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 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 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 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.

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.

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.

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*

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 assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.