[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].

Objective:To investigate the association between peak growth hormone(GH) levels and body fat mass as well as body fat percentage in children with short stature.Methods:This retrospective study included 477 children diagnosed with short stature at the Affiliated Hospital of Jining Medical University between January 2021 and November 2024, based on data from the Growth and Development Disease Follow-up Cohort Study(GDDSD) in Shandong Province. Clinical data including anthropometric measurements, laboratory tests, and body composition were collected. The relationship between GH peak and body fat mass and percentage were analyzed using smooth curve fitting and multiple piecewise linear regression models.Results:In univariate linear regression analysis, both body fat mass and body fat percentage were positively correlated with age, height, weight, body mass index, triglycerides, low density lipoprotein-cholesterol, fasting blood glucose, total body water, protein, and skeletal muscle mass(all P<0.05), and negatively correlated with GH peak and high density lipoprotein-cholesterol. After adjusting for potential confounding factors, a nonlinear relationship was observed between GH peak and both body fat mass and body fat percentage, with inflection points at 6.80 ng/mL and 7.75 ng/mL, respectively. When GH peak was below the inflection point, it was significantly negatively correlated with body fat mass and percentage( P<0.001). However, when GH peak exceeded the inflection point, the associations were no longer statistically significant( P>0.05). Conclusions:This study demonstrates a nonlinear relationship between peak GH levels and body fat percentage in children with short stature. At lower GH peaks, both body fat mass and body fat percentage increase significantly, which may contribute to an elevated future risk of cardiovascular disease.

Objective:To investigate the association between peak growth hormone(GH) levels and body fat mass as well as body fat percentage in children with short stature.Methods:This retrospective study included 477 children diagnosed with short stature at the Affiliated Hospital of Jining Medical University between January 2021 and November 2024, based on data from the Growth and Development Disease Follow-up Cohort Study(GDDSD) in Shandong Province. Clinical data including anthropometric measurements, laboratory tests, and body composition were collected. The relationship between GH peak and body fat mass and percentage were analyzed using smooth curve fitting and multiple piecewise linear regression models.Results:In univariate linear regression analysis, both body fat mass and body fat percentage were positively correlated with age, height, weight, body mass index, triglycerides, low density lipoprotein-cholesterol, fasting blood glucose, total body water, protein, and skeletal muscle mass(all P<0.05), and negatively correlated with GH peak and high density lipoprotein-cholesterol. After adjusting for potential confounding factors, a nonlinear relationship was observed between GH peak and both body fat mass and body fat percentage, with inflection points at 6.80 ng/mL and 7.75 ng/mL, respectively. When GH peak was below the inflection point, it was significantly negatively correlated with body fat mass and percentage( P<0.001). However, when GH peak exceeded the inflection point, the associations were no longer statistically significant( P>0.05). Conclusions:This study demonstrates a nonlinear relationship between peak GH levels and body fat percentage in children with short stature. At lower GH peaks, both body fat mass and body fat percentage increase significantly, which may contribute to an elevated future risk of cardiovascular disease.

ObjectiveThis study aims to examine the effect of Rhei Radix et Rhizoma-Coptidis Rhizoma on reducing insulin resistance in db/db mice by regulating the adenylate activated protein kinase （AMPK）/UNC-51-like kinase 1 （ULK1）/key molecule of autophagy， benzyl chloride 1 （Beclin1） pathway and elucidate the underlying mechanism. MethodSixty 6-week-old male db/db mice were studied. They were randomly divided into the model group， metformin group （0.26 g·kg^-1）， and low-， middle-， and high-dose groups （2.25， 4.5， 9 g·kg^-1） of Rhei Radix et Rhizoma-Coptidis Rhizoma. A blank group of db/m mice of the same age was set， with 12 mice in each group. After eight weeks of continuous intragastric administration， the blank group and model group received distilled water intragastrically once a day. The survival status of the mice was observed， and fasting blood glucose （FBG） was measured using a Roche blood glucose device. Fasting serum insulin （FINS） was measured using an enzyme-linked immunosorbent assay， and the insulin resistance index （HOMA-IR） was calculated. Hematoxylin-eosin （HE） staining was performed to observe the pathological changes in the liver of the mice. The protein expression levels of AMPK， Beclin1， autophagy associated protein 5 （Atg5）， and p62 in liver tissue were determined by using Western blot. The protein expression levels of autophagy associated protein 1 light chain 3B （LC3B） and ULK1 in liver tissue were determined using immunofluorescence. Real-time fluorescence quantitative PCR （Real-time PCR） was used to measure mRNA expression levels of AMPK， Beclin1， Atg5， ULK1， and p62. ResultCompared with the blank group， the model group exhibited a significant increase in body mass （P<0.01）. Additionally， the levels of FBG， FINS， and HOMA-IR significantly changed （P<0.01）. The structure of liver cells was disordered. The protein expression levels of AMPK， Beclin1， and Atg5 in liver tissue were significantly decreased （P<0.01）， while the expression level of p62 protein was significantly increased （P<0.01）. The expression levels of mRNA and proteins were consistent. Compared with the model group， the body mass of the metformin group and high and medium-dose groups of Rhei Radix et Rhizoma-Coptidis Rhizoma was significantly decreased （P<0.05）. FBG， FINS， and HOMA-IR were significantly decreased （P<0.05，P<0.01）. After treatment， the liver structure damage in each group was alleviated to varying degrees. The protein expressions of AMPK， Beclin1， Atg5， LC3B， and ULK1 were increased （P<0.05，P<0.01）， while the protein expression of p62 was decreased （P<0.01）. The expression levels of mRNA and proteins were generally consistent. ConclusionThe combination of Rhei Radix et Rhizoma-Coptidis Rhizoma can effectively improve liver insulin resistance， regulate the AMPK autophagy signaling pathway， alleviate insulin resistance in db/db mice， and effectively prevent the occurrence and development of type 2 diabetes.

ObjectiveTo investigate the effect and mechanism of Zhenwutang on renal oxidative damage in the mouse model of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency via the nuclear factor erythroid 2-related factor-2 （Nrf2）/heme oxygenase-1 （HO-1）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodTwenty-five 7-week-old SPF-grade male db/m mice and 95 7-week-old SPF-grade male db/db mice were adaptively fed for a week. A blank group was set with the db/m mice without treatment， and the other mice were administrated with Rhei Radix et Rhizoma decoction and hydrocortisone for the modeling of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency. The modeled mice were randomized into the model， irbesartan （25 mg·kg^-1）， and high-， medium-， low-dose （33.8， 16.9， 8.45 g·kg^-1） Zhenwutang groups （n=15） and administrated with corresponding drugs for 8 weeks. The survival status of mice was observed， and the traditional Chinese medicine （TCM） syndrome score was recorded. The indicators related to spleen-kidney Yang deficiency， fasting blood glucose （FBG）， and renal function indicators were determined. Hematoxylin-eosin staining was employed to observe the histopathological changes of the renal tissue in each group. Biochemical kits were used to determine the oxidative stress-related indicators in the renal tissue. Real-time polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels， respectively， of Nrf2， HO-1， glutamate-cysteine ligase catalytic subunit （GCLC）， and GPX4 in the renal tissue of mice in each group. ResultCompared with the blank group， the modeling increased the TCM syndrome score （P<0.05）， elevated the estradiol （E₂） and FBG levels （P<0.05）， lowered the testosterone （T）， triiodothyronine （T3）， and tetraiodothyronine （T4） levels （P<0.05）， and weakened the renal function （P<0.05）. In addition， the modeling led to glomerular hypertrophy and glomerular mesangial and basal thickening， decreased the catalase （CAT） activity， total antioxidant capacity （T-AOC）， and glutathione （GSH） content （P<0.05）， increased the malondialdehyde （MDA） content （P<0.05）， and down-regulated the mRNA and protein levels of Nrf2， HO-1， GCLC， and GPX4 in the renal tissue （P<0.05）. Compared with the model group， high and medium doses of Zhenwutang decreased the TCM syndrome score and E₂ content （P<0.05）， increased the T， T3， and T4 content （P<0.05）， improved the renal function （P<0.05）， alleviated the pathological changes in the renal tissue， increased CAT， T-AOC， and GSH （P<0.05）， reduced MDA （P<0.05）， and up-regulated the mRNA and protein levels of Nrf2， HO-1， GCLC， and GPX4 in the renal tissue （P<0.05）. ConclusionZhenwutang can improve the general state and renal function and reduce the oxidative damage and pathological changes in the renal tissue of db/db mice with spleen-kidney Yang deficiency by regulating the Nrf2/HO-1/GPX4 signaling pathway.

ObjectiveTo investigate the pharmacological action and mechanism of Shuangshenling granules in treating chronic renal failure in rats，providing laboratory data to support clinical application of Shuangshenling granules. MethodSD rats （150-180 g），half males and half females in number，were used，with ten rats designated as the normal group，ten as the sham operation group，and the remaining rats undergoing chronic renal failure modeling induced by 5/6 nephrectomy. Two weeks after operation，serum creatinine （SCr） and blood urea nitrogen （BUN） levels were measured via orbital blood sampling to select successful model rats. Based on SCr values，the rats were evenly divided into the model group，Shenshuaining positive group （0.84 g·kg^-1·d^-1），and high，medium，and low dose groups of Shuangshenling granules （4.8，2.4，1.2 g·kg^-1·d^-1），with ten animals in each group. Each treatment group received drugs at 10 mL·kg^-1 via intragastric administration once daily for six weeks. At 2，4，6 weeks after administration，SCr，BUN，24-hour urine volume，total urinary protein （UTP），urinary creatinine （UCr），creatinine clearance rate （CCr），serum albumin （SAlb），and total serum protein （STP） were measured. Following the experiment，kidney tissues were dissected for pathological examination. The expression levels of autophagy-related proteins，including PTEN-induced kinase 1 （PINK1），E3 ubiquitin-protein ligase parkin （Parkin），and microtubule-associated protein 1 light chain 3B （LC3B），were detected by immunofluorescence. ResultCompared with the normal group，the model group exhibited significantly increased levels of SCr，BUN，24-hour urine volume，UTP，and UCr （P<0.01），and decreased levels of SAlb and STP （P<0.01）. CCr showed an initial increase followed by a decrease. Histopathological results revealed glomerular hyperplasia and atrophy，with varying degrees of mesangial cell reduction，blood stasis in the glomeruli，and significant widening of Bowman's capsule. Visceral parietal layer cells were displaced or absent，leading to incomplete and damaged glomeruli. A large number of protein casts were present in the proximal and distal convoluted tubules，with reduced and displaced cells，swelling in some tubules，and interstitial inflammatory exudation predominantly comprising lymphocytes and a small number of neutrophils. Compared with the model group，all dose groups of Shuangshenling granules significantly reduced levels of SCr，BUN，24-hour urine volume，UTP，and UCr （P<0.05，P<0.01） and increased SAlb and STP levels （P<0.01） at 2，4，and 6 weeks after administration. The three dose groups also improved CCr and alleviated renal pathological injury in varying degrees at 2-6 weeks after administration. Immunofluorescence results showed that the expression levels of PINK1，Parkin，and LC3B were significantly reduced in the model group compared with the normal group，whereas all dose groups of Shuangshenling granules significantly upregulated the expression levels of PINK1，Parkin，and LC3B compared with the model group. ConclusionShuangshenling granules significantly improved renal function and pathological injury in rats with chronic renal failure，likely through the upregulation of PINK1-mediated autophagy.

Objective:Using the established epilepsy patient database to validate the efficacy of the web-based epilepsy diagnosis and anti-seizure medications (ASM) selection tool, EpiPick, for domestic epilepsy patients.Methods:The retrospective collection of clinical data was conducted on patients aged 10 and above who were diagnosed with epilepsy at the Comprehensive Epilepsy Center of the First Affiliated Hospital of Kunming Medical University from January 2017 to December 2020, with regular follow-up and complete information. According to the first ASM recommended by the EpiPick tool and whether they are consistent with the actual ASM used by patients, patients were divided into EpiPick group and clinical group to verify the effectiveness of the EpiPick tool in selecting ASM. The drug retention rate, Engel score, and cumulative probability of no consecutive episodes within 30 months after using the first ASM were compared between the 2 groups, and Kaplan-Meier survival curves were drawn. Finally, the diagnostic results provided by the EpiPick tool were compared with the actual types of epileptic seizures diagnosed clinically, and consistency tests were performed.Results:A total of 364 epilepsy patients were included, including 237 in the EpiPick group and 127 in the clinical group. The ASM retention rates of patients in the EpiPick group and clinical group were 67.9%(161/237) and 56.7%(72/127), respectively, with statistically significant differences (χ2=4.534, P=0.039). Grades Ⅰ, Ⅱ, Ⅲ and Ⅳ according to the Engel scores in the EpiPick group patients who took the first ASM after diagnosis accounted for 47.3%(112/237), 14.8%(35/237), 12.7%(30/237), and 25.3%(60/237), respectively, compared to the clinical group of 32.3%(41/127), 11.8%(15/127), 11.0%(14/127), and 44.9%(57/127), respectively. There was a statistically significant difference in Engel scores between the 2 groups (χ2=14.968, P=0.002). The cumulative seizure-free rates in the EpiPick group at the 1st, 6th, 12th, 30th month and above after starting the first ASM were 73.8%, 61.2%, 53.2%, and 50.6%, respectively, which in the clinical group were 52.0%, 44.1%, 40.2%, and 33.5%, respectively. The logrank test showed a statistically significant difference in the cumulative probability of consecutive seizure freedom between the 2 groups ( HR=0.644 ,95% CI 0.476-0.871 ,P<0.001). After grouping by seizure type [focal seizures (196 cases) and generalized seizures (168 cases)], the cumulative seizure-free rates at the 1st, 6th, 12th, 30th month and above after starting ASM were significantly higher in the EpiPick group than in the clinical group (comparison between the 2 groups in patients with focal seizures: HR=0.654, 95%CI 0.443-0.964, P=0.004; comparison between the 2 groups in patients with generalised seizures: HR=0.586, 95%CI 0.361-0.954, P=0.014). Among 364 patients, 293 cases were clinically diagnosed with seizure classification consistent with the classification results of EpiPick tool. Agreement between the algorithm and the experts in classifying generalized seizures was 83.9%(104/124), which in classifying focal seizures was 78.8%(189/240; Kappa=0.591, P<0.001). Conclusion:Web-based EpiPick tool is suitable to be used to select the first ASM, and is portable for Chinese non-epilepsy specialists to choose ASM for epilepsy patients.

Objective Neuromuscular electrical stimulation(NMES)-evoked kinesthetic information in muscle spindle can be purely extracted from the mixed motor and sensory afferents using Ischemic nerve block(INB).This study aims to investigate the somatosensory cortical response evoked by NMES activating muscle spindle afferents in forearm.Methods All subjects performed four experimental tasks designed according to a 2×2 factors,including one factor of the INB state(without INB and within INB)and the other of the stimulation intensity(above and below motor threshold).During the experiment,we recorded EEG data with 64 channels and then beta event-related desynchronization(Beta ERD)were utilized quantize somatosensory cortical excitability evoked by the tasks.The subjective perception about the sensation and movement of the right hand were evaluated by a psychophysical test after the right wrist was performed by INB.Results INB significantly reduced beta ERD on the contralateral somatosensory cortex evoked by NMES above the motor threshold,and there was significant difference of NMES-evoked beta ERD values on the contralateral somatosensory cortex between above and below motor threshold.Meanwhile,contralateral dominance of NMES-evoked beta ERD on the somatosensory cortex was transferred to ipsilateral hemisphere under INB.Conclusion INB can significantly reduce NMES-evoked somatosensory cortical response above motor threshold and decrease cortical perception on the stimulus intensity,which may be due to INB resulting in rapid functional reorganization of somatosensory cortex.

Peptidylarginine deiminases 2(PADI2)is an enzyme that catalyzes the conversion of arginine residues to citrulline on protein peptides.Aberrant activation of PADI2 can induce excessive tissue inflammation and immune responses,thereby exacerbating the progression of autoimmune diseases(ADs).Through citrullination,PADI2 modifies protein structure and immunogenicity,influencing the production of autoantibodies and regulating the activity of immune cells such as neutrophils and macrophages.This review provides an overview of PADI2's functions and its pivotal role in ADs,with the objective of elucidating the mechanisms underlying ADs pathogenesis and identifying novel therapeutic targets and strategies for related diseases.

Peptidylarginine deiminases 2(PADI2)is an enzyme that catalyzes the conversion of arginine residues to citrulline on protein peptides.Aberrant activation of PADI2 can induce excessive tissue inflammation and immune responses,thereby exacerbating the progression of autoimmune diseases(ADs).Through citrullination,PADI2 modifies protein structure and immunogenicity,influencing the production of autoantibodies and regulating the activity of immune cells such as neutrophils and macrophages.This review provides an overview of PADI2's functions and its pivotal role in ADs,with the objective of elucidating the mechanisms underlying ADs pathogenesis and identifying novel therapeutic targets and strategies for related diseases.