BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

BACKGROUND:The imbalance between bone resorption and bone formation in microgravity environments leads to significant bone loss in astronauts.Current research indicates that bone loss under microgravity conditions is the result of the combined effects of various cells,tissues,and systems. OBJECTIVE:To review different biological effects of microgravity on various cells,tissues,or systems,and summarize the mechanisms by which microgravity leads to the development of osteoporosis. METHODS:Databases such as PubMed,Web of Science,and the Cochrane Database were searched for relevant literature from 2000 to 2023.The inclusion criteria were all articles related to tissue engineering studies and basic research on osteoporosis caused by microgravity.Ultimately,85 articles were included for review. RESULTS AND CONCLUSION:(1)In microgravity environment,bone marrow mesenchymal stem cells tend to differentiate more into adipocytes rather than osteoblasts,and hematopoietic stem cells in this environment are more inclined to differentiate into osteoclasts,reducing differentiation into the erythroid lineage.At the same time,microgravity inhibits the proliferation and differentiation of osteoblasts,promotes apoptosis of osteoblasts,alters cell morphology,and reduces the mineralization capacity of osteoblasts.Microgravity significantly increases the number and activity of osteoclasts.Microgravity also hinders the differentiation of osteoblasts into osteocytes and promotes the apoptosis of osteocytes.(2)In a microgravity environment,the body experiences changes such as skeletal muscle atrophy,microvascular remodeling,bone microcirculation disorders,and endocrine disruption.These changes lead to mechanical unloading in the bone microenvironment,insufficient blood perfusion,and calcium cycle disorders,which significantly impact the development of osteoporosis.(3)At present,the mechanism by which microgravity causes osteoporosis is relatively complex.A deeper study of these physiological mechanisms is crucial to ensuring the health of astronauts during long-term space missions,and provides a theoretical basis for the prevention and treatment of osteoporosis.

Objective To observe the clinical efficacy and safety of filiform-heated needle combined with Qingbu Huacuo Decoction in the treatment of acne of damp-heat due to spleen deficiency syndrome.Methods Seventy patients with acne of damp-heat due to spleen deficiency syndrome admitted to the seventh clinical Medical School of Guangzhou University of Chinese Medicine from May 2023 to March 2024 were randomly divided into the observation group and the control group according to random number table method,with 35 patients in each group.Health education was given to the patients in both groups.The control group was given oral administration of Doxycycline Hyclate Tablets combined with filiform-heated needle for treatment,and the observation group was treated with filiform-heated needle combined with Qingbu Huacuo Decoction orally,the course of treatment for the two groups covered six weeks.After six weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes in Global Acne Grading System(GAGS)score and Quality of Life-Acne(Qol-Acne)score,as well as the traditional Chinese medicine(TCM)syndrome scores before and after treatment were observed.The changes of skin barrier function indicators such as trans epidermal water loss(TEWL)content,skin moisture content,and sebum content before and after treatment were compared between the two groups of patients.Moreover,the safety of the two groups and the occurrence of adverse reactions were evaluated.Results(1)After treatment,the GAGS scores of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,with a statistically significant difference(P<0.05).(2)After treatment,the Qol-Acne scores of the patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving the three aspects of self-perception,emotional functioning,and self-assessment,with a statistically significant difference(P<0.05),and the observation group was slightly superior to the control group in improving social functioning,but the difference being not statistically significant(P>0.05).(3)After treatment,the content of TEWL,skin moisture,and sebum of patients in the two groups were significantly improved(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(4)After treatment,the TCM syndrome scores of the two groups of patients were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,with a statistically significant difference(P<0.05).(5)The total effective rate was 94.29%(33/35)in the observation group and 74.29%(26/35)in the control group.The clinical efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(6)Comparison of the incidence of adverse reactions between the two groups,the difference being not statistically significant(P>0.05).Conclusion Filiform-heated needle combined with Qingbu Huacuo Decoction in the treatment of acne of damp-heat due to spleen deficiency syndrome can significantly improve the clinical symptoms of patients,thus improving their quality of life,with good safety.

Objective To observe the clinical efficacy of modified Danggui Yinzi combined with thumb-tack needling for subcutaneous embedding in the treatment of chronic spontaneous urticaria(CSU)of wind dryness due to blood deficiency type.Methods A total of 68 cases of patients admitted to the dermatology wards and outpatient clinics of The Seventh Clinical School of Guangzhou University of Chinese Medicine with a definitive diagnosis of CSU of wind dryness due to blood deficiency type were selected as the study subjects from July 2023 to February 2024.The patients were randomly divided into the observation group and the control group according to the random number table method,with 34 cases in each group.The control group was treated with Cetirizine Dihydrochloride Tablets,and the observation group was treated with modified Danggui Yinzi combined with thumb-tack needling for subcutaneous embedding based on the treatment of the control group,the course of treatment covered four weeks.After one month of treatment,the clinical efficacy of the two groups was evaluated,and the changes in Urticaria Activity Score(UAS)and Dermatology Life Quality Index(DLQI)scores and traditional Chinese medicine(TCM)syndrome scores before and after treatment were observed in the two groups.The changes of serum total immunoglobulin E(total IgE)levels before and after treatment in the two groups were compared.The safety and recurrence cases of the two groups were evaluated.Results(1)The total effective rate was 91.18％(31/34)in the observation group and 70.59％(24/34)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P＜0.05).(2)After two,three,and four weeks of treatment,the UAS scores of the patients in the two groups were improved significantly(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.01).(3)After treatment,the DLQI scores and TCM syndrome scores of the patients in the two groups were improved significantly(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.01).(4)After treatment,the total IgE levels of patients in the two groups were improved significantly(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.01).(5)The comparison of the incidence of adverse reactions between the two groups showed that the difference being not statistically significant(P＞0.05).(6)In the follow-up after the completion of treatment,the recurrence rate was 5.88％(2/34)in the observation group and 23.53％(8/34)in the control group,and the recurrence rate of the observation group was significantly lower than that of the control group,the difference being statistically significant(P＜0.05).Conclusion Modified Danggui Yinzi combined with thumb-tack needling for subcutaneous embedding in the treatment of CSU of wind dryness due to blood deficiency type can significantly alleviate the clinical symptoms of the patients,improve their quality of life,and reduce the recurrence rate.

BACKGROUND:Fluid shear stress plays an important role in osteoblast proliferation and apoptosis.However,whether Caveolin-1 is involved in the process of fluid shear stress-induced proliferation and apoptosis in osteoblasts is unknown. OBJECTIVE:To explore the role of Caveolin-1 in fluid shear stress-regulated osteoblast proliferation and apoptosis. METHODS:The MC3T3-E1 osteoblasts in good growth status were selected and loaded with fluid shear stress at an intensity of 1.2 Pa for different times(0,30,60,90 minutes).The expression of Caveolin-1 protein was observed and conditions with a time of 60 minutes were screened for the experiment.MC3T3-E1 cells were divided into control group,fluid shear stress group,fluid shear stress+pcDNA 3.1 group(control),fluid shear stress+pcDNA Cav-1 group(plasmid overexpression),and intervened with fluid shear stress and overexpression of Cav-1,respectively.The expression of molecules related to proliferation and apoptosis in MC3T3-E1 cells was detected by qRT-PCR and western blot.In addition,the proliferative activity of MC3T3-E1 cells was detected by cell counting kit-8 and EdU assay;and cell apoptosis was detected by Hoechst 33258 and flow cytometry. RESULTS AND CONCLUSION:The expression of Caveolin-1 in MC3T3-E1 cells was significantly down-regulated after loading fluid shear stress,and the expression level was lowest after 60 minutes.Overexpression of Caveolin-1 attenuated the proliferation-promoting and apoptosis-suppressing effects of fluid shear stress in MC3T3-E1 cells.In conclusion,Caveolin-1 has a vital role in fluid shear stress-regulated osteoblast proliferation and apoptosis,which may offer a potential therapeutic strategy for osteoporosis.

Objective:To explore the genetic basis for a child featuring global developmental delay and epilepsy.Methods:A child who had presented at Guangzhou Women and Children′s Medical Center Liuzhou Hospital on February 19, 2023 was selected as the study subject. Clinical data of the child was collected. The child was subjected to whole exome sequencing, and candidate variant was validated by Sanger sequencing and bioinformatic analysis.Results:The child, an 8-month-old girl, had manifested with global developmental delay, epilepsy, and hyperlactacidemia. Cranial MRI revealed diverse hypomyelinating leukodystrophies. Electroencephalogram showed slow background activities. Genetic testing revealed that she has harbored a homozygous variant of the SLC25A12 gene, namely c. 115T>G (p.Phe39Val), for which both of her parents were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be of uncertain significance (PM2_Supporting+ PM3_Supporting+ PP3_Moderate+ PP4_Moderate). I-Mutant v3.0 software predicted that the variant may affect the stability of protein product. Conclusion:The homozygous c. 115T>G (p.Phe39Val) variant of the SLC25A12 gene probably underlay the pathogenesis of the disease in this child.

Objective:To investigate the value of fibrinogen to albumin ratio (FAR), creatinine to albumin ratio (CAR) and platelet to lymphocyte ratio (PLR) in predicting the poor prognosis of hyperlipidemic acute pancreatitis (HLAP).Methods:Clinical data of HLAP patients admitted to the hospital from January 2021 to January and December 2023 were retrospectively collected. According to the prognosis, the patients were divided into two groups: good prognosis group and poor prognosis group.The independent risk factors of HLAP in different prognostic groups were obtained by multivariate Logistic regression analysis. Receiver operating characteristic (ROC) curves were plotted to evaluate the prognostic value of FAR, CAR and PLR alone and in combination.Results:A total of 118 patients with HLAP were included, including 69 patients with good prognosis and 49 patients with poor prognosis.The difference of heart rate, lymphocyte, triglyceride, albumin, creatinine, urea nitrogen, blood calcium, blood glucose, C-reactive protein, procalcitonin, fibrinogen, FAR, CAR, PLR, Bedside indicator of acute pancreatitis Severity score, Acute Physiology and Chronic Health status score, hospitalization time assessment between the two groups was statistically significant ( P<0.05). Multivariate Logistic regression analysis showed that FAR (odds ratio ( OR) = 25.949, 95% confidence interval (95% CI):3.190 ~ 211.080, P = 0.002), CAR ( OR = 1.453, 95% CI:1.095 ~ 1.928, P = 0.010) and PLR ( OR = 1.005, 95% CI: 1.001 ~ 1.009, P = 0.020) were independent risk factors for poor prognosis in HLAP patients. ROC curve analysis showed that the area under the ROC curve (AUC) of FAR, CAR and PLR to predict poor prognosis of HLAP patients were 0.823, 0.781 and 0.652, respectively.The AUC of FAR combined with CAR, FAR combined with PLR and CAR combined with PLR were 0.840, 0.845 and 0.849, respectively.The combined ability of FAR, CAR and PLR to predict poor prognosis in HLAP patients was (AUC=0.875,95% CI:0.814 ~ 0.937). When the cut-off value was 0.387, the sensitivity was 83.7%, and the specificity was 79.7%. Conclusions:The prognostic value of FAR, CAR and PLR in HLAP patients is better than that of single or pairwise combination.

Purpose/Significance The paper systematically reviews the application and research progress of large language models(LLMs)in the medical field,analyzes the key challenges and opportunities,and provides references for related research.Method/Process The systematic literature review method is adopted to comprehensively review the relevant literature published in recent years,fo-cusing on the latest progress of medical LLMs.The application results,research status and challenges of LLMs in medical natural lan-guage processing(NLP)tasks are analyzed.Result/Conclusion The application of LLMs in the medical field has a broad prospect,and the future research should focus on the technical progress and the improvement of ethical norms.On the one hand,the pace of technologi-cal innovation should be accelerated,and on the other hand,strict compliance with ethical standards should be ensured to jointly promote the sustainable development of LLMs technology in the medical field.

Objective To analyze the general condition,etiological characteristics,antibiotic use,treatment and prognosis of adult patients with pyogenic liver abscess(PLA)in order to improve the diagnosis and treatment of PLA.Methods The clinical data of adult patients diagnosed with PLA who were hospitalized in Tianjin Medical University General Hospital from December 2019 to December 2022 were retrospectively analyzed,including general information,pathogen culture and antimicrobial susceptibility testing results,treatment and outcomes.The etiological characteristics and the use of clinical anti-infective drugs were analyzed.Results A total of 280 adult patients with PLA were enrolled,including 161 males and 119 females(male/female ratio:1.35:1).The average age was 63.1±13.6 years.PLA was most frequently found in the patients of 50-80 years of age.The most common route of infection was cryptogenic infection(55.7％).The most common underlying disease was diabetes mellitus(41.1％).The positive rate of bacterial culture was 28.4％from blood,and 80.3％from pus.Klebsiella pneumoniae and Escherichia coli were the most common bacteria isolated from blood culture and pus culture.A total of 14 strains of antibiotic-resistant bacteria were identified,including 3 strains of extended-spectrum β-lactamase(ESBLs)-producing K.pneumoniae,3 strains of ESBLs-producing E.coli,1 strain of carbapenem-resistant K.pneumoniae,and 1 strain of carbapenem-resistant E.coli.There were 2 strains of methicillin-resistant Staphylococcus,3 strains of high level ampicillin and aminoglycoside resistant Enterococcus,and 1 strain of vancomycin-resistant Enterococcus.The gram-negative pathogens showed the lowest susceptibility rate to levofloxacin(82.3％)and the highest susceptibility rate to imipenem(98.2％).Overall,the gram-negative pathogens were generally susceptible to cephalosporins/β-lactamase inhibitor combinations,penicillins/β-lactamase inhibitor combinations,aminoglycosides,glycylcyclines,cephamycins,carbapenems and sulfonamides.Cephalosporins/β-lactamase inhibitor combinations are the most commonly used initial empirical treatment for PLA.Conclusions PLA is more common in men,especially the patients of 50-80 years of age and those complicated with diabetes mellitus.K pneumoniae was the major pathogen,which was sensitive to most commonly used antibiotics.The empirical treatment is mainly cephalosporins/β-lactamase inhibitor combinations.Carbapenems were also used frequently.Attention should be paid to unnecessary combination therapies and irrational use of antibiotics.

Ferrets offer an advantage in nonclinical studies of anti-infective drugs because of their ability to be infected with and spread pathogenic microorganisms,especially viral strains,without the need for host adaptation.Additionally,the clinical symptoms exhibited by infected ferrets are very similar to those of humans.Although ferrets play a very important role in the research and development of antiviral drugs,the scope of their application remains limited.This may be related to the lack of corresponding national standards for laboratory animal feeding and application of ferrets as well as the lack of specific diagnostic and detection reagents.This paper summarizes the characteristics of ferrets as infectious disease models with a summary and analysis of the application direction of ferrets in anti-infective drug research.Our aim is to promote further standardization of the use of ferrets.