Objective:To investigate the protective effect of naringenin on acute lung injury related with sepsis; To discuss its possible mechanism.Methods:Totally 30 male SD rats were randomly divided into sham-operation group, model group, naringin low-, medium- and high-dosage groups, with 6 rats in each group. The sepsis-related acute lung injury model was established by cecal ligation and puncture in all groups except the sham-operation group. After modeling, naringin low-, medium- and high-dosage groups were given naringin 20 mg/kg, 40 mg/kg and 80 mg/kg, respectively for gavage, while the sham-operation group and the model group were given the same volume of distilled water by gavage, once a day, for 2 days. Pathological changes in lung tissue were observed using HE staining. The levels of 1L-1, IL-6 and IL-18 in bronchoalveolar lavage fluid (BALF) were measured by ELISA; the expression of TNF-α in lung tissue was detected by immunofluorescence histopathology; the expressions of TGF-β1, TGF-βR1 and Smad2 were detected by Western Blot. An agonist group and a naringin plus agonist group were set up, with 6 mice in each group, and the expressions of TGF-β1 and Smad2 protein in the lung tissue of each group were detected by immunohistochemical staining to verify the effect of naringin on the expressions of TGF-β1 and Smad2 protein.Results:Compared with the model group, the pathological injury of lung tissue in naringin groups were obviously alleviated, and the levels of IL-1β, IL-6 and IL-18 in BALF decreased ( P<0.01), the protein expressions of TNF-α, TGF-β1, TGF-βR1 and Smad2 in lung tissue decreased ( P<0.01 or P<0.05). Further verification found that the expressions of TGF-β1 and Smad2 in the agonist group increased ( P<0.01), while the expressions of TGF-β1 and Smad2 in the naringin agonist group decreased ( P<0.01). Conclusion:Naringin can reduce the inflammatory response in the lung of the rats to protect against sepsis-related acute lung injury, and its protective effect could be related to the inhibition of the TGF-β1/Smad2 signaling pathway.

Objective:To prepare seven standard strains of 2019 novel coronavirus (2019-nCoV), including wild type (WT) strain, Beta variant, Delta variant, Omicron variants (BA.2, BA.5, BQ.1, XBB.1 branches), which could be used to apply for national standard strains.Methods:According to cytopathic effect (CPE), virus titer, whole-virus-genome-sequencing and detection of mycoplasma, the basic biological characteristics of clonal isolation were determined through plaque purification technology.Results:The CPE was mainly characterized by cell shrinkage and exfoliation in Vero cells after infection with seven 2019-nCoV clonal isolations (WT, Beta, Delta, Omicron, BA.2, BA.5, BQ.1 and XBB.1 branches). The result of mycoplasma detection were negative and titers of the clonal isolation from 2nd to 5th generations were stable at 10 5-10 8 TCID 50/ml; the electron microscope showed that the virions were all round or elliptical, with a diameter between 60 nm and 140 nm. The subtypes of 7 strains were identified by whole-virus-genome-sequencing and phylogenetic analysis, with genomic stability after the fifth successive generations of clonal isolation. Conclusions:The series clonal isolation of 2019-nCoV with typical CPE of coronavirus, clear morphological structure, good viral activity and stable genetic characteristics were prepared, and they could be used to apply for national standard strains.

Objective:To investigate the role and underlying mechanisms of methyltransferase (Mettl) 3 in the process of angiotensin Ⅱ (Ang Ⅱ)-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis.Methods:C57BL/6J mice were used, in cell experiments, mouse renal pericytes were isolated and cultured using magnetic bead sorting. These pericytes were then induced to transdifferentiate into myofibroblasts with 1×10 6 mmol/L Ang Ⅱ, which was the Ang Ⅱ group, while pericytes cultured in normal conditions served as the control group. Successful transdifferentiation was verified by immunofluorescence staining, Western blotting, and real-time reverse transcription PCR (RT-qPCR) for α-smooth muscle actin (α-SMA). The levels of m6A modifications and related enzymes (Mettl3, Mettl14), Wilms tumor 1-associated protein (WTAP), fat mass and obesity protein (FTO), ALKBH5, YTHDF1, YTHDF2, YTHDC1, YTHDC2, YTHDC3 were assessed by Dot blot, RT-qPCR and Western blot. Mettl3 expression was inhibited in cells using lentivirus-mediated Mettl3-shRNA transfection, creating sh-Mettl3 and Ang Ⅱ+sh-Mettl3 groups, while lentivirus empty vector transfection served as the negative control (Ang Ⅱ+sh-NC group). The impact of Ang Ⅱ on pericyte transdifferentiation was observed, and the expression of downstream phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway proteins, including PI3K, AKT, phosphorylated AKT at serine 473 (p-AKT (S473)), and phosphorylated AKT at threonine 308 (p-AKT (T308)), were examined. PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time. The reversibility of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was assessed by adding the AKT activator SC79 to the Ang Ⅱ+sh-Mettl3 group. In animal experiments, mice were divided into these groups: sham group (administered 0.9% sterile saline), Ang Ⅱ group (infused with Ang Ⅱ solution), sh-Mettl3 group (injected with Mettl3 shRNA lentivirus solution), Ang Ⅱ+sh-Mettl3 group (infused with Ang Ⅱ solution and injected with Mettl3 shRNA lentivirus solution), and Ang Ⅱ+sh-Mettl3+SC79 group (administered Ang Ⅱ solution and Mettl3 shRNA lentivirus, with an additional injection of SC79). Each group consisted of six subject mice. Blood pressure was measured using the tail-cuff method before and after surgery, and serum creatinine, urea, and urinary albumin levels were determined 4 weeks post-surgery. Kidney tissues were collected at 28 days and stained using hematoxylin-eosin (HE) and Masson′s trichrome to assess the extent of renal fibrosis. Results:Primary renal pericytes were successfully obtained by magnetic bead sorting, and intervened with 1×10 6 mmol/L Ang Ⅱ for 48 hours to induce pericyte-to-myofibroblast transdifferentiation. Dot blot results indicated higher m6A modification levels in the Ang Ⅱ group compared to the control group ( P<0.05). RT-qPCR and Western blot results showed upregulation of Mettl3 mRNA and protein levels in the Ang Ⅱ group compared to the control group (both P<0.05). In the Ang Ⅱ+sh-Mettl3 group, Mettl3 protein expression was lower than that in the Ang Ⅱ group, with reduced expression levels of α-SMA, vimentin, desmin, fibroblast agonist protein (FAPa) and type Ⅰ collagen (all P<0.05). Compared to the control group, PI3K mRNA expression level was elevated in the Ang Ⅱ group, along with increased p-AKT (S473) and p-AKT (T308) expressions. In the Ang Ⅱ+sh-Mettl3 group, PI3K mRNA expression and p-AKT (S473) and p-AKT (T308) levels were decreased (all P<0.05). The half-life of PI3K mRNA was shorter in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ+sh-NC group (2.34 h vs. 3.42 h). The ameliorative effect of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was reversible by SC79. Animal experiments showed higher blood pressure, serum creatinine, urea, and 24-hour urinary protein levels, and a larger fibrosis area in the Ang Ⅱ group compared to the sham group (all P<0.05). The fibrosis area was smaller in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ group ( P<0.05), but increased again upon addition of SC79. Conclusion:Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.

Objective A high sodium(HS)diet is believed to affect bone metabolism processes.Clarifying its impact on osseointegration of titanium(Ti)implants holds significant implications for postoperative dietary management of implanted patients. Methods This investigation probed the impact of sodium ions(Na+)on neovascularization and osteogenesis around Ti implants in vivo,utilizing micro-computed tomography,hematoxylin and eosin staining,and immunohistochemical analyses.Concurrently,in vitro experiments assessed the effects of varied Na+concentrations and exposure durations on human umbilical vein endothelial cells(HUVECs)and MC3T3-E1 cells. Results In vivo,increased dietary sodium(0.8%-6.0%)led to a substantial decline in CD34 positive HUVECs and new bone formation around Ti implants,alongside an increase in inflammatory cells.In vitro,an increase in Na+concentration(140-150 mmol/L)adversely affected the proliferation,angiogenesis,and migration of HUVECs,especially with prolonged exposure.While MC3T3-E1 cells initially exhibited less susceptibility to high Na+concentrations compared to HUVECs during short-term exposure,prolonged exposure to a HS environment progressively diminished their proliferation,differentiation,and osteogenic capabilities. Conclusion These findings suggest that HS diet had a negative effect on the early osseointegration of Ti implants by interfering with the process of postoperative vascularized bone regeneration.

Objective To investigate the effect of progesterone receptor membrane component 1(PGRMC1)mediated autophagy on the sensitivity of liver cancer cells to 125I particles irradiation.Methods Hepatoma cell lines Huh7 and LM3 were exposed to different doses(0,2,4,6 and 8 Gy)of 125I particles,and cell autophagy was observed by transmission electron microscopy(TEM).Then,autophagy inhibitor chloroquine(CQ),agonist rapamycin(Rapa),and PGRMC1 inhibitor AG-205 were used respectively to verify that PGRMC1-mediated autophagy plays a key role in the sensitivity of hepatocellular carcinoma cells to 125I particle irradiation.Cell proliferation,colony formation and apoptosis were detected by CCK-8 assay,clonal formation test and flow cytometry,respectively.The expression levels of PGRMC1,microtubule-associated protein light chain 3-Ⅰ(LC3-Ⅰ),LC3-Ⅱ and p62 were detected by Western blotting.Results Different doses of 125I particles irradiation significantly decreased the proliferation and clonogenesis of Huh7 and LM3 cells(P＜0.05),and increased the apoptotic cells(P＜0.01),in a dose-dependent manner.Compared with the 0 Gy group,the ratio of LC3-Ⅱ/LC3-Ⅰ in Huh7 and LM3 cells was obviously increased,and the expression of p62 was significantly down-regulated in the 6 Gy group.The proliferation capacity and clonal formation ability of Huh7 and LM3 cells were decreased significantly,and their apoptotic cells were increased notably in the 6 Gy+CQ group than the 6 Gy group,while the above results were on the contrary in the 6 Gy+Rapa group.The 6 Gy+AG205 group had notably decreased LC3-Ⅱ/LC3-Ⅰ ratio in the Huh7 and LM3 cells,up-regulated p62 expression,reduced cell proliferation capacity and clone formation ability,and enhanced cell apoptosis when compared with the 6 Gy group,and the above results of the 6 Gy+PGRMC1 group were opposite.Conclusion Increment of PGRMC1 induced by 125I irradiation can promote autophagy,increase the proliferation and clonogenesis,and reduce the apoptosis in hepatocellular carcinoma cells.

Objective:The repair of small and medium-sized defects in the oral has always been a challenge,free skin flap and distal pedicled tissue flaps are difficult to meet clinical needs,and the traditional under-chin flap has the risk of donor-area injury.This study aims to investigate the efficacy of V-shaped folded submental flap in the repair of small-sized and medium-sized oral defects. Methods:The clinical data of 28 patients with oral defect lesions,who were hospitalized in the Department of Stomatology,Third Xiangya Hospital of Central South University from March 2019 to December 2022,were retrospectively analyzed.Patients were divided into a V-shaped folded group(17 cases)and a conventional group(11 cases)according to different surgical methods.The V-shaped folded group was treated with a V-shaped folded submental flap for postoperative soft tissue repair,while the conventional group was treated with a conventional submental flap for repair.The postoperative follow-up time was 6-48 months.The survival status,repair time,and repair effect of the 2 groups were compared. Results:There was no significant difference in flap survival rate,flap size,flap preparation time,repair surgery time,and postoperative hospital stay between the 2 groups(all P>0.05).At 6 months after the surgery,the V-shaped folded group had no difficulty in raising the head or everting the lower lip,no"cat ear"deformity in the submental skin.Scars in the V-shaped folding group were hidden at the lower edge of the mandible.The wound aesthetics and functional scores in the V-shaped folded group were significantly higher than those in the conventional group(both P<0.05). Conclusion:The V-shaped foldable submental flap has the advantages of flexible design,simple preparation,reliable blood supply,and protection of the donor area,which can effectively protect the appearance of the chin and avoid functional disorders.

Objective To analyze the epidemiological characteristics and risk factors of antibiotic-associated diarrhea (AAD) in children with pneumonia in Chongzhou, Sichuan Province, and to provide a theoretical basis for the diagnosis and treatment of AAD in children with pneumonia. Methods A total of 394 children with pneumonia admitted to our hospital from June 2018 to June 2021 were selected and divided into control group and AAD group according to whether the children had AAD. Univariate analysis and logistic regression were used to analyze the risk factors of pediatric pneumonia complicated with AAD. Results There were 79 cases of children with pneumonia complicated with AAD (20.05%). The average age of the ADD group was significantly lower than that of the control group (P<0.05). There were significant differences between the two groups in age of onset, length of hospital stay, type of antibiotics combined use, duration of antibiotics application, proportion of bacterial use of probiotics, and type of antibiotics (P<0.05). The age of onset <3 years old, duration of antibiotics application ≥5 days, combined use of three kinds of antibiotics, use of cephalosporin antibiotics, and no use of probiotics are independent risk factors for AAD in children with pneumonia. Conclusion The risk of AAD in children with pneumonia in Chongzhou is high, and the main pathogens are Candida and Escherichia coli. For children with cephalosporin antibiotics use, long application time of antibiotics, and onset age <3 years old, early application of probiotics should be done to reduce the risk of pediatric pneumonia complicated with AAD.

Objective To analyze the distribution of disease types of the epilepsy patients in southern Sichuan,and to provide guidances for the clinical diagnosis and treatment of epilepsy.Methods The complete medical records of inpatients with epilepsy in southern Sichuan who were clearly diagnosed in the Affiliated Hospital of Southwest Medical University from August 2014 to July 2017 were collected and sorted,and classified according to the latest revision of the epilepsy disease standard of the International AntiEpilepsy Alliance in 2017,and the distribution of disease types of these patients were statistically analyzed.Results A total of 454 patients with epilepsy were included in the study,with a male to female ratio of 1.54∶ 1,and the average age is (39.38 ±22.38) years.There were 71 patients under 15 years old,139 cases from 15 years old to 40 years old,189 cases from 41 years old to 65 years old,and 55 cases from over 65 years old.The patients in all ages were mainly classified as generalized onset,and the patients with different origins were mainly motor seizures.The focal onset were most common in the patients with epileptiform spasm from 40 days to 14 years old.The patients of generalized onset were mostly tonic-clonic seizures and under 65 years old.And the patients of unknown onset were mainly concentrated in 15-65 years old and mainly epileptic spasms.Conclusions Most of the patients with epilepsy in southern Sichuan are middle-aged and elderly,and the patients of all ages of different origins are mainly motor seizure,and the distribution of disease types of these patients are different.Moreover,the tonic-clonic seizure and epileptiform spasm are the most common types in these patients.

Objective To investigate the distribution of the general etiology of hospitalized patients with epilepsy in Southwest China and the etiological distribution of epilepsy patients of different ages.Methods The complete medical records of hospitalized patients with epilepsy diagnosed in our hospital from August 2014 to July 2017 were collected,the overall cause of the disease was classified,and the etiology distribution of different age groups was analyzed.Results A total of 665 eligible patients were enrolled.The overall etiology of epilepsy was structural (398/665,59.8％),infectious (122/665,18.3％) and metabolic (12/665,1.8％).The etiological and genetic causes were rare.Childhood and adolescent epilepsies were mainly due to unknown,viral infection,intracranial vascular malformations and cortical development disorders.As for etiology in adults,traumatic brain injury accounted for 18.0％ (68/380),cerebral hemorrhage accounted for 18.7％ (71/380),and brain tumors accounted for 17.1％ (65/380).Elderly patients with epilepsy accounted for 59.6％ (106/178) of stroke and other cerebrovascular diseases,followed by traumatic brain injury (17/178,9.6％) and neoplastic disease (17/178,9.6％).Conclusions The etiology of hospitalized epilepsy patients in Southern Sichuan is mainly structural lesions.And cerebrovascular disease,intracranial infection,brain trauma and tumor are the most common etiologies,but there are different etiologies at different ages.

Objective To investigate the impact of workplace bullying,general self?efficacy,self?es?teem on mental health of nurses. Methods With random sampling,450 nurses from six hospitals in Nanning of Guangxi were selected to complete questionnaire survey. Results 34.7% of nurses were reported to have been subjected to bullying at their workplace. Workplace bullying(23.78±6.94) showed significantly nega?tive relationship with mental health(36.63±4.53)( r=-0.32, P<0.01),while general self?efficacy(26.86± 4.82) and self?esteem(30.62±4.08) showed significantly positive correlations with mental health( r=0.45, 0.44, P<0.01). Workplace bullying had a significantly negative effect on mental health ( β=-0.25, P<0.01) ,and the relationship was affected by general self?efficacy and self?esteem. Conclusion Workplace bullying can influent nurses' mental health through self?esteem and the relationship is moderated by general self?efficacy.