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The treatment of preeclampsia is delivering women and extracting the placenta, but the Chinese Society of Obstetrics and Gynecology guidelines do not recommend the delivery of babies without severe features. The objectives of the study were to compare the effectiveness and safety of nifedipine and phytosterol in combination with nicardipine for the management of severe preeclampsia. Women (19–32 years; gestation age ≥ 30 weeks) with the complication of severe preeclampsia have received 10 mg of oral nifedipine (pregnant women received 10 mg of oralnifedipine, n = 112) or 1 mg/h intravenous nicardipine (pregnant women received 1 mg/h intravenous nicardipine (ND cohort), n = 115) or oral 10 mg nifedipine and 500 mg phytosterol (pregnant women received oral 10 mg nifedipine and 500 mg phytosterol (np cohort), n = 111) until 150/100 mmHg blood pressure was achieved. The time required to achieve the desired blood pressure control was 13 minutes shorter in the NP cohort compared to the NF (p < 0.0001, t = 11.605), and 3 minutes shorter compared to the ND (p < 0.0001, t = 2.79) cohorts. Stillbirths were reported in 14 (13%), 28 (24%), and 10 (9%) infants, and 13 (12%), 26 (23%), and 10 (9%) infants died from the NF, ND, and NP cohorts, respectively. The undesirable tocolytic effect was reported in 17 (15%) women of the ND cohort. Phytosterol with nifedipine has a synergistic or additive effect on the management of preeclampsia with fewer adverse outcomes.

Objective: Developmental and epileptic encephalopathies (DEEs) can result from dominant, gain of function variants of neuronal ion channels. More than 450 de novo missense variants of the sodium channel gene SCN8A have been identified in individuals with DEE. Methods: We studied a mouse model carrying the patient Scn8a variant p.Asn1768Asp. An AAV‐PHP.eB virus carrying an allele‐specific single guide RNA (sgRNA) was administered by intracerebroventricular injection. Cas9 was provided by an inherited transgene. Results: Allele‐specific disruption of the reading frame of the pathogenic transcript generated out‐of‐frame indels in 1/4 to 1/3 of transcripts throughout the brain. This editing efficiency was sufficient to rescue lethality and seizures. Neuronal hyperexcitability was reduced in cells expressing the virus. Interpretation: The data demonstrate efficient allele‐specific editing of a dominant missense variant and support the feasibility of allele‐specific therapy for DEE epilepsy. ANN NEUROL 2024;96:958–969 [ABSTRACT FROM AUTHOR]

Background The management of multidrug-resistant tuberculosis (MDR-TB) remains challenging. Treatment outcome is influenced by multiple factors; the specific roles of diabetes and glycemic control remain uncertain. This study aims to assess the impact of glycemic control on drug exposure, to investigate the association between drug exposure and treatment outcomes, and to identify clinically significant thresholds predictive of treatment outcome, among patients with diabetes. Methods This multicenter prospective cohort study involved patients with confirmed MDR-TB and diabetes. Drug exposure level was estimated by noncompartmental analysis. The minimum inhibitory concentrations (MICs) were determined for the individual Mycobacterium tuberculosis isolates. The influence of poor glycemic control (glycated hemoglobin ≥7%) on drug exposure and the associations between drug exposure and treatment outcome were evaluated by univariate and multivariate analysis. Classification and regression tree analysis was used to identify the drug exposure/susceptibility thresholds. Results Among the 131 diabetic participants, 43 (32.8%) exhibited poor glycemic control. Poor glycemic control was independently associated with decreased exposure to moxifloxacin, linezolid, bedaquiline, and cycloserine, but not clofazimine. Additionally, a higher ratio of drug exposure to susceptibility was found to be associated with a favorable MDR-TB treatment outcome. Thresholds predictive of 6-month culture conversion and favorable outcome were bedaquiline area under the concentration–time curve (AUC)/MIC ≥245 and moxifloxacin AUC/MIC ≥67, demonstrating predictive accuracy in patients, regardless of their glycemic control status. Conclusions Glycemic control and optimal TB drug exposure are associated with improved treatment outcomes. This dual management strategy should be further validated in randomized controlled trials of patients with MDR-TB and diabetes. [ABSTRACT FROM AUTHOR]

Background: Isoniazid-resistant, rifampicin-susceptible tuberculosis (Hr-TB) is the most frequent drug-resistant tuberculosis (DR-TB) in the world, and unfavorable outcomes of Hr-TB are more common compared to drug-susceptible TB. Considering there is no optimal regimen accepted worldwide, we undertook a retrospective cohort study in eastern China to estimate incidence trends and risk factors associated with unfavorable outcomes of Hr-TB. Methods: Between January 2012 and December 2022, all Hr-TB patients' information was extracted from the Tuberculosis Information Management System (TIMS), which is a national electronic information platform, to record TB patients' clinical information in this study. The incidence of Hr-TB was determined by the mid-year population according to census data published by the government. We categorized treatment regimens depending on fluoroquinolone (FQ) use, and potential risk factors were analyzed using multivariable logistic regression. Results: A total of 3116 Hr-TB patients fulfilled the inclusion criteria and were enrolled in this study. The average annual rate of Hr-TB in the 11 years under investigation was 0.34 per 100,000 and increased to 0.53 per 100,000 until 2019. In total, six different treatment regimens were utilized in the study sites, and less than 1% of regimens adopted FQ. There was no difference in the unfavorable outcomes between the FQ-included and FQ-excluded groups (p = 0.22). The average treatment duration was 7.06 months, and the longest treatment was 26 months. Approximately 20% (637/3116) of Hr-TB patients had unfavorable outcomes, and 60.13% (383/637) of them proceeded to multidrug-resistant tuberculosis (MDR-TB). Treatment duration and a positive smear at the end of the 5th month were significantly associated with unfavorable outcomes (p < 0.001). Conclusion: The unfavorable treatment outcomes of Hr-TB are still high in eastern China, and the efficacy of FQ-containing regimens needs to be validated for Hr-TB treatment. [ABSTRACT FROM AUTHOR]

Water-soluble myo-inositol phosphates have long been characterized as second messengers. The signaling properties of these compounds are determined by the number and arrangement of phosphate groups on the myo-inositol backbone. Recently, higher inositol phosphates with pyrophosphate groups were recognized as signaling molecules. 5-Diphosphoinositol 1,2,3,4,6-pentakisphosphate (5PP-InsP5) is the most abundant isoform, constituting more than 90% of intracellular inositol pyrophosphates. 5PP-InsP5 can be further phosphorylated to 1,5-bisdiphosphoinositol 2,3,4,6-tetrakisphosphate (InsP8). These two molecules, 5PP-InsP5 and InsP8, are present in various subcellular compartments, where they participate in regulating diverse cellular processes such as cell death, energy homeostasis, and cytoskeletal dynamics. The synthesis and metabolism of inositol pyrophosphates are subjected to tight regulation, allowing for their highly specific functions. Blocking the 5PP-InsP5/InsP8 signaling pathway by inhibiting the biosynthesis of 5PP-InsP5 demonstrates therapeutic benefits in preclinical studies, and thus holds promise as a therapeutic approach for certain diseases treatment, such as metabolic disorders. [ABSTRACT FROM AUTHOR]

The association between smoking exposure and latent tuberculosis infection (LTBI) has been investigated in a few studies; however, further investigation is needed. In this study, the 2011–2012 NHANES population was used to evaluate smoking exposure and LTBI risk. A total of 7042 participants with available LTBI results and without active tuberculosis were included for analysis. Smoking was defined as participants who smoked at least 100 cigarettes in their life. Both univariable and multivariable analysis were adopted to evaluate smoking exposure, as well as related factors on the risk of LTBI. LTBI rates among current smokers (12.1%) and former smokers (9.9%) were higher than non-smokers (5.9%). However, current smokers and former smokers were not significantly associated with LTBI risk when compared to non-smokers after adjusting by age and sex in the multivariable analysis. Meanwhile, we found that passive smoking was not associated with LTBI (adjusted odds ratio (AOR), 0.85; 95%CI, 0.66–1.09). In multivariable analysis, current smoking was associated with LTBI (OR, 1.67; 95%CI, 1.28–2.19), while former smokers had an increased OR of LTBI, but the OR did not reach statistical significance (OR, 1.15; 95%CI, 0.90–1.48). Household tuberculosis (TB) contact was also related to LTBI (OR, 1.93; 95%CI, 1.25–2.99). However, BMI and diabetes were not found to be associated with LTBI. Smoking, especially current smoking, was significantly associated with LTBI. LTBI screening should be recommended for active smokers. Former smoking and passive smoking exposure were not found to have a significant relationship with LTBI risk. However, the high LTBI rate among quitters indicated we should pay more attention to former smokers with LTBI. [ABSTRACT FROM AUTHOR]

Due to the complexity of the microstructure of porous media, it is of great significance to explore the heat transport mechanism in porous media in many engineering applications. In this study, an expression for effective thermal conductivity (ETC) of porous media embedded with randomly distributed damaged tree-like bifurcation networks is derived based on the theory of thermodynamics and fractal features of tree-like bifurcation networks. We investigate the effect of heat conduction and heat convection in porous media embedded with randomly distributed damaged tree-like bifurcation networks on the ETC of the porous media. It is found that our fractal model has good consistency with the existing available experimental data. In addition, the influence of the microstructural parameters of the model on heat transfer in the porous media is analyzed in detail. The research results can provide significant theoretical guidance for the development and design of heat transfer systems. [ABSTRACT FROM AUTHOR]

Background The evidence-base for mass tuberculosis screening among persons with diabetes (PWD) is poor. We evaluated the yield and costs of mass screening among PWD in eastern China. Methods We included individuals with type 2 diabetes from 38 townships in Jiangsu Province. Screening comprised of physical examinations, symptom screening, and chest X-rays; smear and culture testing were performed through clinical triage. We assessed the yield and number needed to screen (NNS) to detect 1 tuberculosis case among all PWD, those with symptoms, and with suggestive chest X-rays. Unit costing was collected to estimate screening costs and to calculate cost per case detected. We performed a systematic review of other mass tuberculosis screening programs concentrated on PWD. Results Of 89 549 screened PWD, 160 were diagnosed with tuberculosis (179 cases per 100 000 persons; 95% confidence interval [CI]: 153–205). The NNS was 560 (95% CI: 513–606), 248 (95% CI: 217–279), and 36 (95% CI: 24–48) among all participants, with abnormal chest X-rays, and symptoms. The cost per case was high overall (US$13 930) but lower with symptoms (US$1037) and high fasting blood glucose levels (US$6807). From systematic review, the pooled NNS to detect one case among all PWD (regardless of symptoms or chest X-ray results) in high- versus low-burden settings was 93 (95% CI: 70–141) versus 395 (95% CI: 283–649). Conclusions A mass tuberculosis screening program focused on PWD was feasible however, the overall yield was low and not cost-efficient. Risk-stratified approaches may be practical among PWD in low- and medium tuberculosis burden settings. [ABSTRACT FROM AUTHOR]

【Abstract】Objective: To evaluate clinical outcome of suture anchors in strengthening both acromioclavicular and coracoclavicular ligaments in the surgical treatment of acromioclavicular joint dislocation. Methods: Twenty-eight patients with acute traumatic Rockwood III, IV and V dislocations of the acromioclavicular joint surgically treated at our institute between October 2010 and January 2012 were recruited. All patients underwent open reduction combined with suture anchors. Function was evaluated using the ConstantMurley shoulder score. Clinical and radiographic shoulder ratings were evaluated using Taft criteria at 3, 6 and 12 months. Results:Two cases with fixation loosening were not included in final statistical analysis. Other patients obtained full joint reposition on immediate postoperative radiographs. Follow-up was performed with an average of 15.6 months (range, 12-19). After early range of motion exercises, 96.2% of the patients (25/26) could abduct and elevate their shoulders more than 90 degrees within postoperative 3 months. There was no infection. Average Constant-Murley score was 96.3 points (range, 94-100) and mean Taft shoulder rating was 10.7 points (range, 8-12) at 12 months. Conclusion: The suture anchor is a relatively simple technique and can avoid screw removal which is helpful in reconstructing both acromioclavicular and coracoclavicular ligaments in acute traumatic acromioclavicular joint dislocation. Key words: Acromioclavicular joint; Dislocations; Surgery; Suture anchors

Globally, air pollution is amongst the most significant causes of premature death. Nevertheless, studies on the relationship between fine particulate matter (PM2.5) exposure and blood lipids have typically not been population-based. In a large, community-based sample of residents in Yixing city, we assessed the relationship between short-term outdoor PM2.5 exposure and blood lipid concentrations. Participants who attended the physical examination were enrolled from Yixing People's hospital from 2015 to 2020. We collected general characteristics of participants, including gender and age, as well as test results of indicators of blood lipids. Data on daily meteorological factors were collected from the National Meteorological Data Sharing Center (http://data.cma.cn/) and air pollutant concentrations were collected from the China Air Quality Online Monitoring and Analysis Platform (https://www.aqistudy.cn/) during this period. We applied generalized additive models to estimate short-term effects of ambient PM2.5 exposure on each measured blood lipid-related indicators and converted these indicators into dichotomous variables (non- hyperlipidemia and hyperlipidemia) to calculate risks of hyperlipidemia associated with PM2.5 exposure. A total of 197,957 participants were included in the analysis with mean age 47.90 years (± SD, 14.28). The increase in PM2.5 was significantly associated with hyperlipidemia (odds ratio (OR) 1.003, 95% CI 1.001–1.004), and it was still significant in subgroups of males and age < 60 years. For every 10 μg/m3 increase in PM2.5, triglyceride levels decreased by 0.5447% (95% CI − 0.7873, − 0.3015), the low-density lipoprotein cholesterol concentration increased by 0.0127 mmol/L (95% CI 0.0099, 0.0156), the total cholesterol concentration increased by 0.0095 mmol/L (95% CI 0.0053, 0.0136), and no significant association was observed between PM2.5 and the high-density lipoprotein cholesterol concentration. After excluding people with abnormal blood lipid concentrations, the associations remained significant except for the high-density lipoprotein cholesterol concentration. PM2.5 was positively correlated with low-density lipoprotein cholesterol and total cholesterol, and negatively correlated with triglyceride, indicating PM2.5 can potentially affect health through blood lipid levels. [ABSTRACT FROM AUTHOR]

In the study of heat transfer in tree-like branching network, neither the heat convection caused by fluid flow in the tree-like branching network nor the asymmetric structure of the tree-like branching network can be ignored. In this work, we assume the porous media is embedded with a tree-like branching network that are characterized by damaged pipes. We investigated the effects of surface roughness on heat conduction and heat convection in the porous media embedded with the damaged tree-like branching network based on the fractal features of tree-like branching networks and the basic theory of thermodynamics. The proposed model for thermal conductivity can be expressed as a function of micro-structural parameters of the composite, such as the relative roughness, the ratio of thermal conductivity of the wall to that of the fluid in the micro-channel, the diameter ratio, the length ratio, the branching level, the number of damaged channels, the total number of branching levels, and the main tube porosity of the porous media. The effects of the micro-structural parameters of the model on its effective thermal conductivity have been analyzed in detail. It is believed that the joint expression of heat conduction and heat convection could enrich and develop the physical study of heat transport in porous media. [ABSTRACT FROM AUTHOR]