BACKGROUND:In mammals,white adipose tissue stores energy,whereas brown adipose tissue dissipates energy.Conversion from White to brown/beige adipocytes is a potential therapeutic strategy to fight obesity,but the molecular mechanisms that drive this process is unclear.OBJECTIVE:To reveal the potential relationship between Hr mutation and adipocyte browning.METHODS:Ten 10-week-old male Yuyi hairless mice and 10 littermate wild-type controls were selected and changes in food intake,body mass and inguinal white adipose tissue mass were recorded.Serum levels of leptin and adiponectin were estimated by ELISA.Glucose tolerance test was used to assess glucose metabolic function and insulin tolerance test was performed to analyze insulin sensitivity.Hematoxylin-eosin staining was performed to observe pathological changes of inguinal white adipose tissue in mice.Real-time fluorescence quantitative PCR and immunofluorescent staining were performed to analyze the expression of genes and proteins associated with browning of white adipose tissue in the groin.RESULTS AND CONCLUSION:(1)Compared with wild-type mice,Yuyi hairless mice had increased brown fat content and ultimately increased glucose tolerance and insulin sensitivity.Hr mutation reduced body mass and inguinal adipose mass in mice,but food intake did not change significantly compared with wild-type mice,suggesting that there was a reduction in body mass and adipose mass but not in food intake.(2)Hematoxylin-eosin staining results showed browning of adipocytes in the inguinal white adipose tissue of Yuyi hairless mice,which became smaller,rounder and accompanied by the appearance of multilocular cells.(3)There was increased level of peroxisome proliferator-activated receptor γ coactivator 1α and activation of thyroid hormone receptor α,uncoupling protein 1,and the mitochondria-shaping genes(nuclear respiratory factor 1and mitochondrial transcription factor A),thereby promoting browning of adipocytes.Thus,Hr mutation activates the peroxisome proliferator-activated receptor γ coactivator 1α/thyroid hormone receptorα/uncoupling protein 1 signaling pathway and increases brown adipose content in mice,thereby promoting energy expenditure and thermogenesis and inhibiting obesity.

BACKGROUND:In mammals,white adipose tissue stores energy,whereas brown adipose tissue dissipates energy.Conversion from White to brown/beige adipocytes is a potential therapeutic strategy to fight obesity,but the molecular mechanisms that drive this process is unclear.OBJECTIVE:To reveal the potential relationship between Hr mutation and adipocyte browning.METHODS:Ten 10-week-old male Yuyi hairless mice and 10 littermate wild-type controls were selected and changes in food intake,body mass and inguinal white adipose tissue mass were recorded.Serum levels of leptin and adiponectin were estimated by ELISA.Glucose tolerance test was used to assess glucose metabolic function and insulin tolerance test was performed to analyze insulin sensitivity.Hematoxylin-eosin staining was performed to observe pathological changes of inguinal white adipose tissue in mice.Real-time fluorescence quantitative PCR and immunofluorescent staining were performed to analyze the expression of genes and proteins associated with browning of white adipose tissue in the groin.RESULTS AND CONCLUSION:(1)Compared with wild-type mice,Yuyi hairless mice had increased brown fat content and ultimately increased glucose tolerance and insulin sensitivity.Hr mutation reduced body mass and inguinal adipose mass in mice,but food intake did not change significantly compared with wild-type mice,suggesting that there was a reduction in body mass and adipose mass but not in food intake.(2)Hematoxylin-eosin staining results showed browning of adipocytes in the inguinal white adipose tissue of Yuyi hairless mice,which became smaller,rounder and accompanied by the appearance of multilocular cells.(3)There was increased level of peroxisome proliferator-activated receptor γ coactivator 1α and activation of thyroid hormone receptor α,uncoupling protein 1,and the mitochondria-shaping genes(nuclear respiratory factor 1and mitochondrial transcription factor A),thereby promoting browning of adipocytes.Thus,Hr mutation activates the peroxisome proliferator-activated receptor γ coactivator 1α/thyroid hormone receptorα/uncoupling protein 1 signaling pathway and increases brown adipose content in mice,thereby promoting energy expenditure and thermogenesis and inhibiting obesity.

Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease closely related to metabolism， which is mainly characterized by abnormal lipid deposition in hepatocytes. In recent years， with the increasing prevalence of obesity and metabolic syndrome， NAFLD has become one of the most common chronic diseases in the world. The pathogenesis of NAFLD is complex and varied， involving the cross-regulation of multiple signaling pathways such as glucose-lipid metabolism， oxidative stress， and inflammation. The TLR4 signaling pathway plays a key role in the development and progression of NAFLD， and abnormal activation of this pathway accelerates the deterioration of NAFLD by promoting the release of pro-inflammatory cytokines， inducing oxidative stress， and exacerbating insulin resistance. Studies have shown that traditional Chinese medicine （TCM） can regulate the TLR4 signaling pathway to alleviate the symptoms and pathological features of NAFLD. The present review summarizes the experimental research progress in the TCM regulation of the TLR4 signaling pathway in treating NAFLD in the past 5 years， covering a wide range of TCM active ingredients （such as polysaccharides， terpenoids， alkaloids， flavonoids） and compound prescriptions. The active ingredients and compound prescriptions of TCM can effectively ameliorate lipid metabolism disorders， reduce insulin resistance， regulate intestinal flora， and inhibit inflammation and oxidative stress by regulating the TLR4 signaling pathway via multiple targets and pathways， thus slowing down the progression of NAFLD. Through in-depth analysis of the pathological mechanisms of NAFLD and exploration of the potential of TLR4 signaling pathway as a therapeutic target， we can provide theoretical support for the application of TCM in the treatment of NAFLD， as well as new perspectives and directions for future clinical research and new drug development， thereby promoting the innovation and development of therapeutic strategies for NAFLD.

OBJECTIVE To analyze the current situation of drug use in domestic aeromedical rescue， and provide references for the development of aeromedical rescue services and the rational use of drugs on board. METHODS All literature on aeromedical rescue in China were retrieved from the databases of SinoMed， CNKI， VIP， and Wanfang data up to September 1st， 2024. Extracting descriptive analysis were conducted on the literature screened by the inclusion and exclusion criteria. RESULTS A total of 36 literature were included. Aeromedical rescue cases had been reported in China since 1985， with a cumulative total of 5 370 cases reported. Prehospital rescue performed 861 cases， with 96.40% of them involving the use of at least 9 categories， totaling at least 10 different drugs， primarily emergency drugs. Interhospital rescue performed 4 509 cases， and 85.23% of them used over 48 kinds of drugs across 19 categories， mainly emergency drugs supplemented by specialty drugs. From the view of transportation， 5 166 air transfers were made by helicopters， of which 88.00% involved the use of drugs， and 204 cases by fixed-wing aircraft， of which 91.18% involved the use of drugs. CONCLUSIONS Drugs are frequently used in aeromedical rescue involving a wide variety of types in China. It is imperative to strengthen the focus on the equipment and rational use of drugs in aeromedical rescue， thereby facilitating the establishment of a standardized theoretical framework.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

Objective:With the help of the advanced ACD Labs/AutoChrom method development software,param-eter simulation design was carried out.Based on the results of software simulation and actual investigation,an HPLC method for the determination of related impurities in safinamide mesylate raw material drug was established.Methods:A Waters Atlantis T3 column(4.6 mm ×250 mm,5 μm)was used.The phosphate buffer with a pH of 7.0 was used as mobile phase A,and acetonitrile was used as mobile phase B.Gradient elution was performed at a flow rate of 1.3 mL·min-1,the detection wavelength was 228 nm,the column temperature was 35 ℃,and the injection volume was 10 μL.Results:Impurities 1-12 in safinamide mesylate could be effectively separated from the main component.The linear ranges were 0.102 1-5.329,0.102 9-5.379 7,0.106 8-4.972 9,0.102 1-5.135,0.103 8-5.314 7,0.097 7-4.869 8,0.095 2-4.760 5,0.095 3-5.109 5,0.050 5-5.287 5,0.098 7-4.885 6,0.102 4-4.997 5,0.050 8-5.134 7 μg·mL-1,respectively.The limits of detection(LOD)were 0.051,0.051 4,0.053 4,0.051 1,0.051 9,0.048 8,0.047 6,0.047 7,0.025 3,0.049 3,0.051 2,0.025 4 μg·mL-1,and the limits of quantification(LOQ)were 0.102 1,0.102 9,0.106 8,0.102 1,0.103 8,0.097 7,0.095 2,0.095 3,0.050 5,0.098 7,0.102 4,0.050 8 μg·mL-1.The accuracy,preci-sion and durability all met the requirements.Conclusion:This method is suitable for the determination and quality control of the related substances of 12 impurities in safinamide mesylate raw materials.

Objective To establish an expert consensus on the management of mini-midline catheters(hereinafter referred to as the'consensus')to guide nurses in standardizing the insertion and maintenance of mini-midline catheters.Methods Evidence was systematically retrieved,scientifically evaluated,and synthesized using evidence-based methods to draft the initial version of the consensus.From December 2023 to July 2024,totally 2 rounds of expert correspondence and 2 rounds of expert panel discussions were conducted to revise the content,resulting in the final version.Results There were 17 experts from tertiary A general hospitals in Beijing,Shanghai,Hunan,Hubei,Sichuan,Jiangsu,Hainan,Guangxi Zhuang Autonomous Region,and Shandong participating in the consultation,with a 100％response rate.In the 2 rounds of expert correspondence,the authority coefficients were 0.947 and 0.962,respectively.The mean importance scores of all items exceeded 4.00 points.The coefficients of variation(CV)were 0-0.32(first round)and 0-0.15(second round).Kendall's concordance coefficients were 0.097 and 0.101(both P＜0.001).The consensus covers 11 sections,including definition,indications,contraindications,qualification training,pre-insertion preparation,catheter insertion,catheter use,catheter maintenance,catheter removal,prevention and management of common complications,and health education.Conclusion The Consensus demonstrates scientific rigor and comprehensively addresses key procedures before,during,and after the insertion of mini-midline catheters,providing actionable guidance for nurses in catheter insertion and maintenance.

OBJECTIVE To evaluate the potential of nanopore sequencing technology for rapid diagnosis of Talaro-myces marneffei(TM)infection.METHODS Nine patients with TM infection admitted to the Fourth People's Hospital of Nanning from May 13,2022 to Aug.3,2023 were retrospectively analyzed.Rapid diagnosis was con-ducted by nanopore sequencing technology,and a comprehensive analysis of their clinical characteristics and treat-ment processes was performed.RESULTS The 9 patients included in the study had infections in various sites such as the lungs,buttocks,blood and cervical lymph nodes.Comorbidities included AIDS,secondary pulmonary tuberculosis,non-tuberculous mycobacterial disease and adult-onset immune deficiency.Patients generally exhibited elevated C-reactive protein levels and erythrocyte sedimentation rates,along with increased neutrophil counts.Some patients had abnormal lymphocyte counts and CD4+/CD8+ratios.Microbiological tests showed positive cultures in 3 cases,positive smears in 2 cases and positive targeted detection in 6 cases.Nanopore sequencing detected various pathogens in the 9 patients.The treatment results indicated that 8 patients improved after medication,with 6 patients having medication regimens adjusted based on nanopore sequencing results.CONCLUSION Nanopore sequencing technology has shown potentials in the auxiliary diagnosis of TM infection,providing timely etiological diagnostic evidence for clinical practice.

Objective To investigate the therapeutic mechanism of Dingkun Dan(DKD)in polycystic ovary syndrome(PCOS)by examining the effects of microRNA-30d-5p on ovarian granulosa cells(GCs).Methods A PCOS rat model was established using dehydroepiandrosterone(DHEA).Normal rat GCs and PCOS rat GCs were cultured in vitro and divided into four groups:blank control group,model group,low-dose DKD group,and high-dose DKD group.After grouping,GCs viability was assessed using the methyl thiazolyl tetrazolium(MTT)assay,GCs apoptosis was analyzed by flow cytometry,and the gene expression of transforming growth factor β1(TGF-β1),Smad2,Smad3,and microRNA-30d-5p in GCs was measured by real-time polymerase chain reaction(RT-PCR),protein expression of TGF-β1,Smad2,and Smad3 in GCs was detected by Western Blot.Results Compared with the blank control group,the model group exhibited significantly decreased GCs viability,increased GCs apoptosis,upregulated mRNA and protein expression of TGF-β1,Smad2,and Smad3,and downregulated microRNA-30d-5p expression,the differences were statistically significant(P＜0.01).Compared with the model group,both low-and high-dose DKD groups showed increased GCs viability,reduced GCs apoptosis,downregulated mRNA and protein levels of TGF-β1 Smad2 and Smad3,elevated microRNA-30d-5p expression,and the differences were statistically significant(P＜0.05 or P＜0.01).Conclusion DKD promotes GCs proliferation by targeting Smad2 via microRNA-30d-5p,suggesting a potential therapeutic role in PCOS-related ovulatory dysfunction.