ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

AIM:This study aims to investigate whether a specific synbiotic,consisting of Bifidobacterium longum subspecies BB536 and fructooligosaccharides,can inhibit colon tumorigenesis by modulating gut flora composi-tion.METHODS:Six-week-old male ApcMin/+mice were randomly divided into control group and synbiotic-treated group,with 8 mice in each group.The mice in synbiotic-treated group received daily gavage of 1×109 CFU/kg of Bifidobacterium longum BB536 and 2 g/kg of fructooligosaccharides,while those in control group were gavaged with sterile water for 10 weeks.The number and size of colon tumors were assessed and compared between the 2 groups.Colon tissue sections were evaluated using hematoxylin-eosin staining,Alcian blue staining,and immunohistochemistry assays.The bacterial compo-sition in the colon was analyzed via 16S rDNA sequencing,and differentially expressed genes were examined through tran-scriptome sequencing and RT-qPCR.RESULTS:The synbiotic treatment significantly enhanced bacterial diversity and increased the relative abundance of Bifidobacterium in the colon(P<0.01).Additionally,the number and size of colon tu-mors were both significantly reduced in the synbiotic-treated mice(P<0.01),along with decreased expression of Ki-67(P<0.01).Concurrently,the number of goblet cells and the expression of epithelial tight junction proteins(ZO-1 and occlu-din)were up-regulated(P<0.05).CONCLUSION:Supplementation with this synbiotic effectively modulated gut flora composition and suppressed colon tumorigenesis in ApcMin/+mice.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

AIM:This study aims to investigate whether a specific synbiotic,consisting of Bifidobacterium longum subspecies BB536 and fructooligosaccharides,can inhibit colon tumorigenesis by modulating gut flora composi-tion.METHODS:Six-week-old male ApcMin/+mice were randomly divided into control group and synbiotic-treated group,with 8 mice in each group.The mice in synbiotic-treated group received daily gavage of 1×109 CFU/kg of Bifidobacterium longum BB536 and 2 g/kg of fructooligosaccharides,while those in control group were gavaged with sterile water for 10 weeks.The number and size of colon tumors were assessed and compared between the 2 groups.Colon tissue sections were evaluated using hematoxylin-eosin staining,Alcian blue staining,and immunohistochemistry assays.The bacterial compo-sition in the colon was analyzed via 16S rDNA sequencing,and differentially expressed genes were examined through tran-scriptome sequencing and RT-qPCR.RESULTS:The synbiotic treatment significantly enhanced bacterial diversity and increased the relative abundance of Bifidobacterium in the colon(P<0.01).Additionally,the number and size of colon tu-mors were both significantly reduced in the synbiotic-treated mice(P<0.01),along with decreased expression of Ki-67(P<0.01).Concurrently,the number of goblet cells and the expression of epithelial tight junction proteins(ZO-1 and occlu-din)were up-regulated(P<0.05).CONCLUSION:Supplementation with this synbiotic effectively modulated gut flora composition and suppressed colon tumorigenesis in ApcMin/+mice.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Purpose To investigate the ultrasound features and classification of pilomatricoma and its correlation with pathological manifestations.Materials and Methods The clinical,ultrasound and pathological data of 76 patients(78 lesions)postoperative confirmed pilomatricoma in Henan Province Hospital of Traditional Chinese Medicine and the the First Affiliated Hospital of Henan University of Traditional Chinese Medicine from July 2014 to August 2021 were analyzed,retrospectively.According to the presence or absence of calcification and the pattern of calcification in the sonogram,they were divided into no calcification type,dotted calcification type,sheet calcification type and complete calcification type.Results Pilomatricoma were most common in children under 10,with predilection location in the face and head.Most lesions were surrounded by hypoechoic halo and calcification,51 of 78 lesions had different degrees of calcification,accounting for about 65.4%;36 lesions were with hypoechoic halo;63 lesions were mainly hypoechoic,accounting for about 80.8%.There were statistical differences in hypoechoic halo(χ2=15.624,P=0.001)and internal echo(χ2=12.801,P=0.021)among different classification pilomatricoma.Shadow cells and basicyte were detected in all 78 lesions,basophil cells were found in the periphery of 50 out of 54 lesions showing hypoechoic halos.The ultrasound manifestations of different types had characteristic changes corresponding to their pathological composition.Conclusion The ultrasound performance varies among the different types of pilomatricoma,and there is a correlation with its pathological changes.Familiarization with the sonographic presentation of pilomatricoma in the different types contributes to the preoperative diagnosis.

Objective::This study aimed to determine the most pertinent factors responsible for placenta accreta spectrum disorders in patients without any history of pregnancy and evaluate their prognostic implications.Methods::This retrospective cohort study included 1009 patients diagnosed with placenta accreta spectrum disorders based on standardized diagnostic criteria across 10 tertiary hospitals in China between January 1, 2018, and December 31, 2018; 45 patients without a history of pregnancy were selected. The collected data mainly included demographic characteristics (including age, operative history, and ultrasound findings) and maternal-fetal outcomes (including any history of intraoperative bleeding, blood transfusion details, maternal-fetal complications, and fetal Apgar scores). SPSS 24.0 was used for statistical analyses. The Mann-Whitney U test and logistic regression were performed; a two-tailed P < 0.050 was considered statistically significant. Results::Ultrasound-based detection of placenta previa ( χ2 = 9.911, P = 0.003) showed a strong association with placenta accreta spectrum types. The severity of placenta accreta spectrum was directly proportional to the likelihood of having coexistent complete placenta previa ( χ2 = 11.626, P = 0.009) and being diagnosed by ultrasound ( χ2 = 5.449, P = 0.047). Blood transfusion also impacted placenta accreta spectrum types in relation to maternal prognosis ( χ2 = 8.785, P = 0.004). On univariate analysis, older age led to more complications ( U = 82.000, P = 0.011), and in vitro fertilization-embryo transfer caused more intraoperative bleeding ( U = 91.500, P = 0.007). Although the 1- and 5-minute Apgar scores were statistically significant, the rates of neonatal asphyxia did not differ ( P > 0.050). Endometrial damage led to lower Apgar scores on both univariate (1 minute: U = 29.500, P = 0.027; and 5 minutes: U = 33.500, P = 0.031) and multivariate (1 minute: β = -1.510, 95% confidence interval, -2.639 to 0.381, P = 0.010; and 5 minutes: β = -0.968, 95% confidence interval, -1.779 to 0.157, P = 0.021) analyses. Conclusion::In patients who had no history of pregnancy, placenta previa was a strong risk factor for severe placenta accreta spectrum disorders. Endometrial damage led to lower Apgar scores; this warrants greater consideration in the clinic.

Objective::This study aimed to determine the most pertinent factors responsible for placenta accreta spectrum disorders in patients without any history of pregnancy and evaluate their prognostic implications.Methods::This retrospective cohort study included 1009 patients diagnosed with placenta accreta spectrum disorders based on standardized diagnostic criteria across 10 tertiary hospitals in China between January 1, 2018, and December 31, 2018; 45 patients without a history of pregnancy were selected. The collected data mainly included demographic characteristics (including age, operative history, and ultrasound findings) and maternal-fetal outcomes (including any history of intraoperative bleeding, blood transfusion details, maternal-fetal complications, and fetal Apgar scores). SPSS 24.0 was used for statistical analyses. The Mann-Whitney U test and logistic regression were performed; a two-tailed P < 0.050 was considered statistically significant. Results::Ultrasound-based detection of placenta previa ( χ2 = 9.911, P = 0.003) showed a strong association with placenta accreta spectrum types. The severity of placenta accreta spectrum was directly proportional to the likelihood of having coexistent complete placenta previa ( χ2 = 11.626, P = 0.009) and being diagnosed by ultrasound ( χ2 = 5.449, P = 0.047). Blood transfusion also impacted placenta accreta spectrum types in relation to maternal prognosis ( χ2 = 8.785, P = 0.004). On univariate analysis, older age led to more complications ( U = 82.000, P = 0.011), and in vitro fertilization-embryo transfer caused more intraoperative bleeding ( U = 91.500, P = 0.007). Although the 1- and 5-minute Apgar scores were statistically significant, the rates of neonatal asphyxia did not differ ( P > 0.050). Endometrial damage led to lower Apgar scores on both univariate (1 minute: U = 29.500, P = 0.027; and 5 minutes: U = 33.500, P = 0.031) and multivariate (1 minute: β = -1.510, 95% confidence interval, -2.639 to 0.381, P = 0.010; and 5 minutes: β = -0.968, 95% confidence interval, -1.779 to 0.157, P = 0.021) analyses. Conclusion::In patients who had no history of pregnancy, placenta previa was a strong risk factor for severe placenta accreta spectrum disorders. Endometrial damage led to lower Apgar scores; this warrants greater consideration in the clinic.

Objective:To analyze the prevalence of malnutrition among human immunodeficiency virus-exposed uninfected (HEU) children and to identify the associated factors in Hunan Province.Methods:All children born to human immunodeficiency virus (HIV)-infected mothers retrieved from Information System of Prevention of Mother-to-Child Transmission of human immunodeficiency virus Management (IPMTCT) in Hunan Province between July 2013 and June 2019 were included. Information including maternal demographic characteristic, maternal comorbidities/complications, anti-retroviral therapy during pregnancy, anti-retroviral prophylaxis for children, birth weight, and disease during follow-up was collected. The length and weight of children at one, three, six, nine, 12 and 18 months of follow-up time points were detected, and the prevalences of stunting, underweight, wasting and malnutrition among HEU children were evaluated. The generalized estimating equation was used to fit the logistic regression model to analyze the associated factors for malnutrition.Results:A total of 656 HEU children were finally included. The prevalences of stunting, underweight, wasting, and malnutrition among HEU children were highest at one month of age, which were 11.9%(78/656), 9.1%(60/656), 7.0%(45/656) and 21.0%(138/656), respectively. Maternal comorbidities/complications (adjusted odds ratio (a OR)=2.30, 95% confidence interval ( CI) 1.48 to 3.58), mono/dual anti-retroviral therapy during pregnancy (a OR=2.38, 95% CI 1.54 to 3.68), birth weight <2 500 g (a OR=2.66, 95% CI 1.69 to 4.21) and disease during follow-up (a OR=1.73, 95% CI 1.10 to 2.70) were the risk factors for malnutrition among HEU children (all P<0.050). Both taking zidovudine (a OR=0.60, 95% CI 0.38 to 0.94) and nevirapine (a OR=0.31, 95% CI 0.18 to 0.52) for anti-retroviral prophylaxis were the protective factors for malnutrition among HEU children (both P<0.050). Conclusions:The prevalence of malnutrition among HEU children is high. The prevalence of malnutrition is affected by maternal comorbidities/complications, anti-retroviral therapy during pregnancy, and birth weight, diseases during follow-up and anti-retroviral prophylaxis for children.