Abnormal activation of the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma （DLBCL）. In recent years， inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors （e.g.， ruxolitinib） and STAT3 inhibitors （direct small-molecule inhibitors， the antisense oligonucleotide， and proteolysis targeting chimeras， etc.） in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile， the development of novel drug delivery systems has significantly enhanced the stability， bioavailability， and targeting ability of the compounds. Furthermore， JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies （such as combinations with B-cell receptor signaling pathway inhibitors， immunomodulators， or other targeted drugs）. However， current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL， and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.

Objective:To synthesize a hydrolysis-resistant urushiol-modified monomer(UMM)to improve the hydrolysis resistance of light-cured composite resin,while reducing the volume shrinkage rate(VS),increasing the double bond conversion rate(DC),and mitigating the potential biosafety concerns of bisphenol A glycidyl methacrylate(Bis-GMA)monomer.Methods:UMM was synthesized by modifying urushiol via an acyl chloride reaction,and its structure was analyzed and characterized using Fourier transform infrared spectroscopy(FT-IR).Control group was consisted of Bis-GMA/triethylene glycol dimethacrylate(TEGDMA)without UMM,while 10%UMM,15%UMM,and 20%UMM groups were prepared by partially replacing Bis-GMA with UMM at mass fractions of 10%,15%,and 20%,respectively.The viscosity of UMM was measured using a rheometer.The DC of light-cured composite resin in various groups was detected by FT-IR spectroscopy,and the VS was calculated.The contact angle of light-cured composite resin in various groups was measured using the sessile drop method,and the water sorption and solubility values were calculated.The mechanical properties of light-cured composite resin in various groups were tested.The in vitro cytotoxicity of light-cured composite resin in various groups was evaluated using the cell counting kit-8(CCK-8)assay.Results:The FT-IR spectra results showed that the absorption peak of the hydroxyl group at 3 402 cm-1 disappeared,while characteristic absorption peaks of-C=O and-C=C appeared at 1 745 and 1 637 cm-1,indicating that urushiol successfully reacted with acryloyl chloride to form UMM.The viscosity of UMM ranged from 25.14 to 29.43 Pa·s.Compared with control group,the DC of light-cured composite resin in 10%UMM,15%UMM,and 20%UMM groups was significantly increased(P<0.05),while the VS was significantly decreased(P<0.05),both in a dose-dependent manner.Compared with control group,the contact angle of light-cured composite resin in 10%UMM,15%UMM,and 20%UMM groups was significantly increased(P<0.05).Compared with 10%UMM group,the contact angle of light-cured composite resin in 15%UMM and 20%UMM groups was further increased(P<0.05).Compared with control group,the water sorption and solubility values of light-cured composite resin in 10%UMM,15%UMM,and 20%UMM groups were significantly decreased(P<0.05),showing a dose-dependent trend.After 24 h of water immersion,compared with control group,the flexural strength(FS)and elastic modulus(EM)of light-cured composite resin in 10%UMM,15%UMM,and 20%UMM groups were significantly decreased(P<0.05),also in a dose-dependent manner.After 7 d of water immersion,compared with control group,the FS of light-cured composite resin in 10%UMM group was significantly increased(P<0.05),while that in 20%UMM group was significantly decreased(P<0.05).Compared with 10%UMM group,the FS of light-cured composite resin in 15%UMM and 20%UMM groups was significantly decreased(P<0.05),exhibiting a dose-dependent trend.Compared with control group,the EM of light-cured composite resin in 15%UMM and 20%UMM groups was significantly decreased(P<0.05),also in a dose-dependent manner.The relative growth rate(RGR)of the L929 cells in control,10%UMM,15%UMM,and 20%UMM groups was above 90%,with no statistically significant differences among groups(P>0.05),and all cytotoxicity results were qualified.Conclusion:A novel low-viscosity monomer UMM is successfully synthesized in this study.All UMM-containing light-cured composite resin formulations exhibit higher DC,lower VS,reduced water sorption and solubility values,improved hydrolysis resistance,and low cytotoxicity.UMM can serve as a potential resin monomer to enhance the hydrolysis resistance of light-cured composite resin.

Objective To investigate the roles of three Tiao-Bu Fei-Shen Traditional Chinese Medicine(TCM)therapies in improving airway mucus hypersecretion in rats with stable chronic obstructive pulmonary disease(COPD).Methods Ninety rats were divided randomly into nine groups:control(Control)group,model(COPD)group,Bu-Fei Jian-Pi Formula(BJF)group,Bu-Fei Yi-Shen Formula(BYF)group,Yi-Qi Zi-Shen Formula(YZF)group,ERK1/2 inhibitor(PD98059)group,Bu-Fei Jian-Pi combined with inhibitor(BJF+PD98059)group,Bu-Fei Yi-Shen combined with inhibitor(BYF+PD98059)group,and Yi-Qi Zi-Shen combined with inhibitor(YZF+PD98059)group.A rat model of COPD was established by exposing rats to cigarette smoke followed by repeated bacterial infection from weeks 1～8.From weeks 9～16,rats in the control and COPD groups were given 2 mL normal saline,rats in the BJF,BYF,and YZF groups were given the three Tiao-Bu Fei-Shen formulas by gavage,and rats in the PD98059,BJF+PD98059,BYF+PD98059,and YZF+PD98059 groups were given PD98059 by intraperitoneal injection for 7 days at the 16th week.Lung function tests were conducted after 16 weeks and lung tissue morphology,lung water content,inflammatory cell count in bronchoalveolar lavage fluid,and serum levels of inflammatory factors were also assessed.Goblet cell proportion was determined by Alcian blue-periodic acid-Schiff staining,and Muc5AC and Muc5B expression levels were detected by immunohistochemistry.mRNA expression levels of ERK1,ERK2,ENaC,CFTR,and AQP5 were detected by polymerase chain reaction and protein expression levels of ERK1/2 and P-ERK1/2 in lung tissue were determined by Western Blot.Results TV,MV,FVC,FEV0.1,FEV0.1/FVC were significantly decreased(P＜0.01)in COPD rats compared with those in the control group.Lung pathology revealed alveolar disorder,massive fracture of the alveolar wall,and severe shrinkage/thickening of the airway wall accompanied by extensive infiltration of inflammatory cells.Lung tissue water content was significantly increased in COPD rats(P＜0.01),while the proportion of macrophages in BALF was significantly reduced(P＜0.01)and the proportions of neutrophils and lymphocytes were significantly increased(P＜0.01).Serum levels of TNF-α and IL-1β were significantly increased in COPD rats(P＜0.05,P＜0.01).The percentage of goblet cells and expression levels of Muc5AC and Muc5B in airway epithelial cells were significantly increased(P＜0.01),mRNA expression levels of ERK1,ERK2,and ENaC in lung tissue were significantly elevated(P＜0.01),while mRNA expression levels of CFTR and AQP5 were significantly decreased(P＜0.01)in COPD rats compared with levels in the control group.The expression of P-ERK1/2,ERK1/2 in lung tissue was significantly increased(P＜0.01)Rats in the treatment groups demonstrated improvements in the above indicators(P＜0.05,P＜0.01)compared with the COPD group,the groups receiving the three Tiao-Bu Fei-Shen formulas combined with PD98059 showing superior efficacy compared with the single treatment groups(P＜0.05,P＜0.01).Conclusions The three tested Tiao-Bu Fei-Shen therapies can ameliorate airway mucus hypersecretion in COPD rats by inhibiting the ERK1/2 signaling pathway.

Antibody-drug conjugate (ADC) has the characteristics of low toxicity and high efficiency, and plays an important role in cancer treatment. However, due to the complexity of its structure, it brings difficulties in pharmacokinetic (PK) bioanalysis. This study established an analytical method for the detection of ADC (RC108) in cynomolgus monkey plasma by ligand-binding assay (LBA) and liquid chromatography tandem mass spectrometry (LC-MS/MS), which was used to analyze and quantify the total antibody, bound antibody and free drug in cynomolgus monkey plasma. Based on the LBA method, rabbit anti-RC108 Fab and mouse anti-MMAE (monomethyl auristatin E) mAb were pre-coated in 96-well plates as the total antibody and antibody binding reagents, respectively. The samples to be tested were added, and then the detection reagents were added in turn. Goat anti-human IgG (H+L)-HRP, chromogenic solution tetramethylbenzidine (TMB), H₂SO₄ terminate the reaction, read data at 450 nm/630 nm wavelength of microplate reader; LC-MS/MS analysis method quantifies MMAE concentration, and refer to relevant regulations for methodological validation. The analytical method for quantifying total antibody, bound antibody and free drug of RC108 drug obtained good accuracy and precision, and the selectivity, dilution linearity, hook effect, parallelism and stability were verified. Meet the requirements of biological analysis. Finally, a bioanalytical method for the determination of the concentration of the test substance RC108 (total antibody, conjugated antibody, free MMAE) in cynomolgus monkey plasma with high sensitivity and high throughput was established by LBA and LC-MS/MS method. Subsequent non-clinical research on PK research in cynomolgus monkeys will provide technical support.

BACKGROUND: Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown. METHODS: Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements. RESULTS: Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R. CONCLUSION PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.
Rats ; Male ; Animals ; Myocardial Reperfusion Injury/metabolism* ; Connexin 43/genetics* ; Sumoylation ; Down-Regulation ; Rats, Sprague-Dawley ; Arrhythmias, Cardiac/drug therapy* ; Myocardial Ischemia/metabolism* ; RNA, Small Interfering/metabolism*

This paper summarized the school nutrition lunch legislations and nutrition status in China and abroad. School lunch system is relatively well-established and mature in Japan， the United States and Sweden and the lunch system has been gradually as an important part of basic education， which is worth learning by other countries and regions. China started its pilot school nutrition lunch program in 1987， and has improved the nutritional status of students， especially the students in rural areas， significantly. However， there still exists certain gaps compared with developed countries. We should actively learn from those countries， so as to provide reference for the formulation and improvement of China’s nutritional lunch policies.

Objective:To investigate the changes of related indicators of right heart hypofunction in patients with primary myelofibrosis (PMF).Methods:The clinical data of 55 PMF patients in the Second People's Hospital of Lianyungang in Jiangsu Province and Jiangsu Province Hospital from January 2015 to August 2019 were retrospectively analyzed. The differences in right heart function-related echocardiographic indexes and biochemical indexes between pre-fibrosis/early stage fibrosis patients and obvious stage fibrosis patients were compared. Single factor linear regression method was used to analyze the correlations of pulmonary artery pressure with biochemical indexes.Results:The hemoglobin level [119 g/L (47-224 g/L) vs. 78 g/L (33-182 g/L)] and platelet count [233×10 12/L (5×10 12/L-984×10 12/L) vs. 117×10 12/L (7×10 12/L-731×10 12/L)] of patients in the pre-fibrosis/early stage fibrosis group were higher than those in the obvious stage fibrosis group, and the differences were statistically significant (both P<0.05). Among 22 patients with complete results of cardiac ultrasound, 90.9% (20/22) patients had increased pulmonary artery pressure, 72.7% (16/22) patients had increased left atrial diameter, and 90.9% (20/22) patients had increased right ventricular diastolic diameter. There were no patients with abnormal ejection fraction. The pulmonary artery pressure [48 mmHg (46-90 mmHg) vs. 33 mmHg (20-50 mmHg) (1 mmHg = 0.133 kPa)], left ventricular diastolic diameter [46 mm (36-50 mm) vs. 47 mm (43-53 mm)] and fractional shortening rate [38.1% (36.0%-38.9%) vs. 35.4% (32.7%-37.8%)] of patients in the pre-fibrosis/early stage fibrosis group were higher than those in the obvious stage fibrosis group, and the differences were statistically significant (all P < 0.05). The pulmonary artery pressure of patients had positive correlations with age ( r = 0.590), serum ferritin (SF) ( r = 0.608), lactate dehydrogenase (LDH) ( r = 0.711) and soluble growth-stimulating expression gene 2 (ST-2) ( r = 0.580)(all P<0.05), and had negative correlation with platelet count ( r = -0.596, P = 0.003). Conclusion:PMF patients are prone to right heart hypofunction, the pulmonary artery pressure is higher in older patients and patients with high SF, LDH and ST-2 levels and low platelet count.

Background Papillary thyroid cancer is the result of a variety of pathogenic factors. The prevalence of papillary thyroid cancer varies greatly in different regions, and the disease is more harmful to women. Objective This study aims to explore the relationship between reproductive factors and papillary thyroid cancer, and to provide basic data for prevention and control of the disease. Methods A 1∶1 age (±3 years) matched case-control study was conducted in 331 pairs of newly confirmed papillary thyroid cancer cases and controls from two hospitals in Shanghai from November 2012 to December 2013. Comparisons were made in the history of menstruation, pregnancy, gynecological and breast diseases, and other variables between the two groups. Results The results of univariate analysis indicated that the proportions of education below bachelor degree, married, and mainly manual workers in the case group were significantly higher than those in the control group (P<0.05); the proportion of those with a family history of thyroid diseases in the case group was significantly higher than that in the control group (P<0.05); the proportions of the cases with irregular menstruation (77.34%), a history of using oral contraceptive or hormone drugs (24.77%), a history of benign gynecological diseases (31.72%), and a history of gynecological surgery (9.67%) were significantly higher than the proportions in the control group (P<0.05). After adjusting potential confounding factors such as history of CT examination, age, kinds of family salt, total iodine intake every day, education level, occupation, marital status, body mass index, and family history of thyroid diseases, the results of multiple logistic regression analysis showed that irregular menstruation (OR=1.767, 95%CI: 1.122-2.782; P=0.014), surgical menopause (OR=12.787, 95%CI: 3.202-51.057; P<0.001), pregnancy >1 time (OR =2.490, 95%CI: 1.196-5.184; P=0.015), and the history of using oral contraceptive or hormone drugs (OR=2.389, 95%CI: 1.338-4.268; P=0.003) were the risk factors of papillary thyroid cancer. Conclusion Irregular menstruation, surgical menopause, history of pregnancy, and history of using oral contraceptive or hormone drugs might be the risk factors of papillary thyroid cancer. To reduce the incidence of papillary thyroid cancer, strengthened health education and rational use of contraceptives are recommended.

Background There are few studies on the diet quality of patients with thyroid cancer, and the relationship between diet quality and thyroid cancer remains uncertain. Objective This study aims to assess the diet quality with the Chinese Health Diet Index (CHDI) and to explore the relationship between diet quality and papillary thyroid carcinoma (PTC). Methods A 1∶1 gender- and age-matched hospital-based case-control study included newly diagnosed PTC patients and matched controls from Shanghai Cancer Hospital and Renji Hospital (East) in Shanghai, China. A structured questionnaire was applied to collect data on general characteristics, history of diseases, dietary intakes, and lifestyles. Food intakes in the past one year were assessed using a validated food frequency questionnaire, from which the CHDI score was calculated. The CHDI, according to the Dietary Guidelines for Chinese Residents, was employed to evaluate the diet quality of the two groups. A multiple conditional logistic regression model was conducted to explore the relationship between diet quality and PTC. Results A total of 350 pairs of cases and controls were recruited. The overall median CHDI score of the cases was lower than that of the controls (67.8 vs. 73.4, P<0.001). The cases had lower median scores of fruits (6.8 vs. 9.5), dairy products (3.6 vs. 5.6), and soybeans (4.6 vs. 5.5) than the controls (P<0.05); the cases had a higher median score of refined grains than the controls (5.0 vs. 4.9), and the percentage of the cases that met diet recommendations for refined grains was higher than the percentage of the controls (65.4% vs. 48.6%) (P<0.05); the cases showed lower median scores of whole grains/beans/tubers, total vegetables, dark vegetables, and fish/shrimps (0.9 vs. 1.4, 3.1 vs. 4.4, 3.6 vs. 5.0, and 3.3 vs. 4.0, respectively), and the percentages of the cases meeting their diet recommendations were lower than the percentages of the controls (6.3% vs. 8.6%, 32.6% vs. 42.0%, 38.6% vs. 50.6%, and 34.0% vs. 40.3%, respectively, P<0.05). The results of multiple conditional logistic regression analysis suggested that qualified and good diet quality were associated with a reduced the risk of PTC (qualified diet quality, OR=0.37, 95%CI: 0.23−0.62; good diet quality, OR=0.19, 95%CI: 0.10−0.36); the statistical significance remained after excluding patients who had a history of benign thyroid conditions (qualified diet quality, OR=0.28, 95%CI: 0.15−0.52; good diet quality, OR=0.20, 95%CI: 0.09−0.43). Conclusion Those with qualified or good diet quality have a lower risk of PTC. PTC patients have insufficient intakes of fruits, dairy, soybeans, whole grains/beans/tubers, vegetables, and fish/shrimps.

Background Thyroid carcinoma is a serious threat to human health in Shanghai and a focus of cancer prevention and treatment. Objective This study aims to assess the relationship between foods rich in iodine and papillary thyroid carcinoma (PTC)．Methods In a hospital-based case-control study matched by gender and age (±3 years old), 402 pairs of cases (new incidences) and controls were included and studied. A validated questionnaire and food frequency questionnaire survey was conducted face to face to obtain demographic characteristics and dietary intake. A multiple conditional logistic regression model was applied to explore the relationship between foods rich in iodine (including seaweeds, kelp, and dried shrimps) and PTC. Results The mean age of the participants was (41.17±11.51) years in this study. Compared with the controls, more cases had a lower education and a manual occupation (P<0.05); more cases were overweight or obese, had a history of benign thyroid conditions, and had a family history of thyroid diseases (P<0.05); the two groups were different in the frequency of CT examination in the past ten years (P<0.05). The results of multiple conditional logistic regression analysis showed that consumption of iodine-rich foods was associated with a lower risk of PTC (for <1 time per week, OR=0.20, 95%CI: 0.12−0.35; for 1−2 times per week, OR=0.18, 95%CI: 0.10−0.33; for ≥3 times per week, OR=0.13, 95%CI: 0.04−0.44) (P<0.05). Specifically, those who consumed seaweeds (for <1 time per week, OR=0.18, 95%CI: 0.11−0.30; for 1−2 times per week, OR=0.11, 95%CI: 0.05−0.23; for ≥3 times per week, OR=0.15, 95%CI: 0.03−0.75), kelp (for <1 time per week, OR=0.28, 95%CI: 0.18−0.43; for ≤2 times per week, OR=0.24, 95%CI: 0.11−0.50), and dried shrimps (for <1 time per week, OR=0.44, 95%CI: 0.29−0.69; for ≤2 times per week: OR=0.34, 95%CI: 0.18−0.65) had a lower risk of PTC (P<0.05). After excluding patients who had a history of benign thyroid conditions, the favorable association remained significant among patients who had consumption of iodine-rich foods, seaweeds, shrimps, and kelp (P<0.05). Conclusion Less PTC patients consume iodine-rich foods than the controls.