OBJECTIVE To investigate the effects of metformin （Met） on liver injury in non-alcoholic steatohepatitis （NASH） rats by regulating the PI3K/AKT/PDGF signaling pathway. METHODS NASH model was constructed by feeding rats with a high- glucose and high-fat diet， and assigned into Model group， Met low-dose group （Met-L group， 100 mg/kg）， Met medium-dose group （Met-M group， 200 mg/kg）， Met high-dose group （Met-H group， 400 mg/kg）， and high dose of Met+PI3K activator group （Met-H+740 Y-P group， 400 mg/kg Met+50 mg/kg 740 Y-P）， with 12 rats in each group. Another 12 rats were regarded as the Control group. Each group of rats was orally administered/injected with the corresponding medication once a day for 6 consecutive weeks. The changes in body weight and liver index of rats were recorded and analyzed. The pathological damage [evaluation of non-alcoholic fatty liver disease activity score （NAS）]， lipid deposition （calculation of the proportion of oil red O-positive staining area）， and fibrosis （calculation of collagen deposition score） were observed in liver tissue of rats. The levels of inflammatory factors [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）] in serum and liver tissue， the levels of serum lipid metabolism indicators [total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）] and liver function indicators [aspartate aminotransferase （AST） and alanine Δ 基金项目 武汉市知识创新专项项目（No.2022020801010588）； aminotransferase （ALT）] were measured. The expression levels of PI3K/AKT/PDGF signaling pathway-related proteins and Caspase-3 in liver tissue of rats were determined. RESULTS Compared with the Control group， body weight， liver index， the levels of serum lipid metabolism indicators and liver function indicators， the levels of IL-6 and TNF-α in serum and liver tissue， the NAS， the proportion of oil red O-positive staining area， the collagen deposition fraction， and the levels of phosphorylated PI3K and AKT proteins， as well as the expression levels of PDGF and Caspase-3 proteins in liver tissue， were all significantly increased （P＜0.05）. The liver tissue showed severe pathological damage， characterized by an abundance of lipid droplets and pronounced collagen deposition. After the intervention with Met， the aforementioned quantitative indicators and pathological changes in rats were significantly improved in a dose- dependent manner （P＜0.05）. 740 Y-P could reverse the improvement effects of high dose of Met on the above indexes of rats （P＜ 0.05）. CONCLUSIONS Met can improve liver damage， and alleviate inflammatory reactions and liver fibrosis of NASH rats， the mechanism of which may be associated with inhibiting PI3K/AKT/PDGF signaling pathway.

ObjectiveTo compare the hepatic bile acid profile between a mouse model of metabolic-associated steatohepatitis （MASH） induced by a high-fat， high-sugar， and high-cholesterol diet combined with intraperitoneal injection of 10% carbon tetrachloride （CCl₄） and MASH cases in clinical practice， and to investigate the feasibility of this model in studying drug interventions on bile acid profile in MASH. MethodsA total of 30 male C57BL/6J mice were randomly divided into control group and model group， with 15 mice in each group. The mice in the control group were given normal diet and drinking water and weekly injections of olive oil， and those in the model group were given a high-fat， high-sugar， and high-cholesterol diet， high-sugar drinking water， and weekly injections of CCl₄+olive oil. At the end of weeks 8， 12， and 16， 5 mice were selected from each group to collect samples. Behavioral assessments were performed， and body weight and liver wet weight were measured； liver pathology and lipid deposition were evaluated by HE staining， SAF scoring， oil Red O staining， the semi-quantitative analysis of stained area， the serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， and liver triglyceride （TG） content； Sirius Red staining was performed for liver tissue to assess liver fibrosis； ultra-performance liquid chromatography-tandem mass spectrometry and targeted metabolomics were used to measure the hepatic bile acid profile， including cholic acid （CA）， glycocholic acid （GCA）， chenodeoxycholic acid （CDCA）， glycochenodeoxycholic acid （GCDCA）， ursodeoxycholic acid （UDCA）， tauroursodeoxycholic acid （TUDCA）， hyodeoxycholic acid （HDCA）， and glycodeoxycholic acid （GDCA）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the control group at the same time point， the model group had disheveled and dull fur， reduced activity， and relatively slow reactions at weeks 8， 12， and 16， as well as significant increases in liver wet weight （P<0.05）， the serum level of ALT （P<0.05）， the content of TG in the liver （P<0.05）， and SAF score （P<0.05）. As for the differentially expressed bile acids in liver tissue， compared with the control group at week 8， the model group had significantly higher levels of CA and CDCA and significantly lower levels of UDCA， TUDCA， HDCA， and GDCA （all P<0.05）； compared with the control group at week 12， the model group had significantly higher levels of CA， GCA， CDCA， and GCDCA and significantly lower levels of UDCA and HDCA （all P<0.05）； compared with the control group at week 16， the model group had significantly higher levels of CA， GCA， CDCA， GCDCA， and TUDCA and significantly lower levels of UDCA， HDCA， and GDCA （all P<0.05）. As for the differentially expressed bile acids in the bile acid pool of liver tissue， compared with the control group at week 8， the model group had significantly higher levels of CA and CDCA and significantly lower levels of UDCA， TUDCA， GDCA， and HDCA （all P<0.05）； compared with the control group at weeks 12 and 16， the model group had significantly higher levels of GCA and GCDCA and significantly lower levels of UDCA， GDCA， and HDCA （all P<0.05）. ConclusionThere are significant changes in the hepatic bile acid profile in a mouse model of MASH induced by a high-fat， high-sugar， and high-cholesterol diet combined with CCl₄， which are similar to the changes in bile acids in MASH cases in clinical practice， suggesting that this model can be used to explore the interventional effect of drugs on the bile acid profile in MASH.

Objective To investigate the number and categories of cognitive subtypes in individuals with First-Episode Schizophrenia(FES)and to explore the potential neurobiological sleep characteristics associated with these distinct cognitive subtypes.Methods The cognitive functions of 45 patients withFES and 40 healthy controls(HCs)were assessed using the MATRICS Consensus Cognitive Battery(MCCB).Latent profile analysis was employed to identify and classify the cognitive subtypes of FES patients.Furthermore,a full-night polysom-nographic recording was conducted to quantify the characteristics of sleep spindle waves.Subsequently,differ-ences in sleep spindle wave features among the identified cognitive subtypes of FES were analyzed and compared.Results Latent Profile Analysis identified two cognitive subtypes among FES patients:a subtype characterized by severe cognitive impairment(SIS,n=32)and another with relatively preserved cognitive function(CRP,n=13).Compared to healthy controls(HCs,n=40),FES patients exhibited increased spindle wave amplitude dur-ing both N2 and N3 sleep stages.Further analysis revealed that the spindle wave duration during the N2 stage was significantly longer in the SIS subtype compared to both CRP and HCs.Similarly,in the N3 stage,the spindle wave duration was longer in SIS than in CRP.Additionally,spindle wave frequency during the N3 stage was higher in both SIS and HCs compared to CRP.Conclusions The results of this study suggest that variations in the fre-quency and duration of spindle waves among different cognitive subtypes may serve as potential neurobiological markers for distinguishing FES cognitive subtypes.

To investigate the prevalence of influenza D virus(IDV)in cattle and swine populations in Jilin Province,China,277 nasopharyngeal swabs were collected from livestock exhibiting influ-enza-like symptoms for IDV detection.Virus isolation was performed using swine testicular(ST)cells for PCR-positive samples,followed by comprehensive analyses including whole-genome se-quencing,phylogenetic analysis,electron microscopic observation of viral morphology,and glycosy-lation site prediction.Two IDV strains were successfully isolated from bovine samples,designated as D/bovine/China/JL22/2024(JL22)and D/bovine/China/JL34/2024(JL34).These strains were demonstrated to have specific hemagglutination activity against turkey red blood cells,while no he-magglutination to chicken,rabbit,or guinea pig erythrocytes.Virus-inoculated ST cells exhibited distinct cytopathic effects(CPE)within 48 h,with a hemagglutination titer of 4 log2 in the culture supernatant.Phylogenetic analysis of the hemagglutinin-esterase-fusion(HEF)gene indicated that these strains were most closely related to the Japanese isolate D/Yamagata2019,belonging to the YAMA2019 lineage.Genomic sequence analysis showed the absence of genetic reassortment in these isolates.In this study,two IDV strains were successfully isolated and characterized,which provides preliminary insights into their genomic sequences and biological properties.The findings confirm the presence of IDV in bovine populations in Jilin Province and provide the fundamental data for future epidemiological surveillance and control strategies of IDV.

Objective:To investigate whether lncRNA SOX2-OT inhibits the proliferation and migration of colorectal cancer(CRC)HCT-116 cells by regulating the miR-215-5p/NIN/RPN12 binding protein 1 homolog(NOB1)signaling pathway.Methods:Cancerous and paired adjacent tissue samples from 29 CRC patients treated at Wuhan Jinyintan Hospital from June 2022 to May 2024 were collected,along with CRC cell lines(SW480,HCT-116,HP116,and LoVo)and normal human colon epithelial HCoApiC cells.The mRNA expression levels of SOX2-OT,miR-215-5p,and NOB1 in CRC tissues and cells were measured using qPCR method.HCT-116 cells were transfected with SOX2-OT knockdown or overexpression plasmids and corresponding negative control plasmids using RNA interference technology,dividing the cells into control group,si-NC group,si-SOX2-OT group,si-SOX2-OT+inhibitor(Inh)NC group,si-SOX2-OT+miR-215-5p Inh group,si-SOX2-OT+oe-NC group,and si-SOX2-OT+oe-NOB1 group.The mRNA expression levels of SOX2-OT,miR-215-5p,and NOB1 in each group of cells were detected using qPCR method.MTT assay,scratch wound healing assay,Transwell chamber assay,and flow cytometry were used to measure cell proliferation,migration,invasion,and apoptosis,respectively.Western blot was applied to detect protein expression levels of E-cadherin,N-cadherin,vimentin,Bcl-2,BAX,PCNA,MMP-9,and NOB1.The targeting relationship between miR-215-5p and SOX2-OT or NOB1 was validated using dual-luciferase reporter gene assays.Results:SOX2-OT and NOB1 mRNA were significantly upregulated,while miR-215-5p was downregulated in both CRC tissues and cells(all P<0.05).In HCT-116 cells with SOX2-OT knockdown,the expression of SOX2-OT and NOB1 mRNA,cell proliferation,wound healing rate,invasive cell number,and protein levels of N-cadherin,vimentin,Bcl-2,NOB1,PCNA,and MMP-9 were significantly reduced(all P<0.05),while miR-215-5p expression,apoptosis rate,and protein levels of E-cadherin and BAX were significantly increased(all P<0.05).Both miR-215-5p knockdown and NOB1 overexpression reversed the inhibitory effects of SOX2-OT knockdown on HCT-116 cells(both P<0.05).miR-215-5p was validated to target SOX2-OT and NOB1.Conclusion:SOX2-OT knockdown upregulates miR-215-5p expression and downregulates NOB1 expression,further inhibiting the proliferation,migration,and invasion of HCT-116 cells and promoting apoptosis.

Objective To investigate the number and categories of cognitive subtypes in individuals with First-Episode Schizophrenia(FES)and to explore the potential neurobiological sleep characteristics associated with these distinct cognitive subtypes.Methods The cognitive functions of 45 patients withFES and 40 healthy controls(HCs)were assessed using the MATRICS Consensus Cognitive Battery(MCCB).Latent profile analysis was employed to identify and classify the cognitive subtypes of FES patients.Furthermore,a full-night polysom-nographic recording was conducted to quantify the characteristics of sleep spindle waves.Subsequently,differ-ences in sleep spindle wave features among the identified cognitive subtypes of FES were analyzed and compared.Results Latent Profile Analysis identified two cognitive subtypes among FES patients:a subtype characterized by severe cognitive impairment(SIS,n=32)and another with relatively preserved cognitive function(CRP,n=13).Compared to healthy controls(HCs,n=40),FES patients exhibited increased spindle wave amplitude dur-ing both N2 and N3 sleep stages.Further analysis revealed that the spindle wave duration during the N2 stage was significantly longer in the SIS subtype compared to both CRP and HCs.Similarly,in the N3 stage,the spindle wave duration was longer in SIS than in CRP.Additionally,spindle wave frequency during the N3 stage was higher in both SIS and HCs compared to CRP.Conclusions The results of this study suggest that variations in the fre-quency and duration of spindle waves among different cognitive subtypes may serve as potential neurobiological markers for distinguishing FES cognitive subtypes.

To investigate the prevalence of influenza D virus(IDV)in cattle and swine populations in Jilin Province,China,277 nasopharyngeal swabs were collected from livestock exhibiting influ-enza-like symptoms for IDV detection.Virus isolation was performed using swine testicular(ST)cells for PCR-positive samples,followed by comprehensive analyses including whole-genome se-quencing,phylogenetic analysis,electron microscopic observation of viral morphology,and glycosy-lation site prediction.Two IDV strains were successfully isolated from bovine samples,designated as D/bovine/China/JL22/2024(JL22)and D/bovine/China/JL34/2024(JL34).These strains were demonstrated to have specific hemagglutination activity against turkey red blood cells,while no he-magglutination to chicken,rabbit,or guinea pig erythrocytes.Virus-inoculated ST cells exhibited distinct cytopathic effects(CPE)within 48 h,with a hemagglutination titer of 4 log2 in the culture supernatant.Phylogenetic analysis of the hemagglutinin-esterase-fusion(HEF)gene indicated that these strains were most closely related to the Japanese isolate D/Yamagata2019,belonging to the YAMA2019 lineage.Genomic sequence analysis showed the absence of genetic reassortment in these isolates.In this study,two IDV strains were successfully isolated and characterized,which provides preliminary insights into their genomic sequences and biological properties.The findings confirm the presence of IDV in bovine populations in Jilin Province and provide the fundamental data for future epidemiological surveillance and control strategies of IDV.

Objective:To investigate the clinical effects of adjustable external fixation traction combined with arthroscopic microfracture in the treatment of osteochondral lesions of the talus (OLT).Methods:A retrospective study was conducted to analyze the data of 27 OLT patients who had been treated at Department of Orthopedics, Beijing Rehabilitation Hospital from May 2017 to March 2022. There were 16 males and 11 females, aged (32.4±7.2) years. Lesion site: 23 medial and 4 lateral cases; Hepple staging: 7 cases at stage Ⅰ, 15 cases at stage Ⅱ, and 5 cases at stage Ⅲ; disease duration: (10.6±3.3) months. All the patients were treated by adjustable external fixation traction combined with arthroscopic microfracture. Recorded were the patients' visual analogue scale (VAS) pain scores and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores at 6 months and 12 months after surgery, levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor- α (TNF- α) at 1 month after surgery, lesion area at 12 months after surgery, and incidence of complications. Results:The follow-up time for this cohort was (16.2±6.7) months. The AOFAS score was (61.52±6.75) points before surgery, (84.15±5.56) points at 6 months after surgery and (95.67±4.30) points at 12 months after surgery. The VAS score was (5.88±1.02) points before surgery, (2.12±0.48) points at 6 months after surgery and (0.66±0.36) points at 12 months after surgery. The two-by-two comparisons between the 3 time points for the above items were statistically significant ( P<0.05). IL-1 was (32.37±6.64) pg/mL, IL-6 (34.04±7.12) pg/mL, and TNF- α (17.89±4.96) ng/L at 1 month after surgery in the 27 patients, all of which were significantly lower than their preoperative levels [(96.63±14.80) pg/mL, (102.33±20.42) pg/mL, and (54.48±9.33) ng/L] ( P<0.05). The lesion area was (28.66±6.52) mm 2 at 12 months after surgery, significantly smaller than the value before surgery [(128.52±11.32) mm 2] ( P<0.05). Infection at the adjustable external fixation needle track occurred in 1 patient and lower limb thrombosis in 2 patients. Conclusion:In the treatment of OLT, adjustable external fixation and traction combined with arthroscopic microfracture can achieve satisfactory results and improve symptoms for the patients.

Objective:To analyze the status of respiratory pathogen detection and the clinical features in children with Mycoplasma pneumoniae pneumonia (MPP). Methods:A prospective, multicenter study was conducted to collect clinical data, including medical history, laboratory examinations and multiplex PCR tests of children diagnosed with MPP from 4 hospitals in China between November 15 th and December 20 th, 2023. The multiplex PCR results and clinical characteristics of MPP children in different regions were analyzed. The children were divided into severe and mild groups according to the severity of the disease. Patients in the severe group were further divided into Mycoplasma pneumoniae (MP) alone and Multi-pathogen co-detection groups based on whether other pathogens were detected besides MP, to analyze the influence of respiratory pathogen co-detection rate on the severity of the disease. Mann-Whitney rank sum test and Chi-square test were used to compare data between independent groups. Results:A total of 298 children, 136 males and 162 females, were enrolled in this study, including 204 children in the severe group with an onset age of 7.0 (6.0, 8.0) years, and 94 children in the mild group with an onset age of 6.5 (4.0, 7.8) years. The level of C-reactive protein, D-dimer, lactic dehydrogenase (LDH) were significantly higher (10.0 (5.0, 18.0) vs. 5.0 (5.0, 7.5) mg/L, 0.6 (0.4, 1.1) vs. 0.5 (0.3, 0.6) mg/L, 337 (286, 431) vs. 314 (271, 393) U/L, Z=2.02, 2.50, 3.05, all P<0.05), and the length of hospitalization was significantly longer in the severe group compared with those in mild group (6.0 (6.0, 7.0) vs. 5.0 (4.0, 6.0) d, Z=4.37, P<0.05). The time from onset to admission in severe MPP children was significantly shorter than that in mild MPP children (6.0 (5.0, 9.5) vs. 9.0 (7.0, 13.0) d, Z=2.23, P=0.026). All patients completed the multiplex PCR test, with 142 cases (47.7%) MPP children detected with 21 pathogens including adenovirus 25 cases (8.4%), human coronavirus 23 cases (7.7%), rhinovirus 21 cases (7.0%), Streptococcus pneumoniae 21 cases (7.0%), influenza A virus 18 cases (6.0%). The pathogens with the highest detection rates in Tianjin, Shanghai, Wenzhou and Chengdu were Staphylococcus aureus at 10.7% (8/75), adenovirus at 13.0% (10/77), adenovirus at 15.3% (9/59), and both rhinovirus and Haemophilus influenzae at 11.5% (10/87) each. The multi-pathogen co-detection rate in severe MPP children was significantly higher than that in mild MPP group (52.9% (108/204) vs. 36.2% (34/94), χ2=10.62, P=0.005). Among severe MPP children, there are 89 cases in the multi-pathogen co-detection group and 73 cases in the simple MPP group. The levels of LDH, D-dimer and neutrophil counts in the multi-pathogen co-detection group were significantly higher than those in the simple MPP group (348 (284, 422) vs. 307 (270, 358) U/L, 0.8 (0.5, 1.5) vs. 0.6 (0.4, 1.0) mg/L, 4.99 (3.66, 6.89)×10 9vs. 4.06 (2.91, 5.65)×10 9/L, Z=5.17, 4.99, 6.11, all P<0.05). Conclusions:The co-detection rate of respiratory pathogens, LDH and D-dimer in children with severe MPP were higher than those with mild MPP. Among severe MPP children the stress response of children in co-detection group was more serious than that of children with simple MPP.