BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms such as bacteria. In addition to the manifestations of systemic inflammatory response syndrome and primary infection lesions， critical cases often have manifestations of organ hypoperfusion. The morbidity and mortality of sepsis have remained high in recent years， which seriously affect the quality of life of the patients. The pathogenesis of sepsis is complicated， in which uncontrollable inflammation is a key mechanism. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a key role in mediating inflammation in sepsis. The available therapies of sepsis mainly include resuscitation， anti-infection， vasoactive drugs， intensive insulin therapy， and organ support， which show limited effects of reducing the mortality. Therefore， finding new therapeutic drugs is a key problem to be solved in the clinical treatment of sepsis. In recent years， studies have shown that traditional Chinese medicine （TCM） can regulate the PI3K/Akt pathway via multiple pathways， multiple effects， and multiple targets to inhibit inflammation and curb the occurrence and development of sepsis， which has gradually become a hot spot in the prevention and treatment of sepsis. Moreover， studies have suggested that TCM has unique advantages in the treatment of sepsis. TCM can regulate the PI3K/Akt signaling pathway to inhibit inflammation， reduce oxidative stress， and control apoptosis in the prevention and treatment of sepsis. Despite the research progress， a systematic review remains to be performed regarding the TCM treatment of sepsis by regulating the PI3K/Akt signaling pathway. After reviewing relevant papers published in recent years， this study systematically summarizes the relationship between PI3K/Akt pathway and sepsis and the role of TCM in the treatment of sepsis， aiming to provide new ideas for the potential treatment of sepsis and the development of new drugs.

ObjectiveBased on the conjoint analysis of transcriptome and metabolome， the key genes in the phenylpropanoid biosynthesis pathway of Lonicera macranthoides were explored， which provided a basis for further exploring the synthesis and regulation mechanism of phenylpropanoid compounds in "Xianglei" L. macranthoides. MethodsThe stem， leaves， and three flowering flowers of "Xianglei" L. macranthoides were selected as experimental materials to construct transcriptome and metabolome. The transcriptome and metabolomics were conjointly analyzed by the Kyoto Encyclopedia of Genes and Genomes （KEGG） database and weighted correlation network analysis （WGCNA）， and the key genes in the phenylpropanoid biosynthesis pathway of L. macranthoides were explored. ResultsIn this study， 77 differential phenylpropanoids and 315 differential genes were found. Through the joint analysis of transcription and metabolism， nine key differential metabolites and four key genes related to them were finally discovered. Among them， cinnamic acid， 5-O-caffeoylshikimic acid，sinapyl alcohol， and chlorogenic acid were higher in flowers， and the content of the iconic effective component， namely chlorogenic acid，decreased sharply during the withering period. Caffeic acid，ferulic acid， 5-hydroxyconiferaldehyde，p-coumaryl alcohol， and syringin were higher in leaves. These four key genes belong to the cinnamic alcohol dehydrogenase （CAD） family， 4-coumaric acid： Coenzyme A （4CL） family， hydroxycinnamyl transferase （HCT） family， and L-phenylalanine ammonlyase （PAL） family genes. ConclusionAmong the four key genes excavated from L. macranthoides， TRINITY_DN42767_c0_g6 is related to the synthesis of p-coumaryl alcohol and sinapyl alcohol. TRINITY_DN43525_c4_g1 uses caffeic acid，ferulic acid，and cinnamic acid as substrates to catalyze the next reaction. TRINITY_DN47958_c3_g4 correlates with the synthesis of 3-p-coumaroyl quinic acid and caffeoyl-CoA， and TRINITY_DN52595_c1_g2 correlates with cinnamic acid synthesis. These findings provide a basis for further exploring the synthesis and regulation mechanism of phenylpropanoids in "Xianglei" L. macranthoides.

The European Association for Cardio-Thoracic Surgery (EACTS) has recently updated and published the "2024 EACTS guidelines on perioperative medication in adult cardiac surgery". Based on the latest evidence, the guidelines have been updated in multiple aspects including underlying disease management, antithrombotic medication, arrhythmia treatment and other supportive care, etc. This paper aims to summarize and interpret the guidelines, in order to promote clinicians’ understanding and optimize perioperative medical treatment in adult cardiac surgery.

Blood brain barrier (BBB) injury is the main pathological manifestation of many neurological diseases. Glycocalyx is the gel layer covering the lumen side of vascular endothelial cells, which plays an important role in regulating BBB function. However, glycocalyx is very fragile and easily damaged in various neurological diseases, leading to BBB destruction. This article focuses on the potential role of glycocalyx in cerebrovascular disease, the possible mechanisms related to glycocalyx and BBB injury, and explores the potential therapeutic strategies for protecting and restoring endothelial glycocalyx.

Objective:To investigate the association between fasting blood glucose (FBG) variability and the risk of developing gestational diabetes mellitus.Methods:Ninety patients with gestational diabetes mellitus admitted to Jiaxing Maternity and Child Health Care Hospital between January 2022 and April 2023 were included in this study. Based on the blood glucose results obtained from the 75 g oral glucose tolerance test, these patients were divided into two groups: the normal blood glucose group (Group A, n = 56) and the elevated blood glucose group (Group B, n = 34). Multivariate logistic binary regression analysis was conducted to identify independent risk factors for gestational diabetes mellitus. Additionally, an analysis was conducted to investigate the association between long-term fasting blood glucose standard deviation (SD FBG), coefficient of variation (CV FBG), average successive variability of fasting blood glucose (ASV FBG), and the severity of gestational diabetes mellitus. Results:The FBG levels [(6.83 ± 1.03) mmol/L vs. (4.62 ± 0.58) mmol/L], 1-hour postprandial blood glucose [(13.03 ± 1.39) mmol/L vs. (11.42 ± 1.04) mmol/L], and 2-hour postprandial blood glucose [(10.23 ± 1.51) mmol/L vs. (9.42 ± 0.74) mmol/L] between the two groups ( F = 887.43, 144.76, 10.39, all P < 0.05). Furthermore, the glycated hemoglobin levels were significantly elevated in Group B [(7.19 ± 1.01) mmol/L] compared with Group A [(5.03 ± 0.42) mmol/L, t =14.15, P < 0.05). When compared with Group A, patients in Group B exhibited significantly higher values for ASV FBG [(0.58 ± 0.23) mmol/L vs. (0.36 ± 0.26) mmol/L], SD FBG [(0.55 ± 0.38) mmol/L vs. (0.41 ± 0.21) mmol/L], and CV FBG [(9.43 ± 2.45) mmol/L vs. (6.94 ± 1.31) mmol/L] ( t = 4.06, 2.25, 6.28, all P < 0.05). Additionally, the age and pre-pregnancy body mass index were significantly higher in Group B compared with Group A ( t = 3.82, 7.53, both P < 0.05). Age, pre-pregnancy body mass index, fasting blood glucose, 1-hour postprandial blood glucose, 2-hour postprandial blood glucose, glycated hemoglobin, ASV FBG, SD FBG, and CV FBG were identified as risk factors for severe gestational diabetes mellitus ( OR = 1.230, 1.887, 301.406, 3.957, 1.947, 41.861, 5.421, 2.057, all P < 0.05). Furthermore, SD FBG, ASV FBG, and CV FBG were positively correlated with the severity of gestational diabetes mellitus ( r = 0.234, 0.555, 0.408, all P < 0.05). Conclusion:Fasting blood glucose variability is positively correlated with the risk of developing gestational diabetes mellitus. Age, pre-pregnancy body mass index, fasting blood glucose, 1-hour postprandial blood glucose, 2-hour postprandial blood glucose, glycated hemoglobin, ASV FBG, SD FBG, and CV FBG are also risk factors affecting the severity of gestational diabetes mellitus.

Objective To observe the correlation between apparent diffusion coefficient(ADC)of sacroiliac joint and spondyloarthritis research consortium of Canada(SPARCC)score in ankylosing spondylitis(AS)patients with different grade sacroiliac joint inflammation.Methods MR examinations of sacroiliac joint were prospectively performed in 35 AS patients(AS group)and 30 healthy controls(HC group).The grade of sacroiliac joint inflammation and SPARCC score in AS group were evaluated according to MRI findings,and the patients were then further divided into bone marrow oedema(BMO)subgroup(n=19)and non-BMO subgroup(n=16)according to whether BMO presented under articular surface or not,and ADC of sacroiliac joint(ADCsacroiliac)were measured.Receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to evaluate the efficacy of ADCsacroiliac for assessing AS sacroiliac joint inflammation grade.Pearson correlation analysis was performed to analyze the correlation between ADCsacroiliac and SPARCC score in AS patients with different grade sacroiliac joint inflammation.Results ADCsacroiliac in BMO subgroup and non-BMO subgroup was(4.85±1.44)×10-4 and(4.30±0.64)×10-4 mm2/s,respectively,being not significantly different(P＞0.05)but both higher than that in HC group([3.32±1.36]×10-4 mm2/s,both P＜0.05).The sensitivity of ADCsacroiliac for assessing grade of sacroiliac joint inflammation in AS patients was 49.44％,51.94％,73.06％and 60.50％,with specificity of 75.00％,78.92％,83.33％and 66.67％,respectively,and AUC of 0.613,0.712,0.837 and 0.645,respectively.ADCsacroiliac was moderately-highly positively correlated with SPARCC score of AS patients with Ⅱ and Ⅲgrade sacroiliac joint inflammation(r=0.580,0.933,both P＜0.05),but no obvious correlation was detected between ADCsacroiliac and SPARCC score of AS patients with Ⅰ or Ⅳ grade sacroiliac joint inflammation(both P＞0.05).Conclusion ADCsacroiliac was positively correlated with SPARCC scores of AS patients with Ⅱ and Ⅲ grade sacroiliac joint inflammation,which could be regarded as a reliable quantitative parameter for monitoring sacroiliac joint BMO.

Gastrointestinal motility disorder is an important cause of digestive system diseases. Patients often suffer from nausea， vomiting， gastric retention， gastroparesis， constipation， and many other symptoms， and their quality of life is seriously reduced. Prokinetic agents are routinely used in clinical practice， but their long-term use is prone to problems such as reduced efficacy and increased adverse reactions. Since the incidence of gastrointestinal diseases has continued to rise globally in recent years， there is an urgent need for clinical development of safe and effective treatment strategies. Aurantii Fructus， a traditional Chinese medicine， has the effect of smoothing Qi and eliminating distention， and it has been used to treat gastrointestinal diseases for thousands of years. In modern clinical practice， it is mainly used for the treatment and auxiliary treatment of various gastrointestinal diseases such as functional dyspepsia， functional constipation， and irritable bowel syndrome. The efficacy is remarkable， and no adverse reactions have been reported at conventional doses. Therefore， it can greatly improve the symptoms of patients with gastrointestinal diseases and improve their quality of life. Modern research has revealed that there are many active components in Aurantii Fructus， among which flavonoids have the highest content and the most types. Flavonoids are the main active components in Aurantii Fructus to regulate gastrointestinal motility. Aurantii Fructus and its active components can affect gastrointestinal hormones， neural pathways， Cajal mesenchymal cells， and other multiple mechanisms. They can adjust gastrointestinal motility and correct gastrointestinal motility disorders， showing potential application value in the treatment of gastrointestinal motility disorders. However， a comprehensive analysis of Aurantii Fructus in this aspect is still lacking. This study summarized the pharmacological activities of active components of Aurantii Fructus extract and its flavonoids， volatile oils， alkaloids， and coumarin on the regulation of gastrointestinal motility and explored the latest research progress on its mechanism. Finally， the adverse reactions of Aurantii Fructus were summarized. It aims to provide a scientific basis for the research and clinical application of Aurantii Fructus and its active components in the regulation of gastrointestinal motility.

BACKGROUND:Internal heat-type acupuncture therapy is a new treatment technique that combines acupuncture therapy with hyperthermia.It has good clinical effects on steroid-induced osteonecrosis of the femoral head,but the mechanism of action is still not fully clear. OBJECTIVE:To explore the possible mechanism of internal heat-type acupuncture therapy in treating steroid-induced osteonecrosis of the femoral head in rabbits. METHODS:Thirty-two New Zealand rabbits were randomly divided into blank group,model group,internal heat-type acupuncture group and shock wave group using a random number table method,with 8 rabbits in each group.The model group,internal heat-type acupuncture group and shock wave group were modeled using methylprednisolone sodium succinate combined with Escherichia coli endotoxin.The internal heat-type acupuncture group received an internal heat-type acupuncture intervention on the buttocks of rabbits,once a week,for 20 minutes each time.The shock wave group received shock wave intervention on the buttocks of rabbits,once a week,with 2 000 beats per session.The blank group and model group were not given any treatment.After 4 weeks of intervention,blood samples and bilateral femoral head samples were collected from experimental rabbits.The levels of tumor necrosis factor-α and interleukin-6 in serum were detected by ELISA;the histomorphology of the femoral head was observed using hematoxylin-eosin staining and the rate of empty lacunae was calculated;the protein expressions of matrix metalloproteinase 2,matrix metalloproteinase 9,matrix metalloproteinase tissue inhibitor 1,and matrix metalloproteinase tissue inhibitor 2 were detected by immunohistochemistry and western blot. RESULTS AND CONCLUSION:Compared with the blank group,the model rabbits showed reduced food intake,mental fatigue,and decreased activity;compared with the model group,the above performance of the experimental rabbits was significantly improved after internal heat-type acupuncture and shock wave treatment.Compared with the blank group,the histomorphology of the femoral head in the model group deteriorated significantly and the rate of empty bone lacuna increased(P<0.001),while the histomorphology of the femoral head in the internal heat-type acupuncture group and shock wave group was significantly improved compared with the model group,and the rate of empty bone lacuna was reduced(P<0.001).The serum levels of tumor necrosis factor-α and interleukin-6 in the model group were significantly higher than those in the blank group(P<0.05),while the serum levels of tumor necrosis factor-α and interleukin-6 in the internal heat-type acupuncture group and the shock wave group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 in the femoral head of the model group were significantly increased,while the expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly decreased(P<0.001);compared with the model group,the protein expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 were significantly decreased,while the protein expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly increased in the internal heat-type acupuncture group and the shock wave group(P<0.001).Overall,these findings indicate that internal heat-type acupuncture may promote the repair of the necrotic femoral head by regulating the levels of matrix metalloproteinases/matrix metalloproteinase tissue inhibitors and serum inflammatory factors,thus treating early steroid-induced osteonecrosis of the femoral head.

ObjectiveTo investigate the promotional effect of astragaloside on the repair and healing of chronic non-healing wounds and its mechanism. MethodA total of 60 male SD rats were constructed with full-layer skin defect wounds on the back， and except for the control （Con） group， the rest were constructed with non-healing wounds， which were then randomly divided into the sham-operation （sham） group， the low-dose astragaloside group， the high-dose astragaloside group， the astragaloside + LY294002 ［phosphatidylinositol 3-kinase （PI3K） inhibitor］ group， and the astragaloside + EX527 ［silencing regulatory protein 1 （SIRT1） inhibitor］ group. The percentage of wound area in each group was observed on the 2nd， 4th， 6th， and 8th days after wound molding. Collagen type Ⅰ alpha 1 （COL1A1） and alpha smooth muscle actin （α-SMA） expressions in the wound tissue were detected by immunofluorescence. Hematoxylin and eosin （HE） staining was performed to determine the pathological structure of the wound. The mRNA expression of inflammatory factors in the wound was measured by real-time polymerase chain reaction （Real-time PCR）， and the expression of proteins related to the SIRT1/ nuclear factor （NF）-κB and PI3K/protein kinase B （Akt） signaling pathways in the wound was tested by Western blot. ResultCompared with the sham group， the percentage of postoperative wound area of rats in both low-dose and high-dose astragaloside groups gradually decreased with time， and the efficacy of the high-dose astragaloside group was better. Compared with the Con group， the fluorescence intensity of COL1A1 in wound tissue of the sham group decreased， while the expression of α-SMA increased. The epithelial tissue was severely damaged， with an increase in the thickness， and a large number of inflammatory cells were seen in the infiltration. The mRNA expression of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-6， and inducible nitric oxide synthase （iNOS） was elevated. The protein expression of NF-κB p65， p-PI3K/PI3K， and p-Akt/Akt was elevated， while SIRT1 expression was decreased （P<0.05）. Compared with the sham group， the fluorescence intensity of COL1A1 and α-SMA increased after astragaloside treatment. The number of epithelial cells increased， and the thickness decreased. The inflammatory cells decreased， and the amount of collagen increased. The mRNA expression of TNF-α， IL-1β， IL-6， and iNOS was decreased， and the protein expression of NF-κB p65， p-PI3K/PI3K， and p-Akt/Akt was decreased. SIRT1 was elevated， and the effect was better in the high-dose astragaloside group （P<0.05）. Compared with the high-dose astragaloside group， inhibition of the PI3K/Akt and SIRT1 pathways by LY294002 and EX527 prevented the therapeutic efficacy of astragaloside on chronic non-healing wounds. ConclusionThe topical application of astragaloside significantly promotes the healing of chronic non-healing wounds in rats， and the mechanism may be related to the activation of the PI3K/Akt pathway and the SIRT1/NF-κB pathway.