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 compare the consistency of liquid chromatography-tandem mass spectrometry(LC-MS/MS)and fully auto-mated chemiluminescent immunoassay(CLIA)methods in measuring plasma aldosterone concentration(PAC)in the elderly patients in intensive care unit(ICU)and to explore the correlation between the levels of aldosterone(ALD)and blood biomarkers.Methods A total of 41 elderly ICU patients were included.PAC was measured using both LC-MS/MS and CLIA methods,followed by methodolo-gy validation and consistency comparison.Meanwhile,a retrospective analysis of the patients'clinical data was conducted,and the cor-relations between ALD and blood biomarkers were analyzed.Results The linear range of the LC-MS/MS method was 15 to 1 500 pg/mL,with a lower limit of quantification of 15 pg/mL.The inter-day and intra-day precisions were both less than 15％,and the re-covery rate was 94％to 99％,with no significant matrix effect.The PAC results detected by CLIA and LC-MS/MS methods were posi-tively correlated(r=0.762 7,P＜0.01),but the consistency between the two methods was poor.Deming regression analysis yielded the equation Y=0.969 6X-16.71,with a slope of 0.970(95％CI:0.890～1.049)and an intercept of-16.71(95％CI:-25.690 to-7.728).Bland-Altman analysis showed that CLIA overestimated PAC by an average of 21.18 pg/mL(95％CI:-25.89 to 68.26 pg/mL)compared to LC-MS/MS,with a bias of 24.02％.In the correlation analysis between ALD and blood biomarkers,ALD showed a significant positive correlation with myoglobin(Mb)(r=0.303,P＜0.05).Conclusion The LC-MS/MS method demonstrated good methodological performance in measuring PAC in the elderly patients in ICU.The consistency between LC-MS/MS and CLIA methods was poor,and the two methods should not be used interchangeably in clinical practice.There was a positive correlation between ALD and Mb,suggesting that ALD may be associated with myocardial injury.

OBJECTIVE To establish a method for the determination of propofol concentration in human plasma and apply it in patients with lymphedema. METHODS The concentration of propofol was determined by UPLC-MS/MS after protein precipitation of plasma samples using thymol as internal standard. The sample was eluted on a Kinetex C18 column with a mobile phase consisting of acetonitrile （A）-water （B） for gradient elution at the flow rate of 200 μL/min. The sample size was 5 μL， and the column temperature was set at 40 ℃. The sample chamber temperature was 15 ℃. Using multi-reaction monitoring mode， the ion pairs for quantitative analysis were m/z 177.0→161.2 （propofol） and m/z 149.0→133.1 （internal standard）， respectively. The above method was used to determine the plasma concentration of propofol in 6 patients with lymphedema. RESULTS The linear range of propofol was 50-5 000 ng/mL （r＝0.995 0）. RSDs of within- and between-batch precision were not more than 8.08%； no endogenous interference， carryover effect， or dilution effect was observed in blank plasma. The extraction recovery ranged from 89.80% to 93.73%， and matrix effects were within the range of 97.93%-101.73%. RSDs of the stability test were all lower than 3.27%. During intraoperative TCI 2-30 min， the plasma concentration of propofol in 6 patients was maintained in the range of 1 865.3-6 056.2 ng/mL， and the propofol was almost excreted within 4-8 h after operation. CONCLUSIONS The established UPLC-MS/MS method in this study can achieve the determination of propofol and a simple and fast sample pretreatment process without derivatization； it is proved to be suitable for the concentration monitoring of propofol in plasma samples of patients with lymphedema.

OBJECTIVE To investigate the impact of the methionine synthase reductase （MTRR） rs10380 C＞T gene polymorphism on methotrexate （MTX） plasma concentration， adverse drug reaction， and prognosis in children with intracranial tumors. METHODS Peripheral blood was collected from children with intracranial tumors， and genomic DNA was extracted. The MTRR rs10380 C＞T genotype was analyzed using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry. The association of the MTRR rs10380 C＞T gene polymorphism with the ratio of MTX plasma concentration to dose （C/D ratio）， adverse drug reaction， tumor recurrence， and metastasis was analyzed. Bioinformatics analysis was used to explore the association of the rs10380 genotype and MTRR gene expression and its possible mechanisms. RESULTS A total of 75 children were included in the study. The distribution frequencies of the wild-type CC genotype and C allele of rs10380 were 62.67% and 81.33%， respectively， while the distribution frequencies of the variant CT genotype and T allele were 37.33% and 18.67%， respectively， which were in accordance with Hardy-Weinberg equilibrium（P＞0.05）. The incidence of electrolyte disorders （51.06%） and tumor metastasis rate （57.45%） in children with the CC genotype were significantly higher than those with the CT genotype （P＜0.05）. No significant differences were observed in the 24-hour and 42-hour C/D ratios and recurrence rates between the two genotypes of children （P＞0.05）. Bioinformatics analysis showed that MTRR protein mainly works in conjunction with 10 proteins， including MMAA， and was involved in various biological processes such as sulfur amino acid biosynthesis. CONCLUSIONS The MTRR rs10380 CC genotype may be a risk factor for electrolyte disorders and tumor metastasis in children with intracranial tumors after MTX chemotherapy.

ObjectiveTo evaluate the changes of the usage of oil， salt， sugar and nutritional knowledge and behavior intervention among diners before and after the establishment of healthy canteens and restaurants in Shanghai. MethodsA comprehensive intervention was conducted through the establishment of healthy canteens and restaurants， encompassing interventions such as oil， salt， and sugar management， improvement of nutritional environment， staffing and training activities， and nutrition labeling guidance. A pre-post self-controlled study design was used to compare changes in oil， salt and sugar usage， as well as diners’ knowledge and behaviors related to nutrition and nutrition labeling， before and after the intervention. ResultsAfter intervention， the total usage of oil， salt， and sugar per meal in the canteens and restaurants decreased by 18.33%， 14.83%， and 13.66%， respectively，and all had statistically significance differences（P<0.001）. The awareness rate of "cooking oil intake"， "salt intake"， and "added sugar intake" among diners increased from 24.07% to 38.04%， 58.52% to 71.28%， and 26.85% to 45.01%， respectively. The awareness rate of "daily food types" and "weekly food types" increased from 43.07% to 56.53% and 49.52% to 64.32%， with significant differences （P<0.001）. The rate of understanding the content of nutrition labels increased from 66.91% to 76.90%， the awareness rate of nutrition labels increased from 53.59% to 69.06%， the rate of active reading of nutrition labels among diners increased from 73.38% to 81.23%， and the rate of selecting and purchasing food based on the information of nutrition labels increased from 69.27% to 77.79%， all of which were statistically significant （P<0.001）. ConclusionThe comprehensive interventions carried out through the creation of healthy canteens and restaurants have significantly impact on usage of oil， salt， and sugar， as well as on the nutritional knowledge and behaviors of diners.

OBJECTIVE To compare the safety of high-dose methotrexate （HD-MTX） via peripherally inserted central catheter （PICC） and totally implantable venous access port （TIVAP） in pediatric patients with malignant brain tumors. METHODS Patients with malignant brain tumors who received HD-MTX via PICCs or TIVAPs in our hospital from July 2018 to April 2022 were retrospectively analyzed. Clinical data were collected to compare differences in blood concentration of methotrexate （MTX），the incidence of adverse events （including adverse drug reactions and catheter-related complications） and length of stay in hospital. Multivariate linear regression was applied to analyze the factors that influenced the blood concentration of MTX. RESULTS A total of 107 patients were included in the study，with 65 patients in the PICC group and 42 patients in the TIVAP group. Blood concentration of MTX at 24 h （C24 h） in TIVAP group was significantly higher than PICC group （[ 126.87±61.99） μmol/L vs. （102.45±48.77） μmol/L，P＜0.05）. There was no significant difference in blood concentration of MTX at 42 h （C42 h），compared with PICC group （P＞0.05）. Results of multivariate linear regression analysis showed that TIVAP was associated with the increase of C24 h（P＜0.05）. No significant differences were observed in the incidence of adverse events and the length of stay in the hospital between 2 groups （P＞0.05）. CONCLUSIONS Risk of adverse events is not increased，although the MTX C24 h level is elevated after administration of TIVAP. TIVAP is a safe choice for HD-MTX therapy with implementing therapeutic drug monitoring.

Background The retail milk tea industry is in a period of rapid development, but there is little research on its nutrient content, which restricts the nutritional guidance of milk tea. Objective To determine the levels of nutrients in best-selling handcrafted milk tea in Shanghai and analyze the nutritional characteristics. Methods In 2018 and 2021, a total of 13 handcrafted milk tea brands with ≥3 branch stores in Shanghai were selected by searching for milk tea on Meituan and Ele.me food delivery platforms, and a total of 122 types of handcrafted milk tea products were collected from the top three sales [milk tea (including all sweetness levels available), milk cover tea, and fruit tea]. National standard methods were used to detect energy, protein, fat, carbohydrate, sugar, trans fatty acid, calcium, caffeine, and tea polyphenol. Results The median energy of the milk tea samples was 310 kJ (per 100 g sample). The main sources of energy were carbohydrate and fat. The levels of energy, protein, and fat in milk cover tea and milk tea were significantly higher than those in fruit tea (P＜0.05), and there was no significant difference in carbohydrate among them. The total sugar, fructose, and glucose levels in milk tea were significantly lower than those in milk cover tea and fruit tea, and the lactose level in fruit tea was significantly lower than those in milk tea and milk cover tea (P＜0.05). Themedian trans fat acid level in milk cover tea was higher than that in milk tea (P＜0.05). The median levels of caffeine and tea polyphenol were higher in milk tea than in milk cover tea (P＜0.05). The levels of energy, carbohydrate, sucrose, total sugar, and calcium in milk tea were positively correlated with the number of ingredients added (0-3) (r=0.386, 0.371, 0.238, 0.698, 0.466, respectively, P < 0.05). The levels of energy, carbohydrate, and total sugar tended to increase with increasing sweetness (P<0.05), and total sugar was mainly sucrose, followed by fructose and glucose. The total sugar levels of the samples labeled sugar free, light sugar, half sugar, less sugar, and regular sugar were 3.40 (2.20, 4.9), 4.97 (4.25, 5.97), 5.80 (4.31, 6.88), 6.59 (5.17, 8.53), and 7.96 (6.82, 9.20) g, respectively; the proportions of the samples containing more than 0.5 g of total sugar were 93.3% for sugar free milk tea, 47.4% for light sugar milk tea, and 94.0% for regular sugar milk tea; the proportion of the regular sugar samples with sugar content greater than 10 g was 18.0% (all samples with nominal sugar content were measured per 100 g). Conclusion The retail handcrafted milk tea in Shanghai is characterized by high energy, high added sugar, high fat, and low protein. It is necessary to standardize the added sugar content and sweetness labeling, strengthen the nutrition education of milk tea, and guide residents to limit its intake.

Background Children and adolescents drink sugar-sweetened beverages (SSBs) frequently. Research has confirmed that SSBs associate with weight gain and overweight or obesity. However, it is unclear whether high SSBs intake associates with abnormal changes in physical growth and glucolipid metabolism before causing adverse health outcomes such as overweight and obesity. Early identification of associated health risks of overconsumption of SSBs have important public health implications. Objective To investigate the differences in physical growth and glucolipid metabolism between different SSBs intake frequency groups in normal weight children and adolescents aged 6-17 years, and to evaluate the early effects of SSBs intake on physical growth and glycolipid metabolism before causing overweight and obesity, aiming to provide a scientific basis for the prevention and control of childhood overweight and obesity and related chronic diseases, and for the formulation of policies on the control of SSBs consumption. Methods Data were from the Shanghai Diet and Health Survey (SDHS) among primary and secondary school students. The participants were normal weight children and adolescents aged 6-17 years. Propensity scores were calculated according to energy intake and physical activity factors, after stratifying by age and gender. Participants were 1:1 matched with the closest propensity scores in the high-frequency (≥1 time·d⁻¹) and the low-frequency (≤1 time·week⁻¹) SSBs intake groups. The outcome indicators were physical measurements such as height, weight, percent of body fat, and waist circumference, and metabolic indicators such as fasting blood glucose, total triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Body mass index (BMI) was calculated. Food frequency questionnaire was used to collect SSBs consumption in the past three months through face-to-face interview. A paired t-test was used to compare the differences in physical and glycolipid metabolic indicators between the high-frequency intake group and the low-frequency intake group of SSBs. Results A total of 431 pairs were obtained. For children and adolescents in grades 6-9, overall height (difference=2.92 cm, P=0.002), weight (difference=2.53 kg, P=0.003), and waist circumference (difference=1.34 cm, P=0.035) were higher in those who consumed SSBs ≥1 time·d⁻¹ than in those who consumed ≤1 time·week⁻¹. For children and adolescents in grades 10-12, overall weight (difference=2.27 kg, P=0.041) was higher in those who consumed SSBs ≥1 time·d⁻¹ than in those who consumed ≤1 time·week⁻¹. Over 95% of the study subjects reported blood glucose and lipid test results within the normal range; but girls in grades 1-5 who consumed SSBs ≥1 time·d⁻¹ had a higher total cholesterol (difference=0.20 mmol·L⁻¹, P=0.027) and low-density lipoprotein cholesterol (difference=0.19 mmol·L⁻¹, P=0.010) than those who consumed ≤1 time·week⁻¹; boys in grades 6-9 who consumed SSBs ≥1 time·d⁻¹ had a lower high-density lipoprotein cholesterol (difference=-0.10 mmol·L⁻¹, P=0.039) than those who consumed ≤1 time·week⁻¹. Conclusion High-frequency intake of SSBs may be associated with higher total cholesterol and low-density lipoprotein cholesterol in normal weight children and adolescents in grades 1-5, and higher weight in normal weight children and adolescents in grades 6-12. There is an urgent need to educate children and adolescents about nutritional health, enhance their ability to make healthy food and beverage choices, and take early interventions to control the intake of SSBs in children.

Sugar reduction and restriction have become one of the most urgent health demands as the number of obese people increases globally. Sugar substitutes (mainly classified into sugar alcohols, natural sweeteners, and artificial sweeteners) have been widely used in food processing as alternatives to sugar for their low energy and high sweetness. Thus, the classification, metabolism pathways, advantages, applications, and human health effects of sugar substitutes, their effects on human health were introduced, and the relationships between sugar substitutes and obesity, diabetes, intestinal microbes, hypertension, and all-cause mortality were emphatically summarized in this paper. Generally, long-term high intake of sugar substitutes is associated with adverse health outcomes such as elevated blood pressure, higher risks of diabetes, cancer, and increased all-cause mortality. Meanwhile, sugar alcohols and natural sweeteners are more likely to associate with beneficial effects on human gut microbial diversity, while artificial sweeteners associate with imbalance of gut microbiota based on available evidence. Current published research focuses on single sugar substitute exposure with varied health effects, while nearly half of commercial sugar substitute products contain two or more sugar substitutes. The effects of exposure to multiple sugar substitutes on human health are not clear yet, so further strengthening the relevant epidemiological and molecular mechanism research is necessary.

Background::The epidemic of overweight and obesity has become a worldwide public health problem. Cardiometabolic diseases may originate in childhood. We investigated the association between percent body fat (PBF) measured by the bioelectrical impedance assay and cardiometabolic risk (CMR) in pediatrics.Methods::This cross-sectional study involved 3819 subjects (6–17 years old) in Shanghai. We assessed the association between PBF and body mass index (BMI) with multiple CMR factors. We examined the risk for cardiometabolic abnormalities attributable to overweight and obesity based on age- and sex-specific PBF Z-scores and BMI Z-scores, respectively. Results::PBF, but not BMI, was positively associated with multiple CMR factors in males and females except for total cholesterol in females (all p < 0.05). Compared with the non-overweight group based on PBF, over-weight and obese subjects had increasingly higher odds ratio of dyslipidemia (2.90 (1.99–4.23), 4.59 (2.88–7.32) for males and 1.82 (1.20–2.75), 2.46 (1.47–4.11) for females) and elevated blood pressure (BP) (3.26 (2.35–4.51), 4.55 (2.92–7.09) for males and 1.59 (1.07–2.34), 3.98 (2.27–6.17) for females). Obesity females showed a higher likelihood for hyperglycemia (2.19 (1.24–3.84)) than non-overweight females. In both sexes, the predictive effect of PBF on dyslipidemia and elevated BP in adolescents was better than that in children. For hyperglycemia, the predictive effect of PBF was better in male adolescents and female children. There was no risk difference for cardiometabolic abnormalities attributable to BMI-based obesity categories. Conclusions::PBF but not BMI was associated with CMR. Overweight and obesity categories based on PBF had an increased risk for cardiometabolic abnormalities in children and adolescents.