OBJECTIVE To evaluate the therapeutic efficacy of 5 regimens of colistin sulfate for common Gram-negative bacilli infection based on pharmacokinetics （PK）/pharmacodynamics （PD） theory and Monte Carlo simulation. METHODS Minimal inhibitory concentration （MIC） data of colistin sulfate against Acinetobacter baumannii， Pseudomonas aeruginosa， Klebsiella pneumoniae， Escherichia coli and Enterobacter cloacae in 2023 were collected from the China Antimicrobial Resistance Surveillance System. Monte Carlo simulation was conducted with the ratio of the area under the concentration-time curve from 0 to 24 hours in the unbound state to the MIC （fAUC0－24 h/MIC） ≥15 as the target value， the probabilities of target attainment （PTA） of 5 regimens of colistin sulfate to achieve the target ratio were obtained at different MIC； and the expected population PTA， specifically the cumulative fraction of response （CFR）， for each regimen within a specific bacterial population was further calculated， to evaluate the therapeutic efficacy of the five colistin sulfate regimens. RESULTS When bacterial MIC≤0.5 µg/mL， PTA of all colistin sulfate regimens （500 000 IU， q12 h； 500 000 IU， q8 h； 750 000 IU， q12 h； 750 000 IU， q8 h； 1 000 000 IU， q12 h） were all more than 90%. When bacterial MIC＝1 µg/mL， PTA for regimen （750 000 IU， q8 h） against A. baumannii， K. pneumoniae， P. aeruginosa， E. coli and E. cloacae， and for regimen （1 000 000 IU， q12 h） against the other four bacterial species （excluding P. aeruginosa） remained above 90%. When bacterial MIC≥2 µg/mL， PTA of 5 colistin sulfate regimens were all lower than 90%. For E. coli， the CFR of only colistin sulfate regimen （500 000 IU， q12 h） was less than 90%； for K. pneumoniae， the CFR of only colistin sulfate regimen （750 000 IU， q8 h and 1 000 000 IU， q12 h） was greater than 90%； for the other three bacteria， CFR of 5 regimens were all less than 90%. CONCLUSIONS When the MIC of Gram-negative bacteria is less than 0.5 µg/mL， colistin sulfate regimen with a routine dose can be selected for treatment. When MIC was 1 µg/mL， an increase in the dosing amount or frequency is required. The empirical treatment of the other four bacterial infections excluding E. coli requires the use of off-label doses.

Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7％of patients met the criteria of LLDAS,while 10.4％of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

BACKGROUND:Gut microbiota is closely related to host energy balance and metabolism.The metabolites of intestinal flora can regulate the occurrence and development of obesity and can be a new target for the prevention and treatment of obesity. OBJECTIVE:To summarize the interaction between the intestinal flora and obesity,as well as the specific mechanism underlying regulation of obesity by metabolites of intestinal flora,thereby providing a new reference and basis for the prevention and treatment of obesity. METHODS:"Intestinal microbiota,intestinal bacteria,intestinal microbiota metabolites,short-chain fatty acids,bile acids,ipopolysaccharide,trimethylamine N-oxide,medium-chain fatty acids,tryptophan derivatives,obesity"were used as search terms in Chinese and English.Literature related to obesity from 1990 to 2022 was retrieved in PubMed and CNKI databases.According to inclusion and exclusion criteria,88 articles were finally selected. RESULTS AND CONCLUSION:Intestinal flora is closely related to the occurrence and development of obesity.For example,changes in the Firmicutes to Bacteroidetes ratio can be used as a biomarker for the diagnosis of obesity,and the occurrence of obesity can be delayed by the colonization of probiotics such as Bifidobacterium breve,Lactobacillus and Akkermansia.Intestinal flora is mainly mediated by the metabolites of intestinal flora to participate in the regulation of obesity.For example,short-chain fatty acid can regulate adipogenesis by regulating signaling pathways such as G protein-coupled receptors 41,43 and peroxisome proliferator-activated receptor γ,thus delaying the occurrence and development of obesity.Bile acids can increase insulin sensitivity and body energy expenditure by promoting the activation of G protein-coupled receptor 5 and farnesol X receptor.In addition,lipopolysaccharide,trimethylamine oxide,medium-chain fatty acids and tryptophan derivatives are also widely involved in the occurrence and development of obesity through various signaling pathways.Further studies have found that metabolites of the same bacterial community exert heterogeneous effects in the specific process of regulating obesity via different signaling pathways.For example,under the influence of high-fat diet,acetic acids can activate the parasympathetic nervous system,leading to hyperphagia and liver insulin resistance and thus accelerating the physiological course of obesity.

BACKGROUND:Intestinal flora and its metabolites can participate in the pathological process of osteoporosis and play an important role in the diagnosis and treatment of osteoporosis.In addition,exercise can regulate the intestinal flora and thus affect the occurrence and development of osteoporosis. OBJECTIVE:To summarize the effects and mechanism of intestinal flora on osteoblasts,osteoclasts,and bone marrow mesenchymal stem cells,and the potential role of exercise-mediated intestinal flora in regulating osteoporosis. METHODS:"Intestinal flora,intestinal bacteria,metabolites of intestinal flora,bone metabolism,osteoporosis,exercise"were selected as keywords.Literatures from 1990 to 2023 were retrieved from PubMed and CNKI databases. RESULTS AND CONCLUSION:Changes in the abundance and diversity of intestinal flora and changes in the levels of intestinal flora metabolites such as trimethylamine oxide and bile acid can be used as biomarkers for the diagnosis of osteoporosis.The imbalance of intestinal flora can lead to intestinal barrier dysfunction and excessive production of lipopolysaccharides and trimethylamine oxide,induce the secretion of tumor necrosis factor-α and other inflammatory cytokines,activate the nuclear factor κB signaling pathway and aggravate oxidative stress,thus promoting osteoclast differentiation,inducing osteoblast apoptosis and affecting bone marrow mesenchymal cell migration.Remodeling intestinal flora homeostasis can inhibit inflammatory response,downregulate oxidative stress,inhibit osteoclast differentiation,promote osteoblast differentiation,and regulate the osteogenic migration of bone marrow mesenchymal cells to prevent and treat osteoporosis.Exercise can regulate intestinal flora homeostasis,improve intestinal barrier function,promote the secretion of short-chain fatty acids and bile acids,down-regulate serum lipopolysaccharide level,reduce oxidative stress,and then inhibit osteocyte apoptosis,inhibit osteoclast differentiation,promote osteoblast differentiation,and regulate osteocyte nutrient metabolism to exert the potential of preventing and treating osteoporosis.

Objective:To discuss the synergistic inhibitory effect of apatinib mesylate(apatinib)combined with radiotherapy(RT)on the hepatocellular carcinoma(HepG2)cells in vitro,and to clarify its related antitumor mechanism.Methods:The HepG2 cells were cultured in vitro and treated with different concentrations of apatinib and/or varying doses of X-rays.MTT method was used to detect the survival rates of the cells in various groups;the inhibitory rates of cell proliferation and the 20％inhibitory concentration(IC20)of apatinib were calculated;the X-ray irradiation dose for subsequent experiments was detected.The HepG2 cells were divided into apatinib group,RT group,and apatinib+RT group(combined group).Flow cytometry was used to detect the apoptotic rates of the cells in various groups;wound healing assay was used to detect the migration rates of the cells in various groups;ELISA method was used to detect the levels of vascular endothelial growth factor(VEGF)in the cell culture supernatant in various groups.Results:The MTT results showed that the IC20 of apatinib was 1.32 μmol·L-1,and this concentration was used for subsequent experiments,and the X-ray irradiation dose for the follow-up experiments was 2 Gy.Compared with control group,the apoptotic rates of the cells in apatinib group and RT group had no significant differences(P＞0.05),while the apoptotic rate of the cells in combined group was increased(P＜0.05).Compared with control group,the migration rates of the cells in apatinib group,RT group,and combined group were decreased(P＜0.05);compared with apatinib group and RT group,the migration rate of the cells in combined group was decreased(P＜0.05).Compared with control group,the levels of VEGF in the cell culture supernatant in apatinib group and combined group were decreased(P＜0.05);compared with apatinib and RT group,the level of VEGF in the cell culture supernatant in combined group was decreased(P＜0.05).Conclusion:Apatinib combined with radiotherapy significantly inhibits the proliferation and migration of the HepG2 cells in vitro and induces the apoptosis;its effect may be related to the inhibition of VEGF secretion by cells.

Objective:To investigate the effects of using a high monounsaturated fatty acid (MUFA) and low carbohydrate formula on blood glucose levels and diarrhea treatment effects in critically ill neurological patients.Methods:A self-controlled before-and-after study design was employed, with 13 patients admitted to the neurology intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from November to December 2023, who were treated with a high MUFA and low carbohydrate formula [Glucerna enteral nutrition (EN) preparation]. Changes in blood glucose parameters within 7 days before and after the use of Glucerna EN preparation were analyzed, including standard deviation ( SD) of blood glucose, mean blood glucose (MG), median blood glucose, mean amplitude of glycemic excursions (MAGE), largest amplitude of glycemic excursions (LAGE), coefficient of variation ( CV) of blood glucose, the incidence of hyperglycemia (> 7.8 mmol/L) and severe hyperglycemia (> 13.9 mmol/L), and daily insulin dose. Changes in total protein (TP), albumin (ALB), hemoglobin (Hb), C-reactive protein (CRP), and white blood cell count (WBC) were observed before and after intervention. Improvement in diarrhea symptoms, Hart diarrhea score, Bristol Stool classification score, and incontinence dermatitis classification were also analyzed before and after the use of Glucerna EN preparation. Results:A total of 13 critically ill neurological patients were enrolled, among whom 9 patients had a history of hyperglycemia and 8 patients had diarrhea symptoms. After intervention with Glucerna, the patients' SD of blood glucose, MG, median blood glucose, MAGE, LAGE, CV of blood glucose, incidence of hyperglycemia, incidence of severe hyperglycemia, and daily insulin dose were all lower than those before the intervention [ SD of blood glucose (mmol/L): 1.83±1.11 vs. 2.10±1.13, MG (mmol/L): 8.87±2.03 vs. 9.75±1.37, median blood glucose (mmol/L): 9.12±1.67 vs. 10.17±0.48, MAGE (mmol/L): 0.66±0.31 vs. 0.78±0.32, LAGE (mmol/L): 4.95±3.64 vs. 5.58±3.10, CV of blood glucose: 16.00% (11.00%, 28.50%) vs. 18.00% (12.50%, 27.50%), hyperglycemia incidence: 47.31% vs. 74.66%, severe hyperglycemia incidence: 6.08% vs. 6.71%, daily insulin dose (U): 5.25 (0.00, 32.59) vs. 20.76 (0.00, 66.88)], with a significant decrease in daily insulin dose after the intervention ( P < 0.05); TP, ALB, Hb, CRP and WBC showed no significant changes before and after the intervention with Glucerna EN preparation. The improvement time of diarrhea symptoms after intervention was (3.50±1.41) days, and the Hart diarrhea score on the seventh day after intervention (4.88±3.48 vs. 10.00±3.38) and the Bristol Stool classification score on the third and seventh days after intervention (5.87±0.35, 5.50±0.53 vs. 6.50±0.53) were significantly lower than before the intervention (all P < 0.05). Before the intervention with Glucerna EN preparation, the classification of incontinence dermatitis was mainly classified as Grade 2 severity (71.43%); after the intervention, it significantly improved by the seventh day, with Grade 1 being the main classification (57.14%). Conclusion:The high MUFA and low carbohydrate formula has a positive effect on blood glucose control and diarrhea treatment in critically ill neurological patients.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

Objective:To investigate the regulatory effect of deoxycytidine kinase (dCK) on ionizing radiation (IR) induced ferroptosis in triple-negative breast cancer (TNBC).Methods:TNBC cell line MDA-MB-231 was used to establish dCK knockdown and different phosphorylation phenotypes cell models, and were treated with ferroptosis activator Erastin and / or ferroptosis inhibitor ferrostatin-1 (Fer-1) combined with / without X-ray irradiation. Cell viability was detected by MTT assay. The level of reactive oxygen species (ROS) was measured by 2′,7′-dichlorofluorescin diacetate (DCFH-DA) staining. The expression levels of dCK, transferrin, transferrin receptor (TfR1), ferroportin (FPN) and ferritin heavy chain 1 (FTH1) were detected by Western blot. Statistical analysis was performed by SPSS 17.0 and Origin 2021 software. Measurement data with normal distribution were expressed by Mean ±SD. The comparison between two groups was conducted by Student t-test. The comparison among three or more groups was performed by one-way analysis of variance. Results:In MDA-MB-231 cells, IR induced cell death was observed and Erastin significantly promoted radiation induced cell death, while Fer-1 was able to reverse radiation induced cell death. Compared with the control group, IR induced cell death was increased, the level of ROS was suppressed in the dCK knockdown group. Erastin combined with IR induced reduced cell death and weakened ROS level. Fer-1 reduced the degree of IR induced cell death, and it could not inhibit the induction of ROS by IR.Compared with the control cells, the rate of cell death was decreased induced by IR, the level of ROS was decreased, the expression of FTH1 was down-regulated after IR in the dCK wild-type (dCK-WT ) or dCK hyperphosphorylated (dCK-S74E) MDA-MB-231 cells. In addition, Erastin promotes IR induced cell death and increased ROS levels, while Fer-1 significantly enhances the degree of reversal of IR induced ROS and cell death in these cells. Conclusions:dCK phosphorylation increases ferroptosis induced by IR in TNBC cells. Targeting dCK may be a novel therapeutic approach to overcome radioresistance in TNBC treatment.

Objective:To observe the efficacy of free transplantation of latissimus dorsi musculocutaneous flap and anterolateral femoral skin flap in repairing the wound after the resection of the scalp squamous cell carcinoma, and to explore the indications of these two skin flaps.Methods:The clinical data of patients with scalp squamous cell carcinoma admitted to the Plastic Surgery Department of the Second Affiliated Hospital of Kunming Medical University from June 2013 to May 2019 were analyzed retrospectively. All patients showed no cancer metastasis examined with CT. None of the patients had systemic diseases such as hypertension, diabetes, vascular disease. The wounds were repaired with free transplantation of latissimus dorsi myocutaneous flaps and anterolateral thigh flaps after extensive tumor resection. The intraoperative vascular variation, the diameter of the anastomosed blood vessel, the length of the vascular pedicle, the flap size, the time of harvesting the flap, the time for anastomosis, the operation time, and the incidences of complications at the donor site and recipient site were measured or recorded in both groups.Results:A total of 21 cases were included, including 14 males and 7 females, aged from 12 to 61 years. Eleven cases were repaired with the latissimus dorsi musculocutaneous flap, and 10 cases with the anterolateral thigh flap. All the 21 flaps survived during the 1 to 2 years follow-up. No vascular variation was found in the latissimus dorsi myocutaneous flap group, whereas 2 cases of vascular variation were found in the anterolateral thigh flap. In the latissimus dorsi myocutaneous flap group, the anastomotic vessel diameter was (2.14±0.09) mm for the artery and (2.49±0.10) mm for the vein. The vascular pedicle length was (6.14±0.28) cm, and the size of the flap was (135.0±20.8) cm 2, the harvesting time was (114.8±3.0) min, the vascular anastomosis time was (20.8±0.8) min, and the operation time was (6.5±0.2) h. In the anterolateral thigh flap group, the anastomotic vessel diameter was (2.15±0.14) mm for the artery and (2.45±0.15) mm for the vein. The vascular pedicle length was (6.80±0.31) cm, and the size of the flap was (159.9±16.4) cm 2, the harvesting time was (119.8±3.6) min, the vascular anastomosis time was (21.5±0.9) min, and the operation time was (6.9±0.2) h. There was no significant difference between the two kinds of flaps in the above parameter. The incidence of total complications at the donor site was higher in the latissimus dorsi myocutaneous flap group (7 cases) than that in the anterolateral thigh flap group (4 cases). The incidence of overall complications at the recipient was lower in the latissimus dorsi myocutaneous flap group (1 case) than that in the anterolateral thigh flap group (2 cases). Conclusions:Both the latissimus dorsi myocutaneous flap and the anterolateral femoral skin flap can achieve good results in repairing the wound after the resection of the scalp squamous cell carcinoma. The latissimus dorsi myocutaneous flap has a constant blood supply, and the operative technique is relatively easy and with low risk, which is more suitable for novices. The anterolateral thigh flap is thin and with fewer complications at the donor site. It is easy to be accepted by patients and can be performed in the supine position, which is more suitable for elderly patients.

Objective:To clarify the mechanism of Fat1 on the proliferation of esophageal squamous cell carcinoma (ESCC).Methods:KYSE450 cells were transfected with Plko.1-puro-GFP-shRNA-Fat1 plasmid and real time polymerase chain reaction (PCR) was used to verify the efficiency of Fat1 knockdown. The effects of Fat1 and extracellular regulated protein kinase (ERK) pathway inhibitor U0126 on the proliferation of ESCC cells were detected by methyl thiazolyl tetrazolium (MTT). Colony formation assay was used to detect the colony formation ability. Cell cycle was detected by live cell imaging. Western blot was used to observe the level of target protein. Mouse xenograft assay was applied to detect the effect of Fat1 knockdown on KYSE450 cell tumor growth. Immunohistochemistry was used to detect the expressions of related proteins in tumor sections.Results:The efficiency of Fat1 knockdown was (77.1±6.9)% in Fat1 sh1 group and (77.7±7.1)% in Fat1sh2 group. Compared with the control group, the cell proliferation and the expression of p-ERK1/2 were significantly increased in Fat1 sh1 and Fat1sh2 group ( P<0.05). After U0126 treatment, the effect of Fat1 knockdown on the proliferation of KYSE450 cells disappeared, and the expression of p-ERK1/2 in KYSE450 cells decreased to a level similar to that in the control group. The number of cell clones in the control group was (72±8), lower than (155±28) and (193±9) in the Fat1sh1 and Fat1sh2 groups, respectively ( P<0.05). In KYSE450 cell, division time was shortened from 1 622±32 min in control group to 1 408±29 min in Fat1 sh1 group, the difference was statistically significant ( P<0.05). Compared with the control group, the tumor volume of Fat1 knockdown group increased significantly. The tumor weight of control group and Fat1 knockdown group were (0.224±0.028) g and (1.532±0.196) g, respectively, at 4 weeks after inoculation, and the difference was statistically significant ( P<0.05). Conclusion:Fat1 inhibits cell proliferation via ERK signaling in ESCC.