Objective:To investigate the effects and mechanism of metformin on the proliferation and expression of fibrotic proteins of human hypertrophic scar (HS) fibroblasts (Fbs).Methods:The study was an experimental study. From June 2021 to June 2022, 5 patients with HS were admitted to the Department of Burns and Cutaneous Surgery of the First Affiliated Hospital of Air Force Medical University, including 3 males and 2 females, aged from 21 to 36 years. HS tissue was collected, Fbs were isolated and cultured, and Fbs of passage 5 to 7 were used for experiment. Fbs were taken and cultured in their respective media supplemented with phosphate buffered solution (PBS) or metformin at final molarities of 5, 10, 20, and 40 mmol/L for 48 hours. The cell proliferation activity was detected using the cell counting kit-8 (CCK-8), and the proliferation inhibition rate of cells was calculated. The content of hydroxyproline in the cell culture supernatant was measured using a hydroxyproline assay kit. The phosphorylation levels of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) in the cells were detected by Western blotting, and the ratios of phosphorylated Akt (p-Akt) to Akt and phosphorylated mTOR (p-mTOR) to mTOR were calculated. After 24 hours of culture, the mRNA expressions of type Ⅰ collagen, type Ⅲ collagen, and α-smooth muscle actin (α-SMA) in the cells were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Another batch of Fbs were divided into control group (with conventional culture), LY294002 group, metformin group, and LY294002+metformin group. LY294002, metformin, and LY294002+metformin were added to the culture media of the last three groups, respectively, with the final molarities of LY294002 and metformin being 20 μmol/L and 10 mmol/L, respectively. CCK-8 was used to detect the cell proliferation activity at 0 (immediately), 24, and 48 hours of culture. After 48 hours of culture, Western blotting was used to detect the phosphorylation levels of Akt and mTOR in the cells, and the ratios of p-Akt to Akt and p-mTOR to mTOR were calculated. The sample size for the cell proliferation inhibition rate experiment was 4, and the sample size for the other experiments was 3.Results:After 48 hours of culture, compared with the cells treated with PBS, the proliferation inhibition rates of the cells treated with 5, 10, 20, and 40 mmol/L metformin were significantly increased (with t values of 10.69, 14.20, 19.73, and 52.54, respectively, P<0.05), the content of hydroxyproline in the culture supernatants of the cells treated with 10, 20, and 40 mmol/L metformin was significantly decreased (with t values of 8.06, 7.86, and 10.25, respectively, P<0.05), and the ratios of p-Akt to Akt in the cells treated with 10, 20, and 40 mmol/L metformin and the ratios of p-mTOR to mTOR in the cells treated with 20 and 40 mmol/L metformin were significantly decreased (with t values of 2.82, 4.28, 9.88, 5.66, and 9.08, respectively, P<0.05). After 24 hours of culture, compared with those treated with PBS, the mRNA expressions of type Ⅰ collagen and α-SMA in the cells treated with 5, 10, 20, and 40 mmol/L metformin and the mRNA expressions of type Ⅲ collagen in the cells treated with 10, 20, and 40 mmol/L metformin were significantly decreased (with t values of 4.35, 8.53, 9.57, 14.77, 4.14, 5.58, 7.89, 9.37, 5.18, 6.85, and 9.15, respectively, P<0.05). At 24 and 48 hours of culture, the proliferation activities of the cells in LY294002 group (with t values of 6.30 and 13.60, respectively) and metformin group (with t values of 6.47 and 10.69, respectively) were significantly lower than those in control group ( P<0.05). After 48 hours of culture, the ratios of p-Akt to Akt in the cells of LY294002 group and metformin group were 0.554±0.027 and 0.681±0.029, respectively, which were significantly lower than 1.053±0.193 in control group (with t values of 4.45 and 3.31, respectively, P<0.05). The ratio of p-Akt to Akt in the cells of LY294002+metformin group was 0.387±0.023, which was significantly lower than that in metformin group ( t=5.95, P<0.05). After 48 hours of culture, the ratio of p-mTOR to mTOR in the cells of LY294002 group was significantly lower than that in control group ( t=4.01, P<0.05), and the ratio of p-mTOR to mTOR in the cells of LY294002+metformin group was significantly lower than that in metformin group ( t=6.05, P<0.05). Conclusions:Metformin can inhibit the proliferation and expression of fibrotic proteins type Ⅰ collagen, type Ⅲ collagen, and α-SMA of human HS Fbs through phosphatidylinositol 3-kinase/Akt/mTOR signaling pathway.

Objective:To investigate the clinical and genetic variation characteristics of a child with autosomal dominant lateral temporal lobe epilepsy caused by de novo variation of the MICAL1 gene. Methods:Clinical data of the patient with autosomal dominant lateral temporal lobe epilepsy caused by MICAL1 gene variation diagnosed in Children′s Hospital of Soochow University in August 2019 were collected. The whole exome sequencing was performed on the core members of the family, and the characteristics of gene variations were analyzed. Results:The proband, a 10 years and 5 months old boy, was admitted to the hospital because of "intermittent convulsions for 7 years". The clinical manifestations included focal or generalized tonic-clonic seizures and hearing aura, with normal language and intellectual development. No abnormalities were found in the T 1 and fluid attenuated inversion recovery sequences of the cranial 3.0 T magnetic resonance imaging and 3D thin-slice magnetic resonance imaging.Long-range video electroencephalogram showed the distribution of spinous and slow spinous waves in the left frontal and temporal areas. The results of whole exome gene sequencing in the core family members showed heterozygous de novo missense variation in the MICAL1 gene of the proband (NM_022765): c.763G>T(exon6)(p.Val255Leu) that had not been reported. According to American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines (2015), the mutation was considered potentially pathogenic. The application of antiepileptic drugs was effective in controlling epileptic seizures. Conclusions:Auditory symptoms are main clinical manifestations for the child with autosomal dominant lateral temporal lobe epilepsy. Antiepileptic drugs can effectively control epileptic seizures of the child, and the MICAL1 gene c.763G>T (p.Val255Leu) mutation is the genetic cause of the proband.

Objective:To investigate the clinical and genetic variation characteristics of a child with autosomal dominant lateral temporal lobe epilepsy caused by de novo variation of the MICAL1 gene. Methods:Clinical data of the patient with autosomal dominant lateral temporal lobe epilepsy caused by MICAL1 gene variation diagnosed in Children′s Hospital of Soochow University in August 2019 were collected. The whole exome sequencing was performed on the core members of the family, and the characteristics of gene variations were analyzed. Results:The proband, a 10 years and 5 months old boy, was admitted to the hospital because of "intermittent convulsions for 7 years". The clinical manifestations included focal or generalized tonic-clonic seizures and hearing aura, with normal language and intellectual development. No abnormalities were found in the T 1 and fluid attenuated inversion recovery sequences of the cranial 3.0 T magnetic resonance imaging and 3D thin-slice magnetic resonance imaging.Long-range video electroencephalogram showed the distribution of spinous and slow spinous waves in the left frontal and temporal areas. The results of whole exome gene sequencing in the core family members showed heterozygous de novo missense variation in the MICAL1 gene of the proband (NM_022765): c.763G>T(exon6)(p.Val255Leu) that had not been reported. According to American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines (2015), the mutation was considered potentially pathogenic. The application of antiepileptic drugs was effective in controlling epileptic seizures. Conclusions:Auditory symptoms are main clinical manifestations for the child with autosomal dominant lateral temporal lobe epilepsy. Antiepileptic drugs can effectively control epileptic seizures of the child, and the MICAL1 gene c.763G>T (p.Val255Leu) mutation is the genetic cause of the proband.

Objective:To investigate the effects and mechanism of metformin on the proliferation and expression of fibrotic proteins of human hypertrophic scar (HS) fibroblasts (Fbs).Methods:The study was an experimental study. From June 2021 to June 2022, 5 patients with HS were admitted to the Department of Burns and Cutaneous Surgery of the First Affiliated Hospital of Air Force Medical University, including 3 males and 2 females, aged from 21 to 36 years. HS tissue was collected, Fbs were isolated and cultured, and Fbs of passage 5 to 7 were used for experiment. Fbs were taken and cultured in their respective media supplemented with phosphate buffered solution (PBS) or metformin at final molarities of 5, 10, 20, and 40 mmol/L for 48 hours. The cell proliferation activity was detected using the cell counting kit-8 (CCK-8), and the proliferation inhibition rate of cells was calculated. The content of hydroxyproline in the cell culture supernatant was measured using a hydroxyproline assay kit. The phosphorylation levels of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) in the cells were detected by Western blotting, and the ratios of phosphorylated Akt (p-Akt) to Akt and phosphorylated mTOR (p-mTOR) to mTOR were calculated. After 24 hours of culture, the mRNA expressions of type Ⅰ collagen, type Ⅲ collagen, and α-smooth muscle actin (α-SMA) in the cells were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Another batch of Fbs were divided into control group (with conventional culture), LY294002 group, metformin group, and LY294002+metformin group. LY294002, metformin, and LY294002+metformin were added to the culture media of the last three groups, respectively, with the final molarities of LY294002 and metformin being 20 μmol/L and 10 mmol/L, respectively. CCK-8 was used to detect the cell proliferation activity at 0 (immediately), 24, and 48 hours of culture. After 48 hours of culture, Western blotting was used to detect the phosphorylation levels of Akt and mTOR in the cells, and the ratios of p-Akt to Akt and p-mTOR to mTOR were calculated. The sample size for the cell proliferation inhibition rate experiment was 4, and the sample size for the other experiments was 3.Results:After 48 hours of culture, compared with the cells treated with PBS, the proliferation inhibition rates of the cells treated with 5, 10, 20, and 40 mmol/L metformin were significantly increased (with t values of 10.69, 14.20, 19.73, and 52.54, respectively, P<0.05), the content of hydroxyproline in the culture supernatants of the cells treated with 10, 20, and 40 mmol/L metformin was significantly decreased (with t values of 8.06, 7.86, and 10.25, respectively, P<0.05), and the ratios of p-Akt to Akt in the cells treated with 10, 20, and 40 mmol/L metformin and the ratios of p-mTOR to mTOR in the cells treated with 20 and 40 mmol/L metformin were significantly decreased (with t values of 2.82, 4.28, 9.88, 5.66, and 9.08, respectively, P<0.05). After 24 hours of culture, compared with those treated with PBS, the mRNA expressions of type Ⅰ collagen and α-SMA in the cells treated with 5, 10, 20, and 40 mmol/L metformin and the mRNA expressions of type Ⅲ collagen in the cells treated with 10, 20, and 40 mmol/L metformin were significantly decreased (with t values of 4.35, 8.53, 9.57, 14.77, 4.14, 5.58, 7.89, 9.37, 5.18, 6.85, and 9.15, respectively, P<0.05). At 24 and 48 hours of culture, the proliferation activities of the cells in LY294002 group (with t values of 6.30 and 13.60, respectively) and metformin group (with t values of 6.47 and 10.69, respectively) were significantly lower than those in control group ( P<0.05). After 48 hours of culture, the ratios of p-Akt to Akt in the cells of LY294002 group and metformin group were 0.554±0.027 and 0.681±0.029, respectively, which were significantly lower than 1.053±0.193 in control group (with t values of 4.45 and 3.31, respectively, P<0.05). The ratio of p-Akt to Akt in the cells of LY294002+metformin group was 0.387±0.023, which was significantly lower than that in metformin group ( t=5.95, P<0.05). After 48 hours of culture, the ratio of p-mTOR to mTOR in the cells of LY294002 group was significantly lower than that in control group ( t=4.01, P<0.05), and the ratio of p-mTOR to mTOR in the cells of LY294002+metformin group was significantly lower than that in metformin group ( t=6.05, P<0.05). Conclusions:Metformin can inhibit the proliferation and expression of fibrotic proteins type Ⅰ collagen, type Ⅲ collagen, and α-SMA of human HS Fbs through phosphatidylinositol 3-kinase/Akt/mTOR signaling pathway.

Heart failure,as a global public health challenge,is experiencing an increasingly severe disease burden.Given the close relationship be-tween the Nitric Oxide-Soluble Guanylate Cyclase-Cyclic Guanosine Monophosphate(NO-sGC-cGMP)signaling pathway and heart failure,this study,through a comprehensive search and review of re-cent literature on the NO-sGC-cGMP pathway and heart failure,aims to outline the mechanism of ac-tion of this signaling pathway and its connection with heart failure,in order to explore new avenues for the treatment of heart failure.

Heart failure,as a global public health challenge,is experiencing an increasingly severe disease burden.Given the close relationship be-tween the Nitric Oxide-Soluble Guanylate Cyclase-Cyclic Guanosine Monophosphate(NO-sGC-cGMP)signaling pathway and heart failure,this study,through a comprehensive search and review of re-cent literature on the NO-sGC-cGMP pathway and heart failure,aims to outline the mechanism of ac-tion of this signaling pathway and its connection with heart failure,in order to explore new avenues for the treatment of heart failure.

OBJECTIVE To investigate the potential therapeutic effect of the sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" from the perspective of immunomodulation and cardioprotection. METHODS Chemical components of the sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" were analyzed by UPLC-Q-TOF-MS and colorimetric methods. Examined tablet’s effects on zebrafish models of macrophage reduction, heart failure, H2O2-induced oxidative stress in myocardial and endothelial cells, and a microglial inflammation model induced by lipopolysaccharide. Immune regulation and cardioprotective effects were evaluated through multiple indicators, including macrophage formation and phagocytosis abilities, anti-neuroinflammation ability, cardiac systolic and diastolic functions, and anti-oxidative stress injury ability in myocardial and endothelial cells. RESULTS The sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" improved macrophage formation and phagocytosis, cardiac systolic and diastolic functions, reduced neuroinflammation, and alleviated oxidative stress in myocardial and endothelial cells, resulting in immunomodulatory and cardioprotective effects. CONCLUSION The sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" maybe a potential therapeutic agent for regulating the immune system and protecting cardiac function.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Purpose/Significance To provide high-quality health information services,to promote the coordinated development of medical and educational services,and to help build a healthy China service system.Method/Process By using the methods of network investigation,literature investigation and telephone interview,the paper investigates the current situation of teaching support services of 30 libraries of medical universities and colleges in China,and analyzes the existing problems from four aspects:teaching resource serv-ices,information literacy services,disciplinary services and service guarantee.Result/Conclusion Libraries of medical universities and colleges should establish and improve the teaching support service system,strengthen discipline teaching support services,provide accu-rate health information services,strengthen regional or departmental collaboration,and innovate intelligent service modes,so as to be-come an important driving force for healthy China initiative.

Objective To understand the basic information of the number, classification, and distribution of radiation work units in non-medical institutions in Shanxi Province, China, and to analyze the status quo of health management and radiation protection measures for radiation workers, so as to provide a scientific basis for occupational exposure protection in non-medical radiation work units and better protect the occupational health rights and interests of radiation workers. Methods A questionnaire survey was conducted to investigate some non-medical institutions in Shanxi Province. On-site testing was carried out to determine the risk factors for radioactive occupational diseases in the selected non-medical institutions. Results In 220 non-medical institutions, there were 340 radiation devices and 2284 radioactive sources. The rate of individual dose monitoring was 92.7% and the rate of occupational health examination was 87.2%. These devices were equipped with 325 detection instruments for radiation protection, 1316 personal protective equipment, and 730 personal dose alarms. Radiation occupational disease risk factors were investigated in 101 institutions. Conclusion The occupational health management of radiation workers in non-medical institutions in Shanxi Province is generally in line with the national standards. However, there is still a big gap with the level of occupational health management in medical institutions. The health administration departments should clarify the management measures for non-medical institutions and strengthen their supervision and management functions.