[Periconceptional maternal homocysteine and birth weight outcomes in offspring: a prospective cohort study].

Objective: To quantify the associations between periconceptional maternal homocysteine (HCY) and offspring's birth weight and risk of small for gestational age (SGA) infant. Methods: The 19 984 mother-child pairs in this prospective cohort study were recruited from the Shanghai preconception cohort; the infants were delivered from 1st September 2016 to 11th November 2022. A standardized questionnaire was used to collect the mothers' demographic information, medical history, dietary supplement use, and maternal complications during pregnancy, and their serum samples were collected. Serum HCY, folate, and vitamin B12 were measured using chemiluminescent microparticle immunoassay based on serum sample drawn at enrollment. Birth weight data were obtained from medical records. Multiple imputation methods were applied to handle missing data in key variables. Multivariable linear regression and Poisson regression models were used to analyze the relationship between maternal HCY concentration during the periconceptional period and the birth weight and SGA risk of the offspring. Results: A total of 9 452 pairs were enrolled preconceptionally and the remaining 10 532 pairs were enrolled in early pregnancy. The proportion of mothers whose pregnancy age was greater than 35 years was 9.2% (1 832/19 984), the proportion of primiparous women was 76.5% (15 283/19 984), the proportion of pre-pregnancy overweight and obesity was 14.0% (2 804/19 984), the proportion of using folic acid supplements before pregnancy was 21.4% (4 272/19 984), and the proportion of those who supplemented with folic acid during early pregnancy was 85.2% (8 976/10 532); gestational diabetes mellitus was in 6.2% (1 245/19 984), gestational hypertensive syndrome in 3.6% (711/19 984). The birth weight of the offspring was (3 297±468) g, and there were 1 962 SGA children (9.8%). The HCY concentration in the overall population in appropriate for gestational age during the periconceptional period was (7.9±3.2) µmol/L, with (8.3±3.7) µmol/L in the preconception subgroup and (7.3±2.4) µmol/L in the early pregnancy subgroup. After adjustment for the covariates of perinatal demographic information, adverse pregnancy outcomes, serum folate and vitamin B12, increased maternal periconceptional HCY was significantly associated with lower offspring birth weight (ß=-2.30, 95%CI -4.43--0.16, P=0.035). Only the early pregnancy subgroup was significantly associated with lower offspring birth weight (ß=-7.39, 95%CI-11.50--3.21, P<0.001). No association was found between peripregnancy HCY and offspring SGA risk. However, elevated HCY in early pregnancy was associated with an increased risk of SGA in the offspring (RR=1.05, 95%CI 1.01-1.08, P=0.002). Periconceptional vitamin B12 was a mediator of the association between HCY and offspring birth weight, accounting for 16.5%, 41.2% and 5.4% of its total effect in the overall periconceptional population, the pre-pregnancy subgroup and the early pregnancy subgroup, respectively. Conclusions: Maternal periconceptional HCY level is associated with lower birth weight in offspring, but not with the risk of SGA. Elevated maternal HCY in early pregnancy subgroup may be associated with increased risk of SGA in offspring.

[Real-world study on the efficacy and safety of first-line antiviral therapy for chronic hepatitis B].

Objective: To clarify the clinical efficacy of first-line oral antiviral drugs tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) in the treatment of chronic hepatitis B (CHB) and their safety profiles with lipid, bone, and kidney metabolism. Methods: 458 CHB cases diagnosed and treated at the Department of Hepatology of Integrated Traditional Chinese and Western Medicine of the Third Hospital of Hebei Medical University from February 2010 to November 2022 were selected. TAF (175 cases), TDF (124 cases), and ETV (159 cases) were used as therapies. At 24 and 48 weeks, the virology, biochemical response, changes in liver stiffness measurement (LSM), and bone, kidney, and blood lipid metabolism safety profiles were compared and analyzed. Results: After 24 and 48 weeks of TAF, TDF, and ETV therapy, HBV DNA load decreased by 3.28, 2.69, and 3.14 log10 IU/ml and 3.28, 2.83, and 3.65 log10 IU/ml, respectively, compared with the baseline, and the differences between the three groups were statistically significant, P < 0.001. The complete virological response rates were 73.95%, 66.09%, 67.19%, and 82.22%, 72.48%, and 70.49%, respectively. The incidence rates of low-level viremia were 16.67%, 21.70%, and 23.08%, while poor response rates were 1.11%, 3.67%, and 4.10%. ALT normalization rates were 64.00%, 63.89%, 67.96%, and 85.33%, 80.56%, 78.64%, respectively, and there was no statistically significant difference among the groups. LSM was significantly improved in patients treated with TAF for 48 weeks, P = 0.022. Serum phosphorus level gradually decreased with the prolongation of TDF treatment. The TAF treatment group had a good safety profile for kidney, bone, and phosphorus metabolism, with no dyslipidemia or related occurrences of risk. Conclusion: There are some differences in the therapeutic effects of first-line anti-HBV drugs. TAF has the lowest incidence of low-level viremia after 48 weeks of treatment and has a good safety profile in kidney, bone, and blood lipid metabolism.

[A single center study on antimicrobial use and bacterial resistance in burn ward].

Objective: To investigate the effect of antibiotics on bacterial resistance through analyzing the use of common antibiotics and the bacterial prevalence in single-center burn ward. Methods: The epidemiological data of pathogenic bacteria and the use of common antibiotics in burn ward of Ruijin Hospital Affiliated to Shanghai Jiaotong University Medical College was investigated in the past 9 years. Bacteria samples were collected from the wounds, catheters, blood, feces, urine and sputum of inpatients in the unit from January 2010 to December 2018. The antibiotics use density was calculated by defined daily doses (DDDs)/(1 000 patient-days). Results: (1) In the proportion of bacteria detected, Staphylococcus aureus was the first and sensitive to glycopeptide antibiotics. Klebsiella pneumonia (19.8%), Pseudomonas aeruginosa (11.9%) and Acinetobacter baumannii (11.5%) were the top three Gram-negative bacteria in 2018; the proportion of Klebsiella pneumoniae was significantly increased (R(2)=0.861, P<0.001). (2) The Pseudomonas aeruginosa resistance rate to ceftazidime (R(2)=0.447, P=0.049) and ciprofloxacin (R(2)=0.663, P=0.008) increased significantly. The Klebsiella pneumoniae resistance rate to piperacillin (R(2)=0.999, P=0.018), meropenem (R(2)=0.999, P=0.023), ciprofloxacin (R(2)=1.000, P=0.010) increased significantly. There was no significant trend in the Acinetobacter baumannii resistance rate. (3) The use density of meropenem increased significantly (R(2)=0.492, P=0.035), and that of ciprofloxacin decreased significantly (R(2)=0.572, P=0.018). (4) Carbapenems use density was positively correlated with resistance rate of Klebsiella pneumoniae to cefoperazone sulbactam (r=0.733, P=0.025), piperacillin tazobactam (r=0.684, P=0.042), cefuroxime (r=0.821, P=0.023), ceftazidime (r=0.741, P=0.022), imipenem (r=0.718, P=0.029), meropenem (r=0.690, P=0.040), amikacin (r=0.750, P=0.020). (5) Ciprofloxacin use density was negatively correlated with the Pseudomonas aeruginosa resistance rate to ceftazidime (r=-0.751, P=0.020), Ciprofloxacin (r=-0.873, P=0.002) and with the Klebsiella pneumoniae resistance rate to cefuroxime (r=-0.767, P=0.044), ceftazidime (r=-0.712, P=0.031), imipenem (r=-0.780, P=0.013), meropenem (r=-0.793, P=0.011), ciprofloxacin (r=-0.871, P=0.002), Sulfamethoxazole/trimethoprim (r=-0.793, P=0.011). Conclusion: Carbapenems can induce Klebsiella pneumoniae to be multiple drug resistance; through the relationship between ciprofloxacin use intensity and drug resistance, the strategy of only restricting a certain antimicrobial agent may not restore the bacterial sensitivity.

The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity.

As NAD(+) is a rate-limiting cosubstrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38-both NAD(+) consumers-increases NAD(+) bioavailability, resulting in SIRT1 activation and protection against metabolic disease. Here we evaluated whether similar effects could be achieved by increasing the supply of nicotinamide riboside (NR), a recently described natural NAD(+) precursor with the ability to increase NAD(+) levels, Sir2-dependent gene silencing, and replicative life span in yeast. We show that NR supplementation in mammalian cells and mouse tissues increases NAD(+) levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high-fat diet-induced metabolic abnormalities. Consequently, our results indicate that the natural vitamin NR could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function.