[Relationship between clopidogrel resistance and genetic variability in Kawasaki disease children with coronary artery lesions].

Objective: To analyze the distribution of clopidogrel metabolism-related gene variability in Kawasaki disease (KD) children with coronary artery lesions (CAL) across different age groups and the impact of genetic variability on the efficacy of clopidogrel antiplatelet therapy. Methods: A retrospective cohort study was conducted. Clinical data were collected from 46 KD children with CAL who were hospitalized in the Cardiovascular Center of Children's Hospital of Fudan University between January 2021 and August 2022 and were treated with clopidogrel, including gender, age, body mass index, course of KD, CAL severity grade, and baseline platelet count. According to their age, the children were divided into ≥2-year-old group and <2-year-old group. Their platelet responsiveness was assessed by adenosine diphosphate-induced platelet inhibition rate (ADPi) calculated via thromboelastography, and children were categorized into high on-treatment platelet reactivity (HTPR) and normal on-treatment platelet reactivity (NTPR) groups. Genotypes of CYP2C19, PON1 and ABCB1 were detected. The t test, one-way analysis of variance and Chi-square test were used for intergroup comparison. Results: Among the 46 KD children with CAL, 34 were male and 12 were female; 37 were ≥2-year-old and 9 were <2-year-old; 25 cases were in the HTPR group and 21 cases were in the NTPR group, with 19 HTPR and 18 NTPR in the ≥2-year-old group, and 6 HTPR and 3 NTPR in the <2-year-old group. Genetic analysis showed that 92 alleles among the 46 children, with frequencies of CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*17, PON1 192Q, PON1 192R, ABCB1 3435C, ABCB1 3435T at 59% (54/92), 32% (29/92), 9% (8/92), 1% (1/92), 36% (36/92), 64% (59/92), 63% (58/92) and 37% (34/92), respectively. Analysis of the impact of genotype on ADPi revealed that in children aged ≥2 years, those with CYP2C19*1/*3 genotype had significantly lower ADPi than those with CYP2C19*1/*1 genotype ((34±15)% vs. (61±29)%, t=2.18, P=0.036). There were also no significant difference in ADPi among children with PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes ((40±22)% vs. (52±33)% vs. (65±27)%, F=2.17, P=0.130), or among those with ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((55±34)% vs. (60±27)% vs. (49±24)%, F=0.33, P=0.719). In <2-year-old group, there were no significant differences in ADPi across CYP2C19*1/*1, CYP2C19*1/*2 and CYP2C19*2*2 genotypes ((40±20)% vs. (53±37)% vs. (34±16)%, F=0.37, P>0.05). There were no significant differences in ADPi across CYP2C19*1/*1 and CYP2C19*1/*3 genotypes ((44±27)% vs. (42±20)%, t=0.08, P>0.05). There were no significant differences in ADPi across PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes (45% vs. (55±27)% vs. (24±5)%, F=1.83, P>0.05). There were no significant differences in ADPi across ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((36±16)% vs. (50±35)% vs. 45%, F=0.29, P>0.05). The risk analysis of HTPR in different genotypes revealed that in children aged ≥2 years, carrying at least 1 or 2 loss-of-function alleles of CYP2C19 was a risk factor for HTPR (OR=4.69, 10.00, 95%CI 1.11-19.83, 0.84-119.32, P=0.033, 0.046, respectively), and PON1 192R homozygosity and carrying at least one PON1 192R allele were protective factors against HTPR (OR=0.08, 0.13, 95%CI 0.01-0.86, 0.01-1.19, P=0.019, 0.043, respectively). Conclusion: KD children aged ≥2 years carrying CYP2C19 loss-of-function alleles and PON1 192Q are more likely to develop HTPR.

[Analysis of core functional components in Yinchenhao Decoction and their pathways for treating liver fibrosis].

OBJECTIVE: To analyze the core functional component groups (CFCG) in Yinchenhao Decoction (YCHD) and their possible pathways for treating hepatic fibrosis based on network pharmacology. METHODS: PPI data were extracted from DisGeNET, Genecards, CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1. The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction. A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets. In cultured human hepatic stellate cells (LX-2 cells), the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay; the effects of these compounds on collagen α1 (Col1a1) mRNA expression and the pathways in 20 ng/mL TGF-ß1-stimulated cells were analyzed using RT-qPCR and Western blotting. RESULTS: A total of 1005 pathogenic genes, 226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained. Benzyl acetate, vanillic acid, clorius, polydatin, lauric acid and ferulic acid were selected for CCK-8 verification, and they all showed minimal cytotoxicity below the concentration of 200 µmol/L. Clorius, polydatin, lauric acid and ferulic acid all effectively inhibited TGF-ß1-induced LX-2 cell activation. At the concentration of 200 µmol/L, all these 4 components inhibited PI3K, p-PI3K, AKT, p-AKT, ERK, p-ERK, P38 MAPK and p-P38 MAPK expressions in TGF-ß1-induced LX-2 cells. CONCLUSION: The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate, vanillic acid, clorius, polydatin, lauric acid and ferulic acid, which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.

[Discussion on the relationship between pathological changes of sciatic nerve and Sarm1 protein expression in rats with n-hexane poisoning].

Objective: To explore the potential evidence of active peripheral nerve necrosis when n-hexane produces toxic effects on peripheral nerves. Methods: In May 2023, 36 SPF grade SD male rats with a body weight of 200-220 g were divided into 4 groups with 9 rats in each group and given normal saline and different doses of n-hexane (168, 675, 2 700 mg/kg) by gavage for 6 consecutive weeks (5 days/week). Three rats in each group were killed at the 2nd, 4th and 6th week, respectively. The spinal cord to sciatic nerve tissue was broken and the supernatant was extracted for SDS-PAGE protein isolation. The expression level of Sarm1 protein was analyzed with the ß-Actin color strip of internal reference protein by Western blot. The expression of Sarm1 protein was analyzed by the gray ratio of the two. At the 6th week, the sciatic nerve sections of the each group were observed by light microscope and electron microscope. Results: The number of axons was obviously reduced by light microscopy. According to electron microscope, myelin lesions were mainly local disintegration, deformation, and different thickness. The deformation of axonal surface became smaller. The axons in the nerve bundle membrane showed degeneration and reduction. The gray ratio of Sarm1 protein and internal reference protein bands in each group had no significant change at the second week of exposure, and the ratio of SARM1 protein to internal reference protein bands was 1.47 in the high dose group at the fourth week, and 1.51 and 1.89 in the middle and high dose group at the sixth week, respectively. Conclusion: Waller's degeneration was observed in sciatic neuropathologic manifestations of n-hexane-poisoned rats, and the expression level of Sarm1 protein increased.

[Clinical application of inferior pancreaticoduodenal artery management in laparoscopic pancreaticoduodenectomy].

Objective: To investigate the clinical effect of proper management of inferior pancreaticoduodenal artery (IPDA) in laparoscopic pancreaticoduodenectomy (LPD). Methods: This is a retrospective case series study. The clinical and pathological data of 70 patients who received LPD due to pancreatic head tumors, periampullary tumors, or distal common bile duct tumors in the Pancreatic Center of the Second Clinical College of Guangzhou University of Chinese Medicine from January to December 2022 were retrospectively collected. There were 47 males(67.1%) and 23 females(32.9%),aged (59.9±12.8)years(range:13 to 87 years).The procedure of IPDA exposure was as follows:a middle approach was utilized to expose the right half of superior mesenteric artery(SMA) and its right branches between the SMA and superior mesenteric vein(SMV) in superior colonic region. In the subcolonic region,SMA trunk exposure via dissection along the jejunal artery from feet to head and identification the association between IPDA and jejunal artery were prior to IPDA root ligation and dissection. The safety and efficacy of intraoperative IPDA handling were assessed based on surgical videos. Follow-up was carried out in outpatient clinic or by telephone, and outpatient follow-up was conducted once every 1 to 3 months after surgery. Results: The percentage of total LPD was 98.6%(69/70),with all patients achieving R0 resection. Nine cases(12.9%) were involved in combined vascular resection and reconstruction,with 1 case (1.4%) requiring additional upper abdominal incision for vascular and gastrointestinal reconstruction,while the remaining eight cases (11.4%) were completed laparoscopically. The mean operative time was (432.7±115.4)minutes(range:282 to 727 minutes),and the mean blood loss was (140.0±125.7)ml(range:20 to 800 ml). Only two patients(2.9%) received fresh frozen plasma transfusion,with an average volume of 650 ml. Reliable ligation and safe handling of the IPDA were achieved in 91.4%(64/70) of cases, with 8.6%(6/70) suffering from IPDA injury-related bleeding. No one was converted to opened surgery. Pathologically,the mean tumor size was (3.3±1.6)cm (range:1 to 7 cm),and the mean number of harvested lymph nodes was 17.0±7.3(range:0 to 46). Lymph node metastasis was observed in 13 cases (18.6%). Five cases (13.2%) developed grade B pancreatic fistula,while no grade C pancreatic fistula occurred. Other complications included bile leakage in one case(1.4%),delayed gastric emptying in two cases(2.9%), lymphatic leakage in 2 cases(2.9%),intra-abdominal infection in 9 cases(12.9%),and fat liquefaction of surgical incision in 1 case(1.4%). Two cases(2.9%) experienced postoperative intra-abdominal bleeding,one due to mesangial bleeding of lesser curvature of the stomach and the other due to oozing from the hepatic arterial sheath. These bleeding events were not concerned with IPDA. The average length of postoperative hospital stay was (15.2±4.6)days(range:9 to 28 days). Conclusion: Proper intraoperative management of IPDA in LPD might reduce IPDA-related bleeding during and after surgery and improve the safety of LPD.

[A study on the hearing protection and intervention effects of silicone earplug usage among manufacturing workers].

Objective: To assess the efficacy of silicone earplugs in protecting workers exposed to noise in a typical manufacturing environment, and to provide training interventions for workers who do not achieve the anticipated noise reduction levels, as well as examining the spectral characteristics of earplug attenuation. Methods: From June to August 2022, a total of 294 noise-exposed workers in two manufacturing enterprises equipped with the same type of earplug were studied by cluster sampling method, by conducting questionnaire surveys, collecting data, fitting tests, and providing trainings, the current noise exposure levels of workers in the industry as well as the perception about the earplug were understood. Additionally, the attenuation before and after intervention in workplace were measured, the spectral characteristics of noise reduction were were described and compared. Results: The percentage of workers with Personal Attenuation Rating (PAR) of 0 is 32.7% (96/294), and the baseline pass rates are all below 60%. There were no significant differences in pass rates based on gender, age, noise exposure, education level, or cognition of earplug effectiveness. After adjusting the way that earplugs are worn or changing the type of earplugs, all workers were able to meet their noise reduction requirements. The median PAR improvement for both companies is above 10 dB. The noise attenuation of the earplug vary with frequency, with lower attenuation at 4 000 Hz and higher attenuation at 8 000 Hz, showing some deviation from the nominal values. Conclusion: The difference between the actual sound attenuation value of earplugs and the nominal value is related to the noise frequency. When using silicone earplugs, attention should be paid to the spectral composition of the noise in the workplace.

Rationale for issuing neuroimaging requests for patients with primary headaches in China.

OBJECTIVE: To investigate the prevalence of neuroimaging in patients with primary headaches and the clinician-based rationale for requesting neuroimaging in China. DATA SOURCES AND STUDY SETTING: This study included patients with primary headaches admitted to hospitals and clinicians in China. We identified whether neuroimaging was requested and the types of neuroimaging conducted. STUDY DESIGN: This was a cross-sectional study, and convenience sampling was used to recruit patients with primary headaches. Clinicians were interviewed using a combination of personal in-depth and topic-selection group interviews to explore why doctors requested neuroimaging. DATA COLLECTION: We searched for the diagnosis of primary headache in the outpatient and inpatient systems according to the International Classification of Diseases-10 code of patients admitted to six hospitals in three provincial capitals by 2022.We selected three public and three private hospitals with neurology specialties that treated a corresponding number of patients. PRINCIPLE FINDINGS: Among the 2263 patients recruited for this study, 1942 (89.75%) underwent neuroimaging. Of the patients, 1157 (51.13%) underwent magnetic resonance imaging (MRI), 246 (10.87%) underwent both head computed tomography (CT) and MRI, and 628 (27.75%) underwent CT. Fifteen of the 16 interviewed clinicians did not issue a neuroimaging request for patients with primary headaches. Furthermore, we found that doctors issued a neuroimaging request for patients with primary headaches mostly, to exclude the risk of misdiagnosis, reduce uncertainty, avoid medical disputes, meet patients' medical needs, and complete hospital assessment indicators. CONCLUSIONS: For primary headaches, the probability of clinicians requesting neuroimaging was higher in China than in other countries. There is considerable room for improvement in determining appropriate strategies to reduce the use of low-value care for doctors and patients.

[Study on the fit testing for the workers wearing hearing protection device in machinery manufacturing enterprises].

Objective: To investigate the occupational noise hazards in five machinery manufacturing enterprises, and to evaluate the individual noise reduction values and influencing factors of workers wearing hearing protection device (HPD) by individual fit testing. Methods: From November 2021 to January 2022, 5 machinery manufacturing enterprises in Bao'an District of Shenzhen were selected to conduct an occupational health survey to understand the noise exposure level of workers. The 3MTM E-A-RfitTM fitness test system was used to test the baseline individual sound attenuation value level (PAR) of the daily wear of the ear protecters for 485 workers in typical noise working positions. Workers whose PAR values could not meet the requirements of noise reduction at work were instructed to wear and repeated tests were conducted. PAR results of the workers before and after the intervention were collected and analyzed. Results: The noise workers who received the suitability test were mainly distributed in 24 types of work, the job noise exposure level was 80.2 dB (A) ~ 95.0 dB (A), and the job noise excess rate was 52.5% (138/263). The median baseline PAR [M (Q(1), Q(3)) ] for 485 workers was 6.0 (0.0, 14.0) dB. The baseline PAR of male workers, those with more than 15 years of working experience, those with more than 15 years of using ear guards, those who considered ear guards comfortable to wear, those with college degree or above, and those exposed to noise level 90 dB (A) were higher, and the difference was statistically significant (P<0.05). A total of 275 workers (56.7%) did not pass the baseline PAR test, and there was no statistically significant difference in the intervention rate of workers in different noise groups (P>0.05). PAR in subjects who did not pass baseline after intervention increased from 0.0 (0.0, 3.0) dB to 15.0 (12.0, 18.2) dB. Conclusion: The workplace noise hazard of machinery manufacturing enterprises is serious, and there is a great difference between the baseline PAR and the nominal value of the hearing guard worn by the noise exposed workers. The intervention measures can effectively improve the protective effect of wearing ear protectors.

Carnosine supplementation improves glucose control in adults with pre-diabetes and type 2 diabetes: A randomised controlled trial.

BACKGROUND AND AIMS: Type 2 diabetes (T2DM) is a major cause of morbidity and mortality globally. Carnosine, a naturally occurring dipeptide, has anti-inflammatory, antioxidant, and anti-glycating effects, with preliminary evidence suggesting it may improve important chronic disease risk factors in adults with cardiometabolic conditions. METHODS AND RESULTS: In this randomised controlled trial, 43 adults (30%F) living with prediabetes or T2DM consumed carnosine (2 g) or a matching placebo daily for 14 weeks to evaluate its effect on glucose metabolism assessed via a 2-h 75 g oral glucose tolerance test. Secondary outcomes included body composition analysis by dual energy x-ray absorptiometry (DEXA), calf muscle density by pQCT, and anthropometry. Carnosine supplementation decreased blood glucose at 90 min (-1.31 mmol/L; p = 0.02) and 120 min (-1.60 mmol/L, p = 0.02) and total glucose area under the curve (-3.30 mmol/L; p = 0.04) following an oral glucose tolerance test. There were no additional changes in secondary outcomes. The carnosine group results remained significant before and after adjustment for age, sex, and change in weight (all>0.05), and in further sensitivity analyses accounting for missing data. There were no significant changes in insulin levels. CONCLUSION: This study provides preliminary support for larger trials evaluating carnosine as a potential treatment for prediabetes and the initial stages of T2DM. Likely mechanisms may include changes to hepatic glucose output explaining the observed reduction in blood glucose without changes in insulin secretion following carnosine supplementation.

Improved Dosimetry with Daily Online Adaptive Radiotherapy for Cervical Cancer: Waltzing the Pear.

AIMS: Standard of care radiotherapy for locally advanced cervical cancer includes large margins to ensure the uterocervix remains within the treatment fields over the course of treatment. Daily online cone-beam adaptive radiotherapy corrects for interfractional changes by adjusting the plan to match the target position during each treatment session, thus allowing for significantly reduced clinical target volume (CTV) to planning target volume (PTV) margins. We hypothesise that reduced margins from daily online adaptive radiotherapy will reduce organ at risk dose without compromising target coverage. MATERIALS AND METHODS: Ten patients with cervical cancer (stage IIB-IIIC2) were treated with definitive chemoradiation using daily online cone-beam adaptive radiotherapy in 25-27 fractions. Initial and all adapted treatment plans were generated with CTV to PTV margins versus standard of care image-guided radiotherapy (IGRT) plans as follows: cervix/uterus/gross tumour volume (0.5 versus 1.5 cm), parametria/vagina (0.5 versus 1.0 cm) and nodal chains and gross nodes (0.5 versus 0.5 cm). IGRT plans were created and copied to synthetic computed tomography scans and contours generated from each daily adapted fraction. The dosimetry of each clinically treated online adapted fraction was compared with emulated IGRT plans. Statistical significance was defined as P < 0.05. RESULTS: Daily online cone-beam adaptive radiotherapy significantly improves bowel bag dosimetry compared with IGRT, with a reduction in V40 by an average of 91.3 cm3 [V40 (-6.2%) and V45 (-6.1%)]. The daily adapted plans showed significant improvements in bladder and rectum [V40 (-25.2% and -36.0%) and V30 (-9.7% and -17.1%), respectively]. Additionally, bone marrow had a significantly reduced dose [V10 (-2.7%) and V20 (-3.3%)]. Daily online cone-beam adaptive radiotherapy improved uterocervix CTV coverage and reduced hotspots compared with IGRT [D95% (+1.6%) and Dmax (-0.9%)]. CONCLUSIONS: Reduced CTV to PTV margins achievable with daily online adaptive radiotherapy improves organ at risk dosimetry and target coverage when compared with standard of care IGRT for locally advanced cervical cancer. The clinical impact of improved dosimetry is currently undergoing investigation.

[Research on the protective effect of hearing protective device for workers exposed to noise in a motor manufacturing enterprise].

Objective: To understand the current situation of noise hazard in a motor manufacturing enterprise, and to explore the protective effect of workers wearing hearing protective device and its possible influencing factors. Methods: In November 2021, a total of 179 noise workers wearing hearing protective devices in a motor manufacturing company in a city were selected as research objects. Personal attenuation rating (PAR) of workers wearing hearing protective devices was measured. Baseline PAR was analyzed for different subgroups of basic demographic information, noise exposure, and the use of hearing protective devices to evaluate the effect of the intervention. Baseline PAR was compared using nonparametric tests. Results: There were 179 workers from 35 positions in 4 types of work, and the over-standard noise rate was 51.2% (42/82), among which the noise exposure intensity of motor equipment debugging workers was the highest [94.4 dB (A) ]. Compared the baseline PAR of different characteristics, it was found that the baseline PAR of male workers, workers whose daily noise exposure time were <8 h, workers who had used the hearing protective devices for 10 to 14 years, and workers who thought the hearing protective devices were comfortable were all higher, and the differences were statistically significant (P<0.05). Baseline PAR passing rate was 43.0% (77/179), and PAR of 102 workers who did not pass baseline test increased from 0 (0, 3) dB before intervention to 14 (12, 16) dB after intervention, with statistical significance (P<0.05) . Conclusion: The noise hazard in this motor manufacturing enterprise is serious, and the protective effect of workers wearing hearing protective devices is not good. Gender, daily noise exposure time, years and comfort of wearing hearing protective device are the possible influencing factors of poor protective effect.

Clinical characteristics and risk factors of diabetic foot ulcers with PAD.

OBJECTIVE: This study aimed to analyze the clinical characteristics of patients with diabetic foot ulcers combined with peripheral arterial disease (PAD) and the risk factors. PATIENTS AND METHODS: A retrospective study was conducted on 120 patients with diabetic foot ulcers in the Second Affiliated Hospital of Dalian Medical University from October 2018 to February 2021. The patients were divided into uncombined with the PAD group (42 cases) and combined with the PAD group (78 cases). The baseline information and clinical indicators were measured from two groups. Univariate and binary logistic regression was used to analyze the risk factors of PAD in patients with diabetic foot ulcers. RESULTS: The proportion of patients with age ≥ 60 years, Wagner grade 4-5 and smoking history in the combined group was higher than that in the uncombined group (p < 0.05). The diastolic blood pressure (DBP) of the combined group was lower than that of the uncombined group, while the C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and glycated hemoglobin (HbA1c) levels of the combined group were higher than those of the uncombined group (p < 0.05). Binary logistic regression analysis showed that age ≥ 60 years, high Wagner grade, smoking, elevated CRP, NLR and HbA1c levels were risk factors for patients with diabetic foot ulcer combined with PAD (OR > 1, p < 0.05). An elevated DBP level was the protective factor for PAD in patients with diabetic foot ulcer (OR < 1, p < 0.05). CONCLUSIONS: Patients with diabetic foot ulcer combined with PAD have the clinical characteristics of poor blood pressure control, long course of disease, and low ABI value. Age ≥ 60 years, high Wagner grade, smoking history, elevated CRP, NLR and HbA1c levels are the risk factors of PAD in patients with diabetic foot ulcer. Increased DBP is protective for PAD in patients with diabetic foot ulcer.

An E-band multi-channel Doppler backscattering system on EAST.

An E-band (60-90 GHz) multi-channel Doppler backscattering (DBS) system with X-mode polarization has been installed on the Experimental Advanced Superconducting Tokamak (EAST), which can measure the turbulence at five different radial locations simultaneously. This system can launch 31 fixed microwave frequencies in the range of 60-90 GHz with a 1 GHz interval into the plasma, and five probing signals are selected by employing a reference signal and multiple filters. During experiments, the frequency of the reference signal is tunable in the E-band, and the selected probing signals can be changed as needed without any other adjustments, which can be performed in one shot or between shots. Furthermore, the incident angle can be adjusted from -10° to 20°, and the wavenumber range is 4-25 cm-1 with a wavenumber resolution of Δk/k ≤ 0.35. Ray tracing simulations are employed to calculate the scattering locations and the perpendicular wavenumber. In this article, the hardware design, ray tracing, and initial results obtained from the EAST plasma will be presented.

[Application and value of body composition measurement in the evaluation of efficacy of bariatric and metabolic surgery].

The use of bariatric and metabolic surgery as a central treatment for obesity has been steadily increasing. BMI, as a widely used metric for assessing obesity, has considerable relevance in the field of metabolic research. However, its limitations, such as its inability to account for variations in fat distribution, remain a subject of considerable controversy. In recent years, there has been a surge of interest in the relationship between changes in body composition and the risk of metabolic disease. Consequently, the study of the effects of bariatric and metabolic surgery on changes in body composition has become a major focus of bariatric and metabolic surgery research. As a potential replacement for BMI, body composition measurements are expected to improve and standardize the assessment of the effectiveness of bariatric and metabolic surgery. This underscores the urgent need for the development of methods and standards for body composition measurement. This paper undertakes a comprehensive review of the existing evidence on the application of body composition measurement techniques for the efficacy evaluation of bariatric and metabolic surgery. The intent is to provide new insights and pave the way for the exploration of future research directions in this area.

Carnosine Did Not Affect Vascular and Metabolic Outcomes in Patients with Prediabetes and Type 2 Diabetes: A 14-Week Randomized Controlled Trial.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality in patients with prediabetes and type 2 diabetes mellitus (T2DM). Carnosine has been suggested as a potential approach to reduce ASCVD risk factors. However, there is a paucity of human data. Hence, we performed a 14-week double-blind randomized placebo-controlled trial to determine whether carnosine compared with placebo improves vascular and metabolic outcomes in individuals with prediabetes and T2DM. In total, 49 patients with prediabetes and T2DM with good glycemic control were randomly assigned either to receive 2 g/day carnosine or matching placebo. We evaluated endothelial dysfunction, arterial stiffness, lipid parameters, blood pressure, heart rate, hepatic and renal outcomes before and after the intervention. Carnosine supplementation had no effect on heart rate, peripheral and central blood pressure, endothelial function (logarithm of reactive hyperemia (LnRHI)), arterial stiffness (carotid femoral pulse wave velocity (CF PWV)), lipid parameters, liver fibroscan indicators, liver transient elastography, liver function tests, and renal outcomes compared to placebo. In conclusion, carnosine supplementation did not improve cardiovascular and cardiometabolic risk factors in adults with prediabetes and T2DM with good glycemic control. Therefore, it is improbable that carnosine supplementation would be a viable approach to mitigating the ASCVD risk in these populations. The trial was registered at clinicaltrials.gov (NCT02917928).

[ARHGAP21 inhibits epithelial-mesenchymal transition by inactivating the WNT signaling pathway in non-small cell lung cancer].

OBJECTIVE: To investigate the role of Rho GTPase-activating protein 21 (ARHGAP21) in regulating the migration and metastasis of non-small cell lung cancer (NSCLC) cells. METHODS: TCGA, CPTAC database were used to analyze the correlation of ARHGAP21 expression level in NSCLC and the patients' prognosis. The expression of ARHGAP21 in clinical specimens of NSCLC tissues was examined using Western blotting and immunohistochemistry. The effect of ARHGAP21 knockdown on migration ability of lung cancer cell lines was examined using Transwell assay and wound healing assay. A nude mouse model with injection of lung cancer H1299 cells via the tail vein was used to examine the effect of ARHGAP21 knockdown on the metastatic ability of the tumor cells. The possible mechanism of ARHGAP21 was predicted by bioinformatics analysis and verified using Western blotting. RESULTS: A low ARHGAP21 expression was associated with poor prognosis of patients with NSCLC (P < 0.05). ARHGAP21 expression was significantly downregulated in lung cancer tissues as compared with the adjacent tissues (P < 0.001). In cultured lung cancer cells, ARHGAP21 knockdown obviously promoted the migration ability of the cells (P < 0.001). In the nude mouse models, injection of H1299 cells with ARHGAP21 knockdown, as compared with the negative control cells, resulted in a greater number of metastatic lung cancer nodules (P < 0.05), which expressed higher levels of N-cadherin and vimentin. Bioinformatic analysis showed a close correlation of ARHGAP21 with APC, GSK3ß, and Axin (P < 0.001). Western blotting showed that ARHGAP21 knockdown significantly decreased ubiquitination of ß-catenin, upregulated N-cadherin and activated the WNT signaling pathway in the lung cancer cells. CONCLUSION: ARHGAP21 downregulation can significantly promote the migration and metastatic ability of NSCLC possibly as a result of WNT signaling pathway activation, which reduces the ubiquitination of ß-catenin by affecting the expressions of APC, GSK3ß, and Axin.

[The clinical value of radical resection of retroperitoneal lipo-lymphatic layer for pancreatic head cancer].

Objective: To investigate the clinical value of the novel approach,radical resection of the retroperitoneal lipo-lymphatic layer (RRRLLL),in the surgical treatment of resectable pancreatic head cancer. Methods: Between June 2020 and June 2022,a total of 221 patients with pancreatic head cancer underwent surgical treatment using the RRRLLL approach(RRRLLL group),while 107 patients received traditional surgical treatment(traditional group) in five high-volume pancreatic centers in China. Data from surgical technique and clinical perioperative outcomes,including lymph node harvested,surgical time,and complications,were analyzed. The RRRLLL group consisted of 144 males and 77 females with an age of (67.5±9.0) years(range:41.3 to 81.1 years). The traditional group included 71 males and 36 females,with an age of (66.3±8.1) years(range:45.1 to 79.2 years). Statistical analysis was performed using the K-S test,Z test,or χ2 test. Results: Pancreaticoduodenectomy was performed successfully in all patients,achieving R0 resection. RRRLLL group surgery required mobilization of retroperitoneal adipose and lymphatic tissues starting from the right edge of the inferior vena cava and extending to the left side,up to the superior mesenteric artery,down to the inferior mesenteric artery,and left to the left side of the aorta,including the perineural and lymphatic tissues around the superior mesenteric artery and the sheath of the mesenteric artery. However,the traditional group did not include the areas mentioned above in the scope of clearance. There were no statistically significant differences between the RRRLLL group and the traditional group in terms of age,sex,tumor size,T stage,and vascular invasion (all P>0.05). However,the number of lymph nodes harvested in the RRRLLL group was significantly higher at 28.7±9.0 (range: 18 to 39) compared to 18.2±8.0 (range: 12 to 21) in the traditional group (Z=-10.691,P<0.05). There were no statistically significant differences in the number of positive lymph nodes,N staging,and postoperative complications between the two groups. Conclusion: The RRRLLL approach improved lymph node dissection compared to the traditional approach,potentially leading to reduced recurrence rates.

[Correlation of cognitive function with intracranial lesions and the degree of depression and anxiety in patients with neuromyelitis optica spectrum disorders].

Objective: To investigate the correlation of cognitive dysfunction with intracranial lesions and symptoms of depression and anxiety in patients with neuromyelitis optica spectrum disorders (NMOSD). Methods: Thirty-one NMOSD patients (7/24 males/females) were enrolled in the Department of Neurology of the Sixth Medical Center of the PLA General Hospital from August 2019 to August 2022. The average age was 42±13 years, and the average education level was 12 (9, 12) years. There were 30 healthy controls, 11/19 males/females, with an average age of 47±9 years and an average education of 12 (9, 15) years. The general clinical data and imaging data were collected, and the subjects were assessed on their cognition, anxiety and depression using the assessment scale approved at home and abroad. A cross-sectional study was conducted on them. The t-test or Wilcoxon test was used for inter-group comparison, and Pearson test or Spearman test was used to explore the correlation between the cognition of NMOSD patients and their intracranial lesions, depression and anxiety. Results: Compared with the healthy control group, NMOSD patients had significantly lower scores on MoCA (Z=-3.10,P=0.002), CRAVLT-N7 (Z=-5.12, P<0.001), CRAVLT-N8 (t=-4.40, P<0.001), ROCF-R (t=-3.10,P<0.01), ROCF-C (Z=-2.72,P<0.01), PASAT-3 (Z=-2.71,P<0.01), PASAT-2 (Z=-3.14,P<0.01), and CWT-A (Z=-3.10,P<0.01)scales. Frontal lobe lesions were negatively correlated with PASAT-2 (r=-0.448, P=0.012) scores, temporal lobe lesions were negatively correlated with CRAVLT-N9 (r=-0.564, P=0.001), and parietal lobe lesions were negatively correlated with MoCA (r=-0.374, P=0.038), PASAT-3 (r=-0.426, P=0.017), and PASAT-2 (r=-0.459, P=0.009) scores; The scores of MoCA (r=-0.392, P=0.029), CRAVLT-N6 (r=-0.396, P=0.028), CRAVLT-N7 (r=-0.415, P=0.020), CRAVLT-N8 (r=-0.406, P=0.023), PASAT-3 (r=-0.537, P=0.002) and PASAT-2 (r=-0.495, P=0.005) scales were negatively correlated with the scores of HAMD assessment, and the scores of PASAT-3 (r=-0.499, P=0.004) and PASAT-2 (r=-0.452, P=0.011) were negatively correlated with the scores of HAMA. Conclusions: The cognitive function of patients with NMOSD is significantly reduced, involving multiple cognitive domains. The cognitive function is affected by the distribution of intracranial lesions and the degree of depression and anxiety.

[Evaluation of the effectiveness of the evidence base multi-discipline critical strategies on the temperature and clinical outcomes in very preterm infants].

To evaluate the effectiveness of intervention plans developed by the evidence base multi-discipline critical strategies (EBPCS) on temperature and clinical outcomes in very preterm infants (VPIs) born at<32 weeks. Clinical data were collected from VPIs born in the delivery room/operating room of Chengdu Women's and Children's Central Hospital from May 1, 2021, to May 31, 2022, who required immediate temperature management and were transferred to the neonatal intensive care unit (NICU) of the hospital. The study population was randomly divided into a control group and an intervention group based on the random number table method, with 108 cases in each group. The control group implemented the conventional temperature management recommended by domestic guidelines, while the intervention group adopted EBPCS interventions compared to the control group. The differences in body temperature and clinical outcomes between the two groups were compared after the implementation of different temperature management strategies. A total of 216 VPIs were included. The intervention group had a lower incidence of hypothermia (30.55% vs. 87.03%, P<0.001), higher mean body temperature admitted to the NICU [(36.56±0.31) ℃ vs. (35.77±0.53) ℃, P<0.001], a lower dose of pulmonary surfactant [(115.94±36.96) mg/kg vs. (151.41±54.68) mg/kg, P=0.014], shorter duration of mechanical ventilation [(5.77±1.26) days vs. (14.19±4.63) days, P=0.006], and lower incidence of intraventricular haemorrhage (12.04% vs. 23.15%, P=0.032). The implementation of temperature intervention strategies developed by the EBPCS for VPIs after birth could prevent and reduce the incidence of hypothermia and improve clinical outcomes.