Metabolic dysfunction-associated steatohepatitis (MASH), a severe type of metabolic dysfunction-associated steatotic liver disease (MASLD), is a leading etiology of end-stage liver disease worldwide, posing significant health and economic burdens. microRNA-320 (miR-320), a ubiquitously expressed and evolutionarily conserved miRNA, has been reported to regulate lipid metabolism; however, whether and how miR-320 affects MASH development remains unclear. By performing miR-320 in situ hybridization with RNAscope, we observed a notable downregulation of miR-320 in hepatocytes during MASH, correlating with disease severity. Most importantly, miR-320 downregulation in hepatocytes exacerbated MASH progression as demonstrated that hepatocyte-specific miR-320 deficient mice were more susceptible to high-fat, high-fructose, high-cholesterol diet (HFHC) or choline-deficient, amino acid-defined, high-fat diet (CDAHFD)-induced MASH compared with control littermates. Conversely, restoration of miR-320 in hepatocytes ameliorated MASH-related steatosis and fibrosis by injection of adeno-associated virus 8 (AAV8) carrying miR-320 in different types of diet-induced MASH models. Mechanistic studies revealed that miR-320 specifically regulated fibroblast growth factor 1 (FGF1) production in hepatocytes by inhibiting regulator factor X1 (RFX1) expression. Notably, knockdown of Rfx1 in hepatocytes mitigated MASH by enhancing FGF1-mediated AMPK activation. Our findings underscore the therapeutic potential of hepatic miR-320 supplementation in MASH treatment by inhibiting RFX1-mediated FGF1 suppression.

OBJECTIVE To investigate the effects of osthole （OST） on renal interstitial fibrosis in diabetic nephropathy （DN） model mice. METHODS The diabetic mice model was established by the tail vein injection of streptozotocin once， and the DN model was established by feeding for 12 weeks after successful modeling of diabetes. Diabetic model mice were randomly divided into model group， low-dose， moderate-dose， high-dose groups （20， 40， 80 mg/kg） of OST， with 10 mice in each group. After successful modeling of diabetes， the mice were given corresponding drugs or solvent （model group） intragastrically， once a day， for consecutive 12 weeks， and the normal control group was set up at the same time. After the last administration， the levels of fasting blood glucose， 24 h urinary protein， serum creatinine （Scr） and blood urea nitrogen were tested in each group. Masson staining was used to observe the deposition of collagen fibers in renal interstitium； the expressions of E-cadherin and vimentin in renal cortex were detected by immunohistochemical staining. The protein expressions of follistatin-like protein 1 （Fstl1） and Snail family transcriptional repressor 1 （Snail1）， the phosphorylation of protein kinase B （Akt） （calculated by p-Akt/Akt） in the renal cortex were detected by Western blot. RESULTS Compared with normal control group， the levels of fasting blood glucose， 24 h urinary protein， Scr and blood urea nitrogen， collagen fiber deposition ratio of renal interstitium， the expression of vimentin， protein expressions of Fstl1 and Snail1， p-Akt/Akt in renal cortex were increased significantly （P＜0.01）， as well as the expression of E-cadherin was decreased significantly （P＜0.01）. Compared with model group， above indexes of OST groups were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Preventive use of OST can effectively reduce fasting blood glucose level， protect renal function and inhibit epithelial-mesenchymal transition of DN model mice， and delay the progression of renal interstitial fibrosis ， the mechanism of which may be associated with the suppression of Fstl1/Akt/Snail1 signaling pathway.

Objective:To explore the early-stage language characteristics of children with autism spectrum disorder (ASD), global developmental delay (GDD), and developmental language disorder (DLD) at the same deve-lopmental level, thus providing references for their diagnosis.Methods:Clinical data of 719 children, involving 382 ASD patients, 198 DLD patients and 139 GDD patients presented to the Children′s Hospital Affiliated to Chongqing Medical University from January 2018 to January 2020 were retrospectively analyzed. Chi- square test was used to compare the developmental distribution of 3 groups.Variance analysis was used to analyze difference of developmental levels among 3 groups.Correlation analysis was used to analyse relationship between language and nonverbal abilities.At the same developmental, student′s t test was used to compare ASD with GDD, ASD with DLD in language ability, and difference of expression with receptive and visual related language. Results:The nonverbal developmental levels of ASD, GDD, DLD children were significantly different ( χ2=414.64, P<0.01). Language abilities were correlated with non-verbal developmental levels( r=0.60, P<0.05). The receptive and visual-related language abilities of ASD children with abnormal developmental level were more delayed compared with that of expressive language ( t=6.97, 3.58, 13.29, 6.85, 9.09, 7.27, all P<0.01). Expressive language of DLD children with normal developmental level was worse than visual-related and receptive language( t=-2.21, -3.61, all P<0.05). In GDD children with mild delayed development, receptive language was worse than expressive and visual-related language ( t=4.12, -4.24, all P<0.01), GDD children with moderate and worse development had worse visual-related and receptive language than the expression ( t=2.46, 2.68, all P<0.01). No significant differences in the expressive, receptive and visual-related language were detected in ASD and DLD children with normal development level and those with delayed development level (all P>0.05). Receptive and visual related language of ASD children with marginal delayed development level were significantly worse than those of DLD children ( t=-4.64, -4.60, all P<0.01), whereas no significant diffe-rence in the expression was detected ( P>0.05). In ASD children with mild delayed developmental level, the receptive and visual-related language were worse than those of GDD children( t=-4.11, -4.68, all P<0.01), whereas no significant difference in the expression was detected ( P>0.05). Conclusions:In early childhood, ASD children with abnormal developmental levels present severe delay in receptive and visual related language.DLD children with normal development have an obvious delay in expressive language.The language abilities of GDD children are globally delayed, especially the receptive language.In the marginal and mild delayed developmental level, ASD is featured by obvious delay of receptive and visual-related language.In normal and worse delayed development levels, the development of language in ASD, DLD and GDD children is similar.

Objective:To determine whether insulin resistance is associated with all-cause mortality in subjects without diabetes.Methods:A total of 505 participants without diabetes, 198 with normal glucose tolerance (NGT) and 307 with impaired glucose tolerance (IGT), were recruited from the Daqing Diabetes Study. The participants were followed up for 30 years. They were stratified into three groups (tertiles) according to baseline homeostasis model assessment of insulin resistance(HOMA-IR) levels, as the HOMA-IR 0, the HOMA-IR 1 and the HOMA-IR 2 groups, to assess the predictive effect of insulin resistance on risk of all-cause mortality.Results:During the 30-year follow-up, 52, 56 and 78 participants died across the three HOMA-IR groups, respectively. The corresponding mortality per 1 000 person-years (95 %CI) were 12.12 (9.56-15.01), 13.10 (10.46-16.03) and 19.91 (16.73-23.15), respectively. Participants in the HOMA-IR 2 group had a significantly higher risk of death than those in the HOMA-IR 0 group after adjustment of age, sex and smoking status ( HR=1.97,95 %CI 1.38-2.81, P<0.001). Cox analyses showed that a one standard deviation increase in HOMA-IR was associated with a 22% increase in the mortality after adjustment of potential confounders ( HR=1.22, 95 %CI 1.08-1.39, P=0.002). Conclusions:Insulin resistance is associated with increased risk of all-cause death in Chinese people without diabetes, suggesting that improving insulin resistance could be beneficial for people without diabetic in reducing risk of long-term all-cause mortality.

Objective:To investigate the physical indices and growth status of preterm children aged 0 to 4 years with different birth weight.Methods:Following the real world research approach, the current study retrospectively collected e-chart information of 8 496 preterm children from the child health care system of the Children′s Hospital of Chongqing Medical University from December 2010 to December 2017, with 203 123 full-term children followed up during the same period as controls. Premature children were divided into normal birth weight (NBW) group, low birth weight (LBW) group, and very low birth weight (VLBW) group based on their birth weights. The weight and length development within 48 months of age of preterm boys and girls in each group were measured and recorded to establish a numerical table and analyze the growth levels, growth rate, and proportionality. The t-test or chi-square test was used for between-group comparison. Results:Of the 8 496 preterm children, 4 839 were girls and 3 657 boys, including 525 in the VLBW group, with an average birth weight of (1.28±0.14) kg, 3 862 in the LBW group, with an average birth weight of (2.07±0.28) kg, and 4 109 in the NBW group, with an average birth weight of (2.86±0.35) kg. The weight at the actual age of 2-<3 months ((5.61±0.96) vs. (5.64±0.78) kg in boys, (5.11±0.67) vs. (5.18±0.71) kg in girls) and the length at the actual age of 8-<10 months ((70.3±2.4) vs. (70.6±2.4) cm in boys, (68.9±2.2) vs. (68.9±2.4) cm in girls) in the NBW group reached the average weight and length of full-term children. The difference of physical growth before 24 months of age between LBW and control group decreased as children age, with that of LBW group approaches the average of full-term children after 24 months of age, with a weight difference of 0.64-0.95 kg and height difference of 1.3-1.7 cm. The weight and height of the VLBW group were lower than those of full-term infants (2.80-2.86 kg and 3.3-4.3 cm, respectively) at 48 months of age. During 2-12 months of age, the corresponding values of the VLBW group were higher than that of the LBW and NBW groups by 0.35 kg and 0.71 kg, respectively. However, the corresponding values of the VLBW group were lower than that of the LBW and NBW groups(0.64 kg and 0.76 kg at 0-2 months of age, 1.04 kg and 1.49 kg at 12-48 months of age, respectively). The rates of delayed development, underweight, and emaciation were the highest in the VLBW group (all P<0.01), while the rates of overweight and obesity were the highest in the NBW group, with that of the VLBW group being lower than LBW group ( P<0.01) at the age of 24-<36 months. Conclusions:Prior to 4 years of age, the time for preterm children to reach the average physical indices of full-term children differ by birth weights, hence warranting further examination of the corrected gestational age for preterm children. Normal birth weight preterm children present with the highest incidence of overweight and obesity and very low birth weight preterm children present with the highest incidence of growth disorders, marking both groups at high risks of malnutrition.

Objective:To explore the language characteristics of children with autism spectrum disorder (ASD) at different developmental levels.Methods:The clinical data of 103 children with ASD who attended the Children′s Hospital of Chongqing Medical University from January 2018 to December 2020 was analyzed retrospectively. They were divided into typical development and abnormal development (including mild and moderate or severe) groups based on developmental diagnostic scale results, and also devided into 2-3, 4-6, and 7-8 years of age groups based on age. The language characteristics of children with ASD at different developmental levels and different ages were compared by Pearson′s chi-square or Fisher′s exact probabilty test, t test, analysis of variance, or Kruskal-Wallis H test. The relationship between language ability and core symptoms of ASD was analyzed by Pearson correlation test. Results:Among 103 children with ASD, 86 were males and 17 were females, with an age of (5.5±1.5) years. A total of 61 children were charactered as typical development and 42 as abnormal (32 mild and 10 moderate or severe). There were no significant differences in developmental scale, overall language, receptive, expressive, syntax, and semantics scores among the three different age groups (all P>0.05). The detection rate of abnormal language ability in the typical development group was significantly lower than that in the abnormal development group (49.2% (30/61) vs. 100.0% (42/42), P<0.01). Receptive, expressive, semantics, and syntax scores of the typical development groups were significantly higher than those of the mildly and moderately or severely abnormal group (89±13 vs. 76±11 vs.71±8, F=18.61, P<0.01; 80±12 vs. 66±8 vs. 58±7, F=29.69, P<0.01; 92±14 vs.78±14 vs. 71±11, F=17.26, P<0.01; 83±10 vs. 71±8 vs. 64±5, F=29.35, P<0.01). Within the abnormal development group, there were no significant correlations between language ability and the core symptoms of ASD ( r=-0.02-0.58, all P>0.05). Within the typical development group, there were no significant correlations between language ability and social interaction, repetitive stereotypes, and limited interests ( r=0--0.22, all P>0.05). However, overall language, receptive, semantics, and expressive language abilities were negatively correlated with communication ( r=-0.28--0.36, all P<0.05), and there was no significant correlation between syntax and communication ( r=-0.24, P>0.05) in typical developmental group. Conclusions:The majority of children with ASD manifest language development disorders, mainly in the aspects of expressive and syntax language. Children with ASD with more delayed developmental level have more severe language disorder. About half children with ASD with normal development have language development disorders. The language ability of children with ASD is minimally correlated with ASD core symptoms.

Objective:To investigate the long-term effects of metabolically healthy obesity on the risks of type 2 diabetes, cardiovascular disease events, and its mortality over a 23-year follow-up.Methods:Based on the results of an oral glucose tolerance test, there were 519 participants with normal glucose tolerance and 630 with newly diagnosed type 2 diabetes enrolled in 1986 and then given to assess the long-term clinical outcomes during the 23-year follow-up in Daqing. Metabolically healthy obesity was defined as the overweight and obese individuals with no metabolic abnormalities (diabetes, hypertension, hyperlipidemia). Finally, we identified 682 participants (350 with normal glucose tolerance and 332 with newly diagnosed diabetes). They were divided into five groups: 211 individuals with metabolically healthy normal weight (MHNW group), 58 with metabolically healthy overweight and obesity (MHO group), 81, 109, 223 were metabolically unhealthy overweight and obesity with hypertension (MUHO group), type 2 diabetes (MUDO group), hypertension and diabetes (MUHDO group). Incidences of type 2 diabetes, morbidity and mortality of cardiovascular disease were compared among these groups.Results:Over 23 years, instead of the morbidity and mortality of cardiovascular disease, the incidence of type 2 diabetes in MHO group was two times higher than in MHNW group ( 24.1%, 12.5/1 000 person years vs 10.9%, 5.2/1 000 person years, P=0.01), with an age, sex, and smoking history-adjusted hazard ratio ( HR) of 2.42 (95% CI 1.24-4.74, P=0.01). The morbidity and mortality of cardiovascular disease in the groups of overweight and obesity with metabolically unhealthy were higher than in MHNW group, and increased across the subjects with MUHO, MUDO, MUHDO ( P<0.05). Conclusion:Compared with metabolically healthy normal weight participants, the metabolically healthy obese group was at increased risk of type 2 diabetes but not cardiovascular disease events and its mortality. On the contrary, the overweight and obese groups with metabolic abnormalities had significant higher incidence of type 2 diabetes, morbidity and mortality of cardiovascular diseases.

Objective: To analyze the clinical characteristics of streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes (S. pyogenes) in the third trimester to improve clinical awareness of this disease. Methods: A retrospective study was conducted to analyze the clinical data of two patients with STSS caused by S. pyogenes in Jinan Maternal and Child Health Care Hospital and nine reported cases of healthy pregnant women infected with S. pyogenes at 28-42 gestational weeks with detailed data retrieved from Chinese National Knowledge Infrastructure and PubMed database from January 1997 to December 2018. Results: The two cases admitted to our hospital were both multiparas, with onset in winter and no specific symptoms in early stage. Disseminated intravascular coagulation (DIC) was developed in both cases on admission. In one case, the fetal heart rate was reduced and disappeared soon after admission. The other patient was diagnosed as stillbirth on admission. Both patients died and blood culture revealed infection of group A streptococcus. Nine previous cases were reported in one Chinese and five English articles. No high-risk pregnancy or premature rupture of membranes was reported in these 11 cases. Among the 11 cases, ten were positive for S. pyogenes indicated by blood or tissue culture and one was positive for streptococcal toxin. Ten cases had high fever and three presented with respiratory symptoms in early stage. Abdominal pain and watery diarrhea were common symptoms and all patients developed multiple organ dysfunction and DIC. Cases occurred in winter or spring were more common. Nine women died within 36 h after the onset of fulminant symptoms. Only two survived and hospitalized for 90 d and 25 d, respectively, after emergent cesarean section indicated by reduced fetal heart rate. Unfortunately, both neonates died after birth. For the babies, there were seven intrauterine fetal deaths, one stillbirth and three live births, but only one survived (whose mother developed respiratory cardiac arrest 90 min after delivery). Conclusions STSS caused by S. pyogenes in pregnant women exacerbates rapidly with a high mortality. Early identification of clinical manifestations and rapid progress of the disease are crucial for early diagnosis and treatment, which may help improve maternal and fetal outcomes.

Objective: To evaluate the precision of image registration between MRI simulation (MRIsim) and CT simulation compared to diagnostic MRI(MRIdiag) and to provide information for further application of MRIsim. Methods: A total of 24 patients who underwent both MRIsim and MRIdiag were enrolled, including 8 patients with gliomas, 8 with nasopharyngeal carcinomas and 8 with prostate cancers. MRIsim and MRIdiag images of each patient were fused with CT. The OARs were delineated on three modalities of images and targets were delineated on fusion image of MRIsim with CT (F_CTMsim) and fusion image of MRIdiag with CT (F_CTMdiag) respectively. The concordance index (CI), Dice′s similarity coefficient (DSC) between the OARs and image similarity index (S) based on images from MRIsim, MRIdiag and CT were evaluated. IMRT plans were designed based targets on F_CTMsim and OARs on CT images, and differences in dosimetry of targets and OARs were evaluated subsequently. Results: Volumes of most OAR from three modalities of images showed no statistically significant difference(P>0.05). All the CI and DSC between the OARs derived from MRIsim and CT were higher than those corresponding values from MRIdiag, and a statistically significant difference was achieved in 50% of these OARs (t=2.58-5.47, P<0.05). The S values of MRIsim and MRIdiag compared with CT were 0.89 and 0.83 respectively (t=5.77, P<0.05). MRIsim improved the S value by 10% (2%-56%) compared with MRIdiag. No further differences in dosimetry were found on all OARs and all targets(P>0.05). Conclusions The precision of image registration can be significantly improved by introducing MRIsim into radiotherapy planning design compared with MRIdiag. However, no significant differences in dosimetry were found on targets produced by rigid registration and manual adjustment method .

OBJECTIVE： To study on the effects of prophylactic administration of Ramulus mori polysaccharides （RMP） on inflammatory response of renal ischemia reperfusion injury （RIRI） model mice and to explore its possible mechanism. METHODS： Totally 60 C57BL/6 mice were randomly divided to sham operation group， model group， atorvastatin group （positive control， 15 mg/kg）， RMP low-dose， medium-dose and high-dose groups （300， 600， 1 200 mg/kg）. Except for sham operation group， RIRI model was induced in other 5 groups. 24 h before surgery， they were given relevant medicine intragastrically， once a day， for consecutive one week. 24 h after reperfusion， the mice were sacrificed. The serum levels of Scr and BUN were detected. The morphological changes of renal tissue were observed under optical microscope. The serum levels of IL-1β， IL-6， IL-10 and TNF-α were determined by ELISA. Western blot assay was used to determine the protein expressions of Toll-like receptor 4 （TLR4）， p38 mitogen-activation protein kinase （p38MAPK） and p-p38MAPK. RESULTS： Compared with sham operation group， the serum levels of Scr and BUN were significantly elevated in model group  （P＜0.01）. RIRI led to typical inflammatory response of renal tissue， widespread renal tubular epithelial cell degeneration and necrosis， and inflammatory cells infiltration. Serum levels of IL-1β， IL-6， IL-10 and TNF-α were increased significantly （P＜0.01）. The protein expressions of TLR4， p38MAPK and p-p38MAPK were increased significantly in renal cortex （P＜0.01）. Compared with model group， serum levels of Scr and BUN were decreased significantly in administration groups （P＜0.05 or P＜0.01）. The pathological damage of renal tissue was improved in varying degrees， especially in the RMP medium-dose and high-dose groups. Serum levels of IL-1β and IL-6 were decreased significantly in administration groups （P＜0.05 or P＜0.01）. Serum levels of IL-10 were further increased in atorvastatin group and RMP high-dose group （P＜0.01）， and serum level of TNF-α was decreased significantly in atorvastatin group and RMP medium-dose and high-dose groups （P＜0.05 or P＜0.01）. The protein expressions of TLR4 and p-p38MAPK in renal cortex were decreased significantly in administration groups （P＜0.05 or P＜0.01）. CONCLUSIONS： RMP prophylactic administration can improve RIRI of mice， the mechanism of which may be associated with relieving the inflammatory response through inhibition of TLR4/p38MAPK signaling pathway.