BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

Objective To observe the clinical efficacy and safety of bevacizumab in the treatment of platinum-resistant ovarian cancer,tubal cancer,peritoneal carcinoma cancer.Methods Patients with platinum resistance ovarian cancer,tubal cancer and peritoneal carcinoma cancer treated with bevacizumab were in included into treatment group.Patients with platinum-resistance in ovarian cancer,tubal cancer and peritoneal carcinoma cancer who received docetaxel chemotherapy during the same period were included into control group.The treatment group was given bevacizumab 5 mg·kg-1 by intravenous infusion once every 2 weeks,and the first intravenous infusion lasted for 90 min,with a total of 4 times of chemotherapy.The control group was given docetaxel 70-75 mg·m-2 by intravenous infusion,once every 3 weeks,1 h each time,a total of 4 times of chemotherapy.The clinical efficacy after chemotherapy,the levels of serum squamous cell carcinoma antigen(SCC-Ag),malignant tumor-related substance group(TSGF),cytokeratin 19 fragment(CYFRA21-1),the changes of tumor markers,immune indexes and the occurrence of adverse drug reactions were compared between the two groups.Results There are 70 cases in treatment group and 50 cases in control group.After four rounds of chemotherapy,the total effective rates of treatment group and control group were 47.14％(33 cases/70 cases)and 30.00％(15 cases/50 cases),with statistically significant difference(P＜0.05).After chemotherapy,the SCC-Ag levels in treatment group and control group were(3.10±1.05)and(5.50±1.95)mg·L-1;TSGF levels were(30.20±9.94)and(56.70±10.45)U·mL-1;CYFRA21-1 levels were(1.03±0.45)and(2.10±0.99)mg·L-1;carcinoembryonic antigen(CEA)levels were(66.81±48.74)and(89.18±56.08)ng·mL-1;the tumor markers CA199 were(110.26±51.36)and(124.13±53.80)U·mdL-1;the gastric cancer antigen(CA724)were(14.70±9.72)and(20.54±18.51)U·mL-1;the CD3+levels were(72.45±9.45)％and(67.10±10.25)％;the CD4+levels were(48.49±9.15)％and(39.56±6.77)％;the CD8+levels were(20.18±3.85)％and(24.02±4.45)％,the differences were all statistically significant(all P＜0.05).There was no significant difference in the incidence of adverse drug reactions between the two groups(P＞0.05).Conclusion Bevacizumab is more effective than docetaxel in the treatment of platinum-resistant ovarian cancer,tubal cancer,peritoneal carcinoma cancer.

Objective: To study the clinical efficacy of biological ceramics (iRoot BP Plus ) and mineral trioxide aggregate (MTA) in direct pulp capping of mature permanent teeth, to provide referrence for clinical application. Methods : Seventy-four patients with pulp exposure due to deep caries or reversible pulpitis in 75 mature permanent teeth were selected and were randomly divided into two groups. iRoot BP Plus were used as pulp capping agents in the treatment group and MTA were used as pulp capping agents in the control group respectively. The clinical efficacy and imaging analysis were performed at 1, 3, 6 and 12 months after operation. Treatment success rate of the two groups were calculated, and the influence of various factors including gender, age, tooth position, cavity, number and size of pulp exposure on the efficacy of direct pulp capping were analyzed. Results : Sixty patients with 61 mature permanent teeth were selected. Twelve mouths after treatment, 61 teeth of 60 patents were completely investigated (iRoot group: 31 teeth 30 patients; MTA group: 30 teeth 30 patients). The success rates of the 2 groups were 90.3% (iRoot BP Plus) and 90.0% (MTA), respectively. There was no statistical difference between 2 groups (P>0.05). Statistical analysis also showed that gender, age, tooth position, cavity, number and size of pulp exposure had no significant difference between the two groups (P>0.05). Conclusion Both iRoot BP Plus and MTA are effective in direct pulp capping of mature permanent teeth with carious pulp exposure, while the operation of iRoot is simple and convenient.

The oral cavity of each person is home to hundreds of bacterial species.While taxa for oral diseases have been studied using culture-based characterization as well as amplicon sequencing,metagenomic and genomic information remains scarce compared to the fecal microbiome.Here,using metagenomic shotgun data for 3346 oral metagenomic samples together with 808 published samples,we obtain 56,213 metagenome-assembled genomes(MAGs),and more than 64％of the 3589 species-level genome bins(SGBs)contain no publicly available genomes.The resulting genome collection is representative of samples around the world and contains many genomes from candi-date phyla radiation(CPR)that lack monoculture.Also,it enables the discovery of new taxa such as a genus Candidatus Bgiplasma within the family Acholeplasmataceae.Large-scale metagenomic data from massive samples also allow the assembly of strains from important oral taxa such as Por-phyromonas and Neisseria.The oral microbes encode genes that could potentially metabolize drugs.Apart from these findings,a strongly male-enriched Campylobacter species was identified.Oral sam-ples would be more user-friendly collected than fecal samples and have the potential for disease diagnosis.Thus,these data lay down a genomic framework for future inquiries of the human oral microbiome.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Objective:To investigate the etiology, pathogenesis, clinical manifestations, and treatment of acute pancreatitis (AP) complicated with spleen infarction.Methods:A case of AP combined with splenic infarction was retrospectively analyzed and the literature was reviewed.Results:AP complicated with splenic infarction suggested that the patient′s condition was serious. The impairment of splenic immune function caused by splenic infarction may be an important cause of severe acute pancreatitis (SAP). Early detection and active treatment can obtain a good prognosis, and anticoagulant or antiplatelet aggregation treatment was not the key treatment.Conclusions:AP combined with splenic infarction may be an risk factor for SAP.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.