Objective To investigate the drug-drug interaction between donepezil hydrochloride and moxifloxacin hydrochloride during combined administration through in vitro liver microsomal metabolism and changes in pharmacokinetic characteristics in rats.Methods A rat liver microsomal incubation system was constructed and optimized.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis of donepezil hydrochloride and high-performance liquid chromatography(HPLC)analysis of moxifloxacin hydro-chloride were performed.The pharmacokinetic and metabolic characteristics of the two drugs,alone and in combination,were compared in vitro using rat liver microsomes and in vivo using rats.Results In the liver microsomal system,the half-life(T1/2)of donepezil hydro-chloride in the combined administration 1 group was prolonged by 29.892％(P＜0.01)and the intrinsic clearance(CLint)was reduced by 23.194％(P＜0.01)compared with the donepezil hydrochloride group.Conversely,the metabolic parameters of moxifloxacin hydrochlo-ride in the combined administration 2 group did not differ significantly from that of the moxifloxacin hydrochloride group(P＞0.05).In the in vivo study,the AUC0～t and AUC0～∞ of donepezil hydrochloride in the combined administration 1 group increased by 44.259％and 44.496％,respectively,maximum plasma concentration(Cmax)increased by 117.723％,T1/2 was prolonged by 98.063％,and CLint was reduced by 35.293％,compared with that in the donepezil hydrochloride group.Moreover,the differences were all statistically significant(P＜0.05).The in vivo study findings were consistent with the results of the in vitro study.Conclusion A drug-drug interaction occurs when moxifloxacin hydrochloride is used in combination with donepezil hydrochloride.Moxifloxacin hydrochloride promotes the absorption of donepezil hydrochloride,inhibits its metabolism,slows its CLint,and increases donepezil exposure in the body.

Objective:To investigate the efficacy and safety of glofitamab in the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 11 patients with relapsed/refractory DLBCL who were treated with glofitamab in Sichuan Provincial People's Hospital from March 2024 to October 2024 were retrospectively analyzed. All patients received glofitamab monotherapy. Dose escalation was required in the first course, and glofitamab at a dose of 30 mg was administered from the second to the 12th course. The general data, clinical manifestations, laboratory examination results, Eastern Cooperative Oncology Group (ECOG) performance score, previous treatment history, therapeutic effect after medication and adverse reactions were collected.Results:Among 11 patients, there were 8 males and 3 females, with the median age [ M ( Q1, Q3)] of 60 (51, 76) years; 1 case was primary central nervous system DLBCL. The median number of prior treatment lines was 3 (2, 3) lines, and 6 cases received ≥3 lines of therapy; 1 case was double DLBCL and 3 cases was complicated with p53 mutations. The median follow-up time was 5 months (2-7 months). After treatment of the median number of glofitamab, 3 cases achieved complete remission, among which 1 case successfully bridged to autologous hematopoietic stem cell transplantation; 1 case had the stable disease and 7 cases achieved partial remission. Grade 1-2 adverse events included mild leukopenia in 3 patients, mild anemia in 4 patients, thrombocytopenia in 1 patient, and lymphopenia in 8 patients. Grade 3 hematologic adverse events included thrombocytopenia in 1 patient and severe lymphopenia in 1 patient. Non-hematological toxicities included mild rash in 1 patient, grade 1 liver dysfunction in 3 patients and inflammatory factor storm in 4 patients. No medication stop or deferral was found in patients due to severe adverse events. Conclusions:Glofitamab demonstrates a high response rate in the treatment of relapsed/refractory DLBCL, with manageable adverse events and a favorable safety.

Objective To investigate differential patterns of oxygenated hemoglobin concentration in prefron-tal cortical regions between major depressive disorder patients with or without psychotic symptoms during verbal flu-ency task(VFT)performance using functional near-infrared spectroscopy(fNIRS).Methods A total of 108 pa-tients with major depression who were hospitalized in the psychiatric department of the hospital from July 2023 to April 2024 were selected as the study objects.They were divided into two groups(n=60)with or without psychotic symptoms(n=48).fNIRS devices were used to measure and compare the changes in the relative concentration of cerebral hemoglobin in 52 brain channels between the two groups during VFT.Re-sults Compared with the unaccompanied group,the relative concentration of cerebral oxygenated hemoglobin in channel 13 was higher(0.003±0.001 vs.0.002±0.001),and the relative concentration of cerebral oxygen-ated hemoglobin in channel 33 was lower(0.003±0.001 vs.0.007±0.002),the difference was statistically significant(P＜0.05).There was no significant difference in the relative concentration of oxygenated hemo-globin in other brain areas between the two groups(P＞0.05).Conclusion There are abnormal oxygen activ-ity in brain functional areas associated with psychotic symptoms,and fNIRS technique is helpful for early as-sessment of cerebral aerobic function in depressed patients with psychotic symptoms.

Objective:To investigate the association of monocyte-to-high-density lipoprotein cholesterol ratio (MHR) with the severity of white matter hyperintensities (WMHs) and its spatial distribution.Methods:Patients admitted to the Department of Neurology, Jiangning Hospital Affiliated to Nanjing Medical University due to various chronic diseases or physical examinations between January 2023 and December 2024 were included retrospectively. Past medical history, clinical and imaging data were collected. The Fazekas scale was used to assess the severity of WMHs. According to the scoring results of periventricular WMHs (PVWMHs) and deep WMHs (DWMHs), WMHs were divided into no/mild group (0-1 points) and moderate/severe group (2-3 points). Multivariate logistic regression analysis was used to determine independent correlation factors for the severity of WMHs, PVWMHs, and DWMHs. Results:A total of 357 patients were included, aged 65.42±9.95 years, with 198 males (55.5%). There were 193 patients (54.1%) in the no/mild group and 164 (45.9%) in the moderate/severe group. Univariate analysis showed that the proportion of patients with hypertension, diabetes, history of cerebral infarction and cerebral hemorrhage, carotid plaque, and age, serum creatinine, monocyte count and MHR in the moderate/severe group were significantly higher than those in the no/mild group (all P<0.05). Multivariate logistic regression analysis showed a significant positive correlation between MHR and the severity of WMHs (odds ratio 3.138, 95% confidence interval 1.042-9.451; P=0.042). Further analysis showed a significant positive correlation between MHR and PVWMHs (odds ratio 3.384, 95% confidence interval 1.111-10.305; P=0.032), but no independent correlation with DWMHs. In addition, age and hypertension, diabetes, history of cerebral infarction and cerebral hemorrhage were significantly positively correlated with the severity of WMHs, PVWMHs and DWMHs. Conclusion:MHR is correlated with the severity of WMHs, and higher MHR is significantly associated with PVWMHs, but not with DWMHs.

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Infectious diseases continue to pose a threat to global public health. Successive global shocks caused by emerging and re-emerging pathogens have continuously challenged existing surveillance systems, highlighting the urgent need to build efficient and precise pathogen surveillance networks. Pathogen genomic databases have been developed rapidly in recent two decades, significantly improving the molecular identification, evolutionary analysis, and transmission tracking of pathogens, and changing disease surveillance strategies and patterns. This paper summarizes the developmental history and current state of pathogen genomic databases, and discusses their applications in public health, including pathogen variation surveillance, emerging or suspected pathogen identification, and epidemiological tracing. Furthermore, this paper systematically analyzes the limitations and key challenges faced by current global health prevention and control system, and suggests the focus of the development of online pathogen databases to address existing shortcomings, ultimately improve global infectious disease surveillance and early warning

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Objective To evaluate the dosimetric impact of interfractional bladder fullness variation in volumetric modulated arc therapy for cervical cancer using artificial intelligence-assisted cone-beam CT(CBCT)image segmentation,and propose an imaging-based quantitative assessment criterion for bladder fullness,providing an objective basis for assessing bladder filling status during clinical treatment.Methods Fifty patients receiving volumetric modulated arc therapy for cervical cancer were selected.The criterion for determining bladder fullness was as follow:if the bladder longitudinal diameter measured on the CBCT mid-sagittal plane was greater than half of the bladder longitudinal diameter measured on the localizable CT,it was defined as≥50%bladder fullness;otherwise,it was defined as<50%bladder fullness.Based on this criterion,two CBCT images were selected for each patient(representing fractions with≥50%and<50%fullness,respectively).Borui auto-contouring system was applied to re-contour the target areas and organs at risk,followed by dose recalculation.Results Compared with≥50%bladder fullness group,<50%bladder fullness group had significantly increased bladder V40,and small bowel Dmax,Dmean,V55,V45,V40(P<0.05),indicating that during interfractional radiotherapy,a CBCT-measured bladder longitudinal diameter less than half of the bladder longitudinal diameter measured on the localizable CT could serve as a predictor for significantly increased radiation dose to the bladder and small bowel.Correlation analysis revealed that bladder volume change showed a positive correlation with bladder Dmax change(R=0.45),a significant negative correlation with bladder V30(R=-0.37),and negative correlations with small bowel Dmax,Dmean,V55,V45,V40(R=-0.31,-0.41,-0.39,-0.49,-0.61).The correlation results indicate that increasing bladder fullness could reduce the radiation dose to the bladder and small bowel.Conclusion Artificial intelligence-assisted segmentation confirms that in interfractional radiotherapy for cervical cancer,when the CBCT-measured bladder longitudinal diameter is less than half of the longitudinal diameter measured on the localizable CT,there is a significant increase in radiation dose to OAR.Maintaining an ideal state of bladder fullness contributes to reducing the radiation dose to the bladder and small bowel.It is crucial to provide patients with adequate bladder management education before treatment and implement strict bladder volume management strategies during treatment fractions.