Objective:To explore the effect of tyrosine kinase inhibitor (TKI) dose reduction regimen in patients with chronic-phase chronic myeloid leukemia (CML) and its prognostic impact.Methods:A retrospective cohort study was conducted. The clinical data of patients with chronic-phase CML treated with reduced-dose TKI in the First Affiliated Hospital of Soochow University between January 2018 and December 2022 were collected. Patients were divided into groups based on Sokal score, European Treatment and Outcome Study long-term survival (ELTS) score, TKI drug classification and dose reduction, and treatment phase. The overall survival (OS), the cumulative incidence of major molecular response (MMR), the cumulative molecular recurrence rate and event-free survival (EFS) among patients in different strata were compared. Kaplan-Meier method was used for survival analysis.Results:Among 154 patients with chronic-phase CML, the median duration [ M ( IQR)] of reduced-dose TKI therapy was 35.4 months (34.9 months); Sokal score high-risk and low-/intermediate-risk groups comprised 20 cases (12.99%) and 134 cases (87.01%), respectively; ELTS score high-risk and low-/intermediate-risk groups comprised 14 cases (9.09%) and 140 cases (90.91%), respectively. Among 154 patients, 83 cases (53.90%) received imatinib therapy, while 71 cases (46.10%) received second-generation TKI; 138 patients (89.61%) maintained stable TKI dosing at the first dose level, and 16 patients (10.39%) maintained it at the second dose level. The induction therapy group comprised 33 patients (21.43%), while the maintenance therapy group included 121 patients (78.57%). The 3-year OS rate of all 154 patients was 90.6%. Patients in the Sokal score high-risk group demonstrated a lower 3-year OS rate compared to those in the low-/intermediate-risk group (64.1% vs. 96.7%) ( P < 0.001); patients in the ELTS score high-risk group had a lower 3-year OS rate compared to those in the low-/intermediate-risk group (62.9% vs. 95.8%) ( P = 0.002). There was no statistically significant difference in the 3-year OS rate of patients receiving the first dose level and those receiving the second dose level (90.6% vs. 90.0%, P = 0.478); there was no statistically significant difference in the 3-year OS rate of the induction therapy group and the maintenance therapy group (88.9% vs. 91.4%, P = 0.868). Among the 33 patients in the induction therapy group, all received the first dose level. After treatment, 28 achieved MMR, and 2 achieved molecular response 4.0 (MR4.0). The cumulative 1-year MMR rate of all patients in reduction therapy group was 95.8%, with a median time to MMR of 8.4 months; patients in the high-risk Sokal score group had a 1-year cumulative MMR rate of 50.0%, which was lower than that of the low-/intermediate-risk group (95.3%) ( P = 0.014); the median time to MMR was 14.7 months and 7.8 months, respectively. The cumulative 1-year MMR rate of patients treated with first-generation TKI was lower than that in those treated with second-generation TKI (65.0% vs. 100.0%, P = 0.034), and the median time to MMR of patients treated with first-generation TKI was longer than that those treated with second-generation TKI (9.1 months vs. 6.9 months). Among the 149 patients who achieved MMR, 5 experienced molecular relapse, resulting in a 3-year cumulative molecular relapse rate of 8.3%. In the Sokal score low-/intermediate-risk group, the 3-year cumulative molecular relapse rate (1.5% vs. 39.8%, P < 0.001), EFS rate (92.3% vs. 57.1%, P < 0.001), and OS rate (100.0% vs. 62.8%, P < 0.001) were better than those in the Sokal score high-risk group. The 3-year cumulative molecular relapse rate and 3-year EFS rate in patients receiving first dose level therapy were better than those in patients receiving second dose level therapy, and the differences were statistically significant (all P < 0.001). Conclusions:Patients with chronic-phase CML can still obtain good outcomes when receiving dose-reduced TKI, while the prognosis of patients in high-risk group is relatively poor. The choice of TKI and the dosage reduction should be individualized based on patients' characteristics.

Objective:To systematically evaluate the global disease burden of neonatal sepsis and other neonatal infections（NSNIs），providing scientific basis for their prevention and control.Methods:Using the Global Burden of Disease（GBD）2021 database，this article calculated the incidence，mortality，and age-standardized rates for NSNIs. Trends were evaluated with Joinpoint regression model，and compared at different socio-demographic index（SDI）levels.Results:From 1990 to 2021，the global age-standardized incidence rate（ASIR）of NSNIs decreased from 78.98 to 62.70 per 100 000 with an with average annual percentage change（AAPC）of -0.73%（ P<0.01）. The age-standardized mortality rate（ASMR）declined from 4.77 to 3.76 per 100 000 with an AAPC of -0.76%（ P<0.01）. In particular，the disease burden was consistently higher among male neonates. Low birth weight was the primary risk factor globally，followed by preterm birth. Regions with lower SDI levels exhibited higher ASIR and ASMR，and household solid fuel air pollution contributed more to NSNIs-related mortality. Conclusion:Although the overall disease burden of NSNIs has declined，male neonates and low-SDI regions still face substantial challenges. Continuous efforts to improve air quality are warranted，and low-SDI regions should further strengthen healthcare infrastructure to enhance diagnostic and treatment quality.

Objective: To analyze the disease burden and risk factors of colorectal cancer in Zhejiang Province from 1990 to 2019, so as to provide the basis for prevention and control of colorectal cancer. Methods: Based on data of 2019 Global Burden of Disease (GDB 2019), disease burden and risk factors of colorectal cancer in Zhejiang Province from 1990 to 2019 was assessed using years of life lost (YLL), years lived with disability (YLD), disability-adjusted life years (DALY). Results: In 2019, the YLL rate, YLD rate and DALY rate caused by colorectal cancer in Zhejiang Province were 496.15/105, 31.81/105 and 527.96/105, respectively. From 1990 to 2019, the YLL rate, YLD rate and DALY rate caused by colorectal cancer in Zhejiang Province increased by 114.90%, 482.60% and 123.38%, respectively, showing increasing trends (average annual percent change values were =2.663, 6.283 and 2.800, respectively,all P<0.05). From 1990 to 2019, the YLL rate, YLD rate and DALY rate in the age groups of 15 to 49 years, 50 to 69 years and 70 years and older showed increasing trends (all P<0.05). In 1990, the top ten risk factors for colorectal cancer in Zhejiang Province were diet low in calcium, diet low in milk, diet low in whole grains, smoking, alcohol use, low physical activity, high fasting plasma glucose, diet high in red meat, diet low in fiber and high body mass index. In 2019, the top ten risk factors for colorectal cancer in Zhejiang Province were diet low in milk, diet low in whole grains, diet low in calcium, alcohol use, diet high in red meat, high body mass index, high fasting plasma glucose, low physical activity, diet low in fiber and diet high in processed meat. Conclusions The disease burden of colorectal cancer in Zhejiang Province showed an upward trend from 1990 to 2019. The top ten risk factors for colorectal cancer remained between 1990 and 2019, while there was a slight change in ranking.

Breast milk is an ideal source of nutrition for the growth and development of infants. The study of metabolomics integrates holistic and dynamic technological approaches, which offers practical feasibility for the analysis of small molecular metabolites in breast milk, including their composition, structure, functionality, as well as their relationship with maternal and infant health. This article provides an overview of the origins and development of breast milk metabolomics, influencing factors, and the relationship between breast milk metabolites and the health of the offsprings.

Acute necrotizing encephalopathy (ANE) is a rare but deadly complication with an unclear pathogenesis. We aimed to elucidate the immune characteristics of H1N1 influenza virusassociated ANE (IANE) and provide a potential therapeutic approach for IANE. Seven pediatric cases from a concentrated outbreak of H1N1 influenza were included in this study. The patients’ CD4+T cells from peripheral blood decreased sharply in number but highly expressed Eomesodermin (Eomes), CD69 and PD-1, companied with extremely high levels of IL-6, IL-8 in the cerebrospinal fluid and plasma. Patient 2, who showed high fever and seizures and was admitted to the hospital very early in the disease course, received intravenous tocilizumab and subsequently showed a reduction in temperature and a stable conscious state 24 h later. In conclusion, a proinflammatory cytokine storm associated with activated CD4+T cells may cause severe brain pathology in IANE. Tocilizumab may be helpful in treating IANE.

Objective To explore the therapeutic effects of estrogen-intervened endothelial progenitor cells( EPCs) transplantation on diabetic ischemic stroke rats. Methods PKH26-labeled diabetic EPCs and estrogen-intervened diabetic EPCs were injected into rats via the tail vein 24 h after cerebral ischemia. Cerebral ischemic volume, behavioral changes, ischemic site vascularization and homing of EPCs were measured 3 d after EPCs injection. Results Compared with diabetic ischemic rats, estrogen-intervened EPCs transplantation had reduced infarct volumes, improved behavioral scores and ischemic site revascularization and promoted homing of EPCs to sites of injury(P<0.05). Conclusion Estrogen-intervened EPCs transplantation had a better therapeutic effect on diabetic ischemic stroke by promoting EPCs homing to injury site and EPCs-medicated neovascularization .

Landfill is one of the important sources of carbon tetrachloride (CT) pollution, and it is important to understand the degradation mechanism of CT in landfill cover for better control. In this study, a simulated landfill cover system was set up, and the biotransformation mechanism of CT and the associated micro-ecology were investigated. The results showed that three stable functional zones along the depth, i.e., aerobic zone (0-15 cm), anoxic zone (15-45 cm) and anaerobic zone (> 45 cm), were generated because of long-term biological oxidation in landfill cover. There were significant differences in redox condition and microbial community structure in each zone, which provided microbial resources and favorable conditions for CT degradation. The results of biodegradation indicated that dechlorination of CT produced chloroform (CF), dichloromethane (DCM) and Cl^- in anaerobic and anoxic zones. The highest concentration of dechlorination products occurred at 30 cm, which were degraded rapidly in aerobic zone. In addition, CT degradation rate was 13.2-103.6 μg/(m²·d), which decreased with the increase of landfill gas flux. The analysis of diversity sequencing revealed that Mesorhizobium, Thiobacillus and Intrasporangium were potential CT-degraders in aerobic, anaerobic and anoxic zone, respectively. Moreover, six species of dechlorination bacteria and eighteen species of methanotrophs were also responsible for anaerobic transformation of CT and aerobic degradation of CF and DCM, respectively. Interestingly, anaerobic dechlorination and aerobic transformation occurred simultaneously in the anoxic zone in landfill cover. Furthermore, analysis of degradation mechanism suggested that generation of stable anaerobic-anoxic-aerobic zone by regulation was very important for the harmless removal of full halogenated hydrocarbon in vadose zone, and the increase of anoxic zone scale enhanced their removal. These results provide theoretical guidance for the removal of chlorinated pollutants in landfills.
Bacteria/metabolism* ; Biodegradation, Environmental ; Carbon Tetrachloride/metabolism* ; Methane/metabolism* ; Waste Disposal Facilities

Temporomandibular disorders (TMD), characterized by pain and dysfunction of the temporomandibular joint, are the most common chronic orofacial pain. However, the etiologies and pathologies of TMD related chronic pain are poorly understood. Functional magnetic resonance imaging (fMRI) measures brain activity by detecting changes associated with blood flow without invasiveness, and has been widely used in chronic pain research. We reviewed recent fMRI studies exploring the brain changes of patients with painful TMD to investigate the role of central nervous system in abnormal pain perception and impaired pain modulation, and to summarize the effects of splint therapy, in the hope of facilitating the clinical diagnosis and treatment of TMD.

OBJECTIVE:To study the mechanism of Aurantii fructus immaturus(AFI)and its main active ingredients in pro-moting gastrointestinal motility of model rats with spleen deficiency. METHODS:170 rats were randomly divided into blank group (10 rats) and modeling group (160 rats),rats in modeling group was induced models with spleen deficiency by bitter cold diar-rhea+irregular diet. After modeling, rats were randomly divided into model group, naringin (NA) low-dose, medium-lose, high-dose groups(3.267,6.535,13.070 mg/mL),neohesperidin(NE)low-dose,medium-lose,high-dose groups(3.865,7.730, 15.460 mg/mL),synephrine(SY)low-dose,medium-lose,high-dose groups(0.252,0.504,1.008 mg/mL),compatibility groups with 3 monomer ingredients (NA-NE-SY) low-dose,medium-lose,high-dose and AFI water decoction low-dose,medium-lose, high-dose groups(0.104,0.208,0.416 g/mL,calculated by crude drug),ig,once a day,10 mL/kg,for 7 d. After the last admin-istration,gastrin (GAS) in serum,and acetylcholine (ACh),motilin (MTL),substance P (SP),vasoactive intestinal peptide (VIP)levels in plasma were detected. RESULTS:Compared with blank group,GAS level in serum and ACh,MTL,SP levels in plasma in model group were reduced(P<0.01),VIP level in plasma was increased(P<0.05). Compared with model group,ex-cept for the GAS level in serum showed no obvious change in NA high-dose group and SY doses groups,other medicine groups were obviously increased (P<0.05 or P<0.01);the ACh levels in serum were obviouly increased in NE high-dose group,SY high-dose group and AFI water decoction low-dose group(P<0.01). MTL levels in plasma were obviously increased in NE medi-um-dose,high-dose groups,SY high-dose group,compatibility low-dose,medium-dose groups and AFI water decoction medi-um-dose,high-lose groups (P<0.05);SP levels in plasma were obviously increased in NA low-dose,medium-dose groups and NE doses groups(P<0.05 or P<0.01);VIP levels were reduced in NA low-dose group,SY high-dose group and AFI water decoc-tion low-dose,medium-lose groups(P<0.05). CONCLUSIONS:AFI may promote the gastrointestinal motility of model rats with spleen deficiency by promoting the secretion of GAS,ACh,MTL,and inhibiting the secretion of VIP;there are differences be-tween AFI and the 3 monomer ingredients in regulation of gastrointestinal hormones.

Objective To study the pain controlling effects of non-pharmaceutical interventions in neonatal intensive care unit (NICU) setting. Methods Infants who received radial artery puncture were assigned into control group, non-nutritive sucking (NNS) group and NNS plus glucose (NNS + GS) group according to their admission sequences. Each group contained 20 patients. Heart rate ( HR), respiratory rate (RR) and oxygen saturation (SpO2 ) before and after the procedure were monitored using Multi-Parameter Monitor ECG. Neonatal pain was evaluated using the preterm infant pain profile (PIPP). Results Among all three groups, after radial artery puncture, HR and RR were significantly increased, and SpO2 was significantly decreased (P < 0. 01). HR, RR and SpO2 variations in NNS group and NNS + GS group were less significant than the control group (P < 0. 05), and recovered to baseline more quickly. During the radial artery puncture, PIPP scores of infants in NNS and NNS + GS group were significantly lower than the control group (P < 0. 01), with NNS + GS group lower than NNS group (P <0. 05). Conclusions HR, RR and SpO2 can be used as physiological indicators of neonatal pain. PIPP score is simple and practical to be used in NICU setting. Both NNS and NNS + GS can partially relieve neonatal pain, and NNS + GS works better.