Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Objective To investigate the level and diagnostic value of microRNA(miR)-483-3p in the serum of patients with essential hypertension(EH).Methods A total of 180 EH patients ad-mitted in Department of Cardiology of Sanya Central Hospital from January 2021 to March 2023 were enrolled as the study group,and another 160 healthy volunteers matched in general clinical data and taking physical examination during the same period were subjected as the control group.RT-qPCR was used to detect miR-483-3p levels in the sera of the 2 groups.Results The levels of TC,TG,LDL-C,SBP,and DBP were significantly higher(P＜0.01),so was the serum miR-483-3p level(2.15±0.57 vs 1.00±0.05,P＜0.01)in the study group than the control group.The serum miR-483-3p level was in an obvious upward trend in the patients with hypertension of grades 1,2,and 3(1.44±0.45 vs 1.79±0.58 vs 3.35±0.64,P＜0.05).The level was positively correlated with hypertension grade in the study group(r=0.745,P=0.000),and the levels of TC,TG,LDL-C,SBP and DBP(P＜0.01).miR-483-3p,TC,LDL-C,SBP and DBP were independent influencing factors for EH(P＜0.05,P＜0.01).The AUC value of serum miR-483-3p level for predicting EH was 0.923(95％CI:0.890-0.949).Conclusion Serum miR-483-3p level is increasing with severi-ty of EH,and has a high diagnostic value for the disease.

Objective:To compare the effect of a 3D-printed ankle and foot orthosis (AFO) with that of a traditional AFO on the recovery of walking function after a stroke.Methods:Thirty-four hemiplegic stroke survivors were randomly divided into an observation group and a control group, each of 17. Both groups were taught good limb placement and given joint mobility, standing and walking training for 4 weeks wearing either a 3D-printed or a conventional AFO. Walking speed, walking endurance, and dynamic balance were evaluated before and after the experiment using the 10-metre walk test (10MWT), the 6-minute walk test (6MWT), and the timed up and go test (TUGT). Integrated electromyography (iEMG) was also performed on each subject′s bilateral rectus femoris, anterior tibialis, and gastrocnemius muscles during walking, and their healthy and affected side iEMG results were compared to assess the activation of the affected lower limb muscles.Results:After treatment, the 10MWT, 6MWT, and TUGT results of both groups had improved significantly, but the observation group′s average results were then significantly better than those in the control group. The iEMG disparities between the healthy and affected sides had also decreased significantly, but on average the disparities in the observation group were significantly smaller than in the control group.Conclusion:Both types of AFO can effectively improve the walking speed, walking endurance, and dynamic balance of hemiplegic stroke survivors and promote muscle activation in the affected lower limb. A 3D-printed AFO is relatively more effective.

Objective To explore the clinical effect of nursing intervention program based on social support and information motivation behavioral model for pregnant women with gestational diabetes mellitus(GDM).Methods A total of 104 pregnant women with GDM admitted to Linping District,the Second Affiliated Hospital of Zhejiang University School of Medicine from February 2020 to February 2022 were selected as study objects,and were divided into experimental group and control group by random number table method,with 52 cases in each group.The pregnant women in control group were given routine nursing intervention,and the pregnant women in experimental group were given social support and information motivation behavioral model nursing intervention based on routine nursing.The depression-anxiety-stress scale,disease cognition and health behavior,blood glucose control during pregnancy,perinatal maternal and infant complications and delivery mode were compared between two groups.Results After the intervention,the scores of depression,anxiety,stress,fasting blood glucose,2-hour postprandial blood glucose and glycosylated hemoglobin of pregnant women in experimental group were significantly lower than those in control group,and the scores of disease cognition,health promoting lifestyle profile and vaginal delivery rate were significantly higher than those in control group(P<0.05).The complication rate of pregnant women and perinatal infants in experimental group was significantly lower than that in control group(P<0.05).Conclusion The nursing intervention program based on social support and information motivation behavioral model has good effect on pregnant women with GDM,which can enable pregnant women to obtain more social support,reduce negative emotions,improve health behaviors,promote blood glucose control,and increase the rate of natural childbirth.

Objective:To investigate genetic variation profiles of δ-globin (HBD gene) and hematological phenotypes in Guangdong population.Methods:Retrospective case analysis was performed in this study. Blood samples of 11 616 couples who participated in free thalassemia screening in Guangzhou from July 2020 to December 2022 were collected which underwent blood routine tests and hemoglobin (Hb) capillary electrophoresis. According to the results, 154 samples were enrolled in this study: (1)group of 35 cases with HbA 2 <2.0% but no HbF band; (2)group of 64 cases with HbA 2 < 2.0% and HbF band; (3)group of 25 cases with HbA 2 <2.0% and suspected HbA 2 variants; (4) group of 25 cases with HbA 2 ≥2.0% and <3.5% and HbF band, as well as abnormal blood routine report [mean corpuscular volume (MCV) <82 fl and/or mean corpuscular hemoglobin (MCH) <27 pg]; (5)group of 5 cases with HbA 2 ≥2.0% and <3.0% accompanied with β thalassemia gene carriers Sanger sequencing was used to detect single nucleotide variants of δ-globin. Results:(1) A total of 22 genetic variations were detected, including 6 de novo variations, and the top 3 genetic variations were respectively c.-127T>C (57.02%, 65/114), c.-80T>C (9.65%, 11/114), c.349C>T (7.89%, 9/114). (2) In group of patients with HbA 2 <2.0% but no HbF band, 22 cases (62.85%, 22/35) had HBD gene variation, including 7 cases with MCV and MCH lower than reference values, 4 cases with α thalassemia; 13 cases had no HBD gene variation, including 12 cases with lower MCV and MCH. Among 19 cases with abnormal blood routine test results, levels of HbA 2 in patients (7 cases) with HBD gene variation were lower compared with those without HBD gene variation (12 cases) ( P<0.01%). (3)In group of patients with HbA 2<2.0% with HbF band, 59 cases (92.18%, 59/64) had HBD gene variations whose mutations all occurred in promoter region, and the HbF were all lower than 5.0%; 5 cases with HbF >5.0% had no HBD gene variation. (4) In group of patients with HbA 2 <2.0% and suspected HbA 2 variants, the detection rate was 100% (25/25) and δ-globin variants <1.0%. (5) In group of patients with HbA 2 ≥2.0% and <3.5% and HbF band accompanied with abnormal blood routine results, no HBD gene variation was found. (6) In group of 5 patients with HbA 2 ≥2.0% and <3.0% with β thalassemia gene carriers, HBD gene variation were found in all cases, and the level of HbA 2 was (2.62±0.17)% and HbF was (3.62±2.22)%. Conclusions:There are various genotypes of HBD gene variation, among which HBD: c.-127T>C is the most common in Guangdong population in China. Mutations in the promoter region may cause decrease in HbA 2 and increase in HbF which is mostly less than 5% but exceeds 5.0% when combined with β thalassemia. Our study enriched the gene mutation profiles of HBD gene in Guangdong population.

The nucleus tractus solitarii (NTS) is one of the morphologically and functionally defined centers that engage in the autonomic regulation of cardiovascular activity. Phenotypically-characterized NTS neurons have been implicated in the differential regulation of blood pressure (BP). Here, we investigated whether phenylethanolamine N-methyltransferase (PNMT)-expressing NTS (NTS^PNMT) neurons contribute to the control of BP. We demonstrate that photostimulation of NTS^PNMT neurons has variable effects on BP. A depressor response was produced during optogenetic stimulation of NTS^PNMT neurons projecting to the paraventricular nucleus of the hypothalamus, lateral parabrachial nucleus, and caudal ventrolateral medulla. Conversely, photostimulation of NTS^PNMT neurons projecting to the rostral ventrolateral medulla produced a robust pressor response and bradycardia. In addition, genetic ablation of both NTS^PNMT neurons and those projecting to the rostral ventrolateral medulla impaired the arterial baroreflex. Overall, we revealed the neuronal phenotype- and circuit-specific mechanisms underlying the contribution of NTS^PNMT neurons to the regulation of BP.
Solitary Nucleus/metabolism* ; Blood Pressure/physiology* ; Phenylethanolamine N-Methyltransferase/metabolism* ; Neurons/metabolism* ; Paraventricular Hypothalamic Nucleus/metabolism*

In the face of a serious occupational disease prevention and control situation, the lack of efficient supervision and regulation methods has become a prominent contradiction. This paper reviewed the progress and application of occupational health grading and classification supervision methods for employers in China in recent years, and analyzed the characteristics and limitations of selected methods. The grading and classification supervision methods have gradually developed from considering only inherent health risk of occupational disease hazards, to considering both inherent attributes of occupational disease hazards and exposure duration. Some regional authorities introduced trial measures for grading and classification of occupational health supervision by embracing exposure level of an occupational disease hazard of interest, associated outcome severity, and occupational health management situation of targeted employers. In October 2022, the National Disease Control and Prevention Bureau issued the Notice on Carrying out Pilot Work of Occupational Health Classification Supervision and Law Enforcement, which further promoted the establishment of a differentiated occupational health supervision model. Grading and classification of occupational health supervision can improve the supervision efficiency of public health administration departments and promote employers to fulfill the main responsibility of occupational disease prevention and control.

Throughout the 1 34-year development of hepatectomy,whether open,laparoscopic,or robotic,it has inherited an anatomical,empirical surgical approach based on morphology,which has not fundamentally changed the two-dimensional diagnosis and treatment of the disease.Over the last 20 years,the diagnosis and treatment of primary liver cancer have undergone profound changes with the advent and evolution of digital intelligent diagnosis and treatment technologies.Three-dimensional visualization techniques have allowed the pre-operative visualization of tumors and complex liver anatomy,changing the traditional two-dimensional diagnosis and treatment paradigm.The development of indocyanine green fluorescence imaging has enabled intraoperative visualization of tumor boundaries at the molecular and cellular levels.The application of augmented reality navigation technology has allowed the visualization of anatomical structures during surgery.Hepatectomy has transformed from traditional empirical surgery into modern intelligent navigation-based minimally invasive surgery,ushering in a new era of digital intelligent liver surgery.This review has summarized the most recent research progress of digital intelligent minimally invasive treatment of primary liver cancer.

Objective:To report 2 young infants of sodium channel related epilepsy with SCN2A gene mutation, and to discuss the clinical characteristics of the disease and the efficacy and safety of lacosamide combined with the literature.Methods:Corresponding information of 2 children hospitalized in the Department of Neurology of Hunan Children′s Hospital in July 2021 and October 2021 was collected, including the symptoms, comprehensive physical examination, blood, cerebrospinal fluid, imaging, electrophysiological examination, diagnosis and treatment process, response to treatment and other clinical data, as well as the sequencing results of the whole exome of the children. The efficacy and safety of lacosamide were analyzed, and the related literatures of the Biomedical Literature Database, Wanfang Data Knowledge Service Platform and Chinese Knowledge Infrastructure Database were searched and reviewed.Results:Both of the 2 cases were girl. Their onset age was within 3 months. The initial symptoms were frequent convulsions and backward development. There was no structural abnormality in the head image. The convulsions could not be controlled according to conventional multidrug treatment. The seizures were quickly controlled with lacosamide. Now they have been followed up for 6 months. No obvious adverse reactions were found. Case 1 gene test results showed the SCN2A gene (chr2:166152333-166246334) heterozygous deletion, SCN1A gene (chr2:166847754-16693013) heterozygous deletion, the deletion size being about 5.72 Mb. Case 2 gene test results showed new missense mutation of SCN2A (c.1285G>A, p.Glu429Lys). There were dozens of seizures every day. They were treated with valproic acid, oxcarbazepine and levetiracetam successively. The seizures could not be controlled. Three focal seizures originated in the left temporal region were detected by electroencephalogram. There was no recurrence on the third day after adding lacosamide, and there was no attack after 5 months of follow-up. No obvious adverse reactions were found during follow-up.Conclusions:Sodium channel related epileptic encephalopathy often starts early, has frequent seizures, and can be accompanied by backward psychomotor development at the same time. The slow sodium channel blocker lacosamide has good efficacy and safety in the treatment of sodium channel-related epilepsy with SCN2A gene mutation or combined SCN1A gene mutation.

Objective To analyze the risk factors of multi-drug resistant organism (MDRO) infection after liver transplantation. Methods The clinical data of 77 recipients undergoing liver transplantation were retrospectively analyzed. According to the incidence of MDRO infection, all recipients were divided into the non-MDRO infection group (n=51) and MDRO infection group (n=26). The infection rate and strain distribution of MDRO in liver transplant recipients were summarized. The risk factors of MDRO infection in liver transplant recipients were identified. Clinical prognosis of all recipients was statistically compared between two groups. Results The infection rate of MDRO after liver transplantation was 34% (26/77), mainly carbapenem-resistant MDRO infection. The main sites of infection included lung, abdominal cavity and incision. Univariate analysis showed that postoperative tracheal intubation ≥48 h, length of intensive care unit (ICU) stay ≥72 h, length of hospital stay ≥30 d, re-operation, continuous renal replacement therapy (CRRT) and tacrolimus (Tac) blood concentration ≥15 ng/mL were the risk factors for MDRO infection after liver transplantation. Cox regression analysis indicated that postoperative tracheal intubation≥48 h, re-operation, CRRT and Tac blood concentration ≥15 ng/mL were the independent risk factors for MDRO infection after liver transplantation. The fatality in the MDRO infection group was significantly higher than that in the non-MDRO infection group [31%(8/26) vs. 10%(5/51), P=0.01]. Conclusions Postoperative tracheal intubation ≥48 h, re-operation, CRRT and Tac blood concentration ≥15 ng/mL may increase the risk of MDRO infection after liver transplantation and affect clinical prognosis of the recipients.