ObjectiveTo analyze the epidemiological characteristics and spatial clustering patterns of brucellosis in humans in Zhangjiakou City, Heibei Province from 2018 to 2023, so as to provide a basis for the prevention and control of brucellosis. MethodsIncidence data of brucellosis in Zhangjiakou City from 2018 to 2023 were collected. Descriptive epidemiological analysis, Joinpoint regression modelling, and spatial autocorrelation analysis were used to analyze the temporal trends and spatial clustering patterns of the epidemic. ResultsA total of 3 812 cases of brucellosis were reported in Zhangjiakou City from 2018 to 2023, with no death case, yielding an average annual incidence rate of 15.43/100 000 (incidence range: 12.82/100 000‒17.76/100 000). Cases of brucellosis occurred year-round, with a distinct seasonal pattern, predominantly concentrated between March and September, peaking in May and June. The male-to-female ratio was 2.58∶1, with a higher incidence in males than that in females. The highest incidence rates were observed in the 40‒<50 years (74.98/100 000) and 50‒<60 years age group (87.14/100 000). The majority of cases were farmers and herdsmen (3 557 cases, 93.31%). Joinpoint regression analyses indicated that from 2018 to 2023, the incidence rate of human brucellosis in pastoral areas of Zhangjiakou City showed a declining trend (APC=-9.70%, 95%CI: -15.31%‒ -4.63%), while the incidence rate in mixed-use areas exhibited an increasing trend (APC=6.90%, 95%CI: 0.17%‒14.30%). Spatial clustering analyses showed that the incidence of brucellosis in Zhangjiakou from 2018 to 2023 was non-randomly distributed across the whole city, with a positive spatial correlation and significant clustering (Moran’s I>0, all P<0.001). Local spatial autocorrelation analyses showed that the high-high clusters were concentrated in the pastoral areas during 2018‒2020. From 2021 onward, the number of high-high clusters in mixed and non-pastoral regions exceeded those in traditional pastoral areas. ConclusionFrom 2018 to 2023, the incidence of brucellosis in Zhangjiakou City showed a declining trend, with significant spatial clustering observed across the city. It is recommended to intensify health education among males aged 40‒<60 years. Scientific livestock management practices should be promoted in non-pastoral and mixed areas, and cross-sectoral quarantine and joint prevention and control efforts should be strengthened as well.

Objective:To investigate the effectiveness and safety of lacosamide (LCM) in pregnant women with epilepsy.Methods:A retrospective study was conducted involving 6 pregnant women with epilepsy who were treated with LCM at the Electroencephalogram Monitoring Center of the Department of Neurology, Xijing Hospital of Air Force Military Medical University from January 2022 to June 2023. Their electroclinical characteristics, seizures during pregnancy, breastfeeding, and follow-up were summarized.Results:The 6 patients were aged 22 to 30 years at the time of pregnancy. Three patients were treated with monotherapy, with a daily dose of LCM ranging from 150 mg to 200 mg, while the other 3 patients were treated with combination therapy, with a daily dose of 150 mg. The seizures of 5 patients decreased during pregnancy compared with progestation except for the case 2 without adherence to Medication. No malformations were observed in the newborns, with the Apgar scores of 9-10 at 1 minute and 5 minutes after birth. The infants showed normal growth, development, intelligence, and motor skills in subsequent assessments. Two patients breastfed their infants, 1 for 6 months and the other for 14 months by the last follow-up, with a daily LCM dose of 150 mg to 300 mg during the breastfeeding. No adverse reactions were observed in the infants.Conclusion:The addition of LCM during pregnancy and lactation showed good effectiveness and safety, with no observed birth malformations.

Objective:To analyze the efficacy of high disinsertion of the levator palpebrae superioris muscle combined with conjoint fascial sheath (CFS) fixation for the treatment of moderate to severe ptosis.Methods:A retrospective study included 20 patients with moderate to severe ptosis treated at the First Affiliated Hospital of Xinxiang Medical University from June 2022 to June 2023. Participants were divided into two groups based on surgical technique. Traditional group [9 patients (16 eyes), 3 males and 6 females, aged 5-32 (18.2±7.1) years]: were treated with standard surgical approach involving levator palpebrae superioris muscle separation starting from the tarsal plate margin combined with CFS fixation. Modified group [11 patients (16 eyes), 5 males and 6 females, aged 6-28 (17.5±6.3) years]: were treated with modified technique utilizing high disinsertion of the levator palpebrae superioris muscle combined with CFS fixation. Outcomes including CFS exposure time, postoperative edema resolution time, complications, and patient satisfaction were compared between the two groups.Results:The CFS exposure time in the traditional group lasted for (37.5±3.0) min, which was significantly longer than that in the modified group of (23.9±1.8) min ( P<0.001). Postoperative edema resolution time in the traditional group was (16.4±1.4) days, which was also longer than that in the modified group of (7.0±0.6) days ( P<0.001). Transient lagophthalmos occurred in all patients postoperatively. The traditional group exhibited 3 cases of mild conjunctival prolapse and 3 cases of chemosis, while the modified group had 1 case of mild conjunctival prolapse and 1 case of chemosis. Patient satisfaction rates were 15/16 eyes in the modified group and 12/16 eyes in the traditional group. Conclusion:The modified technique involving high disinsertion of the levator palpebrae superioris muscle combined with CFS fixation demonstrates superior effectiveness in correcting moderate to severe ptosis.

Aim To explore the potential mechanism of metformin on ATP-binding cassette transport A1(ABCA1)expression.Methods J774A.1 macrophages were treated with metformin and cycloheximide,and ABCA1 expression was determined by Western blot.His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin.Co-immunoprecipitation(Co-IP)was used to test the binding ability of ABCA1 and ubiquitin.Candidate E3 ubiquitin-protein ligases(CE3)of ABCA1 were identified through Co-IP-based pro-teomics.The MIB1 plasmid was constructed and transferred into HEK293 cells,and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression.Results Metformin increased the expression of ABCA1 in J774A.1 cells(P<0.01),and inhibited ABCA1 degradation(P<0.05).Metformin disrupted the binding of ABCA1 to ubiquitin(P<0.05).The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways re-lated to cell development,inflammation and immune defense.Metformin may upregulate ABCA1 protein expression via MIB1(P<0.05).Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system(UPS),and MIB1 might act as a candidate E3 ubiquitin-protein ligase(CE3)for ABCA1.

Objective:To assess the value of whole exome sequencing (WES) for the diagnosis of early-onset genetic diseases among infants aged 0 to 6 month in Ningbo region.Methods:268 infants presented at the Women and Children′s Hospital Affiliated to Ningbo University from January 2022 to June 2024 undergoing WES-based genetic testing were enrolled. Peripheral blood samples were collected from the infants and their parents and subjected to WES. Pathogenic variants were identified by clinical manifestations. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. EC2023-017).Results:Among the 268 infants, 124 (46.3%) had phenotype-explaining genetic variants. For 42 family-based WES tests, 20 (47.62%) were abnormal, whilst in 226 single-person WES tests, 104 (46.02%) had abnormalities, with 76 (33.63%) verified by parental testing. In 96 fully family-verified cases, 31 were de novo, 40 were parent-inherited, 25 were single-parent-inherited. These included 35 inborn metabolic errors, 28 rare syndromes, 9 neurodevelopmental disorders, 4 musculoskeletal diseases, 5 congenital deafness, 2 mitochondrial diseases, 4 endocrine diseases, and 9 others. Among these, there were 7 pathogenic copy number variations (all deletions), 3 chromosomal abnormalities, and 85 single-nucleotide variations. One case of Beckwith-Wiedemann syndrome was detected by methylation MLPA. Among the single-nucleotide variants, 114 pathogenic/likely pathogenic variants were identified in 61 genes, with common ones including missense variants (64.04%), frameshifting variants (20.18%) and splicing variants (4.39%). Conclusion:WES can offer effective diagnosis for hereditary diseases with specific/non-specific manifestations. For early-age infants, higher detection rates may be attained for inborn metabolic errors, rare syndromes, neurodevelopmental disorders, congenital deafness, and musculoskeletal diseases. Compared with single-person WES, family-based WES can attain a higher diagnostic efficiency.

Objective:To investigate the vaccination rate of 23-valent pneumococcal polysaccharide vaccine (PPV23), identify determinants of vaccination willingness, and analyze barriers to vaccination among community-dwelling elderly in Xinzhuang Town of Shanghai Minhang District.Methods:This cross-sectional study was conducted in Xinzhuang Town of Shanghai Minhang District from November to December 2024. An online questionnaire was distributed via WeChat groups of neighborhood committees to community-dwelling elderly (aged≥60 years) using a convenience sampling method. The questionnaire covered basic demographic information, health status, knowledge and awareness about pneumonia and PPV23, attitudes toward PPV23 vaccination, and vaccination behavior. The χ2 test and multivariate logistic regression analysis were employed to identify factors influencing the PPV23 vaccination rate and willingness to vaccination among the elderly. Results:A total of 667 questionnaires were collected and 612 were valid (91.8%). Among 612 responders there were 223 males (36.44%) and 389 females (63.56%), and 304 (49.67%) aged 70-79 years. In all respondents, 185 (30.23%) had previously received PPV23, while 427 (69.77%) had not. Reasons for non-vaccination included unawareness of vaccine necessity (31.85%, 136/427), self-perceived good health (31.15%, 133/427), concerns about adverse reactions (21.08%, 90/427), and lack of physician recommendation (14.52%, 62/427). In all participants, 65.85%(403/612)expressed willingness for vaccination and 34.15%(209/612) did not have willingness. Factors significantly influencing vaccination willingness included negative perception of vaccine efficacy ( OR=2.750, 95% CI:1.077-7.023), concerns about adverse reactions ( OR=2.568, 95% CI:1.258-5.242), low awareness of pneumonia and PPV23 vaccine ( OR=11.608, 95% CI:4.177-32.258), perceived vaccination inconvenience ( OR=0.457, 95% CI:0.248-0.844), and belief in good health negating need ( OR=2.658, 95% CI:1.361-5.190) (all P<0.05). Conclusions:Suboptimal PPV23 vaccination rates and low willingness among community-dwelling elderly in Shanghai Xinzhuang Town are driven by knowledge gaps and perceptual barriers. Targeted interventions should prioritize physician engagement, accessible vaccination services, and public education addressing safety and efficacy concerns.

The paper reports a 32-year-old female acute myeloid leukemia patient who developed graft-versus-host disease after paternal hematopoietic stem cell transplantation, which subsequently led to renal thrombotic microangiopathy. She subsequently required a kidney transplant from the same donor 5 years later due to renal failure. Considering that both the bone marrow and kidney were from the same donor and the recovery of renal function was favorable, immunosuppressive therapy was discontinued after a short course of anti-rejection treatment, with maintained stable kidney function. This case suggests that under the condition of high chimerism, allogeneic hematopoietic stem cell transplantation and kidney transplantation from the same donor can achieve immune tolerance, potentially improving solid organ transplantation success rate. The findings provide a novel therapeutic approach for solid organ transplantation following allogeneic hematopoietic stem cell transplantation.

Objective:To investigate the disease burden, clinical characteristics and independent risk factors affecting in-hospital outcomes of children with congenital heart disease (CHD) combined with heart failure (HF) in China.Methods:(1) Descriptive study: based on the global burden of disease study 2021, available data on children under 15 years of age with CHD and HF in China from 1990 to 2021 were collected. The prevalence and trends in different age subgroups (<1 year, 1-<2 years, 2-<5 years, 5-<10 years, 10-<15 years) were analyzed, and the annual percentage change (EAPC) was estimated using linear regression. (2) Retrospective cohort study: a total of 1 062 children with CHD and HF from a multicenter study on pediatric HF in China were included. The children were divided into two groups:<2 years group and 2-<18 years group. Data on demographics, clinical features, diagnosis, treatments, and in-hospital outcomes were analyzed. Mann-Whitney U test and chi-square test were used for group comparisons.Multivariable Logistic regression was applied to identify factors influencing outcomes (in-hospital mortality and adverse cardiovascular events). Results:(1) From 1990 to 2021, the number of children with CHD and HF in China increased from 333 000 (95% uncertainty interval ( UI) 271 000-405 000) to 368 000 (95% UI 296 000-459 000), a growth of 10.8% (95% UI 5.0%-16.6%). Concurrently the prevalence rate increased from 104.5 (95% UI 85.1-127.3) per 100 000 to 142.0 (95% UI 114.0-176.8) per 100 000, a growth of 35.9% (95% UI 28.7%-43.0%), with an EAPC of 1.5% (95% CI 1.2%-1.8%). Although the number of cases in the<1 year and 1-<2 years groups decreased by 41.0% and 25.6%, respectively, the prevalence in all age groups showed an upward trend:<1 year EAPC 0.6% (95% CI 0.5%-0.7%); 1-<2 years EAPC 0.9% (95% CI 0.8%-1.0%); 2-<5 years EAPC 1.2% (95% CI 1.0%-1.4%); 5-<10 years EAPC 1.5% (95% CI 1.2%-1.8%); 10-<15 years EAPC 2.1% (95% CI 1.9%-2.3%). (2) The multicenter study revealed that among 1 062 hospitalized children, 528 (49.7%) were male and 534 (50.3%) were female, with the age at admission of 5.4 (2.2,18.2) months. The majority of the children (77.9%, 827/1 062) were under 2 years of age, whereas 22.1% (235/1 062) were aged between 2-<18 years. Children with complex congenital heart defects accounted for the highest proportion (48.6%, 516/1 062), while those with isolated CHD made up 31.5% (335/1 062). Statistically significant differences were observed in several variables in demographics, clinical features, diagnosis, treatments, and outcomes between the two age groups (all P<0.05). The use of renin-angiotensin-aldosterone system inhibitors (41.1%, 436/1 062) and beta-blockers (8.7%, 92/1 062) was lower in hospitalized children with CHD and HF. Logistic regression identified complex CHD ( OR=7.73, 95% CI 2.24-26.63; OR=3.17, 95% CI 1.92-5.23), pulmonary hyperperfusion ( OR=2.15, 95% CI 1.01-4.18; OR=2.00, 95% CI 1.35-2.97), left ventricular ejection fraction<55% ( OR=2.13, 95% CI 1.08-4.21; OR=2.80, 95% CI 1.45-5.56), arterial oxygen partial pressure ( OR=0.99, 95% CI 0.98-0.99; OR=0.99, 95% CI 0.98-0.99), and serum calcium levels ( OR=0.31, 95% CI 0.17-0.58; OR=0.42, 95% CI 0.28-0.62) as independent risk factors for in-hospital mortality and cardiovascular events. Conclusions:The disease burden of CHD combined with HF in China has shown a continuous upward trend from 1990 to 2021, with higher growth rates in older age groups. Complex CHD, pulmonary hyperperfusion, left ventricular ejection fraction <55%, arterial oxygen partial pressure, and serum calcium concentration are independent risk factors for in-hospital mortality and cardiovascular events.

Objective:To evaluate the relationship between trimethylamine N-oxide (TMAO) and high glucose-hypoxia/reoxygenation (H/R) injury in rat cardiomyocytes and the role of endoplasmic reticulum stress (ERS).Methods:Normally cultured rat H9C2 cardiomyocytes were divided into 4 groups ( n=24 each) by using a table of random numbers: high glucose control group (HC group), high glucose-H/R group (H/R group), high glucose-H/R + TMAO group (T group), and high glucose-H/R + TMAO + 4-phenylbutyric acid group (P group). The high glucose-H/R injury model was established by incubating cells in high-glucose (25 mmol/L glucose) medium for 72 h, followed by 4 h of hypoxia in glucose-free medium and 4 h of reoxygenation in high-glucose medium. T group was incubated with 400 μmol/L TMAO for 72 h before hypoxia, and P group was incubated with 400 μmol/L TMAO and 1 mmol/L 4-phenylbutyric acid for 72 h before hypoxia. At 4 h of reoxygenation, the cell viability was detected by CCK-8 assay, the apoptosis rate, ROS level and opening of mitochondrial permeability transition pore (mPTP) were measured by flow cytometry, the mitochondrial membrane potential (MMP) was determined by JC-1 staining, the content of ATP was measured by luciferase method, and the expression of activating transcription factor 4 (ATF4), activating transcription factor 6 (ATF6), B-cell lymphoma 2-associated X protein (BAX), glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1α (IRE1α) was detected by Western blot. Results:Compared with HC group, the cell survival rate, MMP and ATP levels were significantly decreased, the apoptosis rate, ROS level and opening of mPTP were increased, and the expression of ATF4, ATF6, BAX, GRP78, PERK and IRE1α was up-regulated in H/R group ( P<0.05). Compared with H/R group, the cell survival rate, MMP and ATP levels were significantly decreased, the apoptosis rate, ROS level and opening of mPTP were increased, the expression of ATF4, BAX, GRP78 and PERK was up-regulated ( P<0.05), and no statistically significant change was found in the expression of ATF6 or IRE1α in T group ( P>0.05). Compared with T group, the cell survival rate, MMP and ATP levels were significantly increased, and the apoptosis rate, ROS level and opening of mPTP was decreased, and the expression of ATF4, ATF6, BAX, GRP78, PERK and IRE1α was down-regulated in P group ( P<0.05). Conclusions:TMAO is involved in the underlying mechanism of high glucose-H/R injury in rat cardiomyocytes, which may be related to the excessive activation of the PERK pathway-mediated ERS and consequent exacerbation of mitochondrial dysfunction.