fer-1 group, the ROS levels ( P<0.001), iron ion concentration ( P<0.001), expression levels of p53 and TfR1 mRNA (both P<0.01) were significantly down-regulated, the cell migration ability was recovered ( P<0.01), and cell apoptosis rate was decreased ( P<0.01) compared with those in the HT group, respectively. Conclusions:HT may induce the ferroptosis of CAL-27 cell line, inhibit cell migration ability and promote cell apoptosis by activating the p53/TfR1 pathway.

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

Objective To investigate the effects and mechnism of abnormal stress promoting macrophage mobility inhibitory factor(MIF),cyclooxygenase 2(COX2)and prostaglandin E2(PGE2)in the progression of temporomandibular joint osteoarthritis(TMJOA).Methods From January 2020 to December 2021,TMJOA and temporomandibular joint internal derangement(TMJID)patients(30 cases in each group,we divided the TMJOA into group TMJ Ⅰ,Ⅱ,Ⅲ according to the stage)who were admitted to TMJOA special clinic of the First Affiliated Hospital of Xinjiang Medical University and accompanied by abnormal occlusion were collected.The pain score of the occlusal state of the patients was evaluated by visual analogue scale.The expression levels of MIF,COX2 and PGE2 in synovial fluid were detected by ELISA.We used the unilateral anterior crossbite for TMJOA(UAC)rats model(the grouped into:UAC-4 weeks,UAC-8 weeks and UAC-12 weeks group),and control group at the same time(grouped into:Ctrl-4 weeks,Ctrl-8 weeks and Ctrl-12 weeks group),each group had 6 rats.The expression levels of MIF,COX2 and PGE2 in serum and synovial fluid of rats were detected by ELISA.The expression levels of IL-1β,IL-18,MIF,COX2 and PTGER2 in temporomandibular joint of rats were detected by Western blotting.The fluid flow shear stress(FFSS)model of fibroblast-like synovial cells(FLSs)was established,and the mRNA and protein expression levels of above indexes were detected by RT-PCR and Western blotting.Results Visual analogue scale evaluation showed that the pain score of TMJOA Ⅰ and Ⅱ group was significantly higher than that of TMJID(P<0.001).ELISA results showed that the expression levels of MIF,COX2 and PGE2 in synovial fluid in TMJOA group were higher than those in TMJID group(P<0.05),and the expression levels were the highest in TMJOA Ⅱ group.Compared with control group,the expressions of MIF,COX2 and PGE2 in serum and synovial fluid at UAC-4 weeks,8 weeks and 12 weeks were slightly higher,and significantly higher at UAC-8 weeks in rat TMJOA model(P<0.05).In addition,the expression trend of protein levels in temporomandibular joint tissues was similar,which showed higher expression levels of IL-1β,IL-18,MIF,COX2 and PTGER2(P<0.05).In the cell model where FFSS interfered with FLSs,with the increase of FFSS,cell with deformation,incomplete cell membrane and reduced number.Compared with control group,the expression levels of IL-1β,IL-18,MIF,COX2 and PGE2(PTGER2)of FLSs were increased in 1,3,5 and 10 dyn/cm2 intervention groups(P<0.05).Conclusion MIF,COX2 and PGE2 were highly expressed in temporomandibular joint synovial fluid of TMJOA patients with malocclusion.And these three factors were also highly expressed in serum and synovial fluid of UAC rats.The abnormal fluid shear stress promotes the secretion of MIF,COX2 and PGE2 by FLSs to participate in joint microenvironment inflammation and accelerate disease progression.

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
Adolescent ; Body Mass Index ; Child ; Child, Preschool ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Male ; Obesity/epidemiology* ; Overweight/epidemiology* ; Puberty ; Puberty, Precocious ; Sexual Development

Objective: To expore the correlation between neck disability, neck pain and muscle strength in cervical pondylosis of office worker, and to provide scientific basis for the prevention and treatment of cervical spondylosis. Methods: In April 2021 ,234 patients with cervical spondylotic myelopathy treated in the Subsidiary Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine from April 2015 to April 2017 were selected, the correlation between Neck Disability Index (NDI) score, neck pain and muscle strength was analyzed using the Spearman rank correlation method. Mann-Whitney U test was used to compare the difference of maximum muscle strength of isometric contraction. Results: NDI score was negatively correlated with neck flexion, extension, and muscle strength in the left and right flexion directions (r(s)=-0.164, -0.169, -0.222, -0.176, P=0.012, 0.010, 0.001 , 0.007). In mild and moderate functional disorder patients, the muscle strength in flexion, extension and left and right flexion direction was greater, the difference was statistically significant (P <0.01). Conclusion: There is a negative correlation between cervical functional disorder and cervical muscle strength in office workers, suggesting that strengthening cervical muscle strength may be a way to improve cervical spine function.
Cervical Vertebrae ; Humans ; Muscle Strength/physiology* ; Neck Muscles/physiology* ; Neck Pain/physiopathology* ; Occupational Diseases/physiopathology* ; Range of Motion, Articular/physiology* ; Spondylosis/physiopathology*

The effect of air pollution on the lung function of adults with asthma remains unclear to date. This study followed 112 patients with asthma at 3-month intervals for 2 years. The pollutant exposure of the participants was estimated using the inverse distance weight method. The participants were divided into three groups according to their lung function level at every visit. A linear mixed-effect model was applied to predict the change in lung function with each unit change in pollution concentration. Exposure to carbon monoxide (CO) and particles less than 2.5 micrometers in diameter (PM_2.5) was negatively associated with large airway function in participants. In the severe group, exposure to chronic sulfur dioxide (SO2) was negatively associated with post-bronchodilator forced expiratory flow at 50%, between 25% and 75% of vital capacity % predicted (change of 95% CI per unit: -0.34 (-0.55, -0.12), -0.24 (-0.44, -0.03), respectively). In the mild group, the effect of SO₂ on the small airways was similar to that in the severe group, and it was negatively associated with large airway function. Exposure to CO and PM_2.5 was negatively associated with the large airway function of adults with asthma. The negative effects of SO₂ were more evident and widely observed in adults with severe and mild asthma than in adults with moderate asthma. Patients with asthma react differently to air pollutants as evidenced by their lung function levels.
Adult ; Air Pollutants/analysis* ; Air Pollution/adverse effects* ; Asthma/epidemiology* ; Beijing/epidemiology* ; Environmental Exposure/adverse effects* ; Humans ; Lung ; Particulate Matter/analysis* ; Sulfur Dioxide/adverse effects*

Senescence of activated hepatic stellate cells (aHSCs) is a stable growth arrest that is implicated in liver fibrosis regression. Senescent cells often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). But little is known about how alanine-serine-cysteine transporter type-2 (ASCT2), a high affinity glutamine transporter, affects HSC senescence and SASP during liver fibrosis. Here, we identified ASCT2 is mainly elevated in aHSCs and positively correlated with liver fibrosis in human and mouse fibrotic livers. We first discovered ASCT2 inhibition induced HSCs to senescence in vitro and in vivo. The proinflammatory SASP were restricted by ASCT2 inhibition at senescence initiation to prevent paracrine migration. Mechanically, ASCT2 was a direct target of glutaminolysis-dependent proinflammatory SASP, interfering IL-1α/NF-κB feedback loop via interacting with precursor IL-1α at Lys82. From a translational perspective, atractylenolide III is identified as ASCT2 inhibitor through directly bound to Asn230 of ASCT2. The presence of -OH group in atractylenolide III is suggested to be favorable for the inhibition of ASCT2. Importantly, atractylenolide III could be utilized to treat liver fibrosis mice. Taken together, ASCT2 controlled HSC senescence while modifying the proinflammatory SASP. Targeting ASCT2 by atractylenolide III could be a therapeutic candidate for liver fibrosis.